Social and behavioral rhythms (SBRs) are related to circadian rhythms well known as central points in the pathophysiology of bipolar disorders. The purpose is to verify in elderly people if having functional SBRs correlated with a positive perception of the quality of life (QoL) and health parameters and if there was an association between dysfunctionality of SBRs and Major Depressive Disorder (MDD). Sample: 141 people aged 65 years (58,9%Female). Each subject was submitted to SBRs Scale (in which higher scores show more dysfunctional SRB); SF-12 for QoL; PHQ-9 for depressive symptoms and underwent blood levels essays including cholesterol and triglyceride. The medical documented lifetime diagnosis including Major Depressive Disorder was taken into account. SBRs Scale score correlated inversely with SF-12 score (r=-0.360, p<0.0001) and positively with PHQ9 (r=0.396, p<0.0001). Lifetime MDD medical diagnosis was associated with a higher score at scale on social rhythms (24.811.9 vs 20.18.0, F=15.848, p<0.0001).The study highlighted, for the first time, that SBRs such as sleep, and nutrition have a role in well-being and that dysregulation of SBRs is related to MDD. Further longitudinal studies with a sufficient number of individuals will have to confirm these data and clarify causal links of the association between QoL and SBRs.

With increasing awareness amongst physicians and improved radiological imaging techniques, the peritoneal cavity is increasingly recognized as an important metastatic site in various malignancies. Prognosis of these patients is usually poor as traditional treatment including surgical resection or systemic treatment is relatively ineffective. Intraperitoneal delivery of chemotherapeutic agents is thought to be an attractive alternative as this results in high tumor tissue concentrations with limited systemic exposure. The addition of hyperthermia aims to potentiate the anti-tumor effects of chemotherapy, resulting in the concept of heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal metastases as it was developed about 3 decades ago. With increasing experience, HIPEC has become a safe and accepted treatment offered in many centers around the world. However, standardization of the technique has been poor and results from clinical trials have been equivocal. As a result, the true value of HIPEC in the treatment of peritoneal metastases remains a matter of debate. The current review aims to provide a critical overview of the theoretical concept and preclinical and clinical study results, to outline areas of persisting uncertainty, and to propose a framework to better define the role of HIPEC in the treatment of peritoneal malignancies.

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents may be beneficial in patients with CPFE, but further studies are needed.

Acute kidney injury (AKI) is a frequent and critical complication in the clinical setting. In rodents AKI can be prevented effectively through caloric restriction (CR), which has also been shown to increase lifespan in many species. In Caenorhabditis elegans (C. elegans) longevity studies revealed that a marked CR-induced reduction of endocannabinoids may be a key mechanism. Thus, we hypothesized that regulation of endocannabinoids, in particular arachidonoyl ethanolamide (AEA), might also play a role in CR-mediated protection from renal ischemia-reperfusion injury (IRI) in mammals including humans. In male C57Bl6J mice, CR significantly reduced renal IRI and led to a significant decrease of AEA. Supplementation of AEA to near-normal serum concentrations by repetitive intraperitoneal administration in CR mice, however, did not abrogate the protective effect of CR. We also analyzed serum samples taken before and after CR from patients of three different pilot trials of dietary interventions. In contrast to mice and C. elegans, we detected an increase of AEA. We conclude that endocannabinoid levels in mice are modulated by CR, but CR-mediated renal protection does not depend on this effect. Moreover, our results indicate that modulation of endocannabinoids by CR in humans may differ fundamentally from the effects in animal models.

Until recently, research on the molecular signatures of HPV-associated head and neck cancers mainly focused on their differences with respect to HPV-negative HNSCCs. However, given the continuing high incidence level of HPV-related HNSCC, the time is ripe to characterize the heterogeneity that exists within these cancers. Here, we review research thus far on HPV-positive HNSCC molecular subtypes, and their relationship with clinical characteristics and HPV integration into the host genome. Different omics data including host transcriptomics and epigenomics, as well as HPV characteristics, can provide complementary viewpoints. Keratinization, mesenchymal differentiation, immune signatures, stromal cells, and oxidoreductive processes all play important roles.

Many neonates undergoing whole body hypothermia (WBH) following moderate to severe perinatal asphyxia suffer from renal impairment. While recent data suggest a WBH-related reno-protection, the differences in serum creatinine (Scr) patterns to reference patterns were not yet reported. We therefore aimed to document Scr trends and patterns in asphyxiated neonates undergoing WBH, and compared these to centiles reference Scr dataset of non-asphyia neonates. Using a systematic review strategy, reports on Scr trends (mean ± SD, or median and range) were collected (day 1-7) in WBH cohorts, and compared to centiles of an earlier reported reference cohort of non-asphyxia cases. Based on 13 papers on asphyxia+WBH cases, a pattern on postnatal Scr trends in asphyxia+WBH cases was constructed. Compared to the reference cohort, mean or median Scr values at birth (>90th centile) and the first two days of WBH (>75th centile) remained clinical relevantly higher in asphyxia+WBH cases, with a subsequent decline to reach at best high or high normal creatinine values (all >50th centile, but mainly >75th centile) from day 4 onwards. Such patterns are valuable to anticipate average changes in renal clearance capacity relevant for pharmacotherapy, but do not yet cover the relevant inter-patient variability observed in WBH cases.

The effect of stress on task performance is complex, too much or too little negatively affects performance; and there exists an optimal level of stress to drive optimal performance. Task difficulty and external affective factors are distinct stressors that impact cognitive performance. Neuroimaging studies showed that mood affects working memory performance and the correlates are changes in haemodynamic activity in the prefrontal cortex (PFC). We investigate the interactive effects of affective states and working memory load (WML) on working memory task performance and haemodynamic activity using functional near-infrared spectroscopy (fNIRS) neuroimaging on the PFC of healthy participants. We seek to understand if haemodynamic responses could tell apart workload related stress from situational stress arising from external affective distraction. We found that the haemodynamic changes towards affective stressor and workload related stress were more dominant in the medial and lateral PFC respectively. Our study reveals distinct affective state-dependent modulations of haemodynamic activity with increasing WML in n-back tasks, which correlate with decreasing performance. The influence of negative affect on performance is greater at higher WML, and haemodynamic activity showed evident changes in temporal, and both spatial and strength of activation differently with WML.

The trace element copper (Cu) is part of our nutrition and essentially needed for several cuproenzymes that control redox status and support the immune system. In blood, the ferroxidase ceruloplasmin (CP) accounts for the majority of circulating Cu and serves as transport protein. Both Cu and CP behave as positive, whereas serum selenium (Se) and its transporter selenoprotein P (SELENOP) behave as negative acute phase reactants. In view that coronavirus disease (COVID-19) causes systemic inflammation, we hypothesized that biomarkers of Cu and Se status are regulated inversely, in relation to disease severity and mortality risk. Serum samples from COVID-19 patients were analysed for Cu by total reflection X-ray fluorescence and CP was quantified by a validated sandwich ELISA. The two Cu biomarkers correlated positively in serum from patients with COVID-19 (R=0.42, p<0.001). Surviving patients showed higher mean serum Cu and CP concentrations in comparison to non-survivors ([mean+/-SEM], Cu; 1475.9+/-22.7 vs. 1317.9+/-43.9 µg/L; p<0.001, CP; 547.2.5 +/- 19.5 vs. 438.8+/-32.9 mg/L, p=0.086). In contrast to expectations, total serum Cu and Se concentrations displayed a positive linear correlation in the patient samples analysed (R=0.23, p=0.003). Serum CP and SELENOP levels were not interrelated. Applying receiver operating characteristics (ROC) curve analysis, the combination of Cu and SELENOP with age outperformed other combinations of parameters for predicting risk of death, yielding an AUC of 95.0%. We conclude that the alterations in serum biomarkers of Cu and Se status in COVID-19 are not compatible with a simple acute phase response, and that serum Cu and SELENOP levels contribute to a good prediction of survival. Adjuvant supplementation in patients with diagnostically proven deficits in Cu or Se may positively influence disease course, as both increase in survivors and are of crucial importance for the immune response and antioxidative defence systems.

(1) Background: Stimulating oropharyngeal transient receptor potential (TRP) channels inhibits muscle cramping by triggering a supraspinal reflex to reduce α-motor neuron hyperexcitability. This study investigated whether longer stimulation of TRP channels via mouth rinsing with PJ is more effective than drinking PJ at inhibiting an electrically induced muscle cramp (EIMC); (2) Methods: Tibial nerve in 11 cramp-prone adults were percutaneously stimulated to elicit an EIMC of flexor hallucis brevis in three trials 1-week apart. At cramp onset participants received mouth rinsing and expelling PJ (25 mL), ingesting PJ (1 mL∙kg-1 body-mass [BM]), or ingesting water (1 mL∙kg-1 BM). Cramp onset and offset by electromyography and severity of discomfort was recorded using a visual analogue scale (VAS); (3) Results: Median time to cramp cessation as a percentage of water was 82.8% ± 14.634 and 68.6% ± 47.782 for PJ ingestion and mouth rinse respectively. These results had large variability and no statistically significant difference was observed. There were also no differences in perceived cramp discomfort between conditions, despite hazard ratios for time to VAS = 0 higher than water for PJ ingestion (22%) and mouth rinse (35%) (p = 0.66 and 0.51 respectively); (4) Conclusions: Data suggest no difference in cramp duration and perceived discomfort between PJ and water.

In this study, we described the most critical risk factors for different malignancies including: breast, prostate, lung, and colorectal carcinoma among others, with an emphasis on modifiable risk factors. We revised the literature review about risk factors involved in the genesis of cancer in various databases, including articles indexed in PUBMED, SCOPUS, PMC, and Google Scholar. Awareness of risk factors enables conscious decisions to be made in an effort to combat malignancies. Knowing risk factors is a mode of fighting malignancy. Diet, lifestyle, practises, and laboratory/clinical interventions were among risk factors of diverse malignancy. Diet, lifestyle, laboratory/clinical interventions all contribute to the genesis and prognosis in a variety of malignancies. We concluded that abstaining from risk factors can prevent the development of many malignancies in a century where this conundrum is raising disproportionately. By informing the public about modifiable risk factors cancer mortality rates can be reduced. It is treated here is to make the public aware of the modifiable risks of cancers.

Alzheimer’s disease (AD) is the most common cause of dementia worldwide. Pathological deposits of neurotoxin proteins within the brain, such as amyloid-Beta and hyperphosphorylated tau tangles, are prominent features in AD. The prion protein (PrP) is involved in neurodegeneration via its conversion from the normal cellular form PrPc, to the infection form PrP Sc. Some studies indicated that posttranslationally modified PrPc isoforms plays a fundamental role in AD pathological progression. Several studies have shown that interaction of Aβ oligomers with N-terminal residues of the PrPc protein region appears critical for neuronal toxicity. The PrPc-Aβ binding always occur in AD brains and is never detected in nondemented controls and the binding of Aβ aggregates to PrPc is restricted to the N-terminus of PrPc.

To reduce the risk of infection of SARS-CoV-2 during the commute to the clinic or due to the contact with medical staff, The American College of Obstetricians and Gynecologists recommended ar-ranging part of the appointments in the form of “telehealth”. The aim of the study was to assess the access to medical care in pregnancy during the Sars-Cov-2 pandemic and the role of telehealth in implementation of prenatal care standards. This is a cross-sectional study. The study group in-cluded 618 women that were pregnant and or gave birth during the COVID-19 pandemic in Poland. The majority of participants experienced difficulties in access to medical care because of the pandemic. Correlation between this experience and the use of hybrid healthcare model was es-tablished. However, affiliation to public or private healthcare group was irrelevant. There was no relationship between healthcare (private/public or in-person/hybrid) and implementation of the prenatal care standards. To ensure safe access to prenatal care for pregnant women, recommen-dations for a hybrid pregnancy management model should be created with detailed information for which appointments patients must be present and which can be done remotely. To reduce movement risk and interpersonal contact, all visits during which tests and screenings take place should be done in-person. Other appointments can be arranged in the form of telehealth

Background: our purpose is to assess the effectiveness and safety of sacubitril/valsartan (SV) in “real-world” patients with heart failure and reduced ejection fraction (HFrEF), including a broader spectrum of patients than those in clinical trials and evaluating variables not previously described in the literature. Methods: real-world study in HFrEF patients (N:204), both in and out-patients, who started SV between October 2017 and December 2018. We performed a prospective analysis with a 12-month follow-up. The study outcomes were effectiveness and safety, measured by individual parameters and combined endpoints, comparing the pre and post practice periods. Results: at the end of follow-up, an improvement of left ventricle ejection fraction (LVEF): 29.8% vs 33.7; p<0.0001, a decrease in NT-proBNP levels (3928 pg/mL vs 2902 pg/mL; p=0.012), number of hospital admissions (141 vs 35; p<0.0001) and percentage of patients with implantable cardioverter defibrillator (ICD) indication (79.9% vs 49.5%; p<0.0001) were observed. Of our population, 81.3% met a combined efficacy endpoint (defined by increase of LVEF, reduction of hospital admission or improvement in functional class). No differences were observed in parameters regarding safety. Conclusions: Sacubitril/valsartan has brought about a revolution in the therapeutic management of HFrEF patients and its use may raise questions about what is considered "optimal medical therapy" prior to implantation of cardiac devices.

SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.

