The quarantine imposed as the response to the COVID 19 pandemic has been related to an increase in cases of thromboembolism in Non-COVID19 patients .We report the case of a patient with pulmonary thromboembolism without usual triggering causes during the quarantine period, related to a previously undiagnosed hypercoagulable condition.

HLA class I alleles constitute established risk factors for non-infectious uveitis and preemptive genotyping of HLA class I alleles is standard practice in the diagnostic work-up. The HLA-A29 serotype is indispensable to Birdshot Uveitis (BU) and renders this enigmatic eye condition a unique model to better understand how the antigen processing and presentation machinery contributes to non-infectious uveitis or chronic inflammatory conditions in general. This review will discuss salient points regarding the protein structure of HLA-A29 using and how key amino acid positions impact the peptide binding preference and interaction with T cells. We discuss to what extent the risk genes ERAP1 and ERAP2 uniquely affect HLA-A29 and how the discovery of a HLA-A29-specific submotif may impact autoantigen discovery. We further provide a compelling argument to solve the long-standing question why BU only affects HLA-A29-positive individuals from Western-European ancestry by exploiting data from the 1000 Genomes Project. We combine novel insights from structural and immunopeptidomic studies and discuss the functional implications of genetic associations across the HLA class I antigen presentation pathway to refine the etiological basis of Birdshot Uveitis.

Despite several attempts by governments and non-governmental organizations to eliminate female genital mutilation or cutting, it is puzzling that this traditional procedure is widely practiced today in many parts of sub-Saharan Africa (SSA). Scholarly arguments on the influence of female genital mutilation on sexual behavior up until now remain inconclusive. The current study sought to examine the association between female genital mutilation and early sexual initiation among girls and young women (AGYW) in SSA. Data from Demographic and Health Surveys (DHS) of 12 SSA countries were combined. A total of 30,089 AGYW (15-24 years) who had ever had sex and had complete information on all the variables of interest were considered. The outcome variable for the study was early sexual initiation. The study employed multilevel logistic regression for the data analysis, with reported odds ratio and associated 95% confidence intervals (CIs). The overall prevalence of female genital mutilation among AGYW was 49.9%, with the highest and lowest prevalence in Guinea (95.8%) and Togo (3.3%) respectively. The prevalence of early sexual initiation was 42.4%, with the highest and lowest prevalence in Niger (59.9%) and Burkina Faso (30.6%) respectively. AGYW who had not experienced female genital mutilation were less likely to have early sexual initiation [OR= 0.74, CI= 0.70-0.78], compared to those who had experienced female genital mutilation, after controlling for significant covariates. The likelihood of early sexual initiation was high among AGYW aged 15-19 [OR=2.38, CI=2.26-2.51] but low among AGYW with secondary education [AOR=0.58, CI=0.54-0.63], those who had never married [OR=0.68, CI=0.60-0.78], those in households with richest wealth quintile [OR=0.64, CI=0.57-0.72], those who were exposed to mass media [OR=0.88, CI=0.83-0.93], and those working [OR=0.91, CI=0.87-0.96]. Not undergoing female genital mutilation in the midst of socio-economic factors (e.g., education level, household wealth) could limit AGYW from early sexual debut. These findings underscore the need for effective campaign and programs (e.g., educational programs, entrepreneurial training, micro-finance schemes) against the practice of female genital mutilation. Policy interventions (e.g., “schooling for the girl-child” initiatives) that might delay early sexual initiation among adolescent girls and young women in the midst of identified socio-economic factors should be developed.

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

Miller Fisher Syndrome (MFS) is a rare variant of Guillain-Barré Syndrome (GBS). It is largely a clinical diagnosis based on the classical features of ataxia, areflexia, and opthalmoplegia. Its clinical evolution is most often favorable. However, other neurological signs and symptoms may also be present. Supportive laboratory studies (positivity of antibodies, CSF albumin-cytological dissociation and nerve conduction studies) are useful especially in uncommon presentations. We report a case of a 74-year-old patient who exhibited dysphonia and difficulty to swallowing previously to the classic triad of ataxia, areflexia, and opthalmoplegia, characteristic of MFS. CSF analysis demonstrates an albumin-cytological dissociation but anti-GQ1b antibody were negative. The patient has spontaneously and completely recovered after several weeks.

Many individuals are wearing face masks improperly at ‘half mask’ and potentially breathing out microbes that can contaminate the air as well as anything below the nose. This note provides the first report that bacteria and fungi breathed out during nasal air exhalation are able to be cultured after landing on blood agar plates. The CFU’s are higher after both 10 breaths and extremely significant for 20 breaths compared to the control plates exposed to the air. Implications of this finding are that going ‘nose commando’ may be able to continue the spread of respiratory diseases such as COVID-19.

The socio-economic benefits of globalization cannot be overemphasized. However, the global spread of infectious diseases has so followed a parallel course. The recent wave of pandemics with emerging new diseases has shown that no part of the world is immune from the spread of infectious diseases. COVID-19 like previous pandemics has exposed inadequacies of our healthcare systems and global capacity for prevention, early detection, and response in pandemic outbreaks. Given the highly interconnected global economy and the high potential for passim spread of infections, every nation must not only come up with concerted efforts to prevent and better prepare for pandemics, international solidarity and engagements will also be critical to ensure a long-lasting and sustainable solution. We are only as strong as our weakest health system, global support to strengthen all health systems around the world is the most effective way to be pandemic – ready. ‘All for one and one for all’.

Background: The COVID-19 has put global health institutions on alert. Organizations such as the CDC and WHO have developed preparedness and prevention checklist of 2019-nCoV infection to be used by public and healthcare professionals. Since COVID 19 pandemic is unexpected and no country aware of it prior to outbreak, there is limited information on the overall preparations of healthcare providers in Ethiopia. Therefore, the aim of this study was to assess early healthcare professionals’ preparedness and response to COVID 19 Pandemic in Oromia regional state, Ethiopia. Methods: The study was conducted on healthcare professionals working in public hospitals of Oromia regional state. The study was carried out by online questionnaire prepared using SurveyMonkey©. The collected data was analyzed and One-way ANOVA was used to determine the significant differences between health professionals working in different hospitals. The statistical significance associations of variables of interest was determined at 95% confidence intervals. Results: Healthcare professionals in the public hospitals of Oromia regional state, Ethiopia perceived that they are not yet well prepared and may not respond to the pandemic quickly and efficiently. Even though, they have positive response towards identifying signs and symptoms, provide education and utilization of PPE, they are still lacking in practical responses like managing cases, implementing emergency plans and isolation procedures from many others. Conclusion: As the Federal Ministry of Health, Ethiopia Public health institute and Oromia health bureau are vigilant and continually conducting preventive measures programs, extensive and maximum effort should be done to improve healthcare providers’ preparedness and response towards any emergency related to COVID-19 pandemic.

The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

Tooth bud removal called Ibyinyo is the practice of removing the developing tooth buds, usually done on an infant, typically performed by traditional healers who believe that this practice will reduce fever and diarrhea in children. This practice is most prevalent in East-African countries, including Rwanda. These procedures are mostly performed in non-sterile conditions using basic sharp instruments. We will discuss the case of a 10-year-old female patient who was presented at the dental clinic, with two malformed permanent canine teeth. Clinical examination revealed malformed enamel and elongated permanent right maxillary canine tooth left mandibular canine tooth with crown malformation. She was also presented with retained (primary) left maxillary lateral incisor tooth and missing left maxillary canine tooth. In addition, the ectopic eruption of left maxillary central incisor tooth and missing permanent right mandibular canine tooth were noted. All these complications resulted from tooth bud removal that the patient had experienced in her early childhood. Her malformed right maxillary and left lower mandibular canine teeth were reshaped, using composite filling materials, to improve her appearance aesthetically. Ibyinyo is preventable damage, done out of ignorance and superstitious practices that can be stopped by growing social awareness. Therefore, educating parents through community-based campaigns on the detrimental consequences of early childhood tooth bud removal through Ibyinyo practice might be helpful to eradicate this harmful and unnecessary practice.

Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demonstrated that systemic administration of the Bin1 monoclonal antibody 99D (Bin1 mAb) developed in our laboratory was sufficient to reinforce intestinal barrier function and preserve an intact colonic mucosa, compared to control subjects which displayed severe mucosal lesions, high-level neutrophil and lymphocyte infiltration of mucosal and submucosal areas, and loss of crypts. Here we report effects of Bin1 mAb on colonic neurons and the gut microbiome that correlate with the benefits of treatment. In the DSS model, we found that induction of UC was associated with disintegration of enteric neurons and elevated levels of glial cells, which translocated to the muscularis at distinct sites. Further, we characterized an altered gut microbiome in DSS treated mice associated with pathogenic proinflammatory characters. Both of these features of UC induction were normalized by Bin1 mAb treatment. With regard to microbiome changes, we observed in particular that Firmicutes were eliminated by UC induction and that Bin1 mAb treatment restored this phylum including the genus Lactobacillus and Akkermansia as beneficial microorganisms. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with a preservation of enteric neurons and an improvement in the gut microbiome, contributing overall to a healthy intestinal tract.

Background: Vasoactive Intestinal Peptide (VIP) is known to bind to and protect the Alveolar Type II cell by blocking replication of the SARS-CoV-2 virus, upregulating surfactant production, blocking apoptosis, and blocking cytokine effects. RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) has been granted Fast Track Designation and is currently in phase 2/3 placebo-controlled trials. FDA has granted Emergency Use IND and Expanded Access Protocol approval for the use of RLF-100 in patients whose comorbidities render them ineligible for inclusion in the ongoing pivotal trial. Methods: This report describes the first 6 patients with Acute Respiratory Failure in Critical COVID-19, enrolled under Emergency Use IND were treated with three successive 12-hour infusions of intravenous Aviptadil at 50/100/150 pmol/kg/hr, while continuing to receive maximal ICU care. Results: Median patient follow-up time is 14 days. So far, all treated patients have survived. Improved radiographic appearance of typical “ground glass” COVID-19 features to varying degrees is seen in all patients within 72 hours. Improvement in blood oxygenation is seen in all patients, with complete remission from respiratory failure in 4 of 6 patients. An average 56% reduction in inflammatory markers was seen, together with a median 4 point reduction in the NIAID Ordinal Scale. 2/6 patients were discharged from the hospital and 1 patient was downgraded to the general medicine floor. Comment: The short term survival of 6/6 patients with respiratory failure in the setting of COVID-19 and major comorbidity is the most dramatic response ever seen with an antiviral agent. Improvement in radiographic appearance, oxygenation requirement, and inflammatory markers is consistent with in vitro evidence of direct anti-viral effect.

Due to its aggressive and invasive nature glioblastoma (GBM), the most common and aggressive primary brain tumour in adults, remains almost invariably lethal. Significant advances in the last several years have elucidated much of the molecular and genetic complexities of GBM. However, GBM exhibits a vast genetic variation and a wide diversity of phenotypes that has complicated the development of effective therapeutic strategies. This complex pathogenesis makes it necessary the development of experimental models that could be used to further understand the disease, and also to provide a more realistic testing ground for potential therapies. In this report, we describe the process of transformation of primary mouse embryo astrocytes into immortalized cultures with neural stem cell characteristics, that are able to generate of GBM when injected in the brain of C57BL/6 mice, or heterotopic tumours when injected iv. Overall, our results show that oncogenic transformation is a fate for NSC if cultured for long periods in vitro. In addition, since no additional hit is necessary to induce the oncogenic transformation, our model may be used to investigate the pathogenesis of gliomagenesis and to test the effectiveness of different drugs throughout the natural history of GBM.

