As medical care aiming to maintain the quality of life for elderly patients is increases, implant treatment for elderly patients is increasing worldwide. Therefore, we aimed to investigate implant stability and the reliability of different measuring devices according to implant placement site and duration in patients aged over 65 years. The study evaluated 60 implants in 60 patients aged ≥ 65 years. The implant placement sites were divided into six evenly distributed sections (n=10) i.e., maxillary right- posterior, A; maxillary anterior, B; maxillary left-posterior, C; mandibular right-posterior, D; mandibular anterior, E; mandibular left-posterior, F. Participants visited the hospital seven times: preoperatively, 1V; implant surgery, 2V; stitch removal, 3V; 1-month follow-up, 4V; 2-months follow-up, 5V; before final-restoration delivery, 6V; and after final-restoration delivery, 7V. The implant stability was evaluated with the Osstell Mentor (ISQ), Periotest M (PTV), and Anycheck (IST). The mean values of ISQ, PTV, and IST were analyzed (α=.05). ISQ, PTV, and IST results of 5V and 6V were significantly higher than those of 2V (P<.05). The lowest ISQ results occurred in E location at 5V and 6V (P<.05). In all mandibular locations, IST results of 7V were significantly higher than those of 2V, 3V, 4V, and 5V (P<.05). ISQ results were negatively correlated with PTV and positively correlated with IST, and PTV was negatively correlated with IST. By considering various factors that affect implant stability, the appropriate implant load application time was determined. This could help increase the implant success rate in elderly patients. And as a diagnostic device for implant stability for evaluation of osseointegration in elderly patients, Anycheck was also able to prove its relative reliability compared to Osstell ISQ Mentor and Periotest M.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease, is the most common respiratory morbidity in preterm infants. "Old" or "Classic" BPD, as per the original description, is less common now. "New BPD," which presents with distinct clinical and pathological features, is more frequently observed in the current era of advanced neonatal care, where extremely premature infants are surviving due to medical advancements. The pathogenesis of BPD is complex and multifactorial and involves both genetic and environmental factors. This review provides an overview of the pathology of BPD and discusses the influence of several prenatal and postnatal factors on its pathogenesis, such as maternal factors, genetic susceptibility, ventilator-associated lung injury, oxygen toxicity, sepsis, patent ductus arteriosus (PDA), and nutritional deficiencies. This in-depth review draws on existing literature to explore these factors and their potential contribution to the development of BPD.

Diseases of the lung account for more than 5 million deaths worldwide and are a burden to healthcare. Improving clinical outcomes including mortality and quality of life involves a holistic understanding the etiopathogenesis, which can be provided by multi-omics integration of lung data. An enhanced understanding of large comprehensive datasets provides opportunities to mine those datasets for features that contribute to prevention and amelioration of disease. In this review, we evaluate lung disease models including animal models, organoids and single cell lines as mechanisms to study multiomics in lung health and disease. We provide examples of lung diseases where multi-omics investigations have provided a deeper insight into pathogenesis that has resulted in improved preventive and therapeutic interventions.

Temporomandibular joint disorders (TMD) are characterized by their multifactorial etiology and pathogenesis. A 3-year prospective study was conducted in a Portuguese TMD department to study the prevalence of different TMD signs and symptoms and their association with risk factors and comorbidities. Five hundred ninety-five patients were included using an online database: EUROTMJ. Most patients were female (80.50 %), with a mean age of 38.20±15.73 years. The main complaints were temporomandibular joint (TMJ) clicking (13.26%), pain (12.49%), and masticatory muscle tension (12.15%). The main clinical findings were myalgia (74%), TMJ clicking (60-62%) and arthralgia (31-36%). Risk factors such as clenching (60%) and bruxism (30%) were positively associated with TMJ pain and myalgia. Orthodontic treatment (20%) and wisdom tooth removal (19%) were positively associated with TMJ clicking, while jaw trauma (6%) tracheal intubation (4%) and orthognathic surgery (1%) were positively associated with TMJ crepitus, limited man-dibular range of motion and TMJ pain, respectively. 42.88% of TMD patients had other associated chronic diseases, most of them were mental behavioral or neurodevelopmental disorders (33.76%), namely, anxiety (20%) and depression (13%). The authors also observed a positively association of mental disorders with the degree of TMJ pain and myalgia. Online database seems to be a relevant scientific instrument for healthcare providers who treat TMD. The authors expect that EUROTMJ database can serve as a milestone for other TMD departments.

Among cross-sectional imaging modalities, computed tomography (CT) is more available and faster; however, magnetic resonance (MR) performs better in terms of sensitivity and specificity, due to its higher contrast resolution. The appearance of peritoneal deposits on CT and MR depends mainly on the primary tumour histology: in case of unknown primary tumour (3-5% of cases), their behaviour at imaging may provide insights on the tumour origin. The time-point of tumour evolution, previous or ongoing treatments and the peritoneal spaces where they occur, also play an important role in determining the appearance of peritoneal deposits. Thus, knowledge of peritoneal anatomy and fluid circulation is mandatory in detection and characterization of peritoneal deposits. Several benign and malignant conditions may show similar imaging features that overlap those of PC, making the differential diagnosis challenging. Clinical history, laboratory findings and previous imaging examinations must be considered to achieve the correct diagnosis.

Total hip arthroplasty (THA) is one of the most successful orthopedic procedures and is highly effective in improving function and quality of life. However, after discharge patients commonly experience edema, which can lead to health consequences and lower quality of life. For these rea-sons, the aim of this study is to evaluate the effectiveness of a specific intermittent leg pneumatic compression on lower limb edema and physical outcomes in patients after total hip arthroplasty, compared to standard conservative treatment. A total of 47 patients were enrolled and randomly allocated into two groups: the pneumatic compression group (PG=24) and the control group (CG=23). We evaluated thigh and calf circumferences, knee and ankle range of motion, pain and walking autonomy. Our results showed a greater reduction in thigh and calf circumference for PG (p<0.001), while other outcomes were similar for the two groups (p>0.05). The combination of standard therapy with pneumatic leg compression was more effective in reducing lower limb edema, thigh, and calf circumferences compared to the use of standard treatment. Our results suggest that pressotherapy treatment is a valuable and efficient option for managing lower limb edema and preventing VTE after THA.

Objective: This systematic review and meta-analysis compared the patient-reported outcomes of intra-articular facet joint injections of normal saline and selected active substances to identify a more effective agent for treating subacute and chronic low back pain (LBP). Methods: The PubMed, Embase, Scopus, Web of Science, and CENTRAL databases were searched for randomized controlled trials and observational studies published in English. A research quality assessment was performed using ROB2 and ROBINS-I. A meta-analysis was conducted using a random-effects model, and the mean differences (MD) with 95% confidence intervals (CI) in efficacy outcomes, including pain, numbness, disability, and quality of life, were assessed. Results: Of the 2,467 potential studies, three were included (247 patients). The active substances and normal saline had similar therapeutic effects on pain within 1 h, after 1-1.5 months, and after 3-6 months, with MD and 95% CI of 2.43 and -11.61 to 16.50, -0.63 and -7.97 to 6.72, and 1.90 and -16.03 to 19.83, respectively, as well as the quality of life after 1 and 6 months. Conclusion: The short- and long-term clinical effects of intra-articular facet joint injections of normal saline are comparable to those of other active substances in patients with LBP.

The prognosis of patients with recurrent or metastatic of the head and neck squamous-cell carcinoma (HNSCC) refractory to platinum-based chemotherapy is severe and, consequently, the identification of therapeutic options for this category of patients is a priority. Nivolumab, an anti- programmed cell death protein 1 (anti-PD-1) monoclonal antibody, has been approved for the treatment of recurrent or metastatic HNSCC after platinum-based therapy progressing. We present the early experience of two academic center including diagnostic, clinical, biological, therapeutic and outcomes characteristics of head and neck cancer (HNC) patients treated with Nivolumab. The purpose of the study is to identify certain peculiarities and to report them compared to the data from the literature in order to generate some hypotheses that coud constitute criteria for the selection of cases with maximum benefit to immunotherapy. Analyzing the data obtained from 18 patients treated in Emergency County Hospital Craiova, "Saint Nectarie" Oncological Hospital Craiova and Euroclinic Oncological Center Iasi January 2020 and March 2023 it could be hypothesized that lower nadir values of neutrophil to lymphocyte ratio (<3.5) and the adition of intensive regimens of chemotherapy and radiotherapy could justify a favorable response in terms of progression free survival (PFS) during immunotherapy with Nivolumab. To our knowledge, the study included the first two cases of second primary malignancy (SPM) in the head neck region treated with Nivolumab. The reported data support a possible benefit of the sequential administration of radiotherapy, immunotherapy for SPM cases. Higher positive dynamic of neutrophil to lymphocyt ratio (NLR) could be associated with worst outcome during immunotherapy. All study observations including the role of infections and antibiotic treatment as well as the possible biomarker value of NLR variation during immunotherapy should be investigated in multicenter clinical trials.

Monkeypox is a zoonotic illness caused by the Orthopoxvirus monkeypox virus (MPXV). Since 1970, outbreaks of MPXV have occurred in several Sub-Saharan African countries. However, from May 2022 to April 2023, recent outbreaks of MPXV occurred in several countries outside of Africa, and these cases quickly spread to over 100 non-endemic countries on all continents. Because of this, in July 2022, World Health Organization declared monkeypox a Public Health Emergency of International. MPXV disproportionately affects men who have sex with men and members of the HIV-infected population. The current strategy for control and pre-exposure prophylaxis or post-exposure prophylaxis for people at high risk is vaccination. In this context, Peru has the fourth-highest number of MPXV cases in Latin America. Because of this, in this review, we describe public health indicators in Peru and reflect on the COVID-19 pandemic so that health authorities can join forces to identify and control MPXV transmission routes.

Parkinson's Disease (PD) is a neurodegenerative disorder that affects the motor system of the human body. Currently, the available treatments are limited and often have undesirable side effects. In this context, the aim of this study was to develop a novel combinational formulation of Apomorphine and Quetiapine and evaluate its efficacy in a rat model of PD. The formulation was prepared using the solvent evaporation technique and characterized for its physicochemical properties. The in-vitro drug release was evaluated using the Franz diffusion cell method, and the pharmacokinetics of the combination was studied in rats. The behavioural and biochemical parameters were evaluated in the rats using the Rotarod, pole test, and biochemical assays. The results showed that the developed formulation had satisfactory physicochemical properties and exhibited sustained drug release. The pharmacokinetic studies showed that the combination exhibited a longer residence time than the individual drugs. The behavioural and biochemical parameters showed that the combination was effective in improving motor function and reducing oxidative stress. In conclusion, the developed Apomorphine and Quetiapine combination formulation showed promising results in improving motor function and reducing oxidative stress in rat model of PD. Further studies are required to evaluate the safety and efficacy of the developed formulation in humans.

Udder health of dairy cows is related to their productivity and welfare. The period from dry-off to calving and early lactation is crucial. Ultrasonography is a useful and practical tool for the examination of the mammary parenchyma and blood flow. This observational study investigated the relationship between udder echotexture features, blood flow volume (BFVol) in the milk vein, milk somatic cell count (SCC) and daily milk yield (DMY) from late lactation, throughout dry period and consecutive early lactation. Seventeen repeated measurements were performed on 21 Holstein cows. The udder parenchyma was examined with B-mode ultrasonography. Udder echotexture was studied using 15 features: Numerical Pixel Value (NPV), Pixel Standard Deviation (PSD), Skewness, Excess, Contrast, Homogeneity, Correlation, Entropy, Run Percentage, Long Run Emphasis, Grey Value Distribution, Runlength Distribution, Gradient Mean Value, Gradient Variance and Percentage of Non-zero Gradients. Blood flow in the milk vein was examined with spectral Doppler. Linear mixed effects models were employed to investigate relationships between BFVol, udder echotexture features, SCC and DMY, throughout the study period. Our models showed that a 1-kg increase in DMY was associated with a significant increase of 0.25 L/min in the expected BFVol, and that a 1,000,000-cells/mL increase in SCC was associated with a significant BFVol decrease of 0.49 L/min, keeping all other variables constant. Multivariable models showed significant associations between DMY and NPV, PSD and Long Run Emphasis, and between SCC and NPV, PSD, Gradient Mean Value, Homogeneity, Gradient Variance and Entropy. In conclusion, udder echotexture and BFVol in the milk vein are related to SCC and milk yield. Ultrasonography can be used for the comprehensive assessment of udder health in the direction of precision dairy farming.

Severe respiratory syncytial virus (RSV) infections in early life have been linked to the development of chronic airway disease. RSV is a potent inducer of reactive oxygen species (ROS) which contributes to inflammation and enhanced clinical disease. NF-E2-related factor 2 (Nrf2) is an evolutionary conserved redox-responsive protein that helps to protect cells and whole organisms from oxidative stress and injury. The role of Nrf2 in the context of viral-mediated chronic lung injury is not known. Herein, we show that RSV experimental infection of adult Nrf2 deficient BALB/c mice (Nrf2-/-; Nrf2 KO) is characterized by enhanced disease, increased inflammatory cell recruitment to the bronchoalveolar compartment, and a more robust upregulation of innate and inflammatory genes and proteins, compared to wild type Nrf2+/+ competent mice (WT). These events that occur at very early time points, lead to increased peak RSV replication in Nrf2 KO compared to WT mice (day 5). To evaluate longitudinal changes of the lung architecture, mice were scanned weekly by high-resolution micro-computed tomography (micro-CT) imaging up to 28 days after initial viral inoculation. Based on micro-CT qualitative 2D imaging and quantitative reconstructed histogram-based analysis of lung volume and density, we found that RSV infected Nrf2 KO mice developed significantly greater and prolonged fibrosis compared to WT mice. Results of this study underscore the critical role of Nrf2-mediated protection from oxidative injury not only in acute pathogenesis of RSV infection, but also in its long-term consequences of chronic airway injury.

Leukotrienes are proinflammatory mediators that participate in the process of atherogenesis and contribute to the development of symptomatic peripheral arterial disease. The aim was to evaluate the relationship between leukotriene E4 (LTE4) and B4 (LTB4) with parameters reflecting endothelial vascular function in patients with chronic lower limb ischemia. This prospective observational study enrolled 50 consecutive patients undergoing endovascular treatment due to chronic lower limb ischemia (Rutherford 3). All participants were followed-up for one year (after 1, 3, 6 and 12 months), with a sequential assessment of urinary LTE4 and LTB4, as well as measures of endothelial and vascular function: Flow-Mediated Dilatation (FMD), Intima-Media Thickness (IMT), corrected Augmentation Index (AI75), Shear Rate (SR), Ankle-Brachial Index (ABI), Toe-Brachial Index (TBI). There was a significant relationship between LTE4 and measures of vascular function: FMD (R2 = 0.69, P&lt;0.001), IMT (R2=0.12, P&lt;0.01), AI75 (R2=0.43, P&lt;0.001), SR (R2=0.48, P&lt;0.001). Similar findings were noted for LTB4: FMD (R2=0.47, p&lt;0.001), IMT (R2=0.23, P&lt;0.001), AI75 (R2=0.61, P&lt;0.001) and SR (R2=0.33, P&lt;0.001). Alterations in parameters were significantly related: ΔLTE4 vs ΔFMD(R2=0.63, P&lt;0.001), ΔSR (R2=0.42, P&lt;0.001) and ΔLTB4 vs AI75(R2=0.40, P&lt;0.001), SR(R2=0. 29, P&lt;0.001). We conclude, that increasing concentrations of LTE4 and LTB4 are associated with impairment of vascular and endothelial function, which may lead to worse endovascular treatment clinical outcomes.

