Aims: The aims of this meta-analysis were to assess: the prevalence of Post-Acute COVID-19 sequalae in HIV positive patients; average time of diagnosis; and meta-regress for possible moderators of PACS.Methods: A standard search strategy was used in PubMed, and then later modified according to each specific database to get the best relevant results. These included Medline indexed journals; PubMed Central; NCBI Bookshelf and publishers' Web sites in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Search terms included “long COVID-19 or post-acute COVID-19 syndrome/sequalae”, “persons living with HIV or HIV. The criteria for inclusion were published clinical articles reporting HIV in association with long COVID-19, further, the average time to an event of post-acute COVID-19 sequelae among primary infected patients with COVID-19. Random-effects model was used. Rank Correlation and Egger's tests were used to ascertain publication bias. Sub-group, sensitivity and meta-regression analysis were conducted. A 95% confidence intervals were presented and a p-value < 0.05 was considered statistically significant. Review Manager 5.4 and comprehensive meta-analysis version 4 (CMA V4) were used for the analysis. The review/trial was PROSPERO registered (CRD42022328509).Results: A total of 43 studies reported post-acute COVID-19 syndrome. Of those, five reported post-acute COVID-19 sequalae in PLHIV. Prevalence of post-acute COVID-19 sequalae was 43.1% (95% CI 20.5% to 68.9%) in persons living with HIV (PLWH). The average time to PACS diagnosis was 4 months at 64% [0.64 (95% CI 0.230, 0.913) (P < 0.0000), I²= 93%] and at one year to PACS diagnosis was at 70 %, however with non-significant correlation (P > 0.05). On comorbidities, asthenia was associated with PACS at 17.6 % [0.176 (95% CI 0.067, 0.385) (P = 0.008), I²= 86%] while fatigue at 82%, however not related with PACS event incidence (P < 0.05). Americas, Asian and European regions showed PACS events rates of 82%, 43% and 19 % respectively (P<0.05) relative to HIV infection. Conclusion: PACS prevalence in PLWH was 43% occurring at an average time of 4 months at 64% and 70 % at 12 months however non-significant with PACS. Asthenia was significantly associated with PACS at 17.6 % while fatigue at 82%, however not related with PACS event incidence. Americas recorded the highest PACS event rates in PLWH.

In this review we extensively describe the main post-translational modifications that give rise to the multiple proteoforms characterized to date in the human salivary proteome and their potential role. Most of the data reported were obtained by our group in over twenty-five years of research carried out on human saliva mainly by applying a top-down strategy. At the beginning we describe the products generated by proteolytic cleavages, which can occur before and after secretion. In this section the most relevant families of salivary proteins are also described. Next, we report the current information concerning the human salivary phospho-proteome and the limited news available on sulfo-proteome. Three sections are dedicated to the description of the glycation and enzymatic glycosylation. Citrullination and N- and C- terminal PTMs and a miscellaneous of other modifications are described in the last two sections. Results highlighting the variation in the level of some proteoforms in local or systemic pathologies are also reviewed along the sections of manuscript to underline the impact and relevance of this information for the development of new diagnostic biomarkers useful in clinical practice.

Abstract Congenital rubella syndrome is a constellation of birth defects that can have devastating consequences, impacting approximately 100,000 births worldwide each year. The incidence is much lower in countries that routinely vaccinate their population. In the US, postnatal immunization of susceptible women is an important epidemiological strategy for the prevention of rubella. However, concerns that co-administration of Rubella vaccine with other immunoglobins (i.e., Rhogam) could comprise vaccine efficacy has produced warnings that can delay the administration of Rubella vaccination postpartum, leaving women susceptible in a subsequent pregnancy. We aimed to address whether co-administration of Rubella vaccine and Rhogam decreased antibody responses as compared to those receiving only Rubella vaccination. This retrospective cohort study utilized clinical data from 80 subjects who received Rubella vaccine and Rhogam after delivery and 43 subjects received Rubella vaccine alone. Maternal demographics, pregnancy complications and rubella status at the start of a subsequent pregnancy were recorded for analysis. Overall, the two cohorts had similar baseline characteristics; however, lower parity was noted in the participants having both Rubella vaccination and Rhogam. Based on maternal antibody IgG index for rubella during the next pregnancy, we observed that 88% of the Rhogam + Rubella vaccine group had positive titers, which was not significantly different than the 81% in the Rubella vaccine only cohort (p=0.36). In conclusion, no differences in the rubella immunity status in a subsequent pregnancy were observed in those mothers administered both Rubella vaccine and Rhogam concurrently. Given these findings, warnings against co-administration of Rubella vaccine in combination with other immunoglobulins should be discontinued.

(1) Background: High-grade cervical dysplasia is primarily caused by human papillomavirus (HPV) infection. Conservative surgery is the preferred treatment approach for this condition. The most commonly employed technique is the loop electrosurgical excision procedure (LEEP), which involves removing the affected portion of the cervix. Excisional treatments are often curative, and complications are typically rare and minor; (2) Methods: The loop electrosurgical excision procedure (LEEP) is the standard method used for conservative surgery in high-grade cervical dysplasia. It entails the excision of the specific area of the cervix where the abnormal cells are present. The procedure employs a wire loop carrying an electrical current to remove the affected tissue; (3) Results: Excisional treatments, such as LEEP, have shown to be effective in treating high-grade cervical dysplasia. They have a high success rate in eliminating abnormal cells and reducing the risk of cervical cancer. Complications associated with LEEP are infrequent and usually minor. Short-term complications may include bleeding, which can be managed easily. Long-term complications may involve cervical canal stenosis, which can impact fertility; (4) Conclusions: Conservative surgery, particularly the loop electrosurgical excision procedure (LEEP), is the preferred and effective treatment for high-grade cervical dysplasia caused by HPV infection. It offers a high cure rate with rare and minor complications. While short-term bleeding is a common occurrence, it is manageable. Long-term complications such as cervical canal stenosis may impact fertility. However, an extremely rare and possibly unique complication described in this case is the development of a vaginorectal fistula. This complication is likely due to indirect thermal injury resulting from compromised tissue. Further research is needed to better understand and prevent such complications.

Abstract: Gastroesophageal reflux disease (GERD), the inflammatory bowel disease (IBD), and mental health issues are significant public health concerns in globally. Although rising peaks observed post-COVID-19, there is a sever paucity in high quality data. Using descriptive analysis, we identified the frequency and associations of age- and gender, sport, genetic, and psychiatric consequences in the coexistence of GERD and IBD in 2067 participants 18 to &gt;60 years with mean age of 26.8 ± 12.9 years. Most were 18 -29 years old (66%, n=1364) of which majority were young Saudi females (72.4%, n=1496). Estimated 1099 (53.2%) were students, 428 (20.7%) were unemployed, and 540 (26.1%) were. The majority were Saudis (94.7%, n= 1957). Psychological syndromes anxiety (60.7%), stress (60.7%), and depression (60.6%) were most frequent; whereas, IBD (48.7%) and GERD (36.3%), respectively were the second and third. In 51 % respondents depression, anxiety, and stress occurred first while in 33.9%, and 24.3% IBD and GERD, respectively, were the first signs. In most respondents (59.2%, n=1178), these signs first appeared recently and 33.6% (n=669) reported occurrence during adult life, and only in 7.2% (n=144) the signs noticed during childhood (7.2%, n=144)). Aggravating factors were 32.9% (n=681) genetic and other factors of which 476 (69.9%) inherited IBD while 215(31.6%) and 175 ((25.7), respectively, inherited psychological (depression, anxiety, and stress) and GERD. However, only 18.3% sought treatment (n=378) and only 66 (3.2%) had colectomy or a colostomy bag. Little over half of the studied population (58.1%, n=1201) were active in outdoor. GERD or IBS and psychological factors (anxiety, depression, and stress), were significantly associated with age (P value =.001).; GERD with old age, IBD with mid-age 40-49 years, and psychological disorders among younger ages. Thus, while mental health issues predispose young millennial women to neurogastroenterological disorders, the IBD and GERD initiate psychological problems in old and mid-ages, respectively. Intriguingly, despite the significantly mosaic global genetic population structures, their lifestyles, and nutritional habits, the pattern of these disorders remains similar. Thus, this is potentially consistent with notion that the gut nerve cells are conserved and that the changes in gut dysbiosis of gut microbiome signatures are responsible. These findings have significant clinical implications in the patient treatment strategies and tailored educational and awareness programs in lifestyle medicine. Future microbiome studies would reveal more insight into the mechanisms of disorders.

The rapid development of quantum computing devices promises powerful machines with capabilities that solve a wide range of problems that traditional computers cannot. Therefore, quantum computers generate new threats at unprecedented speed and scale and specifically pose an enormous threat to encryption. Lattice-based cryptography is considered to be the rival to a quantum computer attack and the future of post-quantum cryptography. So, cryptographic protocols based on lattices have a variety of benefits, like security, efficiency, lower energy consumption, and speed. In this work, we study the most well-known lattice-based cryptosystems while a systematic evaluation and comparison is presented also, and focuses on their strengths and weaknesses.

Temperature is a critical factor that influences the proliferation of pathogens in hosts. The impact of temperature on pathogens is commonly explored in controlled and constant temperatures. Experiments under varying environmental temperature are becoming more frequent, however, testing every temperature scenario à la carte is unachievable. One example of this is the human pathogen Vibrio parahaemolyticus (Vp) in oysters. Here, a predictive model was developed for predicting the growth of Vp in oysters under varying ambient temperature. The model was fitted and evaluated against data from experiments studying growth and inactivation of Vp in oysters at eight constant temperatures. Once evaluated, Vp dynamics in oysters were estimated at different post-harvest varying temperature scenarios affected by water and air temperature, and different ice treatment timing. The model performed adequately under varying temperature, reflecting that (i) increasing temperature, particularly in hot summers, favors a rapid Vp growth in oysters, resulting in a very high risk of gastroenteritis in humans after consumption of a serving of raw oysters, (ii) pathogen inactivation due to day/night oscillations, and more evidently, due to ice treatments, (iii) ice treatment is much more effective limiting risk of illness when applied immediately onboard compared to dockside. The model results to be a promising tool for improving the understanding of the Vp-oyster system and support studies on public health impact of pathogenic Vp associated with raw oyster consumption. Although robust validation of the model predictions is needed, initial results and evaluation show the potential of the model to be easily modified to match similar systems where the temperature is a critical factor shaping the proliferation of pathogens in hosts.

Sepsis is a life-threatening condition with high hospital mortality. Elevated mortality has also been observed in patients after hospital discharge due to post-sepsis syndrome (PSS). The etiology of PSS is still not entirely known, but it involves inflammation. Plasma extracellular vesicles (EVs) are recognized as a unique mechanism of intercellular communication in inflammatory processes. It has been reported that EV microRNA (miRNA) production during the acute sepsis phase may persist until after disease resolution and is associated with PSS. We employed mass spectrometry and qPCR analysis to determine the protein and miRNA composition of plasma-derived EVs of 36 patients during sepsis-related hospitalization, immediately after ICU discharge (post-sepsis), and three, six, twelve, and up to 36 months post-sepsis. We determined that patients’ immune system cells were the primary EV source. Fifteen differentially expressed EV miRNAs (DEmiRs) were identified in samples from septic patients compared to the control group. Predictive analyses revealed that these DEmiRs could influence inflammation by modulating pathways mediated by NF-κB, STAT3, and TLR4 signaling activation. Thirteen miRNAs (-15b-5p,-16-5p,-20a-5p,-25-3p,-27a-3p,-29a-3p,-30d-5p,-93-5p,-146a-5p,-148a-3p,-191-5p,-195-5p,-223-3p) were downregulated in the death group compared to the survivor group, making them candidate prognostic markers of ICU survival. One year after ICU discharge, the expression of miR-21-5p and miR-195-5p were decreased in the survivor group. The miRNAs identified in the present study represent potential biomarkers for the survival prognosis of post-sepsis patients.

This study is a cross-sectional survey involving physicians around Indonesia aimed to explore physician hesitancy to treat COVID-19 patients after experiencing COVID-19 infection coupled with associated occupational risk factors. The questionnaire was distributed via contact information from the Indonesian Physician Association database. Out of 383 participants, 25.6% suffered from moderate symptoms of COVID-19 and 2.9% were admitted for critical care. Hesitancy to treat suspected, probable, or confirmed COVID-19 patients was found in 20.3% of physicians. A higher hesitancy rate was found in older physicians and those with less experience in treating COVID-19 patients. Specialist trainees and those who work in public hospitals were physicians with the lowest hesitancy in treating COVID-19 patients. There is a significant hesitancy in treating COVID-19 patients among physicians who have suffered from COVID-19 which calls for further action by management and policy makers.

Plastid gene expression involves many post-transcriptional maturation steps resulting in a complex transcriptome composed of multiple isoforms. Although short read RNA-seq has considerably improved our understanding of the molecular mechanisms controlling these processes, it is unable to sequence full-length transcripts. This information is however crucial when it comes to understand the interplay between the various steps of plastid gene expression. Here, the study of the Arabidopsis leaf plastid transcriptome using Nanopore sequencing showed that many splicing and editing events were not independent but co-occurring. For a given transcript, maturation events also appeared to be chronologically ordered with splicing happening after most sites are edited.

The influence of post-processing conditions on the magnetic properties of amorphous and nanocrystalline microwires have been thoroughly analyzed, paying attention on the influence of magnetoelastic, induced and magnetocrystalline anisotropies on the hysteresis loops of Fe-, Ni- and Co-rich microwires. We showed that magnetic properties of glass-coated microwires can be tuned by the selection of appropriate chemical composition and geometry in as-prepared state or further considerably modified by appropriate post-processing, which consists of either annealing or glass-coated removal. Furthermore, stress-annealing or Joule heating can further effectively modify the magnetic properties of amorphous magnetic microwires owing to induced magnetic anisotropy. Devitrification of microwires can be useful for either magnetic softening or magnetic hardening of the microwires. Depending on the chemical composition of the metallic nucleus and on structural features (grain size, precipitating phases) nanocrystalline microwires can exhibit either soft magnetic properties or semi-hard magnetic properties. We demonstrated that the microwires with coercivities from 1 A/m to 40 kA/m can be prepared.