Coronavirus is believed to have originated from a wet market in Wuhan, China, and has spread all over the world, resulting in a large number of hospitalizations and deaths. Social scientists are just beginning to understand its consequences on human behavior. One policy that public health officials put in place to help stop the spread of the virus were stay-at-home/shelter-in-place lockdown-style orders. Schools, Colleges and Universities across the country have now been shut down till now due to Covid-19. Some Governments in India impose lockdown to reduce the crises created by this unknown virus. It is now difficult to make final assessments by school, school leaving examinations and entrance tests for undergraduate and post-graduate courses. This disruption implies for students across the socio-economic spectrum, both in terms of learning outcomes , food and economic security. Here the aim is to discuss the implications of lockdown-induced in schools in both urban and rural areas in India.The whole world implemented a nationwide lockdown to curb the transmission of the virus. A survey was over Five hundred families to complete a questionnaire with questions around symptoms of depression, anxiety, stress, and family affluence. The humans who do not have enough supplies to sustain the lockdown were most affected Families with affluence were found to be negatively correlated with stress, anxiety, and depression. Stress, anxiety, and depression more than others are seen in students and healthcare professionals. The main aim of the paper is to find out how symptoms of depression, anxiety and stress on parents due to COVID-19.

Bovine tuberculosis (bTB) outbreaks, caused by Mycobacterium bovis infection, are a costly animal health challenge. Understanding factors associated with the duration of outbreaks, known as breakdowns, could lead to better disease management policy development. We undertook a retrospective observational study (2012-2018) and employed Finite Mixture Models (FMM) to model the outcome parameter, and to investigate how factors were associated with duration for differing subpopulations identified. In addition to traditional risk factors (e.g. herd size, bTB history), we also explored farm geographic area, parcels/farm fragmentation, metrics of intensity via nitrogen loading, and whether herds were designated controlled beef finishing units (CBFU) as potential risk factors for increased duration. The final model fitted log-normal distributions, with two latent classes (k) which partitioned the population into a subpopulation around the central tendency of the distribution, and a second around the tails of the distribution. The latter subpopulation included longer breakdowns of policy interest. Increasing duration was positively associated with recent (<3 yrs) TB history and the number of reactors disclosed, (log) herd size, beef herd-type relative to other herd types, number of land parcels, area, and being designated a controlled finishing unit (“feedlot”), and having high annual inward cattle movements within the “tails” subpopulation. Breakdown length was negatively associated with year of commencement of breakdown (i.e. a decreasing trend) and non-significantly with the organic nitrogen produced on the farm (N kg/hectare), a measure of stocking density. The latter finding may be due to confounding effects with herd size and area. Most variables contributed only moderately to explaining variation in breakdown duration, that is, they had moderate size effects on duration. Herd-size and CBFU had greater effect sizes on the outcome. The findings contribute to evidence-based policy formation in Ireland.

Background: The associations between long-term exposure to particulate matters (PM) in residential ambiance and obesity are comparatively less elucidated among young adults. Methods: Using 2017 Community Health Survey data with aged 19−29 participants in 25 communities, Seoul, the relationship between obesity and long−term PM10 levels of living district was examined. We defined obesity as overweight (25≤BMI&lt;30) or obese (30≤BMI) using Body Mass Index (BMI) from self-reported anthropometric information. Analysis was conducted sampling weighted logistic regression models by fitting municipal PM10 levels according to individual residence periods with 10 years and more residing in a current municipality. Socio-demographic factors were adjusted over all models and age−specific effect was explored among aged 19–24 and 25–29. Results: Total study population are 3,655 [men 1,680 (46.0%) and aged 19–24 1,933 (52.9%)] individuals. Among the communities with greater level of PM10; 2001–2005, associations with obesity were increased for overall with residence period; 10 years ≤ [Odds ratio, OR 1.071, 95% Confidence interval (CI) 0.969–1.185], 15 years ≤ [OR 1.118, 95% CI 1.004–1.245], and 20 years ≤ [OR 1.156, 95% CI 1.032–1.294]. However, decreased associations were detected for PM10; 2006–2010, and age–specific effects were modified according to the residence period. Conclusions: Although currently PM10 levels are decreasing, higher levels of PM10 exposure at the residential area during the earlier life-time may contribute in increasing obesity among young adults.

It is not established whether SARS-CoV-2 (COVID-19) patients with movement disorders, are at greater risk for more serious outcomes than the larger COVID-19 population beyond the susceptibility associated with greater age. We reviewed electronic health records and conducted telephone interviews to collect the demographics and clinical outcomes of patients seen at our Movement Disorders Center who tested positive for COVID-19 from 8 March 2020 through 6 June 2020. Thirty-six patients were identified, 23 men and 13 women, median age of 74.5 years. They primarily carried diagnoses of idiopathic Parkinson disease (n=22; 61%) and atypical parkinsonism (n=7; 19%) with the balance having other diagnoses. Twenty-seven patients (75%) exhibited alteration in mental status and fifteen (42%) had abnormalities of movement as common manifestations of COVID-19; in 61% and 31%, these were the presenting symptoms of the disease. 67% of patients in our cohort required hospitalization, and the mortality rate was 39%.. These data demonstrate that in patients with movement disorders, the likelihood of hospitalization and death after contracting COVID-19 was substantially greater than in the general population. Patients with movement disorders frequently presented with altered mental status, generalized weakness, or worsening mobility but not anosmia.

Nociceptive threshold (NT) testing is widely used for the study of pain and its alleviation. The end point is a normal behavioural response which may be affected by restraint or unfamiliar surroundings leading to erroneous data. Remotely controlled thermal and mechanical NT testing systems were developed to allow free movement during testing and were evaluated in cats, dogs, sheep, horses and camels. Thermal threshold (TT) testing incorporated a heater and temperature sensor held against the animal’s shaved skin. Mechanical threshold (MT) testing incorporated a pneumatic actuator attached to a limb containing a 1 - 2mm radiused pin pushed against the skin. Both stimuli were driven from battery powered control units attached on the animal’s back, controlled remotely via infra-red radiation from a hand held component. Threshold reading was held automatically and displayed digitally on the unit. The system was failsafe with a safety cutout at a preset temperature or force as appropriate. The animals accepted the equipment and behaved normally in their home environment enabling recording of reproducible TT (38.5 – 49.8°C) and MT (2.7 – 10.1N); precise values depended on species, the individual and the stimulus characteristics. Remote controlled NT threshold testing appears to be a viable refinement for pain research.

The purpose of this study was to assess the extent to which self-esteem and depression mediated the influence of internalized stigma on life satisfaction among Korean out-of-school youths. Cross-sectional data on 318 youths provided information on perceived stigma, self-esteem, depression, life satisfaction, and personal characteristics. A multinomial logistic regression analysis was followed by structured path analysis to investigate the mediation effects. Internalized stigma was negatively associated with life satisfaction. Self-esteem significantly mediated the influence of stigma on depression and the influence of depression on life satisfaction. Further, stigma directly and significantly influenced depression. This study demonstrated that self-esteem and depression were important to the relationship between internalized stigma and life satisfaction. Implications for possible policies and programs with the aim of helping out-of-school youths to integrate and lead successful satisfying lives are discussed.

Purpose: Recently introduced molecules namely long non-coding RNAs (lncRNAs) are associated with various diseases, including breast cancer, and they may have the potential to act as biomarkers. Invasive ductal carcinoma (IDC) is a frequently observed type of breast cancer that diagnosis through immunohistochemical methods. However, no reliable non-invasive markers such as circulating markers have been introduced for it, so far. Materials and methods: The relative quantitation (RQ) of two lncRNAs, RP11-445H22.4 and TINCR, was measured in tumoral tissues and paired adjacent non-tumoral tissues (PANTs) as well as in plasma samples using real-time polymerase chain reaction (RT-PCR). Furthermore, promoter methylation of the two lncRNAs genes was assessed using methylation-specific PCR (MSP). In order to compare the diagnostic values, plasma levels of CA 15-3 were measured as a conventional circulating biomarker using ELISA. The receiver operating characteristic (ROC) curve was used to illustrate the sensitivity and specificity of the potential biomarkers. Results: The RP11-445H22.4 and TINCR genes were upregulated in tumor tissues compared to PANTs (RQ_{RP11-445H22.4} = 2.7, RQ_TINCR = 4.4). Furthermore, the presence of RP11-445H22.4 and TINCR in the plasma of patients was significantly more than healthy controls (RQ_{c.RP11-445H22.4} = 4.12, RQ_c.TINCR = 4.16, P<0.001). The promoters of RP11-445H22.4 and TINCR genes were hypomethylated in the tumoral tissues with a negative correlation with their gene expression. Conclusion: Based on the findings, it can be speculated that the expression levels of these two lncRNAs as well as their promoter methylation can be considered as a therapeutic target and potential biomarker for breast carcinoma.

Exercise induced bronchoconstriction (EIB) is a common complication of athletes and individuals who exercise regularly. It is estimated that about 90% of patients with underlying asthma experience EIB. Sex differences in the prevalence of asthma have been widely reported, with higher rates in boys vs. girls before puberty, and higher rates in women than men after puberty. Because atopy has been reported to occur at higher rates in athletes than in non-athletes, in this study we investigated sex differences in EIB and atopy in athletes. A systematic literature review identified 60 studies evaluating EIB and/or atopy in post-pubertal adult athletes (n=7501). Collectively, these studies reported: 1) a 23% prevalence of EIB in athletes; 2) a higher prevalence of atopy in male athletes vs. females; 3) a higher prevalence of atopy in athletes with EIB; and 4) a significantly higher rate of atopic EIB in male vs. female athletes. Our analysis indicates that the physiological changes that occur during exercise may differentially affect male and female athletes, and suggest an interaction between male sex, exercise, and atopic status in the course of EIB. Understanding these sex differences is important to provide personalized management plans to athletes with underlying asthma and/or atopy.