The snATAC + snRNA platform allows epigenomic profiling of open chromatin and gene expression with single-cell resolution. The most critical assay step is to isolate high-quality nuclei to proceed with droplet-base single nuclei isolation and barcoding. With the increasing popularity of multiomic profiling in various fields, there is a need for optimized and reliable nuclei isolation methods, mainly for human tissue samples. Herein we compared different nuclei isolation methods for cell suspensions, such as peripheral blood mononuclear cells (PBMC, n=18) and a solid tumor type, ovarian cancer (OC) (n=18), derived from debulking surgery. Nuclei morphology and sequencing output parameters were used to evaluate the quality of preparation. Our results show that NP-40 detergent-based nuclei isolation yields better sequencing results than collagenase tissue dissociation for OC, significantly impacting cell identification and analysis. Given the utility of applying such techniques to frozen samples, we also tested frozen preparation and digestion (n=6). A paired comparison between frozen and fresh samples validated the quality of both specimens. Finally, we demonstrate the reproducibility of scRNA and snATAC + snRNA platform, by comparing the gene expression profiling of PBMC. Our results highlight how the choice of nuclei isolation methods is critical for obtaining quality data in multiomic assays. It also shows that the measurement of expression between scRNA and snRNA is comparable and effective for cell type identification.

CRCMSS/pMMR contain a significantly increased fraction of TREM2+ macrophages (TAMs) and CD66+ neutrophils (TANs) together with decrease of CD4-CD8-CD3+ double negative T lymphocytes (DNTs); no differences were revealed by the analysis of myeloid and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells display an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-γ. These findings confirm the immune suppressive microenvironment of CRCMSS/pMMR characterized by dense infiltration of TAMs, occurrence of TANs, lack of DNTs, T-cell exhaustion and interferon-γ unresponsiveness by host and tumor cells. Appropriate bypass strategies should consider these combinations of immune escape mechanisms in CRCMSS/pMMR.

Lifestyle physical activity (PA) and nutrition are known to be effective interventions in preventing and managing obesity related comorbidities is adult populations, but less so in children and adolescents. We examined the effectiveness of lifestyle interventions in children from minority ethnic populations in western high-income countries. Our systematic review included 53 studies involving 26045 children from minority ethnic populations within western countries, who followed lifestyle intervention programs lasting between 8 weeks and 5 years with an aim to prevent and/or manage childhood obesity and associated comorbidities, including adiposity and cardiometabolic risks. Studies were heterogenous in terms of lifestyle intervention components (nutrition, PA, behavioural counselling) and settings (community vs. schools and after schools). Our meta-analysis included 31 eligible studies and showed no significant effects of lifestyle interventions when they focused on body weight and body mass index (BMI) outcomes [pooled BMI mean change = -0.09 (95% CI -0.19, 0.01), p=0.09]. This was irrespective of the intervention program duration (< 6 months vs. ≥ 6 months), type (PA vs nutrition/combined intervention) and weight status (overweight or obese vs no normal weight), all showed no significant effects in the sensitivity analysis. Nonetheless, 19 of the 53 studies reported reduction in BMI, BMI z scores and body fat percentage. However, majority of lifestyle interventions adopting a quasi-design with a combined primary and secondary obesity measures (11 out of 15 studies), were effective in reducing obesity comorbidities of cardiometabolic risks including metabolic syndrome, insulin sensitivity, and blood pressure in children with overweight and obesity. Preventing childhood obesity and associated comorbidities in children from high-risk ethnic minority groups is best achieved using a combined PA and nutrition intervention approach, which jointly target preventing obesity and cardiometabolic disease primary and secondary outcomes, especially measures of diabetes, hypertension, and cardiovascular disease.

Functional gastrointestinal disorders (FGIDs) are common in children and adolescents. In recent years, interest in the role of diet in the treatment of FGIDs has increased. Currently, interest focus-es on the low-FODMAP diet (LFD), the fructose- or lactose-restricted diet (FRD or LRD), the glu-ten-free diet (GFD), and the Mediterranean diet (MD). In this review, we focus on the role of these dietary patterns in the FGIDs most commonly diagnosed in clinical practice, namely irritable bowel syndrome (IBS), functional abdominal pain (FAP), functional dyspepsia (FD), and func-tional constipation (FC). Fifteen clinical trials were systematically reviewed (both RCTs and sin-gle arm clinical trials). We demonstrated the lack of high-quality intervention trials. Based on current evidence, low-FODMAP diet, LRD, FRD, or GFD have no place in daily practice for the management of children and adolescents with FGIDs. Nevertheless, some patients with IBS or RAP may have some benefit from the use of a low-FODMAP diet or FRD/LRD. Limited data sug-gest that MD may be promising in the management of FGIDs, especially in IBS patients, but more data are required to investigate the mechanisms of its protective effects.

The objective of this study was to compare the pathogens and susceptibilities of the current automated rule-based technology (RBT) antibiogram with one manually collected through chart review with additional rules applied. This study was a 2-year, retrospective cohort study and included all bacterial cultures within the first 30 days from patients admitted to a single Burn Center. The current RBT antibiogram served as the control and new antibiogram versions were created using additional rules and compared to the control. Six-hundred fifty-seven patients were admitted (61% excluded for lack of cultures). Fifty-nine percent had at least one hospital acquired risk factor with over one-third having recent illicit drug use and one-third having a recent hospitalization. Of the 410 cultures included, 57% were Gram-negative and half were from wound infections. Sensitivities were significantly different when comparing manual and the RBT version after including factors, such as days since admission, presence of hospital acquired risk factors, or previous antibiotic courses. Recommended empiric Gram-negative antibiotics changed from double coverage to a single β-lactam with > 90% susceptibility. The susceptibilities between first and subsequent courses were dramatically different. Before developing an antibiogram or interpreting the output, it is important to consider which automated criteria are utilized, especially for units with extended lengths of stay.

Urethral prolapse (UP) is a rare condition in which the distal urethral mucosa protrudes circularly from the external urethral meatus. Urethral prolapse is seen in two age groups: prepubertal girls and postmenopausal women. The fact that it is seen in older women shows that it may be acquired. Causes of acquired UP include weakening of smooth muscle layers secondary to estrogen deficiency, chronic cough, chronic constipation, trauma, recurrent urinary tract infections, pelvic radiotherapy, and sexual abuse. The priority in treatment is conservative management, such as manual reduction, sitz baths, topical estrogen creams, and antibiotics. The general consensus is to switch to surgical treatment in patients who do not benefit from a conservative approach. In this case report, we describe the surgical treatment of a 56-year-old postmenopausal female patient with necrotic UP who presented with urinary retention.

At present, the applications and efficacy of non-ionizing radiations (NIR) in oncotherapy are limited. In terms of potential combinations, the use of biocompatible magnetic nanoparticles as heat mediators has been extensively investigated. Nevertheless, the development of more efficient heat nanomediators that may exhibit high specific absorption rates still is an unsolved problem. Our aim was to investigate if externally applied magnetic fields and a heat-inducing NIR affect tumor cell viability. To this end, under in vitro conditions, different human cancer cells (A2058 melanoma, AsPC1 pancreas carcinoma, MDA-MB-231 breast carcinoma) were treated with the combination of electromagnetic fields (EMFs, using solenoids) and hyperthermia (HT, using a thermostated bath). The effect of NIR was also studied in combination with standard chemotherapy and targeted therapy. An experimental device combining EMFs and high intensity focused ultrasounds (HIFU)-induced HT was tested in vivo. EMFs (25 T, 4h) or HT (52C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approx. 16%, 50%, and 21% of controls values in A2058, AsPC1, and MDA-MB-231 cells, respectively. Increased lysosomal permeability, release of cathepsins into the cytosol and mitochondria-dependent activation of cell death are the underlying mechanisms. Cancer cells could be completely eliminated combining EMFs, HT and standard chemotherapy or EMFs, HT and anti-Hsp70-targeted therapy. As a proof of concept, in vivo experiments performed in AsPC1 xenografts showed that combination of EMFs, HIFU-induced HT, standard chemotherapy and a lysosomal permeabilizer induces a complete cancer regression.

Background: The use of barbed sutures for pharyngoplasty techniques is a new trend in sleep apnea surgery, but little is known about its short-term results depending on the different techniques. The objective of this study was to compare the surgical results in two different centers using barbed sutures in which the main difference was the loops performed in the soft palate. Methods: This is a retrospective study of patients with obstructive sleep apnea (OSA) operated in two centers. A statistical analysis comparing the ENT department of the Ospedale Morgagni-Pierantoni from Forlí with the ENT department of Dr. Peset University Hospital was performed. Results: The final sample size was 138 patients (70 from Forlí and 68 from Valencia). In both series, a significant improvement was observed in OSA patients with significant reductions in respiratory events not related to weight reduction. The mean delta Apnea-Hypopnea index was 13.36 (SD 21.3) in Forlí and 22.8 (SD 22.05) in Valencia (p<0.05). Forlí’s series had a higher proportion of multilevel surgeries than Valencia's and a lower proportion of tonsillar hypertrophy. Conclusion: The number of loops performed in the soft palate may improve the surgical results, nevertheless, this must be confirmed in prospective studies.

The aim of this pilot study was to investigate whether single nucleotide polymorphisms (SNP) in the gene encoding the catalytic subunit of glutamate cysteine ligase (GCLC) are associated with the risk and clinical features of psoriasis. A total of 944 unrelated individuals, including 474 patients with a diagnosis of psoriasis and 470 healthy controls, were recruited for the study. Six common SNPs in the GCLC gene were genotyped using the MassArray-4 system. Polymorphisms rs648595 (OR=0.56 95%CI 0.35-0.90, Pperm=0.017) and rs2397147 (OR=0.54 95%CI 0.30-0.98, Pperm=0.05) were associated with susceptibility to psoriasis in males. In the male group, diplotype rs2397147-C/C×rs17883901-G/G was associated with decreased risk of psoriasis (FDR-adjusted P=0.014), whereas diplotype rs6933870-G/G×rs17883901-G/G (FDR-adjusted P=0.045) showed association with increased disease risk in females. Joint effects of SNPs with tobacco smoking (rs648595 and rs17883901) and alcohol abuse (rs648595 and rs542914) on the risk of psoriasis were observed (Pperm≤0.05). Furthermore, we found multiple sex-independent associations between GCLC gene polymorphisms and various clinical features such as earlier disease onset, the psoriatic triad, and specific localizations of skin lesions. The present study is the first to show that polymorphisms of the GCLC gene are significantly associated with the risk of psoriasis and related to its clinical features.

Atherosclerosis is a dynamic, chronic and progressive process that involves the vascular bed (coronary and peripheral). Risk factors are associated with the progression rate and with the evolution of atherosclerosis. There are traditional risk factors and non-traditional risk factors, all of them lead to endothelial dysfunction. Endothelial dysfunction plays a key factor in atherosclerosis. It accompanies hypercholesterolemia, diabetes, hypertension, cigarette smoking – leading to the development of atherosclerosis. Endothelial dysfunction can be reversed by treating hyperlipidemia and other damaging processes, and the mechanism is believed to be associated with an increase in vascular endogenous NO. PAD is a devastating disease, leading to leg pain and amputation. Until now the optional treatments don’t cure or prevent the uneventful outcome, but may slow the downhill progression. We summarize the updated knowledge of the management of PAD and suggest a novel approach to treat patients with PAD, using stem cells technology and a special novel endovascular device that will deliver the cells continuously on the long run and may halt the progression of atherosclerosis or even cure PAD.

Coronavirus 19 disease (COVID-19) may be complicated by thrombotic events, particularly venous thromboembolism (VTE), which have been reported both in critically ill hospitalized patients and in individuals with mild symptoms. It is known that the chronic use of oral contraceptive pills (OCPs) is associated with higher risk of VTE. To date, there are only few reports concerning the association of OCPs and VTE/pulmonary embolism (PE) in COVID-19 patients. Given that during the convalescent phase of disease, a state of endothelial dysfunction, hypercoagulability and a low-grade inflammation may be persistent, the occurrence of thromboembolic events following acute COVID-19 infection may be not surprising. Herein, we report a case of high-risk PE detected in a post-COVID-19 young woman under hormonal contraception, which required thrombolytic treatment. A number of prothrombotic phenomena, such as overweight, hormonal contraceptive therapy, recent COVID-19 infection and prolonged immobilization, might have synergically contributed to the development of a sublethal thromboembolic event.

Background: Hepatic interstitial T-lymphocytes (T-Li), Natural Killer (NK) and NK-T cells play an important role in both innate and adaptive immunity and contribute to the regulation of ischemia/reperfusion injury (IRI) after transplantation of abdominal organ. Methods: The cellular concentrations and phenotypes of NK, T-Li, NK-T were analyzed retrospectively in a consecutive series of hepatic perfusates after surgical removal of whole livers on the bench previously collected from adult multi-organ donors after brain death. (DBD), and compared with the demographic and pathological characteristics of the patients transplanted at our Institute with kidneys taken from the same donors. The liver interstitial cells were purified from the perfusate by density gradient centrifugation and the phenotype was determined by flow cytometric investigation using the following immunological markers: CD3, CD4, CD8 and CD56 in order to determine the relative percentage of T-Li, NK-T and NK cells. Results: The perfusates of 42 DBDs, and the related clinical outcome of kidney transplant recipients from 2010 to 2020, were analyzed. T-Li were significantly associated with the time in days of delayed functional recovery of transplanted kidneys (DGF) (p = 0.02), to onset of secondary infection from Cytomegalovirus (p = 0.03). On COX analysis, percent cell concentration of T-Li and time to DGF were significantly associated with an increased relative risk (HR) of organ survival (HR = 1.038, p = 0.04; and HR = 1.029, p = 0.01, respectively). The specificity of the NK and NK-T cell proportions were not associated with any relevant clinical outcomes in kidney transplant patients. Conclusions: The present study points to a new potential role of T-Li cells detected in the context of liver perfusate DBD, and could detect potential impacts in organ allocation, surgical harvesting techniques and in the analysis of IRI pathophysiological events after kidney transplants from multi-organ DBDs.