We investigated the radioclinical outcomes of naviculectomy and limited/tailored soft-tissue releases in a short series of ambulatory children with complex/intractable congenital vertical talus subsets namely neglected, multiple operated and recurrent patients. We postulated that this technique will yield satisfactory radioclinical outcomes and minimal complications because it avoids extensive surgical release/trauma that is otherwise classically recommended for complex congenital vertical talus (CVT). The cohort consisted of five -four boys, one girl- complex CVT children with neglected, multiple operated and/or recurrent subsets. Patients were included if manipulative casting techniques were deemed unlikely to produce a plantigrade foot. Patients underwent naviculectomy with variable on-demand limited soft tissue releases. Two patients had bilateral affection and two had a non-idiopathic aetiology. The mean age was 5.2 years (4 to 6.25) and mean follow-up was 2.3 years (1 to 3). We reported satisfactory outcomes as per foot posture, function, overall parent satisfaction including pain and radiography per lateral views of talar-axis-first metatarsal base angle on the short/intermediate term. Whereas manipulative casting is unlikely to yield lasting outcomes in ambulatory children with complex subsets of CVT, extensive surgical soft-tissue releases have unfavourable long-term complications. As a substitute, naviculectomy as a form of resection arthroplasty created a practical and affordable third way between manipulative casting with minimally invasive surgery and the extensive surgical soft tissue releases on the short/intermediate term.

Background: Clinical cases reports with snake accidents show that venom bite induces increased oxidative stress including several markers of lipid peroxidation and other oxidative stress marker in plasma. Methods: The main findings of this work were performed with BthTx-II on paw edema of animals treated with the toxin and biochemical measurement of COX-2, PGE2, MDA and the effects of peroxiredoxin inhibitors on edema and myotoxicity were also evaluated. Results: The results show that edema and myotoxocity induced by PLA2 (BthTx-II) induces a strong mobilization of arachidonic acid and an increase in cellular oxidative stress as measured by increased malondialdehydo (MDA) concentration and protein carbonylation. Thus, these findings establish the strong link between oxidative stress, arachidonic acid mobilization and that these events may explain the presence of oxidative stress markers in snake-bitten patients. Experiments performed with animals previously treated with commercially purchased inhibitors showed enzymes such as thioredoxin (TXN), thioredoxin reductase (TXNRD) and other glutathione (GSH)-related antioxidant defenses could play an essential role controlling and defining the end of edema on the late phase of PLA2 BthTx-II-induced process. Conclusion. This study showed that thioate-dependent antioxidant enzymes play an important role in resolving the edema induced by BthTx-II.

The onset of the Coronavirus 2019 (COVID-19) pandemic has challenged the worldwide healthcare sector, including dentistry. The highly infectious nature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and risk of transmission through aerosol generating procedures has profoundly impacted the delivery of dental care services globally for months causing prioritization of critical dental needs and suspension of routine dental procedures. As dental practices with strengthened infection control strategies and preventive measures are re-opening in the “new normal” period, it is the responsibility of healthcare professionals to constantly analyze new data and limit the spread of COVID-19 in dental care settings. With the new variants of SARS-CoV-2 rapidly emerging in different geographic locations, a definite need to comply more than ever with the rigorous public health measures to mitigate COVID -19 transmission exists. The aim of this article is to provide dental clinicians with essential information regarding both the spread of SARS-CoV-2 virus and protective measures against COVID-19 transmission in dental facilities. By compiling guidance and standard protocols recommended by credible national and international organizations, this article serves as an aid to navigating through this unprecedented time with ease. Much to learn about COVID-19 exists and because of constant ongoing research, we are not aware of all of the newly found information. However, in this paper, we reviewed the available literature recommended for the best current practices that must be taken for a dental office to function safely and successfully.

Bovine respiratory disease is still a major concern in feedlots and has major economic impact. Another consequence of respiratory infections is the use of antimicrobial molecules to control bacterial pathogens. This can participate to the emergence and shedding of antimicrobial re-sistance that can threaten animal as well as human health. Appeasing pheromones with their capacity to reduce stress and thus their ability to preserve the functions of the immune system have been proposed to reduce the use of antimicrobial substances. In the current report we as-sessed the effect of appeasing pheromone administration on bovine health and performance during the fattening period. Zootechnical and health parameters as well as whole blood immune transcript expressions were measured over weeks in young bulls to determine the effect of the pheromone. We observed a reduction of clinical signs at day 30 in young bulls who received the pheromone and a higher expression of interleukin 8 transcripts in this group than in the control group. Our results are in line with previous reports in bovine and other mammals and ask for further studies to shed more light on the beneficial impact of appeasing pheromones and to de-cipher their exact mechanisms of action.

3,4-dihydroxyphenylacetaldehyde (DOPAL) is the focus of the catecholaldehyde hypothesis for the pathogenesis of Parkinson disease and other Lewy body diseases. The catecholaldehyde is produced via oxidative deamination catalyzed by monoamine oxidase (MAO) acting on cytoplasmic dopamine. DOPAL is autotoxic, in that it can harm the same cells in which it is produced. Normally DOPAL is detoxified by aldehyde dehydrogenase (ALDH)-mediated conversion to 3,4-dihydroxyphenylacetic acid (DOPAC), which rapidly exits the neurons. Genetic, environmental, or drug-induced manipulations of ALDH that build up DOPAL promote catecholaminergic neurodegeneration. A concept derived from the catecholaldehyde hypothesis imputes deleterious interactions between DOPAL and the protein alpha-synuclein (S), a major component of Lewy bodies. DOPAL potently oligomerizes S, and S oligomers impede vesicular and mitochondrial functions, shifting the fate of cytoplasmic dopamine toward MAO-catalyzed formation of DOPAL—destabilizing vicious cycles. Direct and indirect effects of DOPAL and of DOPAL-induced misfolded proteins could “freeze” intra-neuronal reactions, plasticity of which is required for neuronal homeostasis. The extent to which DOPAL toxicity is mediated by interactions with S, and vice versa, are poorly understood. Because of numerous secondary effects such as augmented spontaneous oxidation of dopamine by MAO inhibition, there has been insufficient testing of the catecholaldehyde hypothesis in animal models. The clinical pathophysiological significance of genetics, emotional stress, environmental agents, and interactions with numerous proteins relevant to the catecholaldehyde hypothesis are matters for future research. The imposing complexity of intra-neuronal catecholamine metabolism seems to require a computational modeling approach to elucidate clinical pathogenetic mechanisms and devise pathophysiology-based, individualized treatments.

Cancer risk is known to increase tremendously when the immune system is suppressed, e.g., as observed in young organ-transplant recipients and AIDS patients. Based on such data, it may be hypothesized that the main reason for the development of clinical cancer is the weakening or suppression of the immune system, and that uncontrolled multiplication of cancer cells occurs when some aspects of the immune system fall below certain critical levels. Therefore, cancer may be prevented and treated by boosting these critical aspects of the immune system so that they are maintained above the critical levels. If multiple immune system boosting interventions are utilized, more aspects of the immune system would be boosted, increasing the likelihood of enhancing the critical aspects of the immune system and generating a cancer preventive and/or therapeutic effect. Clinical trials are needed to validate this approach for cancer prevention and treatment. If validated, the proposed approach could result in a major reduction of the death and suffering caused by cancer in the world.

Headaches are among the most prevalent and disabling disorders and there are several patients’ unmet needs in current pharmacological options, while a growing interest is focusing on nutritional approaches as non-pharmacological treatments. Among these, the most promising seems to be the ketogenic diet (KD). Exactly 100 years ago, KD was used to treat pediatric forms of drug-resistant epilepsy, but progressively applications of this diet also involved adults and other neurological disorders. Evidence of KD effectiveness in migraine comes from 1928, but in the last years different groups of research and clinicians paid attention to this therapeutic option to treat patients with drug resistant migraine and cluster headache, and/or comorbid with metabolic syndrome. Here we describe all the existing evidence on the potential benefits of KDs in headaches, explore in deep all the potential mechanisms of action involved in the efficacy, and synthesize results of working meetings of an Italian panel of experts on this topic. Aim of the working group is the creation of a consensus on indications and clinical practice to treat with KDs patients with headache. The results here we present are the base for further improvement in the knowledge and application of KDs in the treatment of headaches.

Background: Acceleration of mass vaccination strategies is the only pathway to overcome the COVID-19 pandemic. Healthcare professionals and students have a key role in shaping public opinion about vaccines. This study aimed to evaluate the attitudes of dental students globally towards COVID-19 vaccines and explore the potential drivers for students' acceptance levels; Methods: A global cross-sectional study was carried out in February 2021 using an online ques-tionnaire. The study was liaised by the scientific committee of the International Association of Dental Students (IADS), and data was collected through the national and local coordinators of IADS member organizations. The dependent variable was the willingness to take the COVID-19 vaccine, and the independent variables included demographic characteristics, COVID-19-related experi-ence, and the drivers of COVID-19 vaccine-related attitude suggested by the WHO-SAGE; Results: A total of 6639 students from 22 countries representing all world regions responded to the ques-tionnaire properly. Their mean age was 22.06 ± 2.79 (17-40) years, and the majority were females (70.5%), in clinical years (66.8%), and from upper-middle-income economies (45.7%). In general, 22.5% of dental students worldwide were hesitant, and 13.9% rejected COVID-19 vaccines. The students in low- and lower-middle-income (LLMI) economies had significantly higher levels of vaccine hesitancy compared to their peers in upper-middle- and high-income (UMHI) economies (30.4% vs 19.8%; p < 0.001); Conclusions: The global acceptance level of dental students for COVID-19 vaccines was suboptimal, and their worrisome level of vaccine hesitancy was influenced by the socioeconomic context where the dental students live and study. The media and social media, public figures, insufficient knowledge about vaccines, and mistrust of governments and the pharmaceutical industry were barriers to vaccination. The findings of this study call for further implementation of epidemiology (infectious diseases) education within undergraduate dental curricula.

In clinical guidelines, such as National Comprehensive Cancer Network guidelines, it is embodied as first therapeutic option the combination of erlotinib and bevacizumab, based on a small clinical trial which included patients with HLRCC. With this case report we bring out another treatment option, not described before, with extraordinary results based on the combination of a check-point inhibitor and a tyrosine-kinase inhibitor, based on theoretical tumor immunogenic environment.

Abstract Traditional plants are known to contain a wide array of secondary metabolites with important biological activity, including anticancer activity. One of such metabolites is saponin; a steroidal or triterpenoid glycoside that is distinguished by its soap forming nature. Different saponins have been characterized and purified so far, and are gaining attention in cancer chemotherapy. Saponins possess incredible structural diversity which has been linked to their activity. They have been implicated in cancer chemoprevention and chemotherapy. Several studies have reported the role of saponins in cancer and their mechanism of actions including cell cycle arrest, antioxidant, cellular invasion inhibition, induction of apoptosis and autophagy. Despite the extensive research and significant anticancer effect of saponins there are no known FDA approved saponin based anticancer drugs due to a number of limitations including toxicities and drug likeness properties. Recent studies have explored options such as structural optimization, combination therapy and drug delivery systems to design saponins with increased efficacy and decreased toxicities. This review discussed the current knowledge on different saponins, their anticancer activity, mechanism of action as well as the current promising research on saponins within the last two decades and recommendations for future studies.

Objective: Studies in Sports Psychology and Sociology have validated causality in team-sport athletes by using emotional intelligence as a variable. This study aimed to examine the causal relationship between the types of autonomy support coaching, emotional intelligence, and interruption intention as psychosocial variables among current taekwondo athletes in Korea.Methods: In this study, 217 adult or university athletes registered in the Korea Taekwondo Association in 2020 were evaluated for the type of autonomy support coaching, emotional intelligence, and interruption intention. Results: Autonomy support coaching recognized by taekwondo athletes has a negative and positive effect on interruption intention and emotional intelligence, respectively. Moreover, emotional intelligence has a negative effect on interruption intention. which revealed that autonomy support coaching has a negative effect on interruption intention through emotional intelligence.Conclusions: Such outcomes can serve as a foundation for athletes to have the opportunity to participate in sports in a mature manner and promote positive changes in sports culture. In other words, the sensibility of the athletes can be harmoniously symmetry.

Intermittent claudication (IC) is the most common symptom of peripheral artery disease (PAD). IC affects the quality of life and results in marked exercise intolerance and limitation to daily activities with increased risk of cardiovascular complications. Exercise training is the first line of conservative management in PAD. However, patients with IC Patient cannot tolerate exercise because of leg discomfort induced by physical effort. This review will address alternative rehabilitation strategies to reduce exercise limitations and improve exercise tolerance in patients with IC.

As a complementary and alternative medicine in the western countries for decades, traditional Chinese medicine (TCM) has been used for more than 2000 years in China. Because of the characteristics of the philosophical style and the unknown mechanism of action, TCM sometimes has been biasedly described as "fraught with pseudoscience". From the scientific basis of the systems biology, here we promoted a novel medical model called the entropic systems medicine which could be applied to scientize TCM in future. In entropic systems medicine, TCM and Western modern biomedicine target the different variables of the entropic system. For instance, while Western modern biomedicine directly targets the phenotypes and its SOCs of macrostates, TCM differently targets the microstates, entropy and entropic force to generate SOTFs gradually causing the differentiated syndromes to be slowly rearranged. The prerequisites to modernize TCM are the entropic systems biology having been well established so that the variables could be precisely monitored and mathematically calculated.