Purpose: During the COVID-19 pandemic, the health care workers (HCWs) at the frontline have been largely exposed to infected patients, running an high risk of being infected by the SARS-CoV-2 virus. This study investigates the epidemiological, clinical and lifestyles characteristics that might play roles in the susceptibility of HCWs to COVID-19 in a hit Italian hospital. Methods:Demographic, lifestyle, work-related and comorbidities data of 1447 HCWs which underwent a nasopharyngeal swab for SARS-CoV-2 were retrospectively collected. For the 164 HCWs positive for SARS-CoV-2, data about safety in the workplace, symptoms and clinical course of COVID-19 were also collected. Cumulative incidence of SARS-CoV-2 infection was estimated. Risk factors for SARS-CoV-2 infection were assessed using a multivariable Poisson regression. Results: The cumulative incidence of SARS-CoV-2 infection among the screened HCWs was 11.33 (9.72-13.21). Working in a COVID-19 ward, being a former smoker (vs being a person who never smoked) and BMI were positively associated with SARS-CoV-2 infection, whereas being a current smoker was negatively associated with this variable. Conclusions: Assuming an equal accessibility and proper use of PPE of all the HCWs of our Hospital, the great and more prolonged contact with COVID-19 patients remains the crucial risk factor for SARS-CoV-2. Therefore, increased and particular care needs to be focused specifically on the most exposed HCWs groups, which should be safeguarded. Furthermore, in order to limit the risk of asymptomatic spread of SARS-CoV-2 infection, the HCWs mild symptoms of COVID-19 should be considered when evaluating the potential benefits of universal staff testing

Background: Dimethylfumarate (DMF) is an orally administered fumaric acid esters (FAE) approved for plaque psoriasis. The most represented adverse event for incidence reported in all studies regarding multiple sclerosis and psoriasis treatment was flushing followed by gastrointestinal and lymphopenia (AEs). We report our experience on effective management strategies in patients with dimethylfumarate fushing induced. Methods: The purpose of our study is addressed to propose feasibles strategies able to mitigate adverse events developing in order to improve therapy compliance. We report our real life experience of 20 patients affected by mild to moderate plaque psoriasis in treatement with DMF 10 male and 10 female, with 45,4 years old mean age underwent to a reducing a daily dosage regimen with DMF from 120 mg to 30 mg tablets. Patients experience flushing around 30-45 minutes after assuming the medication.per day. Results: Patients achieving a good adherence and efficacious results in terms of PASI 75 reduction after 16 weeks of treatment. Conclusion: DMF is efficacious and has a favorable benefit–risk profile, thanks to the possibility of implementing posology strategies in order to optimize adherence to the therapy.

Introduction: The tumour suppressor protein p53 commonly referred to as guardian of the genome plays important role in preserving the genome through the regulation of programmed cell death, DNA repair, energy metabolism, cell cycle entry or exit and senescence. Mutations in p53 can either result to a loss of tumour suppressor function or gain of oncogenic properties. Hence, mutations in p53 are the most frequent genetic mutational alteration in human cancers, associated with worse prognosis and more aggressive disease outcome. Methods: To assess the mutational hotspots and conserved regions of p53, I analyzed 76 complete p53 protein sequences covering whole exons from the NCBI GenBank database. Multiple sequence alignment (MSA) was done using ClustalX version 2.1. Results: Thirty-five (19) mutations were identified with more frequent mutations in amino acid (aa) position 72 and 79 (Exon 4), amino acid deletion in codon 112-122 (Exon 4), codon 213 (Exon 6), codon 248 (Exon 7), codon 273 (Exon 8) and codon 278 (Exon 8). Mutations at amino acid position 79, 248, 278 located in the DNA-binding domain exhibited more than one alteration in same position. Conclusions: Findings from this study revealed the prevalence of mutations in the DNA binding domain of p53 and the structure-function effect of the mutations. Assessing the pattern and frequency of p53 alterations, and analyzing it thoroughly for each carrier, could help in identifying correlations between p53 status and outcome and possible candidate for gene therapy.

This systematic review investigates the failure rate and marginal bone loss (MBL) of dental implants placed in Solid-organ transplant (SOT) patients compared to healthy controls. Three databases (PubMed, Web of Sciences and the Cochrane Library) were searched up to June 2020 (PROSPERO CRD42019124896). Case-control and cohort studies reporting data failure rate and marginal bone loss (MBL) of dental implants placed in SOT patients were included. The risk of bias of observational studies was assessed through the Newcastle-Ottawa Scale (NOS). Four case-control studies fulfilled the inclusion criteria, all of low risk of bias. Meta-analyses revealed consistently lower implant failure rate than control populations at patient and implant levels. SOT patients had a significant difference of -18% (p-value <0.001) of MLB towards healthy patients. SOT status poses no serious threat to implant survival. Overall, this group of patients presented lower levels of dental implant failure rate and marginal bone loss compared to otherwise healthy patients. Further intervention trials with wider sample size and longer follow-ups are necessary to confirm these summary results.

Identified by the eponym “Edwards’ Syndrome,” trisomy 18 (T18) represents the second most common autosomal trisomy after T21. The pathophysiology underlying the extra chromosome 18 is a nondisjunction error, mainly linked with the advanced maternal age. More frequent in female fetuses, the syndrome portends high mortality, reaching a rate of 80% of miscarriages or stillbirths. The three-step evaluation includes first trimester screening for fetal aneuploidy using a combination of maternal age, fetal nuchal translucency thickness, fetal heart rate and maternal serum free ß-hCG and PAPP-A; followed by the research for fragments of fetal DNA in maternal blood; and, finally, invasive techniques leave to the established diagnosis. Starting with the first trimester scan, selected ultrasound findings should be investigated to define not only the impact of the genetic problem on the fetus, but also to address the prenatal counselling. Previous series underline that T18 is not uniformly lethal. An active dialogue on the choices in the management of infants with T18 has emerged, sustained by the transition from the comfort care to the intervention attitude. Survival rates for individuals with supposedly fatal conditions have increased. In this novel scenario, an ad hoc counselling is pivotal. To support it, a comparative analysis by pictorial assays between ultrasound and autopsy findings could be beneficial. We provide an illustrative tool from a clinical case managed in early second trimester, with the purpose to strive a balanced approach in the hard choice faced by couples of fetuses with T18.

Background: This study discerns surgeons’ attitudes and practices in the determination of heart valve replacement for patients with endocarditis due to intravenous drug use (IVDU-IE). We aimed to identify factors contributing to surgeons’ decision-making process for initial and recurrent surgical heart valves, and the availability of institutional guidance. Methods: An IRB approved, anonymous mixed-methods survey instrument was designed and validated with 24 questions. Cardiothoracic surgeons in the U.S. and globally were recruited with a total of 220 enrolling in the study with 176 completing every question on the survey. Results: A cluster analysis revealed that although surgeons can be divided into sub-groups based on their previous experience with valve replacements, these groups are not perfectly homogenous, and the number of identified clusters is dependent on technique used. ANOVA analysis revealed that the variables that most clearly divided the surgeons into subgroups were, in order of importance, years of practice, number of valve replacements, and geography. Conclusions: Our analysis showed heterogeneity among cardiothoracic surgeons regarding how they make clinical decisions regarding re-operative valve replacement related to IVDU-IE Therefore, an opportunity exists for an interprofessional team to develop guidelines to decrease variability in surgical decision-making regarding valve replacement associated with IVDU-IE

Canine Hemangiosarcoma (HSA) is a devastating cancer affecting blood vessels in numerous sites within the body that is primarily seen in middle to older aged dogs. It is marked by its rapid aggressive metastatic pathology that often results in a lack of apparent symptoms in early stages. In most cases, disease becomes apparent due to hemorrhagic events following the rupture of the malignant vascular cell structures that can capture and pool blood cells, resulting in necrosis of the affected tissues. The poor survival times in affected patients cause a hindrance to the ability to carry out large scale studies, leaving numerous knowledge gaps to be filled in future research. The pathologic similarities between this and human angiosarcoma (HA) provides the potential for translatable research to be carried out that would improve outcomes across species. Here, current knowledge is outlined in order to improve understanding HSA holistically and suggest future direction. Emphasis is placed on the potential to improve veterinary practices in ways that will improve the ability to quickly and accurately diagnose patients in order to establish better client communication and provide clarity in collaborating to create the best informed treatment plan possible.

Celecoxib as adjuvant therapy has been shown in a small randomized trial for Covid-19 to prevent clinical deterioration and rapidly improve thoracic computerized axial tomography (CT-chest)¹. Multiple descriptive trials of high dose famotidine (both inpatient and outpatient) have demonstrated clinical response^2,3,4. We describe the rapid clinical responses after increasing the celecoxib dosage to 400mg bid with high dose famotidine 80mg qid in both a critical inpatient who on baseline required 40 liters per minute high flow nasal insufflation and an outpatient who declined admission but had critical Covid-19 biomarkers.

Emerging and reemerging pathogens is a global challenge for public health. Recently, a novel coronavirus disease emerged in Wuhan, Hubei province of China, in December 2019. It is named COVID-19 by World Health Organization (WHO). It is known to be caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that affects the lower respiratory tract and manifests as pneumonia in humans. Coronaviruses (CoVs) are structurally more complicated as compared to other RNA viruses. This viral epidemic has led to the deaths of many, including the elderly or those with chronic disease or compromised immunity. Viruses cause infection and diseases in humans of varying degrees, upper respiratory tract infections (URTIs) cause common cold while lower respiratory tract infections induce pneumonia, bronchitis, and even severe acute respiratory syndrome (SARS). The costs of COVID-19 are not limited. It equally affects all the medical, sociological, psychological, and economic aspects globally. This is regarded as the third deadly outbreak in the last two decades after Severe Acute Respiratory Syndrome SARS (2002–2003) and Middle East Respiratory Syndrome MERS (2012). Based on the sequence homology of SARS-CoV-2, different animal sources including bats, snakes, and pangolins have been reported as potential carriers of this viral strain. Real-time RT-PCR represents the primary method for the diagnosis of new emerging viral strain SARS-CoV-2. The transmission dynamics suggest that SARS-CoV-2 is transmitted from person-to-person through direct contact or coughing, sneezing, and by respiratory droplets. Several anti-viral treatments including lopinavir/ritonavir, remdesivir, chloroquine phosphate, and abidor are also suggested with different recommendations and prescriptions. Protective and preventive strategies as suggested by various health organization i.e. WHO and US Center for Disease Control and Prevention (CDC) must be adopted by everyone. This review covers the important aspects of novel COVID-19 including characteristics, virology, symptoms, diagnostics, clinical aspects, transmission dynamics, and protective measures of COVID-19.

Heart Rate Monitors (HRMs) are an indispensable tool for controlling training parameters of healthy athletes. They became a source of information about stress heart rhythm disturbances, recognized as unexpected increases in heart rate (HR), which can be life-threatening for athletes. Most HRMs do not recognize the type of arrhythmia, confusing them with artifacts. The aim of the study was to assess the usefulness of ECG recording functions by sports HRMs among endurance athletes, coaches, and physicians in comparison with other basic and hypothetical functions. We conducted 3 surveys among endurance athletes (76 runners, 14 cyclists, and 10 triathletes), as well as 10 coaches and 10 sports doctors to obtain information on how important ECG recording is, and what functions of HRMs should be improved to meet their expectations in the future. The respondents were asked questions regarding use and hypothetical functions, as well as preference for HRM type (optical/strap). For athletes, the 4 most important functions were distance traveled, pace, instant heart rate, and information about reaching the oxygen threshold. ECG recording was the 8th and 9th most important for momentary and continuous, respectively. Coaches opined more importance to ECG recording. Doctors placed ECG recording as most important. All participants preferred optical HRMs to strap HRMs. Research on the improvement and implementation of HRM functions shows slightly different preferences of athletes compared to coaches and doctors. Suspected arrhythmia increases the value of the HRM’s ability to record ECGs during training by athletes and coaches. For doctors, this is the most desirable feature in any situation. Considering the expectations of all groups continuous ECG recording during training will significantly improve the safety of athletes.