Antimicrobial resistance has become a significant public health problem globally with multidrug resistant Gram negative (MDR-GN) bacteria being the main representatives. The emergence of these pathogens in neonatal settings threatens the well-being of vulnerable neonatal population given the dearth of safe and effective therapeutic options. Evidence from studies mainly in adults is now available for several novel antimicrobial compounds, such as new β-lactam/β-lactamase inhibitors (e.g. ceftazidime-avibactam, meropenem-vaborbactam, imipenem/cilastatin-relebactam), although old antibiotics such as colistin, tigecyclin and fosfomycin are also encombassed in the fight against MDR-GN infections that remain challenging. Data in the neonatal population are scarse, with few clinical trials enrolling neonates for the evaluation of efficacy, safety and dosing of new antibiotics, while the majority of old antibiotics are used off-label. In this article we review data about some novel and old antibiotics that are active against MDR-GN bacteria causing sepsis and are of interest to be used in the neonatal population.

As a result of scientific technological advancements in medical diagnostics, treatment modalities of non-communicable and communicable diseases, and palliative care approaches, the life expectancy of women is soaring than men across the globe, due to the longer telomere length and other protective factors. The main symptoms of menopause broadly be divided into psychological somatovegetative and urogenital. Neglected menopausal symptoms can lead to debilitating comorbidities which may end up in mortalities. Fortunately, modern treatment and therapeutic formalities based on pharmaceutical preparations, as well as lifestyle- modifications have provided long-lasting relief for the pre-menopausal woman. This can be done as per her preference if she is knowledgeable, resourceful, and cheerful. Menarchae is the “ alpha” and menopause is the “omega” phase in the reproductive lifecycle of any woman. Reproductive health is essentially an integral part of women’s health. In this 4^th industial revolution era information technology and digital science go hand in hand to improve the quality of life of populations across the globe irrespective of their educational and professional status. Health literacy among disadvantageous sub populations increased. Positive attitudes, perception and evidence-informed knowledge on adolesecent girls about not only ‘period pains’ but menopausal symptoms as an inevitable phase in a woman’s reproductive health may make a better sense at the dawn of evidence based medicine even in a low middle income country like Sri Lanka. Hence, this timely communication strengthens by, Do not fear when menopause is near: The Importance of a Preparatory Time and Space to face the consequences of Menopaus. How to forget the fact that alpha and the omega are inevitable phases in woman’s reproductive health trajectory. Moreover, the importance of a preparatory time and space well in advance preferably in peri-menopausal time to prevent and control the inevitable health consequences. Moreover, to invest in menopause for a brighter future in the modern personalized medicine era based on global scientific evidence.

Repeated exposure to environmental ozone causes a chronic state of oxidative stress. This state is present in chronic degenerative diseases and induces a loss of control of the inflammatory response. The dysfunction of redox system and failures in control the inflammatory responses are involved in a vicious circle that maintains and increases the degenerative process. Intestine also responds to secondary reactive species formed by exposure to ozone doses, generating noxious stimuli that increase degenerative damage. This review aims to elucidate how environmental pollution, mainly by ozone, induces a state of chronic oxidative stress with the loss of regulation of the inflammatory response, both in the intestine and in the brain, where the functionality of both structures is altered and plays a determining role in some neurodegenerative and chronic degenerative diseases. For this purpose, we searched for information on sites like the Cochrane Library Database, PubMed, Scopus, and Medscape. Reviewing the data published, we can conclude that environmental pollutants are a severe health problem. Ozone pollution has different pathways of action, both molecular and systemic, and participates in neurodegenerative diseases such as Parkinson's and Alzheimer's disease as well in bowel diseases as Inflammatory Bowel Disease, Crohn's Disease and Irritable Bowel Syndrome.

Macrophage-derived chemokine belongs to the CC subfamily. It is produced by dendritic cells (DCs) and macrophages with or without external stimulation. We have previously shown a statistically significant depletion of MDC/CCL22 concentrations in a number of studies concerning COVID-19. These shifts in concentrations demonstrated stability unrelated to the SARS-CoV-2 genetic variant and remained noticeable even in convalescent patients. In this work, we analyze MDC/CCL22 dynamics in various diseases, including those that manifest with inflammation in lung tissue. In addition, we provide our hypothesis on such a decrease in MDC/CCL22 concentrations in COVID-19. If its secretion by producer cells is unperturbed, then it is possible for viral products to bind to this chemokine and to block its functional activity. There is, however, another possible explanation directly linked to depletion in DC subpopulations and the inhibition of their function. We also discuss MDC/CCL22's role in the immunology of novel coronavirus infection, based on both our own data and other studies.

: Studies on the effects of non-nutritive sweeteners (NNSs) in pregnant women are scarce are conflicting. A major challenge is to accurately assess NNS intake, especially in countries where many foods and beverages have been reformulated with the progressive replacement of sugar by NNSs, due to the implementation of new nutrition labelling policies for preventing obesity. This study aimed to develop and valid a food frequency questionnaire (FFQ) to examine the intake of NNSs in pregnant women. This questionnaire was tested in 29 women in their eighth month of gestation, compared to a 3-day dietary records (3-DR). FFQ validity was assessed using Spearman´s correlation coefficient, Lin´s concordance correlation coefficient (CCC) and Bland-Altman plots. Spearman correlations between NNS FFQ and 3-DR ranged from 0.50 for acesulfame K to 0.83 for saccharin. The CCC ranged from 0.22 to 0.66. Bland-Altman plots showed an overestimation of saccharin, sucralose and steviol glycosides intake by the NNS FFQ, and an underestimation of acesulfame K and aspartame, compared to 3-DR. Overall, the most frequently consumed NNS was sucralose None of the participants exceeded the acceptable daily intake for any of the NNSs evaluated. The FFQ of NNSs appears to be a reasonably valid tool for assessing NNS consumption in pregnant women.

Background and Objectives: Acute lung injury (ALI) is an inflammatory response in the lung caused by bacteria, viruses, trauma and other factors that results in lack of alveolar surfactant and subsequently respiratory distress. Endothelial-to-mesenchymal transition (EndoMT) is closely related to ALI-induced pulmonary fibrosis development and progression. This study examined the effect of milk fat globulin factor 8 (MFGE8) knockdown and overexpression on lipopolysaccharide (LPS)-induced EndoMT. Methods: Total MFGE8 activity in patients with acute respiratory distress syndrome (ARDS) and healthy volunteers was assessed using a colorimetric kit. In vitro, cell morphology was observed by microscopy, and invasion and migration were tested by Transwell and scratch assays. Specific siRNAs were transfected into HLMECs to downregulate MFGE8, and CD31 and α-SMA protein expression was detected by fluorescence microscopy and FCM. MFGE8, BMP, Smad 1, Smad4, Smad5, Snail, CD31 and α-SMA protein and gene expression was assessed by western blotting (WB) and qRT‒PCR. In vivo, the changes in cell morphology and alveolar septum in the lung of mice (C57BL/6, aged 7-8 weeks, male) were observed by H&E staining. In addition, ECM deposition in lung tissue was detected by Masson staining. CD31 and α-SMA protein expression in lung tissue was measured by WB. Results: The serum level of MFGE8 was lower in the ARDS group than in the control group. MFGE8 was identified as a protective factor associated with hospital survival. In vitro, the treatment of human lung microvascular endothelial cells (HLMECs) with LPS for 96 h clearly changed the cells from the typical cobblestone shape of ECs to spindle-like fibroblasts. The scratch and Transwell assay results indicated that endothelial cell migration and invasion were enhanced in the LPS group compared with the control group. Fluorescence microscopy, FCM, WB and PCR showed that LPS greatly inhibited CD31 (endothelial marker) expression and increased α-SMA (mesenchymal marker) expression. These data showed that LPS could induce EndoMT in HLMECs. Notably, siRNA-treated HLMECs yielded the same results. The administration of rhMFGE8 to HLMECs in the LPS or LPS+siRNA group ameliorated the changes in cell morphology and decreased cell migration and invasion. rhMFGE8 attenuated the effect of LPS or LPS+siRNA on EndoMT induction by increasing CD31 and decreasing α-SMA protein and gene expression. Moreover, activation of BMP/Smad1/5-Smad4 signalling in response to LPS and Snail (related to EndoMT transcription factors) expression were increased by MFGE8 knockdown but inhibited by rhMFGE8. In vivo, H&E staining revealed a thickened alveolar septum in the LPS group, and the thickness increased over time; in contrast, rhMFGE8 reversed this effect. ECM deposition occurred early in ALI induced by LPS and increased over time, and the administration of rhMFGE8 reversed this effect. WB showed that LPS inhibited CD31 protein expression and increased α-SMA protein expression in lung tissue. Conclusions: rhMFGE8 exerts a protective effect early in LPS-induced EndoMT through BMP/Smad1/5/Smad4 signalling and could be a therapeutic target in ALI.

In post mortem analyses, SARS-CoV-2 was found in the middle ear of some, but not all patients with COVID-19 disease. It is not clear whether SARS-CoV-2 penetrated the ear passively post mortem, or existed in the middle ear of living patients during, and perhaps also after infection. This study investigates whether SARS-CoV-2 can be found in the middle ear of living patients during ear surgery. Swabs from the nasopharynx, the filter connected to the tracheal tube and secretion from the middle ear were collected during middle ear surgery. All samples were tested for the presence of SARS-CoV-2 with PCR. History of vaccination, COVID-19 and contact with SARS-CoV-2-positive individuals were recorded preoperatively. Postoperative SARS-CoV-2 infection was noted at the follow-up visit. Overall 63 participants (62%) were children and 39 (38%) were adults. SARS-CoV-2 was found in the middle ear and in the nasopharynx of two and four CovEar Study participants, respectively. The filter connected to the tracheal tube was sterile in all cases. Cycle threshold (ct) values of the PCR test were between 25.94 and 37.06. SARS-CoV-2 penetrates into the middle ear of living patients and can be found in asymptomatic patients. The presence of SARS-CoV-2 in the middle ear may have implications for ear surgery and can pose a risk of infection for operating room staff. It may also directly affect the audio-vestibular system.

More than 1 million women are diagnosed annually worldwide with a gynecological cancer. Most gynecological cancers are diagnosed at late stage, either because lack of symptoms such as in ovarian cancer or limited accessibility to primary prevention in low-resource countries such as in cervical cancer. Here, we extend the studies of AR2011, a stroma-targeted and tumor microenvironment responsive oncolytic adenovirus (OAdV) whose replication is driven by a triple hybrid promoter. We show that AR2011 was able to replicate and lyse in vitro fresh explants obtained from human ovarian cancer. uterine cancer, and cervical cancer. AR2011 was also able to strongly inhibit the in vitro growth of ovarian malignant cells obtained from human ascites fluid. The virus could synergize in vitro with cisplatin even on ascites-derived cells obtained from patients heavily pretreated with neoadjuvant chemotherapy. AR2011(h404) a dual transcriptionally targeted derived virus armed with hCD40L and h41BBL under the regulation of the hTERT promoter, showed a strong efficacy in vivo both on subcutaneous and intraperitoneally established human ovarian cancer in nude mice. Preliminary studies in an immunocompetent murine tumor model showed that AR2011(m404) expressing the murine cytokines was able to induce an abscopal effect. The present studies suggest that AR2011(h404) is a likely candidate as a novel medicine for intraperitoneal disseminated ovarian cancer.

The aim was to assess the precision and accuracy of cephalometric analyses performed by artificial intelligence (AI) with and without human augmentation. Four dental professionals with varying experience levels and AI identified 31 landmarks on 30 cephalometric radiographs twice. These landmarks were re-identified by all examiners with the aid of AI. Precision and accuracy were assessed by using intraclass correlation coefficients (ICCs) and mean absolute errors (MAEs). AI revealed the highest precision with a mean ICC of 0.97, while the dental student had the lowest (mean ICC: 0.77). AI/human augmentation method significantly improved precision of the orthodontist, resident, dentist, and dental student by 3.26%, 2.17%, 19.75%, and 23.38%, respectively. The orthodontist demonstrated the highest accuracy with a MAE of 1.57 mm/˚. AI/human augmentation method improved the accuracy of the orthodontist, resident, dentist, and dental student by 12.74%, 19.10%, 35.69%, and 33.96%, respectively. AI demonstrated excellent precision and good accuracy in automated cephalometric analysis. The precision and accuracy of the examiners with the aid of AI improved by 10.47% and 27.27%, respectively. The AI/human augmentation method significantly improved the precision and accuracy of less experienced dental professionals to that of an experienced orthodontist.

Left atrial dysfunction is associated with exercise intolerance and poor prognosis in heart failure (HF). The effects of exercise training on atrial function in patients with HF with mid-range ejection fraction (HFmrEF) are unknown. The purpose of the present study was to assess the effects of a 12-weeks supervised concurrent, aerobic continuous plus resistance, exercise training (SCT) pro-gram on left atrial function of patients with HFmrEF. The study included 70 stable patients, who were randomly assigned into two groups: SCT with (three session/week) or a control (CON) group directed to follow contemporary exercise preventive guidelines at home. Before starting the training program and at 12-weeks, all patients performed: ergometric test, 6-minute walk test and echocardiography. At 12-weeks, exercise duration at ergometric test and distance walked at 6-minute walk test presented a significant greater increase in the SCT compared to control (be-tween-groups p 0.0001 and p 0.004 respectively). Peak atrial longitudinal strain and conduit strain presented an increase of 29% and 34% respectively in the SCT and were unchanged in the CON (between-groups p 0.008 and p 0.001 respectively). Peak atrial contraction strain increased of 21% in the SCT with no changes in the CON (between-groups p 0.002). Left ventricular global longi-tudinal strain increased significantly SCT compared to control (between-groups p 0.03). In con-clusions SCT improved left atrial and left ventricular function in HFmrEF

Nutraceuticals are bioactive compounds present in foods, utilized to ameliorate health, prevent diseases, and support the proper functioning of the human body. They have gained attention due to their ability to hit multi-targets and act as antioxidants, anti-inflammatory agents, and modulators of immune response and cell death. Therefore, nutraceuticals are being studied to prevent and treat liver ischemia–reperfusion injury (IRI). This study evaluated the effect of a nutraceutical solution formed by resveratrol, quercetin, omega-3 fatty acid, selenium, ginger, avocado, leucine, and niacin on liver IRI. IRI was performed with 60 min of ischemia and 4 hours of reperfusion in male Wistar rats. Afterward, the animals were euthanized to study hepatocellular injury, cyto-kines, oxidative stress, gene expression of apoptosis-related genes, TNF-alpha and Caspase 3 proteins, and histology. Our results show that the nutraceutical solution was able to decrease apoptosis and histologic injury. The suggested mechanisms of action are a reduction in gene expression and the Caspase 3 protein and a reduction in the TNF-alpha protein in liver tissue. The nutraceutical solution was unable to decrease transaminases and cytokines. These findings suggest that the nutraceuticals used favored the protection of hepatocytes and their combination represent a promising therapeutic proposal against liver IRI.