Immunostaining is an essential histochemical technique for analyzing pathogenesis and making a histopathological diagnosis. The needs are prompted by technical development and refinement, commercial availability of a variety of antibodies, deepened knowledge of immunohistochemical markers, accelerated analysis of morphofunctional correlations, progress in molecular target therapy, and the expectation of advanced histopathological diagnosis. However, immunostaining does have various pitfalls and caveats. We should learn from mistakes and failures, as well as from false positivity and false negativity. The present review article describes various devices, technical hints and trouble-shooting guides to keep in mind in performing immunostaining.

Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into 4 different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD+) for their molecular activity. Functionally, most of the HDAC isoforms can regulate β cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting the novel interventional strategies for metabolic disorders/complications.

Introduction: To indentify the most effective actors(authors, countries, and journals) about composite resin restorations in the period 2000-2020.Material and Methods: An electronis research was conducted in the Scopus database by selecting the words ‘composite resin’ and ‘restoration and English language, article and review types, dentistry field. Their bibliometric data including publication title, authorship, citation count, citation dentistry, year of publication, country and institution of origin, journal of publication, study design, and keywords were extracted and analyzed.Results and Discussion: To our knowledge, this is the first bibliometric article on composite resin restorations. This study provides information about authors, institutions and countries that contribute to significant improvements in composite resin restorations. From 2000 to 2020, there were 7118 articles published from 99 countries.Articles originate primarily from the USA and Brazil. Results indicate that the USA, Brazil, Germany, Turkey, the United Kingdom, Japan, Swtizerland, Italy, Netherlands and India are the leading countries in composite resin restoration research and account for 51.8% of the total number of publications. The total number of citations are 158.404, corresponding to 22 citations per paper publication. During the time period examined, 776 hot articles and 228 classic articles on composite resin restorations were found.The journal with the most publications is ‘Operative Dentistry’. The publishing houses of the top 10 journals are from 4 countries: USA(6),Netherlands(2),Germany(1),Japan(1). The most cited article within the boundaires of this study is Ferracane’s article titled ‘Resin composite-State of the art’, which was published in Dental Materials in 2011 and received 913 citations.

Posterior capsule opacification (PCO) is the most common complication of cataract surgery. It causes a gradual deterioration of visual acuity, which would otherwise remain improved after a successful procedure. Despite recent advances in ophthalmology, this complication has not been eradicated and the incidence of PCO can be as high as 10%. This article reviews the literature concerning the pathomechanism of PCO and examines the biochemical pathways involved in its formation and methods to prevent this complication. We also review the reported tests performed in cell cultures under laboratory conditions, in experimental animal models, and in ex vivo human lens capsules. Finally, we describe research involving human eyes in the clinical setting and pharmacological methods that may reduce the frequency of PCO. Due to the multifactorial eti-ology of PCO, in vitro studies make it possible to assess the factors contributing to its complica-tions and search for new therapeutic targets. Not all pathways involved in cell proliferation, mi-gration, and contraction of the lens capsule are reproducible in laboratory conditions; moreover, PCO in humans and laboratory animals may be additionally stimulated by various degrees of postoperative reactions depending on the course of surgery. Therefore, further studies are necessary.

Background: This study presents the experience gained in the Newborn Intensive Care Unit (NICU) at “M. S. Curie” Emergency Clinical Hospital for Children in Bucharest after performing a series of bedside surgery interventions on newborns with congenital diaphragmatic hernia (CDH). We evaluate the advantages, complications, immediate and long-term outcome as well as the morbidity. Methods: We conducted a retrospective analysis of the data for all patients operated on-site be-tween 2011 and 2020, in terms of pre- and post-operative stability, procedures performed, com-plications and outcomes. Results: Our study is based on data from ten cases of newborns, term or small for gestation age with birthweights ranging from 2300 to 3300 grams, operated, on average, on the fifth day of life. The main reasons for operating on-site were the hemodynamical instability and the need to ad-minister inhaled Nitic Oxide (iNO) and HFOV ventilation. There were no unforeseen events dur-ing surgery, no immediate postoperative complications and no surgery related mortality. One noticed drawback was the unfamiliarity of the surgery team with the new operating environment. Conclusions: Our experience indicates that bedside surgery improves the likelihood of survival for critically ill neonates suffering from CDH. No immediate complications could be associated with this practice. Keywords: congenital diaphragmatic hernia, severe pulmonary hypertension, bedside surgery, NICU infrastructure

Abstract: Targeted ubiquitination and proteasomal degradation regulates various cellular pathways, and the discovery that CPT induced rapid proteasomal degradation of topoI is the primary mechanism of CPT resistance was novel and compelling. CPTs are used extensively to treat various solid tumors like colorectal, gastric, pancreatic, ovarian and small cell lung cancer. The response rate is low and the classical mechanisms of drug resistance are yet to be validated. Remarkably, CPT resistant cells degrade topoI rapidly by UPP and recently we’ve published the molecular determinants of this pathway. To further understand the UPP mediated CPT resistance mechanism we used targeted proteasome prohibition by ixazomib (MLN9708) to stabilize topoI and determine its impact on CPT resistance. CPT resistant and sensitive cancer lines were both treated with ixazomib in combination with CPT. The CPT induced rate of topoI degradation, and its stabilization by ixazomib, was visualized and estimated by immunohistochemistry, immunofluorescence and immunoblotting assays, MTT and subG1 assays provided the drug sensitivity. Our results demonstrate that cells that degrade topoI rapidly are very resistant to CPT, and ixazomib significantly inhibits CPT induced topoI degradation. Notably, inhibition of proteasomal degradation by ixazomib overcomes the drug resistance and sensitizes the cells for CPTs.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform Cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

Objective On the eve of the summer Olympic Games in Tokyo research focus has shifted on the core temperature responses of elite athletes competing in the heat. In the absence of the field data of core temperature during Olympic sailing competition aim of the present study was to identify core temperature response during the Tokyo 2020 Olympic Test Event. Methods Four elite athletes from Olympic sailing (177.5±5.2 cm, 71.1±7.4 kg, body mass index 22.5±1.4 kg/m2, 24.8±3.7 yrs, VO2max 50.6±7.2 mL/min/kg)): 2 males and 2 females participated in the study. Core temperature was recorded using e-Celsius ingestible capsules, heart rate using a heart rate monitor. Ambient conditions in direct sunlight were measured using portable meteo station. Results Core temperature was recorded at water environment via an ingestible capsule in 4 sailors during the training (T), and competition (C), respectively. Ambient conditions in direct sunlight were hot and humid: during training temperature were 30.9°C±1.7°C and relative humidity 81.4%±2.8%, corresponding to a wet-bulb globe temperature of 41°C±4°C and during competition temperature was 31.2°C±2.3°C and relative humidity 87.2%±4.4%, corresponding to a wet-bulb globe temperature of 45.2°C±8.9°C. Core temperature increased during training reaching higher peak values (38.6°C±0.4°C) and during competition (38.9°C±0.4°C). The highest temperature recorded was 39.4°C (C). Conclusion The current study provides unique information into the core temperature parameters under heat stress in elite Olympic sailors during training and race event.

Parascaris sp. is the only ascarid parasitic nematode in equids and one of the most threatening infectious organisms in horses. Only a limited number of compounds are available for treatment of horse helminthiasis and Parascaris sp. worms have developed resistance to the three major anthelmintic families. In order to overcome the appearance of resistance, there is an urgent need for new therapeutic strategies. The active ingredients of herbal essential oils are potentially effective antiparasitic drugs. Carvacrol is one of the principal chemicals of essential oil from Origanum, Thymus, Coridothymus, Thymbra, Satureja and Lippia herbs. However, the antiparasitic mode of action of carvacrol is poorly understood so far. Here, the objective of the work was to characterize the activity of carvacrol on Parascaris sp. nicotinic acetylcholine receptors (nAChRs) function both in vivo with the use of worm neuro-muscular flap preparations and in vitro with two-electrode voltage-clamp electrophysiology on nAChRs expressed in Xenopus oocytes. We have developed a neuromuscular contraction assay on Parascaris body flaps and obtained acetylcholine concentration-dependent contraction responses. Strikingly, we observed that 300 µM carvacrol fully and irreversibly abolished Parascaris sp. muscle contractions elicited by acetylcholine. Conversely, carvacrol antagonized acetylcholine-induced currents from both the nicotine-sensitive AChR and the morantel-sensitive AChR subtypes. Thus, we show for the first time that the body muscle flap preparation is a tractable approach to investigate the pharmacology of Parascaris sp. neuro-muscular system. Our results suggest an intriguing mode of action for carvacrol being a potent antagonist of muscle nAChRs of Parascaris sp. worms which may account for its antiparasitic potency.

Hadhramout Initiative Against Corona (HIAC ) formed a working group of clinicians relevant to the management of COVID-19 to formulate clinical practice guidelines (CPG) for clinicians caring for the patients infected with COVID-19 in Yemen. The regional guidelines on the management of COVID-19 were thoroughly reviewed and its applicability was assessed for Yemen. HIAC’s recommendations covered (2) sections: the first one is the diagnosis, including case definition, risk stratification of the affected cases, investigations (prioritization of reverse transcription-polymerase chain reaction (RT-PCR) testing, D-dimer, chest x-ray, and chest computed tomography, while the second part covers the treatments (mainly Favipiravir, Remdesivir, Hydroxychloroquine, and Glucocorticoid, Anticoagulants, and Supportive measures). In conclusion, the adoption of cost-effective and evidence-based guidelines in Yemen will standardize the management of the patients infected with COVID-19 and protect both the patients and the health care workers from malpractice.

In this paper, we run for all INDIA mutations and variants a biomathematical numerical method for analysing mRNA nucleotides sequences based on UA/CG Fibonacci numbers proportions (Perez, 2021). In this study, we limit ourselves to the analysis of whole genomes, all coming from the mutations and variants of SARS-CoV2 sequenced in India in 2020 and 2021. We then demonstrate - both on actual genomes of patients and on variants combining the most frequent mutations to the SARS-CoV2 Wuhan genomes and then to the B.1.617 variant - that the numerical Fibonacci AU / CG metastructures increase considerably in all cases analyzed in ratios of up to 8 times. We can affirm that this property contributes to a greater stability and lifespan of messenger RNAs, therefore, possibly also to a greater INFECTUOSITY of these variant genomes.

Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the road for the emerging nanomedicine as a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 was reported in lung, colon, metastatic breast cancers and bladder squamous carcinoma. Accordingly, there has been a growing interest in using sildenafil as monotherapy or chemoadjuvant in EPR augmentation and management of different types of cancer. Sildenafil had been reported to increase the sensitivity of tumor cells of different origins to the cytotoxic effect of chemotherapeutic agents with augmented apoptosis mediated through inducing the expression of Bad and Bax proapoptotic proteins. It was also reported that the use of sildenafil prior to the administration of Doxorubicin (DOX) increased its EPR-related concentration in breast cancer tissues by 2 folds. Further, a substantial reason of anticancer chemotherapeutic failure is due to multidrug resistance (MDR), exacerbated by the overexpression of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCCs. Sildenafil has demonstrated inhibitory effects on the efflux activity of ABCC4, ABCC5, ABCB1, and ABCG2, ultimately reversing MDR caused by these transporters. In this review, we critically examine the overall potential of sildenafil in enhancing EPR-based anticancer drug delivery pointing up the outcome of the most important related preclinical and clinical studies.

Protamine is a natural cationic peptide mixture mostly known as a drug for the neutralization of heparin and as a compound in formulations of slow-release insulin. Protamine is also used for cellular delivery of nucleic acids due to opposite charge-driven coupling. This year marks60 years since the first use of Protamine as a transfection enhancement agent. Since then, Protamine has been broadly used as a stabilization agent for RNA delivery. It has also been involved in several compositions for RNA-based vaccinations in clinical development. Protamine stabilization of RNA shows double functionality: it not only protects RNA from degradation within biological systems, but also enhances penetration into cells. A Protamine-based RNA delivery system is a flexible and versatile platform that can be adjusted according to therapeutic goals: fused with targeting antibodies for precise delivery, digested into a cell penetrating peptide for better transfection efficiency or not-covalently mixed with functional polymers. This manuscript gives an overview of the strategies employed in protamine-based RNA delivery, including the optimization of the nucleic acid’s stability and translational efficiency, as well as the regulation of its immunostimulatory properties from early studies to recent developments.

Breast cancer (BC) is the most common cancer diagnosed in women worldwide. Approximately 70% of BC patients have the luminal subtype, which expresses hormone receptors (HR+). Adjuvant endocrine treatments are the standard of care for HR+/HER2- BC patients. Over time, approximately 30% of those patients develop endocrine resistance and metastatic disease. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacies in increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic BC patients. CDKi blocks kinases 4/6, preventing G1/S cell cycle transition. However, not all patients respond to CDKi, and those who do respond ultimately develop resistance to the combined therapy. Studies in tumour tissues and cell lines have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. Over the last few years, liquid biopsy has contributed relevant information. Circulating tumour materials are potential prognostic markers for determining patient prognosis in metastatic luminal BC, for monitoring disease and for treatment selection. This review outlines the different studies performed using liquid biopsy in patients with HR+ metastatic BC treated with CDKi plus endocrine therapy. We focus mainly on those studies that describe possible resistance mechanisms in circulating tumour-derived material.