Rheumatoid arthritis (RA); is a chronic systemic autoimmune disease which causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of disease-modifying anti-rheumatic drugs (DMARDs) can influence treatment efficacy and toxicity. This study explored the relationship between DMARD metabolising gene variants and plasma metabolite levels in RA patients. DMARD metabolite concentrations were determined by tandem mass-spectrometry in plasma samples from 100 RA patients with actively flaring disease, collected at two intervals. Taqman-probes were used to discriminate single nucleotide polymorphism (SNP) genotypes in cohort genomic DNA: rs246240 (ABCC1), rs1476413 (MTHFR), rs2231142 (ABCG2), rs3740065 (ABCC2), rs4149081 (SLCO1B1), rs4846051 (MTHFR), rs10280623 (ABCB1), rs16853826 (ATIC), rs17421511 (MTHFR) and rs717620 (ABCC2). Mean plasma concentrations of methotrexate (MTX) and MTX-7-OH metabolites were higher (p<0.05, C.I. 95%) at baseline in rs4149081 GA genotype patients. Patients with rs1476413 SNP TT or CT alleles in the have significantly higher (p<0.001, 95% C.I) plasma poly-glutamate metabolites at both study time points and correspondingly elevated disease activity scores. Patients with the rs17421511 SNP AA allele reported significantly lower pain scores (p<0.05, 95% C.I.) at both study intervals. Genotyping strategies could help prioritise treatments to RA patients most likely to gain clinical benefit, whilst minimizing toxicity.

To predict how the COVID-19 pandemic progresses, we developed a systematic method for predicting disease outcomes. In the method, we evaluate how personal disease outcomes are mainly affected by viral concentration and exposure time and four defense mechanisms: human innate immunity/host response, acquired immune response, inflammation resolution and micro circulation, and the available space in the thorax cage. By considering how pandemic measures affect viral exposure and those mechanisms, we found many pandemic measures are misused or abused to deliver long-term adverse impacts. We noted that lifestyles have been changed as a result of movement restriction measures. By using the method, we found that altered lifestyles are predicted to raise infection rate, disability and death risks in the future. We show that a person can use personal, environmental, emotional factors to reduce infection rate and death risk. To prove the validity of this finding, we extensively examined medical research models, holistic and reductionist models, epidemiological models, disease risk factors, etc, and found that population methods are unfit for studying holistic health, statistical population does not exist in most clinical trials, mathematical models were misused for studying disease properties for a population, mathematical equations for modeling personal diseases are beyond human ability to solve, statistical models are misused, population-derived treatments are inherently dangerous to patients, vaccines have limited benefits due to unique lung structure and rapid RNA mutation, and immune system damage is caused by fast viral replication rate. We found that altering biological properties to improve the defense mechanisms could prevent a super majority of deaths and prevent the virus from reaching a point to damage the immune system. For vulnerable persons, such measure is a viable strategy for surviving from the pandemic. As a whole, holistic personalized medicine is more powerful than population-based reductionist treatment by one to several orders of magnitudes. We urge people do their parts to force the medical establishment to abandon population treatment models that are responsible for failure of medicine and dissemination of misleading and factually wrong information on the effectiveness of medical treatments.

The effect of Alzheimer's disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. Alzheimer's disturbs the life of at least five million persons in the USA. CD4+ T cells could both exacerbate and reduce AD symptoms. Regulating CD4+ T cells homing to the leaky blood-brain barrier (BBB) constitutes a new hope for enhancing AD prognosis. Alzheimer's drugs such as Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Razadyne) and memantine are known to play an important part in regulating the neurotransmitters mechanisms. However, little is known about the effect of these drugs on CD4+ T cells homing. In this review, we focus on current and new drugs that could modulate CD4+ T cells interactions with the BBB in AD.

Rats fed a high-fat diet with a single streptozotocin (STZ) injection developed obesity, prediabetes, cardiac hypertrophy and diastolic dysfunction. Here we aimed to explore the renal consequences of prediabetes in the same groups of rats. Male Long-Evans rats were fed normal chow (CON; n = 9) or high-fat diet containing 40% lard and were administered STZ at 20 mg/kg (i.p.) at week four (prediabetic rats, PRED, n = 9). At week 21 cardiac functions were examined (Koncsos et al., 2016) and blood and urine samples were taken. Kidney samples were collected for histology, immunohistochemistry and for analysis of gene expression. High-fat diet and streptozotocin increased body weight gain and visceral adiposity, and plasma leptin, elevated fasting blood glucose levels, impaired glucose and insulin tolerance, despite hyperleptinemia, plasma C-reactive protein concentration decreased in PRED rats. Immunohistochemistry revealed elevated collagen IV protein expression in the glomeruli, and Lcn2 mRNA expression increased, while Il-1β mRNA expression decreased in both the renal cortex and medulla in PRED vs. CON rats. Kidney histology, urinary protein excretion, plasma creatinine, glomerular Feret diameter, desmin protein expression and cortical and medullary mRNA expression of TGF-β1, Nrf2, PPARγ were similar in CON and PRED rats. Reduced AMPKα phosphorylation of the autophagy regulator Akt was the first sign of liver damage, while serum lipid and liver enzyme levels were similar. In conclusion, glomerular collagen deposition and increased lipocalin-2 expression were the early signs of kidney injury, while most biomarkers of inflammation, oxidative stress and fibrosis were negative in the kidneys of obese, prediabetic rats with mild heart and liver injury.

This study aimed to rank cancers based on the strength of the relationship between the comprehensive mRNA expression levels of the most harmful or protective genes and patient survival. Using The Cancer Genome Atlas dataset that includes the RNA sequencing and c linical data, we investigated not only gene specific prognostic availability, but also comprehensive prognostic availability of prognostic genes filtered by the Cox coefficient values, and ranked cancers using a specially designed prognostic indicator. Usi ng Kaplan Meier plots, we found that cancers vary in the strength of the influence of their prognostic genes, and can be ranked based on this finding. There is a high probability that the treatment developed by using methods that reduce or increase the exp ression levels of biomarkers, for cancers that ranked at the bottom will not be efficient. The results of this study could be used as scientific evidence for the same.

Abstract Mastitis is a common disease of dairy animals. The source of mastitis infection may be regarded as contagious or environmental. A wide range of pathogens including bacteria, viruses, fungi, and the toxins of these pathogens can cause the disease. Mastitis is generally associated with poor hygienic and husbandry practices. The primary reservoir of infection is the mammary gland. The infectious agent enters through the milk canal, interacts with the mammary tissue/cells and multiplies. Most contagious mastitis causing pathogens are spread during milking. Most other species are opportunistic invaders from the cow's environment.

Cervical cancer is a common malignancy in women and has a poor prognosis.More and more studies have shown that autophagy disorder is closely related to the occurrence of tumors. However, the prognostic role of autophagy gene in cervical cancer is still unclear. In this study, we constructed the risk signatures of autophagy related genes to predict the prognosis of cervical cancer. The expression profiles and clinical information of autophagy gene sets were downloaded from the TCGA and GES52903 queues as training sets and validation sets. The cervical normal tissue expression profile data from UCSC XENA website is GTEx data as a supplement to TCGA normal cervical tissue. Univariate COX regression analysis of 17 different autophagy genes with the Consensus approach tumor samples from the TCGA is divided into six subtypes, and the clinical traits in the six subtypes have different distribution, with further then absolute shrinkage and selection operator (LASSO) and multiariable COX regression method finally got seven autophagy genetic risk model is constructed, in the training set, the survival rate of high risk group is lower than the low risk group (p < 0.0001), the validation set,The AUC area of the receiver operating characteristic (ROC) curve, the training set is 0.894, and the verification set is 0.736. We find that the high and low risk score is closely related to the TMN stage (All P is less than 0.05).The nomogram shows that the risk score combined with other indicators such as age, G,T,M, and N better predicts 1-year, 2-year, 3-year survival, and the DCA curve shows that the risk model combined with other indicators produces better clinical efficacy.Then immune cells in 28 in the enrichment score, there were statistically significant differences, high and low risk most GSEA enrichment analysis, the main enrichment in G2 / M checkpoint high-risk score, Genes defining epithelial and mesenchymal transition, raised in response to the low oxygen levels (hypoxia) gene, gene is important to the mitotic spindle assembly, these are closely related with the occurrence of tumor . In conclusion, our constructed autophagy risk signature may be a prognostic tool for cervical cancer.

In this paper we explore extending the concept of common cross-study Common Data Element concepts beyond simple demographics to cover disease-specific concepts relevant to imaging. We test interactively linking the resulting database to the associated images in a federated manner. We examine the use of existing standards, not only for terminology, but for interchange of serialized data in forms familiar to imaging and clinical trials specialists and their dedicated systems. Our intent is to perform preliminary work to inform both the upcoming Imaging Data Commons specifically, as well as more general integration projects beyond imaging.

Many universities and colleges worldwide suspended classroom teaching due to the novel coronavirus pandemic and switched to online teaching. The current cross-sectional study was carried out to analyze the impact of lockdown due to coronavirus disease 2019 (COVID-19) pandemic on the academic performance of veterinary medical students and researchers. Veterinary medical students and researchers were invited to answer an online google form questionnaire. A total of 1398 participants were from 92 different countries answered the questionnaire with response rate of 94.52%. The data showed that COVID-19 pandemic lockdown affected the academic performance of most participants (96.7%) with varying degrees. The mean evaluation scores for the online education in general was 5.06 ± 2.43 while that for the practical parts was 3.62± 2.56. Although online education provides an opportunity for self-study. The main challenge online education faces in veterinary medical science is how to give practical lessons. Since most of the subjects are practical; therefore, it is not easy to learn it online. Students think that it is difficult to fulfill the veterinary competencies only with online education system. Online education can be improved by making it more interactive, showing medical procedures in real situations, giving concise information, and providing 3D virtual tools to mimic the real situation.

The SARS-CoV-2 virus that causes the COVID-19 disease has wreaked havoc on the world community in terms of every imaginable parameter. The research output on COVID-19 has been nothing short of phenomenal, especially in the medical and biomedical sciences, where the search for a potential vaccine is being conducted in earnest. Much of the advanced research has been distributed in the leading medical journals, including the Journal of the American Medical Association (JAMA), where the latest research is distributed on a daily basis. The purpose of this paper is to provide some perspectives on 44 interesting and highly topical research papers that have been published in JAMA, at the time of writing, within the past two weeks. The diverse topics include public health, general medicine, internal medicine, oncology, paediatrics, geriatrics, and biostatistics.