Erectile dysfunction (ED) is a common and feared complication of radical prostatectomy (RP) for prostate cancer. Recently, tissue engineering is being attempted for post-prostatectomy ED, with controlled interactions between cells, growth factors, and extracellular matrix (ECM) being important for nerve regeneration's structural integrity. In this study, we evaluated the effects of biomechanical ECM patch on human bone marrow-derived mesenchymal stem cells (hBMSCs) morphology and behavior in bilateral cavernous nerve injury (BCNI) rat model. The ECM patch, made of decellularized human fibroblast-derived ECM (hFDM) and a biocompatible polyvinyl alcohol (PVA) hydrogel, was tested with human bone marrow-derived mesenchymal stem cells (hBMSCs) on a bilateral cavernous nerve injury (BCNI) rat model. In vitro analysis showed that the hFDM/PVA + hBMSCs patches significantly increased neural development markers. In vivo experiments demonstrated that the rats treated with the hFDM/PVA patch had higher ICP/MAP ratio, a higher ratio of smooth muscle to collagen, increased content of nNOS, higher levels of eNOS protein expression, and a higher cGMP level compared to the BCNI group. These results indicate that the hFDM/PVA patch is effective in promoting angiogenesis, smooth muscle regeneration, and nitrergic nerve regeneration, which could contribute to improved erectile function in post-prostatectomy ED.

Equine-assisted services (EAS) are being increasingly used as complementary interventions for military veterans who have experienced trauma. However, there is limited evidence of benefit for this population and almost no literature describing desired potential outcomes and possible mechanisms of action. The aim of this article is to address these gaps by reviewing the extant literature of animal-assisted interventions in general, and equine-assisted services in particular, with the goal of providing guidance for future investigations in the field. Currently, the field is in the early stage of scientific development, but published results are promising. Interventions that enhance treatment compliance and/or outcomes could benefit this population. Preliminary results, reviewed herein, indicate that EAS interventions might benefit the military veteran population by enhancing treatment engagement and therapeutic alliance, as well as contributing to symptom reduction and resulting in various transdiagnostic benefits. It is recommended that future studies include exploration of potential beneficial outcomes discussed herein as well as investigate suggested mechanisms of action.

: Background: Parkinson’s disease (PD) is a chronic, progressive illness with a profound impact on health-related quality of life, and it is crucial to know what factors influence quality of life throughout the course of the disease. This study aimed to evaluate PD patients’ motor and non-motor symptoms to compare symptom severity between PD clinical phenotypes and to assess the impact of disease symptoms on quality of life in a cohort of Latvian patients. Methods: We evaluated 43 patients with Parkinson’s disease. Fourteen patients had tremor-dominant (TD) PD, twenty-five patients had postural instability/gait difficulty (PIGD), and four patients had a mixed phenotype. Results: The patients’ mean age was 65.21 years, and the disease’s mean duration was 7 years. The most common non-motor symptoms were fatigue (95.3%), sleep disturbance (83.7%), daytime sleepiness (83.7%), and pain and other sensations (81.4%). PIGD patients had a higher prevalence of depressed mood, daytime sleepiness, constipation, light headedness on standing, cognitive impairment, and severe gastrointestinal and urinary disturbances (as assessed using the SCOPA-AUT domains) compared with TD patients. A high prevalence of fatigue was assessed in both disease subtypes. Health-related quality of life significantly statistically correlated with MDS-UPDRS parts III and IV (r = 0.704), the Hoehn and Yahr scale (r = 0.723), as well as the SCOPA-AUT scale’s gastrointestinal (r = 0.639), cardiovascular (r = 0.586), thermoregulatory (r = 0.566) and pupillomotor domains (r = 0.597). Conclusion: The severity of motor symptoms, as well as non-motor symptoms, such as fatigue, apathy, sleep problems and daytime sleepiness, pain, and disturbances in gastrointestinal and cardiovascular function, negatively affect PD patients’ health-related quality of life. Thermoregulatory and pupillomotor symptoms also significantly affect PD patients’ well-being.

Background: The objective of the present study was to evaluate the formation of biofilm in bone patellar tendon bone grafts (BPTB grafts) and to compare it to the formation of biofilm formation in quadrupled hamstring anterior cruciate ligament grafts (4xHt graft). Methods: A descriptive in vitro study was conducted. One 4xHt graft and one BPTB graft were prepared. They were then contaminated with a strain of S. epidermidis. Later, a quantitative analysis was carried out by means of microcalorimetry and sonication with plating. Additionally, a qualitative analysis was carried out by means of electron microscopy. Results: No significant differences were found between the bacterial growth profiles of 4xHt graft and BPTB graft in microcalorimetry and colony counting. In the samples analyzed with electron microscopy, no specific biofilm growth pattern was identified upon comparing BPTB graft to 4xHt graft. Conclusions: There were no significant differences at either the quantitative or qualitative level when comparing bacterial growth in BPTB graft to that in 4xHt graft. Therefore, the presence of sutures in 4xHt graft cannot be established as a predisposing factor for increased biofilm growth in this in vitro study.

Objective: The Asia-Pacific region (APAC) represents a unique environment for the publication of biomedical research, particularly industry-funded research. Awareness and adoption of international guidelines on ethical publication practices continues to increase across APAC, but the reframing and expansion of many of the recommendations in the Good Publication Practice (GPP) 2022 guidelines versus GPP3 published in 2015 have important implications for publishing industry-funded biomedical research in the region. Methods: This manuscript provides practical guidance for stakeholders in APAC on interpreting and applying the recommendations made in the GPP 2022 guidelines. Results: Key focus areas include navigating new opportunities for communicating industry-funded research, such as plain language summaries, social media, and preprints; implementing formal processes to improve the integrity of published research in APAC; and methods of promoting transparency and inclusion when publishing industry-funded research. Key APAC-specific issues, including encore presentations, leadership on publication ethics in the region, access to professional resources, and support for educating regional stakeholders are also discussed. Conclusions: Overall, this review offers a pragmatic guide for stakeholders in industry-sponsored research on applying GPP 2022 in practice with a focus on effectively integrating these guidelines in an APAC context.

The medical use of Cannabis has a very long history. Although many principles are present in cannabis, called cannabinoids, Δ9tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD) and can-nabinol (CBN) are the three main cannabinoids most present and described. CBD itself is not re-sponsible for psychotropic effects of cannabis since does not produce the typical behavioral effects associated to the consumption of this drug. Cannabidiol (CBD) has recently gained growing at-tention in modern society and seems to be more and more explored in dentistry. Several subjective findings suggest some therapeutic effects of CBD, which are strongly supported by research evi-dence. However, there is a plethora of data regarding CBD’s mechanism of action and therapeutic potential, which are in many cases contradictory. We will first provide an overview of scientific evidence on the molecular mechanism of CBD’s action. Furthermore, we will map the recent de-velopments regarding possible oral benefits of CBD. In summary, we will highlight CBD’s prom-ising biological features for dentistry application, despite exiting patents suggest current the compositions for oral care as the main interest for industry.

Recessive dystrophic epidermolysis (RDEB) is a rare, inherited and currently incurable skin blistering disorder characterized by cyclically recurring wounds coexisting with chronic non-healing wounds. In a recent clinical trial three intravenous infusions of skin-derived ABCB5+ mesenchymal stromal cells (MSCs) to 14 patients with RDEB improved healing of wounds that were present at baseline. Since in RDEB even minor mechanical forces perpetually provoke the development of new or recurrent wounds, a post-hoc analysis of patient photographs was performed to specifically assess the effects of ABCB5+ MSCs on new or recurrent wounds by evaluating 174 wounds that occurred after baseline. During 12 weeks of systemic treatment with ABCB5+ MSCs the number of newly occurring wounds declined. When compared to the previously reported healing responses of the wounds present at baseline, the newly occurring wounds healed faster, and a greater portion of healed wounds remained stably closed. These data suggest a previously undescribed skin-stabilizing effect of treatment with ABCB5+ MSCs and support repeated dosing of ABCB5+ MSCs in RDEB to continuously slow the wound development and accelerate the healing of new or recurrent wounds before they become infected or progress to a chronic, difficult-to-heal stage.

Introduction: The aim of our study was to assess the role of ECG-gated Coronary CT Angiography (CCTA) in the diagnosis, imaging follow-up, and treatment guidance in post-procedural/surgical interventions of the heart and thoracic aorta (PTCA, TAVI, PMK/ICD placement, CABGs).

Euryale ferox, which belongs to the family of Nymphaeaceae, has been widely distributed in China, India, Korea, and Japan. The seeds of E. ferox (EFS) have been categorized as superior food for 2000 years in China, based on its abundant nutrients including polysaccharides, polyphenols, sesquineolignans, tocopherols, cyclic dipeptides, glucosylsterols, cerebrosides, and triterpenoids. These constituents exert multiple pharmacological effects, such as antioxidant, hypoglycemic, cardioprotective, antibacterial, anticancer, antidepression, and hepatoprotective properties. There are very few summarized reports on E. ferox, albeit with its high nutritional value and beneficial activities. Therefore, we collected the reported literatures (since 1980), medical classics, databases, and pharmacopeia of E. ferox, and summarized the botanical classification, traditional uses, phytochemicals, and pharmacological effects of E. ferox, which will provide new insights for the further research and development of EFS-derived functional products.

A clinical case of atypical endophthalmitis in an 82-year-old patient who underwent complicated cataract phacoemulsification. Clinical manifestations showed signs of a bacterial process, however, the treatment was not effective. Antifungal therapy had yielded positive results, despite the low probability of a fungal etiology of the process.

: Background: Pseudomonas aeruginosa is an opportunistic pathogen involved in number of hospital acquired infections such as catheter-associated urinary tract infections, bacteremia, septicemia, skin infections and ventilator-associated pneumoniae. Biofilm formation is an important trait implicated in chronic infections, such as cystic fibrosis and chromic pulmonary obstruction. Method: A total of 266 isolates were collected from the Armed Forces Institute of Pathology (AFIP). Antibiotic susceptibility was assessed by double disk synergy testing. ESBL and Modified Hodge testing was performed for phenotypic confirmation of carbapenemases. Molecular screening of the genes was done by PCR. Micro-dilution broth method was used to determine minimum inhibitory concentrations of antibiotics. Biofilm formation was done by micro-titer plate assay. Results: Overall, 20% of the P. aeruginosa isolates were extensively drug resistant (XDR-PA) and 25% were multi-drug-resistant (MDR-PA). Likewise, 43% of the isolates were ESBL producers and carbapenemase production was detected in 40% of the isolates. Molecular analysis confirmed occurrence of different resistant factors in ESBL positive isolates; 67% carried bla-TEM, 62% bla-CTXM-15, 41% bla-SHV, 34% bla-CTXM-14 and 33% bla-OXA-1. In addition, 68% of carbapenem-resistant isolates were positive for bla-NDM-1, 25% for bla-OXA-48 and 22% for bla-KPC-2. Biofilm formation was tested for 234 isolates, out of which 28% were strong biofilm formers. Moderate and weak biofilm formers were 46% and 23% respectively. Overall, ciprofloxacin, levofloxacin and cefepime showed inhibitory effects on P. aeruginosa biofilms. Antibiotics in combination showed strong synergistic effects (ciprofloxacin &amp; cefepime); while gentamicin and cefepime resulted into complete eradication of P. aeruginosa biofilm. Conclusion: We confirm strong synergistic effects of gentamicin and cefepime that completely eradicated P. aeruginosa biofilm. We further confirm inhibitory effects of ciprofloxacin, levofloxacin and cefepime on P. aeruginosa biofilms.

Chia seed, high in dietary-fiber and protein, may have potential to increase satiety. However, previous studies are confounded by differences in energy intake, and none investigated doses &lt;7g. We compared the subjective appetite and glycaemic responses elicited by 30g cookies containing 0, 3, 5 or 7g chia seed (CS0, CS3, CS5 or CS7, respectively, 140-150kcal, 7-8g fat, 4g protein, 0-2g dietary-fiber, 16g available-carbohydrate) using a randomized, double-blind, cross-over design. Overnight-fasted heathy adults (24 males, 22 females; mean±SD age 37±13y; BMI 27.4±3.9kg/m²) consumed test-cookies and had appetite and plasma-glucose measured before and intermittently for 3h after eating. Data were analyzed by ANOVA with Tukey’s test to adjust for multiple comparisons; the criterion for significance was 2-tailed p&lt;0.025 for the primary endpoints of total area under the curve (tAUC0-3h) for hunger and fullness. Hunger tAUC0-3h was similar among treatments (p=0.49) but fullness differed (p=0.019) with tAUC0-3h after CS3&gt;CS7 (mean±SEM) (140±9 vs 122±10mm×h, p&lt;0.025). Mean incremental glucose AUC0-2h after CS3, CS5 and CS7, respectively, were 22%, 23% and 30% less than CS0 (p&lt;0.05). Thus, although chia reduced glycemic responses, we were unable to demonstrate a significant effect of ≤7g chia seed on the primary endpoints of hunger or fullness tAUC0-3h versus control.

The purpose of the study was to evaluate the success of procedural conscious sedation, using inhaled equimolar nitrous oxide-oxygen (NOIS – EMONO), in patients undergoing routine dental and oral surgery procedures in a Swiss university hospital setting. Materials and methods: The authors conducted a retrospective cohort study of patients that underwent NOIS-supported procedures between 2018 and 2022 at the oral surgery department of the University Hospital of Geneva (HUG), Switzerland. The primary outcome was the measurement of the procedure success and efficacy as defined by the European Society of Anesthesiology. Secondary objectives included the analysis of the types of treatments performed, their indications, patient behavior, and the patient - clinician satisfaction score. Results: 55 patients were included in the study, 85% underwent surgical procedures, the remaining 15% underwent restorative and preventive procedures. The overall treatment success rate was 98.2%, and 97.9% for surgically treated patients. 62% of patients appeared relaxed, calm, and serene, while 16% expressed pain or fear during the procedure. Infiltrative administration of local anesthesia caused stress in 22% of patients, this was significantly lower in sub cohorts who received local topical anesthetics (0%) or a combination of systemic and local topical analgesics (7%). Patients (75%) and clinicians (91%) were satisfied with the procedure. Conclusion: Inhaled equimolar nitrous oxide-oxygen procedural sedation used during dental procedures and oral surgery results in high treatment success and satisfaction rates. The administration of additional topical anesthetics helps reduce the anxiety and stress related to infiltrative anesthesia. Further dedicated studies and prospective trials are needed to confirm these findings.

