Background: Superspreading events are important drivers of the SARS-CoV-2 pandemic. By analyzing two outbreaks associated with choir rehearsals in March 2020, we demonstrate the risk of indoor, long-range (LR) transmission and singing, to help prevent similar outbreaks. Methods: We conducted two retrospective cohort studies and obtained demographic, clinical, laboratory and contact data, performed SARS-CoV-2 serology, whole genome sequencing (WGS), calculated LR transmission probabilities, measured particle emissions of selected choir members, and calculated particle air concentrations and inhalation doses.Results: We included 65 (84%) and 42 (100%) members of choirs 1 and 2, respectively. WGS confirmed strain identity in both choirs and the primary case of choir 1 (transmitting presymptomatically). Particle emission rate when singing was 7 times higher compared to talking. In choir 1, the median concentration of primary cases’ emitted particles was 8 times higher, exposure at least 30 minutes longer and room volume smaller than in choir 2, resulting in markedly different estimated probabilities for LR transmission (median: 89% vs. 18%, 95%CI: 80-95% vs. 6-36%). Observed AR in choir 1 (89%) was significantly higher than in choir 2 (24%). According to a risk model, first transmission in choir 1 occurred likely after 7 minutes of singing. The number of inhaled particles emitted by an infectious case, sufficient to infect 50% of exposed, was calculated to 1039-2883 particles (95%CI).Conclusions: Even in large rooms, singing of an infectious person may lead to secondary infections through LR exposure within minutes. Given the potential for presymptomatic infectiousness, greatest caution is required wherever aerosols can accumulate.

Background: Clozapine use is precarious due to its side effects - neurological, cardiovascular, and hematological; however, it is the gold standard in the therapy of resistant schizophrenia (TRS) in adults and harshly underused. Objective: Our purpose is to systematically examine the most recent data regarding clozapine in order to update the knowledge in pharmacological mechanisms, therapy benefits versus side effects to optimize its use in the context of a narrow and scarce of resources pathology, with particularities in the COVID-19 pandemic. (2) Data sources: We performed an accurate search in the primary sources of Databases (PubMed, BMC Public Health, Global Health, Cross Ref, Scopus, Web of Science, and Google Scholar) with specific keywords: “clozapine” and “schizophrenia,” “risks” agranulocytosis” “TRS” “bipolar affective disorder” “pregnancy” “early-onset schizophrenia” “resistance”. Study eligibility criteria: we extracted information regarding drug treatment, side effects profile, and efficacy for each trial; (3) Results: Of all the searched data we selected RCT’s, C.T.’s, reviews, systematic reviews, and meta-analyses; Data were converted and analyzed in a random-effects model. We included 45 studies, centered on six main topics in the search area: (a) treatment-resistant schizophrenia, (b) use in bipolar disorder, (c) side effects during the clozapine therapy - agranulocytosis, metabolic side effects, pharmacogenetic severity markers, dysmetabolic side effects, pulmonary embolism, seizure risk – (d) safety of clozapine in pregnancy, (e) clozapine resistance and ECT augmentation, (f) clozapine therapy and COVID-19 infection. Limitations: _______(4) Conclusions and implications of key findings: (a) The genetic vulnerability postulates predictors of severity so clozapine doses should be personalises for each patient based on pharmacogenetic testing; patients with a lower genetic risk may benefit from a more relaxed hematological monitoring schedule; (b) Pulmonary embolism associated with clozapine has a mortality rate of 36.36%, prophylactic measures for venous thromboembolism for six months after initiating therapy is mandatory; (c) Convulsive episodes are not an indication for stopping the treatment, side effect (s.e.) incidence increases with the dose, the plasma concentration of clozapine (1300 ng/ml) it is a better s. e. predictor than the dosage; (d) clozapine refractory improves up to 69% early-onset schizophrenia, assesed by the Brief Psychiatric Rating Scale (BPRS) (e) more pharmacogenetic studies of the Romanian schizophrenic patients are needed in relation with the clozapine therapy in order to define more precise safety margins; (f) COVID-19 infection may enhance clozapine toxicity generating an increased risk of pneumonia therapy must be continued with proper monitoring of the white blood count and with the decrease of the clozapine dose by half until three days after the subside of the fever; psychiatrists and healthcare providers must act togheder. As in the past four decades, research has failed to generate effective novel psycho-pharmaceuticals, there is an urgent need to enhance the access to clozapine for people with TRS at the worldwide level. The progress of pharmacogenetic researches, endocrinology, genetic testing - offer the psychiatrists nowadays the chance to use this drug at its highest potential in a personalized manner for every patient - minimizing the adverse side-effects.

Cameroon's national vaccination campaign was launched on April 12, 2021, amid a nationwide outbreak of COVID-19 with two types of vaccines. This study provides preliminary evidence of the level of coverage of the population and gives an early overview of the challenges, the achievements and the lessons learned. COVID-19 vaccine administration data were obtained from data of the Cameroon Ministry of Public Health. Descriptive statistical analyses were conducted. Thirty days after the introduction of COVID 19 vaccines, five percent of the target population was vaccinated. Women represented one third of the people vaccinated regardless of age and health conditions. Although AEFI reported were minor and scanty with both vaccines, the majority of the vaccinated did not come back for their second dose. There is a need to build confidence among eligible beneficiaries in order to expand the benefits of vaccination to control the current pandemic. The country is still far below the target which could be worrisome given that the uptake is slow and, the 391 200 doses of the AstraZeneca are going to expire in August 2021. This study offers insights into those early efforts as a contribution to significant discussions about upcoming approach to improve service delivery and uptake.

Wound infections evidently appeared in times of World War I that accounted a significant mortality and morbidity rate among injured soldiers. Currently, around 11 million people worldwide require medical treatment for wound infections and 300,000 die every year due to untreated wound infection. The extensive use of antibiotics to treat wound infection leads to emerging new microbial strains that are resistant to many antibiotics. There is a growing concern on the emergence and re-emergence of drug-resistant pathogens such as multi-resistant bacterial strains. Hence, the development of new antimicrobial compounds or the modification of those that already exist to improve antibacterial activity is a high priority area of research. During the past few decades, nanotechnology has arisen with new promising technology for synthesis of nanobiomaterials. Metallic nanoparticles (NPs) are considered as new alternative treatment with superior antibacterial activity. In this study, new formulation of titanium oxide (TiO2) NPs with different sizes were synthesized and characterized. Genotoxicity, mutagenicity and antibacterial activities of TiO2 NPs against the causative agents of wound infection were investigated. Antibacterial activity of TiO2 NPs was conducted against three ATCC ® bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa. The results clearly illustrate a superior antibacterial activity of all newly formulated TiO2 NPs against the most causative agents of wound infection. Most of our TiO2 NPs showed non-genotoxic and non-mutagenic results at the maximum concentrations. Findings of this study will enhance the future of the therapeutic strategies against the resistant pathogenic strains that cause wound infections.

This review focuses on the evidence for neurotherapeutics for Attention Deficit Hyperactivity Disorder (ADHD). EEG-Neurofeedback has been tested for about 45 years with latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback of frontal activations in ADHD using functional magnetic resonance imaging or near-infrared spectroscopy, finding no superior effects over control conditions. Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements. Trigeminal nerve stimulation has shown to improve ADHD symptoms with medium effect in one RCT. Modern neurotherapeutics are attractive due to their relative safety and potential neuroplastic effects. However, they need to be thoroughly tested for clinical and cognitive efficacy across settings and beyond core symptoms and for their potential for individualised treatment.

Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) is the virus that caused COVID-19 around the world. The disease starts off as a flu-like symptom and then eventually spreads in the human body.Infections are easily transmitted from human to human which makes it more severe among individuals. SARS-CoV-2 virus is in the same family of viruses SARS and MERS.As of today, there is no approved vaccine that can cure COVID-19. However, potential treatments showing promising improvement results among affected COVID-19 patients. In this review, the effectiveness of the current treatments for COVID-19 has been explored.

Steroid analysis is important in the clinical assessment of endocrine function in health and disease. Although tandem mass spectrometry methods coupled with chromatographic separation are considered the gold standard analytical technique in this setting, enabling profiling of multiple steroids in a single sample, sample processing can be labour-intensive. Here we present a simple, efficient automated 96-well Supported Liquid Extraction method with dichloromethane/isopropanol as organic solvent, carried out on a Extrahera automated sample handler (Biotage), which completes sample preparation of 80 plasma samples (200µL) in 90 minutes. Compounds were separated on a Kinetex C18 column (150x3mm;2.6um) using a mobile phase of methanol and water (0.1% formic acid). The run time was 16 minutes on a Nexera uHPLC system (Shimadzu) with a QTrap 6500+ linear ion trap mass spectrometer (AB Sciex). Precisions ranged 8.1 to 18.1% RSD, bias -10.1-5.8%, and extraction recoveries 73.5-111.9%. LOQs ranged between 0.025–0.500 ng/mL.

Psychedelics extracted by plants have been used in religious, spiritual and mystic practices for millennia. In 1957, Dr. Hofmann have identified and synthesized the prodrug psilocybin, a substance present in more than 200 species of psychedelic mushrooms. Although the limitations related to the scientific design of many studies, clinical observations performed during the 1950s and the 1960s have shown a potential therapeutic effect of psilocybin in patients affected by depressive symptoms, anxiety, and conversion disorder. Psilocybin was classed as a schedule I substance in 1970, but the fascination for psychedelics remained almost unchanged over time promoting a new scientific interest starting from the 1990s. Recent studies provided further evidences supporting the suggestive hypothesis of a therapeutic use of psilocybin for treating various psychiatric disorders including: pathological anxiety, mood depressive disorder and addiction.

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

(1) Background: Reactive oxygen species (ROS) play a crucial role in the preparation of the normal wound healing response. Therefore, a correct balance between low or high levels of ROS is essential. Antioxidant dressings that regulate this balance is a target for new therapies. The purpose of this review is to identify the compounds with antioxidant properties that have been tested for wound healing and to summarize the available evidence on their effects. (2) Methods: A literature search was conducted and included any study that evaluated the effects or mechanisms of antioxidants in the healing process (in vitro, animal models, or human studies). (3) Results: Seven compounds with antioxidant activity were identified (Curcumin, N-acetyl cysteine, Chitosan, Gallic Acid, Edaravone, Crocin, Safranal, and Quercetin) and 46 studies reporting the effects on the healing process of these antioxidants compounds were included. (4) Conclusions: These results highlight that numerous novel investigations are being conducted to develop more efficient systems for wound healing activity. The application of antioxidants is useful against oxidative damage and accelerates wound healing. Designing biomaterials that can scavenge excess reactive oxygen species requires new technologies and further research, especially human studies.

Drug discovery has been initially attributed to coincidence or trial and error where the traditional approach was complex, lengthy, and expensive. Conventional drug discovery methods require the costly random screening of synthesized compounds or natural products. Another downside for this approach is the wide dependency on the experimental use of animals for in vi-vo testing. Currently, in silico modeling has become a vital tool for drug discovery and repurposing, and molecular docking is being used to find the best matching between a ligand and a molecule. Practical application of in silico docking will predict the biomolecular interactions between the drug and the target host. Beauvericin (BEA) is an emerging mycotoxin produced by the entomopathogenic fungus Beauveria bassiana. Originally investigated for its pesticide capability, BEA is now considered as a molecule of interest for its potentially diverse biotechnological applications in the pharmacological industry and the field of medicine. In this manuscript, we will provide an overview of the repurposing of BEA into a potentially superior therapeutic molecule in a broad range of diseases. Furthermore, considerable attention has been given to the fundamental role of in silico techniques to i) further investigate the spectrum of this secondary metabolite and ii) elucidate the pathways of BEA for its promising therapeutic action

(1) Background: The purpose of this study is to evaluate the full arch scan accuracy (precision and trueness) of nine digital intra-oral scanners and four lab scanners. Previous studies have compared the accuracy of some intra-oral scanners, but as this is a field of quickly developing technologies, a more up-to-date study was needed to assess the capabilities of currently available models.; (2) Methods: The present in vitro study compared nine different intraoral scanners (Omnicam 4.6; Omnicam 5.1; Primescan; CS 3600; Trios 3; Trios 4; Runyes; i500 and DL206) as well as four lab light scanners (Einscan SE; 300e; E2 and Ineos X5) to investigate the accuracy of each scanner by examining the overall trueness and precision. Ten aligned and cut scans from each of the intra-oral and lab scanners in the in vitro study were brought into CloudCompare. A comparison was made with the master STL using the CloudCompare 3D analysis best-fit algorithm. The results were recorded along with individual standard deviation and a colorimetric map of the deviation across the surface of the STL mesh; a comparison was made to the master STL, quantified at specific points. ; (3) Results: In the present study, the Primescan had the best overall trueness (17.3 ± 4.9). Followed by (in order of increasing deviation) the Trios 4 (20.8 ± 6.2), i500 (25.2 ± 7.3), CS3600 (26.9 ± 15.9), Trios 3 (27.7 ± 6.8), Runyes (47.2 ± 5.4), Omnicam 5.1 (55.1 ± 9.5), Omnicam 4.6 (57.5 ± 3.2) and Launca DL206 (58.5 ± 22.0). Regarding the lab light scanners, the Ineos X5 had the best overall trueness with (0.0 ± 1.9). Followed by (in order of increasing deviation) the 3Shape E2 (3.6 ± 2.2), Up3D 300E (12.8 ± 2.7), and Einscan SE (14.9 ± 9.5); (4) Conclusions: This study confirms that all current generations of intra-oral digital scanners can capture a reliable, reproducible full arch scan in dentate patients. Out of the intra-oral scanners tested, no scanner produced results significantly similar in trueness to the Ineos X5. However, the Primescan was the only one to be statistically of a similar level of trueness to the 3Shape E2 lab scanner. All scanners in the study had mean trueness of under 60-micron deviation. While this study can compare the scanning accuracy of this sample in a dentate arch, the scanning of a fully edentulous arch is more challenging. The accuracy of these scanners in edentulous cases should be examined in further studies.

Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English-language publications from 2008 – 2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimizing safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found few, but no serious, adverse events associated with phage therapy. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.

Past public health crises (e.g. tobacco, alcohol, opioids, cholera, HIV, lead, pollution, venereal disease, even COVID-19) have been met with interventions targeted both at the individual and all of society. While the healthcare community is very aware that the global pandemic of non-communicable diseases (NCD’s) has its origins in our Western ultraprocessed food diet, society has been slow to initiate any interventions other than public education, which has been ineffective, in part due to food industry interference. This article provides the rationale for such public health interventions, by compiling the evidence that added sugar, and by proxy the ultraprocessed food category, meets the four criteria set by the public health community as necessary and sufficient for regulation — addiction, toxicity, ubiquity, and externalities (how does your consumption affect me?). To its credit, some countries have recently heeded this science and have instituted sugar taxation policies to help ameliorate NCD’s within their borders. This article also supplies scientific counters to food industry talking points, in order to guide both scientists and policy makers in instituting further appropriate public health measures to quell this pandemic.

Transplant of human cancer cells into zebrafish larvae has emerged as a useful methodology in cancer research. Zebrafish have very low husbandry costs, are amenable to large-scale drug screening, and are unmatched for optical clarity in live animal imaging. However, there is currently no consensus on the ideal methods for xenograft of human cancer cells into zebrafish. Here, we have examined the effects of transplant site and housing temperature on both zebrafish larvae and human cancer cells using survival analyses, metabolomic approaches, and in vivo imaging. Our data show that while zebrafish larvae can adapt to the ideal conditions for mammalian cells, human cancer cells are highly sensitive to both temperature change and transplant site. Human cells housed in slightly cooler than physiologic temperatures had a significantly altered metabolism that resulted in changes in growth, survival, and response to chemotherapy. Cancer cells xenografted into the yolk of the larvae also had reduced proliferation and drug response compared to those xenografted into the soma, in part due to the differences in metabolites available at these sites. In total, temperature and transplant site can have profound effects on xenografted cells. Standardization of zebrafish xenograft methods will enhance data reproducibility between individual laboratories.

The enzyme-coupled transient receptor potential channel subfamily M member 7, TRPM7, has been associated with immunity and immune cell signalling. Here, we review the role of this remarkable signalling protein in lymphocyte proliferation, differentiation, activation and survival. We also discuss its role in mast cell, neutrophil and macrophage function and highlight the potential of TRPM7 to regulate immune system homeostasis. Further, we shed light on how the cellular signalling cascades involving TRPM7 channel and/or kinase activity culminate in pathologies as diverse as allergic hypersensitivity, arterial thrombosis, and graft versus host disease (GVHD), stressing the need for TRPM7 specific pharmacological modulators.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19 , is considered a pathogen with animal origin, mainly transmitted human to human. It has been experimentally and naturally demonstrated that several animals can be infected by SARS-CoV-2. There are strong evidences that minks are highly susceptible to SARS-CoV-2 infection, since several cases of human to mink infection have been reported, and it has been suggested mink to human infection exists, which so far it is the most reliable example of a zoonotic event of COVID-19 . However, all these cases reported are form mink farms, with the exception of one case in the USA in which the virus was detected in a mink located in the wild, but it was demonstrated that the animal was infected on a fur farm. In the present work, we have detected SARS-CoV-2 RNA in two wild American minks (Neovison vison) in Valencian Community (Eastern Spain) during invasive species trapping campaigns. The animals were trapped from areas known for harbouring self-sustained populations, far away from the nearest fur farm. SARS-CoV-2 RNA was detected in mesenteric lymph nodes samples by RT-PCR. A partial region of the Spike protein gene was amplified and sequence obtaining a 397 nt size sequence. Phylogenetic analysis shown that both sequences were identical to the consensus variant SARS CoV-2 sequence (from Wuhan). This research describes the first infection report of a true wild American mink not related to infected fur farms or direct contact with humans, which is believed to be the first example of wild animals in which SARS-CoV-2 has been detected.

Globally, over the past several months millions of persons contracted the coronavirus disease 2019 (COVID-19) resulting in significant mortality. Health care systems are negatively impacted including the care of individuals with cancers and other chronic diseases such as chronic active hepatitis, cirrhosis and hepatocellular carcinoma. There are various probable pathogenic mechanisms that have been presented to account for liver injury in COVID-19 patients such as hepatotoxicity cause by therapeutic drugs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the bile duct cells and hepatocytes, hypoxia and systemic inflammatory response. Liver biochemistry tests such as AST, ALT, GGT and ALP are deranged in COVID-19 patients with liver injury. Hepatocellular damage results in the elevation of serum AST and ALT levels in early onset disease while a cholestatic pattern that develops as the disease progress causes higher levels of ALP, GGT, direct and total bilirubin. These liver biochemistry tests are prognostic markers of disease severity and should be carefully monitored in COVID-19 patients. We conducted a systematic review of abnormal liver biochemistry tests in COVID-19 and the possible pathogenesis involved. Significant findings regarding the severity, hepatocellular pattern, incidence and related clinical outcomes in COVID-19 patients are highlighted.

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.

Background: The Royal College of Surgeons in Ireland - Bahrain (RCSI Bahrain) was closed due to COVID 19. The aim of this paper is to present our experience, in managing teaching and learning, during this pandemic. Methods: Following, ethical approval, several meetings were held with the senior faculty and student representatives to select alternative virtual approaches for teaching, learning and assessment with evidence-based instructional design. Informed consent was obtained from all study participants. All procedures were carried out in accordance with relevant guidelines and regulations. In alignment with global scenario, we decided upon early graduation for our students, and expedited the clinical examinations, with special permission from health and education ministries. Two major clinical examinations were redesigned to form a single hybrid clinical examination with two parts. Following all COVID 19 preventive measures, students were taken in groups of seven and simulated patients were substituted for real patients. No more than 40 students were present at any point of time, with no more than 10 examined in one block. 149 out of 152 RCSI students attended the clinical examinations and 524 students from the three RCSI campuses attended the written online examination. A structured survey was conducted to elicit students’ perceptions and participation was entirely voluntary. Results: 82% of students were happier to be joining the workforce early and, 22% expressed concerns. A comparison of student performance in these examinations against the equivalent components from semester one yielded no significant deviation in student performance, illustrating that the quality was consistent. Conclusion: We recommend that the government accredit online or distance learning programmes and explore appropriate methodologies for evaluation of online learning and assessment. Incorporating practical/clinical training, will continue to be a great challenge.

Gender Identity Dysphoria (GID) is a condition characterized by a strong and persistent identification with the opposite sex. These people consider themselves victims of a sort of biological accident: "a soul in a wrong body". There are numerous theories on the origin of transsexualism: genetic, hormonal and psychological causes have been hypothesized, but those currently most accredited are the neuroanatomical ones. The cornerstones of hormone conversion therapy (Gender Affirming Hormone Therapy, GAHT) are feminizing hormones for transgender women (MtFs) and virilizing for transgender males (FtMs). GID can be present among adolescents and older people. For adolescents is now accepted reversible treatment of puberty withdrawal with hormones that stops the progression of pubertal development in the biological direction not accepted; for elderly people is suggested GAHT in reduced doses. Physicians should consider and discuss with people with GID about fertility preservation, general and cancer risks. We present also data of 127 transsexual patients enrolled at the Garibaldi-Nesima Andrology Clinic in Catania (Italy) from 2003 to 2020. To optimize the conversion treatment with sex hormones, transsexuals require long-term follow-up. GAHT must be performed by a doctor who is familiar with these problems. Therefore, the “do-it-yourself” trend and the lack of medical and laboratory checks over time should be absolutely discouraged. Before proceeding with the surgical sex reassignment, it is recommended to refer to an endocrinologist and psychologist or psychiatrist for a period of 2-3 years. The transition surgical conclusion process must be practiced by a quality surgical team.

Incidence of autoimmune diseases increases. Antinuclear antibodies (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in health increased over last decades, especially among young people. ANA in health occur in low concentrations, with prevalence up to 50% in some populations, which demands a cutoff revision. The review deals with origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing in additive combinations according to the concept of the mosaic of autoimmunity. Not only titer, but the HEp-2 IFA staining patterns, like AC-2, is also important. Accepting autoantibodies as a kind of bioregulators, not only upper, but also lower borders of their normal range should be determined. Not only their excess, but also lack of them or “autoimmunodeficiency” could be a reason of disorders.

Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements on the treatment of TBI, neuroprotection is one of the upcoming improvements. Citicoline has been used in the management of brain ischemia related disorders, such as TBI. Citicoline has biochemical, pharmacological, and pharmacokinetic characteristics that make it a potentially useful neuroprotective drug for the management of TBI. A short review of these characteristics is included in this paper. Also, a narrative review of almost all the published or communicated studies performed with this drug in the management of patients with head injury is included. Based on the results obtained in these clinical studies, it is possible to conclude that citicoline was able to accelerate recovery of consciousness and to improve the outcome of this kind of patients, with an excellent safety profile. Thus, citicoline could have a potential role in the management of TBI.

Starting from early 2020, the COVID-19 pandemic has caused a morbidity and mortality excess worldwide. Containment strategies rely firstly on rapid and sensitive laboratory diagnosis with molecular detection of the viral genome in respiratory samples being the gold standard. Reliability of diagnostic protocols could be affected by SARS-CoV-2 genetic variability. In fact, mutations occurring during SARS-CoV-2 genomic evolution can involve the regions targeted by the diagnostic probes. Following a review of the literature and an in silico analysis of the most recently described virus variants (including the UK B 1.1.7 and the South Africa 501Y.V2 variants), we conclude that the described genetic variability should have minimal or no effect on the sensitivity of existing diagnostic protocols for SARS-CoV-2 genome detection. However, given the continuous emergence of new variants, the situation should be monitored in the future, and protocols including multiple targets should be preferred.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating condition, probably of multifactorial etiology. No effective approved drugs are currently available for its treatment. Several studies have proposed symptomatic treatment with melatonin and zinc supplementation in chronic illnesses; however, little is known about the synergistic effect of this treatment on fatigue-related symptoms in ME/CFS. The primary endpoint of the study was to assess the effect of oral melatonin plus zinc supplementation on fatigue in ME/CFS. Secondary measures included participants’ sleep disturbances, anxiety/depression, and health-related quality of life. A proof-of-concept, 16-week, randomized, placebo-controlled, double-blind trial was conducted in 50 ME/CFS patients assigned to receive either oral melatonin (1 mg) plus zinc (10 mg) supplementation (n = 24) or matching placebo (n = 26) once daily. Endpoint outcomes were evaluated at baseline and then reassessed at 8 and 16 weeks of treatment and 4 weeks after treatment cessation, using self-reported outcome measures. Treatment was safe and well-tolerated. The most relevant results were the significant reduction in the perception of physical fatigue in the active group at the final follow-up versus placebo (p < 0.05), and the significant improvement in the physical component summary at all follow-up visits in the experimental group. Our findings suggest that oral melatonin plus zinc supplementation for 16 weeks is safe and potentially effective in reducing fatigue and improving the quality of life in ME/CFS. This clinical study was registered on ClinicalTrials.gov (NCT03000777).