Blackberry is a fruit that has high nutritional value, a factor that has expanded its consumption worldwide. However, due to the fragility of the fruits and the high incidence of postharvest diseases, the fruits have a short shelf life. Thus, the objective of this study was to evaluate whether the application of coatings based on microfibrillated cellulose (NC) and lemongrass essential oil (EO) nanoparticles can prolong the shelf life of blackberry fruits after harvest. EO-coated blackberry fruits at nanocellulose concentrations were analyzed as follows: 0; 0.2; 0.4; 0.6 and 0.8%, in addition to the control treatment of which neither essential oil nor nanocellulose was used, for each treatment five repetitions were used. The fruits were analyzed soon after the application of the cover and at three and six days after storage. Fruit quality was assessed by soluble solids (SS), titratable acidity (TA), pH, fresh weight loss (FWL) and colorimetric parameters such as luminosity, hue angle and fruit peel chroma. Coating on EO (1000 ppm) blackberries combined with NC at concentrations of 0.2, 0.4 and 0.6% is promising in preserving blackberry fruits and reducing the process color reversal, up to six days of storage. The 0.4% NC + 1000 ppm EO conjugated coating showed no SS changes in blackberry fruits during the six days of storage.

Background and Objectives: Due to huge demand and availability of Banana, innovative cost effective method is necessary to promote and smoothen the banana production among farmers commercially mitigating the demand. Method and Materials: In this study, we feed cow dung mixture along with Urea, TSP, MoP, water to the distal part of rachis after cutting down male bud as soon as the female flowers matured into fruits (T1). The effect of this method was then compared with two control groups; one with the same strategy except fertilizer applied on root following ring method (C1, Positive control) and another was male flower untouched without applying fertilizer on rachis or root (C2, Negative control). Results and Conclusion: T1 showed more than double increase in length than controls. In the same way, in case of shape (diameter), T1 (0.46 cm) showed twice as better growth in the C1 (0.22 cm) and C2 (0.18 cm). Trend analysis showed the test group T1 curve is much steeper than the control groups suggesting faster growth rate than the other two. Finally, the cost of fertilizers for T1 per plant was estimated 0.091 USD while for positive control C1 it was 2.9 USD. This study shows an approach to be effective and economic comparing to traditional method of fertilizer application, which can be adapted as a new method of banana production.

Synergistic effects between reactions, reagents and catalysts can lead to minor heats of reaction and occur as an inherent result of multi-component reactions (MCRs) and their extensions. They enable syntheses to be performed at a low energy level and the number of synthesis steps to be drastically reduced in comparison with ‘classical’ two-component reactions. The very high potential for variability, diversity and complexity of MCRs additionally generates an extremely diverse range of products, thus bringing us closer to the aim of being able to produce tailor-made and extremely low-priced materials, drugs and libraries.

Abstract A multiple number of studies provide evidence that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, securing thereby survival and comfort of life. Vasopressin interacts with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone ACTH, and multiple steroid hormones, as well as through interactions with steroids in the target organs. The interactions are facilitated by positive and negative feedbacks occurring between specific components of the HPA axis with engagement of other regulatory molecules. Altogether AVP and HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by the cellular stress combined with hypoxia, and by metabolic, cardiovascular and respiratory disorders, neurogenic stress and inflammation. Growing evidence indicates that central and peripheral interactions of AVP and steroid hormones are reprogrammed in cardiovascular diseases and that the rearrangements play either beneficial or harmful effects. The present review highlights specific mechanisms of interactions of AVP and steroids at cellular and systemic levels and analyses consequences of inappropriate cooperation between various components of the AVP-HPA system for the regulation of the cardiovascular system and energy balance in cardiovascular and metabolic diseases.

The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

In this study, we propose the Signal Integration Reconstruction Peak Detection (SIRPD) algorithm for reliable Cardiac Beat Interval (CBI) measurement using functional Near-Infrared Spectroscopy (fNIRS) signals. This algorithm enhances reliability by identifying a regular waveform in cerebral blood flow associated with heartbeats. The SIRPD algorithm assesses the Signal Quality Index (SQI) per channel, discards signals from unavailable channels, and interpolates oxygenated and total hemoglobin concentration signals, thereby boosting resolution and integrating the signal into a single channel. The integrated and smoothed signal is transformed to identify the most significant periodic waveform, from which the CBI is extracted. Validated with data from 20 healthy subjects who simultaneously recorded fNIRS and ECG signals, our findings confirm the equivalence of the CBI derived from ECG and calculated through the SIRPD algorithm from fNIRS (R^2 = .98, RMSE = .011, ICC = .991). We also extracted heart rate variability (HRV) features, confirming no significant difference in all features between ECG and fNIRS devices. Uniquely, this study regards the fNIRS heart signal not as an artifact source but as a valuable bio signal. The proposed method, which allows for the detection of cardiac beat intervals from cerebral blood flow oscillations, suggests the potential clinical applicability of fNIRS as an auxiliary indicator for various cardiovascular factors.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Abstract: A progressive neurological disorder was observed in a male neutered Weimaraner. Clinical signs included fecal incontinence, lethargy, moderate paraparesis, proprioceptive pelvic limb ataxia, falling, cognitive decline, incoordination, decreased interest in food, changes in posture, and episodes of trance-like behavior. Neurologic signs were first observed at approximately 4 years, 10 months of age and progressed slowly. Magnetic resonance imaging showed generalized brain atrophy with areas of white matter pathology. Humane euthanasia was elected at 6 years, 7 months of age due to increasing severity of the neurological signs. Autoflorescent intracellular granules were observed in the cerebral and cerebellar cortexes, optic nerve, and cardiac muscle of the affected dog. These abnormal inclusions in the cerebral cortex and cardiac muscle immunolabeled with antibodies to mitochondrial ATP synthase subunit c protein, like that observed in the neuronal ceroid lipofuscinosis group of lysosomal storage diseases. Immunolabeling also demonstrated pronounced neuroinflammation in brain tissues. The ultrastructural appearances of the disease-related inclusion bodies in the brain and optic nerve were quite variable. The ultrastructure and locations of many of the inclusions in the nervous tissues suggested that they were derived, at least in part, from the myelin surrounding axons. The storage bodies in the cardiac muscle were located in mitochondria-rich regions and consisted of parallel arrays of membrane-like components interspersed with electron-dense flocculent material. The disease was characterized by pronounced abnormalities in the myelin of the brain and optic nerve consisting of distinctive areas of ballooning between the layers of myelin. The whole genome sequence generated from the affected dog contained a homozygous G-to-A missense mutation in CNP, which encodes proteins with CNPase enzyme activity and a structural role in myelin. The mutation predicts a Thr42Met amino acid sequence substitution. Genotyping of archived Weimaraner DNA samples identified an additional G>A variant homozygote with a clinical history and brain lesions similar to those of the proband. Of 292 Weimaraners and over 4,000 other dogs of various breeds, the proband and the other Weimaraner that exhibited similar signs were the only two that were homozygous for the CNP missense variant. CNPase immunolabeling was widespread in brain tissues from normal dogs but was undetectable in the same tissues from the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the late-onset Weimaraner disorder likely results from the missense mutation that results in CNPase deficiency, leading to myelin abnormalities, accumulation of lysosomal storage bodies, and brain atrophy. Similar disorders have been associated with different CNP variants in Dalmatians and in human subjects.

Myotonic dystrophy is a hereditary disorder with systemic involvement. The Italian Neuro-Cardiology Network (INCN-RNC) is a unique collaborative experience involving neurology units combined with cardio-arrhythmology units. The INCN facilitates the creation of integrated neuro-cardiac teams in Neuromuscular Disease Centers for the management of cardiovascular involvement in the treatment of MD1.

Purpose of the study: to reveal how the transfusion and the refraining from it affects the neuro-vascular unit in the congenital heart defects correction with cardiopulmonary bypass. Materials and methods: in vitro research, we formed a model of a neurovascular unit, which contains neu-rons, astrocytes and endothelial cells. This cellular model was cultivated in hypoxia conditions with the oxygen saturation levels of 1, 2, 3, 4%. In addition, this unit was cultivated with the pa-tient's serum adding in two different groups - with minimal and maximal levels of system in-flammatory response that we estimated by IL-6 level. Results: We found that during incubation in hypoxic conditions, the level of transendothelial resistance changed in groups with oxygen levels of 1% and 2% only after 4 hours. When we cultivated neurovascular unit cells with patients' sera, we found a minimal level of transendothelial resistance at 4 hours that increased after 24 hours. Permeability analysis showed that its level significantly decreased in the 1% and 2% oxygen group at 60- and 90-minutes relative to the control group. Conclusion: the system inflammatory response has more expressed but less long effect on the neurovascular unit model than hypoxia.

Electrocardigraphy remains as a first-line evaluation method for cardiac function, recording the electrical activity of the heart from the body surface. Since atrial activation is seen on the ECG as P-wave, several factors are known to impact the appearance of the P-wave, such as direction of electric impulse, conduction abnormalities and anatomical characteristics of the atria. The aim of this retrospective study was to find statistically significant associations between anatomy of pulmonary veins (PVs) osberved in cardiac computed tomography (CT) and P-wave appearance during sinus rhythm on resting ECG. For each patient, a resting 12-lead ECG was recorded, the field of analysis was P wave – its’ duration, morphology and axis. The evaluation of the CT scan recordings was performed by creating 3D models of the left atrium and analyzing anatomy of the PVs and left atrial appendage (LAA). Noteworthy correlations were found: anatomy of the left PVs showed an association with LAA volume, LAA morphology and P-wave notching in lead II. The right PVs demonstrated relation with P wave axis and amplitude. Although these correlations cannot be classified as strong, they may play a role in significant scientific discoveries in future research projects.

This work presents patient radiation dose data for pediatric interventional cardiology procedures in a large hospital in Colombia. The data collection period was from April 2020 to July 2022. The local DRLs were calculated as the 3rd quartile of patient dose data distributions for kerma area-product (Pka) values. The sample of collected clinical procedures (255) was divided into diagnostic and therapeutic procedures and grouped into five weight and five age bands. The Pka differences found between diagnostic and therapeutic procedures were statistically in all weight and age bands, except the group between 1-5 years. The local DRLs were 69 Gy/cm2 (< 5 kg), 3.44 Gy/cm2 (5-<15 kg), 8.87 Gy/cm2 (15-<30 kg), 10.51 Gy/cm2 (30-<50 kg) y 22.61 Gy/cm2 (50-<80 kg), respectively. In conclusion, from comparing our results with other existing DRL values, we are similar to other centers and scope to continue optimizing the radiation dose values. This will contribute to setting national diagnostic reference levels (DRLs) for Colombia in the near future.

In this study, we designed a functional neuro-cardiac model to help us examine the role of neuronal regulation and confirm the importance of neural innervation techniques for cardiac tissue regeneration. A three-dimensional (3D) bioprinted neuro-cardiac scaffold composed of a mixture of gelatin-alginate and alginate-genipin-fibrin hydrogels was developed with a 2:1 ratio of AC16 cardiomyocytes (CMs) and retinoic acid differentiated SH-SY5Y neuronal cells (NCs) respectively. A unique semi-3D bioprinting approach was adopted where the CMs were mixed in the cardiac bioink and printed using an anisotropic accordion design to mimic the physiological tissue architecture in vivo. The voids in this 3D structure were methodically filled in using a NCs-gel mixture and cross-linked. Confocal fluorescent imaging using Microtubule-associated protein 2 (MAP-2) antibodies for labeling NCs, and the MyoD1 antibody for CMs revealed functional coupling between the two cell types in the final cross-linked structure. This data confirmed the development of a physiologically functional neuro-cardiac model that can be used to study neuro-cardiac modulation under physiological and pathological conditions.

Despite the 12-lead electrocardiogram (ECG) being the gold standard in evaluating clinical presentations of arrythmias of various kinds, several notable limitations, namely in accuracy and localization, have recently garnered concern with respect to administering appropriate therapeutic measures. The following text puts these limitations under the spotlight, highlighting the difficulty and challenging nature of standard ECG analysis and therapeutic measures, while simultaneously showing a novel body surface electrocardiographic mapping system that utilizes 3D spatial imaging and pinpoint localization algorithms in order to compensate for the shortcomings of the standard ECG, thereby providing higher precision data collection. We provide a brief overview of the novel device in a selection of arrhythmic demographics, along with its validity and reliability, while illustrating the benefits and positive outcomes of its utility.

Except for a few species, the outer shape of vertebrates normally is characterized by bilateral symmetry. The inner organs, on the other hand, normally are arranged in bilaterally asymmetric patterns, which are of special importance for the normal function of the cardiovascular system of lung-breathing vertebrates. Deviations from the normal organ asymmetry can occur in the form of mirror imagery of the normal arrangement (situs inversus), or in the form of arrangements that have the tendency for development of bilateral symmetry, either in a pattern of bilateral left-sideness (left isomerism) or bilateral right-sidedness (right isomerism). The latter two forms of visceral situs anomalies are called “heterotaxy syndromes”. During the past 30 years, remarkable progress has been made in uncovering of the genetic etiology of heterotaxy syndromes. However, the pathogenetic mechanisms causing the spectrum of cardiovascular defects found in these syndromes remain poorly understood. In the present report, a spontaneous case of left cardiac isomerism found in a HH-stage 23 chick embryo is described. The observations made in this case suggest that hearts with left cardiac isomerism may have the tendency for development of a non-compaction cardiomyopathy caused by defective development of the proepicardium.