NCX 470, a nitric oxide (NO)-donating bimatoprost, was shown to ameliorate ocular hemodynamics and retinal physiology in rabbits following endothelin-1 (ET-1)-induced ischemia/reperfusion. Here we used the same model to compare NCX 470 (0.1% bid) to Lumigan® (bimatoprost 0.01% ophthalmic solution, LUM) and bimatoprost administered at equimolar dose as NCX 470 (0.072%, BIM). Intraocular pressure (IOP), ophthalmic artery resistive index (OA-RI) and electroretinogram (ERG) were computed prior to treatment and at various time-points thereafter. Gluthatione (GSH), 8-Hydroxy-2-deoxyguanosine (8-OH2dG), Interleukin-1beta (IL-1β), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6) and Caspase-3 protein expression and activity were determined in retina at week 6. ET-1 increased IOP (VEHIOP_Baseline=20.5±0.8 and VEHIOP_Week6=24.8±0.3mmHg) and OA-RI (VEHOA-RI_Baseline=0.36±0.02 and VEHOA-RI_Week6=0.55±0.01) while it reduced rod/cone responses. Oxidative stress, inflammation and apoptotic markers were also increased in ET-1-treated eyes. NCX 470 prevented IOP (NCX 470IOP_Week6=18.1±0.6mmHg) and OA-RI (NCX 470OA-RI_Week6=0.33±0.01) changes and restored ERG amplitude; these effects were only partially shared by LUM or BIM. Additionally, NCX 470 reduced oxidative stress, inflammation and apoptosis in retina of treated eyes. BIM and LUM were numerically less effective on these parameters. Data suggest that NCX 470 repeated ocular dosing ameliorates ocular hemodynamics and retinal cell dysfunction consequent to ischemia/reperfusion via both, NO- and bimatoprost-mediated mechanisms.

Severe combined immunodeficiency (SCID) is a primary inherited immunodeficiency that could be fatal, usually due to opportunistic infections caused by bacteria, viruses, fungi, and protozoa if left untreated. Opportunistic infections are the most common presentation of SCID these include viral, fungal, or intracellular bacteria, and infection should prompt immunological investigation. This review aimed to provide a comprehensive approach to the microrganisms associated with severe combined immunodeficiency (SCID) and its management. The authors described SCID as a syndrome and summarized the different microorganisms that affect children and how they are managed.

This study aimed to evaluate contrast-enhanced mammography (CEM) and compare breast lesions on CEM and breast magnetic resonance imaging (MRI) using 5 features. We propose to create a flowchart for BI-RADS classification of breast lesions on CEM based on the Kaiser score (KS) flowchart for breast MRI. Included were 68 subjects (women and men; median age 61.4 ± 11.6 years) who were suspected of having a malignant process in the breast based on digital mammography (MG) findings. The patients underwent breast ultrasound (US), CEM, MRI, and biopsy of the suspicious lesion. There were 47 patients with malignant lesions confirmed by biopsy and 21 patients with benign lesions, for each of which a KS was calculated. In the patients with malignant lesions, the MRI-derived KS was 9 (IQR 8-9), its CEM equivalent was 9 (IQR 8-9), and BI-RADS was 5 (IQR 4-5). In patients with benign lesions, MRI-derived KS was 3 (IQR 2-3), its CEM equivalent was 3 (IQR 1.7-5), and BI-RADS was 3 (IQR 0-4). There was no significant difference between the ROC-AUC of CEM and MRI (P=0.749). In conclusion, there were no significant differences in KS results between CEM and breast MRI. The KS flowchart is useful for evaluating breast lesions on CEM.

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), defines as an idiopathic, chronic, relapsing, inflammatory disease affecting the gastrointestinal tract and leading to chronic damage. Endoscopy with biopsies is considered the gold standard for IBD diagnosis, whereas magnetic resonance (MRI) for CD extension and complication assess-ment. However, the latter are invasive procedures; thus, the need for a reliable, accessible and noninvasive way to perform IBD diagnosis and monitoring in the tight control era, like intestinal ultrasound (IUS) is. Compared to endoscopy and MRI, IUS has shown reliable diagnostic accuracy in assessing CD and UC severity and extension. Performing IUS in a point-of-care setting (POCIUS) can guide the clinician in driving the diagnostic and therapeutic pathway, thus accel-erating clinical decisions. POCIUS performed with pocket devices can represent the future of physical examination in outpatient or inpatient examination. Accordingly, we performed a liter-ature review about the application of IUS in CD and UC diagnosis. Furthermore, we explored the technical aspects of this imaging technique and its application in a point-of-care setting.

Amphetamine is a psychostimulant drug with a high risk of toxicity and death when misused. Abuse of amphetamines is associated with an altered organic profile, which includes omega fatty acids. Low omega fatty acid levels are linked to mental disorders. Using the Comparative Toxicogenomic Database (CTD), we investigated the chemical profile of the brain in amphetamine-related fatalities and the possibility of neurotoxicity. We classified amphetamine cases as low (0-0.5 g/ml), medium (&gt;0.5 to 1.5 g/ml), and high (&gt;1.5 g/ml) based on amphetamine levels in brain samples. All three groups shared 1-octadecene, 1-tridecene, 2,4-di-tert-butylphenol, arachidonic acid, docosahexaenoic acid (DHA), eicosane, and oleylamide. We identified chemical-disease associations using the CTD tools and predict an association between docosahexaenoic and arachidonic acids and curated conditions like autistic disorder, disorders related to cocaine, Alzheimer's disease, and cognitive dysfunction. An amphetamine challenge may cause neurotoxicity in the human brain due to a decrease in omega-3 fatty acids and an increase in oxidative products. Therefore, in cases of amphetamine toxicity, supplement therapy may necessitate preventing omega-3 fatty acid deficiency.

Vaginal ecosystem is a unique environment where, in physiological conditions, lactobacilli dominate. However, also pathogenic microbial species, responsible of vaginitis and vaginosis, can harbor vaginal microbiota. To extend the data published by De Seta and Larsen in Pathogens (2021), here we analyzed both the anti-Candida and anti-inflammatory properties of the vaginal gel formulation, Respecta® Balance Gel (RBG), commercialized as an adjuvant to treat vaginitis and vaginosis. We evaluated its activity by an in vitro model where a monolayer of A-431 vaginal epithelial cells was infected by Candida albicans in the presence of RBG or the placebo formulation (pRBG). Specifically, we tested the RBG capacity to counteract C. albicans virulence factors as well as their anti-inflammatory properties. Our results show that, unlike the placebo, RBG reduces ,reduces, C. albicans adhesion, its capacity to form hyphae and C. albicans-induced vaginal cell damage. Interestingly, both RBG and pRBG reduce LPS-induced IL-8 secretion (being RBG the most effective) demonstrating that also the placebo retains anti-inflammatory properties. By our experimental approach we highlight the possible role of farnesol on such effects, but we would like to point out that lactic acid, polydextrose and glycogen too must be relevant in the actual application. Taken together, our results show that RBG impairs C. albicans virulence and is able to reduce the inflammation in the vaginal environment, ultimately allowing the establishment of a balanced vaginal ecosystem.

The field of anesthesia has always been at the forefront of innovation and technology, and the integration of Artificial Intelligence (AI) represents the next frontier in anesthesia care. The use of AI and its subtypes such as machine learning has the potential to improve efficiency, reduce costs, and improve patient outcomes. AI can assist with decision-making, but its primary advantage lies in empowering anesthesiologists to adopt a proactive approach to address clinical issues. However, further research and validation are needed to fully understand the benefits and limitations of these applications in clinical practice. Moreover, the ethical implications of AI in anesthesia must also be considered to ensure that patient safety and privacy are not compromised. This paper aims to provide a comprehensive overview of AI in anesthesia, including its current and potential applications, and the ethical considerations that must be considered to ensure the safe and effective use of the technology.

Interpreting khat-related fatalities is challenging due to a lack of data on cathinone and cathine reference concentrations in postmortem tissues. This study investigated the autopsy findings and toxicological results of Khat-related fatalities in Saudi Arabia's Jazan region from January 1, 2018 to December 31, 2021. All confirmed cathine and cathinone results in postmortem blood, urine, brain, liver, kidney, and stomach samples were recorded and analyzed. Autopsy findings and the manner and cause of death of the deceased were assessed. Saudi Arabia's Forensic Medicine Center investigated 651 fatality cases over four years. Thirty postmortem samples were positive for khat's active constituents, cathinone and cathine. The percentage of khat-related fatalities was 3% in 2018 and 2019, and increased from 4% in 2020 to 9% in 2021, when compared to all fatal cases. They were all male ranging in age from 23 to 45. Firearm injuries (10 cases), hanging (7 cases), road traffic accident (2 cases), head injury (2 cases), stab wounds (2 cases), poisoning (2 cases), unknown (2 cases), ischemic heart disease (1 case), brain tumor (1 case), and choking (1 case) were responsible for deaths. 57% of postmortem samples tested positive for khat only, while 43% tested positive for khat with other drugs. Amphetamine is the drug most frequently involved. Cathinone and cathine average concentrations were 85 and 486 ng/mL in blood, 69 and 682 ng/mL in brain, 64 and 635 ng/mL in liver, and 43 and 758 ng/mL in kidney. The 10th–90th percentiles of blood concentrations of cathinone and cathine were 18 – 218 ng/mL and 222 – 843 ng/mL, respectively. These findings show that 90% of khat-related fatalities had cathinone concentrations greater than 18 ng/mL and cathine concentrations greater than 222 ng/mL. According to the cause of death, homicidal was most common in fatalities involving khat alone (77%). More research is required, especially toxicological and autopsy findings, to determine the involvement of khat in crimes and fatalities. This study may help forensic scientists and toxicologists investigate khat-related fatalities.

Knee Osteoarthritis (KOA), the most common knee degenerative disease, involve a slow destructive process, leading to disability and ultimately total knee replacement. The progression of KOA is related to the loss of rheological properties of the synovial fluid (SF), due to slow immunological, inflammatory and enzymatic processes that cleave the hyaluronic acid (HA) and decrease the concentration of specific proteins. Since no effective treatments have been found to halt the progression of KOA, injection of HA-based viscoelastic gels combined with physiotherapy (PT) is an alternative to symptomatic therapies. In order to evaluate the effect of viscosupplementation and PT on the SF characteristics, the SF aspirated from the KOA was spectrophotometrically and rheological analyzed, comparing the receiving groups of HA Kombihylan® and groups that received Kombihylan® and complex PT. In patients treated with PT, SF extracted 6 weeks after viscosupplementation had a superior elastic moduli (G') and viscous moduli (G") profile behavior, having a homogeneous distribution of proteins and polysaccharides in the SF, stimulating stronger interactions. In the absence of PT the G' and G" profiles are non-uniform, suggesting an unorganized supplemented SF with some clustering phenomena, proteins aggregation and a low level of entanglement between HA and macromolecular components in the SF.

Histoplasmosis is a systemic mycosis of universal distribution, highly endemic in the Americas. It is caused by a dimorphic fungus Histoplasma capsulatum var. capsulatum. It affects both immunocompetent and immunocompromised individuals where progressive and disseminated forms are observed. A very important risk factor is HIV infection/AIDS, with a mortality rate of 20-40% in Latin America. The diagnosis of this mycosis is made by conventional and molecular methods or by antigen and antibody detection. This study evaluated the sensitivity and specificity of a commercial kit for the detection of Histoplasma antigen by an EIA (HC-Ag) technique in 50 patients with histoplasmosis associated with AIDS. In addition, its performance was compared with that of other diagnostic techniques routinely used in our laboratory. HC-Ag had a sensitivity (S) of 94%, specificity (E) 95.5%, positive predictive value (PPV) 94% and negative predictive value (NPV) 95.5%. The delay time of the results was 4 days, similar to that of antibody detection and n-PCR and much less than that of blood cultures. The combination of methods improved S and NPV: 100%; with similar values in E and PPV. The HC-Ag method demonstrated its usefulness in the diagnosis of progressive disseminated histoplasmosis and the combination of methods is a good option to increase sensitivity and decrease the time to reach the diagnosis of certainty. This allows improving the strategy in the management of the disease and decreasing its case-fatality rate.

Over the last decades, the increased incidence of metabolic disorders such as type 2 diabetes and obesity has motivated researchers to investigate new enzyme inhibitors. In this study, the inhibitory effects of synthetic amino acid derivatives (PPC80, PPC82, PPC84, PPC89, and PPC101) on the activity of digestive enzymes was assessed by in vitro assays. The inhibitory effect was determined by the inhibition percentage and the 50% inhibitory concentration (IC50), and the mechanism of action was investigated by Lineweaver–Burk plots. PPC80, PPC82, and PPC84 inhibited pancreatic lipase (IC50 of 1.67–10.23 x 10-1 mmol/L). The activity of pancreatic α-amylase was suppressed by PPC80, PPC82, PPC84, PPC89, and PPC101 (IC50 of 1.62–5.19 x 10-1 mmol/L). Finally, PPC84, PPC89, and PPC101 also showed a potent inhibitory effect on α-glucosidase (IC50 of 0.51–3.53 x 10-1 mmol/L). PPC80 and PPC82 followed a non-competitive inhibition mechanism against pancreatic lipase, while PPC84 acted through competitive inhibition. The inhibition of pancreatic α-amylase by the derivatives was non-competitive, as well as for PPC84, PPC89 and PPC101 against α-glucosidase. The results suggest that these synthetic amino acid derivatives have inhibitory potential against digestive enzymes and may be used as therapeutic agents to control metabolic disorders.

Background: In regenerative dentistry the graft material influences the success. It should act as an osteoconductive scaffold, providing a mineral substrate during resorption and inducing the activity of osteoinductive cells capable of producing new bone, platelet growth factors, and cell differentiation factors inducing the differentiation of undifferentiated mesenchymal cells into. Given that dentin shares many biochemical characteristics with bone tissue, it has recently attracted considerable interest as a biomaterial for bone repair. The aim of this study is to compare two grinder types in order to determine the optimal method for producing dentinal particles using a mechanical grinder. Materials and methods: A sample of 40 natural human teeth without restorations, prostheses or root canal treatments was used and divided into two groups subjected to two different grinder speeds (high-speed and low-speed). The high-speed showed a greater dispersion (53.5+-9.89% of the tooth) due to the pulverisation (highly thin granules) of part of the tooth. The low-speed grinder does not pulverize the dentin and the percentage of tooth loss is 9.16+/-2.34%. Conclusion: The low-speed gringer allows to save a major part of the tooth and to have a maximum quantity of graft material but requires more time. Further studies must be promoted to optimise the grinding procedures.

Recent studies show that repetitive transcranial magnetic stimulation (rTMS) improves cognitive and motor functions in patients with Parkinson’s Disease (PD). Gamma rhythm low-field magnetic stimulation (LFMS) is a new non-invasive rTMS technique that generates diffused and low-intensity magnetic stimulation to deep cortical and subcortical areas. To investigate potential therapeutic effects of LFMS in PD, we subjected an experimental mouse model to LFMS (as early treatment). We examined the LFMS effect on motor functions as well as neuronal and glial activities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced male C57BL/6J mice. Mice received MPTP injection (30 mg/kg, i.p., once daily for 5 days) followed by LFMS treatment, 20 minutes each day for 7 days. LFMS treatment improved motor functions compared to the sham-treated MPTP mice. Further, LFMS significantly improved tyrosine hydroxylase (TH) and decreased glial fibrillary acidic protein (GFAP) levels, in substantia nigra pars compacta (SNpc) and non- significantly in striatal (ST) regions. LFMS treatment improved neuronal nuclei (NeuN) level in SNpc. Our findings suggest that early LFMS treatment improved the neuron survival and in turn, motor functions in MPTP intoxicated mice brain. Further investigation is required to clearly define the molecular mechanisms by which LFMS improves motor and cognitive function in PD patients.