Appropriate diagnostic testing to identify persons infected with SARS-COV-2 is a vital part of a health system’s ability to control the global pandemic of COVID-19 disease. The primary purpose of this review is to provide an overview of the mass testing strategy implemented throughout the UAE and the overall impact it has made on containing and controlling the spread of the disease. This study describes the mass testing strategy and capacity of the UAE during the pandemic of the new coronavirus SARS-COV-2. The UAE has conducted 15 million polymerase chain reaction (PCR) tests to SARS-COV-2, as of 15 November 2020. The number of tests per day varied from 10,000 by the end of March to 120,000 tests per day in November 2020. The mass testing initiative across the entire UAE forms an integral part of a bigger strategy focusing on testing, tracing contacts and isolating positive cases.

The treatment of viral infections is challenging owing to the intricate structure and metabolism of the viruses. In addition, they can highjack host cellular metabolism, mutate and adapt to harsh environmental conditions. The novel coronavirus (SARS-CoV-2) displays further resilient attributes, making its eradication even more difficult. SARS-CoV-2 is an enveloped virus whose replication can be targeted by limiting the substrates available for structural incorporation. One such molecule that limits substrate availability and has received much attention lately is 2-Deoxy-d-glucose (2-DG). SARS-CoV-2 infection induces glycolysis, impairs mitochondrial function, and damages the infected cells. Administration of 2-DG can inhibit increased glycolytic flux and some other metabolic processes to cause the cessation of viral replication. This article provides a review of the mechanism of action and safety concerns associated with administering 2-DG in the treatment of COVID-19. The drug can have adverse effects on normal cell metabolism since it targets cells non-selectively, possibly in a dose-dependent manner. In addition, the drug has limited use in SARS-CoV-2 infection associated with stroke, hypoxic-ischemic encephalopathy, and critical illness.

We analyzed the characteristics of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infected children during lock-down period in Catalonia (Spain), and their transmission role within the households. Among 295 traced household contacts of 89 pediatric patients, children were classified as final index cases in only 3.4% of the traced homes.

The Coronavirus 2 (SARS-CoV-2) infection is a global pandemic that has affected millions of people worldwide. The advent of vaccines, however, has permitted some restitution. Aside from the respiratory complications of the infection, there is also a thrombotic risk attributed to both the disease alongside the vaccine. There are no reliable data for the risk of thromboembolism in SARS-CoV-2 infection in patients managed out with the hospital setting. A literature review was performed to identify the pathophysiological mechanism of thrombosis from the SARS-CoV-2 infection including the role of Angiotensin-Converting Enzyme receptors. The impact of the vaccine and likely mechanisms from thrombosis following vaccination was also clarified. Finally, the utility of the vaccines available against the multiple variants is also highlighted. The systemic response to SARS-CoV-2 infection is still relatively poorly understood, but several risk factors have been identified. The roll-out of the vaccines worldwide has also allowed the lifting of lockdown measures and a reduction in the spread of the disease. The experience of the SARS-CoV-2 infection, however, has highlighted the crucial role of epidemiological research and the need for ongoing studies within this field.

Abstract Introduction:The Robert Koch Institute (RKI) managed the exchange of cross-border contact tracing data between public health authorities (PHA) in Germany and abroad during the COVID-19 pandemic. Aim: We aimed to describe the extent of RKI cross-border contact tracing and the challenges experienced. Methods:We analysed cross-border COVID-19 contact tracing events from 03 February to 05 April 2020 using information exchanged through the European “Early Warning Response System” (EWRS) as well as communication with International Health Regulation (IHR) national focal points. We described events by PHA involved, number of contact persons and exposure context. Results:The RKI processed 467 events, initiating contact to PHA 1,099 times (median 1, IQR [1;2]) and sharing data on 5,099 contact persons. Of 327 (70%) events with known exposure context, most common reported were exposures on aircraft 64 (14%), on cruise ships 24 (5%) and exposures related to non-transport contexts 210 (45%). Cruise ship and aircraft exposures yielded higher median numbers of authorities contacted (10[2;16], 4[2;11]) and contact persons (60 [9;269], 2[1;3]) than non-transport related exposures (1[1;6] and 1[1;2]), respectively. The median time spend on contact tracing activities was the highest for cruise ships: 5 days [IQR 3;9]. Conclusion:In the current COVID-19 pandemic cross-border contact tracing is considered a critical component of the outbreak response. While the majority of international contact tracing activities did not relate to exposure events in transport, they contributed substantially to the workload. The numerous communications highlight the need for fast and efficient global outbreak communication channels between PHA.

Chemotherapy is a standard therapeutic option for triple-negative breast cancer (TNBC); however, its effectiveness is often compromised by drug-related toxicity and resistance development. Herein, we aimed to evaluate whether an improved antineoplastic effect could be achieved in vitro and in vivo in TNBC by combining dovitinib, a multi-kinase inhibitor, with calcitriol, a natural anti-cancer hormone. In vitro, cell proliferation and cell-cycle distribution were studied by sulforhodamine B-assays and flow cytometry. In vivo, dovitinib/calcitriol effects on tumor growth, angiogenesis and endothelium activation were evaluated in xenografted mice by caliper measures, Itgb3-immunohistochemistry and 99mTc-RGD2-tumor uptake. The drug combination elicited a synergistically improved antiproliferative effect in TNBC-derived cells, which allowed a 7-fold dovitinib dose-reduction. Mechanistically, the co-treatment induced cell death and accumulation in S and G2/M phases, while inhibited tumor growth to a greater extent than each compound alone. Tumor uptake of 99mTc-RGD2 was reduced by dovitinib, suggesting angiogenesis inhibition, which was corroborated by decreased endothelial cell growth and tumor vessel density. In summary, calcitriol synergized dovitinib anticancer effects in vitro and in vivo, allowing for a significant dose-reduction of dovitinib, while maintaining its antiproliferative potency. Our results suggest the beneficial convergence of independent antitumor mechanisms of dovitinib and calcitriol to inhibit TNBC-tumor growth.

The present work evaluates the food effect on the absorption of rivaroxaban (Riva), a BCS II drug, from the orally administered commercial immediate-release tablet (Xarelto IR) using physiologically based pharmacokinetic (PBPK) and conventional in vitro- in vivo correlation (IVIVC) models. The bioavailability of Riva upon oral administration of Xarelto IR tablet is reported to exhibit a positive food effect. The PBPK model for Riva was developed and verified using the previously reported in vivo data for oral solution (5 and 10 mg) and Xarelto IR tablet (5 and 10 mg dose strength). Once the PBPK model was established, the in vivo performance of the tablet formulation with the higher dose strength (Xarelto IR tablet 20 mg in fasted and fed state) was predicted using the experimentally obtained data of in vitro permeability, biorelevant solubility and in vitro dynamic dissolution data using United States Pharmacopeia (USP) IV flow-through cell apparatus. In addition, the mathematical IVIVC model was developed using the in vitro dissolution and in vivo profile of 20 mg strength Xarelto IR tablet in fasted condition. Using the developed IVIVC model, the pharmacokinetic (PK) profile of the Xarelto IR tablet in fed condition was predicted and compared with the PK parameters obtained via the PBPK model. A virtual in vivo PK study was designed using a single-dose, 3-treatment cross-over trial in 50 subjects to predict the PK profile of the Xarelto® IR tablet in the fed state. Overall, the results obtained from the IVIVC model were found to be comparable with that from the PBPK model. The outcome from both the model pointed to the positive food effect on the in vivo profile of the Riva. The developed models thus can be effectively extended to establish bioequivalence for the marketed and novel complex formulations of Riva such as amorphous solid dispersions.

Diffuse large B cell lymphoma (DLBCL), the most frequent type of non-Hodgkin lymphoma in adulthood, remains challenging clinical issues. Despite enhanced remission rates can be achieved, there are one-third of patients who will not respond to current treatment or will relapse with resistant disease, necessitating ongoing efforts on effective treatment strategies and agents. The vacuole H+-ATPase inhibitor bafilomycin A1 is broadly used to block late stage of autophagy flux at high concentration. In this study, we show that, to our surprise, bafilomycin A1 effectively inhibited and killed DLBCL cells at nanomolar concentrations (5nM). Bafilomycin A1 targeted cell cycle regulators cyclin D1 and cyclin E2 to induce cell cycle arrest in G0/G1 phase. Meanwhile, it induced caspase-dependent apoptosis with concomitant cleaved caspase-3 and Parp. Furthermore, we found that bafilomycin A1 inhibited autophagy flux at both early and late stages of the autophagy flux through activating ERK and mammalian target of rapamycin signaling, as well as by inhibiting the degradation of autolysosomes. We speculated that bafilomycin A1 as autophagy inhibitor might enhance the effect of DLBCL chemotherapeutic drug rituximab. Accordingly, our results provided evidence that the combination of bafilomycin A1 with rituximab enhanced the inhibition of DLBCL cells notably. Taken together, our data suggest that bafilomycin A1 may be a promising candidate drug in the therapy of diffuse large B cell lymphoma.

Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet need for tissue repair strategies to treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), and patients with chronic complex and recalcitrant wounds. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling). Many different PRP formulations have been evaluated, originating from human, in vitro, and animal studies. However, recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, progress has been made in understanding PRP technology and the concepts for bioformulation, and new research directives and new indications have been suggested. In this review, we will discuss recent developments regarding PRP preparation and composition regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, serotonin (5-HT) effects and pain killing. Furthermore, we discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes. Lastly, we will review the effect of certain drugs on PRP activity, and the combination of PRP and rehabilitation protocols.

Tissue Doppler Imaging (TDI) is a non-invasive, echocardiographic imaging technique that measures myocardial motion velocity throughout the cardiac cycle using Doppler principles. While conventional Doppler techniques assess blood flow velocity by sensing high-frequency, low amplitude signals from small, fast-moving blood cells, TDI uses the same Doppler principles to instead measure high-amplitude, lower-velocity signals of myocardial tissue. Methods A literature review was conducted to survey and review studies investigating the limitations, strengths, physical principles, novel methods, applications in diseased states, and prognostic capabilities of TDI. These articles were further screened for inclusion, and those deemed ineligible or irrelevant to the scope of the review were discarded. In total, 19 studies were included in the qualitative synthesis. Results TDI is shown to be an effective method for detailed quantification of cardiac function. It provides an early means of diagnosing cardiac dysfunction and is a valid prognostic indicator for various forms of heart disease. TDI's versatility and precision allows clinicians to predict the clinical course of disease, leading to early intervention and the selection of targeted care management plans for many cardiac pathologies. Despite imaging limitations like angle dependence and incapacity for passive and active motion differentiation, further investigation continues to reveal novel TDI methodologies that advance the scope of this imaging technique.

Many of the wide-ranging symptoms of COVID-19 have not been associated previously with a respiratory illness. A similarity between these atypical symptoms and the symptoms of malnutrition was observed. To investigate, a comparison of COVID-19 symptomatology with recognised states of malnutrition showed a significant relationship that was further explored in a review of the literature. This hypothesis links the atypical symptoms to the effects of increasing protein malnutrition. The rapid appearance of malnutrition symptoms at the beginning of the COVID-19 infection is concurrent with the rapid cell proliferation of the immune system. Although previous work has, in general, assumed that the body is capable of providing for the needs of the immune system during infection, heightened immune activity from the commencement of COVID-19 could require an early increase in energy yielding sources. Should insufficient availability of protein resources occur, this could quickly lead to malnutrition. Any continuing insufficiency, during the active phase of the virus, might result in widespread depletions in the tissues and the consequential malfunctioning of many organs. A new appraisal of the immune system requirements needed to counteract the impact of the novel virus, COVID-19, could show the potential benefit for earlier protein intervention in the disease process. This hypothesis could also have relevance for other life situations where a rapid cell proliferation might occur.

Low back pain (LBP) is a leading cause of disability. It significantly impacts the patient’s quality of life, limits their daily living activities, and reduces work productivity. To reduce the burden of LBP, several pharmacological and non-pharmacological treatment options are available. This review summarizes the role of heat therapy in the management of LBP. First, we outline the common causes of LBP, then discuss the general mechanisms of heat therapy on (LB)P, and finally review the published evidence regarding the impact of heat therapy in patients with acute or chronic non-specific LBP. This review demonstrates that continuous, low-level heat therapy provides pain relief, improves muscular strength, and increases flexibility. Therefore, this effective, safe, easy-to-use, and cost-effective non-pharmacological pain relief option is still relevant in modern clinical practice.

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.