This article aims to review the screening and diagnostic tools for eating disorders (ED). Eating disorders represent a complex pathology defined by an imbalance between hunger and satiety, installed in an emotional, traumatic, or conflictive context. Recently, the emphasis regarding ED is focused on the link between genetics, mental pathology, and the somatic and metabolic phenotype and early detection. Early detection and intervention can assure a better recovery and can improve a lot the quality of life of these patients. Methods: We selected ten articles of central importance on the topic in a systematic search on eight databases, articles selected on the type of scales, and size of the study. Results: We identified eight questionnaire scales used in large trials in ED disorders in the scanned literature, choose because we consider it the most accurate and the ones that evaluate best the pathology and the elements that are important as specific traits in ED. There are interview-type scales and self-administered scales. Interview scales are characterized by assessments of symptoms and diagnosis, while self-administered assess particular traits and the possibility of further development of eating disorders. The majority of the scales evaluated were described and used in adult populations. From all the scales assessed and analyzed, only three are described at the child population – it is EAT-26 (> 16 years), EDI-3 (>13 years), and ANSOCQ (> 13 years). Conclusions: It is essential to develop specific scales for people under 18 years of age, given the increasing incidence of ED among children and the need for early detection and appropriate intervention. Early detection of ED in children implies a simple and accurate evaluation at the primary care level or in schools, as the course of the disease can be subclinical for several years. Moreover, the need for accurate scales and telemedicine testing and diagnosis is of high importance during the COVID-19 pandemic as youth are at particular risk being psychologically affected due to disrupted education and social interactions - at a critical time.

Oxygen is a pulmonary vasodilator and plays an important role in mediating circulatory transition from fetal and postnatal period. Alveolar oxygen tension (PAO2) and pulmonary arterial PO2 are the main factors that influence hypoxic pulmonary vasoconstriction (HPV). Inability to achieve adequate pulmonary vasodilation at birth leads to persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen is the mainstay of PPHN management. However, optimal monitoring of oxygenation to achieve low pulmonary vascular resistance (PVR) and optimize oxygen delivery to vital organs is not known. Noninvasive pulse oximetry measures peripheral saturations (SpO2) and ranges 91-95% are recommended during acute PPHN management. However, for a given SpO2, there is wide variability in arterial oxygen tension, especially with variations in hemoglobin type (transfusions), pH and body temperature. This review evaluates the role of alveolar, preductal, postductal, and mixed venous oxygen tension and SpO2 in the management of PPHN. Translation and clinical studies suggest maintaining an arterial oxygen tension of 50-80 mmHg to help decrease PVR and optimize pulmonary vasodilator management. Nevertheless, there are no randomized clinical trials evaluating outcomes in PPHN based on targeting SpO2 or PO2. However, most critically ill patients have umbilical arterial catheters and postductal arterial oxygenation may not be an accurate assessment of oxygen delivery to vital organs or factors influencing HPV. The mixed venous oxygen tension from umbilical venous catheter blood gas may assess pulmonary arterial PO2 and potentially predict HPV. It is crucial to conduct randomized controlled studies with different PO2/SpO2 ranges and compare outcomes in PPHN.

Osteoarthritis is a painful, disabling condition which is increasing in prevalence as a result of an ageing population. With no recognised disease limiting therapeutics, arthroplasty of the hip and knee is the most common and effective treatment for lower limb osteoarthritis, however lower limb arthroplasty has a finite life-span and a proportion of patients will require revision arthroplasty. With increasing life expectancy and an increasing proportion of younger (<65 years) patients undergoing arthroplasty, the demand for revision arthroplasty after implant failure is also set to increase. Statins are cholesterol modulating drugs widely used for cardiovascular risk reduction which have been noted to have pleiotropic effects including potentially influencing arthroplasty survival. In vitro studies have demonstrated pleiotropic effects in human bone cells, including enhancement of osteoblastogenesis following simvastatin exposure, and in vivo studies have demonstrated that intraperitoneal simvastatin can increase peri-implant bone growth in rats following titanium tibial implant insertion. There is evidence also that statins may also influence osseointegration, enhancing bone growth at the bone-implant interface, subsequently improving the functional survival of implants. Data from the Danish Hip Arthroplasty Registry and Clinical Practice Research Datalink in the UK suggest a reduction in the risk of lower limb revision arthroplasty in statin ever-users vs never users, and a time dependent effect of statin administration on reduction in risk of revision. In this article we review the clinical and scientific evidence linking statins and risk of revision arthroplasty.

Neuroinflammation, defined as inflammatory reactions mediated by cytokines, chemokines, reactive oxygen species, and secondary messengers in the central nervous system (CNS) including the brain and spinal cord is the basis of many neurological disorders. Recently, erythropoietin (EPO) has been considered and studied as a modulator of neuroinflammation. On this article minireview of pathophysiology of neuroinflammation and the neuroprotective effects of EPO is discussed and a case of subacute huge subdural hematoma with double mydriasis operated urgently, treated with low daily dose (vs high dose once or twice a month in the literature) of EPO and recovered fully and discharged home with good consciousness is reported. In addition, the probable unfavorable outcome of erythropoietin administration in patients with neuroinflammation in COVID-19 is considered.

Objectives: to assess the knowledge level of parents from the central region of Saudi Arabia about oral health and care of preschool children and its relation with sociodemographic variables, parents‟ self-perception toward their dental health, importance of teeth and frequency of dental visits. Methods: a random sample of 754 parents participated in this cross-sectional study and completed an internationally accepted questionnaire. Chi square test and logistic regression analysis were used to analyze the data (p<0.05). Results: mean knowledge score of the parents was 4.8 (out of 11). Less than 20% of the parents were knowledgeable about the best position for tooth brushing, the concentration of fluoride in a child‟s toothpaste, timing of first dental check-up, and best time to give a sugary snack. Mothers, parents with high educational level and family income, parents with positive attitude towards teeth and excellent self-perception of their dental health were significantly more likely to score higher (p<0.05). Conclusions: knowledge of parents about oral health and care of preschool children in the central region of Saudi Arabia was deficient. Gender, education level of parents, family income, attitude about teeth and self-perception of parents‟ own dental health were factors which influenced their knowledge. To improve parents‟ knowledge, role of health professionals should be improved and TV commercials directed toward the areas which had gaps in knowledge.

The intracellular calcium concentration ([Ca2+]i) modulation plays a key role in the regulation of cellular growth and survival in normal cells and failure of [Ca2+]i homeostasis is involved in tumor initiation and progression. Here we show that inhibition of Furin by its naturally occurring inhibitor the prodomain ppFurin in the MDA-MB-231 breast cancer cells resulted in enhanced SOCE through TRPC6 activation that associated reduced cells malignant phenotype. Expression of ppFurin in a stable manner in MDA-MB-231 and the melanoma MDA-MB-435 cell lines inhibits Furin activity as assessed by in vitro digestion assays. Accordingly, cell transfection experiments, revealed that the ppFurin-expressing cells are unable to process adequately the PC substrates proVEGF-C and proIGF-1R. Compared to MDA-MB-435 cells, expression of ppFurin in MDA-MB-231 significantly induces Ca2+ entry which is impaired by silencing of TRPC6 expression. Analysis of TRPC6 activation revealed its up-regulated tyrosine phosphorylation in ppFurin-expressing MDA-MB-231 cells. The expression of ppFurin in MDA-MB-231 cells reduced their viability and ability to migrate and enhanced their sensitization to the apoptosis inducer hydrogen peroxide. These findings suggest that Furin inhibition by ppFurin may be a useful strategy to interfere with Ca2+ mobilization leading to breast cancer cells malignant phenotype repression and reduction of their resistance to treatments.

Age-related sarcopenia meaningfully increases the risks of functional limitations and mortality in the elderly. Although circulating microRNAs (c-miRNAs) are associated with aging-related cellular senescence and inflammation, the relationships between c-miRNAs and sarcopenia in the elderly remain unclear. This study investigates whether circulating myo-miRNAs and inflammation-related miRNAs are associated with sarcopenia in the elderly. This study recruited 77 eligible subjects (41 males and 36 females) from 597 community-dwelling older adults, and then divided into normal (n=24), dynapenic (loss of muscular function without mass, n=35), and sarcopenic groups (loss of muscular function with mass, n=18). Moreover, myo-miRNAs (c-miRNA-133a and c-miRNA-486), inflammation-related miRNAs (c-miRNA-21 and c-miRNA-146a), and inflammatory-related cytokine levels in plasma were determined using quantitative polymerase chain reaction and ELISA, respectively. The results demonstrated that sarcopenic group exhibited lesser skeletal muscle mass index (SMI), handgrip strength, and gait speed, as well as, lower c-miR-486 and c-miR-146a levels, compared to those of normal and dynapenic groups. Moreover, c-miR-486 level was positively related to SMI (r=0.334, P=0.003), whereas c-miR-146a level was positively associated with SMI (r=0.240, P=0.035) and handgrip strength (r=0.253, P=0.027). In the receiver operating characteristic analysis for predicting sarcopenia, the area under the curve in c-miR-486 was 0.708 (95% confidence interval: 0.561-0.855, P=0.008) and c-miR-146a was 0.676 (95% CI: 0.551-0.801, P=0.024). However, no significant relationships were observed between SMI/ handgrip strength/gait speed and plasma myeloperoxidase/interleukin-1?/interleukin-6 levels. In conclusion, myo-miRNA (c-miR-486) and inflammation-related miRNA (c-miR-146a) are superior to inflammatory peroxide/cytokines in plasma for serving as critical biomarkers of age-related sarcopenia.

Background:Peripheral neuropathy (PN) can result in either partial or complete loss of distal sensation resulting in an increased fall risk. Walkasins^® uses a shoe insert to detect the magnitude and direction of sway and sends signals to a leg unit that provides sensory balance cues. The objective of this case report is to describe the long-term influence of the Walkasins^® lower limb sensory neuroprosthesis on balance and gait for an individual with diabetic PN.Case Description:A fifty-one-year-old male with a 3-year history of PN and a 10-year history of type II diabetes mellitus was fitted with Walkasins^® and utilized the shoe inserts 8-10 hours/day for more than 1 year. Although, vibration and tactile thresholds were severely impaired at his 1^st metatarsophalangeal joint and the lateral malleolus bilaterally he could perceive tactile stimuli from the Walkasins^® above the ankles.Outcomes:Following Walkasins^® use, his Activities-specific Balance Confidence Scale (ABC) scores improved from 33% to 80%. His mean Vestibular Activities of Daily Living (VADL) scores decreased from 3.54 to 1. His Functional Gait Assessment (FGA) scores increased from 13/30 to 28/30 and his miniBESTest scores improved from 15/28 to 26/28. Gait speed increased from 0.23 m/sec to 1.5 m/sec. The patient described a decrease in pain and cramping throughout his lower extremities and an increase in function.Discussion:Gait and balance improved with the use of the Walkasins^® and participation in the Neuro Wellness Program. This improvement suggests that the use of sensory substitution devices, such as the Walkasins^®, may replace sensory deficits related to gait and balance dysfunction experienced by patients with PN. Further research is needed to determine if other patients will have a similar response and what the necessary threshold of sensory function is to benefit from use of the Walkasins^®.

Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids like total cholesterol (TCH), LDL- and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. This study aimed to investigate the relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities and erythrocyte membrane fluidity in 58 depressive children and adolescents, as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children's Depression Inventory (CDI), lipid profile by standard biochemical procedures, LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. We are the first to report that omega-3 FAs increase after 12 weeks of supplementation large HDL subfractions (anti-atherogenic) and decrease small HDL subfractions (pro-atherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder.