Middle-aged adults can start to be affected by some arterial diseases, such as abdominal aortic or popliteal artery aneurysms, lower extremity arterial disease, internal carotid or renal artery or subclavian artery stenosis. These vasculopathies are often paucisymptomatic before manifesting themselves with dramatic complications. Therefore, early detection of peripheral artery disease (PAD) and aneurysmal disease is fundamental to reduce the risk of major adverse cardiovascular and limb events. Furthermore, PAD carries a high correlation with silent coronary artery disease (CAD). This study focuses on the most common PADs and aneurysmal diseases, in the attempt to summarize some key points which should selectively drive screen. Since it is evident how we are not in the human and economic possibilities to instrumentally screening wide populations, deep knowledge of semeiotics and careful anamnesis must play a central role in our daily activity as physician. The presence of some risk factors for atherosclerosis, or an already known history of CAD, can raise the clinical suspecion of PAD or aneurysmal disease after a careful clinical history and a deep physical examination. The clinical suspicion must then be confirmed by a first-level ultrasound investigation and, if so, adequate treatments can be adopted to prevent dreadful complications.

Prediction of survival in very preterm infants is very important in terms of clinical medicine and parent counseling. In this prospective study involving 96 very preterm infants, we evaluated whether metabolomic analysis of gastric fluid and urine samples obtained soon after birth could predict survival on days of life (DOL) 3 and 15 as well as overall survival up to hospital discharge. Gas chromatography-mass spectrometry (GC-MS) profiling was used. Uni- and multivariate statistical analyses were carried out to evaluate significant metabolites and their prognostic value. Differences in several metabolites were identified between survivors and non-survivors at the time-points of the study. Binary logistic regression showed that certain metabolites in the gastric fluid including arabitol as well as succinic, erythronic and threonic acids was associated with DOL 15 and overall survival. Gastric glyceric acid was also associated with DOL 15 survival. Urine glyceric acid could predict survival on DOL 3 and overall survival. In conclusion, non-surviving preterm infants showed a different metabolic profile compared survivors showing a significant discrimination with the use of GC-MS-based gastric fluid and urine analysis. Results of this study support the usefulness of metabolomics in developing survival biomarkers in very preterm infants.

Platinum-resistant high-grade serous ovarian cancer (HGSOC) is invariably a fatal disease, so a central goal in ovarian cancer research is to develop novel strategies to overcome platinum resistance. Treatment is thus moving towards personalized therapy. However, validated molecular biomarkers to predict patients’ risk of developing platinum resistance are still lacking. Extracellular vesicles (EVs) are promising candidates for biomarkers. EpCAM-specific EVs are largely unexplored biomarkers in predicting chemoresistance. Using transmission electron microscopy, nanoparticle tracking analysis and flow cytometry, we compared the characteristics of EVs released from a cell line derived from a clinically confirmed cisplatin-resistant patient (OAW28) and EVs released from two cell lines from tumors sensitive to platinum-based chemotherapy (PEO1, OAW42). We showed that characteristics of EVs released from the HGSOC cell line of chemoresistant patients had higher heterogeneity in size, a larger proportion of medium/large (&gt;200nm) EVs and a higher number of released EpCAM-positive EVs of different sizes, although expression of EpCAM predominated, especially on those larger than 400 nm. We also determined a strong positive correlation between the concentration of EpCAM-positive EVs and expression of cellular EpCAM. These results may contribute to prediction of platinum resistance in the future, although they should first be validated in clinical samples.

Anti-islet autoantibodies serve as key markers in immune-mediated type 1 diabetes (T1D) and slowly-progressive T1D (SPIDDM), also known as latent autoimmune diabetes in adults (LADA). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), tyrosine phosphatase-like protein IA-2 (IA-2A), and zinc transporter 8 (ZnT8A) are currently employed in the diagnosis, pathological analysis, and prediction of T1D. GADA can also be detected in non-diabetic patients with autoimmune diseases other than T1D and may not necessarily reflect insulitis. Conversely, IA-2A and ZnT8A serve as surrogate markers of pancreatic β-cell destruction. Combinatorial analysis of these four anti-islet autoantibodies demonstrated that 93-96% of acute-onset T1D and SPIDDM cases were diagnosed as immune-mediated T1D, while the majority of fulminant T1D cases were autoantibody-negative. Evaluating the epitopes and immunoglobulin subclasses of anti-islet autoantibodies help distinguish between diabetes-associated and non-diabetes-associated autoantibodies and is valuable for predicting future insulin deficiency in SPIDDM (LADA) patients. Additionally, GADA in T1D patients with autoimmune thyroid disease reveals the polyclonal expansion of autoantibody epitopes and immunoglobulin subclasses. Recent advancements in anti-islet autoantibody assays include nonradioactive fluid-phase assays and the simultaneous determination of multiple biochemically defined autoantibodies. Developing a high-throughput assay for detecting epitope-specific or immunoglobulin isotype-specific autoantibodies will facilitate more accurate diagnosis and prediction of autoimmune disorders.

The effects of the consumption of an extract of the brown seaweed Ascophyllum nodosum (BSW) on postprandial glucose and insulin response to white bread were investigated in an acute, randomized, double-blind, three-arm, crossover, controlled trial in healthy, normoglyacemic subjects. Sixteen subjects were administrated either control white bread (50 g total digestible carbohydrates), or white bread with either 500 mg or 1000 mg of BSW extract. Biochemical parameters were measured in venous blood over 3h. Significant inter-individual variation in the glycaemic response to white bread was observed. Analysis of the response of all subjects to either 500 mg or 1000 mg of BSW extract versus control revealed no significant effects of treatments. The variation in response to the control was used to classify individuals into glyacemic responders and non-responders. In the sub-cohort of 10 subjects with peak glucose levels after white bread above 1mmol/L we observed a significant decrease in maximum levels of plasma glucose after the intervention meal with 1000 mg of extract, compared with control. No adverse effects were reported. Further work defining all factors that determine “responders” to the effects of brown seaweed extracts and identify the cohort that would benefit the most from their consumption, is warranted.

Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) is characterized by biphasic seizures following febrile viral infections and delayed reduced diffusion of the cerebral white matter on magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) (bright tree appearance, BTA). However, hypoxic encephalopathy with biphasic seizures and AESD-mimicking imaging findings has not been reported. Herein, we report an case of hypoxic encephalopathy due to suffocation with concomitant biphasic seizures and BTA, mimicking AESD. On day 1, a 5-month-old female was found face down with breathing cessation and deteriorating consciousness level. The electroencephalography (EEG) revealed periodic epileptic discharges, suggesting possible nonconvulsive status epilepticus. Despite the improvements in consciousness level and EEG abnormalities on day 2, her consciousness level deteriorated again with generalized tonic-clonic seizures on day 3, and head MRI-DWI revealed restricted diffusion predominantly in the subcortical areas, suggesting BTA. Treatment for acute encephalopathy resolved clinical sei-zures and EEG abnormalities. The persistence of abnormal EEG, reflecting abnormal excitation and accumulation of neurotoxic substances caused by hypoxia, may have contributed to the devel-opment of AESD-like findings. As hypoxic encephalopathy causes AESD-like biphasic seizures, monitoring the consciousness level, seizure occurrence, and EEG abnormalities even after acute symptoms have temporarily improved following hypoxia is essential.

Inflammation is an underlying problem for many disease states and has been implicated in iron deficiency (ID). This study aimed to determine whether iron status is improved by epigallocate-chin-3-gallate (EGCG) through reducing inflammation. Thirty-two male Sprague-Dawley rats were randomly divided into four groups (n = 8 each): positive controls, negative controls, lipo-polysaccharide (LPS, 0.5 mg/kg body weight), and LPS + EGCG (LPS plus 600 mg EGCG/kg diet). Iron status, hepcidin, C - reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were measured. There were no differences in treatment groups compared with control in CRP, hepcidin, and liver iron concentrations. Serum iron concentrations were significantly lower in the LPS (p=0.02) and the LPS+EGCG (p=0.01) than in the positive control group. Compared to the positive control group, spleen iron concentrations were significantly lower in the negative con-trol (p<0.001) but not with both LPS groups. SAA concentrations were significantly lower in LPS + EGCG group compared to LPS alone group. IL-6 concentrations were significantly higher in LPS+EGCG (p= 0.004) than in any of the three groups. EGCG reduced SAA concentrations but did not affect hepcidin or improve serum iron concentration or other iron markers.

This review brings together the current knowledge regarding the risk factors, and the clinical, radiologic and histological features of both post-COVID-19 interstitial pul-monary fibrosis (PCPF) and Idiopathic Pulmonary Fibrosis (IPF) with a particular fo-cus on describing the similarities and the disparities between the fibrotic changes in these two diseases. It is important to highlight the common points of PCPF and IPF to observe if they are some targetable changes to improve patient outcomes. The litera-ture review was performed using numerous databases to identify relevant articles published in English through October 2022. This review would help clinicians, pathologists and researchers to make an accurate diagnosis, which can be useful in identifying the group of patients who can be selected for antifibrotic therapies, and future therapeutic perspectives.

Abstract: Advanced high-grade serous ovarian carcinoma is a serious malignant neoplasm with a late diagnosis and high mortality rate. Even when treated with standard therapy, such as surgery followed by carboplatin and paclitaxel chemotherapy, the prognosis remains unfavorable. Im-munotherapy is a treatment alternative that requires further study. Therefore, we aimed to evaluate the expression of the immunotherapy markers: PD-1, PD-L1, CD8, MSI (MLH1, MSH2, MSH6, and PMS2), and p53 in the paraffin samples of high-grade serous ovarian carcinoma. A retrospective study of 28 southern Brazilian patients with advanced serous ovarian carcinoma (EC III or IV) was conducted between 2009 and 2020. The expression of these proteins was evaluated using im-munohistochemistry, and the results were correlated with the patients' clinicopathological data. At diagnosis, the mean age was 61 years, and the most common clinical stage (60%) was EC III. Among the cases, 84.6% exhibited p53 overexpression, 14.8% had MSI, 92.0% were sensitive to platinum, and more than 50.0% relapsed after treatment. Patients with MSI had a lower CD8/PD-1 ratio and more relapses (p=0.03). In conclusion, analysis of immunotherapeutic markers in paraf-fin-embedded samples of advanced serous ovarian carcinoma is feasible and may assist in prog-nosis.

Longer operating time in radical prostatectomy may escalate the risk of perioperative complications. Various factors like cancer extent, procedure’s level of difficulty, habitus and previous surgeries may lengthen robotic assisted radical prostatectomy (RARP) and therefor compromise outcomes. Objective: this study investigates the influence of operating time on outcomes after RARP in real life settings in a monocentric single surgeon study. Methods: 500 consecutive patients who underwent RARP between April 2019 and August 2022 were included. Patients were divided in three groups. Short (n=157; 31.4%) under or equal to 120 minutes, average (n=255; 51%) between 121 and 180 minutes, long (n=88; 17,6%) above 180 minutes console-time. Demographic, baseline and perioperative data were analyzed and compared between groups. Univariate logistic regression was completed to investigate the association between console-time and outcomes and to predict factors which may prolong surgery. Results: hospital stay and catheter days were significantly longer in group 3 with medians 6 and 7 days (p<0.001 and <0.001, respectively). Those findings were confirmed in univariate analysis, p=0.012 for Catheter days and p<0.001 for Hospital stay. Moreover, major complications were higher in patients with longer procedures p=0.008. Prostate volume was the only predictor for prolonged console time (p=0.005). Conclusion: RARP is a safe procedure and most patients will be discharged uneventfully. Yet longer console-time is associated with longer hospital stay, catheter days and major complications. Caution has to be taken in large prostate to avoid longer procedures, which may prevent postoperative advert events.

The purpose of this work was to evaluate a novel methodology developed by Digital Blood Corporation (DBC) to calculate critical blood values using four non-invasive measured values as input. The values obtained using a point-of-care testing (POCT) device were utilized for comparison and reference. Radial arterial blood was collected for the POCT comparator analysis using the Abbott i-STAT^® device. The non-invasive methodology from DBC requires four parameters to be directly measured: temperature, hemoglobin, pO2, and pCO2. Subsequently, sodium, potassium, chloride, ionized calcium, total carbon dioxide, pH, bicarbonate, and oxygen saturation are calculated using an algorithm. The agreement between the POCT and DBC’s methodology was analyzed using Bland-Altman difference plots. For a second data set, pO2 and pCO2 values collected with the POCT were used as input for DBC’s algorithm to test its robustness. Data from 37 healthy ambulatory individuals, mean age: 42.4 + 13 years; range: 18-64 years, were included in the primary analysis. In the case of the non-invasive gained four input values the greatest variation between POCT and DBC’s approach was observed for pO2 and consequently for algorithm values that depend upon pO2 precision. Replacing transcutaneous pO2 and pCO2 with POCT values demonstrates the principal ability of DBC’s algorithm to predict the additional 8 blood values in sufficient agreement with a standard POCT device in healthy patients. The algorithm developed by DBC appears to be robust in the case of healthy patients but does need the four measured input values with preciseness comparable to a POCT device to give reliable and clinically relevant results. The present study thus serves as a proof of concept to facilitate future study and further development of this methodology into a non-invasive device.

This study aimed to establish and verify the validity of an acoustic simulation method during sustained phonation of the Japanese vowels /i/ and /u/. The study participants were six healthy adults. First, vocal tract models were constructed based on computed tomography (CT) data, such as the range from the frontal sinus to the glottis, during sustained phonation of /i/ and /u/. Next, cylindrical shapes virtually extended by 12 cm were added to the vocal tract models to imitate the trachea between the tracheal bifurcation and lower part of the glottis. The Kirchhoff–Helmholtz integral equation was formulated as the wave equation for sound propagation, and the boundary element method was used for discretization. As a result, the relative discrimination thresholds of the vowel formant frequencies for /i/ and /u/ against actual voice were 1.1%–10.2% and 0.4%–9.3% for the first formant and 3.9%–7.5% and 5.0%–12.5% for second formant, respectively. In the vocal tract model with nasal coupling, a pole–zero pair was observed at around 500 Hz, and for both /i/ and /u/, a pole–zero pair was observed at around 1000 Hz regardless of the presence or absence of nasal coupling. These findings demonstrated that /i/ and /u/ could be simulated with high validity in a vocal tract model constructed from CT data obtained during sustained phonation using the boundary element method.