Gout is the most common form of inflammatory arthritis. Hyperuricaemia is the pre-requisite for gout and is influenced by variable modifiable and non-modifiable risk factors. Clinical features unique for gout are due to deposition of monosodium urate (MSU) crystal in articular and extra articular tissues. Among various treating agents, anti-inflammatory drugs and urate lowering therapies (ULT) are used widely and successfully, however, non-medicinal means are also effective in the disorder. In their updated guidelines, ACR (2012) and EULAR (2016) recommended both medicinal and non-medicinal approaches that could be used in treating gout, though some of the recommendations are based on lower level of evidence. Moreover, researchers’ continued effort in finding new gout managing agents appear promising, for example, role of Lesinurad in gout management (CLEAR1, CLEAR2). In this new synthesis the author is aimed to provide updated information on gout management based on a systematic review including published work within last ten years between 2008 and 2018 and for this purpose, using ‘clinical trials in gout management’ string, published worked searched in PubMed database from 1st September 2018 to 30 October 2018. Besides the recent ACR and EULAR evidence based management guidelines, the author reviewed another 91 (total 93) articles to make this new draft – 39 articles describe role of pharmacological agents and 54 describe different gout risks, pharmacokinetics/pharmacodynamics of ULT, association between raised sUA level and renal impairment, efficacy of non-pharmacological agents in reducing sUA. According to published work, anti-inflammatory agent is the most appropriate drug group in mitigating inflammatory symptoms of gout, though they often adversely affect over other vital 2 organs with impaired function. Besides ULT, uricase analogues are also found useful in non refractory gout. Since anti-inflammatory agents and ULT contraindicate in some clinical conditions, intra-articular steroid and or adrenocorticotropic hormone (ACTH) are appropriate alternatives instead. However, head-to-head comparison between different NSAIDs, NSAID and prednisolone, NSAID and colchicine are yet to perform. Use of combined anti-inflammatory preparations in gout is also based on lower level of evidence. Regarding effective maximum dose and long-standing impact of ULT on vital organs we are yet to reach a conclusion. Likewise, non-medicinal approaches are widely using in achieving target sUA level, though some of them are based on biased study outcomes and or study with inadequate power, requiring further analysis. Among non-pharmacological approaches, life-style modification, restriction of purine rich diets, avoidance of gout inciting agents are important, but inconclusive. Educating patients’ about diseases, risk factors, available treatment options and side effects from them are also important in terms of achieving sUA level, nevertheless too much counseling sometimes could be worthless.

Background: Extremely rare progressive diseases like Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) can be neonatally lethal and therefore go undiagnosed or are difficult to treat. Recent sequencing efforts have linked this disease to mutations in GPX4, with consequences in the resulting enzyme, glutathione peroxidase 4. This offers potential diagnostic and therapeutic avenues for those suffering from this disease, though the steps toward these treatments is often convoluted, expensive, and time-consuming. Main body: The CureGPX4 organization was developed to promote awareness of GPX4-related diseases like SSMD, as well as support research that could lead to essential therapeutics for patients. We provide an overview of the 21 published SSMD cases and have compiled additional sequencing data for four previously unpublished individuals to illustrate the genetic component of SSMD, and the role of sequencing data in diagnosis. We outline in detail the steps CureGPX4 has taken to reach milestones of team creation, disease understanding, drug repurposing, and design of future studies. Conclusion: The primary aim of this review is to provide a roadmap for therapy development for rare, ultra-rare, and difficult to diagnose diseases, as well as increase awareness of the genetic component of SSMD. This work will offer a better understanding of GPx4-related diseases, and help guide researchers, clinicians, and patients interested in other rare diseases find a path towards treatments.

During 2019, the number of patients suffering from cough, fever and reduction of WBC’s count increased. At the beginning, this mysterious illness was called “fever with unknown origin”. At the present time, the cause of this pneumonia is known as the 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The SARS-CoV-2 is one member of great family of coronaviruses. Coronaviruses can cause different kind of illnesses including respiratory, enteric, hepatic, and neurological diseases in animals like cat and bat. Coronaviruses are enveloped positive-stranded RNA viruses. The SARS-CoV-2 has some particular structures for binding to host cells, reproducing itself in cells and damaging human cells. The SARS-CoV-2 can bind angiotensin-converting enzyme 2 (ACE‐2) receptors and cause various difficulties for human. The SARS-CoV-2 can cause either not-serious issues like fever and cough or serious concerns such as multi-organ failure. Source(s) of SARS-CoV-2 is under debate. Malayan pangolin and bat are the most suspicious candidate for being sources of the SARS-CoV-2. The SARS-CoV-2 can be transmitted by various ways such as transmitting from infected human to healthy human and can make severe pneumonia, which can lead to death. The SARS-CoV-2 can infect different kind of people with different ages, races, and social and economic levels. The SARS‐CoV‐2 infection can cause various sorts of clinical manifestations like cough and fever and intensity of signs and symptoms depends on sufferer conditions. Clinicians use all of available documents and tests like laboratory, histopathological and radiological findings for diagnosing new cases and curing patients with high accuracy. At the present time, there is no particular way for treating SARS-CoV-2 infection; neither antiviral drugs nor palliative agents. It seems that the best way for standing against the SARS-CoV-2 infection is preventing from it by social distancing and vaccination. This review tries to prepare an essential brief update about SARS-CoV-2 infection for clinicians.

In January 2019, the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) published an opinion on risks related to the presence of hazardous chemicals in infant diapers. ANSES found that health reference values were largely exceeded for polycyclic aromatic hydrocarbons (PAHs), dioxins (PCCD/Fs) and dioxin-like polychlorobiphenyls (DL-PCBs). The levels of formaldehyde and of some fragrances were also considered potentially unsafe. Therefore, ANSES concluded that actions have to be taken to restrict levels of these contaminants in diapers. Under the exposure scenario deemed the most reliable by ANSES, estimates of cancer risks of the most potent PAHs detected in diapers exceeded 10-3 and hazard quotients for neurobehavioral effects attained values up to 66. Regarding dioxins and DL-PCBs, ANSES derived a hazard quotient of 12 for the risk of decreased sperm count at adult age. The aim of this critical review was to examine whether the exposure and risk assessment conducted by ANSES contained potential flaws that could explain such a high exceedance of health reference values. The review will also put into perspective the exposure from diapers with that from breast milk whose benefits for child’s health are undisputable despite contamination by PAHs, dioxins and DL-PCBS.

Discovery of microRNAs (miRNAs) twenty years ago, has advocated a new era of “Molecular Genetics”. About 2000 miRNAs are present, that regulate one third of the genome. MiRNAs dysregulated expression may contribute to several diseases including tumor growth. Their presence in body fluids, reflecting levels alteration in various cancers, merit circulating miRNAs as the “next generation biomarkers” for early stages tumor diagnosis and/or prognosis. Herein, we performed a comprehensive literature search focusing on the origin, biosynthesis and role of miRNAs and summarized the foremost studies centering on miRs value as non-invasive biomarkers in different non-communicable diseases, including various cancer types. Moreover, during chemotherapy many miRNAs were linked to multidrug resistance, via modulating numerous biological processes and/or pathways that will be highlighted as well.

Watching the international COVID-19 epidemics unfold during February and early March 2020, we began to highlight how outbreaks in care homes were inevitable, given the vulnerable patients in close proximity, and pressures on social care to help relieve pressure on the NHS. We suggested public health measures would significantly impact on care homes. Specifically we felt all homes would have multiple individuals isolated within days of introduction of guidance requiring isolation of new cough (or fever), and that a clear definition of an outbreak would be needed that differentiated COVID19 from influenza. We share the experiences of a GP practice looking after 900 nursing or dual registration care homes in the London Borough of Ealing in the early stages of the COVID19 Pandemic 2020. We believe that the altered presentation of cases of COVID19 in care homes contributed to the size of outbreaks, and that keeping COVID19 out of homes is the only way to manage this disease, with early isolation and complete segregation of positive and negative cases. We have seen over 300 suspected cases resulting in four fold (n=175) average monthly death rates, three fold usual issue of anticipatory medications, and approximately 32% mortality rate (up to 43% in over 90’s). Discharge pathways from hospital and admissions to care homes must be clear and robust. COVID19 naïve patients should not be admitted to units with outbreaks and COVID19 positive patients should not be admitted to anything other than a designated “hot” home until risk of contagion is passed. Some patients are testing positive at over 30 days since initial mild symptoms.

Background: Patients with mild cognitive impairment end up progressing to Alzheimer’s disease (AD) leading to straining burden on public health. R. officinalis long been known as the herb of remembrance and can be a potential cognition enhancer for AD. The aims of the review were to summarize the qualitative and quantitative aspects of R.O and its active constituents in enhancing the cognition. MATERIALS AND METHOD Google scholar and PubMed structured search to find relevant studies that assessed the effect of R.O extract or any of its active constituents on cognitive performance in animals. Data extraction: Following information from each included study was extracted: (1) article information (2) characteristics of study animals (3) type of intervention; type, dose, duration, and frequency of administration of R.O (4) type of outcome measure. Data synthesis: Data were analyzed using Review Manager (RevMan 5.3, 2014] and meta-analysis was performed for the outcome measures on all relevant tasks within the included papers by computing the standardized mean difference ps. RESULTS. 23 studies for qualitative and fifteen for meta-analysis were selected. From fifteen included papers, 22 studies with 35 comparisons were meta-analyzed. Effect sizes for intact animals and impaired animals respectively was (mean g and 95% CI 1.19 [0.74, 1.64; 0.57 [0.19,0.96]. The R. officinalis had positive effect on both groups of animals. The subgroup analyses exhibited substantial unexplained heterogeneity between studies. Mechanisms of R.O was anticholinesterase, procholinergic, antioxidant, anti-amyloid, neuroprotective and anti-inflammatory agent CONCLUSIONS: R.O improves cognitive function. Limitations: Considerable heterogeneity between studies.

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.

Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function and behavior are discussed. Finally, the promising therapeutic potential of psychobiotics to modify gut microbial ecology in order to improve mental well-being is presented. Here we show that the individual contribution of nutrients, their interaction with other micro-and macronutrients, and the way in which they are organized in the food matrix are of crucial importance for normal neurocognitive development.

Obesity is associated with increased morbidity and mortality and impaired quality of life. Weight losse is associated with improvement or even cure of cardiovascular risk factors with cardiometabolic benefit. nonsurgical measures for weight loss is rarely successful in the long term. Bariatric surgery has achieved clear success in reversing the abnormal metabolic profile associated with obesity. Pre surgical evaluation is important to rule out any medical or psychological problems that increased the surgical mortality or adversely affect the outcome.

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.

Background Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. Despite being rapidly taken up by practitioners, datapoints from which to derive them were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define - for the first time - the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care. Methods and findings The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a two day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high, middle, and low income countries. Considering each of the six indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2-5 (intermediate) and >5 year (full) timeframes. We removed one of the original six indicators (one of two financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. Conclusions To track global progress toward timely access to quality SAO care, these indicators – at the basic level - should be implemented universally. Intermediate and full evolutions will assist in developing national surgical plans, and collecting data for research studies.

Background: Alzheimer’s disease affecting about 24 million people world-wide. The socio-economic burden on world-economies costing more than 172 billion US $ annually for the US alone. Objectives: To prepare aqueous extract of T. foenum graecum seeds (FSE) to explore the possible treatment for cognitive deficit in experimental animals. Materials and methods: FSE was subjected to preliminary phytochemical evaluation and antioxidant effect using free radical scavenging method (DPPH). All the animal behavior was video recorded with no human intervention during observation and animal groupings were blinded to avoid investigator bias. Different doses of FSE (5%, 10% and 20%), control, standard (Piracetam, 200 mg/kg, IP.) were given for male albino mice a period of 15 days followed by cognitive assessment in elevated plus maze and novel objection recognition tests. Ttransfer latencies and time exploring novel and familiar objects were recorded in respective tests. Retention of this learned-task was examined again 24 h later and inflexion ratio (IR) and discriminative index (DI) were calculated respectively. Next in the second set of experiment same groups and treatments were continued but scopolamine was administered to all the groups except normal control one hour after the last dose and examined similarly. Results: FSE showed potential antioxidant effect and a dose dependent increase in transfer latency and improved DI indicating a nootropic effect. FSE at 20% showed significant reversal of scopolamine induced dementia in the second set of experiment. Conclusion: FSE improved memory as well as reversed the chemically induced memory deficits in experimental mice.