Aortic rupture is known as one of the potential causes of sudden cardiac death in athletes. Nevertheless, adaptation strategies for aortic root dilation in athletes vary. The purpose of this study was to investigate aortic root adaptation to physical workload and to determine if aortic root’s and left ventricle sizes are contingent upon the physical workload. Echocardiography was applied to 151 subjects to measure the aortic root at aortic valve annulus (AA) and at sinus of Valsalva (VS). 122 were athletes (41 females and 81 males) and 29 were non-athletes (14 females and 15 males). Of the 41 female athletes, 32 were endurance athletes, and 9 strength athletes. From 81 male athletes, 56 were endurance athletes, and 25 were strength athletes. AA and VS mean values for the body surface area were presented as rAA and rVS. Left ventricle (LV) meaures incuded LV end-diastolic diameter (LVEDD), interventricular septum thickness in diastole (IVSTd), LV posterior wall thickness in diastole (LVPWTd), LV mass (LVM), LV mass index, LV end-diastolic diameter index (LVEDDI). Results indicated that VS was higher in female athletes (28.9±2.36mm) than in non-athletes (27.19±2.87mm, p=0.03). On the other hand, rAA was higher in strength athletes (12.19±1.48mm/m2) than in endurance athletes (11.12±0.99mm/m2, p=0.04). Additionally, rVS and rAA were higher in female strength athletes (17.19±1.78mm/m2, 12.19±1.48mm/m2) than female basketball players (15.49±1.08mm/m2, p=0.03, 10.75±1.06 mm/m2, p=0.02). Statistically significant positive moderate correlations were found between VS and LVEDD, LVM, IVSTd, LVPWTd, rVS and LVEDDI parameters in all athletes. The diameter of Valsalva sinus was greater in female athletes compared to non-athletes. The rAA mean value for body surface area was greater in female athletes practising strength sports as compared to their counterparts who were practising endurance sports. The diameter of the aortic root at sinuses positively correlated with the LV size in all athletes. Trial was registered at ClinicalTrials.gov Identifier: NCT03656861, September 3, 2018 (retrospectively registered).

-529391451442Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).0Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Abstract: SARS-CoV-2 vaccination offered the opportunity to get out of the pandemic and thereby worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe but side effects are being reported more frequently as more and more people around the world become treated. Myo-pericarditis is the major, but not the only cardiovascular complication of this vaccine, hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database emerged that heart rhythm disorders after Covid vaccination are not uncommon and deserve more clinical and scientific attention. Since Covid vaccine is the only vaccination to have been related to this side effect questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit is clearly in favor of vaccination heart rhythm disorders are not a negligible issue and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we investigated the potential mechanism for the Covid vaccine to impact on cardiac electrophysiology and cause heart rhythm disorders.

This study sought to investigate the problem of losses along the milk value chain in Nandi and Kakamega Counties in Kenya. Using semi structured questionnaire, quantitative data were collected from different stages of the value chain consisting of 400 dairy farmers proportionally and randomly selected in Chesumei and Ikolomani sub counties; 15 cooperatives, 40 transporters, 20 milk bars, 17 supermarkets. Additionally Key informant interviews and focus group discussions we held with extension staff and farmers, respectively.The results showed losses occurred at all stages of the value chain in Nandi and Kakamega Counties with the highest losses at Cooperative (50.6%), collection centres (33.7%) and milk bars (7.5%). Annual milk loss was estimated to be 260,000 litres and 20,000 litres in Nandi and Kakamega counties respectively. The economic value of losses per year was estimated at KES 13 million (USD 100 000). Significant factors (P<0.001) influencing milk losses at farm level were: type of cow housing, level of training of milker, mixing morning and evening milk and Lack of cooling facilities. In cooperatives, poor roads, poor preservation of milk and mastitis influenced post harvest losses (PHL) causing milk rejection due to spoilages; while transporters attributed PHL to storage during transportation. Inadequate storage facilities and milk handling practices influenced PHL in milk bars while supermarkets attributed PHL to poor packaging materials and short shelf life. The most important causes of milk PHL along the chain were spoilages, spillages, adulteration and physical dirt. Key interventions to minimize PHL should target improvement of rural road infrastructure connecting farmers to markets; milk storage facilities and capacity building on milk handling practices for all actors. A sustainable PHL reduction should entail policy dialogue on milk payment system based on quality rather than quantity.

Lessons learned and risk-based outcomes from modernising the Australian Standard for post-mortem inspection and disposition judgement of beef, sheep, goat and pig carcases are described. Initial Risk Profiles identified priorities for quantitative assessments. The main difficulty encountered was the paucity of quantified performance of current inspection. Resolving this involved acquiring gross abnormality data representing regional production/proportional abattoir volumes, the range of gross abnormalities appearing nationally, proportional occurrence at carcase sites, and seasonality to enable comparisons. Evidence and discussion are provided for associated challenges experienced including preventing contamination, use of food chain information to support amendment, inspection as a part of industry Quality Assurance and opportunities to improve inspector training. Criteria considered by the Competent Authority for determination of equivalence of alternative post-mortem inspection techniques included comparisons of public health risk, non-detection rates for gross abnormalities, and microbial contamination resulting from inspection activities, as appropriate. Most gross abnormalities detected arose from animal health and welfare conditions affecting wholesomeness and did not present as food safety hazards. Non-detection rates between current and alternative inspection (observation) were negligible. A Quantitative Risk Assessment for Cysticercus bovis was conducted. Carcases with multiple gross abnormalities predominantly reflected historic infections (prior septicaemia) where trimming achieved wholesomeness unless cachexic.

Objectives This study aimed to evaluate the eicosanoid and pro-resolutive parameters in Post Covid Syndrome (PCS) patients during 12 weeks of a supplementation with a marine oil enriched in SPMs. Patient and methods The study was conducted in 53 adult patients with a PCS. The subjects included must have had a positive COVID-19 test (PCR, fast antigen test, or serologic test) and persistent symptoms related to COVID-19 at least 12 weeks before their enrolment in the study. The following parameters were evaluated: Polyunsaturated fatty acids: EPA, DHA, ARA, DPA, Specialized Pro-resolving mediators (SPMs) 17-HDHA, 18-HEPE, 14-HDHA, resolvins, maresins, protectins, and lipoxins. The eicosanoids group included prostaglandins, thromboxanes, and leukotrienes. The development of the clinical symptoms of fatigue and dyspnea were evaluated using the Fatigue Severity Scale (FSS) and the Modified Medical Research Council (mMRC) Dyspnea Scale. Three groups with different amounts of intake were evaluated: daily use of 500mg, 1500mg, and 3000mg were compared to a control group without use of the product. Results In the serum from PCS patients, an increase of 17-HDHA, 18-HEPE, 14-HDHA could be observed. Also, a decrease in the ratio between the pro-inflammatory and pro-resolutive lipid mediators was detected. Both differences were significant (p < 0.05). There were no differences between the three treatment groups. Fatigue and dyspnoea showed a trend to improve after supplementation in all groups. Conclusions A clear enrichment in serum of the three monohydroxylated SPMs could be observed also at a dosage of 500 mg per day. In the same way, a clear improvement in fatigue and dyspnoea was observed with this dosage. Clinical Trial Registry: ISRCTN13270662.

Amid increasing deforestation, surface fires reaching the forest understory are one of the primary threats to Amazonian ecosystems. Despite extensive research on post-fire mortality in woody species, literature on palm resilience to fire is scant. This study investigates post-fire mortality in four understory palms—Bactris maraja Mart., Chamaedorea pauciflora Mart., Geonoma deversa (Poit.) Kunth, Hyospathe elegans Mart., and juvenile individuals of Euterpe precatoria Mart. Objectives included: a) comparing post-fire responses; b) developing mortality models based on severity variables; and c) evaluating if diameter protects bud stems from heat flux. Conducted at the edge of an Ombrophylous Forest in Alto Juruá Acre, Brazil (7°45'S, 72°22'W), the experiment subjected 85 individuals to controlled burning in a 1 m² area near the stipe, with temperature sampling using K thermocouples. Results showed varying mortality rates among species, with larger stipe diameter correlating to reduced mortality. Canopy burning patterns significantly influenced mortality, especially for Euterpe precatoria. Species exhibited diverse regrowth capacities, with B. maraja showing the highest number and tallest basal resprouts. This study underscores post-fire plant mortality as a critical indicator of fire severity, essential for understanding its ecological impacts.

This study introduces a hardware accelerator to support various Post-Quantum Cryptosystem (PQC) schemes, addressing the quantum computing threat to cryptographic security. PQCs, while more secure, also bring significant computational demands, especially problematic for lightweight devices. Previous hardware accelerators are typically scheme-specific, which is inefficient given the National Institute of Standards and Technology (NIST)'s multiple finalists. Our approach focuses on the shared operations among these schemes, allowing a single design to accelerate multiple candidate PQCs at the same time. This is further enhanced by allocating resources according to performance profiling results. Our compact, scalable hardware accelerator supports four of NIST PQC finalists, achieving an area efficiency of up to 81.85\% compared to the current state-of-the-art multi-scheme accelerator while supporting twice as many schemes. The design demonstrates average throughput improvements ranging from 0.97$\times$ to 35.97$\times$ across the four schemes and their main operations, offering an efficient solution for implementing multiple PQC schemes within constrained hardware environments.

Non-woven jute (NWJ) produced from the carpet industry waste was oxidized by H2O2 or alkali treated by NaOH and compared with water-washed samples. Changes in the structure of the NWJ, tracked by XRD, showing that both chemical treatments disrupt hydrogen bond networks between cellulose Iβ chains of the NWЈ fibers. Thereafter, nano carbon nitride (nCN) was impregnated, using layer-by-layer technique, onto water washed jute sample (nCN-Jw), NaOH treated sample (nCN-Ja) and H2O2 treated sample (nCN-Jo). Analysis of the FTIR spectra of the impregnated samples, revealed that nCN anchors to the water washed NWЈ surface through hemicellulose and secondary hydroxyl groups of the cellulose. In the case of chemically treated samples nCN is preferentially bonded to the hydroxymethyl groups of cellulose. The stability and reusability of nCN-J samples were assessed by tracking the photocatalytic degradation of Acid Orange 7 (AO7) dye under simulated solar light irradiation. Results from up to ten consecutive photocatalytic cycles demonstrated varying degrees of effectiveness across different samples. nCN-Jo and nCN-Ja samples exhibited declining effectiveness over cycles, attributed to bond instability between CN and jute. In contrast, the nCN-Jw sample consistently maintained high degradation rates over ten cycles, with a dye removal percentage constantly above 90%.

Beaches are among the habitats most frequented by migratory birds for breeding and/or wintering. However, threats such as human pressure and sea level rise can reduce the availability of these habitats for different species. The presence of alternative areas, such as salt pans and brackish habitats, is essential for many migratory shorebird populations. This study addresses the post-breeding dispersal of the Kentish plover (Charadrius alexandrinus) in the Iberian Peninsula by analysing C and N isotopes in feathers. The study was conducted at six locations along the Iberian coast, which were categorized in three areas: NW Atlantic coast, the Atlantic coast of Andalusia and the Mediterranean coast. Although linear mixed models did not reveal any significant effects of sex or coastal area on isotopic levels, the variability in the data suggests different habitat-use strategies in the post-reproductive period. Birds from the northwest of the Iberian Peninsula exhibit greater fidelity to a single habitat type, i.e. coastal beaches, while populations from the Mediterranean coast and the Atlantic coast of Andalusia show different individual dispersal strategies, occupying coastal habitats and freshwater wetlands. The lack of alternative habitats for the northwest Iberian population, the reduction in available habitat due to rising sea levels and human pressure together pose a serious threat to the survival of this species, already with an unfavourable conservation status.

Background: Traumatic events adversely affect the clinical course of obsessive-compulsive disorder (OCD). Our investigation explores the correlation between prolonged interpersonal trauma and the severity of symptoms related to obsessive-compulsive and anxiety disorders. Methods: The study follows a cross-sectional and observational design, employing the International Trauma Questionnaire (ITQ) to examine areas linked to interpersonal trauma, the Hamilton Anxiety Rating Scale (HAM-A), and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to assess anxious and obsessive-compulsive symptoms, respectively. Descriptive analysis, analysis of variance (ANOVA), and logistic regression analyses were conducted. Results: We recruited 107 OCD-diagnosed patients, categorizing them into subgroups based on the presence or absence of complex post-traumatic stress disorder (cPTSD). The ANOVA revealed statistically significant differences between the two groups in the onset age of OCD (p=0.083), psychiatric familial history (p=0.023), HAM-A, and Y-BOCS (p=0.000). Logistic regression indicated a statistically significant association between the presence of cPTSD and Y-BOCS scores (p=0.000). Conclusion: The coexistence of cPTSD in OCD exacerbates obsessive-compulsive symptoms and increases the burden of anxiety. Further advancements in this field are crucial for mitigating the impact of early trauma on the trajectory of OCD and associated anxious symptoms.

Background and aims: For many surgical procedures, spinal anesthesia is a reliable and efficient anesthetic approach. Numerous drugs have been reported to be administered to intrathecal local anesthetics as adjuvants to increase the efficacy of spinal anesthesia. There is little evidence of the effect of intrathecal dexmedetomidine on pain scores and the consumption of analgesia postoperatively. Methods: After obtaining ethical approval, demographical and clinical data of patients who underwent surgical procedures under spinal anesthesia with intrathecal dexmedetomidine or fentanyl was collected and analyzed. Results: In this study with 96 patients, intrathecal dexmedetomidine (group D) resulted in significantly lower post-operative pain scores compared to intrathecal fentanyl (group F) (p=0.000). Across various surgical types, including Orthopedic, General, Urology, and Obs/Gyne procedures, group D consistently displayed reduced pain scores (p&lt;0.001). The number of patients who needed post-operative analgesia was significantly higher in group (F) than in group (D) (40 vs 23, p=0.002). Conclusion: Compared to fentanyl, intrathecal dexmedetomidine as an adjuvant to local anesthesia was found to lower post-operative pain scores and decrease the need for post-operative analgesia.

ICT and digital technology adoption, sustainable development, community empowerment and local wisdom and destinations uniqueness are keywords that will be further explored in the de-velopment of tourism villages in Kenderan as the most importance of tourism destinations de-velopment from the village level. Therefor this research is aimed at developing suitable model for post smart or wise tourism village through proposing Culture and Tradition Festival and the application of a circular economy. Circular economy development in tourism villages focuses on the application of sustainable production principles in the tourism value chain, namely in creating tourism experiences together with tourists (co-creation of experience) and integrated in a tourism system that supports environmental sustainability. This research is applied research conducted with a sequential mixed method research by conducting qualitative research through expert judgment and quantitative research by circulating questionnaire to tourists visiting Kenderan village, while the collected data is analyzed by Structural Equation Modelling to see the rela-tionship between variables. The results of this research show that creative event as the locality aspects of tourist village, digital competence, and sustainability practice are the building blocks of post smart tourism village, while digital competence and sustainable practice have significant mediating effect of locality on post smart tourism village. To make tourism village possesses sustainable competitive advantages, the village must explore and promote its locality aspects to differentiate its tourist village by identifying the valuable, rare, inimitable and non-substitutable tourism resources. The implication of this research is that to develop smart tourism destination wiser and distinctive, tourist village should explore their local values and resources, embed them into its tourism basic components and core resources, and co create, distribute, deliver and promote it to global market through technology adoption and global sustainability value.