A sixty-six-year-old woman with a strong family history of breast cancer noted gradual onset of axillary lymph node enlargement in 2019. Axillary lymph node biopsies disclosed Lymph node involvement by Chronic Lymphocytic Leukemia (CLL/SLL). Immunophenotype analysis of nodal tissue and of bloodstream leukemic cells in immunohistochemistry and flow cytometry and next generation molecular diagnostics confirmed CLL/SLL. Replicate absolute peripheral blood lymphocyte counts in excess of 5.0 x 10e3/microliter confirmed the numerical threshold for diagnosis of Chronic Lymphocytic Leukemia in the bloodstream. FISH studies disclosed an immunoglobulin “mutation negative” CLL/SLL genotype without a light chain restriction pattern. No translocations or germline mutations were present. Borrelia spirochetes in the bloodstream were detected with simultaneous high spirochetemia of both borrelia miyamotoi and borrelia burgdorferi. FISH hybridization of leukemic lymphocytes disclosed extensive borrelia invasion of the cytoplasm and of the nucleus compartments of CLL/SLL tumor cells. Retrospective studies of the patient’s archival stored blood smears obtained three years prior in 2016 at age 63 disclosed no evidence of CLL/SLL but confirmed asymptomatic bloodstream borrelia miyamotoi and borrelia burgdorferi borrelia infection. Lyme serology had been reported as negative in 2016. Additionally, retrospective FISH DNA hybridizations focused on preleukemic bloodstream Lymphocytes disclosed rare borrelia spirochetal adherence to benign blood lymphocytes in the year 2016 in the preleukemic blood smears. This case report is the very first to describe precursor chronic asymptomatic Lyme borreliosis and Miyamotoi borrelia bloodstream infections three years prior to the diagnosis of Rai Stage 1 Chronic Lymphocytic leukemia.

Canine hypoadrenocorticism is a rare chronic disease, which demands intense dog-owner interaction, as its treatment requires to be individualised. The aim of this study was a qualitative analysis of the challenges owners face when dealing with the disease, especially regarding its management and how this affects quality of life. By promoting an online discussion between owners, we transcribed and summarised their experiential knowledge in dealing with the disease. Owners were recruited for the online seminars via social media. After a theoretical introduction, participants were free to share experiences and ask questions. The recorded events were retrospectively analysed. Twenty-four owners of 22 Addisonian dogs took part in four events. Owners felt most “traumatised” when experiencing their dog’s acute adrenal crisis. The initial adjustment phase and distinguishing the non-specific symptoms of hypoadrenocorticism from those of other diseases were also challenging. Overall, owners were well informed on the disease and committed to its long-term adjustment. Adrenal crisis and the initial adjustment phase may be more burdening to owners than expected. Understanding what their clients’ concerns are, can help veterinarians provide better care and reduce the negative impacts of canine hypoadrenocorticism. Promoting peer to peer support, as well as providing a framework for participative communication might also help.

The aim of this study was to evaluate and compare the fracture resistance of definitive zirconia dioxide restorations obtained using a computer-aided design and manufacturing (CAD/CAM) system. Methods: Two groups of ten samples were analyzed for each material (n: 20), the first group was Zolid Gen X Amann Girrbach (ZGX) and the second group was Cercon HT Dentsply Sirona (CDS). The restorations were designed with identical parameters and milled with a CAD/CAM system. Each specimen was load tested at a speed of 0.5 mm/min with a direction parallel to the major axis of the tooth and with an initial preload of 10N until fracture using a universal testing machine (Universal/Tensile Testing Machine, Autograph AGS-X Series) equipped with a 20 kN load cell. The results obtained were recorded in Newtons (N), using software connected to the testing machine. Results: Statistically significant differences were found, and the fracture toughness of the monolithic zirconia crowns was lower in the CDS group (1744.84 ± 172.8 N), compared to the ZGX group (2387.41 ± 516 N). Conclusions: The monolithic zirconia CAD-CAM zirconia crowns showed sufficient fracture strength to be used in posterior molar and premolar zones with either material as they withstood fracture loads greater than the maximum masticatory force.

The number of published studies on curcuminoids in cancer research, including its lead molecule curcumin and synthetic analogs, has been increasing substantially during the past two decades. Insights on the diversity of inhibitory effects they produced on a multitude of pathways involved in carcinogenesis and tumor progression were provided. As this wealth of data was obtained in a setting of various experimental and clinical data, this review first aimed at presenting a chronology of discoveries and an update on their complex in vivo effects. Secondly, there are many interesting questions linked to their pleiotropic effects. One of them, which is a growing research topic, relates to their ability to modulate metabolic reprogramming. This review will also cover the use of curcuminoids as chemosensitizing molecules, that can be combined with several anticancer drugs for reversing the phenomenon of multidrug resistance. Finally, current investigations in these three complementary research fields raise several important questions that will be put in the prospects for the future research related to the importance of these molecules in cancer research.

Background: Knowledge of vascular anatomy and its possible variations is essential for performing embolization or revascularization procedures and complex surgery in the pelvis. The obturator artery (OA) is a branch of the anterior division of the internal iliac artery (IIA), and it has the highest frequency of variation between branches of the internal iliac artery. Possible anomalies of the origin of the obturator artery (OA) should be known when performing pelvic and groin surgery, where its control or ligation may be required. The purpose of this systematic review and meta-analysis, based on Sanudo’s classification, is to analyse the origin of the obturator artery (OA) and its variants. Methods: Thirteen articles, published between 1952 and 2020, were included in this systematic review and meta-analysis. Results: The obturator artery (OA) was present in almost all cases (99.8%): the pooled prevalence estimate for internal iliac artery (IIA) was 77.7% (95% CI 71.8% – 83.1%) vs 22.3% (95% CI 16.9% – 28.2%) for the external iliac artery (EIA). In most cases, the obturator artery (OA) originated from the anterior division trunk of the internal iliac artery (IIA) (61.6%). Conclusion: Performing preoperative radiological studies to know the pelvic vascular pattern and having awareness to evaluate possible changes in the obturator artery can reduce the risk of iatrogenic injury and complications

The majority of EGFR mutations (85–90%) are exon 19 deletions and L858R point mutation of exon 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon mutations (10-15% of EGFR mutations). Predominant mutation types in this category include exon 18 point mutations, exon 21 L861X, exon 20 insertions and exon 20 S768I. This group presents a heterogeneous prevalence, partly due to the different testing methods and to the presence of compound mutation, which in some cases leads to shorter overall survival and different sensitivity to different TKIs than simple mutations. EGFR-TKI sensitivity may also vary depending on the specific mutation and the tertiary structure of the protein. The best strategy remains uncertain and the data of TKIs efficacy are founded of few prospective and some retrospective series. Newer investigational agents are still under study and there are no other approved specific treatment targeting uncommon EGFR mutations. Defining the best treatment option for this patient population remain un unmet medical need. The objective of this review is to evaluate existing data on outcomes, epidemiology and clinical characteristics of lung cancer patients with rare EGFR mutations, with a focus on intracranial activity and response to immunotherapy.

The aim of this research was to evaluate the essential oil of Cymbopogon schoenanthus (L.) Spreng. (C. schoenanthus) from Burkina Faso in cytotoxic activity against LNCaP cells, derived from prostate cancer, and HeLa cells, derived from cervical cancer. Antioxidant activities were evaluated in vitro. Essential oil (EO) was extracted by hydrodistillation and analyzed by GC / FID and GC / MS. Thirty-seven compounds were identified, the major compounds being piperitone (49.9%), alpha terpinene isomer (24.02%), elemol (5.79%) and limonene (4.31%). EO exhibited a poor antioxidant activity, as shown by the inhibition of DPPH radicals (IC50 =1730 ± 80 µg/mL) and ABTS+. (IC50 = 2890 ± 26.9 µg/mL). Conversely, EO decreased the proliferation of LNCaP and HeLa cells with respective IC50s of 135.53 ± 5.27 µg/mL and 146.17 ± 11 µg/mL. EO also prevented LNCaP cell migration and led to the arrest of their cell cycle in the G2/M phase. Altogether, this work points out for the first time that EO of C. schoenanthus from Burkina Faso could be an effective natural anticancer agent.

Asthma causes chronic coughing, wheezing, dyspnea, and chest pressure. This study assessed asthmatic patients' knowledge, attitudes and awareness of bronchial asthma and proper education on its meaning, risk factors, symptoms, diagnosis, management, and prevention practice. We performed a cross-sectional interventional asthma KAP survey in Erbil, Iraq. We adapted a validated study questionnaire from KAP studies in other nations to the Erbil situation and culture. In Erbil, Kurdistan, Iraq, two major hospitals' asthma clinics were studied. We chose 250 asthmatic ICU patients from October 2018 to July 2019. Health education was comprehensive. The health education program used a Kurdish PowerPoint with a printout. 25 groups got two-weeks of one-hour health education pre-intervention. Each group was questioned before, 2 and 12 weeks after health education. All data were analyzed by SPSS v26. The mean age of the respondent was 37.52±15.16 with 48.7 % respondent having a positive family history of asthma. After 2weeks of health education intervention, respondent have a higher knowledge score, positive attitudes compared to pre-education and after 12 weeks of education with a significant difference (P < 0.001) with improvised prevention practice. Health education programs led to considerable improvements in asthmatic patients' knowledge, attitudes, and practices regarding their condition. After receiving health education for a period of two weeks, the majority of the participants answered correctly regarding asthma, its causes, and the elements that trigger asthma attacks.

Abstract: This paper outlines the methodology and results for a two species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA) ) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport model incorporates the convection-diffusion equation in scalar form (dimensionless) with a two species (free-drug and bound-drug) mass transport setup including reversible equilibrium reaction source terms for the free and bound-drug states to account for the pharmaco-kinetic reactions in the arterial wall. The relative reaction rates of the added source terms control the interconversion of drug between the free and bound-drug states. The model is solved by a 2-D finite-volume method for discretizing and solving the free and bound drug transport equations with anisotropic vascular drug diffusivities. This model is an improvement over our previously developed model using the finite-difference method. A dimensionless characteristic scaling pre-analysis was conducted a priori to evaluate the significance of implementing the reaction source terms in the transport equations. This paper reports the findings of an investigation of the interstitial flow profile into the arterial wall and the free and bound drug diffusion profiles with a parametric study of varying polymer drug concentration (low and high), tortuosity, porosity, and Peclet and DamKöhler numbers over the course of 400 hours (16.67 days). The results also reveal how a single species drug delivery model that neglects both a reversible binding reaction source term and the porosity and tortuosity of the arterial wall cannot accurately predict the distribution of both the free and bound drug.

Migraine is a debilitating neurovascular disorder characterized by recurrent headache attacks of moderate to severe intensity. Calcitonin gene-related peptide (GGRP), which is abundantly expressed in trigeminal ganglion (TG) neurons, plays a crucial role in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, activates the trigeminovascular system. In the present study, we investigated CGRP mRNA expression in TG neurons in a CSD-based mouse migraine model. Our in situ hybridization analysis showed that CGRP mRNA expression was observed in smaller neuronal populations. CSD did not significantly change the density of CGRP mRNA-synthesizing neurons in the ipsilateral TG. However, the cell sizes of CGRP mRNA-synthesizing TG neurons were significantly larger in the 48 h and 72 h post-CSD groups than in the control group. The proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters less than 14 μm became significantly less at several time points after CSD. In contrast, we found significantly greater proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters of 14–18 μm at 24 h, 48, and 72 h post-CSD. We deduce that the CSD-induced upward cell size shift in CGRP mRNA-synthesizing TG neurons might be causative of greater disease activity and/or less responsiveness to CGRP-based therapy.

Introduction: The application of external fixation devices consists of wires insertion through the skin and soft tissue to the bone. We examined the possible analgesic effect of stimulating an acupoint by the fixation wires which mimics the acupunctures treatment. Material and methods: retrospective work. Between 2015 to 2018 107 patients were treated with an external fixation for a tibial fracture. 33 patient files were found to be eligible for the review. Patients were retrospectively divided into two groups: the study group included patients with a wire inserted through the ST36 (Zu San li) acupoint location, the control group had the wire inserted elsewhere. Patient's record was reviewed for 5 days following surgery. Data collected included analgesic consumption and pain level recorded on a visual analog scale (VAS). Results: 33 patients were included in the review. 20 patients in the study group and 13 served as the control group. In the study group VAS average was Mean (M)=1.4853 ± 1.30 while in the control group M=2.3885± 1.77 with no statistical relevance (P>0.05). Only on day 4 the study group had less pain than the control: M=0.40 ± 0.843, versus M=2.57 ± 2.149 (Mann=Whitney Z= -2.413, P<0.05). No statistical difference was found between groups in relation to analgesic consumption. Conclusions: In patients suffering from a tibial fracture treated with an Ilizarov external fixation device, locating a wire in the anatomical location of acupoint ST 36 had no effect on analgesic consumption and a minimal effect on patients’ pain levels.

In this review, we aimed to understand the relationship between SARS-CoV-2 infection and preeclampsia severity in infected pregnant women. Pregnant women with SARS- CoV-2 infection have been shown to have a significantly increased risk of maternal death, ICU admission, preterm delivery, and stillbirth compared with those without infection. The risk of preeclampsia also increases in pregnant women infected with SARS-CoV-2, particularly in those with severe symptoms. We emphasize the im-portance of specialized clinical management to prevent poor pregnancy outcomes in this situation. The association between COVID-19 and preeclampsia (PE) is likely due to multiple mechanisms, including the direct effects of the virus on trophoblast function and the arterial wall, acute atherosis, local inflammation leading to pla-cental ischemia, exaggerated inflammatory responses in pregnant women, SARS-CoV-2-related myocardial injury, cytokine storm, and thrombotic microan-giopathy. Emphasis has been placed on the potential impact of COVID-19 on pregnant women, specifically in relation to thrombotic complications, placental dysfunction, and cardiovascular dysfunction. Undoubtedly, one of the diagnostic tools to differentiate between COVID-19-induced preeclampsia-like syndrome and true preeclampsia is the use of biomarkers, such as the sFlt-1/PlGF ratio. We wish to highlight the potential for COVID-19-induced myocardial injury in pregnant women and the associated in-crease in maternal mortality rate. Vaccination against COVID-19 in the general population and in pregnant women in particular, drastically reduced the severity of the disease. There is an urgent need to continue the follow-up of these women and their children to detect the appearance of sequelae of the disease or peristent COVID 19

Non-alcoholic steatohepatitis (NASH), which is the most severe manifestation of non-alcoholic fatty liver disease (NAFLD), has been recognized as a major hepatocellular carcinoma (HCC) catalyst. However, the molecular mechanism of NAFLD-NASH-HCC sequence remains unclear and a specific and effective treatment for NASH has not yet been established. The progress in this field depends on the availability of reliable preclinical models which show the steady progress to NASH, liver cirrhosis, and HCC. However, most of NASH mouse models that have been described to date develop NASH generally for more than 24 weeks and there is an uncertainty of HCC development. To overcome such shortcomings of experimental NASH studies, we established a novel NASH-HCC mouse model with very high reproducibility, generality, and convenience. We treated male C57BL/6J mice with a newly developed choline-deficient and methionine-restricted high-fat diet (CDMRHFD) for 60 weeks. Treatment of CDMRHFD for 3 weeks revealed marked steatosis, lobular inflammation, and fibrosis, histologically diagnosed as NASH. Liver cirrhosis was observed in all mice with 36-week treatment. Liver nodule emerged at 12 weeks of the treatment, and diameter >2 mm liver tumors developed in all mice at 24 weeks of the treatment. In conclusion, our rapidly progressive and highly reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical development and research on the pathogenesis of human NAFLD-NASH-HCC. Our mouse model would be useful for the development of novel chemistry for NASH-HCC-targeted therapies or HCC prevention strategies.