This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive the third dose of coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. Accordingly, the study included participants who provided answer in the questionnaire whether they have an intent to receive the third dose of vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate booster vaccination were retrieved. Among the 2439 participants with mean (±SD) age of 52.6±18.9 years, and median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that younger age (OR=0.98; 95% CI: 0.96-1.00) and higher antibody level (OR=2.52; 95% CI: 1.27-4.99) are positively associated with the third vaccine hesitancy. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had significant impact on the third vaccination behavior. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken in these groups that are likely to hesitate the third vaccine, subsequently increasing booster contact rate.

Rivea hypocrateriformis (Desr.) Choisy is a robust woody climbing shrub of the genus Rivea which is found in India, Nepal, Sri Lanka, Pakistan, Bangladesh, Myanmar and Thailand. R. hypocrateriformis is a promising medicinal herb with enormous helpful and wellbeing advancing impacts. R. hypocrateriformis has been utilized as a customary medication for a long time to treat rheumatic pain, fever, urogenital problem, snake bite, cough, piles, malaria, and skin disease. Apart from the traditional uses its leaves and young shoots are cooked and eaten as a vegetable and for preparation of bread with millet flour. This review comprehensively summarizes the up-to-date information on the botanical characterization, distribution, traditional uses, phytochemistry, pharmacology and toxicity study of R. hypocrateriformis. Phytochemical investigation has been revealed that alkaloids, glycosides, coumarins, flavonoids, xanthones, stilbenes, and other organic compounds are contained in R. hypocrateriformis. Crude extracts and isolated compounds have exhibited numerous pharmacological activities such as anovulatory effect, antifertility activity, antiarthritic, antimicrobial, anticancer, antioxidant, hepatoprotective, antilithiatic, antimitotic. R. hypocrateriformis is a promising restorative spice with monstrous remedial and wellbeing advancing impacts. Along these lines, further investigations on the bioactive mixtures and systems of R. hypocrateriformis are justified. Extra clinical and toxicological examinations are expected to assess its wellbeing.

The Covid-19 pandemic has severely tested the mental health of frontline health care workers. A repeated cross-sectional study can provide information on how their mental health evolved during the various phases of the pandemic. The intensivists of a COVID-19 hub hospital in Rome were investigated with a baseline survey during the first wave of the pandemic in April 2020 and were contacted again in December 2020, during the second wave. 152 of the 205 eligible workers responded to an online questionnaire designed to measure procedural justice, occupational stress (effort/reward imbalance), sleep quality, anxiety, depression, burnout, job satisfaction, happiness, and turnover intention. Workers reported a further increase in workload and compassion fatigue, which had already risen during the first wave, and a marked reduction in the time devoted to meditation and mental activities. A low level of confidence in the adequacy of safety procedures and the need to work in isolation, together with an increased workload and lack of time for meditation were the most significant predictors of occupational stress in a stepwise linear regression model. Occupational stress was, in turn, a significant predictor of insomnia, anxiety, low job satisfaction, burnout, and intention to leave the hospital. The number of workers manifesting symptoms of depression increased significantly to exceed 60%. Action to prevent occupational risks and enhance individual resilience cannot be postponed.

The intensive care units in North West London are part of one of the oldest critical carenetworks in the UK, forming a mature and established strategic alliance to shareresources, experience and knowledge for the benefit of its patients. North WestLondon saw an early surge in COVID-19 admissions, which urgently threatened thecapacity of some of its intensive care units even before the UK government announcedlockdown. The pre-existing relationships and culture within the network allowed itsmembers to unite and work rapidly to develop agile and innovative solutions, protectingany individual unit from becoming overwhelmed, and ultimately protecting its patients.Within a short 50-day period 223 patients were transferred within the network todistribute pressures. This unprecedented number of critical care transfers, combinedwith the creation of extra capacity and new pathways, allowed the region to continue tooffer timely and unrationed access to critical care for all patients who would benefitfrom admission. This extraordinary response is a testament to the power and benefitsof a regionally networked approach to critical care, and the lessons learned maybenefit other healthcare providers, managers and policy makers, especially in regionscurrently facing new outbreaks of COVID-19.

Introduction: Exams are a relatively stressful period for all students, especially undergraduate medical students. Exams bring anxiety and stress for the students. Some students experience such high stress that it hinders their academic productivity and reduces their exam performance. The aim of this study is to assess the effects of pre-exam anxiety on the academic performance of medical students. Methods: Two hundred and twenty-five final year medical students completed Westside Test Anxiety (WTA) Scale one month before their exams. Grade Point Average (GPA) of these students was noted when the results were announced. Data was processed and analyzed using SPSS v 22.0Results: The mean anxiety score on WTA scale was 3.46 ± 0.87. All students (100%) who scored ≤ 2.50 GPA were highly-extremely highly anxious. In the 2.51-3.00 GPA group, 46% were highly-extremely highly anxious, 32% were moderately anxious, and 21% had low to normal anxiety. In the 3.01-3.50 GPA group, 30% were highly-extremely highly anxious, 30% were moderately anxious, and 39% had low to normal anxiety. In the 3.51-4.00 GPA group, 29% were highly-extremely highly anxious, 23% were moderately anxious, and 47% had low to normal anxiety. The correlation coefficient between GPA and test anxiety of students was -.314 which shows inverse relationship.Conclusion: Pre-exam anxiety and stress imparts negative effects on the exam performance of final year medical students. Poor academic performance was associated with high to extremely high pre-exam anxiety while high achievers had relatively lower anxiety levels.

Skeletal muscle atrophy is one of the major side effects of high dose or sustained usage of glucocorticoids. Pyroptosis is a novel form of pro-inflammatory programmed cell death that may contribute to skeletal muscle injury. Trimetazidine, a well-known anti-anginal agent, can also improve skeletal muscle performance both in human and mice. We here showed that dexamethasone induced atrophy, evidenced by the increase of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) expression , and the decrease of myotube diameter in C2C12 myotubes. Dexamethasone also induced pyroptosis, indicated by upregulated pyroptosis-related protein NLRP3, Caspase-1 and GSDMD. Knockdown of NLRP3 or GSDMD attenuated dexamethasone-induced myotube pyroptosis and atrophy. Trimetazidine administration ameliorated dexamethasone-induced muscle atrophy both in vivo and in vitro. Moreover, trimetazidine improved exercise tolerance, as evidenced by increased running distance and running time, as well as increased skeletal muscle mass in dexamethasone-treated mice. Mechanically, trimetazidine could reverse dexamethasone-induced activation of pyroptosis both in C2C12 myotubes and in mice. Taken together, our present study demonstrated that NLRP3/GSDMD pathway-mediated pyroptosis was involved in dexamethasone-induced skeletal muscle atrophy. Trimetazidine could partially alleviate dexamethasone-induced skeletal muscle atrophy, and increase the diameter of C2C12 myotubes via inhibiting pyroptosis. Thus, trimetazidine might be a potential therapeutic compound for the prevention of muscle atrophy in glucocorticoid-treated patients.

Buprenorphine, an analogue of thebaine, is a Schedule III opioid in the United States used for opioid-use disorder and as an analgesic. Research has shown drugs like buprenorphine have a complicated pharmacology with characteristics that challenge traditional definitions of terms like agonist, antagonist, and efficacy. Buprenorphine has a high affinity for the mu (MOR), delta (DOR), kappa (KOR), and intermediate for the nociceptin opioid receptors (NOR). Buprenorphine is generally described as a partial MOR agonist with limited activity and decreased response at the mu-receptor relative to full agonists. In opioid naïve patients, the drug’s analgesic efficacy is equivalent to a full MOR agonist, despite decreased receptor occupancy and the “ceiling effect” produced from larger doses. Some argue buprenorphine’s effects depend on the endpoint measured, as it functions as a partial agonist for respiratory depression, but a full-agonist for pain. Buprenorphine’s active metabolite, norbuprenorphine, attenuates buprenorphine's analgesic effects due to NOR binding and respiratory depressant effects. The method of administration impacts efficacy and tolerance when administered for analgesia. There have been eleven-thousand reports involving buprenorphine and minors (age < 19) to US poison control centers, the preponderance (89.2%) with children. The consequences of prenatal buprenorphine exposure in experimental animals and humans should continue to be carefully evaluated. In conclusion, buprenorphine’s characterization as only a partial mu-agonist is an oversimplification. Contemporary research shows the traditional explanation of the pharmacology of buprenorphine does not take into account changes to receptor theory, pharmacological terminology, route of administration, and biologically active major metabolites.

Background: The abrupt implementation of COVID-19 lockdown had impacted the management of diabetes mellitus. Limited access to health facilities and alterations in daily lifestyle put metabolic control among patients at risk. Thus, we observed the differences in metabolic control parameters in diabetic patients before and during the lockdown. Methods: We performed searches from five databases. Meta-analyses were done using random or fixed-effect approaches with glycemic control parameters (HbA1c, RBG, FBG, TIR, TAR, TBR) as primary outcomes. Mean difference (MD), Confidence Interval (CI), and p-value were calculated. Lipid profile presented as secondary outcome. Results: 21 studies with 3992 diabetic patients were included in the study. Meta-analysis presented an increase on HbA1c of T1D and T2D patients [MD=+0.06% (95%CI -0.10–0.23), I²=77%, p=0.45], TBR of T1D patients [MD=-0.05% (95%CI -0.38–0.28), I²=0%, p=0.77], FBG of T2D patients [MD=+3,47 mg/dL (95%CI 1.22–5.73), I²=0%, p=0.002], and lipid profile on qualitative analysis. However, TIR, TAR, and RBG of T1D patients were improved [MD=+3.52% (95%CI 0.29–6.74), I²=76%, p=0.03; MD=-3.36% (95%CI -6.48–-0.25), I²=75%, p=0.03; MD=-0.91 mg/dL (95%CI -4.52–6.34), I²=88%, p=0.74]. Conclusion: Lockdown enforcement did not worsen the glycemic control parameter in diabetic patients. Particular parameters inclined to improve during the lockdown.

In Italy HPV vaccination was implemented for girls since 2007 but its coverage was lower than recommended level. Sicily is one of the Italian administrative regions with lower vaccination coverage, ranging in the birth cohorts 1996–1999 from 59% to 62%. Aim of the study was to investigate factors associated with refusal of anti-HPV vaccination among young adult women of Palermo, Italy. A cross-sectional study was conducted through the administration of a telephone questionnaire, consisting of 23 items on HPV infection and vaccination knowledge based on Health Belief Model framework. The eligible population were young women with at least a previous vaccination among all included in Sicilian Vaccination schedule, without starting or completing anti-HPV vaccination schedule. Overall, 141 young women were enrolled, of them 84.4% were unvaccinated and 15.6% had at least one dose of HPV vaccine. In multivariate analysis, factors associated with the failure to perform the HPV vaccination were degree as school level (OR = 10.2, p = 0.041), lower participation at school seminar on HPV (OR = 0.2, p = 0.047) and lower perception of anti-HPV vaccine benefits (OR = 0.4, p = 0.048). Public health educational program focusing and tailored on benefits perception of anti-HPV vaccine and HPV disease severity, especially if carried out at school, can improve HPV vaccination uptake.

The new coronavirus disease 2019 (COVID-19) pandemic is an emerging situation with high rates of morbidity and mortality, in the pathophysiology of which inflammation and thrombosis are implicated. The disease is directly connected to the nutritional status of patients and a well-balanced diet is recommended by official sources. Recently, the role of platelet activating factor (PAF) was suggested in the pathogenesis of COVID-19. In the present review several micronutrients (vitamin A, vitamin C, vitamin E, vitamin D, selenium, omega-3 fatty acids, minerals), phytonutrients and Mediterranean diet compounds (olive oil, fish, honey, plant foods) with potential anti-COVID activity are presented. We further underline that the well-known anti-inflammatory and anti-thrombotic actions of the investigated nutrients and/ or holistic dietary schemes, such as the Mediterranean diet, are also mediated through PAF. In conclusion, although there is no single food to prevent coronavirus, the aim is to follow a healthy diet containing PAF inhibitors in order to target both inflammation and thrombosis and try to avoid or/and reduce the deleterious effects of the COVID-19 epidemic.

Background Due to the Covid-19 pandemic and the strict national policies regarding social distancing behavior in Europe, America and Australia, people became reliant on social media as a means for gathering information and a tool for staying connected to family, friends and work. This is the first trans-national study exploring the experiences and challenges of using social media while in lockdown or shelter in place during the current pandemic. Methods This study was part of a wider cross-sectional online survey conducted in Norway, UK, USA and Australia during April/May 2020. The research question was to explore the experiences and challenges of social media users during the Covid-19 pandemic. 3810 people took part in the survey and 1991 responses were included in the analysis . Thematic analysis was conducted independently by two researchers. Results Three overarching themes identified were: Emotional/Mental Health, Information and Being Connected. Participants experienced that using social media during the pandemic amplified anxiety, depression, fear, panic, anger, frustration and loneliness. They felt that there was information overload and social media was full of misleading or polarized opinions from which was difficult to switch off. Nonetheless, participants also thought that there was an urge for connection and learning which was positive and stressful and the same time. Conclusion Using social media while in shelter in place or lockdown could have a negative impact on the emotional and mental health of the population. These findings give a clear insight into practical recommendations for policy and practice on the importance of strengthening mental health care in the community and investing in health workers to support the mental health needs of the public.