Type-2 diabetes mellitus (T2DM) have been strongly associated with single nucleotide polymorphisms (SNPs) in the TCF7L2 gene. This study investigated the association between rs12255372, rs7903146 and T2DM in a Ghanaian population. A case-control study design was used for this study. A total of 106 T2DM patients and 110 control participants were selected. Basic data collected included body mass index, blood pressure and socio-demographics. Fasting blood samples were collected and used for serum lipid analysis, HbA1c, plasma glucose estimation and DNA extraction. Common and allele-specific primers were designed for genotyping using the Modified Tetra-Primer Amplification assay. Associations were evaluated using logistic regression models. The rs7903146 risk variant was significantly associated with 2.16 vs 4.06 increased odds for T2DM in patients <60 years vs ≥60 years. Both rs7903146 and rs12255372 are significantly associated with increased odds of T2DM in women, overweight/obese; T2DM negative family history (T2DM-NFH) and low-HDL-C. In a multivariate model, rs7903146 but not rs12255372 was significantly associated with 2.18, 5.01 and 2.25 increased odds of T2DM, under the codominant, recessive and additive model, respectively (p<0.05). The association between rs7903146 and rs12255372 with T2DM is more highly associated in a subgroup- women and those with T2DM-NFH, yet have cardiometabolic risk.

Hypertrophic cardiomyopathy (HCM) is a common inherited heart disorder complicated by left ventricle outflow tract (LVOT) obstruction, which can be treated with surgical myectomy. To date, no reliable biomarkers for LVOT obstruction exist. To determine whether metabolomic biomarkers for obstruction can be identified, we conducted metabolomic profiling on plasma samples of 18 HCM patients before and after undergoing surgical myectomy to measure changes in the plasma metabolome in the postoperative state. Plasma was collected approximately 4 weeks before surgery at the preoperative visit and approximately 3 months after the surgery at the postoperative visit. We found that 215 metabolites were altered in the postoperative state (p-value &lt; 0.05). Identified metabolites that were significantly reduced post-myectomy included metabolites of heme, such as bilirubin, and phenylacetylglutamine, a biomarker of urea cycle disorders, which suggests that liver and kidney function are improved in the postoperative state. Markers of arginine metabolism such as homoarginine and dimethylarginine are also decreased in the postoperative state, suggestive of reduction in nitric oxide production, inflammation and heart failure after surgery. 3-hydroxybutyrate (BHBA) was also decreased, suggesting possible increased fatty acid utilization and a return to normal heart function. 12 of these metabolites were notably significant after adjusting for multiple comparisons (q-value &lt; 0.05), including bilirubin, PFOS, PFOA, 3,5-dichloro-2,6-dihydroxybenzoic acid, 2-hydroxylaurate, trigonelline and 6 unidentified compounds, which support improved kidney and liver function and increased lean soft tissue mass. These findings suggest improved organ metabolic function after surgical relief of LVOT obstruction in HCM and further underscore the beneficial systemic effects of surgical myectomy.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a broad array of clinical signs. In this study, we aimed to use intravenous immunoglobulins (IVIG), called intacglobin, as a monotherapy to manage SLE in three patients. Laboratory investigations for SLE diagnosis were performed, including the detection of anti-nuclear antibodies (ANA) and SLE confirmation by detecting high titers of anti-dsDNA antibodies. C3 and C4 serum levels were assessed, as well as the determination of immunoglobulins. The SLEDAI score was measured to determine whether a significant degree of disease activity existed and as a prognostic value. The evaluation of any chest infection was performed by chest-X-ray. The patients were treated with five–ten g/day of IVIG for six consecutive days, followed by five–ten g/month. Immunological evaluation demonstrated that patients presented with a flare of SLE with high titers of ANA and anti-dsDNA antibodies, low C3 and C4, and elevated immunoglobulin levels. The SLEDAI score falls from 10 to below 3, and chest infections in some patients are cleared up. The postulated mechanisms of action of IVIG demonstrated that it could be used as an immunosuppressor, immunomodulator, and antimicrobial agent in patients with SLE.

Background: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. Methods: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In each group, treatment results were assessed depending on whether or not tocilizumab was used. Results: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/ml, p &lt;0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p=0.043), RR = 2.1 (95% CI 1.0-4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p=0.013), RR = 0.50 (95% CI 0.25-0.99). Сonclusions: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients it contributed to reduced mortality.

Tempeh is an Indonesian traditional food, made from white soybean seeds by fermentation with Rhizopus mold. Soybean seeds content high isoflavone glycosides. Isoflavones can act as phytoestrogen, antioxidant and improves memory. Isoflavone glycosides are poorly absorbed in the human body, but the aglycone isoflavones absorbed quickly. Rhizopus mold hydrolize isoflavone glycosides to be aglycone isoflavones during tempeh production. This research was aimed to know the best room temperature and time of fermentation for making soybean tempeh with high content of isoflavones. After rinsing and boiling, the soybean seeds than fermented with Rhizopus oligosporus. Three conditions were applied: (a) ambient temperature (27-32oC) without air circulation, (b) 27±0.5 oC, and (c) 30±0.5 oC both with air circulations. Inner temperature of tempeh was recorded hourly. Total isoflavones were measured with UV spectrophotometer every 6 hours. Based on this study, fermentation at (a) condition caused the tempeh too hot and rotted quickly. Fermentation at (b) and (c) conditions produced tempeh with good quality. Tempeh ripening was reached between 32-32 hours with inner temperature 32-33oC. Fermentation for 72 hours at condition (b) was chosen because its high total isoflavones content (0.089% w/w), but decrease about 20% compare to soybean seeds (0.112% w/w).

Carnivore protoparvovirus 1 (CPPV-1) is a DNA virus causing gastrointestinal disease and immunosuppression in various terrestrial carnivores. Domestic dogs and cats are considered the primary CPPV-1 reservoirs. The habitat overlaps of wild carnivores and free-roaming dogs increases the threat of CPPV-1 transmission between them. This study explored the CPPV-1 distribution among wild carnivores through PCR screening and compared the DNA sequences of the partial capsid protein (VP2) between wild and domestic carnivores. In total, 181 samples were screened for the CPPV-1 VP2 gene, including 32 masked palm civets (Paguma larvata), 63 Chinese ferret badgers (Melogale moschata), and 86 crab-eating mongooses (Herpestes urva), from 2015 to 2019 in Taiwan. The average prevalence of CPPV-1 was 17.7% (32/181), with the highest prevalence in masked palm civets (37.5%). In addition, a masked palm civet was coinfected with two CPPV-1 strains. Among the 33 partial VP2 gene sequences, 23 were identical to sequences amplified from domestic dogs and cats in Asia and the remaining 10 were identified for the first time. This study demonstrated that CPPV-1 has circulated between domestic and wild carnivores in rural Taiwan. Therefore, further population control and health management of free-roaming domestic carnivores are recommended.

Nowadays, the human population is facing the third and may be the worst pandemic caused by human coronaviruses (CoVs). The virus was first reported in Wuhan, China on 31 December 2019 and spread within short time to almost all countries of the world. Genome analysis of the early virus isolates has revealed high similarity with SARS-CoV and hence the new virus was officially named SARS-CoV-2. Since CoVs have the largest genome among all RNA viruses, they can adapt many point mutation and recombination events; particularly in spike gene, that enable these viruses to rapidly change and evolve in nature. CoVs are known to cross the species boundaries by using different cellular receptors. SARS-CoV-2 is believed to originate in bats and transmitted to human being through an ill-defined intermediate host. In the current review, different aspects of SARS-CoV-2 biology and pathogenicity are discussed including virus genetics and evolution, spike protein and its role in evolution and adaptation to novel hosts, and virus transmission and persistence in nature. In addition, the immune response developed during SARS-CoV-2 infection is demonstrated with special reference to the interplay between immune cells and their role in disease progression. We believe that SARS-CoV-2 outbreak will not be the last and spillover of CoVs from bats will continue. Therefore, establishing intervention approaches to reduce the likelihood of future CoVs spillover from the natural reservoirs is a priority.

Without impacting the dental sciences, breakthroughs in technology and applications could not be accomplished. In the advancement of technology and information technology, dentistry and dental materials have been fully active, so much so that they have revolutionized dental techniques. Material & methods; We want to produce the first series of articles in this review on the use of digital techniques and software, such as Smile Concept Digital. The goal is to gather all the findings on the use of this program and to highlight the fields of use. The analysis included forty-nine articles, the latter discussing the use of Digital Smile Design and the area of use. The research aims to classify the dental fields are using "digitization." Change is constant in this field and will be increasing Interest in dentistry by recommending the speed and reliability of outcomes for care planning. Conclusion: As seen in the study, the digital workflow facilitates recovery that is reliable both from an aesthetic and functional point of view. The current area of use of Digital Smile Design techniques in the different branches of medicine and dentistry as well as knowledge have emerged from this research

As in glaucoma and other optic neuropathies cellular dysfunction often precedes cell death, sensitive assessment of retinal ganglion cell (RGC) function represents a key outcome measure for neuroprotective strategies aimed at targeting distressed but still viable cells. Here we offer a conceptual framework to identify progressive stages of RGC dysfunction leading to cell death in mouse models of glaucoma and other optic neuropathies based on non-invasive pattern electroretinogram (PERG), to differentiate phenotypic and altered RGC response dynamics, to assess susceptibility to stressors and to assess reversible dysfunction.

Introduction: Otitis media with effusion (OME) is common in pediatric primary care consultations. Its etiology is multifactorial, although it has been proven that inflammation factors mediate and that immunity is in a phase of relative immaturity. The objective of this study was to assess the effects of the Traditional Mediterranean Diet (TMD) modulating inflammation and immunity in patients diagnosed with OME.

Treating infections caused by Pseudomonas aeruginosa is increasingly difficult due to high antimicrobial resistance, materialized through the presence of multiple resistance strains, as well as due to rapid development of resistance throughout treatment. The present survey was conducted to investigate the antibiotic susceptibility profile of Pseudomonas aeruginosa pathogens, in two University Veterinary hospitals from different geographical regions of Romania (i.e., south-west - Timisoara county and north-east – Iasi county) involved in canine superficial infections. A total of 142 swab specimens were collected from dogs with superficial infections (superficial skin infections, otitis externa, perianal abscess), with the aim of assessing the presence of Pseudomonas aeruginosa, based on phenotypic and molecular characterization. Fifty-eight samples (40.84%; 58/142) were positive for Pseudomonas aeruginosa (according to their confirmed morphological and molecular features). Susceptibility to usual antibiotics used in the treatment of canine skin conditions was tested for all Pseudomonas strains that were isolated from canine superficial infections, using the Kirby Bauer disc diffusion method. Drug resistance was observed in the case of all tested antibiotics. The susceptibility rate of P. aeruginosa strains that were tested in this study was in the following order: ampicillin sulbactam (55.17%; 32/58), followed by ceftazidime (53.44%; 31/58), aztreonam (51.72%; 30/58), amikacin (44.82%; 26/58), azithromycin (41.37%; 24/58), gentamycin (37.93%; 22/58), cefepime (36.20%; 21/58) meropenem (25.86%; 13/58), piperacillin-tazobactam (25.86%; 13/58) imipenem (22.41%; 13/158), ciprofloxacin (17.24%; 10/58) tobramycin (8.62; 5/58), and polymyxin B (1.72; 1/58) respectively. The results highlight the importance of antibiotic susceptibility testing in Pseudomonas aeruginosa isolates from dogs with superficial infections, in order to use an adequate treatment plan for the management of the skin condition, and other pathology (otitis externa and perianal abscesses).

Safe administration of highly cytotoxic chemotherapeutic drugs is a challenging problem in cancer treatment due to the adverse side effects and collateral damage to non-tumorigenic cells. To mitigate these problems, new promising approaches, based on the paradigm of controlled targeted drug delivery (TDD), utilizing drug nanocarriers with biorecognition ability to selectively target neoplastic cells, are being considered in cancer therapy. Herein, we report on the design and testing of a nanoparticle-grid based biosensing platform to aid in the development of new targeted drug nanocarriers. The proposed sensor grid consists of superparamagnetic gold-coated core-shell Fe₂Ni@Au nanoparticles, further functionalized with folic acid targeting ligand, model thiolated chemotherapeutic drug doxorubicin (DOX), and a biocompatibility agent, 3,6,-dioxa-octanethiol (DOOT). The employed dual transduction based on electrochemical and enhanced Raman scattering detection have enabled efficient monitoring of the drug loading onto the nanocarriers, attached to the sensor surface, as well as the drug release under simulated intracellular conditions. The grid’s nanoparticles serve here as the model nanocarriers for new TDD systems under design and optimization. The superparamagnetic properties of the Fe₂Ni@Au NPs aid in nanoparticles’ handling and constructing a dense sensor grid with high plasmonic enhancement of the Raman signals due to the minimal interparticle distance.

With the onset of the COVID19 pandemic, information technology has played a critical role in healthcare. A broad spectrum of information technology tools and applications played an essential role to create awareness of the COVID19 vaccination drive and its health benefits. We use the COVID-19 Global Beliefs, Behaviors, and Norms Survey for analysis of prevalence and factors associated with vaccination drives among men and women aged 20-80 years in 60 countries worldwide. Our analysis of the global survey offers a unique perspective about the role of information technology associated with vaccination drives involving social norms and human behavior among 437,236 respondents. The international survey was organized using a pre-registered randomized experiment demonstrating the role of technology in reaching out to people based in diverse communities and evaluating their beliefs, behavior, and social norms. The study shows that vaccine acceptance can vary due to descriptive norms. Our analysis shows 65.06% of people all over the globe are willing to get vaccinated and a large proportion of the population thinks that the COVID19 pandemic is a viable threat to the community and preventive measures need to be taken including vaccination drives.