Seizure development relies on two factors. One is the existence of an overexcitable neuronal network and the other is a trigger that switches normal activity of that network into a paroxysmal state. While mechanisms of local overexcitation have been the focus of many studies, the process of triggering remains poorly understood. We suggest that, apart from the known exteroceptive sources of reflex epilepsy – visual, auditory or olfactory, there is a range of interoceptive triggers, relevant for seizure development in Temporal Lobe Epilepsy (TLE). The hypothesis proposed here aims to explain the prevalence of epileptic activity in sleep and in drowsiness states and provide a detailed mechanism of seizure triggering by interoceptive signals.

Background: Endoscopic Ultrasound (EUS) is widely used for the diagnosis of bilio-pancreatic and gastrointestinal (GI) tract diseases, for the evaluation of subepithelial lesions, and for sampling of lymph nodes and solid masses lo-cated next to the GI tract. The role of Artificial Intelligence in healthcare in growing. This review aimed to provide an overview of the current state of AI in EUS from imaging to pathological diagnosis and training. Methods: AI algorithms can assist in lesion detection and characterization in EUS by analysing EUS images and identifying suspicious areas that may require further clinical evaluation or biopsy sampling. Deep learning tech-niques, such as convolutional neural networks (CNNs), have shown great potential for tumour identification and subepithelial lesion (SEL) evaluation by extracting important features from EUS images and using them to classify or segment the images. Results: AI models with new features can increase the accuracy of diagnoses, provide faster diagnoses, identify subtle differences in disease presentation that may be missed by human eyes, and provide more information and in-sights into disease pathology. Conclusions: The integration of AI in EUS images and biopsies has the potential to improve the diagnostic accura-cy, leading to better patient outcomes and to a reduction of repeated procedures in case of non-diagnostic biopsies.

Mothers’ own milk (MOM) for premature babies is considered a life-saving drug for its proven protective action against the complications of prematurity and for the effects on the outcome in the short and long term, especially the neurological one. We studied the use of the MOM for WLBWs over a 5-year period. Statistical comparisons concerned data on feeding with the MOM during stay in NICU and at discharge with respect to maternal and neonatal variables (gestational age, birth weight, type of pregnancy if single or twin, maternal age) and to feeding data (timing of the start of the Minimal Enteral Feeding and the availability of the MOM, the achievement of the Full Enteral Feeding, the type of nutrition at discharge). We observed an increase, between 2017 and 2021, of MOM use (p=0.003). The availability of the MOM occurred on average on the fourth day of life and improved over the years. Start of MEF with human milk averaged 1.78 days and 54.3% of VLBWs received MEF with donor milk on the first day of life (50% within the first 6 hours). The average MOM at discharge was 47.6% with 36.1% exclusive MOM (EMOM) and an increase from 45.8% in 2017 (EMOM 33.3%) to 58.82% (EMOM 41.18%) in 2021. The mean average daily growth of the weight improved (p<0.001) during this period. There is no statistical difference between infants fed with MOM and those fed with bank milk. The maternal age, the start day of the MOM feeding and gestational age have a significant impact on the type of feeding at discharge.

Uveal melanoma represents the most prevalent form of primary malignant intraocular tumor in adults. Historically, enucleation was considered the gold-standard approach in the treatment of uveal melanoma. Nowadays, radiotherapy is the most commonly used therapy, aiming at a better quality of life. However, radiotherapy can result in several ocular complications, some of which may be vision-threatening. Radiation-induced dry eye, scleral necrosis, cataract, rubeosis iridis, neovascular glaucoma, radiation retinopathy and maculopathy and optic neuropathy are the most common. This article aims to summarize the current literature on the ocular complications after radiotherapy, their clinical features, risk factors and management strategies. A thorough understanding is crucial for ophthalmologists and oncologists to provide optimal patient care, improve visual outcomes, and minimize long-term complications.

Climate change and exposure to environmental pollutants play a key role in the onset and aggravation of allergic diseases. As different climate-dependent patterns of molecular immunoglobulin E (IgE) reactivity have been regionally described, we sought to investigate the evolving allergen exposome in distinctive allergic phenotypes, and subtropical weather conditions through a Precision Allergy Molecular Diagnosis (PAMD@) model. Concurrent sensitization to several house dust mites (HDM) and storage mite molecules were broadly dominant in the investigated cohort, followed by the major cat allergen Fel d 1, and regardless of the basal allergic disease. Although a complex repertoire of allergens was recognized, a steadily increasing number of IgE binding molecules was associated with the complexity of the underlying atopic disease. Besides the highly prevalent IgE responses to HMD major allergens, Der p 21, Der p 5, and Der p 7 also showed as serodominant molecules, especially in those subjects bothered with asthma and atopic dermatitis. The accurate characterization of the external exposome at the molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease in terms of personalized diagnosis and therapy.

Knowledge of the biological effects of molecular hydrogen (H2), hydrogen gas, is constantly expanding giving a reason for optimism for several healthcare practitioners regarding management of multiple diseases, including socially significant ones. However, mechanisms underlying the biological effects of H2 are still being actively argued. In this review, we focus on mast cells as a potential target for H2 at the level of a specific tissue microenvironment. H2 regulates processing of pro-inflammatory components of the mast cell secretome and their entry into the extracellular matrix; this can significantly affect the state of the integrated-buffer metabolic environment and the structure of the immune landscape of the local tissue microenvironment. The analysis performed highlights several potential mechanisms for developing the biological effects of H2 and offers great opportunities for translating the obtained findings into clinical practice.

Oxidative stress driven by several environmental and local airway factors associated with chronic obstructive bronchiolitis, a hallmark feature of COPD, plays a crucial role in the disease pathomechanism. Unbalance between oxidants and antioxidant defense mechanisms not only amplifies the local inflammatory processes, but it also worsens cardiovascular health and contribute to the COPD related cardiovascular dysfunctions and mortality. The current review summarizes recent developments in our understanding of different mechanisms contributing to oxidative stress and its countermeasures with special attention to those that link local and systemic processes. Major regulatory mechanisms orchestrating these pathways are also introduced together with some suggestions for further research on the field.

The enteric nervous system (ENS) is a neural network referred to as "the brain in the gut" because of its similarities to the central nervous system (CNS). The ENS consists of numerous types of neurons and glial cells distributed in two intramuscular plexuses that span the length of the intestine and control coordinated smooth muscle contractile activity and other intestinal functions. It is well-established that reciprocal communication exists between the brain and the gastrointestinal tract. Although the ENS can function independently, it is connected to the CNS through the afferent and efferent pathways of the parasympathetic and sympathetic nervous systems. In addition to regulating ENS function by the CNS, these connections are likely to be critically involved in the pathophysiology of Parkinson's disease (PD). PD is a common neurodegenerative disorder that presents with non-motor and motor symptoms. Surprisingly, ENS lesions have been shown to occur very early in the disease, even before CNS involvement. This has led to the postulation that the ENS may be central to the pathophysiology of PD. Autopsy studies have shown that α-synuclein (αS) aggregates in PD patients are found both in the substantia nigra (SN) and the ENS. Therefore, it has been hypothesized that the pathological process leading to PD may initially occur in the ENS years before the appearance of motor features. This process induces misfolding and aggregation of αS in specific subtypes of neurons in the CNS. Finally, it spreads retrogradely in the CNS through preganglionic vagal fibers to the dorsal motor nucleus of this nerve and to other central nervous structures. In addition to the presumed role in the spread of the disease process, it has also been suggested that pathological changes in the ENS might be involved in the gastrointestinal dysfunction frequently seen in Pd patients. Starting from the evidence in animal models and using a translational point of view, in this review, we aim to summarize the role of the ENS in the pathogenesis of PD and how this system could be modulated for a novel therapeutic approach. While acknowledging the presumed role of the microbiome in the gut-brain axis, we will shift the focus from this point of view to focus more on the neurons of the ENS.

Blood flow-restricted training (BFR) is constantly growing in popularity. Despite growing evidence of the significant influence of BFR training on different body functions, its impact on the vascular system, especially the arteries, is controversial. Therefore, the objective of our study was to analyze how BFR exercise, compared to other types of exercise without restriction of blood flow or other active intervention, influences arterial functions and angiogenesis in adults. Studies comparing the effect of BFR versus non-BFR training on arterial parameters are divided into three categories. Endothelial function, angiogenesis, and other vasculature functions. The search was based on three databases (Cochrane Library, PubMed®, Embase). In this systematic review, 38 studies were included. Meta-analysis revealed a more significant improvement in flow-mediated dilatation (FMD) (p=0.002) and the production of the primary angiogenesis biomarker Vascular Endothelial Growth Factor (VEGF) (p=0.009) after training in BFR compared to nonBFR (p=0.002). Analysis of pulse wave velocity, ankle-brachial index, systolic blood pressure, or heart rate did not show a significant difference in changes between BFR and non-BFR training. Other parameters examined were not sufficiently provided to be included in the meta-analysis. The results obtained, present trends suggesting the significant impact of BFR training on endothelial functions and angiogenesis. Unfortunately, there is still a lack of multicenter randomized clinical trials, including many participants, that are necessary to confirm the advantage of BFR over non-BFR activity.

Background: Sensor usage in the classical scientific process has allowed new experimentation in medicine. We report on the design process of a MEMS sensor being used for muscle trauma evaluation in diagnosing acute compartment syndrome (ACS), a medical ailment costing society billions of dollars per year. Objectives: Modeling the disease with scientific process allows a more complete under-standing of the disease. The goal was to formulate a hypothesis that could be tested to aid in making the diagnosis of ACS accurately. Methods: Scientific process was observed throughout the disease modelling process. Background information was improved and clarified, new pre-clinical models were de-signed and verified, a hypothesis built on pressure measurement with MEMS sensors was carried out, and the testing of the model as verified against previous clinical data was accomplished. Results: Scientific process resulted in hypothesis generation around the relationship of intracompartmental pressure measurement and the disease process and therapy. This resulted in new understanding of ACS, accurate modelling, and sensor design resulting in a MEMS device that has an extremely high sensitivity and specificity (over 99%) in treating and diagnosing the disease. Conclusion: MEMS sensor technology defines the new gold standard of implanting a sensor in a muscle compartment that allows accurate diagnosis of ACS with continuous trends in pressure.

Kidney fibrosis is a complex polyetiological progressive disease manifesting as an intraorgan proliferation of the connective tissue with the appearance of cicatricial changes. However, pathogenetic mechanisms of renal fibrosis remain poorly understood. The paper highlights features of the protease phenotype and histotopography of mast cells (MCs) found in the kidney, as the key players in extracellular matrix remodeling in nephrofibrosis, detected in a patient diagnosed with "nephrosclerosis with the non-functioning upper pole of the duplex right kidney in the junction of refluxing megaureter of the upper pole of the duplex right kidney". The highest content of MCs was found in the kidney areas with fibrotic changes. MCs were actively involved in the development of inflammatory and fibrotic changes in limited loci of the specific tissue microenvironment of the kidney through targeted secretion of tryptase, chymase, and carboxypeptidase A3 to the vascular endothelium, nephron epithelium, interstitium cells, and components of the intercellular substance. The formation of a profibrotic environment in the kidney interstitium was facilitated by epigenetic effects of tryptase promoting epithelial-mesenchymal transition (EMT) of the nephron epithelium. A selectively increased number and targeted secretory activity of MCs in limited loci of the kidney parenchyma without visible pathological changes evidence a trigger pathogenetic role of specific proteases in the formation of a local microenvironment with a profibrogenic metabolic profile. Thus, MCs are actively involved in the mechanisms of formation and evolution of fibrogenic niches in the kidney; this fact can be used to develop new strategies for therapeutic options of tubulointerstitial fibrosis resulted from chronic kidney injury. Further study of the molecular phenotype of mast cells reveals new fundamental mechanisms of fibrosis pathogenesis being a significant tool for personalized therapy in nephrology.

Our prior studies have shown that B type Natriuretic Peptide (BNP) decreases absorption from the gastrointestinal (GI) tract. Since non-muscle myosin-type II (NMM-II) is known to have a role in epithelial tight junction regulation, we aimed to test whether BNP has an effect on the localization and expression of NMM-II in the intestinal villi. We treated wild type mice with a 10 ng/g intravenous bolus of BNP followed by infusion of BNP at 1ng/g/minute vs. vehicle control. The mice were then euthanized and intestinal tissue isolated and sectioned. The tissue was immune-stained for NMM-II and examined using fluorescence microscopy. The tissue section not treated with antibody to NMM-II was used as a methodological control to evaluate the non-specific binding. Scanning electron micrographic images were taken to compare structural differences between the two groups. Western blotting was performed to compare the regional protein expression of NMM-II and associated proteins including smooth muscle actin, kinesin, and E cadherin in small intestinal tissue between BNP vs. vehicle infused mice. Fluorescence microscopy revealed markedly increased localization of NMM-II at the crypts and core of intestinal villi of the jejunum, ileum and colon of BNP treated mice compared to vehicle. Transmission electron microscopy revealed that the microvilli of BNP treated mice assumed the distinctive appearance of ‘relaxed’ microvilli compared to vehicle. Such decrease in contractility was previously shown to decrease para-cellular permeability of epithelia. Our observation indicates that BNP alters the localization of NMM-II in intestinal villi and makes the intestinal villi structures assume a state of decreased permeability of the apical junctional complex. Further characterization of this process and understanding the specific mediators involved could lead to the identification of novel therapeutic targets for various disease states such as heart failure and malabsorption.

A population-based seroepidemiological and molecular survey for detection of earlier and re-cent SARS-CoV-2 infection was done in children aged 14 years or less in Tehran between 19 September 2020 and 21 June 2021. Demographic data, COVID-19 symptoms and infection status were recorded and IgG antibodies and RNA of SARS-CoV-2 were detected in sera and nasopha-ryngeal swab samples, respectively. Out of 1517 participants, cardinal symptoms of COVID-19 (fever >38 oC and/or cough and/or diarrhea) were detected in 18% and serological history of SARS-CoV-2 infection and PCR positivity were confirmed in 33.2% and 10.7% of the weighted-population, respectively. SARS-CoV-2 infection was significantly higher among 10–14-year-old children. Active infection was significantly higher in symptomatic children and during autumn 2020 and spring 2021. The RT-qPCR positivity was related to contact with in-fected persons. RT-qPCR positivity was significantly higher among families with a lower socio-economic status, while no association between RT-qPCR- or seropositivity was determined with household size, underlying diseases, or gender. In conclusion, high SARS-CoV-2 infection prev-alence and seroprevalence was detected in children in Tehran in different seasons. The infection was significantly higher in older age children, and those with a positive-history of close contact with infected cases and/or lower socioeconomic status.