Objective: To assess the recovery of voice in patients with unilateral vocal cord paralysis after thyroid surgery following treatment with nursing intervention combined with voice training. Methods: Thirty patients with unilateral vocal cord paralysis and hoarseness for 6-12 months post-thyroid surgery were selected. They first underwent two weeks of psychological and cognitive intervention, followed by a psychological resilience assessment, and then proceeded with 12 weeks of voice training. This training primarily included muscle relaxation exercises, breathing training, and phonation exercises. A comparative analysis was conducted on the patients' voice parameters before and after the training, including jitter, shimmer, maximum phonation time (MPT), noise to harmonic ratio (NHR), and the Voice Handicap Index (VHI) scores. Results: After psychological and cognitive intervention, scores for optimism, resilience, and self-strength among the 30 patients increased. Post-voice training, reductions were observed in jitter, shimmer, NHR, and VHI scores, the Maximum Phonation Time (MPT) increased compared to pre-training, with the difference being statistically significant (P<0.05). Conclusion: Nursing intervention combined with voice training can effectively improve voice quality in patients with unilateral vocal cord paralysis after thyroid surgery.

Background: Chronic post-surgical pain is a condition persisting at least three months after surgery. It is estimated that 25-60% of patients who underwent breast cancer removal surgery suffer from post-mastectomy pain syndrome and occurred anxiety, depression, sleep disturbance and catastrophizing. Physical activity can reduce the risk of chronic diseases and has a good impact on mood and cognitive function. Aim of this study was to evaluate the effects of physical activity on the intensity of pain, depression and anxiety in women underwent mastectomy for breast cancer removal. Methods: A prospective observational unicentric cohort study was performed. Patients were female underwent unilateral or bilateral mastectomy. Numerical Rating Scale (NRS), was used to assess pain intensity, Beck’s Depression Inventory (BDI) for depression and Generalized Anxiety Disorders-7 (GAD-7), for anxiety evaluation. Physical activity was assessed by International Physical activity questionnaire (IPAQ). Interleukin (IL)-17, IL-1β, cortisol, adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) were also evaluated in the blood of patients. All the evaluation was assessed 3 and 6 months after the surgery. Results: Adequate physical activity reduced intensity of pain, depression and anxiety symptoms in women affected by post-mastectomy pain syndrome. Moreover, adequate active women, showed a reduction of biomarkers of inflammation, cortisol, ACTH and an increase of BDNF. Conclusions: Our results suggest that physical activity can improve quality of life, reducing intensity of pain, inflammatory markers and it can be useful in the reduction of associated anxiety and depression.

Keywords: Post-Stroke; Hyperbaric oxygen therapy; Sequelae; Feasibility; Out-patient.

Considering the importance of assessing the impacts resulting from a sport career, this study aimed at developing and validating a semi-structure interview guide suitable for quantifying the socio-demographic and epidemiological profile of former professional football players. Based on the theoretical frameworks and several methodological procedures, an interview guide was de-veloped, consisting of 3 areas of conceptual organization (A1. Biographical data; A2. Career data; and A3. Post-Career Transition data) and 8 data collection categories (C1. Personal data; C2. Pro-fessional data; C3. Socio-demographic pathway in the post-career; epidemiological pathway; C4. Epidemiological pathway; C5. Moment of leaving the career; C6. Socio-demographic pathway in post-career; C7. Epidemiological pathway in the post-career; and C8. Perceptions on post-career planning). The construction and validation of the interview guide following 4 steps: Ad hoc con-struction of the interview guide (step 1); Review of the interview guide by a panel of experts (step 2); Definition of procedures and protocol for the application of the interview (step 3); Application of the pilot study for face validation of the interview guide (step 4). Thus, in procedural terms, four stages were considered for the construction and validation of the interview guide, namely the Ad hoc construction of the interview guide (i), the review of the in-terview guide by a panel of experts (ii), definition of procedures and protocol for the application of the interview (iii), and the application of the pilot study for the face validation of the interview guide (iv). The results showed that the interview guide for the study of the impacts of the sports careers on the quality of life of Portuguese former football players shows reliability for the collec-tion of qualitative and quantitative information from the respective content analysis. The use of the interview guide characterizes the path of former player, providing information and knowledge on the socio-demographic and epidemiological impact factors resulting from their post-career (sports retirement).

This study intricately explores the evolving tapestry of Christmas celebrations in a post-pandemic era, where tradition delicately intertwines with technology. The literature review presents a global panorama of Christmas observances, delving into varied religious perspectives. Within this exploration, a Southeast Asian country discreetly initiates its festivities as early as September—a nuanced response to the profound significance of Christmas. Navigating the digital age, the paper dissects the impact of virtual gatherings, the surge in e-commerce, and digital church services on festive traditions. Employing diverse research methods, including thematic analysis, nuanced insights are synthesized from extensive literature reviews, interviews, and observations. Scrutinizing challenges posed by the digital divide, the erosion of personal connections in virtual gatherings, and sustainability concerns in online celebrations, the qualitative research methodology reveals the interplay between tradition and technology. The paper contemplates the future of Christmas in this transformative era, offering implications for future celebrations, technology developers, policymakers, and beyond. This endeavor invites contemplation on the dynamic interplay shaping the festive landscape and prompting reflection on future celebrations.

In conclusion, this qualitative exploration has unveiled the profound and essential impact of music on psychological well-being, especially in the post-pandemic world. Through in-depth literature reviews, informal interviews, and observations with thirty CAS participants from SMC, the researcher uncovered ten salient themes that collectively illustrate music's multifaceted role as a potent remedy. These findings showcase how music serves as an emotional outlet, a cognitive enhancer, and a source of inspiration. The emotional depth and spiritual resonance participants associate with music underscore its capacity to address diverse human needs, making it an indispensable tool in navigating the complexities of our post-pandemic reality. Moreover, the cognitive benefits observed, such as improved concentration and focus, are particularly pertinent in the context of remote work and education, highlighting music's necessity in our daily lives. Additionally, this study emphasizes the vital role of virtual music communities in fostering social connections, even amidst physical isolation, further underscoring the enduring relevance of music in these challenging times. This research contributes to the expanding knowledge of music's impact on well-being, offering a holistic perspective encompassing spiritual, emotional, social, and cognitive dimensions. It enriches existing music psychology theories and invites further exploration into the mechanisms underpinning music's diverse effects. These insights have practical implications for fields such as mental health, education, and remote work, where music can be utilized as an essential tool for stress reduction and emotional regulation. This is highlighted further in the Suggested songs that can help sought the mind, body, spirit and soul. Looking ahead, future research could delve deeper into the long-term impact of music engagement on well-being and explore the universality of music's benefits through cross-cultural studies. Overall, music, as illuminated by this study, stands as a timeless and indispensable companion, offering solace, inspiration, vitality, and connection in the face of any contemporary challenges.

ACE2 impact on the severity of COVID-19 is widely discussed but still controversial. To estimate its role in aspects of the main risk factors and comorbidities, we involved post-COVID-19 patients in Ternopil region (Ukraine). Recruitment period was July 2020 to December 2021. Medical records, treatment modalities and outcomes were recorded and analyzed. Serum human ACE2 protein was measured with Cusabio ELISA kits (Houston, TX, USA). Statistical analysis was performed with SPSS21.0 software (SPSS Inc., Chicago, IL, USA). The level of ACE2 serum protein was significantly higher (p < 0.001) in patients with mild symptoms compared to more severe course of disease, and inversely had changed from 1 to 90 days after recovery. In patients with mild COVID-19, ACE2 level significantly decreased over time, while among critical patients, it increased by 34.1percent. Such results could be explained by ACE2 shedding from tissues into circulation. Loss of the membrane-bound form of the enzyme decreases the virus entry into cells. Our studies did not identify any sex-related ACE2 serum levels correlation. The most common comorbidities were hypertension, cardiovascular diseases, respiratory diseases and diabetes mellitus. All comorbidities except respiratory diseases contribute to the severity of disease and correlate with ACE2 blood serum level.

The long-term laboratory aspects of the effects of COVID-19 on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical-laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older hospitalised in the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. Inflammatory markers such as ferritin > 300 U/L were observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST > 25 U/L, and GGT ≥ 50 or 32 U/L were associated with ALT > 29 U/L. There was a correlation between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID, especially in those hospitalised in the acute phase. In addition, ALT > 29 U/L was associated with other markers of liver injury, such as LDH, GGT, and ferritin.

In the Valpolicella area (Verona - Italy) Vitis vinifera cv. Corvina is the main grape variety used to produce Amarone wine. Before starting the winemaking process, the Corvina grapes are stored in a withering (i.e., dehydrating) warehouse until about 30% of the berry weight is lost (WL). This practice is followed to have the chemical metabolites concentrate in the berry and enrich the Amarone wine in aroma and antioxidant compounds. In compliance with the guidelines and strict Amarone protocol set by the Consorzio of Amarone-Valpolicella, withering must be carried out by setting the grapes in a suitable environment, either under controlled relative air humidity (RH) conditions and wind speed (WS) – no temperature modification is to be applied – or, following the traditional methods, in open-air natural environmental conditions. In general, the two processes have different dehydration kinetics due to the different conditions in terms of temperature, RH, and WS, which affect the accumulation of sugars and organic acids and the biosynthesis of sec-ondary metabolites such as stilbenes and glycoside aroma precursors. For this study, the two grape-withering processes were carried out under controlled (C) and not-controlled (NC) condi-tions and the final compositions of the Corvina dried grapes were compared also to evaluate the effects on the organoleptic characteristics of Amarone wine. The findings highlighted differences between the two processes mainly in terms of the secondary metabolites of the dried grapes, which affect the organoleptic characteristics of Amarone wine.

Post-Shoah Christology is embedded in the unique relationship of Jews and Christians, especially Jesus’ Jewishness and the Jewish roots of Christianity, as well as Christian moral failures towards Jews before and during the Shoah. Essential for contemporary Christianity, a vibrant post-Shoah Christology confronts three main challenges, each demanding a different response. The first challenge is the reality that soon there will be no more first-generation witnesses to the Final Solution. Such is an inevitable challenge that has to be faced and prepared for. Religious pluralism is the second challenge, and includes a number of related threads, yet should ultimately be embraced. The third challenge is the (inevitable?) loss of memory, passion, and urgency, a willful forgetfulness by Christians towards the importance of the Jewish-Christian relationship, and especially, Christian failure in the Shoah. This challenge demands robust refutation and ongoing struggle. Before addressing these challenges, I will first further define and highlight the need for a post-Shoah Christology and will conclude this article with three general and three concrete hopes for a viable post-Shoah Christology.

Two ligands, 1, 3-bis(4-carboxyphenyl)imidazolium chloride and 4, 4՛-bipyridine, were employed to prepare nickel and zinc azolium based MOFs, 1 and 2 by the mixed ligand solvothermal approach. The positively charged azolium moieties in the imidazolium linker resulted in a charged environment in the as-synthesized frameworks. As a result, 1 and 2 demonstrated preferential adsorption of CO2 over methane molecules in the gas phase adsorption due to the higher quadruple moment of CO2, which interacts more with the positively charged frameworks. Besides, in aqueous media, 1 and 2 exhibited incredible adsorption efficiency for anionic dyes. In the following, MOF 1 was metallated at the carbene site of the azolium linker to generate the novel heterogeneous catalyst 1-Pd, which was successfully applied for Sonogashira and Suzuki-Miyaura coupling reactions without losing its activity after three cycles.

n our previous paper, we showed that the so-called quantum entanglement also exists in classical mechanics. The inability to measure this classical entanglement was rationalized with the definition of a classical observer which collapses all entanglement into distinguishable states. It was shown that evidence for this primary coherence is Newton’s third law. However, in reformulating a "classical entanglement theory" we assumed the existence of Newton’s second law as an operator form where a force operator was introduced through a Hilbert space of force states. In this paper, we derive all related physical quantities and laws from basic quantum principles. We not only define a force operator but also derive the classical mechanic's laws and prove the necessity of entanglement to obtain Newton’s third law.

Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed post-mortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients’ ages ranged from 59 to 81, including 3 males and 1 female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the post-mortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.

In 2010, Parties to the Convention on Biological Diversity (CBD) adopted the Strategic Plan for Biodiversity 2011–2020 to address the loss and degradation of nature. Subsequently, most biodiversity indicators continued to decline. Nevertheless, conservation actions can make a positive difference for biodiversity. The emerging Post-2020 Global Biodiversity Framework has potential to catalyze efforts to ‘bend the curve’ of biodiversity loss. Thus, the inclusion of a goal on species, articulated as Goal B in the Zero Draft of the Post-2020 Framework, is essential. However, as currently formulated, this goal is inadequate for preventing extinctions, and reversing population declines; both of which are required to achieve the CBD’s 2030 mission. We contend it is unacceptable that Goal B could be met while most threatened species deteriorated in status and many avoidable species extinctions occurred. We examine the limitations of the current wording and propose an articulation with robust scientific basis. A goal for species that strives to end extinctions and recover populations of all species that have experienced population declines, and especially those at risk of extinction, would help to align actors towards the transformative actions and interventions needed for humans to live in harmony with nature.