Diabetes is a chronic disease that often causes progressive complications in the elderly. Along with the decline in cognitive function in the elderly, it causes dependence on disciplined management of diabetes mellitus. This dependence causes a very important mentoring role to be given. The purpose of this study is to provide knowledge, attitudes, and family skills to care for the elderly with diabetes mellitus at home through the empowerment of elderly cadres in Lampung. This research method is a quasi-experimental research with a control group design with a total of 64 elderly respondents and 64 families selected by simple random sampling technique. The assessment used an instrument for assessing family abilities that the researcher developed included aspects of knowledge, attitudes, and skills. The results of the dependent t-test analysis showed a significant increase in the knowledge and skills variable in the intervention group (0.000) but decreased in the attitude variable with p 0.198. Meanwhile, the increase in value also occurred in the attitude and skill variables in the control group. So that the results of the independent t-test only showed a significant difference in the attitude score (0.000) with the highest score in the control group. So that there is no significant increase in the ability of the family after the implementation of elderly cadres empowerment.

TSPO-PET tracers are sensitive to a single-nucleotide-polymorphism (rs6971-SNP) resulting in low (LAB), medium (MAB) and high (HAB) affinity binders, but the clinical relevance for [18F]GE-180 is still unclear. We evaluate the impact of rs6971-SNP on in vivo [18F]GE-180 binding in healthy brain and in pseudo-reference tissue in neurooncological and neurodegenerative diseases. Standardized uptake values (SUV) of [18F]GE-180-PET were assessed using a manually drawn region of interest in the fronto-parietal and cerebellar hemisphere. SUVs were compared between LAB, MAB and HAB in controls, glioma, 4-repeat tauopathies (4RT) and Alzheimer’s disease (AD) subjects. Second, SUVs were compared between patients and controls within their rs6971-subgroup. After exclusion of patients with prior therapy, n=24 LABs (n=7 controls, n=5 glioma, n=6 4RT, n=6 AD) were analysed. Age- and sex-matched MABs (n=38) and HABs (n=50) were selected. LABs had lower fronto-parietal and cerebellar SUVs when compared to MABs and HABs, but no significant difference was observed between MABs and HABs. Within each rs6971 group no SUV difference between patients and controls was detected in the pseudo-reference tissues. The rs6971-SNP affects [18F]GE-180 quantification, revealing lower binding in LABs when compared to MABs/HABs. Fronto-parietal and cerebellar ROIs were successfully validated as pseudo-reference regions.

Abstract Aim: To determine the efficacy of health beliefs model –based intervention in changing the belief related to substance use among university student in Mosul city-Iraq. Design: A randomized controlled trial. Methods: A probability (simple random sample) of (N=80) undergraduate student in different specialties would be selected. The study sample will be recruited from (4) colleges in the University of Mosul's Engineering, Sciences, Medicine and Education Colleges. The sample will be randomly assigned into experimental and control groups of (40) undergraduate student for each group. Such chosen is employed of pool of topics that have the criteria contain students who have using on (Smoking, Hookah, Drug abuse and Alcohol).For during from 25of October / 2019 till 1 of February/2021. Data is analyzed using the "Statistical Package for Social Science" (SPSS) software for Windows (V:26). Results: This finding indicated that before the intervention, mean scores for all concepts of HBM, add to Motivation, Control, and behaviors intensions of students they were almost equal. However, after the intervention were significantly different in the study group, while it was not significant in the control group. Conclusion:This study concluded that designing an HBM-based study could affect students' understanding and their behaviors in the field of substance abuse. Considering the positive correlation between construct of HBM, particularly in "perceived benefits and perceived severity" related to students’ beliefs. These beliefs implied a significant correlation with each other and with the attention to the prevention of addiction.

Background: The rising prevalence of obesity has a significant impact on obstetrics practice regarding maternal and perinatal complications includes recurrent miscarriage, pregnancy-induced hypertension, preeclampsia, gestational diabetes, and prolonged labor. Objective: To assess the impact of obesity on pregnancy and neonatal outcomes among Saudi women. Methods: The study was conducted at King Abdul-Aziz Medical City, Jeddah. Design: A cross-sectional retrospective design. A total number of 186 participants were recruited from July to Dec.2018 according to eligibility criteria. The data were collected retrospectively by a review of the chart records of the labor and delivery department. Results: The mean (SD) age of participants was 31.94(5.67) years old; two-thirds were in obesity class1. There was a significant association between obesity and pre-existing thyroid disease and induced hypertension class3. However, episiotomy showed that obesity class3 was significantly different from obesity class2. Conclusion: This study concludes obesity affects the outcomes of pregnant Saudi associations between obesity and preeclampsia, perineal tears, and episiotomy variables, and other variables reflect no associations. Recommendations: Further studies are needed to generalize the results. This study endorses the pregnant women start the antenatal follow-up from 1st trimester so, the data will be available on the system for research.

Introduction.Sars-CoV-2 infection poses particular problems in pregnancy, as the infection more frequently causes severe complications than in unaffected pregnant women, or non-pregnant women with SARS-CoV-2 infection. Now that vaccination is available and rapidly getting implemented worldwide, the question arises whether pregnant women should be vaccinated, and if so, whether they should get priority. Methods. Available scientific data and available guidelines about vaccination against SARS-CoV-2 were collected by the Guideline Committee of the International Society of Infectious Diseases in Obstetrics and Gynecology (ISIDOG), and were analyzed, discussed and summarized as guidelines for health care workers caring for pregnant women. Concluding statements were graded according to the Oxford Evidence Based Medicine Grading System. Results. There is evidence to consider pregnancy as a risk factor for serious complications of COVID-19 infection, even in the absence of additional risk factors, such as hypertension, diabetes and obesity which increase these risks even more in pregnancy. Currently available data slightly favor mRNA-based vaccines above vector-based vaccines during pregnancy and breastfeeding, until more safety data become available. Conclusion. ISIDOG advices policy makers and societies to prioritize pregnant women to receive vaccination against SARS-CoV-2, and favor the mRNA vaccines until further safety information becomes available.

The aim of the study was to examine the use of video-based communication and its association with loneliness, mental health and quality of life in older adults (60-69 years versus 70+ years) during the COVID-19 pandemic. A cross-sectional online survey was conducted in Norway, UK, USA and Australia during April/May 2020, and 836 participants in the relevant age groups were included in the analysis. Multiple regression analyses were conducted to examine associations between use of video-based communication tools and loneliness, mental health and quality of life within age groups, while adjusting by sociodemographic variables. Video-based communication tools were found to be more often used among participants aged 60-69 years (60.1%), compared to participants aged 70 or above (51.8%, p < 0.05). Adjusting for all variables, use of video-based communication was associated with less loneliness (β = -0.12, p < 0.01) and higher quality of life (β = 0.14, p < 0.01) among participants aged 60-69 years, while no associations occurred for participants in the oldest age group. The use of video-based communication tools was therefore associated with favorable psychological outcomes among participants in their sixties, but not among participants in the oldest age group. The study results support the notion that age may influence the association between use of video-based communication tools and psychological outcomes amongst older people.

ABSTRACTIntroduction:Human Immunodeficiency Virus (HIV) is a global health problem that is almost recorded in every country. The long-term and long-term negative impacts of HIV cases are stigma and discrimination in people with HIV (PLHIV). The purpose of this study is to find out the stigma and discrimination felt by PLHIV.Method:This study design of systematic review from 4 electronic databases namely Scopus ScienceDirect, Sage and ProQuest by using keywords tailored to Medical Subject Headings (MeSH) including "Stress", "covid", "nursing", "hospital". This study uses PICOS framework to prevent research bias and analysed using descriptive analysis.Results:The results of the analysis of the article showed from 761 articles have been identified title, abstract and full-text so that recorded 15 articles that can be reviewed. The article consists of various designs, namely RCT, cross sectional and qualitative studies. Analysis shows that stigma and discrimination are social phenomena that manifest in several social areas.Conclusion:Stigma and discrimination in people with HIV (PLHIV) is still common, stigma is carried out by the wider community to their own families. The family approach is necessary to improve well-being as well as improve the social community of the family.

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.

Neither tumor growth nor regression is truly spontaneous, but both may under special circumstances be driven by similar events. We describe a sequence of processes that typically leads to tumor progression but may on occasion inadvertently result in regression. A possible procedure for reducing tumor mass through a controlled intervention is also outlined.

There is a growing number of evidence-based indications for pharmacogenetic (PGx) testing. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. In an observational cohort study we included subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. PGx-guided pharmacotherapy management was supported by the PGx expert system SONOGEN XP. The primary study outcome was PGx-based changes and recommendations regarding current and potential future medication. PGx-testing was triggered by specific drug-gene pairs in 102 subjects, and by screening in 33. Based on PharmGKB expert guidelines we identified at least one “actionable” variant in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4 %), and other current pharmacotherapy in 23 (22.5%). Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized expert consultations with interdisciplinary collaborations.

Background: Patients with atrial fibrillation (AF), lasting >48 h, considered for cardioversion, are recommended ≥3 weeks of oral anticoagulation before sinus rhythm restoration because of high risk of development of left atrial thrombosis (LAT) and stroke. However, the optimal duration of anticoagulation in the presence of overt LAT is unknown. Methods: An open-label study, aiming to investigate the prevalence of spontaneous echo con-trast (SEC) and LAT before and after 3 weeks of direct oral anticoagulant (DOAC) treatment. We included 51 consecutive patients (50.9% males), mean age 69.3±7.4 years with paroxys-mal/unknown duration of AF, considered for cardioversion, who agreed to have transesophage-al echocardiography at enrollment and 3 weeks later. Results: At baseline SEC was present in 26 (50.9%) and LAT in 10 (19.6%) of 51 patients. After 3 weeks on DOAC, SEC persisted in 12 (25.0%) and LAT in 7 (14.5%) of 48 patients, p<0.05 vs base-line. Factors, associated most strongly with persistence of SEC/LAT were left atrial appendage (LAA) emptying velocity <20 cm/s (OR=2.82), LAA lobes >2 (OR=1.84) and indexed left atrial volume ≥34 ml/m2 (OR=1.37). Conclusions: The recommended minimal period of 3 weeks of oral anticoagulation lead to SEC/LAT resolution in 47% of our patients. To our opinion, LA/LAA morphology and function should be taken into account when determining the duration of DOAC treatment before planned cardioversion.

Background: To determine vitamin D supplementation frequency among infants, factors that influence adherence, and reasons for discontinuation of initiated vitamin D. Methods: This cross-sectional study was conducted using a questionnaire administered to the mothers via a face-to-face interview on 560 infants aged from 1 to 24 months admitted to outpatient clinics from June to December 2017. Results: A total of 351 infants were administered vitamin D, and the rate of supplementation in the first year of life was 83%, while it was only 28% between 13 and 24 months. The rate of vitamin D supplementation was higher among infants who were exclusively formula-fed (p<.05). When the data were analyzed using logistic regression analysis, only visit family physicians seems to be a statistically significant independent variable in increasing supplementation (p<.05). Compared with family refusal, the rate of discontinuation of vitamin D by the healthcare providers was higher after the first year of life (p<.05). The rates of vitamin D discontinuation by healthcare providers, especially by nurses who considered the duration of supplementation adequate, were statistically significantly higher when compared with the fontanel closure and other reasons (p<0.05). Conclusions: The rate of vitamin D supplementation was higher among families who visited family physicians, which suggests the importance of well-baby visits. Since vitamin D supplementation was less common among exclusively breastfed infants, mothers should be educated. Healthcare professionals need further education about the importance of vitamin D supplementation and indications for discontinuation.

Drug repositioning (also called drug repurposing) is a strategy for identifying new therapeutic targets for existing drugs. This approach is of great importance in pharmacology as it is a faster and cheaper way to develop new medical treatments. In this paper, we present, to our knowledge, the first application of multiplex-heterogeneous network embedding to drug repositioning. Network embedding learns the vector representations of nodes, opening the whole machine learning toolbox for a wide variety of applications including link prediction, node labelling or clustering. So far, the application of network embedding for drug repositioning focused on heterogeneous networks. Our approach for drug repositioning is based on multiplex-heterogeneous network embedding. Such method allows the richness and complexity of multiplex and heterogeneous networks to be projected in the same vector space. In other words, multiplex-heterogeneous networks aggregate different multi-omics data in the same network representation. We validate the approach on a task of link prediction and on a case study for SARS-CoV2 drug repositioning. Experimental results show that our approach is highly robust and effective for finding new drug-target associations.

Background: Of the many side effects suffered by cancer patients, those related to cognitive performance have become increasingly prominent in clinical practice. We know that chemotherapy generates a series of side effects, such as nausea and vomiting, alopecia, and so on, which can be counteracted by complementary medication. However, in the case of post-chemotherapy cognitive impairment, or chemo brain, these cannot be controlled with drug therapies. However, before any intervention can be considered, it is necessary to know exactly what cognitive impairment is being triggered. For this reason, we decided to study the cognitive status of breast cancer patients. Methods: analytical, prospective, three-measure longitudinal, intrasubject unifactorial, non-probabilistic and accidental assignment study. The sample came from the Medical Oncology Department at Hospital de Salamanca, in Spain. Cognitive function (Trail Making Test and Stroop Test) was established as the primary variable; the presence of sleep disorders (Insomnia Severity Index, ISI) and anaemia (haemoglobin levels in blood) were analysed as secondary variables, in addition to intervening variables (age, stage, type of carcinoma, radiotherapy, menopause, social support network, marital status, years of schooling and employment status). Results: We recruited 151 individuals according to the selection criteria. We can confirm that factors including anaemia, menopause, patient support network and marital status, years of schooling, and employment status did affect the cognitive performance of the patients in the study. In contrast, sleep disorders, age, radiotherapy treatment, stage of disease, and type of carcinoma did not affect the cognitive performance of the cancer patients. Conclusions: Chemotherapy does impact the cognitive performance of breast cancer patients.