The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common, paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyse available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

Background – The profound impact of COVID-19 on the U.S. healthcare industry cannot be overstated. Telemedicine utilization exploded virtually overnight as healthcare systems, hospitals, and clinical practices rushed to implement this delivery model to ensure accessibility and continuity of patient care access across myriad service lines and dimensions. Objective – The purpose of this systematic literature review is to examine the measures that were implemented to accommodate community and individual patient needs not only to afford access to critical services, but to also maintain safety standards for affected parties. Methods – Boolean operators were crafted with the expressed intent of identifying articles within multiple database domains germane to our chosen topic. Results – 52,206 articles were captured from a general search query and subsequently distilled to 44 through group consensus based on pertinence to our basic research question. The four health service lines identified encountered similar, surmountable obstacles in their care delivery models, but adapted accordingly to the respective needs of their patient populations. Conclusion – This review showcased the healthcare industry’s ability to rapidly acclimate and change due to the pervasive spread of COVID-19 throughout the U.S. Although imperfect, unique responses were developed within telemedicine platforms to broadly and effectively mitigate disruptions in care and treatment modalities.

Current case definitions of schizophrenia (DSM-5, ICD), made through a consensus among experts, are not cross-validated and lack construct reliability validity. The aim of this paper is to explain how to use bottom-up pattern recognition approaches to construct a reliable and replicable nomothetic network reflecting the direct effects of risk resilience (RR) factors, and direct and mediated effects of both RR and adverse outcome pathways (AOPs) on the schizophrenia phenome. This study was conducted using data of 40 healthy controls and 80 patients with schizophrenia. Using partial least Squares (PLS) analysis, we found that 39.7% of the variance in the phenomenome (lowered self-reported quality of life) was explained by the unified effects of AOPs (IgA to tryptophan catabolites, LPS, and the paracellular pathway, cytokines, and oxidative stress biomarkers), the cognitome (memory and executive deficits), and symptomatome (negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, formal thought disorders); 55.8% of the variance in the symptomatome was explained by a single trait extracted from AOPs and the cognitome; and 22.0% of the variance in the latter was explained by the RR (Q192R polymorphism and CMPAaase activity, natural IgM, and IgM levels to zonulin). There were significant total effects (direct + mediated) of RR and AOPs on the symptomatome and phenomenome. In the current study, we built a reliable nomothetic network that reflects the associations between RR, AOPs, and the phenome of schizophrenia and discovered new diagnostic subclasses of schizophrenia based on unified RR, AOPs, and phenome scores.

Glucocorticoids promote muscle atrophy by inducing a class of proteins called atrogenes, resulting in reductions in muscle size and strength. In this work, we evaluated whether a mouse model with pre-existing diet-induced obesity had altered glucocorticoid responsiveness. We observed that all animals treated with the synthetic glucocorticoid dexamethasone had reduced strength, but that obesity exacerbated this effect. These changes were concordant with more pronounced reductions in muscle size, particularly in Type II muscle fibers, and potentiated induction of atrogene expression in the obese mice relative to lean mice. Furthermore, we show that the reductions in lean mass do not fully account for the dexamethasone-induced insulin resistance observed in these mice. Together these data suggest that obesity potentiates glucocorticoid-induced muscle atrophy.

COVID-19 pandemic event requires a rapid response from various organizations at the international and national levels. One important response is the provision of information sharing facilities and monitoring of the spread of cases around the world, JHU CSSE developed the Dashboard in January 2020 and followed by WHO the same month for the WHO COVID-19 dashboard. Both dashboards have distributed information as expected by the user with their respective pros and cons. JHU CSSE Dashboard provides faster information with good access to mobile device users even though the display and color selection are less attractive. Information on the WHO COVID-19 Dashboard is often late but more data appearances and variations and comparisons between countries can be made. In the Indonesian context, ESSC for COVID-19 Geoportal as Esri Indonesia initiative has been developed with the support of data and information from various parties and developed with the principles of big data management which are fully supported by adequate spatial portal developer software from Esri. Particularly in Indonesia, there is not yet an adequate system to support spatial based decision making at the local level, therefore the development of a GIS dashboard to support provincial and district governments is highly recommended.

Phylogeny construction can help to reveal evolutionary relatedness among molecular sequences. The spike (S) gene of SARS-CoV-2 is the subject of an immune selective pressure which increases the variability in such region. This study aimed to identify mutations in the S gene among SARS-CoV-2 sequences collected in the Middle East and North Africa (MENA), focusing on the D614G mutation, that has a presumed fitness advantage. Another aim was to analyze the S gene sequences phylogenetically. The SARS-CoV-2 S gene sequences collected in the MENA were retrieved from the GISAID public database, together with its metadata. Mutation analysis was conducted in Molecular Evolutionary Genetics Analysis software. Phylogenetic analysis was done using maximum likelihood (ML) and Bayesian methods. A total of 553 MENA sequences were analyzed and the most frequent S gene mutations included: D614G=435, Q677H=8, and V6F=5. A significant increase in the proportion of D614G was noticed from (63.0%) in February 2020, to (98.5%) in June 2020 (p<0.001). Two large phylogenetic clusters were identified via ML analysis, which showed an evidence of inter-country mixing of sequences, which dated back to February 8, 2020 and March 15, 2020 (median estimates). The mean evolutionary rate for SARS-CoV-2 was about 6.5 × 10^-3 substitutions/site/year based on large clusters’ Bayesian analyses. The D614G mutation appeared to be taking over the COVID-19 infections in the MENA. Bayesian analysis suggested that SARS-CoV-2 might have been circulating in MENA earlier than previously reported.

Brucellosis is a multi-system infectious disease that exhibits with various manifestations and complications. Neurobrucellosis is a rare but serious presentation of brucellosis that can be discovered in every stages of the disease. Laboratory tests and physical examination and patient history are generally the basis for diagnosing the disease. It has both insidious and prolonged clinical course of the disease and long-term therapies. Also the most common pattern of exhibition is subacute or chronic. We reported a case of young female who had history of painless weakness in the right lower limb (proximal and distal) that started gradually and had progressed over the time, and after a month she felt weakness in the left lower limb with the same pattern. Lumbosacral Magnetic resonance imaging (MRI) with and without contrast was shown evidence of enhancement thickening of caudal equina ventral roots. Brucella antigen titer was positive, the result was 1/160. And other clinical tests were normal. Patient treated with Intravenous injection (IV) Rifampicin and Intravenous Cotrimoxazole. patient was discharged with good health and continuinng all two medications for 5 months. The descision was taken to report this case as a result of entire respond in patient’s illness after a enduring disease. Neurobrucellosis is a treatable disease in which it would be better to consider a high indication of suspicion. Due to if ignored, it may cause significant morbidity and mortality.

Rotaviruses are highly infectious and typically transmitted by fecal-oral route via in the tropics and leading the cause of diarrheal deaths in children of developing countries, besides causing significant economic impacts like neonatal disease agents of domestic animals. This present report aims to present the clinical and diagnostic findings of two confirmed cases of rotavirus (RV) infection in orphaned Leopardus tigrinus (Schreber, 1775) and Leopardus pardalis (Linnaeus, 1758), the first register of the infection by group A rotavirus in these species. Both felids were rescued in the Pará State Amazon Brazil by the IBAMA (the Brazilian Institute of Environment and Renewable Natural Resources), and treated by veterinarians into intensive care ward in a public Environmental Park of Belém city. After the adaptation period to the quarantine, these animals showed non-specific symptoms of acute fulminant gastroenteritis. Rotavirus group A antigen was identified in blood and faecal samples of L. tigrinus analyzed by immunochromatography (ICG) and immunoassay methods (ELISA) at the Virology Laboratory of the Institute Evandro Chagas. The animals died within few days during the clinical exacerbation unresponsive to current treatment, its necropsies and histopathological analysis were performed in the Laboratory of Veterinary Pathology of the Federal Rural University of Amazonia (UFRA). Despite the compatible pathologic findings of rotavirus infection in both animals, the atypical hemorrhagic character was a curious finding, considering the presumed etiology.

The performance of choice-reaction tasks during athletic movement has been demonstrated to evoke unfavorable lower limb biomechanics. However, the mechanism of this observation is unknown. We conducted a systematic review examining the association between 1) the biomechanical and functional safety of unplanned sports-related movements (e.g. jumps/runs with spontaneously indicated landing leg/cutting direction) and 2) markers of perceptual-cognitive function (PGF). A literature search in three databases (Pubmed, ScienceDirect, Google Scholar) identified five relevant articles. Study quality, rated by means of a modified Downs & Black checklist, was moderate to high (average: 13.5/16 points). Four of five papers, in at least one parameter, found either an association of lower PGF and reduced task safety or significantly reduced task safety in low vs. high PGF performers. Yet, as a) the outcomes, populations and statistical methods of the included trials were highly heterogeneous and b) only two out of five studies had an adequate control condition (pre-planned movement task), evidence was classified as conflicting. In sum, PGF may represent a factor increasing injury risk during unplanned sports-related movements but future research strengthening the evidence of this association is warranted.

Rapid and continuing advances in biomarker testing are not being matched by uptake in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre-eminently in many cancers, but also in an ever-wider range of conditions – notably BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, the implementation of genetic testing in clinical routine setting is still challenging. Development is impeded by country-related heterogeneity, data deficiencies, and lack of policy alignment on standards, approval – and the role of real-world evidence in the process - and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe's industrial competitiveness and innovation require an appropriate policy framework – starting with an update to outdated recommendations.

Rheumatoid arthritis (RA) is a complex disease triggered by the interaction between genetics and environment, especially through the shared epitope (SE) and cell surface calreticulin (CSC) theory. However, the available evidence shows that genetic diversity and environmental exposure cannot explain all the clinical characteristics and heterogeneity of RA. In contrast, recent studies demonstrate that epigenetics play important roles in the pathogenesis of RA, especially DNA methylation and histone modification. DNA methylation and histone methylation are involved in innate and adaptive immune cell differentiation, and migration, proliferation, apoptosis, and mesenchymal characteristics of fibroblast-like synoviocytes (FLS). Epigenetic-mediated regulation of immune-related genes and inflammation pathways explains the dynamic expression network of RA. In this review, we summarized the comprehensive evidence to show that methylation of DNA and histones is significantly involved in the pathogenesis of RA and could be applied as a promising biomarker in the disease progression and drug response prediction. We also explained the advantages and challenges of the current epigenetics research in RA. In summary, epigenetic modules provide a possible interface, through which genetic and environmental risk factors connect to contribute to the susceptibility and pathogenesis of RA. Additionally, epigenetic regulators provide promising drug targets to develop novel therapeutic drugs for RA. Finally, DNA methylation and histone modifications could be important features for providing a better RA subtype identification, to accelerate personalized treatment and precision medicine.