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.

Psoriasis is a chronic, multisystem, inflammatory disease. The typical clinical cutaneous manifestation of psoriasis is scaly erythema or plaque, limited or widely distributed. However, psoriasis is far beyond the skin involvement and provides many challenges, including associated comorbidities. In this review, we classify psoriasis as cutaneous and systemic psoriasis, according to the clinical diversity and associated comorbid diseases, and recommend classification criteria for psoriasis. The key objective of this novel classification is to raise awareness of the complexity of this multifaceted disease and help to better understand and manage this complex disease comprehensively.

Background. Restoring large defects with proximal caries extending below the cemento-enamel junction and cavity margins located beneath the gingival tissues represents a very common clinical situation. The aim of this article is to propose a clinical classification of the localization subgingival margins of cavity.Material and methods. Diagnosis is carried out by periodontal probe perpendicular to the long axis of the tooth in the deepest point of the cavity’s margin. To describe the localization subgingival margins of cavity we use exponent which value is equal to the distance (integer number expressed in millimeters) of the level of epithelial attachment to the margin of the cavity. Three periodontal examiners, with >10 years of periodontal practice, were required to attend a calibration session aimed at the validation of the proposed classification. Results. The intrarater and interrater agreement among the localization subgingival margins of cavity: for intrarater agreement ranged from 0.74 to 0.95 (almost perfect agreement), whereas interrater agreement ranged from 0.26 to 0.59 (moderate agreement).Conclusions. The classification the localization subgingival margins of cavity is useful for reaching a more precise diagnosis.

The cause and prevention of recurrent aphthous stomatitis (also called aphthous ulcers or canker sores) are still unknown. This may be due in part to ignorance of the risk factors present in susceptible people. In this systematic review (PROSPERO record #CRD42019122214), we show that most of the risk factors for the disease are single nucleotide genetic polymorphisms in genes related to the functioning of immune system (TLR4, MMP9, E-selectin, IL-1 beta and TNF-alpha). Single nucleotide genetic polymorphisms do not constitute a modifiable risk. This indicates that, at least in part, susceptibility to recurrent aphthous stomatitis is hereditary, and that these factors cannot be modified.

Background University students’ psychological health is linked to their academic satisfaction. This study aimed to investigate students’ psychological health and academic satisfaction in the context of COVID-19 and academic year-end stress. Methods Standardized self-filled scales for anxiety, depression, stress, psychological well-being, and an ad-hoc COVID-19 stress scale were used in this cross-sectional study. Participants were first- to third-year students of eight different health-related tracks in Geneva, Switzerland. Descriptive statistics and hierarchical regression analyses were applied. Results In June 2020, out of 2835 invited students, 433 (15%) completed the survey. Academic satisfaction was a stronger mental health predictor than COVID-19, which mainly predicted stress and anxiety. Lower academic satisfaction scores were significantly associated with stress (β = -.53, p < .001), depression (β = -.26, p < .001), anxiety (β = -.20, p < .001), while higher scores with psychological well-being (β = .48, p < .001). Being female was strongly associated with anxiety and stress but not with depression or psychological well-being. Lower age was associated with stress only. The nature of the academic training had a lesser impact on mental health and the academic year none. Compared to students starting the academic year, year-end students reported significantly lower academic satisfaction, higher depression, and particularly higher anxiety and stress. There was, however, no difference in psychological well-being. Conclusion Students suffer more from anxiety, stress, depression, and lower satisfaction with studies at the end of the academic year than at the beginning. Academic satisfaction plays a more substantial role than COVID-19 in predicting students’ overall mental health status. Training institutions should address the underlying factors that can enhance students’ academic satisfaction, especially during the COVID-19 period, in addition to ensuring that they have a continuous and adequate learning experience, as well as access to psychosocial services that help them cope with mental distress and enhance their psychological well-being.

Skin involvement is an overlooked aspect in the management of paediatric patients with type 1 diabetes. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: “children”, “pediatric/paediatric patients”, “skin”, “skin disorders”, “type 1 diabetes”. Dermatological side effects are frequently observed among diabetic children and adolescents. Insulin-induced lipodystrophies and allergic contact dermatitis caused by insulin pumps or glycaemic sensors are the most common skin reactions in these patients. Furthermore, several diabetes-associated skin diseases such as necrobiosis lipoidica, granuloma annulare, vitiligo, and bullosis diabeticorum may already be present in paediatric age. Paediatric diabetes specialists should pay attention to their patients’ skin so as to recognize these disorders, identify the potential causes, and choose the most suitable treatment. Finally, the evaluation of skin concentrations of advanced glycation end-products using non-invasive diagnostic techniques may be used to assess the risk of chronic complications of diabetes as early as adolescence.

Patients with schizophrenia (SCZ) are at high risk of cardiovascular disease (CVD) due to an inherited predisposition, a sedentary life style and the use of antipsychotic medications. Several approaches have been taken to minimize this risk but results continue to be unsatisfactory. A potential alternative is prescribing Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs decrease platelet aggregation and reduce the risk of coronary heart disease in patients with depression. We therefore aim to investigate whether there is evidence that supports the use of SSRIs to reduce the risk for CVD in SCZ. A systematic review of the literature revealed five published reports relating to the impact of SSRIs on CV risk in SCZ. Three trials assessed the influence on metabolic parameters of fluvoxamine when combined with clozapine. Two of those studies found improvements with fluvoxamine. Of the other two reports, one indicates SSRIs as a group caused minimal but statistically significant increments in total cholesterol, LDL and triglyceride. The second report suggests that when SSRIs are combined with antipsychotics, the metabolic impact depends on the antipsychotic prescribed. While there are promising results, further studies are needed to establish the impact of SSRIs on CV risk in SCZ.

Adolescents’ daily life has dramatically changed during the COVID-19 era due to the social restrictions that have been imposed, including closures of schools, leisure centers and sport facilities. The purpose of this study was to examine levels of well-being and mood and their relations with physical (in)-activity and eating behaviors in adolescents during a lockdown period in Greece. A total of 950 adolescents (Mean Age = 14.41years ± 1.63) participated in a web-based survey while education was online and organized sport activities were interrupted. Participants showed poor well-being, insufficient physical activity levels and moderate scores of healthy eating behavior. Hierarchical regression analysis showed that, after controlling for the effect of gender and body mass index, increased physical activity and healthier eating behavior predicted better well-being, whereas sedentariness predicted worse well-being. Furthermore, it was revealed that days of physical activity per week was a stronger predictor of well-being than minutes of physical activity per week, and that both in-house and out-of-house physical activity were beneficial. Considering that well-being was below the threshold recommended by the WHO as indicative of possible depressive symptoms, measures to increase physical activity and improve eating behavior should become a priority for communities and policy makers.

Maxillomandibular advancement (MMA) is a surgical intervention that reduces the symptoms of obstructive sleep apnea via anterior repositioning of the upper and lower jaws. Pre-operative orthodontic alignment is often a critical component in aiding MMA. Orthodontia are important in intraoperative anchorage for intermaxillary fixation, healthy post-operative occlusion, and post-operative skeletal stability. Sequential clear aligners (SCA) refer to removable orthodontic appliances that are replaced at regular intervals to stimulate dental migration without the use of bonded hardware. These aligners have demonstrated efficacy in aiding orthognathic surgery for dentofacial deformities, which share some technical similarities with MMA for OSA. Here, we explore the treatment protocol for MMA followed by post-operative SCA treatment. Our experiences show that post-operative orthodontic treatment with SCAs results in similarly successful post-operative surgical outcomes given that the patient’s pre-operative occlusion is stable.

Introduction: COVID-19 pandemic has affected HCPs in multiple way. It has caused psychological impact in form of anxiety, depression, and insomnia. In this study, we aim to study and compare the stress level, anxiety and depression among HCPs who are posted in special COVID-19 units with the HCPs who are not posted in COVID-19 units.Methods: This cross-sectional study was conducted in June 2020, at various hospitals of Karachi, Pakistan. All health care professionals (HCPs) were invited to participate. A total of 301 HCPs completed this study, who were divided into two groups; those who are posted in COVID-19 ward (Group A) and those who are not (Group B). Psychological Impact was English version of the Depression Anxiety Stress Scale - 21 (DASS-21).Results: In Group A, 70.5% had moderate, severe, or extremely severe depression compared to 49.2% in group B. In Group A, 75.4% had moderate, severe, or extremely severe anxiety compared to 44.7% in group B. In Group A, 80.3% had moderate, severe or extremely severe stress compared to 54.2% in group B. Anxiety, depression and stress were significantly higher in HCPs who were posted in COVID-19 ward compared to those who were not posted in COVID-19 wardConclusion: There was significantly higher anxiety, stress and depression in health care professionals posted in COVID-19 ward. Both the government and health care agencies should take responsibility for protecting the psychological well-being of health care communities all over the world and ensuring a healthy work environment.

There has been a steady rise in the recognition of Menstrual Hygiene Management (MHM) as a pressing public health issue due to several advocacy campaigns against its high cost. However, not much of such recognition has been given to it outside the non-profit sector in Nigeria. This is paradoxical considering that most menstruators in Nigeria cannot afford MHM whose cost is considered high even in developed countries. We estimated that the average lifetime cost of MHM in Nigeria is $1,120 per menstruator and $113.57 billion for the entire menstruating population. Although this cost is relatively lower than in other countries, Nigeria’s low income level explains why there is a high prevalence of period poverty among menstruators in Nigeria. This paper discusses the intersected impacts of the cost of MHM and period poverty on the average Nigerian menstruator, his/her family, the economy, the environment and the United Nations Sustainable Development Goals. To alleviate the discussed negative effects, we suggested, as a key recommendation, the national shift from the use of disposable MHM products to that of reusable ones.

In contrast to Th1 immune responses against pathogenic viruses and bacteria, the incipient events that generate Th2 responses remain less understood. Part of the difficulty in identifying universal operating principles stems from the diversity of entities against which cellular and molecular Th2 responses are produced. Indeed, such responses are launched towards harmful macroscopic parasites and noxious substances such as venoms but also against largely innocuous allergens. This suggests that the canonical understanding about sensing and recognition applied to Th1 responses may not be translatable to Th2 responses. This review will discuss processes and signals known to occur in Th2 responses, particularly in the context of food allergy. We propose that perturbations of homeostasis at barrier sites induced by external or internal subverters that either activate the immune system or lower its threshold activation are the major requirement for allergic sensitization. Innate signals produced in the tissue under these conditions equip dendritic cells with a program that shapes an adaptive Th2 response.

Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signalling takes part in all four wound healing phases: hemostasis, inflammation, proliferation and remodelling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration and treatment of dermal diseases, including the stem cell-derived, plant-derived and engineered EVs.

Background: Selection and application of suture materials, has gained more importance especially with the increasing number of patients seeking oral surgeries. Since lying in a bacterial-filled environment, sutures make the tissue prone to infection. Suture material plays an important role in the reduction of the risk of infection. This study aimed to assess the success rate of an antibacterial suture named Vicryl Plus in preventing bacterial growth in the surgical site of the mandibular third molar. Methods: 27 patients were included in this double-blinded randomized clinical trial study. Surgical Extraction of the mandibular wisdom tooth was done and the incision was managed by randomly using Vicryl Plus and Vicryl sutures. After 7 days, sutures were removed and assessed microbiologically. Predominant species of Streptococcus mutans and Lactobacillus were assessed as well as the total number of colonies on each suture. Results: There was a significant difference between two suture materials in colony number-length ratio of lactobacillus (p-value= 0.031) and total bacterial colonies (p-value=0.016); but not for S. mutans species (p-value=0.201). Conclusion: Antibacterial Vicryl suture can be a useful tool for the reduction in the rate of surgical site infection in high-risk cases and situations.