We aimed to evaluate the safety of maternal Tdap we assessed health events by examining the difference in birth and hospital-related outcomes of infants with and without fetal exposure to Tdap. This was a retrospective cohort study using linked administrative datasets. The study population were all live-born infants in New Zealand (NZ) weighing at least 400 grams at delivery and born to women who were eligible for the government funded, national-level vaccination program in 2013. Infants were followed from birth up to one year of age. There were a total of 69,389 eligible infants in the cohort. Of these, 8,299 infants were born to 8,178 mothers exposed to Tdap (12%), primarily between 28-38 weeks gestation as per the national schedule. Among the outcomes, we found a reduced risk for moderate to late preterm birth, low birth weight, small for gestational age, large for gestational age, respiratory distress syndrome, transient tachypnea of newborn, tachycardia or bradycardia, haemolytic diseases, other neonatal jaundice, anaemia, syndrome of infant of mother with gestational diabetes, and hypoglycemia in infants born to vaccinated mothers. There was no association between maternal Tdap and stillbirth, infant Apgar score at 5 minutes after birth, microcephaly, asphyxia, sepsis or infection, or hypoxic ischemic encephalopathy. Infant exposure to Tdap during pregnancy was associated with a higher mean birthweight (not clinically significant) and higher odds for ankyloglossia and neonatal erythema toxicum diagnoses. There were insufficient observations to allow examination of the effect of Tdap on extreme preterm and very preterm birth, and infant death. Overall, we found no outcomes of concern associated with the administration of Tdap during pregnancy.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

Soccer is the most played sport worldwide, with over 265 million participants. It is an incredibly demanding sport, with many different technical skills and physical loads placed on the body. This makes post-match recovery strategies amongst high level soccer players of great importance. The aim of this review is to summarize the existing literature on stretching for post-match recovery, examining its relation to injury prevention, Delayed Onset Muscle Soreness (DOMS), and performance. Scientific evidence of the highest quality and relevance was extracted and reviewed. Despite its common practice, evidence does not support static stretching as a modality to improve recovery post-match amongst soccer players. Larger trials with important outcome measures are needed to determine if a post-match stretching regimen to facilitate recovery exists.

The current urban environment is faced with the potential threat of frequent natural disasters, and the sustainable development of post-disaster community has become a global issue. As an intrinsic motivation influencing the social interaction and capital operation of community, social network is an important mechanism promoting such sustainable development. However, the difference in social network caused by different member structure, spatial arrangement and management mechanism of post-disaster communities in different reconstruction modes has influenced such sustainable development process. Therefore, reasonable selection of reconstruction mode is crucial. This paper applied analytic hierarchy process to comprehensively measure and compare the social network strength in post-disaster communities in the four reconstruction modes adopted by the government of China, i.e. unified planning and unified construction, unified planning and independent construction, in situ reconstruction and relocation resettlement, with communities after the 2008 Sichuan earthquake in Chengdu, China as study objects from the perspective of three social relations (the relations between residents and residents, residents and managers, and residents and servers). The results showed that strong connections are generally presented in the social network of post-disaster communities in unified planning modes, that the strength is significantly higher than that of those in non-unified planning modes, and that the strength of UPIC communities is the highest. Meanwhile, government intervention, residents’ free participation and market operation are positively correlated to government trust, community interaction and community service respectively. The positive impact of government intervention is the most significant, but it has a peak value. No government management and excessive government intervention will exert negative impacts. The coordination of government, society and market is the key contents of post-disaster community reconstruction. The reconstruction modes based on “government leadership, resident participation and market operation” may become a feasible path for such sustainable development.

Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability and function. Here, we summarize these key regulatory events, with emphasis on how these affect their multi-functionality in health and disease.

Background: Heart failure (HF) remains a challenging healthcare issue, necessitating innovative therapies like cardiac resynchronization-defibrillation therapy (CRT-D). However, defining CRT-D responders lacks uniformity, impeding effective clinical evaluation. This study explores diverse CRT-D responder definitions, encompassing functional, echocardiographic, and laboratory criteria. Materials & Methods: A single-center study involving 132 CRT-D patients scrutinized responder criteria, including NYHA stage, LVEF increase, and proBNP decrease. Statistical analyses, such as Kaplan–Meier curves and Cox hazard regression, were employed to evaluate responder characteristics and survival outcomes. Results: Responder rates varied across criteria, revealing nuanced patient profiles. CRT-D responders, defined by NYHA decrease, LVEF increase, or proBNP decrease, exhibit improved survival rates after 2 and 3 years (p < 0.050). Young age, absence of recent myocardial infarction, and normal right ventricular, echocardiographic parameters emerge as predictors for positive response. In part, drug-based HF therapy correlates with increased responder rates. Cox regression identified LVEF ≥ 5% and proBNP decrease ≥ 25% as independent predictors of extended survival. Conclusions: CRT-D responder definitions exhibit considerable variability, emphasizing the need for a nuanced, patient-centered approach. Factors like right ventricular function, drug therapy, atrial fibrillation, and renal function influence responses. The study enriches our understanding of CRT-D response, contributing to the foundation for personalized HF management.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterized by multiple risk factors and associated conditions. HFpEF prevalence is rising, and its prognosis remains poor after the first hospitalization. Using a two-hit HFpEF murine model, we aimed at studying cardiac reverse remodelling after stopping the causing stress (Angiotensin II [AngII]) and a high-fat diet [HFD]; MHS) and introducing voluntary exercise. We studied in young male and female C57Bl6/J mice fed or not with an HFD (60% calories from fat) the cardiac response to AngII (1.5 mg/kg/day for 28 days). Then, MHS was stopped, and VE was started for another four weeks (RR). We studied the effects of MHS and RR on the circulatory microRNA (miR) profile (miRNome) and the myocardial miRNome to characterize the cardiac and non-cardiac response of small RNAs. AngII alone and MHS but not the HFD caused cardiac hypertrophy (CH), left ventricular (LV) concentric remodelling and left atrial enlargement in male mice. HFD-induced CH and LV concentric remodelling only in female mice. Four weeks after RR, CH, LV concentric remodelling and atrial enlargement were reversed. We performed bulk circulatory and LV miR sequencing. We did not observe differences linked to biological sex. RR restored normality for circulatory miRNome, whereas LV miRNome remained relatively similar to the one after MHS. Among the 25 most abundant circulatory miRs, ten were modulated by MHS (9 upregulated). In the LV, 8 of the 25 most abundant miR were upregulated by MHS, and 10 were downregulated. MiRNomes from AngII, HFD or MHS shared many common modulated miRs (32), suggesting that the overall response of organs producing the bulk of circulatory small non-coding RNA was similar even for seemingly different stress.

This report elucidates the first surgical correction of an infundibular muscular ventricular septal defect (VSD) in a one-year-old Ragdoll cat via cardiac arrest using cardiopulmonary bypass, a method that is rarely used in feline cardiac surgery. VSDs can lead to congestive heart failure and pulmonary hypertension, particularly in patients with large shunts. This case involved a VSD that was atypically located and classified under the Soto classification instead of the standard Kirklin classification. Detailed echocardiography revealed that the defect required intervention owing to left heart and main pulmonary artery enlargement. Despite the VSD being located on the contralateral side, as anticipated in the preoperative examinations, the choice of median sternotomy allowed for successful closure of the defect. Conversely, the insertion of two cannulas into the ascending aorta resulted in damage to the adjacent thoracic duct, causing transient chylothorax, which resolved with conservative treatment. Cardiac arrest induced by a cardioplegic solution facilitated the surgical procedure, although it has led to anemia in cats. However, on postoperative day 490, the patient exhibited only minor residual shunting with normalized heart size, and remained healthy. This technique appears to be a viable treatment option for congenital heart disease in cats.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies using various types of stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity of unlimited proliferation and differentiation to cardiomyocytes, are a promising cell source for myocardial regeneration therapy. This review discusses the current status of cardiac regenerative therapy using iPSCs.

Background and Objectives Transpulmonary thermodilution has gained interest in recent years. It measures cardiac output (CO), stroke volume (SV), but also calculates global end diastolic indexed volume (GEDVI), and global ejection fraction (GEF). GEDVI is a static variable of cardiac preload. GEF provides information regarding cardiac function. GEF algorithm depends on SV and GEDVI. Therefore, in hypovolemic patients with decreased preload, SV or GEDVI could be decreased, and lead to altered GEF. The aim of our work was to evaluate whether impairment in GEDVI and SV may constitute a limitation for the interpretation of GEF in hypovolemic patients. A secondary objective was to determine factors independently associated with impaired GEF. Materials and Methods A retrospective study was conducted. Statistical analysis was performed by means of Mann Whitney and student t test. To determine correlation between GEF with SV, or GEF with GEDVI Pearson's coefficient was used. To determine factors independently associated with the presence of impaired GEF, binary logistic regression was performed. Results We included 113 patients with shock. Differences in mortality were detected in GEF (21[16-28] survivors versus 18 in non survivors[11-26]; p= 0.01). 38(34%) patients had hypovolemia. 44(39%) of them had depressed GEF values. Hypovolemic patients had lower GEF values than non-hypovolemic patients (16 [12-22] vs 20 [15-27]; p=0.01). Both SV and GEDVI had a statistically significant correlation with GEF (SV (Pearson's r 0.74; (p=0.00)) and GEDVI (Pearson's r -0.25; (p=0.00)). The only factors independently associated with low GEF were low SV and low GEDVI. Conclusion Hypovolemic patients frequently show low GEF values. We found correlation between SV and GEDVI with GEF. Low SV and low GEDVI were associated with low GEF. This could constitute a limitation in the interpretation of GEF and cardiac pump function. Hypovolemic patients could have low GEF without implying disorders in cardiac contractility.

The aim of this retrospective study was to identify myocardial injury after COVID-19 inflamation and to explore whether myocardial damage could be a possible cause of the persistent symptoms following COVID-19 infection in previously healthy individuals. The study included 139 patients who were enrolled between January-June 2021, mean age 46.7±15.2 years, 68 were men, 71 were women without known cardiac or pulmonary diseases. All patients underwent clinical work up, lab. analyses, cardiac ultrasound, and CMR on 1.5 T scanner using a recommended protocol for morphological and functional assessment before and after contrast media application with multi-parametric sequences. In 39% of patients late gadolinium enhancement (LGE) was found as a sign of myocarditis. Fibrinogen was statistically significantly higher in patients with LGE than in those without LGE, (4.3±0.23 vs 3.2±0.14g/L, p<0.05; respectively), as well as D-dimer (1.8±0.3 vs 0.8±0.1 mg/L FEU). Also troponin was statistically significantly higher in patients with myocardial LGE (13.1±0.4ng/L) compared to those with normal myocardium (4.9±0.3ng/L, p<0.001). We demonstrated chest pain, fatigue and elevated troponin to be independent predictors for LGE. Septal LGE was shown to be predictor for arrhythmias. The use of CMR is a potential risk stratification tool in evaluating outcomes following COVID-19 myocarditis.

Cardiac amyloidosis is caused by amyloid fibrils that deposit in the myocardial interstitium, causing restrictive cardiomyopathy and eventually death. The electromechanical, inflammatory, and autonomic changes due to amyloid deposition result in arrhythmias. Atrial fibrillation is by far the most common arrhythmia. Rate control strategy is generally poorly tolerated due to restrictive filling physiology and heart rate dependance, favoring adoption of rhythm control strategy. Anticoagulation for stroke prophylaxis is warranted irrespective of CHA2DS2Vasc score in patients with favorable bleeding profile; data on left appendage closure devices is still insufficient. Ventricular arrhythmias are also not uncommon and the role of implantable cardioverter-defibrillator in cardiac amyloidosis is controversial. There is no evidence of improvement in outcomes when used for primary prevention in these patients. Bradyarrhythmia is most commonly associated with sudden cardiac death in cardiac amyloidosis. Pacemaker implantation can help provide symptomatic relief but does not confer mortality benefit.

Background: We aimed to evaluate whether baseline GLS and NT-proBNP and their changes after cardiac resynchronization therapy (CRT) can predict the long-term clinical outcomes and the echocardiographic-based response to CRT (defined by 15% relative reduction in left ventricular end-systolic volume). Methods: We enrolled 143 patients with stable, ischemic heart failure (HF) undergoing CRT-D implantation. NT-proBNP and echocardiogram were obtained before and 6 months after. The patients were followed-up (median: 58 months) for HF-related deaths and/or HF hospitalizations (primary endpoint) or HF-related deaths (secondary endpoint) Results: 84 patients achieved the primary and 53 the secondary endpoint, while 104 patients were considered as CRT-responders and 39 as non-responders. At baseline, event-free patients had higher absolute GLS values (p&lt;0.001) and lower NT-proBNP serum levels (p&lt;0001) than those achieving primary endpoint. A similar pattern was observed in favor of CRT-responders vs non-responders. In Cox regression analysis, lower baseline absolute GLS value (HR=0.77;95%CI, 0.51-1.91; p=0.002), higher baseline NT-proBNP levels (HR=1.55;95%CI, 1.43-2.01;p=0.002) and diabetes (HR=1.27;95%CI, 1.12-1.98;p=0.003) were associated with lower incidence of primary endpoint. Conclusions: In HF patients undergoing CRT-D, baseline GLS and NT-proBNP concentrations may serve as prognostic factors, while they may predict the echocardiographic-based response to CRT.

Fatal hemoptysis secondary to severe pulmonary veins stenosis is an exceptional late complication of radiofrequency ablation for atrial fibrillation. We report the case of a 53-year-old male with a history of atrial fibrillation treated by radiofrequency ablation and admitted in our center 6 months after the initial procedure because of aggravating dyspnea and fatigability. Transthoracic echocardiography showed moderate dilation of right heart cavities, severe pulmonary hypertension, and a turbulent flow in superior pulmonary veins. The cardiologist suspected pulmonary vein(s) stenosis and cardiac computed tomography (CT) angiography was performed with findings of severe stenosis of the right superior, right inferior and left inferior pulmonary veins, near-occlusion of the left superior pulmonary vein and the vein draining the apical segment of the right lower lobe. The CT scan also revealed soft tissue attenuation of the mediastinum posterior to the left atrium suggesting fibrosing mediastinitis together with parenchymal findings consistent with pulmonary venooclusive disease and an area of hemorrhagic infarction. Fatal hemoptysis occurred 3 days after the evaluation before any treatment was attempted. In conclusion, severe pulmonary stenosis remains a rare but severe complication of radiofrequency ablation. Prevention is the key element together with an early diagnosis as the entity is potentially life-threatening.