7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid obtained from a natural origin (Tussilago farfara)has proved to be effective in minimizing various side effects associated with opioids and nonsteroidal anti-inflammatory drugs. The current study focused on investigating the effects of ECN on neuropathic pain induced by partial sciatic nerve ligation (PSNL) by mainly focusing on oxidative stress, inflammatory and apoptotic proteins expression in mice. Neuropathic pain was induced in mice by PSNL surgery performed on day 1 and ECN (1 and 10 mg/kg, i.p.), was administered once daily for 11 days, starting from the third day after surgery. ECN post-treatment was found to reduce hyperalgesia and allodynia in a dose dependent manner. ECN significantly reversed the severity of neuropathic pain by improving distress symptoms and survival rate. ECN remarkably reversed the histopathological abnormalities associated with oxidative stress, apoptosis and inflammation. Furthermore, ECN prevented the suppression of antioxidants (glutathione, glutathione-S-transferase, catalase, superoxide dismutase, NF-E2-related factor-2 (Nrf2), hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase) by PSNL. Moreover, pro-inflammatory cytokines (tumor necrotic factor alpha, interleukin 1 beta, interleukin 6, cyclooxygenase-2 and inducible nitric oxide synthase) expression was reduced by ECN administration. Treatment with ECN was successful in reducing caspase-3 level consistent with the observed modulation of pro-apoptotic proteins. Additionally, ECN showed protective effect on the lipid content of myelin sheath as evident from FTIR spectroscopy which showed the shift of lipid component bands to higher values. Thus, anti-neuropathic potential of ECN might be due to inhibition of oxidative stress, inflammatory mediators and pro-apoptotic proteins.

This literature review has been compiled to form an evidenced-based review on the standards for Dental Practices in their choice and use of personal protective equipment (PPE) within the COVID-19 Pandemic and beyond: it is prepared on the basis of the current best available evidence. The review encompasses risk management strategies for both Dental Personnel and Patients in the application and use of Face Masks & Respirators.In summation, from the evidence available, it is apparent that in the lab setting N95/FFP2 masks are superior in their efficiency but in the clinical setting such a difference is not seen as clearly. As such the minimum standard of care should be that of a standard surgical mask. Faced with the emergence of the virulent disease that is Covid-19, it is logical to use FFP2/N95 respirator masks in aerosol generating procedures where they offer greater resistance to fluid penetration and a better face seal when adequately fit tested as a gold standard. But if a dry field isolation technique involving high volume evacuation is used, there is no clear benefit of respirator masks (N95/FFP2 or N99/FFP3) when balanced with the extra risk of compliance, cost and comfort in wearing a standard fluid-resistant surgical mask.

Current oncological developments are based on improved understanding of genetics, and especially the discovery of genes whose alterations affect cell functions with consequences for the whole body. Our work is focused on the most important of these genes, the BARD1 and its oncogenic role in breast cancer. Most importantly, the study points to new avenues in the treatment and prevention of the most frequent female cancer based on BARD1 research. The BARD1 and BRCA1 proteins have similar structures and functions, and they combine to form the new molecule BARD1-BRCA1 heterodimer. Through ubiquitination, this heterodimer has significant effects on individual proteins, enabling, among others, the destruction of damaged DNA fragments. Ubiquitination, as well as stabilizing chromatin, or regulating the number of centrosomes, confirms the protective cooperation of BARD1 and BRCA1 in the stabilization of the genome. The overexpression of the oncogenic isoforms BARD1β and BARD1δ permit cancer development. The introduction of routine tests, for instance, to identify the presence of the BARD1β isoform, would make it possible to detect patients at high risk of developing cancer. On the other hand, introducing BARD1δ isoform blocking therapy, which would reduce estrogen sensitivity, may be a new line of cancer therapy with potential to modulate responses to existing treatments. It is possible that the BARD 1 gene offers new hope for improving breast cancer therapy.

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system is thought to synergistically play a role in the increased disease severity in younger age groups. Although vaccines remain the best solution for protecting this vulnerable population, no vaccines are available for those under 6 months, and for infants aged 6 months to 2 years, the vaccine elicits a dampened immune response. Dampened immune responses may be due to unique features of the infant immune system and a lack of pre-existing immunity. Unlike older children and adults, the infant immune system is Th2 skewed and has less antigen presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. To provide better protection against influenza virus infection and disease in infants, more research must be conducted to understand the imprinting event. We contend that by understanding influenza imprinting in the context of the infant immune system and the infant’s immature respiratory tract, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets, which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune development, current vaccine strategies, respiratory development, and the importance of researching the imprinting event in infant animal models to develop more effective and protective vaccines for young children.

Recent preclinical studies have shown the potential benefits of short-term calorie reduction (SCR) on cancer treatment. In this integrative review, we aimed to identify and synthesize current evidence regarding the feasibility, process, and effects of SCR in cancer patients receiving chemotherapy. PubMed, Cumulative Index to Nursing and Allied Health Literature, Ovid Medline, PsychINFO, and Embase were searched for original research articles using various combinations of Medical Subject Heading terms. Among the 311 articles identified, seven studies met the inclusion criteria. The majority of the reviewed studies was small randomized controlled trials or cohort study with fair quality. The results suggest that SCR is safe and feasible. SCR is typically arranged around the chemotherapy with the duration ranging from 24 to 96 hours. Most studies examined the protective effects of SCR on normal cells during chemotherapy. The evidence supports that SCR had the potential to enhance both physical and psychological wellbeing of patients during chemotherapy. SCR is a cost-effective intervention with great potential. Future well-controlled studies with sufficient sample sizes are needed to examine the full and long-term effects of SCR and its mechanism of action.

The COVID-19 appears as a catastrophic health risk with psychological, emotional, social and relational implications. From the early stages of the virus spread, the elderly population was identified as the most vulnerable and the health authorities have rightly focused on such frailest population. Conversely, less attention was paid to emotional and psychological dimension of children and adolescents. Actually, they were less at risk quoad vitam or quoad valetudinem, nevertheless they had to face a reality of anxiety, fears and uncertainties. The current study investigated state anxiety and emotion awareness in a healthy sample of older adolescents, 84 females and 64 males, aged 17 to 19, during the pandemic lockdown, using Self-rating Anxiety Scale and the Italian Emotion Awareness Questionnaire. An unexpected anxious phenomenology, impacting the anxiety ideo-affective domain, was found, while the somatic symptomatology appeared to be less severe. The highest anxiety symptom were the breathing difficulties. These findings supported the hypothesis that the COVID-19 pandemic may be a risk condition for an increased state anxiety in older adolescents and suggest the need to provide 1. an effective, empathic communication system with the direct participation of older adolescents, 2. a psychological counseling service for stress management of adolescents.

The temperature of the indoor environment is important for health and wellbeing especially at the extremes of age. The study aim was to undertsand the relationship between self-reported thermal sensation and extremity skin temperature in care home residents with and without dementia. The Abbreviated Mental Test (AMT) was used to discriminate residents to two categories, those with and those without dementia. After acclimatisation, measurements included: tympanic membrane temperature, thermal sensation rating followed by infrared thermal mapping of non-dominant hand and forearm. Sixty-nine afebrile adults (60-101 years of age) were studied in groups of two to five, in mean ambient temperatures of 21.4^oC-26.6^oC (median 23.6^oC). Significant differences were observed between groups; thermal sensation rating (p=0.02), tympanic temperature (p=0.01), fingertip skin temperature (p=0.01) and temperature gradients; fingertip-wrist p=0.001 and fingertip-distal forearm, p=0.001.

Transporter associated with antigen processing 1 (TAP1) gene codes for a transporter protein, which is responsible for tumor antigen presentation in the MHC I or HLA complex. A defect in the gene results in an inadequate tumor tracking. TAP1 may also influence multi drug resistance, which is an extreme threat in providing treatment by drugs which are chemotherapeutic. The gene of TAP1 was analyzed bioinformatically. It gave us prognostic data as a confirmation of whether it should be used as a biomarker. The expression level and pattern analysis were conducted using ONCOMINE, GENT2 and GEPIA2 online platforms. Samples with different clinical outcomes were investigated for expression and promoter methylation analysis was done in cancer vs normal tissues using UALCAN. The copy number alteration and mutation frequency and expression in different cancer studies were analyzed using cBioPortal. The PrognoScan and KM plotter survival analysis of significant data (p-value<0.05) was representing graphically. Pathway and Gene ontology analysis of gene correlated to TAP1 gene was presented using bar charts. After arranging the data in a single panel and correlating expression to prognosis, understanding mutational and alterations and comparing pathways, TAP1 may be a potential novel target to evade a threat against chemotherapy and the study gives new aspects to consider for immunotherapy in human breast, lung, liver and ovarian cancer.

Late onset Pompe disease is a recessive lysosomal storage disease. Clinical features include skeletal muscles deficiency and diaphragm weakness. Clinical management relies on supportive treatment and mechanical ventilation in patents with chronic respiratory failure. M mode ultrasound and tissue Doppler imaging can be used to assess and to follow up diaphragm function.

Indoor dusts are collectively formed from anthropogenic and atmospheric activities. Particle matter 10 (PM10) is inhalable and causes significant inflammation by interaction with the pulmonary epithelial barrier. The mediators involved in bronchial epithelial cells response to dust are remined unknown. The air-liquid interface of our lung on chip model was exposed to indoor dust collected from highly polluted houses in Delhi, India. The media were collected after 4 days and cytokine levels were measured. We found that the concentration of IFN, IFNγ, Interleukin-6 (IL-6), IL1b, TNFa, and Granulocyte monocyte colony stimulating factor (GM-CSF) were significantly increased after exposure to indoor dust. IFN type I pathways were a major response from dust exposure. Further investigation is needed to determine the mechanism of action and targets of dust in bronchial epithelial cells.

Prevalence of overweight and obesity are escalating globally among the general population. However, there are limited evidence on the trends and prevalence of overweight /obesity in the military setting. Increased rates of injuries, low work productivity, incurred higher healthcare costs and prematurely discharge from service are consequences of overweight/obesity among the military. Therefore, we aimed to systematically describe the trends and prevalence of overweight and obesity in the military population, by regions and military service branches. Databases including PubMed, Scopus, Web of Science and Google Scholar were used. Inclusion criteria were military population (inclusive of all service branches) with BMI reported as the overweight/obesity indicator. Population related to military but not exclusively military personnel such as the retirees, the veterans and their dependents were excluded. From the 27 included studies, 13 were published between year 2010 to 2014 and half were conducted in the United States. Overall, studies showed increasing trend in the prevalence of overweight (30% to 50%) and obesity (2% to 30%); only one study showed a decreasing trend of 0.9% and 0.6% for the prevalence of overweight and obesity respectively. However, the rates of increment differed between countries, where Asian countries demonstrated lower overweight prevalence compared to the United States and the European countries. In conclusion, the military population is not protected from overweight and obesity. Interventions should be implemented to prevent overweight / obesity among the military personnel.

Since its 2013 emergence in the Americas, chikungunya virus (CHIKV) has posed a serious threat to public health. Early and accurate diagnosis of the disease, though currently lacking in clinics, is integral to enable timely care and epidemiological response. We developed a dual detection system: a CHIKV antigen E1/E2-based enzyme-linked immunosorbent assay (ELISA) and a lateral flow test using high-affinity anti-CHIKV antibodies. The ELISA was validated with 100 PCR-tested acute Chikungunya fever samples from Honduras. The assay had an overall sensitivity and specificity of 51% and 96.67%, respectively, with accuracy reaching 95.45% sensitivity and 92.03% specificity at a Ct cutoff of 22. As the Ct value increased from 22, ELISA sensitivity decreased. We then developed and validated two lateral flow tests using independent antibody pairs. The sensitivity and specificity reached 100% for both lateral flow tests using 39 samples from Colombia and Honduras at Ct cutoffs of 20 and 27, respectively. For both lateral flow tests, sensitivity decreased as the Ct increased after 27. Because CHIKV E1/E2 are exposed in the virion surfaces in serum during the acute infection phase, these sensitive and specific assays demonstrate opportunities for early detection of this emerging human pathogen.