Background: Suicide attempts (SA) frequently occur in patients with mood disorders and schizophrenia, which are both accompanied by activated immune-inflammatory and nitro-oxidative (IO&NS) pathways. Methods: We searched PubMed, Google Scholar, and Web of Science, for articles published from inception until February 1, 2021. We included studies that compared blood biomarkers in psychiatric patients with (SA+) and without SA (SA-) and heathy controls and we combined different IO&NS biomarkers into immune, inflammatory, and neurotoxic profiles and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence interval (CI).Findings: Our search included 51 studies comprising 4.945 SA+ patients and 24.148 controls. We stratified the control group into healthy controls and SA- patients. SA+ patients showed significantly (p<0.001) increased immune activation (SMD: 1.044; CI: 0.599-1.489), inflammation (SMD: 1.109; CI: 0.505, 1.714), neurotoxicity (SMD: 0.879; CI: 0.465, 1.293), and lowered neuroprotection (SMD: 0.648; CI: 0.354, 0.941) as compared with healthy controls. When compared with SA- patients, those with SA+ showed significant (p<0.001) immune activation (SMD: 0.290; CI: 0.183, 0.397), inflammation (SMD: 0.311; CI: 0.191, 0.432), and neurotoxicity (SMD: 0.315; CI: 0.198, 0.432), and lowered neuroprotection (SMD: 0.341; CI: 0.167, 0.515). Patients with current, but not lifetime, SA showed significant (p<0.001) levels of inflammation and neurotoxicity as compared with controls. Conclusions: Patients with immune activation are at a higher risk of SA which may be explained by increased neurotoxicity due to inflammation and nitro-oxidative stress. This meta-analysis discovered new biomarkers of SA and therapeutic targets to treat individuals with SA.

After a long waited span, the whole world could see the ray of covid-19 vaccine to resist the planet to watch the death procession. But some country people especially the people of Bangladesh keep them aside to take the vaccination. This study aims to understand the perception towards the COVID-19 vaccination program in Bangladesh and the targeted subject is the university student as they are suffering highly depression nowadays. Higher education has been affected globally as a result of the COVID-19 pandemic in 223 countries. Moreover, for this pandemic situation, the university students can not complete their graduation which binds them to enter their professional career. Alike all of the developed countries, as well as developing countries, Bangladesh, also considered vaccination as an effective measure to protect the peoples from the Covid-19 virus. This study targeted three psychological factors of the university students and surveyed 322 students from the different universities in Bangladesh to understand their perception regarding vaccines. Moreover, it is seen that most of the students doubt the effectiveness of the vaccine which interrupts them from taking the vaccine willingly.

Background: Nearly two-thirds of acute stroke patients have dysphagia. Dysphagia is difficulty to swallow food or liquids. Early detection of dysphagia is crucial in stroke patients as a result of increased morbidity and mortality due to malnutrition and respiratory tract infections. Aim: Our purpose was to conduct a literature review of dysphagia screening for stroke patient. Methods: We used the bolean operator to search articles of “or” and “and” with the key words were "Dysphagia" or “Screening”, AND "Stroke" or Acute Stroke” AND "Nursing". Data based used were Scopus, Proquest and Science Direct with inclusion criteria using full text in English which published from 2019 to 2021. We obtained 240 articles and then we screened by reading the main focus of articles with paying attention to the topics and the suitability of article content.Result: Twenty five publications relating to dysphagia screening met the inclusion criteria. There are five methods of dysphagia screening performed by nurses or other health workers: 1) a simple Questionnaire Test (4QT) method; 2) Water Swallow Test (WST) method; 3) Bed Side Screening Tool for Dysphagia (BSTD) method; 4) Volume Viscosity Swallow Test (V-VST) method; 5) EAT-10 method.Conclusion: screening is the first step in the identification of swallowing impairment or dysphagia of stroke patient. Dysphagia is an independent predictor of poor patient outcome and prolonged recovery time. Nurse has an important role to conduct a screening and must ensure that the selected tools has high reliability and concurrent validity. Key Words: Dysphagia, Nursing, Screening, Stroke

Drug repurposing, the practice of utilizing existing drugs for novel clinical indications, has tremendous potential for improving human health outcomes and increasing therapeutic development efficiency. The goal of multidisease multitarget drug repurposing, also known as shotgun drug repurposing, is to develop platforms that assess the therapeutic potential of each existing drug for every clinical indication. Our Computational Analysis of Novel Drug Opportunities (CANDO) platform for shotgun multitarget repurposing implements several pipelines via large scale modelling and simulation of interactions between comprehensive libraries of drugs/compounds and protein structures. In these pipelines, each drug is described by an interaction signature that is then compared to all other signatures that are then sorted and ranked based on similarity. Pipelines within the platform are benchmarked based on their ability to recover known drugs for all indications in our library, and predictions are generated based on the hypothesis that (novel) drugs with similar signatures may be repurposed for the same indication(s). The drug-protein interactions in the platform used to create the drug-proteome signatures may be determined by any screening or docking method but the primary approach used thus far has been an in house similarity docking protocol. In this study, we calculated drug-proteome interaction signatures using the publicly available molecular docking method Autodock Vina and created hybrid decision tree pipelines that combined our original bio- and cheminformatic approach with the goal of assessing and benchmarking their drug repurposing capabilities and performance. The hybrid decision tree pipeline outperformed the corresponding two docking-based pipelines it was synthesized from, yielding an average indication accuracy of 13.3% at the top10 cutoff (the most stringent), relative to 10.9% and 7.1% for its constituent pipelines, and a random control accuracy of 2.2%. We demonstrate that docking based virtual screening pipelines have unique performance characteristics and that the CANDO shotgun repurposing paradigm is not dependent on a specific docking method. Our results also provide further evidence that multiple CANDO pipelines can be synthesized to enhance drug repurposing predictive capability relative to their constituent pipelines. Overall, this study indicates that pipelines consisting of varied docking based signature generation methods can capture unique and useful signal for accurate comparison of drug-proteome interaction signatures, leading to improvements in the benchmarking and predictive performance of the CANDO shotgun drug repurposing platform.

The COVID-19 pandemic is a devastating blow to the entire world community and changes the order of human life. All efforts and strategies are being carried out to contain and reduce the spread of the SARS-COV-2 virus, both by tightening the health protocol and using vaccines to the public. Currently, several vaccines are available and have passed phase 3 clinical trials, such as vector vaccines (Gamaleya Sputnik V Russia, University of Oxford/AstraZeneca, CanSino, and Janssen Pharmaceutical Companies), mRNA-based vaccines (Moderna/BioNTech/Fosun Pharma/Pfizer), inactivated vaccines (SinoVac and SinoPharm from China, Covaxin from Bharat Biotech India), and adjuvanted recombinant protein nanoparticles (Novavax from the USA) are expected to be able to suppress the spread of the virus and produce a minimum of 70 percent herd-immunity in a population. Each vaccine's efficacy varies from the lowest, namely the Sinovac vaccine (CoronaVac) 50% to the highest the Novavax vaccine (NVX-Cov2373) 96% effectivity value. Moreover, further rigorous research is still being carried out for the development of an effective and efficient vaccine.

The US opioid overdose epidemic has risen to an all-time high. Prescription opioids often serve as a gateway to illicit opioids which have appreciable overdose potential. Recent investigations have highlighted the efficacy and safety of marijuana-based products for pain management. Providing alternative pain treatment options may help mitigate the opioid epidemic. The distribution of codeine, fentanyl, hydrocodone, morphine, and oxycodone per 100K people and by 3-digit zip codes and overdose rates from 2014 to 2018 in California, which legalized recreational marijuana in 2016, were compared to Texas, where marijuana is functionally prohibited. Drug weights were obtained from the Automation of Reports and Consolidated Orders System and converted to oral morphine milligram equivalents. Overdose data was retrieved from the Centers for Disease Control’s WONDER database. California (-43.7%) and Texas (-27.3%) showed significant reductions in cumulative opioid distribution from 2014 to 2018. Opioid distribution per 100K people decreased -38.9% in California relative to -26.4% in Texas. Opioid and heroin overdoses increased between 1999 and 2019 by +11.6% in California but +272.7% in Texas. This evidence supports marijuana legalization as a mitigating factor to the opioid epidemic and opioid misuse.

Tumor-associated macrophages are a key component in the tumor microenvironment, secreting extracellular vesicles (EVs) such as exosomes and other various factors for intercellular communication. However, macrophage-derived EVs heterogeneity and their cytotoxicity to cancer cells has not been well understood. Here, we aimed to separately isolate various types of macro-phage-EVs by size exclusion chromatography (SEC) method and investigate EV transmission and cytotoxicity to oral cancer cells. For fluorescence-labeling of cellular and EV membranes, palmitoylation signal-fused GFP and tdTomato were expressed in THP-1 monocytic cells and HSC-3 oral cancer cells, respectively. We found that fluorescence-labeled EVs secreted by macrophages were highly transmissive to oral cancer cells than those from parental monocytic cells. In a co-culture system and conditioned medium (CM), a macrophage-secreted unidentified factor was cytotoxic to oral cancer cells. We fractionated macrophage-derived EVs by the SEC method and performed western blotting to characterize various EV types. Three fractions were characterized: small exosomes (EXO-S: < 50 nm) fraction containing HSP90α, HSP90β, CD63 (EV marker) and β-actin; large exosomes (EXO-L: 50-200 nm) fraction containing CD9 (EV marker) and HSP90β; large EVs (100-500 nm) fraction. Notably, the macrophage-derived small exosomes fraction was cytotoxic to oral cancer cells, while large exosomes and large EVs were not. There-fore, it was implicated that macrophage-derived small exosomes are cytotoxic with high trans-mission potential to cancer cells.

Purpose of the study was to explore the association of cognition with hazardous drinking, binge drinking and alcohol use disorder in schizophrenia and schizoaffective disorder. Cognitive deficits are common in schizophrenia. Alcohol might be associated with additional cognitive impairment in schizophrenia patients. The study population included 3362 schizophrenia and schizoaffective disorder patients in Finland. Hazardous drinking was screened with the AUDIT-C (Alcohol Use Disorders Identification Test for Consumption) screening tool. Binge drinking was obtained from the AUDIT-C. Alcohol use disorder (AUD) diagnoses were obtained from the national registrar data. Participants performed two computerized tasks from the Cambridge automated neuropsychological test battery (CANTAB) on tablet computer: the 5-choice serial reaction time task (5-CSRTT), or, reaction time (RT) test and the Paired Associative Learning (PAL) test. Association of alcohol use with RT test and PAL test was analyzed with log-linear regression and logistic regression, respectively. After adjustment for age, education and age at first psychotic episode, hazardous drinking in females was associated with lower median RT. Compared to never binge drinkers, male and female participants drinking 6 or more doses of alcohol monthly or less had lower median RT. In the PAL test both first trial memory score (FTMS) and total errors adjusted score (TEAS) were associated with better performance in males drinking 6 or more doses of alcohol weekly or more and in females drinking 6 or more doses monthly or less. Higher PAL TEAS was associated with AUD in females Some positive associations between alcohol and cognition were found in male and female schizophrenia and schizoaffective disorder patients with hazardous drinking and binge drinking.

Bone involvement occurs in 75% of patients with Gaucher disease (GD), and comprises structural changes, debilitating pain, and bone density abnormalities. Osteoporosis is a silent manifestation of GD until a pathologic fracture occurs. Thus early diagnosis is crucial for identifying high-risk patients to prevent irreversible complications. Thirty-one patients with GD were assessed prospectively to identify predictive markers associated with bone density abnormalities, osteopenia (OSN), and osteoporosis (OSR). Subjects were categorized into three cohorts based on T- or Z- scores of bone mineral density (BMD): In GD cohort with no bone complication (Z-score≥-0.9; T-scores≥-1), the OSN group (-1.8 ≥ Z-score ≥ -1; -2.5 ≥ T-score ≥ -1) and OSR group (Z-score ≤ -1.9; T-scores ≤ -2.5). Serum levels of TRAP5b, RANKL, OPG, and RANK were quantified by enzyme-linked immunosorbent assays. TRAP5b was increased in GD and showed a positive correlation with GD biomarkers, including plasma glucosylsphingosine (Lyso-Gb1), macrophage activation markers CCL18 and chitotriosidase. The highest levels of TRAP5b was measured in patients with osteoporosis. The elevation of RANKL and RANKL/OPG ratio correlated with osteopenia in GD. Elevation of TRAP5b, RANKL, and RANKL/OPG indicate osteoclast activation in GD. TRAP5b is a potential bone biomarker for GD with the ability to predict the progression of bone density abnormalities.