The visual system is regulated by the nervous through neurotransmitters, which play an important role in visual and ocular functions. One of those neurotransmitters is acetylcholine, a key molecule that plays a diversity of biological functions. On the other hand, acetylcholinesterase, the enzyme responsible for the hydrolysis of acetylcholine, is implicated in cholinergic function. However, several studies showed that in addition to their enzymatic functions, Acetylcholinesterase exerts non-catalytic functions. In recent years, the importance of evaluating all possible functions of acetylcholine-acetylcholinesterase has been evidenced. Nevertheless, there is evidence that suggests cholinesterase activity in the eye can regulate some biological events both in structures of the anterior and posterior segment of the eye and therefore in the visual information that is processed in the visual cortex. Hence, the evaluation of cholinesterase activity could be a possible marker of alterations in cholinergic activity not only in ocular disease but also in systemic diseases.

With increasing fatalities, the COVID-19 pandemic constitutes a formidable global health challenge. The causative agent, SARS-CoV-2 constantly tests the efficacy of the immune system of its victims. The protective ability of the innate immune system as the first responder largely determines the progression of disease and its clinical prognosis. Evidence suggests that mortalities associated with COVID-19 are largely due to hyperinflammation and a dysregulated immune response. Consequently, the degree of the release of pro-inflammatory cytokines such as IL1, IL-6, and TNF alpha remarkably distinguishes between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for laboratory tests, and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. With respect to the SARS-CoV-2 and the host cell, this literature review focuses on the dynamics of the COVID-19 disease highlighting on the pathogenesis, and the markers of Cytokine Storm. It also proffers solutions by critically looking at the current and potential pharmacological agents that are or can be used to mitigate and manage cytokine storms.

This bibliometric review is aimed to analyze the top 100 most-cited publications in dentistry and to compare its outcomes with similar analysis done by Feijoo et al., [1]. A literature search was performed using the Elsevier's Scopus without any restriction of language, publication year or study design. Of 336381 articles, the top 100 were included based on their citation count which ranged from 638 to 4728 citations (Feijoo et al., 326 to 2050). Most productive decade was the 2000s with 40 articles on the list (Feijoo et al., 1980s: 26). Marx RE (7%) was the major contributor in this study (Feijoo et al., Socransky SS: 9%) and a whopping 48% articles generated from the USA. 26% of top 100 articles focused periodontology (Feijoo et al., periodontology: 43%), while 17% of the total were published in the Journal of Dental Research (Feijoo et al., Journal of Clinical Periodontology: 20%). Most of the publications were narrative reviews/expert opinion (36%), (Feijoo et al., case series: 22%) and were within the evidence level V (64%) (Feijoo et al., 54%). The citation count that a paper secures is not necessarily a reflection of research's quality, however, the current analysis provides latest citation trends in dentistry.

The NETTER-1 study has proven peptide receptor radionuclide therapy (PRRT) to be one of the most effective therapeutic options for metastatic neuroendocrine tumors (NETs), improving progression-free survival and overall survival. However, PRRT response assessment is challenging and no consensus on methods and timing has yet been reached among experts in the field. This issue is owing to the suboptimal sensitivity and specificity of clinical biomarkers, limitations of morphological response criteria in slowly growing tumors and necrotic changes after therapy, a lack of standardized parameters and timing of functional imaging, and the heterogeneity of PRRT protocols in the literature. The aim of this article is to review the most relevant current approaches for PRRT efficacy prediction and response assessment criteria in order to provide an overview of suitable tools for safe and efficacious PRRT.

Besides external high-energy photon or proton beam therapy, targeted radionuclide therapy (TRNT) is an alternative approach to deliver radiation to cancer cells. TRNT is distributed within the body by the vascular system and allows targeted irradiation of a primary tumor and all its metastases, resulting in substantially less collateral damage to normal tissues as compared to ex-ternal beam radiotherapy (EBRT). It is a systemic cancer therapy, tackling systemic spread of the disease, which is the cause of death in most cancer patients. The α-emitting radionuclide bis-muth-213 (213Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth, and general considerations for designing a 213Bi-radiopharmaceutical are provided. Finally, we will provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.

This study used structural equation modelling (SEM) to evaluate the direct effect of sex and age on stroke types and outcomes in Tertiary Health Facilities in Rives State, Nigeria. The study was a cross-sectional retrospective hospital-based research that utilized specific stroke patients’ information between 2015-2019. The study obtained the sex and age, stroke type (ischemic/hemorrhagic), and outcomes (No disability/disability/death) from the records. The retrieved data was Microsoft Excel (2016), then analyzed using SPSS (version 21, Amos) and STATGRAPHICS centurion (Stat Point Tech., Inc.). From the result, out of the recorded 1916 stroke patients, 1229 (64.1%) were female, while 687 (35.9%) were males. The older adults (>55 years) had more recorded cases (n=1289) than young adults (ages 18–35 years; n=77) and middle-aged adults (ages 36–55 years, n=550). The SEM results showed that age was significantly associated with stroke type (P<0.001) and outcomes (P=0.038), while sex was significantly associated with stroke outcomes (P<0.001). The likelihood of death was 1.3 times higher in hemorrhagic stroke than ischemic stroke. In conclusion, age and sex had direct effects on stroke type, while age had a direct effect on stroke outcome. Hemorrhagic stroke was more likely to cause death than ischemic stroke in the studied population.

Background: Nursing services provided by nurses are based on knowledge and competence in the field of nursing science developed in accordance with Client needs, scientific developments, and the demands of globalization. These health services include nursing services that are carried out responsibly, accountably, with quality, and safely by nurses who have obtained registration and permission to practice. Nursepreneur is innovation and courage to take risks and is ready to work hard to achieve goals with optimism. Which has important components namely: 1) quality, 2) role, 3) option and success. The post-pandemic new world, especially in the health care system, continues to grapple with the demands of costs to provide patient care and safety. By using the application of the nursing theory model. Purpose :. Assessing scientific studies on the application of evidence-based intervention in wound care using nursing theory, identifying the important role of telenursing in improving nursing services in Nerspreneurship, Method: literature study Conclusion: Telenursing in nursing focuses on providing nursing care through information technology, such as telephone, computers, and the Internet that can be used to improve treatment outcomes among older people, especially those with low literacy skills and low financial status (Esmaeilpour-BandBoni et al., 2020). The statement from the results of the study refutes that Telenursing is intended for patients who have higher education and middle and upper economic states.

Sedation is a ubiquitous practice in ICUs and NCCUs. It has the benefit of reducing cerebral energy demands, but also precludes an accurate neurologic assessment. Because of this, sedation is intermittently stopped for the purposes of a neurologic assessment, which is termed a neurologic wake-up test (NWT). NWTs are considered to be the gold-standard in continued assessment of brain-injured patients under sedation. NWTs also produce an acute stress response that is accompanied by elevations in blood pressure, respiratory rate, heart rate, and ICP. Utilization of cerebral microdialysis and brain tissue oxygen monitoring indicates that this is not mirrored by alterations in overall cerebral metabolism, and seldom affects oxygenation. The hard contraindications for the NWT are preexisting intracranial hypertension, barbiturate treatment, status epilepticus, and hyperthermia. However, hemodynamic instability, sedative use for primary ICP control, and sedative use for severe agitation or respiratory distress are considered significant safety concerns. Despite ubiquitous recommendation, it is not clear if additional clinically relevant information is gleaned through its use, especially with the contemporaneous utilization of multimodality monitoring. Various monitoring modalities provide unique and pertinent information about neurologic function, however, their role in improving patient outcomes and guiding treatment plans has not been fully elucidated. There is a paucity of information pertaining to the optimal frequency of NWTs, and if it differs based on type of injury. Only one concrete recommendation was found in the literature, exemplifying the uncertainty surrounding its utility. The most common sedative used and recommended is propofol because of its rapid onset, short duration, and reduction of cerebral energy requirements. Dexmedetomidine may be employed to facilitate serial NWTs, and should always be used in the non-intubated patient or if propofol infusion syndrome (PRIS) develops. Midazolam is not recommended due to tissue accumulation and residual sedation confounding a reliable NWT. Thus, NWTs are well tolerated in most patients and remain recommended as the gold-standard for continued neuromonitoring. Predicated upon one expert panel, they should be performed at least one time per day. Propofol or dexmedetomidine are the main sedative choices, both enabling a rapid awakening and consistent NWT.

Hypertension is a chronic non-communicable disease which is one of the main causes of serious cardiovascular disease death in the community. The level of treatment and health control for hypertensive patients is still not optimal due to lack of information. Aim was to identify various current methods of health education by nurses and their impact on hypertensive patients. Method Literature review research. The literature was obtained from the Scopus, Sage and PubMed databases with the keywords "Intervention" OR "Methods" AND "Nursing" AND "Hypertension". There are seven literatures that are determined to meet the requirements of the inclusion criteria. Results found three types of health education methods performed by nurses: 1) direct health education methods; nurses meet and meet face to face with patients in the form of individual teaching or training, 2) indirect health education methods; nurses are not face-to-face but use telephone or mobile communication aids to convey information and send SMS about health, and use internet-based websites to convey health information, 3) combined health education methods; nurses face to face with patients and follow-up care is carried out by indirect health education methods. The impact of health education methods carried out by nurses on hypertensive patients is that the level of patient adherence increases in treatment, increased knowledge levels, better blood pressure control, healthy lifestyle practices, adherence to diet, improved quality of life, and positive nurse-patient feedback occurs. in fulfilling mutually agreed upon treatment appointments. Conclusion health education methods carried out by nurses have a very positive impact on disease management and prevention of risk factors for complications in hypertensive patients.

Coronaviruses (CoVs) are a well-known group of viruses in veterinary medicine. We currently know four genera of Coronavirus, alfa, beta, gamma and delta. Wild, farmed and pet animals are infected with CoVs belonging to all four genera. Seven human respiratory coronaviruses have still been identified, four of which cause upper respiratory tract diseases, specifically, the common cold, and the last three that have emerged cause severe acute respiratory syndromes, SARS-CoV-1, MERS-CoV and SARS-CoV-2. In this review we briefly describe animal coronaviruses and what we actually know about SARS-CoV-2 infection in farm and domestic animals.

Abstract: COVID-19 in 2020 brought challenges to the Brazilian public health system with an emerging virus with respiratory contagion called SARS-CoV-2. There are few studies in Brazil and in some countries, on the increased incidence of certain viral respiratory infections, includ-ing H1N1 and coronavirus and their association with low levels of vitamin D, zinc and iron. The aim of this study was to demonstrate that the deficit of vitamin D, zinc and iron has an impact on the infectious process of patients with COVID-19 and to establish new forms of prevention for the worsening of COVID-19 in the human body. Data were collected from medical records and test results from patients being followed up during the treatment period for COVID-19. Patients with low blood levels of vitamin D, zinc and iron during the treatment period of COVID-19 had a higher percentage of worsening and complications requiring hospitalization in intensive care beds. The ingestion of vitamin D, zinc and iron in the treatment period of patients with COVID-19 in addition to being an immunological protector against SARS-CoV-2 and alleviating the process of worsening the disease can also act as a biomarker in cases of this disease.

Growing evidence has revealed the implication of germline variation in cancer predisposition and prognostication. Here, we describe an analysis of putatively disruptive rare variants across the genomes of 726 patients with B-cell lymphoid neoplasms. We discovered a significant enrichment of 26 genes in germline protein truncating variants (PTVs), affecting cell signaling (MET, JAK2, ANGPT2), energy metabolism (ACO1) and nucleic acid metabolism and repair pathways (NT5E, DCK). Interestingly, some of these variants were restricted to either chronic lymphocytic leukemia (CLL) (i.e., ANGPT2 and AKR1C3) or B-cell lymphoma cases (PNMT, TPT1 and IGHMBP2). Additionally, we detected 1,675 likely disrupting variants in genes associated with cancer, of which 44.75% were novel events and 7.88% were PTVs. Among these, the most frequently affected genes were ATM, BIRC6, CLTCL1A and TSC2. Homozygous or compound heterozygous variants were detected in 28 cases; and coexisting somatic events were observed in 17 patients, some of which affected key lymphoma drivers such as ATM, KMT2D and MYC. Finally, we observed that variants in the helicase gene WRN were independently associated with shorter survival in CLL. Our study results support an important role for rare germline variation in the pathogenesis, clinical presentation and disease outcome of B-cell lymphoid neoplasms.