Background: Galectin-3 (Gal-3) overexpression is associated with fibroblastic proliferation and the production of collagen, resulting in increased cardiac fibrosis and remodelling. Aim of the study was to investigate on the expression of Gal-3 in hypertrophic hearts. We examined 19 surgical specimens taken from interventricular septum of 8 patients with Tetralogy of Fallot, 4 patients with aortic valve stenosis, 1 cardiac explant affected from dilated cardiomyopathy, and 6 myocardial biopsies of patients submitted to heart transplantation. Methods: All the samples were routinely processed, stained with Hematoxylin-Eosin, Trichromic stain and elastic fiber stain and selected by having the morphological features of myocardial hy-pertrophy: myocytolysis, nuclear pleomorphism, interstitial fibrosis. Results: At immunohistochemistry, myocardial fibers showed cytoplasmic expression of Gal-3 in the 4 patients with aortic valve stenosis (diffuse in 3 and mild in 1), in the 1 patient with cardiac explant (mild) and in the 4/6 transplanted hearts (mild and focal in 3 and diffuse in 1). The 8 patients affected from Tetralogy of Fallot and 2 patients with transplanted hearts resulted negative. Conclusions: The results agreed with the hypothesis that Gal-3 may play a role in cardiac hyper-trophy; its expression in myocardial fibers is not related with the morphological aspects as suggested by the absence in pediatric cases. The presence in myocardial biopsies taken from transplanted hearts would suggest a possible role in predicting clinical outcome of such patients.

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic method. The multitude of different etiological factors, the diversity of the clinical picture and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated diseases that in their natural course can lead to myocardial involvement, but also the iatrogenic cause of myocarditis due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, changes in ECG and echocardiography has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive diagnostic gold standard for diagnosis and clinical follow-up of thses patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening patients with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.

The metabolism of lipoproteins, which regulates the transit of the lipid to and from tissues, is crucial to maintaining cholesterol homeostasis. Cardiac remodeling is referred to as a set of molecular, cellular, and interstitial changes that, following injury, affect the size, shape, function, mass, and geometry of the heart. Acetyl coenzyme A (acetyl CoA), which can be made from glucose, amino acids, or fatty acids, is the precursor for the synthesis of cholesterol. In this article, authors explain concepts behind cardiac remodeling, its clinical ramifications, and the pathophysiological roles played by numerous various components, such as cell death, neurohormonal activation, oxidative stress, contractile proteins, energy metabolism, collagen, calcium transport, inflammation, and geometry. The levels of cholesterol are traditionally regulated by two biological mechanisms at the transcriptional stage. First, the SREBP transcription factor family regulates the transcription of crucial rate-limiting cholesterogenic and lipogenic proteins, which in turn limits cholesterol production. Immune cells become activated, differentiated, and divided, during an immune response with the objective of eradicating the danger signal. In addition to creating ATP, which is used as energy, this process relies on metabolic reprogramming of both catabolic and anabolic pathways to create metabolites that play a crucial role in regulating the response. Because of changes in signal transduction, malfunction of the sarcoplasmic reticulum and sarcolemma, impairment of calcium handling, increases in cardiac fibrosis, and progressive loss of cardiomyocytes, oxidative stress appears to be the primary mechanism that causes the transition from cardiac hypertrophy to heart failure. De novo cholesterol production, intestinal cholesterol absorption, and biliary cholesterol output are consequently crucial processes in cholesterol homeostasis. In the article's final section, the pharmacological management of cardiac remodeling is explored. The route of treatment is explained into different steps: including, promising, and potential strategies. This chapter offers a brief overview of the history of the study of cholesterol absorption as well as the different potential therapeutic targets.

Cardiac regeneration is a critical endeavor in the treatment of heart diseases, aimed at repairing and enhancing the structure and function of damaged myocardium. This review offers a comprehensive overview of current advancements and strategies in cardiac regeneration, with a specific focus on regenerative medicine and tissue engineering-based approaches. Stem cell-based therapies, which involve the utilization of adult stem cells and pluripotent stem cells hold immense potential for replenishing lost cardiomyocytes and facilitating cardiac tissue repair and regeneration. Tissue engineering also plays a prominent role employing synthetic or natural biomaterials, engineering cardiac patches and grafts with suitable properties, and fabricating upscale bioreactors to create functional constructs for cardiac recovery. These constructs can be transplanted into heart to provide mechanical support and facilitate tissue healing. Additionally, the production of organoids and chips that accurately replicate the structure and function of the whole organ is an area of extensive research. Despite significant progress, several challenges persist in the field of cardiac regeneration. These include enhancing cell survival and engraftment, achieving proper vascularization, and ensuring the long-term functionality of engineered constructs. Overcoming these obstacles offering effective therapies to restore cardiac function could improve the quality of life for individuals with heart diseases.

The non-coding RNAs (ncRNAs) are indispensable for controlling genes and genetic programming during development, as well as for health and cardiovascular diseases. Cardiac arrhythmia is a frequent cardiovascular disease, which has a complex pathology. Recent studies have shown that ncRNAs are also associated with cardiac arrhythmias. Many non-coding RNAs and/or genomes have been reported as a genetic background for cardiac arrhythmias. Arrhythmias may be affected by several functional and structural changes in the myocardium. Therefore, ncRNAs might be indispensable regulators of gene expression in cardiomyocytes, which could play a dynamic role in regulating the stability of cardiac conduction and/or in the remodeling process. Although it remains almost unclear how ncRNAs regulate the expression of molecules for controlling the cardiac conduction and/or in the remodeling process, gut microbiota and immune system within the intricate networks might be involved in the regulatory mechanisms. This study would discuss them and provide a research basis for ncRNAs modulation, which might support the development of emerging innovative therapies against cardiac arrhythmias.

Background: Trans-septal endocardial left ventricle lead placement is an alternative technique used capture the left ventricular endocardially but it is use is limited due lack of evidence, practice uptake and clinical trials. we evaluated the efficiency of the procedure, post procedural complication rate, rate of thromboembolic events as well as changes in echocardiographic parameters, brain natriuretic peptide (BNP) level and the New York Heart Association (NYHA) class. Results: TSLV lead implant is safe, improves ejection fraction, LVEDV, LVESV, LVIDd. Significantly reduces NTproBNP levels and NYHA class. Stroke rate was reported only in one patient (9%), noticeably, this particular patient was on DOAC rather than anti-vitamin K antagonists. In this group, patients, who were on Warfarin , were not reported to have any thrombo-embolic events. Discussion: Trans-septal endocardial LV lead implant in patients with a failed CS approach remains a viable alternative however, there is a higher risk of stroke amongst these patients, as well as more procedure related risk of complications compared to conventional CRT. The data analysis demonstrates that patients undergoing a TSLV lead implant due to a failed trans-venous approach have more advanced heart failure, defined by their higher NYHA class compared to conventional trans-venous CRT implant groups. Their pre TSLV implant, echocardiographic parameters are also worse compared to trans-venous CRT implant group

Background: In recent years, the assessment and guidance of cardiopulmonary resuscitation (CPR) quality using noninvasive and invasive monitoring techniques have been increasingly recommended. In this study, we introduce a new physiological monitoring system that simultaneously measures arterial pressure (AP), venous pressure (VP), and cerebral tissue oxygen saturation (SctO2) during CPR. Methods: This prospective observational study was conducted at a single center (Kagoshima City Hospital). Adult out-of-hospital patients aged ≥18 years with an intravenous femoral arterial line, venous line, and SctO2 monitor were included. We measured femoral arterial pressure (FAP) and femoral venous pressure (FVP) invasively if catheters were immediately inserted into the femoral artery and vein for potential candidates who require interventions such as extracorporeal cardiopulmonary resuscitation but did not receive such interventions as a result. Results: We observed several representative cases that provided the following insights: We presented several cases, including two patients with significant increases in FVP and low SctO2 values, and in both cases, return of spontaneous circulation (ROSC) was not achieved. In contrast, we also presented two cases in which CPR resulted in higher FAP compared to FVP and an upward trend in SctO2 values was observed, and both instances achieved ROSC. Conclusion: We presented a simultaneous physiological monitoring system that can monitor AP, VP, and SctO2 during CPR. Further case accumulations will be necessary to assess the variations in hemodynamic status during CPR and the association between each hemodynamic status and outcomes after cardiac arrest.

Introduction: The choice of Cardiac Preservation Solution (CPS) for myocardial protection at the time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm Heart Transplantation (HTx) outcomes. Thus, we retrospectively analyzed our adult HTx performed with two different CPS, during a period of 12 years, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score. Methods: From January 2009 to December 2020, 154 adult HT were performed in our hospital. Patients were divided in two groups according to the CPS used: St. Thomas (n=75, group P 1) and HTK-Custodiol (n=79, group P 2). The choice of CPS was related to an institutional policy; from 2009 to 2015, St. Thomas solution was exclusively used, and after that, HTK-Custodiol alone. Results: There was no significant difference between the two groups in terms of preoperative and intraoperative features. Postoperatively, the Custodiol group showed significantly lower inotropic score (p&lt;0.0001), mean rejection score (p= 0.036) and 30 days mortality (p=0.0068). The use of HTK-Custodiol was the only variable that improved midterm survival (HTK-Custodiol vs St Thomas, HR= 0.20 (95% CI: 0.069 -0.6) p=0.0039). Conclusion: In our single center experience, using HTK-Custodiol as myocardial protection during heart procurement leads to improved outcomes after HTx, including postoperative inotropic score, rejection score, 30-days mortality and midterm survival.

Background: It remains unclear whether transfer RNA-derived small RNAs (tsRNAs) play a role in pathological cardiac hypertrophy (PCH). We aimed to clarify the expression profile of tsRNAs and disclose their relationship to the clinical phenotype of PCH and the putative role. Methods: Small RNA sequencing was performed in the plasma of PCH patients and healthy volunteers. In a larger sample size and angiotensin Ⅱ (Ang II)-stimulated H9c2 cells, the data were validated by real-time qPCR. The atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were examined in Ang II-stimulated H9c2 cells. The role of tsRNAs in the pathogenesis of PCH was explored by bioinformatics analysis. Results: A total of 4185 differentially expressed tsRNAs were identified, of which 4 and 5 tsRNAs were observed to be significantly differentially upregulated and downregulated expressed. Of the 5 down-regulated tsRNAs, 4 of them were verified to be significantly down-regulated in the larger sample group, among which tRF-30-3JVIJMRPFQ5D, tRF-16-R29P4PE, tRF-21-NB8PLML3E, and tRF-21-SWRYVMMV0 had areas under the curve to diagnose concentric hypertrophy. The 4 down-regulated tsRNAs were negatively correlated with left ventricular posterior wall dimensions in PCH patients (r=-0.4227; r=-0.4517; r=-0.5567; r=-0.4223). The levels of ANP and BNP as well as cell size were decreased in Ang II-stimulated H9c2 cells with 21-NB8PLML3E mimic transfection. Bioinformatics analysis revealed that the target genes of tRF-21-NB8PLML3E were mainly enriched in the metabolic pathway and involved in the regulation of ribosomes. Conclusion: The plasma tsRNAs tRF-21-NB8PLML3E might be considered biomarkers in patients with PCH with early screening potential.

Fabry disease (FD) is a X-linked inheritable storage disease caused by deficiency of al-pha-galactosidase causing lysosomal overload of sphingolipids. FD cardiomyopathy is character-ized by left ventricular (LV) hypertrophy and should be considered in differential diagnosis with all the other causes of LV hypertrophy. An early diagnosis of FD is very important because the enzyme replacement therapy (ERT) may change the fate of patients by blocking both cardiac and systemic involvement and improving prognosis. Diagnosis may be relatively easy in young patients with the typical signs ans symptoms of FD, but in male patients with late onset of disease and in females, diagnosis may be very challenging. Morphological and functional aspects are not specific for FD, which cannot be diagnosed or excluded by echocardiography. Cardiac magnetic resonance (CMR) with tissue characterization capability, is the preferred technique for the differential diagnosis of LV hypertrophy. The finding of decreased myocardial T1 value in LV hypertrophy is very specific for FD. Late gadolinium enhancement (LGE) is found in late stage of disease but it is useful to predict the cardiac response to ERT and to stratify the prognosis.

Hyperleptinemia potentiates the effects of many atherogenic factors, such as inflammation, platelet aggregation, migration, hypertrophy, proliferation of vascular smooth muscle cells, and endothelial cell dysfunction. The present study analysed the effects of long-term hyperleptinemia in an in vivo myocardial ischemia-reperfusion model to demonstrate whether the in vivo deleterious effect also affects cardiac structure and function. Rats by were subcutaneously administered leptin for 8 days to estimate the involvement of the JAK/STAT pathway. Data from 58 male Wistar rats were included in the final analysis. Myocardial infarction (MI) was modelled by the 30-minute ligation of the main left coronary artery followed by 120-minute reperfusion. Hemodynamic measurements, electrocardiography monitoring, echocardiography, myocardial infarct size and area at risk, blood biochemical parameters, leptin, IL-6, TNF-alpha, FGF-21, and cardiomyocyte morphology were measured. Statistical analyses were performed using IBM SPSS Statistics v.26. Seven-day hyperleptinemia in rats led to increased an blood pressure and heart rate, myocardial hypertrophy, impaired LV function, an increased frequency of ischemic arrhythmias, dyslipidaemia, systemic inflammation, and an increased size of induced myocardial infarction. The blockade of the JAK/STAT signalling pathway effectively reversed the negative effects of leptin, including increased blood pressure and total cholesterol.

The ryanodine receptor (RyR) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal and cardiac muscles and plays a key role in excitation-contraction coupling. The activity of the RyR is regulated by many intracellular factors such as divalent cations (Ca2+ and Mg2+), nucleotides, associated proteins, and reactive oxygen species. Since these intracellular factors change depending on the condition of the muscle, e.g., exercise, fatigue, or disease states, the RyR channel activity will be altered accordingly. In this review, we describe how the RyR channel is regulated under various conditions and discuss the possibility that the RyR acts as a sensor for change in the cellular environment of muscles.