Background: Circulating tumor cells (CTC) have relevance as prognostic markers in breast cancer. However, the functional properties of CTCs or their molecular characterization have not been well-studied. Experimental models indicate that only a few cells can survive in the circulation and eventually metastasize. Thus, it is essential to identify these surviving cells capable of forming such metastases. Methods: We isolated viable CTCs from 50 peripheral blood samples obtained from 35 patients with advanced metastatic breast cancer using RosetteSepTM for ex vivo culture. The CTCs were seeded and monitored on plates under low adherence conditions and with media supplemented with growth factors and Nanoemulsions. Phenotypic analysis was performed by immunofluorescence and gene expression analysis using RT-PCR and CTCs counting by Cellsearch® system. Results: We found that in 75% of samples the CTC cultures lasted more than 23 days, predicting a shorter Progression-Free Survival in these patients, independently of having ≥ 5 CTC by Cellsearch®. We also observed that CTCs before and after culture showed a different gene expression profile. Conclusions: the cultivability of CTCs is a predictive factor. Furthermore, the subset of cells capable of growing ex vivo show stem or mesenchymal features and may represent the CTC population with metastatic potential in vivo.

Clinical education is a method that is applied to formal nurse education as a step to provide real and direct learning experiences in the nursing environment correctly and effectively. The success of education in a clinical setting certainly requires the support of teaching nurses (clinical instructors) who have credibility and competence in terms of knowledge, attitudes and skills and are actively involved in professional activities. The diversity of backgrounds of nurses and students, including patients, certainly contributes to a shift in paradigms and perspectives for the nursing environment both in education and in clinical settings in health services. Responding to this cultural diversity, it is important to prepare knowledge and understanding related to transcultural nursing issues, intercultural communication and clinical education which explores the socio-cultural elements in the implementation of staff, students and patients. Purpose: The purpose of this literature review is to identify the extent to which nurse educators play a role by including socio-cultural and transcultural aspects in efforts to develop the quality of education in clinical practice environments in the millennium era. Method: The method of writing this article uses 11 literature review, the publication year period 2019,2020 and 2021 with sources from 4 databases such as science Direct, Scopus, ProQues and Elsevier. The review guidelines used are based on Prisma and the Joanna Briggs Institutute. The level of eligibility is identified through the title, abstract, research methodology as well as the type of scholarly journal and full text. Results: The results of the reviews found are presented in a narrative form. The results of the review study found that there were 11 articles explaining the competence of clinical education based on the socio-cultural approach, which is an educational strategy in the clinical area that integrates transcultural elements of nursing, intercultural communication, collaboration, self-directed with the principles of openness, honesty, and mutual respect in the implementation of team interaction and collaboration. The development of interpersonal relationships is also an important role that educators must have in helping to introduce the nurse orientation process to the organizational environment and other professional teams so that the achievement of satisfaction with clinical education is able to improve the performance of nurses and students perfectly. Conclusion: Clinical education which is supported by the competence of nurse educators (clinical instructors) who have individual and professional competences has a role to play in improving clinical learning outcomes by both students and nurses with a socio-cultural and transcultural strategic approach that will create satisfaction with the achievement of clinical competence and performance effectively.

Since SARS-CoV-2 has spread all over the world, one of the key questions is how long immunity works for protecting hosts from infection. However, it was difficult to distinguish reinfection from re-detected positive cases caused by other reasons. We confirmed 23 re-detected positive cases in Sapporo City in 2020, and among them, the case with 205-days interval from initial onset to the second confirmation date was found. We calculated the probability of observing more than one case with over d-days interval of re-detection, pobs, to find out whether the case with 205-days interval had the similar epidemiological characteristic with others or not. We found that 5th percentile and its 95% confidence interval of pobs was 118 (45, 216) for Sapporo City data and 92 (86, 98) for KCDC data. This result indirectly suggested the case with 205-days interval was reinfection.

Blood and/or urine levels of 27 heavy metals were determined by ICPMS in 41 patients with dilated cardiomyopathy (DCM) and 29 presumably healthy subjects from the Katanga Copperbelt (KC), in the Democratic Republic of Congo (DRC). After adjusting for age, gender, education level, and renal function, DCM probability was almost maximal for blood concentrations above 0.75 and 150 µg/dl for arsenic and copper, respectively. Urinary concentrations above 1 for chromium, 20 for copper, 600 for zinc, 30 for selenium, 2 for cadmium, 0.2 for antimony, 0.5 for thallium and 0.05 for uranium, all in μg/g of creatinine, were also associated with increased DCM probability. Concurrent and multiple exposures to heavy metals, well beyond permissible levels, are associated with increased probability for DCM. Study findings warrant screening for metal toxicity in case of DCM and prompt public health measures to reduce exposures in the KC, DRC.

Background: A person living with HIV / AIDS bargains with stressors such as discrimination, stigma depression, and several psychological impacts. The stressors experienced by people with HIV/ AIDS will certainly have an impact on daily activities, welfare, and management of medications which in general will have an impact on the quality of life. To deal with these stressors, it is necessary to have good and proper coping from within the PLWHA. Coping strategies need to be owned and carried out by PLWHA in order to respond adaptively to the stressor conditions experienced. Purpose: The aim of this review is to describe the stress experienced and the coping strategies used among PLWHA. Methods: This literature review used keywords in the search for international references are coping strategy, stressor, HIV-AIDS. Inclusion criteria: selection of titles that are relevant to the formulation of the problem and objectives, full-text articles in English, articles published from 2019 to 2021. The exclusion criteria used were coping strategy articles that did not involve HIV patients. Search references from electronic database sources namely ProQuest, CINAHL, and ScienceDirect.Six articles that are deemed worthy of analysis are then discussed or analyzed. Results: Age, gender and sexual orientation have contributed to the emerging stressor among PLWHA. The internal and external coping strategies focusing on the problem are important for PLWHA in handling the stressor. Conclusion: People with HIV-AIDS have many stressors in their lives, but they also have proper coping strategies depending on their internal and external conditions.

Prothrombotic thrombocytopathy mimicking heparin-induced thrombocytopenia has been observed in patients with severe COVID-19 and after immunisation with the Vaxzevria vaccine. Herein, we discuss the pathogenesis of this disorder focusing on the possible involvement of anti-platelet factor 4 (PF4) autoantibodies.

Background: The level of students' understanding of the knowledge of patient safety concepts in infection prevention and control and awareness of treatment is in the low category. Clinical education that provides problem-based learning models in real areas helps students to better understand patient safety. This study is designed to analyze the evaluation and reflection of the role of nursing education institutions in the achievement of patient safety competencies by nursing students.Method: "Searching for articles in research journals is obtained from Sciencedirect, Ebscohost, Garuda, Proquest and Scopus. As many as 228 articles were obtained consisting of nursing journals and health journals with the keywords clinical education, competence, and patient safety. After that, the screening process was carried out based on the inclusion criteria and obtained 25 articles that met the criteria. "Results: the results of the evaluation show that there is a big role in educational institutions in designing curricula, learning models, and clinical education models in an effort to achieve patient safety competencies in nursing students.Conclusion: the learning model about patient safety organized by many educational institutions is considered ineffective in producing the achievement of patient safety competencies for nursing students. This makes it necessary to develop models, reform the patient safety curriculum that is embedded in real areas in clinical education practice

Background: The incidence of fracture and surgery of the hip and lower extremities is still high. Long postoperative bed rest has the potential to increase the incidence of various complications that may increase the morbidity and mortality rate of patients after hip and lower extremities surgery. Aim: This literature review aimed to identify the effects of early mobilization in hip and lower extremity postoperative. Method: Search for articles on several databases such as ProQuest, ScienceDirect, CINAHL, Medline, Wiley Online and Scopus, using the Boolean operator by combining several keywords according to the literature review topic, with inclusion criteria are published in the last 3 years (2019-2021), used a quantitative design, written in English and full text articles. A total of 435 articles were obtained, then screened and reviewed, so that there were 16 (sixteen) eligible articles.Result: There were 11 (eleven) effects of early mobilization, i.e. reducing length of stay, reducing the risk of deep vein thrombosis (DVT), reducing pulmonary infections (pneumonia), reducing urinary tract infections, reducing the risk of wound infection, improving extremity function and ability to walk, reducing postoperative pain, reducing the risk of pressure sores, reducing postoperative delirium, reducing readmission and lowering hospitalization costs. Conclusion: This literature review showed that early mobilization is safe and effective in postoperative patients to reduce the risk of complications and adverse events. Nurses and health workers who care for patients could implement early mobilization and motivate patients to be cooperative in undergoing early mobilization.

Many aging adults experience some form of hearing problems that may arise from auditory peripheral damage. However, it has been increasingly acknowledged that hearing loss is not only a dysfunction of the auditory periphery but results from changes within the entire auditory system, from periphery to cortex. Damage to the auditory periphery is associated with an increase in neural activity at various stages throughout the auditory pathway. Here, we review neurophysiological evidence of hyperactivity, auditory perceptual difficulties that may result from hyperactivity, and outline open conceptual and methodological questions related to the study of hyperactivity. We suggest that hyperactivity alters all aspects of hearing – including spectral, temporal, spatial hearing – and, in turn, impairs speech comprehension when background sound is present. By focusing on the perceptual consequences of hyperactivity and the potential challenges of investigating hyperactivity in humans, we hope to bring animal and human electrophysiologists closer together to better understand hearing problems in older adulthood.

Background Although aminoglycosides are often used as treatment for Gram-Negative infections, optimal dosing regimens remains unclear, especially in ICU patients. This is due to a large between- and within-subject variability in the aminoglycosides’ pharmacokinetics in this population. Objective The review provides comprehensive data on the pharmacokinetics of aminoglycosides in patients hospitalized in ICU by summarizing all published PopPK models in ICU patients for amikacin, gentamicin, and tobramycin. The objective was to determine the presence of a consensus on the structural model used, significant covariates included, and therapeutic targets considered during dosing regimen simulations. Methods A literature search was conducted from the Medline/PubMed database, using the terms: ‘amikacin’, ’gentamicin’, ’tobramycin’, ‘pharmacokinetic(s)’, nonlinear mixed effect’, population’, ‘intensive care’ and ‘critically ill’. Results Nineteen articles were retained where amikacin, gentamicin and tobramycin pharmacokinetics were described in six, eleven and five models, respectively. Two-compartment model best described amikacin and tobramycin pharmacokinetics, whereas one-compartment model majorly described gentamicin pharmacokinetics. The most recurrent significant covariates were renal clearance and bodyweight. Across all aminoglycosides, mean interindividual variability in clearance and volume of distribution were 41.6% and 22.0%, respectively. A common consensus for an optimal dosing regimen for each aminoglycoside was not reached. Conclusion This review showed models developed for amikacin, from 2015 until now and for gentamicin and tobramycin from the past decades. Despite growing challenges of external evaluation, the latter should be more considered during model development. Further research including new covariates, additional simulated dosing regimens and external validation should be considered to better understand aminoglycosides pharmacokinetics in ICU patients.

Establishing macrometastases at distant organs is a highly challenging process for cancer cells, with extremely high attrition rates. A very small percentage of disseminated cells have the ability to dynamically adapt to their changing micro-environments through reversibly switching to another phenotype, aiding metastasis. Such plasticity can be exhibited along one or more axes – epithelial-mesenchymal plasticity (EMP) and cancer stem cells (CSCs) being the two most studied, and often tacitly assumed to be synonymous. Here, we review the emerging concepts related to EMP and CSCs across multiple cancers. Both processes are multi-dimensional in nature; for instance, EMP can be defined on morphological, molecular and functional changes, which may or may not be synchronized. Similarly, self-renewal, multi-lineage potential, and anoikis and/or therapy resistance may not all occur simultaneously in CSCs. Thus, arriving at rigorous functional definitions for both EMP and CSCs is crucial. These processes are dynamic, reversible, and semi-independent in nature; cells traverse the inter-connected high-dimensional EMP and CSC landscapes in diverse paths, each of which may exhibit a distinct EMP-CSC coupling. Our proposed model offers a potential unifying framework for elucidating the coupled decision-making along these dimensions and highlights a key set of open questions to be answered.

Cardiovascular disease is the first leading cause of death in the world. Patients with cardiovascular disease may experience various problems, including physiological and psychological problems. Apart from pharmacological therapy, complementary therapy is necessary as a support to conventional medicine. This review aims to describe complementary and alternative therapies for pain and anxiety in patients with cardiovascular disease. This review utilized data from ProQuest, ScienceDirect, and PubMed with search keywords of "Complementary" AND "Nursing" AND "Pain" AND "Anxiety" AND "Coronary artery disease". Ten articles that met the inclusion criteria were analyzed. The results show that nursing actions increasingly develop along with the patient needs. One form of holistic nursing action is complementary and alternative therapy (CAT) that consists of three categories: body-based methods, mind therapies, and sensory therapies. CAT has positive impacts on patients with heart disease. It can reduce anxiety and pain, lower blood pressure, and improve the quality of life. This review also shows that CAT has a positive impact on the recovery of patients with heart disease. Proper therapeutic management should be implemented to reduce the risks of physiological and psychological problems in patients.

Nosocomial infections can be transmitted by contaminated hospital surfaces with resistant pathogens. conventional sanitations are not efficiently contributing to removing resistant pathogens. Bacteriophages suggest as decontaminating agents, safe, their selective ability to kill specific bacteria. This work aimed to assess the efficiency of a phage in removing Pseudomonas aeruginosa from different hard surfaces. The decontamination ability of phages w was tested in vitro against Pseudomonas aeruginosa strain. Cystoviridae Phages with titer (2 × 1012 PFU/mL) can efficiently reduce viable bacterial cells on contaminated surfaces. The treated surfaces with alcohol 70% and phage showed an evident drop of bacterial cell number from 1 h to 24 h. These results suggest that bacteriophages are biocontrol agents removing nosocomial infection pathogens transmitted by contaminated surfaces in the hospital environment.