This work investigated the effects of manufacturing variations including coil resistance, initial pod mass, and e-liquid color on coil lifetime and aerosol generation of Vuse ALTO pods. Random samples of pods were used until failure (where e-liquid was consumed, and coil resistance increased to high value indicating a coil break). Initial coil resistance, initial pod mass, and e-liquid net mass ranged between 0.89 to 1.14 [], 6.48 to 6.61 [g], and 1.88 to 2.00 [g] respectively. Coil lifetime with light color e-liquid was (mean) = 149, (standard deviation) = 10.7 puffs while pods with dark color e-liquid was = 185, = 22.7 puffs with a difference of ~36 puffs (p &lt;0.001). Total mass of e-liquid consumed until coil failure was = 1.93, = 0.035 [g]. TPM yield per puff of all test pods for the first session (brand new pods) was = 0.0123, = 0.0003 [g]. During usage, TPM yield per puff of pods with light color e-liquid was relatively steady while it was continuously decreasing for pods with dark e-liquid. Coil lifetime and TPM yield per puff were not correlated with either variation in initial coil resistance or variation in initial pod mass. The absence of e-liquid in the pod is an important factor in causing coil failure. Small bits of the degraded coil could be potentially introduced to the aerosol. There is a potential correlation of e-liquid color with both coil lifetime and TPM yield per puff. Change of e-liquid color might have been a result of oxidation which changed some nicotine into nicotyrine.

Motorcycles can be considered a new form of smart vehicle when taking into account their small and modern structure and due to the fact that nowadays they are used in the new role of ambu-lance to rapidly reach emergency patients in large cities with traffic congestion. However, there is no study regarding the measuring of access time for motorcycle ambulances in large cities of Thailand. Therefore, this study aims to compare access times to patients between motorcycle ambulances and conventional ambulances, including analysis of the use of AED installed on motorcycle ambulances to contribute to the sustainable development of public health policies. In two hundred and seventy-one operations, it was found that the times from dispatch to vehicle (ambulance and motorlance) being en route and times from the 1669 center (center for com-mand-and-control EMS in Thailand) call receipt to arrival on scene (response time) of motorcycle ambulances was shorter than that of a conventional ambulance and the use of AED on a motor-cycle ambulance can increase the chances of survival for patients with cardiac arrest outside the hospital in public places where AEDs are not available and in all cases where access to an AED was less than eight minutes.

Both types of surgical guides – with and without metal sleeves are founded beneficial in clinical studies. The aim of this in vitro study was to compare time of surgical procedure in dental implantology depending of used type of the surgical guide. Ten three dimensional (3D) printed models of lower jaws were prepared based on complete virtual model of patient clinical conditions with missing teeth 37, 46 and 47. Five of this models were used for implant sites preparation performed with use of surgical guide without metal sleeves and dedicated surgical kit, and next five were used for the same procedure performed with surgical guide with metal sleeves and dedicated surgical kit. Time of implant site preparation were measured and noted. Statistical analysis was performed using Student’s t test for independent samples. Difference of time in both groups were founded as statistically significant (t=-9.94; df =28; p=0.0000). Type of surgical guide is important factor which can impact on time of implant site preparation and all surgical procedure.

Hip fractures are an important socio-economic problem in western countries. Over the past 60 years orthogeriatric care has improved the management of older patients admitted to hospital after suffering hip fractures. Orthogeriatric co-management units have increased quality of care, reducing adverse events during acute admission, length of stay, both in-hospital and mid-term mortality, as well as healthcare and social costs. Nevertheless, a large number of areas of controversy regarding the clinical management of older adults admitted due to hip fracture remain to be clarified. This narrative review, centered in the last 5 years, combined the search terms “hip fracture”, “geriatric assessment”, “second hip fracture”, “surgery”, “perioperative management” and “orthogeriatric care”, in order to summarise the state of the art of some questions such as the optimum analgesic protocol, the best approach for treating anemia, the surgical options recommendable for each type of fracture and the efficiency of orthogeriatric co-management and functional recovery.

Client or patient satisfaction is a very important indicator in determining service quality, patient satisfaction with various factors, but the main determining factor for patient satisfaction is the nurse, because nurses are medical personnel who are always near the patient and almost approaching the treatment that the client receives always involves the nurse. In it, therefore, nursing services, namely in the form of nursing care, are important to penetrate patient satisfaction. The purpose of this paper is to determine the effect of the quality of nursing services in increasing patient satisfaction. The method used in this research was a literature study which is analyzed from 25 articles searched through Google Scholar and Pubmed and selected based on indexes, namely Scopus, Sinta 1, and 2 and the topics discussed. The results showed that if the quality of service of nursing or nursing care can significantly increase patient satisfaction.

Introduction Color vision deficiency (CVD) constitutes one of the frequently observed eye disorders in all human populations. Color is a prominent sign utilized in the medical profession to study and identify histopathological specimens, lab instruments, and patient examination. Color deficiency affects the medical skills of students resulting in poor clinical examination and color appreciation. There is no effective screening of CVD at any level of the medical profession. Hence, this study was aimed to determine the prevalence of CVD among medical students. Materials and methods This was a cross-sectional study conducted from September 2019 to February 2020 over a period of six months in Karachi, Pakistan. All medical students aged 18-21 years of either gender enrolled in the first and second years of medical college were included in this study. The examination was performed during daylight. Ishihara plates were placed at a distance of 75 cm from the subject and tilted so that the plane of the paper lies perpendicular to the line of vision. Students were given five seconds to read the plate and one examiner was instructed to mark the checklist. A score of less than 12 out of 14 red/green test plates (not including the demonstration plate) was considered as a CVD. All statistical analysis was performed using Statistical Package for Social Sciences version 20.0 (Armonk, NY: IBM Corp). Results The mean age of the medical students was 19.61± 1.22 years. There were (n=123) 53.0% females and (n=111) 47.0% males. Most of the medical students (n=131, 56.0%) belonged to the upper-middle-class socioeconomic group. CVD was observed in (n=13) 6.0%of medical students. Age (p=0.001) and socioeconomic status (p=0.001) were the only demographic factors significantly associated with color deficiency. Conclusions Color deficiency, although an unnoticed concern, is fairly common among medical students. Medical students must be screened for CVD as this will enable them to be aware of their limitations in their future observational skills as a doctor and devise ways of overcoming them in clinical practice.

Advances in machine learning (ML) and artificial intelligence (AI) are transforming the way we treat patients in ways not even imagined a few years ago. Cancer research is at the forefront of this movement. Infertility, though not a life-threatening condition, affects around 15% of couples trying for a pregnancy. Increasing availability of large datasets from various sources creates an opportunity to introduce ML and AI into infertility prevention and treatment. At present in the field of assisted reproduction, very little is done in order to prevent infertility from arising, with the main focus put on treatment when often advanced maternal age and low ovarian reserve make it very difficult to conceive. A shift from this disease-centric model to a health centric model in infertility is already taking place with more emphasis on the patient as an active participator in the process. Poor quality and incomplete data as well as biological variability remain the main limitations in the widespread and reliable implementation of AI in the field of reproductive medicine. That said, one of the areas where this technology managed to find a foothold is identification of developmentally competent embryos. More work is required however to learn about ways to improve natural conception, the detection and diagnosis of infertility, and improve assisted reproduction treatments (ART) and ultimately, develop clinically useful algorithms able to adjust treatment regimens in order to assure a successful outcome of either fertility preservation or infertility treatment. Progress in genomics, digital technologies and advances in integrative biology has had a tremendousimpact on research and clinical medicine. With the rise of ‘big data’, artificial intelligence, and the advances in molecular profiling, there is an enormous potential to transform not only scientific research progress, but also clinical decision making towards predictive, preventive, and personalized medicine. In the field of reproductive health, there is now an exciting opportunity to leverage these technologies and develop more sophisticated approaches to diagnose and treat infertility disorders. In this review, we present a comprehensive analysis and interpretation of different innovation forces that are driving the emergence of a system approach to the infertility sector. Here we discuss recent influential work and explore the limitations of the use of Machine Learning models in this rapidly developing area.

C-C Chemokine receptor type 5 (CCR5) is expressed on the CD4 T cell surface where CXCR4 and CCR5 expressions are controlled differently during the activation of T cells and with the binding of interleukin type-2 (IL-2). IL-2 can upregulate CCR1 and CCR2 in CD45R01 T cells and increase the T lymphocyte chemotaxis toward CC-chemokines. CD4+ T cells are either apart of the T helper 1 or Th1 lymphocytes that release interferon gamma (IFNγ) and lymphotoxin that provide cellular immunity to internal pathogens and T helper cells type 2 (Th2), which secrete interleukins 4 and 5 (IL-4 and IL-5). IL-4 and IL-5 cause an allergic and humoral immune response to parasites. Th2 lymphocytes use CCR3 chemokine receptors. CCR5 and CXCR3 chemokine receptors are specific for CD4+ Th1 and Th2 lymphocytes. CCR5Δ32 is a 32-base-pair deletion of the CCR5 gene. CCR5 is a co-receptor for the entrance of the human immunodeficiency virus-1 (HIV-1). CCR5Δ32 creates a malfunction of the CCR5 protein that can prevent HIV-1 infection. However, the CCR5Δ32 32-base-pair deletion is not prevalent and predominant in many populations worldwide and there also exist more genetic variations of CCR5 known as CCR5-SNPs. An alternative polymorphism was identified based on the CCR5 gene that was identified as a A to G (A/G) point mutation. This point mutation is located at the 59029 locus on the promoter that lowers the expression rate of CCR5. Gurdol et al. found activity at the promoter of CCR5/590029G was 45% lesser than the CCR5/59029A. The genetic variations of CCR5 SNPs also include: 2459G>SNP of CCR5, C101X, CCR5 gene position at -2273, and the A to G SNP mutation found in two South African blacks. Therefore, more studies are needed to find more and varied chemokine polymorphisms that are present in many diverse populations in the world. The aim of this literature review is to describe the immense impact of CCR5 SNP mutations on viral infection susceptibility, on the pathogenesis of chronic conditions, to endorse the increased discovery of more novel CCR5 SNPs, and to show the significant potential of anti-CCR5 therapies to treat multiple diseased conditions.

Effective pandemic management requires understanding the level of community knowledge, attitude of people and preparedness towards COVID-19. This study aimed to assess the knowledge, attitude and preparedness toward COVID-2019 among Bangladeshi general people. A cross sectional survey was conducted from 20th March 2020 to 20th April 2020 among 1007 Bangladeshi adult people. A convenience sampling strategy was utilized and the data was collected through a self-administered questionnaire. Chi-square test was used to identify the gender differences regarding knowledge, attitude and preparedness towards COVID-19. Respondents predominately used social media to inform themselves about COVID-19 (68.10%) and female used social media more than male (p<0.001). Female had more correct knowledge about staying home with sickness and/or symptoms to contain the COVID-19 transmission (p=.02). While male had more negative attitude about staying out during the pandemic than female (<0.001) and men were less likely to take preventative measures than female counterparts. A number of people were still believing the myths like “COVID-19 can transmit via mosquito” (9.14%) and male had more incorrect knowledge regarding this (p<0.001). Moreover, 17.81% of the respondents thought that COVID-19 can spread in warm weather. Some findings are directing us to a knowledge gap among general population in Bangladesh which calls for uncovering those aspects. Adequate and effective communication are necessary so that general people can stay alert with positive attitude and hygienic practices to fight against this ongoing crisis.

Let us all take a moment to talk, once again, about this new coronavirus pandemic that the world has been facing since November 2019 and about its global response. After a short period marked by the pandemic underestimation risk by most governments, the Western world went nuts and overreacted, most probably so as not to be accused of inaction. In many cases, the overall benefits of the chosen policies were not sufficiently questioned, which resulted in many side effects on global health .The medical motto “primum non nocere”, a moral principle everyone should at least consider following, was evidently not taken into account. It has been overlooked, and the virus has become an obsession, to the extent that nearly everything else, even the most valuable things in life, is still now under appreciated if not simply ignored. This review highlighted facts against this simplistic, one-dimensional view.

In the present study, fish were exposed to sub-lethal doses of CuONPs (68.92 ± 3.49 nm) (10, 20, and 50 mg/L) for a long exposure period (25 days). Compared to the control group (0.0 mg/L CuONPs), a significant dose-dependent elevation in blood urea and creatinine values, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase enzyme activities were evident in CuONPs-exposed groups (P &lt; 0.05). Fish exposure to 50 mg/L CuONPs significantly upregulated the transcription of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin 12, and interleukin 8), heat shock protein 70, apoptosis-related gene (caspase 3), and oxidative stress-related (superoxide dismutase, catalase, and glutathione peroxidase) genes in liver and gills of the exposed fish in comparison with those in the control group (P &lt; 0.05). Moreover, varying histopathological injuries were noticed in the hepatopancreatic tissues, posterior kidneys, and gills of fish groups correlated to the examined exposure dose of CuONPs. In summary, our results provide new insights and helpful information for better understanding the mechanisms of CuONPs toxicity in Nile tilapia at hematological, molecular levels, and tissue levels.

(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.