Several performance-enhancing or ergogenic drugs have been linked to both significant adverse cardiovascular effects and increased cardiovascular risk. Even with increased scrutiny on the governance of performance-enhancing drugs (PEDs) in professional sport and heightened awareness of the associated cardiovascular risk, there are some who are prepared to risk their use to gain competitive advantage. Caffeine is the most commonly consumed drug in the world and its ergogenic properties have been reported for decades. Thus, the removal of caffeine from the World Anti-Doping Agency (WADA) list of banned substances, in 2004, has naturally led to an exponential rise in its use amongst athletes. The response to caffeine is complex and influenced by both genetic and environmental factors. Whilst the evidence may be equivocal, the ability of an athlete to train longer or at a greater power output cannot be overlooked. Furthermore, its impact on the myocardium remains unanswered. In contrast, anabolic steroids are recognised PEDs that improve athletic performance, increase muscle growth and suppress fatigue. Their use, however, comes at a cost, afflicting the individual with several side effects, including those that are detrimental to the cardiovascular system. This review addresses the effects of the two commonest PEDs, one legal, the other prohibited, and their respective effects on the heart, as well as the long-term implications.

A newly identified novel coronavirus named as severe acute respiratory syndrome-related coronavirus2 (SARS‐CoV 2) has given rise to the global pandemic. SARS-CoV2 which causes coronavirus disease 2019 (COVID-19), is a positive-stranded RNA virus with nucleocapsid. It binds to host angiotensin-converting enzyme2 (ACE2) receptor through surface glycoprotein (S protein). These ACE 2 receptors are attached to the cell membranes of many organs. Thus, COVID-19 does not only result in acute respiratory distress syndrome but also affects multiple organ systems, requiring a multidisciplinary approach to manage this disease. COVID-19 can damage the myocardial cells and result in fulminant myocarditis, acute cardiac injury, cardiomyopathy, heart failure, cardiogenic shock, or arrhythmia. COVID-19 seeds harmful immune response through cytokine storm leading to indirect organ damage. In this literature review, the available data is comprehended regarding cardiovascular complications in COVID-19, and the correlation of biomarkers with the disease activity is discussed. This literature review also highlights the important treatment options and outcomes of the individual study.

The cardioprotective effects of volatile anesthetics versus total intravenous anesthesia (TIVA) are controversial, especially in patients undergoing non-cardiac surgery. Using current generation high-sensitivity cardiac troponin (hs-cTn), we aimed to evaluate the effect of anesthetics on the occurrence of myocardial injury after non-cardiac surgery (MINS). From February 2010 to December 2016, 3555 patients without preoperative hs-cTn elevation underwent non-cardiac surgery under general anesthesia. Patients were grouped according to anesthetic agent; 659 patients were classified into a propofol-remifentanil total intravenous anesthesia (TIVA) group, and 2896 patients were classified into into a volatile group. To balance the use of remifentanil between groups, a balanced group (n=1622) was generated with patients who received remifentanil infusion in the volatile group, and two separate comparisons were performed (TIVA vs. volatile and TIVA vs. balanced). The primary outcome was occurrence of MINS, defined as rise of hs-cTn I ≥ 0.04 ng/mL within postoperative 48 hours. The secondary outcomes were 30-day mortality, postoperative acute kidney injury (AKI), and adverse events during hospital stay (mortality, type I myocardial infarction (MI), and new-onset arrhythmia). In propensity-matched analyses, the occurrence of MINS was lower in the TIVA group compared to the volatile group (OR 0.642; 95% CI 0.450-0.914; p = 0.014). However, after balancing the use of remifentanil, there was no difference between groups in the risk of MINS (OR 0.832; 95% CI 0.554-1.251; p-value = 0.377). There were no significant associations between the two groups in type 1 MI, new-onset atrial fibrillation, in-hospital and 30-day mortality before and after balancing the use of remifentanil. However, the incidence of postoperative AKI was lower in the TIVA group (OR 0.362; 95% CI 0.194-0.675; p-value = 0.001). After balancing the use of remifentanil, volatile anesthesia and TIVA showed comparable effects on MINS in patients undergoing non-cardiac surgery without preoperative myocardial injury. Further studies are needed on the benefit of remifentanil infusion.

Cardiac β₂-adrenergic receptors (ARs) are known to inhibit collagen production and fibrosis in cardiac fibroblasts and myocytes. The β₂AR is a Gs protein-coupled receptor (GPCR) and, upon its activation, stimulates generation of cyclic 3', 5'-adenosine monophosphate (cAMP). cAMP has two effectors: protein kinase A (PKA) and the exchange protein directly activated by cAMP (Epac). Epac1 has been shown to inhibit cardiac fibroblast activation and fibrosis. Osteopontin (OPN) is a ubiquitous pro-inflammatory cytokine, mediating also fibrosis in several tissues, including the heart. OPN underlies several cardiovascular pathologies, including atherosclerosis and cardiac adverse remodeling. We have found that the cardiotoxic hormone aldosterone transcriptionally upregulates OPN in H9c2 rat cardiac myoblasts, an effect prevented by endogenous β₂AR activation. Additionally, CRISPR-mediated OPN deletion enhances cAMP generation in response to both b₁AR and β₂AR activation in H9c2 cardiomyocytes, leading to upregulation of Epac1 protein levels. These effects render β₂AR stimulation capable of completely abrogating transforming growth factor (TGF)-β-dependent fibrosis in OPN-lacking H9c2 cardiomyocytes. Finally, OPN interacts constitutively with G_as subunits in H9c2 cardiac cells. Thus, we have uncovered a direct inhibitory role of OPN in cardiac β₂AR anti-fibrotic signaling via cAMP/Epac1. OPN blockade could be of value in the treatment and/or prevention of cardiac fibrosis.

Emerging evidence suggests that patients suffering from COVID-19 may experience neurocognitive symptoms. Besides, other studies indicate a probable association between leukocyte telomere length (LTL) and neurocognitive changes in subjects with post-COVID-19 condition. Our study was designed to determine the correlation between telomere length and cognitive changes in subjects post-COVID-19. The study included 256 subjects, categorized based on SARS-CoV-2 infection from 2020 to 2023. On the other hand, those subjects who have a psychiatric diagnosis are considered. Besides, the MoCA and MMSE scales were applied. Telomere length was determined using a Polymerase Chain Reaction, and statistical analysis was employed ANOVA and X2 tests. We identified a decrease in LTL in individuals with post-COVID-19 conditions compared to those without SARS-CoV-2 infection (p≤0.05). However, no association was found between LTL and cognitive impairment in subjects post-COVID-19. The findings suggest that LTL is affected by SARS-CoV-2 infection. Nonetheless, this important finding requires further research by monitoring neurological changes in subjects with post-COVID condition.

Rationale: Post-hepatectomy liver failure (PHLF) remains a significant risk for patients undergoing partial hepatectomy (PHx). Reliable prognostic markers and treatments to enhance liver regeneration are lacking. Plasma nanoparticles, including lipoproteins, exosomes, and extracellular vesicles (EVs), can reflect systemic and tissue-wide proteostasis and stress, potentially aiding liver regeneration. However, their role in PHLF is still unknow. Methods: Our study included 9 patients with hepatocellular carcinoma (HCC) undergoing PHx: 3 patients with PHLF, 3 patients undergoing the Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) procedure and three matched controls without complications after PHx. Patient plasma was collected before (PRE), 1 and 5 days (POD1, POD5) after PHx. EVs were isolated by ultracentrifugation and extracted proteins subjected to quantitative mass spectrometry using a super-SILAC mix prepared from primary and cancer cell-lines. Results: We identified 2625 and quantified 2570 proteins in EVs in PHx patients. Among these, 53 proteins were significantly upregulated and 32 were downregulated in patients with PHLF compared to those without PHLF. Furthermore, 110 proteins were upregulated and 78 were downregulated in PHLF compared to patients undergoing ALPPS. The EV-proteomic signature in PHLF indicates significant disruptions in protein translation, proteostasis, intracellular vesicle biogenesis, as well as alterations in proteins involved in extracellular matrix (ECM) remodeling, metabolic and cell cycle pathways, present already before PHx. Conclusion: Longitudinal proteomic analysis of EV´s circulating in human patient plasma undergoing PHx uncovers proteomic signatures associated with PHLF which reflect dying hepatocytes and endothelial cells and are present before PHx already. Our results support EVs as potential biomarkers and therapeutic targets for liver regeneration and failure.

Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world’s population. PTSD is associated with several medical and neurological comorbidities. It has been suggested that these are due to accelerated aging, and that changes in telomere length (TL) and telomerase enzyme activity may serve as biomarkers of this process. Early research in this field suggested that TL was significantly reduced in PTSD. The current review was conducted to provide a critical analysis of recent clinical and translational research on telomere length and telomerase in PTSD. The results of 26 clinical studies suggest that TL in PTSD is highly variable, and may be influenced by methodological, demographic, trauma-related and psychosocial factors. There is no evidence for altered telomerase activity in PTSD, though this was hypothesized by earlier workers in the field. Translational research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL in PTSD depends on several variables that are specific to individuals and groups. Other markers of cellular aging, such as epigenetic changes, may be more specific indices of accelerated aging in patients with PTSD.

Abstract Introduction: Long COVID (LC) affects multiple systems and has a significant health impact on patients and society. Therefore, long COVID services should address patients’ needs through a holistic assessment and monitoring of patients’ symptoms. Aim: The aim was to understand which of the symptoms were most and least likely to improve, after our rehabilitation intervention so that the rehabilitation measures in the clinic could be modified to meet patients’ needs. At the same time, we wanted to assess the feasibility of using C19-YRS ELAROS application in monitoring of LC symptoms during and after the rehabilitation clinic attendance. Methodology: In this study, a total of 50 patients who have attended long COVID rehabilitation clinic in Salford, UK; were assessed by using digitalised C19-YRS ELAROS application. A total of 100 eligible initial and final post rehabilitation assessments were analysed. Conclusion: Pain and anxiety symptoms were the two most likely symptoms to improve after intervention at LC rehabilitation clinic, whereas swallowing difficulty is least likely to improve. Issues with caring for family/ social life (symptoms affecting social role) are likely to worsen even after treatment. It is feasible to monitor and track Long COVID symptoms utilising the digitalised version of C19-YRS via the ELAROS App. This also allows the tracking of symptoms overtime.

Coffee has become a significant commodity for the people of Indonesia, including in Bener Meriah Regency. However, the quality of coffee remains low, partly due to deficiencies in the post-harvest process. This study aimed to analyze coffee farmers' post-harvest process in the Permata Sub-district and identify strategies to enhance coffee quality through farmers' institutions. The research method was qualitative, with data collection techniques comprising in-depth interviews and observation. The findings indicated that most coffee farmers in the Permata Sub-district lacked comprehensive post-harvest processing, impacting the coffee quality. The recommendations of this study emphasize the importance of strengthening coffee farmers' institutions, such as coffee farmer groups, to improve farmers' knowledge and skills in conducting optimal post-harvest processing following specialty coffee standards.

With the rapid growth of large language models (LLMs), there is increasing demand for memory and computation in LLMs. Recent efforts on post-training pruning of LLMs aim to reduce the model size and computation requirements, yet the performance is still sub-optimal. In this paper, we present a plug-and-play solution for post-training pruning of LLMs. The proposed solution has two innovative components: 1) Relative Importance and Activations (RIA), a new pruning metric that jointly considers the weight and activations efficiently on LLMs; and 2) Channel Permutation, a new approach to maximally preserve important weights under N:M sparsity. The two proposed components can be readily combined to further enhance the N:M semi-structured pruning of LLMs. Our empirical experiments show that RIA alone can already surpass all existing post-training pruning methods on prevalent LLMs, e.g., LLaMA ranging from 7B to 65B. Furthermore, N:M semi-structured pruning with channel permutation can even outperform the original LLaMA2-70B on zero-shot tasks, together with practical speed-up on specific hardware. Our code is available at: https://github.com/biomedical-cybernetics/Relative-importance-and-activation-pruning

Purpose: Post-pandemic management of COVID-19 infections and any emergent outbreaks is as an endemic disease remains a public health concern. Vaccine hesitancy may continue to hamper efforts to respond any new disease outbreaks and future epidemics. This qualitative study aimed to explore factors influencing covid-19 vaccine acceptance and hesitancy in Kenya too gain deeper insights on this issue. Methods: The study was implemented in Western Kenya using key informant interviews. Fourteen (14) key informants were purposively selected for the study. All interviews were transcribed and analyzed using thematic analysis. Interpretation of findings was done within the framework of the Health Belief Model. Key findings: Knowledge was a critical factor in combatting misinformation and fostering vaccine acceptance among participants in this study. Misinformation included rumors that the vaccine lowers immunity and was intended for population control. Cues to action included influence from political and opinion leaders and observing the loss of life among unvaccinated individuals. Perceived barriers to vaccine uptake included fear of vaccine safety, side effects, long waiting times at that time of our study, fear of contracting the COVID-19 at vaccination sites, family/spousal influence on vaccine uptake and fear of the unknown with the vaccine. Conclusion: Findings from this study provides insight into areas for targeted strategies for managing Covid-19 vaccinations and future pandemics. Within the framework of the Health Belief Model, this study identified salient barriers and facilitators of COVID-19 vaccine hesitancy that may be helpful to inform future pandemic response.

Background: Scientific literature on COVID-19 is still limited about long-term impacts on the all-body systems and they treatments. The aim of the study was to create a safe protocol-based in-tervention to improve functional and equilibrium abilities in older adults impacted by COVID-19. Methods: The study completed 46 people (intervention group: n=26; control group: n=20). Re-sistance training (RT) was held twice a week, 60 min per session for 8 weeks. The postural stability and quality of life questionnaire (WHQOOL) were conducted during pre- and post-testing. Results: Results indicated significant differences in overall stability index (OSI) with eyes open (EO), ante-rior-posterior stability index (APSI) EO, fall risk index 6-2 (FRI6-2) values in males (p

Introduction: Hospitalization in a COVID-19 unit represents a significant source of stress and psychological distress for patients. Our study aims to determine the factors of psychological distress in the therapeutic and psychosocial management of patients hospitalized with a COVID-19 infection. Methods: This cross-sectional study was carried out over 8 months at the COVID-19 zone of the CHU HASSAN II of FES. 99 patients were evaluated within days of diagnosis by psychometric scales of anxiety, depression, and post-traumatic stress. In the course of this follow-up, we found the presence of psychological impacts in these patients, and we tried to find correlating factors between the occurrence of psychiatric disorders and the set of factors related to sociodemographic data, hospitalization course and treatments taken, as well as family support. Results: 35% of patients had scores in favor of post-traumatic stress disorder, 37% of the patients had definite depression and 50% had anxiety. Post-traumatic stress, depression, and anxiety were correlated with sociodemographic factors, hospitalization, treatments received, and length of stay. Conclusion: The prevalence of anxiety-depressive disorders and post-traumatic stress disorder was high in patients with COVID-19, hence the interest in providing psychological and psychosocial care in the emergency department.