Background: We aimed to describe the patterns, management, and outcome of traumatic femoral shaft fractures. Methods: An observational descriptive retrospective study was conducted for all trauma patients admitted with femoral shaft fractures between January 2012 and December 2015 at the only level 1 trauma center and tertiary hospital in the country. Data were analyzed and compared according to the time to intramedullary nailing, mechanisms of injury and age groups. Main outcomes included in-hospital complications and mortality Results: A total of 605 cases were analyzed, with mean age of 30.7±16.2 years. The majority of fractures were unilateral (96.7%) and 91% were closed fractures. Three-fourth of fractures were treated by reamed intramedullary nailing (rIMN); antegrade in 80%. The pyriform fossa nails were used in 71.6% while trochanteric entry nails were used in 28.4%. Forty-five (8.9%) of fractures were treated with external fixator, 37 (6.1%) had conservative management. Traffic-related injuries occurred more in patients aged 14-30 years whereas; injuries related to fall were significantly higher in patients aged 31-59 years. Thirty-one patients (7.8%) had rIMN < 6 h post-injury, 106 (25.5%) had rIMN < 6-12 h and 267 (66.8%) had rIMN > 12 h. The implant type, duration of surgery, DVT prophylaxis, in-hospital complications and mortality were comparable among the three treatment groups. Conclusion: In our center, the frequency of femoral fracture is 11% which mainly affects severely injured young males due to traffic-related collisions or falls. Further multicenter studies are needed to reach a consensus for the appropriate management based on the location and timing of injury

Background: Laryngopharyngeal reflux (LPR) is a common disease in otolaryngology characterized by an inflammatory reaction of the mucosa of the upper aerodigestive tract caused by digestive refluxate enzymes. LPR has been identified as etiological or favoring factor of laryngeal, oral, sinonasal or otological diseases. In this case-series, we reported atypical clinical presentation of LPR in patients presenting in our clinic with reflux. Methods: A retrospective medical chart review of 351 patients with LPR treated in the European Reflux Clinic in Brussels, Poitiers and Paris was performed. In order to be included, patients had to report atypical clinical presentation of LPR, consisting of symptoms or findings that are not described in reflux symptom score and reflux sign assessment. The LPR diagnosis was confirmed with 24-hour hypopharyngeal-esophageal impedance pH-study and patients were treated with a combination of diet, proton pump inhibitors and alginates. The atypical symptoms or findings had to be resolved from pre- to posttreatment Results: From 2017 to 2021, 21 patients with atypical LPR were treated in our center. The clinical presentation consisted of recurrent aphthosis or burning mouth (N=9), recurrent burps and abdominal disorders (N=2), posterior nasal obstruction (N=2), recurrent acute suppurative otitis media (N=2), severe vocal fold dysplasia (N=2), and recurrent acute rhinopharyngitis (N=1), tearing (N=1), aspirations (N=1) or tracheobronchitis (N=1). Abnormal upper aerodigestive tract reflux events were identified in all of these patients. Atypical clinical findings resolved and did not recur after an adequate anti-reflux treatment. Conclusion: LPR may present with various clinical presentations including mouth, eye, tracheobronchial, nasal or laryngeal findings, which may all regress with an adequate treatment. Future studies are needed to better specify the relationship between LPR and these atypical findings through analyses identifying gastroduodenal enzyme in the enflamed tissue.

Possible alterations of maternal immune function due to psychological stress may reflect immunoactive factor levels in breast milk. This study aimed to assess the association between maternal distress and breast milk levels of secretory IgA (SIgA), IgM, IgG, and lactoferrin (LF). We hypothesized this association is moderated by maternal social support achieved from others during lactation. The study group included 103 lactating mothers and their healthy 5-months-old infants. Maternal distress was determined based on the State Anxiety Inventory and the level of salivary cortisol. Social support was assessed using Berlin Social Support Scales. Breast milk samples were collected to test for SIgA, IgM, IgG, and LF using the ELISA method. Milk immunoactive factors were regressed against maternal anxiety, social support, salivary cortisol, and infant gestational age using the general regression model. Maternal anxiety was negatively associated with milk levels of LF (β=-0.22, p<0.05) and SIgA (β=-0.29, p<0.01), while social support was positively associated with milk IgG (β=0.25, p<0.05). Neither anxiety nor social support was related to milk IgM. No association was found between the level of maternal salivary cortisol and immunoactive factors in milk. Our results suggest that maternal psychological well-being and social support may affect milk immune properties.

Abstract Background: Premature babies have a greater risk for having health issues after being discharged from the hospital whilst the mother ability to provide premature baby care still has many issues as well. Interventions are needed to be given to mothers at home to improve the ability of mothers to care their premature babies. Methods: Search for articles used the bolean operator of “or” and “and” with the keywords used were “preterm or premature”, “intervention or program”, and “mother and home”. Data based used were Sciencedirect, Ebscohost, PubMed, SAGE, Proquest and Scopus with inclusion criteria using full text in English from 2018 to 2021. There were 428 articles obtained, the articles were then screened by reading the main focus of articles with paying attention to the topic and the suitability of article content and we obtained 13 suitable articles. Results: The interventions at home carried out for mothers and premature babies were divided into two namely the follow-up interventions from the hospital and the interventions carried out at the patient's home. Seven articles about research of interventions that were as a combination from hospital intervention with follow-up hospital intervention plus five full interventions at the patient's home. Interventions were provided through home visits (12 articles) and by telephone (1 article). The results of the article analysis resulted in 4 main themes of intervention for mothers and premature babies, they were health education, counceling, support, and care for premature babies. Conclusion: Quality care is essential for the best health, growth and development of premature babies. Interventions need to be carried out by health workers to ensure the readiness and ability of mothers to care for their babies. Maternal readiness and abilities can be improved by providing health education, counseling, support and care for premature babies.

Background: global longitudinal strain (GLS) measures myocardial deformation and is a sensitive modality for detecting subclinical myocardial dysfunction and predicting cardiac outcomes. The accuracy of speckle-tracking echocardiography (STE) is dependent on temporal resolution. A novel software enables relatively high frame rate (Hi-FR) (~200 fps) echocardiographic images acquisition which empowers us to investigate the impact of Hi-FR imaging on GLS analysis. The goal of this pilot study was to demonstrate the feasibility of Hi-FR for STE. Methods: In this prospective study, we acquired echocardiographic images using clinical scanners on patients with normal left ventricular systolic function using Hi-FR and conventional frame rate (Reg-FR) (~50 FPS). GLS values were evaluated on apical 4-, 2- and 3-chamber images acquired in both Hi-FR and Reg-FR. Inter-observer and intra-observer variabilities were assessed in Hi-FR and Reg-FR. Results: There were 143 resting echocardiograms with normal LVEF included in this study. The frame rate of Hi-FR was 190 ± 25 and Reg-FR was 50 ± 3, and the heart rate was 71 ± 13. Strain values measured in Hi-FR were significantly higher than those measured in Reg-FR (all p < 0.001). Inter-observer and intra-observer correlations were strong in both Hi-FR and Reg-FR. Conclusions: We demonstrated that strain values were significantly higher using Hi-FR when compared with Reg-FR in patients with normal LVEF. It is plausible that higher temporal resolution enabled the measurement of myocardial strain at desired time point. The result of this study may inform clinical adoption of the novel technology. Further investigations are necessary to evaluate the value of Hi-FR to assess myocardial strain in stress echocardiography in the setting of tachycardia.

Discovery of novel variants from data derived from local population provides confident targets for developing biomarkers for personalized medicine. Biomarker discovery would be an important tool in advancing and utilizing the concept of precision and personalized medicine in the clinic. We identified the need to generate high quality sequencing data from local population and understand the pattern of occurrence of variants in colorectal cancer patients. In this report, we used archived samples from Saudi Arabia and used Ampliseq Comprehensive Cancer panel to identify novel somatic variants. We report a comprehensive analysis of next generation sequencing results with a coverage of >300X. We identified 466 novel variants which were previously unreported in COSMIC and ICGC databases. We analyzed the genes associated with these variants in terms of their frequency of occurrence, probable pathogenicity and clinicopathological features. Among pathogenic somatic variants, 174 were identified for the first time in large intestine. APC, RET and EGFR genes were most frequently mutated. Higher number of variants were identified in left colon. Occurrence of variants in ERBB2 was significantly correlated with those of EGFR and ATR genes. Network analyses of the identified genes provide functional perspective of the identified genes and suggest affected pathways and probable biomarker candidates. This report lays the ground work for biomarker discovery and identification of driver gene mutations in local population.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case fatality rates of approximately 30%. There are few treatment options for SFTSV infection. SFTSV RNA synthesis is conducted using a virus-encoded complex with RNA-dependent RNA polymerase activity that is required for viral propagation. This complex and its activities are, therefore, potential antiviral targets. A library of small molecule compounds was screened using a high-throughput screening (HTS) based on an SFTSV minigenome assay (MGA) in a 96-well microplate format to identify potential lead inhibitors of SFTSV RNA synthesis. The assay confirmed inhibitory activities of previously reported SFTSV inhibitors, favipiravir, and ribavirin. A small-scale screening using MGA identified four candidate inhibitors that inhibited SFTSV minigenome activity by more than 80% while exhibiting less than 20% cell cytotoxicity with selectivity index (SI) values of more than 100. These included mycophenolate mofetil, methotrexate, clofarabine, and bleomycin. Overall, these data demonstrate that the SFTSV MGA is useful for anti-SFTSV drug development research.

Risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well-defined in resident physicians and fellows (trainees). We aimed to identify sociodemographic, occupational and community factors associated with SARS-CoV-2 infection among trainees during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in New York City (NYC). In this retrospective cohort study, we administered an electronic survey between June 26 and August 31, 2020 to trainees at the Mount Sinai Health System in NYC to assess risk factors for SARS-CoV-2 infection between February 1 and June 30, 2020. We used Bayesian generalized linear mixed effect regression and structural equation models to examine associations. SAR-CoV-2 infection was determined by self-reported IgG antibody and reverse transcriptase-polymerase chain reaction results and confirmed with laboratory results. Among 2354 trainees invited to participate, 328 (14%) completed the survey and reported test results. The cumulative incidence of SARS-CoV-2 infection was 20.1%. Assignment to medical-surgical units (odds ratio [OR], 2.51; 95% CI, 1.18-5.34), and training in emergency medicine, critical care and anesthesiology (OR, 2.93; 95% CI, 1.24-6.92) were independently associated with infection. Deployment to care for unfamiliar patient populations was protective against infection (OR, 0.16; 95% CI, 0.03-0.73). Community factors were not significantly associated with infection after adjustment for occupational factors. Our findings may inform tailored infection prevention strategies for trainees responding to the COVID-19 pandemic.

The global burden of antimicrobial resistance is on the rise, resulting in higher morbidity and mortality in our communities. The spread of antimicrobial resistance in the environment and development of resistant microbes is a challenge to the control of antimicrobial resistance. Approaches, such as antimicrobial stewardship programmes, and enhanced surveillance, have been devised to curb its spread. However, particularly in lower- and middle-income countries, the overall extent of antimicrobial resistance, and knowledge on on-going surveillance, stewardship or investigation efforts, re often poorly understood. This study aimed to look at the efforts that have been undertaken to combat antimicrobial resistance in Uganda as a means of establishing an overview of the situation, to help inform future decisions. We conducted a systematic literature review of the PubMed database to assess the efforts that have been done in Uganda to investigate and combat antimicrobial resistance. A search combining keywords associated with antimicrobial resistance were used to look up relevant studies between 1995 and 2020 on surveillance of antimicrobial resistance in Uganda, and susceptibility of microbes to different drugs. The search yielded 430 records, 163 of which met the inclusion criteria for analysis. The studies were categorized according to country and region, the type of antimicrobial resistance, context of the study, study design and outcome of the study. Antibacterial resistance and antimalarial resistance had the most published studies while antiviral and antifungal resistance each were represented by very few studies. Most studies were conducted in humans and hospital settings, with very few in veterinary and One Health contexts. The results from our work can inform public health policy on antimicrobial stewardship as it contributes to understanding the status of antimicrobial resistance surveillance in Uganda, and can also help to guide future research efforts. Notably, a One Health approach needs to be followed with re-spect to surveillance of antimicrobial resistance to better understand the mechanisms of resistance transfer across the human-animal–environment interface, including additional investigation in antiviral and antifungal resistance.

Diffuse large B cell lymphoma (DLBCL) is curable with chemoimmunotherapy in ~65% of patients. One of the hallmarks of the pathogenesis and resistance to therapy in DLBCL is inhibition of apoptosis, which allows malignant cells to survive and acquire further alterations. Inhibition of apoptosis can be the result of genetic events inhibiting the intrinsic or extrinsic apoptotic pathways, as well as their modulators, such as the inhibitor of apoptosis proteins, P53, and components of the NF-kB pathway. Mechanisms of dysregulation include upregulation of anti-apoptotic proteins and downregulation of pro-apoptotic proteins via point mutations, amplifications, deletions, translocations, and influences of other proteins. Understanding the factors contributing to resistance to apoptosis in DLBCL is crucial in order to be able to develop targeted therapies that could improve outcomes by restoring apoptosis in malignant cells. This review describes the genetic events inhibiting apoptosis in DLBCL, provides a perspective of their interactions in lymphomagenesis, and discuss their implication for the future of DLBCL therapy.