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p&lt;0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).

This study aimed to investigate the effect of adding Mirror Visual Feedback Therapy (MFT) after Dry Needling (DDN) on sensitivity and motor performance in patients diagnosed with Post-Needling pain from Myofascial Trigger Points (MTrPs) in lateral elbow pain patients. A randomized, controlled, two-arm pilot trial following Consolidated Standards of Reporting Trials (CONSORT) was conducted at the European University of Madrid between February 1, 2023, and June 2, 2023. A total of 49 patients (F=23, M=26) were randomly assigned to the Experimental Group Deep Dry Needling, Ischemic Compression, Cold Spray, Stretching, and Mirror Therapy (n=25), and the others receiving the same interventions without Mirror Therapy (n=24). Pre- and post-treatment assessments encompassed Post-needling pain (VAS), pressure pain threshold (PPT), two-point discrimination threshold (TPDT), and maximum hand grip strength (MHGS). Post-needling pain intensity in the EG showed statistically significant reductions (MD = 0.400, SEM = 0.271, W = 137.00, p = 0.047) following the addition of MT to the DDN protocol. Similarly, PPT exhibited significant improvements (MD = 0.148 Kg/cm2, SEM = 0.271, W = 262.00, p < 0.001). However, TPDT and MHGS did not show significant differences between initial and post-treatment measurements. The addition of MFT to DDN for MTrPS in lateral elbow pain reduced Post-needling pain and influenced on sensory perception in lateral elbow pain patients with Myofascial Trigger Points. Despite observed clinical effects not reaching statistical significance, these findings offer valuable insights for future research considerations.

Past research suggests a continuity between perception and memory, as reflected in influences of orienting of spatial attention by cues presented after a visual target offset (post-target cues) on target perception. Conducting two experiments, we tested and confirmed this claim. Our study revealed an elevated reliance on post-target cues for target detection with diminishing target visibility, leading to better performance in validly versus invalidly cued trials, indicative for contrast gain. We demonstrated this post-target cueing impact on target perception without a postcue response prompt, meaning that our results truly reflected a continuity between perception and memory rather than a task-specific impact of having to memorize the target due to a response prompt. We further showed an influence of attention by the post-target cues with cues presented away from a clearly visible target, meaning that visual interactions at the target location provided no better explanation of our results. Our results generalize prior research with liminal targets and confirm the view of a perception-memory continuum, so that visual target processing is not shielded against visuospatial orienting of attention elicited by events following offset of the visual target.

One of the main challenges of the globalization became the increased destabilization and frequent economic crises. In general, managing an economic crisis is a particularly difficult task for any economy (developed or developing, and regardless the size). In the context of globalization, the process faces additional challenges. On the one hand, the world economy witnessed a shift from traditional purely economic instruments to more financial mechanisms of economic development. Indeed, the liberalization of the economy since the 1990s complicated the traditional trends of the world market development, resulting in significant fluctuation of the growth rates between different countries and regions. To respond to this evolution, governments and international organizations changed well-established strategies. For example, financial sector found itself given expanded role in economic development, with, different financial mechanisms used as key variables to evaluate an economic growth. On the other hand, the increased role of financial sector in a globilised world, increased financial relations among individual states and thus, interdependences. This “financial globalization” causes important fluctuations in the system and, as a result, causes instability in socio-economic development. Thus, an economic crisis of any important economy soon becomes a global issue (financial crisis of 2008, economic crisis of 2020).The recent global economic crisis due to the Covid-19 world pandemic, appeared to be unique for several reasons. First, it highlighted the transnational and origin-specific nature of the crisis. Second, it appeared to be the first case when non-economic factors caused a major economic crisis. As a result, this crisis turned out to be particularly difficult to predict and to manage. In this case, the main strategy of the global post-crisis rehabilitation became the restoration of the economy's predictability and ensuring its ability to obey the classical principles. According to the Organic Law on "Economic Freedom" of the European Union (2011), any factor which increases the equilibrium amount of output is reflected in the economic rehabilitation plan. Such exogenous factors are primarily fiscal mechanisms, i.e. - Reduction of taxes and increase of state expenditures. This crisis caused important structural problems with their effects on public expenditures (especially health expenditures, to the public expenditures, economic growth, price stability and budget balance) in both, developed and developing countries. Nearly every state declared an increase in public debt, inflation, and unemployment rates, while an important decrease was shown in growth rates and capital outflows. As the crisis due to the world pandemic was radically different from previous economic crises, it was difficult to manage it efficiently at the initial stage. It was complicated to forecast the scenarios of the unknown crisis with non-standard nature which was more linked to epidemiologic factors than objective economic law. The dynamics of crisis resolution depended on correct forecasting and effective implementation of global, but especially country-based reforms. More importantly, this crisis showed the important role of individual states to manage the global crisis. The traditional function of a government to ensure country’s socio-economic growth and security, increases in an extraordinary environment, such as sharp economic fluctuations and crises. In such contexts, the centralized management functions are sharply activated. The global pandemic processes have updated the economic essence of the state. The large scale of the latest economic crisis due to the world pandemic has determined the need for mutually coordinated development of anti-crisis plans of different countries. In today's dynamic landscape, modern global systems are redefining the standards and priorities of national economic policies. The economic status of countries is changing significantly as a result of their participation in these systems. As a result of these changes, today's global economy is marked by the proliferation of regionalism and the emergence of spatial economic frameworks. Thus, classical economic concepts are evolving, giving rise to a new model known as economic nationalism. This paradigm shift is generating new risks, which are increasing in severity and scope. The overriding objective of economic policy is now to ensure and predict stable development. Reflections are underway to meet the challenges of economic equilibrium and its social and institutional sustainability.In addition to the decentralization of the unified governance system, the global economy is characterized by the activation of centralized governance elements within individual countries. This requires the development of new norms for global cooperation and the careful balancing of national integration and development factors. The question of government's influence on the economy and the delegation of its powers becomes relevant once again. Effective coordination of public administration is based on the principle of decentralized government, which is a key element of a democratic model of society and facilitates the transfer of management tools to the public. The key objectives of this research are focused on the optimal distribution of state functions and the study of hierarchical principles of territorial organization within the country, fiscal mechanisms for the distribution of powers, as well as the particularities of the structuring of the spatial economy and its budgetary provisioning mechanisms.The example of the last two economic crisis showed that contemporary anti-crisis strategies should reflect several considerations. First, it becomes impossible to develop a single unified model of crisis management. Even in the context of important economic and financial globalization, the current decentralization and new spatial economic processes make it necessary to find a balance between the local priorities and global interests. Second, the role of non-economic crisis-causing factors increases compared to economic determinants. That is why international and country-based reforms should aim at not only economic rehabilitation, but also on the social, cultural and environmental restorations. Third, it becomes difficult to correctly predict the consequences of the crisis and thus, the effects of the anti-crisis strategy. Consequently, the success of the post-crisis rehabilitation of the countries' economies depends significantly not only on the effective realization of their own plan, but also, in general, on the specificities of the global economy and on the ability of the world markets to overcome the negative consequences of a crisis. In this context, the development of complex post-crisis platforms and state post-crisis strategies is the priority. The most effective component in the anti-crisis strategy is the monetary instruments of economic management. As for the determinant of successful functioning of economy, the priority should be given to the regulation of exchange rate, interest rate and inflationary processes. A state anti-crisis programs should reflect the crisis prevention strategy, which, on its turn, should differentiate the economic functions of the state and crisis management mechanisms according to the specific trends of given processes. It should aim at gaining stable development of the economy. Additionally, an anti-crisis plan should reflect the role of the society in the development process and its mental changes under crisis conditions. The state should be responsible for establishing and monitoring anti-crisis management mechanisms, financial recovery of the country and formation of correct relations. It is especially important to ensure economic security, to stabilize the development process and standard of living, to support the private sector and small entrepreneurship, to increase economic freedom, to ensure effective distribution of labor and capital, and others. All strategies of the anti-crisis platform should be focused on social results, as it should contribute to a fair distribution of income and to poverty reduction.

Knowledge of post-larval swordfish (Xiphias gladius) ecology in the world’s oceans is incomplete as they are rarely found in ichthyoplankton samplings or commercial catches and individuals are difficult to observe in the marine ecosystem. Analyses of stomach contents of apex predators can provide otherwise unobtainable ecological insights. Two well-preserved bills of post-larval swordfish were identified among the partially digested stomach contents of an adult male dolphinfish (Coryphaena hippurus) caught in the northern Tyrrhenian Sea. The lower jaw to fork lengths of the two predated swordfish were estimated at respectively, 18 and 22 cm, corresponding to 81- and 99-day-old swordfish hatched in the 2022 spawning season. This analysis and recent information on the reproductive dynamics of swordfish in the same area reported in the literature shed light not only on the early stages of swordfish growth but also on dolphinfish ecology in the Tyrrhenian Sea. The two species share the same habitat and are both caught with commercial pelagic surface longlines. Environmental shifts associated with climate change could unpredictably modify the reproduction dynamics, growth, recruitment and distribution of both species. This knowledge is important for the sustainable management of regional fisheries.

The Hollow fiber membrane contactor (HFMC) is an intensification process that combines membrane and absorption technologies, being a technology in expansion, so the dynamics of this process is crucial for an increase in industrial scale-up. In this manuscript a rigorous dynamic model of an HFMC is developed and simulated in Python software for the absorption of post-combustion CO2 using a monoethanolamine (MEA) solution, which was validated using available data in literature in steady state. Dynamic simulations were performed to analyze the model's capability to predict the effect of disturbances on the responses of CO2 capture ratio and loading. Four distinct experiments were conducted by step changes and pulse disturbances at the following variables: gas and liquid volumetric flow rates, CO2 composition in flue gases, and CO2 lean load. The gas phase showed a faster response compared to the liquid. The CO2 capture ratio and rich loading presented opposite responses when disturbing both liquid flows, and for the composition and lean loading variations, the capture ratio presented an inverse response characteristic, while the loading showed a delayed response. As the model proved to be capable of returning to the reference state, it can potentially be used for control studies purposes.

The COVID-19 pandemic necessitated a profound shift to online education, impacting students across various educational levels. This research, drawing from a comprehensive survey of 1,000,000 students, delves into the surge in demand for online education during the pandemic and its potential enduring implications. The study scrutinizes factors steering this transition, the perceived effectiveness of online education, challenges encountered by students, and their anticipated preferences for the future. Results unveil nuanced perspectives among K-12, undergraduate, and postgraduate students, with safety, flexibility, and accessibility emerging as pivotal influencers. The findings offer valuable insights into challenges faced and future preferences, enlightening educational stakeholders about the dynamic needs of students and contributing to the ongoing evolution of the post-pandemic educational landscape.

Background: Alongside their long-term effects - post-concussion syndrome (PCS) - mild traumatic brain injuries (mTBI) are significant public health concerns. Currently, there is a lack of reliable biomarkers for diagnosing and monitoring mTBI and PCS. Exosomes are small extracellular vesicles secreted by cells that have recently emerged as a potential source of biomarkers for mTBI and PCS due to their ability to cross the blood-brain barrier and reflect the pathophysiology of brain injury. This study aimed to investigate the role of salivary exosomal biomarkers in mTBI and PCS. Methods: A systematic review using the PRISMA guidelines was conducted, and studies were selected based on their relevance to the topic. Results: Studies have shown that exosomal tau, phosphorylated tau (p-tau), amyloid beta (Aβ), and microRNAs (miRNAs) are potential biomarkers for mTBI and PCS. Specifically, elevated levels of exosomal tau and p-tau have been associated with mTBI and PCS, as well as with repetitive mTBI. Dysregulated exosomal miRNAs have also been observed in individuals with mTBI and PCS. Additionally, exosomal Prion cellular protein (PRPc), coagulation factor XIII (XIIIa), synaptogyrin-3, IL-6, and aquaporins have been identified as promising biomarkers for mTBI and PCS. Conclusion: Salivary exosomal biomarkers have the potential to serve as non-invasive and easily accessible diagnostic and prognostic tools for mTBI and PCS. Further studies are needed to validate these biomarkers and to develop standardized protocols for their use in clinical settings. Salivary exosomal biomarkers can improve the diagnosis, monitoring, and treatment of mTBI and PCS, leading to improved patient outcomes.

Background. There are few studies about post myocardial infarction follow-up using telemedicine. We organized a post-discharge telemedicine service with a dedicated team. To do this, it was necessary that all stakeholders involved in the organization and use of the telemedicine service were properly educated and informed. Methods. We designed a theoretical-practical mini-course, to train healthcare personnel and increase skills, with excellent learning outcomes and satisfaction. Thereafter, we enrolled patients affected by acute myocardial infarction with ST elevation (STEMI), MINOCA (myocardial infarction with no obstructive coronary atherosclerosis), Takotsubo syndrome or spontaneous coronary dissection, and high-risk acute myocardial infarction without ST elevation (NSTEMI). At discharge, the cardiology technician performed counselling for the patient; using regional platforms, televisit at 1 and 4 months monitored major adverse cardiac events (MACE), heart failure, arrhythmias, unstable angina and non-cardiovascular events, therapy adherence, target therapy and customer satisfaction. Results. Between November 2021 and February 2023, we enrolled 110 patients: 72% affected by STEMI, 22% by NSTEMI. At the 1-month follow up, 12 patients did not reach pressure target and 23 patients did not reach LDL target. We observed three in hospital readmission, three in hospital visits for further investigation and one death. To date, a four months follow up was performed for 54 patients. No readmissions or deaths occurred. We detect a rate of 96% of customer satisfaction. Conclusion. A health coordination center with a dedicated team makes televisit safe as a follow-up for post myocardial infarction patients. Before, it is fundamental for healthcare professionals the acquisition of theoretical knowledge and updates and the acquisition of manual, technical and practical skills.