Rapid and continuing advances in biomarker testing are not being matched by take-up in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre-eminently in many cancers, but also in an ever-wider range of conditions. One of the paradigmatic examples is BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, development is impeded by data deficiencies, and lack of policy alignment on standards, approval – and the role of real-world evidence in the process - and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe's industrial competitiveness and innovation require an appropriate policy framework – starting with an update to outdated recommendations.

An effective behavior changes program is the first-line of prevention for youth obesity. However, effectiveness in prevention of adolescent obesity requires several approaches, with special attention paid to disordered eating behaviors and psychological support among other environmental factors. The aim of this systematic review was to compare the impact of two types of obesity prevention programs, inclusive of behavior change components on weight outcomes. Energy-balance studies were aimed at reducing calories from high-energy sources and increasing PA levels, while “shared risk factors for obesity and eating disorders” focused on reducing disordered eating behaviors to promote a positive relationship with food and eating. A systematic search of ProQuest, PubMed, PsycInfo, SciELO, and Web of Science identified 8825 articles. Twenty were considered “energy-balance” and fifteen “shared-risk factors for obesity and eating disorders”. Overall, energy-balance studies were unable to support a maintenance weight status, diet, and PA over time. Shared risk factors programs also did not result in significant differences in weight status over time. However, the majority of shared risk factors studies demonstrated reduced body dissatisfaction, dieting, and weight-control behaviors. More research is needed to examine how a shared risk factor approach can address both obesity and eating disorder.

Granulomatosis with polyangiitis (GPA) is an autoimmune disease which is a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis that frequently affects the lungs and kidneys. However, GPA limited to a single organ has also been reported. A 73-year-old man was admitted for back pain and fever. We detected elevated levels of inflammatory markers and myeloperoxidase-ANCA. Magnetic resonance imaging indicated diffuse inflammation of the back and psoas muscles. Histology showed degenerated muscle fibers and granulomatosis vasculitis with mixed lymphoplasma cell infiltration. High-dose methylprednisolone therapy improved his symptoms. A final diagnosis of GPA limited to the muscles was made.

BACKGROUND: From March to April 2020, Spain was the center of the SARS-CoV-2 pandemic, particularly Madrid with approximately 30% of the cases in Spain. The aim of this study is to report the suspected serious adverse drug reactions (SADRs) in COVID-19 patients versus non-COVID-19 patients detected by the prospective pharmacovigilance program based on automatic laboratory signals (ALSs) in the hospital (PPLSH) during that period. We also compared the results with the suspected SADRs detected during the same period for 2019. METHODS: All ALSs that reflected potential SADRs (including neutropenia, pancytopenia, thrombocytopenia, anemia, eosinophilia, leukocytes in cerebrospinal fluid, hepatitis, pancreatitis, acute kidney injury, rhabdomyolysis and hyponatremia were prospectively monitored in hospitalized patients during the study periods. We analyzed the incidence and the distribution of causative drugs for the COVID-19 patients. RESULTS: The incidence rate of SADRs detected in the COVID-19 patients was 760.63 (95% CI 707.89–816.01) per 10,000 patients, 4.75-fold higher than the SADR rate for non-COVID-19 patients (160.15 per 10,000 patients,95% CI 137.09–186.80), and 5.84-fold higher than the SADR rate detected for the same period in 2019 (130.19 per 10,000 patients, 95% CI 109.53–154.36). The most frequently related drugs were tocilizumab (59.84%), dexketoprofen (13.93%), azithromycin (8.43%), lopinavir-ritonavir (7.35%), dexamethasone (7.62%), and chloroquine/hydroxychloroquine (6.91%). CONCLUSIONS: The incidence rate of SADRs detected by the PPSLH in patients with COVID-19 was 4.75-fold higher than that of the non-COVID-19 patients. Caution is recommended when using medications for COVID-19 patients, especially drugs that are hepatotoxic, myotoxic, and those that induce thromboembolic events.

Mycobacterium abscessus is a non-tuberculous mycobacteria notoriously known for causing severe, chronic infections. Treatment of these infections is challenging due to either intrinsic or acquired resistance of M. abscessus to multiple antibiotics. Despite prolonged poly-antimicrobial therapy, treatment of M. abscessus infections often fails, leading to progressive morbidity and eventual mortality. Great research efforts are invested in finding new therapeutic options for M. abscessus. Clofazimine and rifabutin are known anti-mycobacterial antibiotics, repurposed for use against M. abscessus. Novel antimicrobials active against M. abscessus include delamanid, pretomanid and PIPD1 and the recently approved beta-lactamase inhibitors avibactam, relebactam and vaborbactam. Previously unused antimicrobial combinations e.g. vancomycin-clarithromycin and dual beta-lactam therapy have been shown to have synergistic effect against M. abscessus in experimental models, suggesting their possible use in multiple-drug regimens. Finally, engineered phage therapy has been reported to be clinically successful in a severe case of disseminated M. abscessus infection. While many of these experimental therapeutics have shown activity against M. abscessus in vitro, as well as intracellular and/or animal models, most have little if any evidence of effect in humans infections. Clinical studies of M. abscesssus treatments are needed in order to reliably determine the value of their incorporation in therapeutic regimens.

Analgesic products for piglet castration are critically needed. This requires extensive animal experimentation such as to meet regulatory-required proof of efficacy. At present, there are no validated methods of assessing pain in neonatal piglets. This poses challenges for investigators to optimize trial design and to meet ethical obligations to minimize the number of animals needed. Pain in neonatal piglets may be subtle, transient and / or variably expressed and, in the absence of validated methods, investigators must rely on using a range of biochemical, physiological and behavioural variables, many of which appear to have very low (or unknown) sensitivity or specificity for documenting pain, or pain-relieving effects. A previous systematic review of this subject was hampered by the high degree of variability in the literature base both in terms of methods used to assess pain and pain mitigation, as well as in outcomes reported. In this setting we provide a narrative review, to assist in determining the optimal methods currently available to detect piglet pain during castration and methods to mitigate castration-induced pain. In overview, the optimal outcome variables identified are nociceptive motor and vocal response scores during castration, and quantitative sensory-threshold response testing and pain-associated behaviour scores following castration.

From the moment the World Health Organization (WHO) declared COVID-19 to be a pandemic disease, COVID-19 began to affect the lives of many healthcare providers worldwide. In response to this pandemic, urology departments and training residency programs implemented urgent measures to reduce outpatient clinics, adopted the use of telemedicine, regulated emergency and outpatient urological procedures, promoted the use of operating theatres, and developed the use of sustainable e-learning alternatives to traditional urology resident/staff educational activities. Here, we review the response of urologists in Saudi Arabia to the COVID-19 pandemic and how they applied both for the patients and for the healthcare of urologist personnel.

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally. Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments. MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis. Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC. These include signaling pathways associated with mucus-secreting cell differentiation [ nuclear factor-κB (NF-кB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF). Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD. Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease. Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion.

Imbalance of homeostasis between the microbial communities and the host system leads to dysbiosis in oral micro flora. DMTU (1,3-di-m-tolyl-urea), is a biocompatible compound that was shown to inhibit Streptococcus mutansbiofilms by inhibiting its communication system (quorum sensing). Here, we hypothesized that DMTU is able to inhibit multispecies biofilms. We developed a multispecies oral biofilm model comprising an early colonizer Streptococcus gordonii, a bridge colonizer Fusobacterium nucleatum, and late colonizers Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans. We performed comprehensive investigations to demonstrate the effect of DMTU on planktonic cells and biofilms. Our findings showed that DMTU inhibits and disrupts multispecies biofilms without bactericidal effects. Mechanistic studies revealed significant down regulation of biofilm and virulence related genes in P. gingivalis. Taken together, our study highlights the potential of DMTU to inhibit polymicrobial biofilm communities and their virulence.

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

In many developed countries, mental health disorders have become problematic, and the economic loss due to treatment costs and interference with work is immeasurable. Therefore, we developed a method to assess individuals’ mental health using emotional components contained in their voice. We propose two indices of mental health: vitality, a short-term index, and mental activity, a long-term index capturing the trends in vitality. To evaluate our method, we used the voices of healthy individuals (n = 14) and patients with major depression (n = 30). The patients were also assessed by specialists using the Hamilton Rating Scale for Depression (HAM-D). A significant negative correlation existed between the vitality extracted from the voices and HAM-D scores (r = -0.33, p &lt; .05). We could discriminate the voice data of healthy individuals and patients having depression with a high accuracy using the vitality (p = .0085, area under the curve = 0.76). Further, we developed a method to estimate stress through emotion instead of analyzing stress directly from voice data. By daily monitoring of vitality using smartphones, we can encourage hospital visits for people before they become depressed or during the early stages of depression, to prevent adverse consequences of depression.

We report the results of our study of approved drugs as potential treatments for COVID 19, based on the application of various bioinformatics predictive methods. The drugs studied include chloroquine, ivermectin, remdesivir, sofosbuvir, boceprevir, and α-difluoromethylornithine (DMFO). Our results indicate that these small molecules selectively bind to stable, kinetically active residues and residues adjoining them on the surface of proteins and inside protein pockets, and that some prefer hydrophobic over other active sites. Our approach is not restricted to viruses and can facilitate rational drug design, as well as improve our understanding of molecular interactions, in general.

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

This study aimed to identify the utility of diffusion-weighted magnetic resonance (MR) imaging with an apparent diffusion coefficient (ADC) map as a predictor of the intrahepatic response of hepatocellular carcinoma (HCC) to cisplatin-based hepatic arterial infusion chemotherapy (HAIC). We retrospectively evaluated 113 consecutive patients with HCC who underwent gadoxetic acid-enhanced and diffusion-weighted MR imaging. The appropriate cutoff for the tumor-to-liver ADC ratio was determined to be 0.741. Of the 113 patients, 51 (45%) presented with a tumor-to-liver ADC ratio < 0.741. Evaluation of the intrahepatic treatment response after 2-3 cycles of HAIC in these 51 patients revealed that 20 patients (39%) experienced an objective response to HAIC. On the other hand, only 10 of the 62 patients with a tumor-to-liver ADC ratio ≥ 0.741 (16%) experienced an objective response. Thus, the objective response rate was significantly higher in patients with a tumor-to-liver ADC ratio < 0.741 than in those with a tumor-to-liver ADC ratio ≥ 0.741 (P = 0.006). Multivariate logistic regression analysis using parameters including perfusion alteration, percentage of a non-enhancing portion, and tumor-to-liver ADC ratio revealed that a tumor-to-liver ADC ratio < 0.741 (odds ratio 3.03; P = 0.015) is the sole predictor of an objective response to HAIC. Overall survival rates were significantly higher in patients with objective responses to HAIC than in those without objective responses (P = 0.001 by log-rank test). In conclusion, patients with unresectable HCC with a tumor-to-liver ADC ratio < 0.741 showed a favorable intrahepatic response to HAIC. Therefore, diffusion-weighted MR imaging can play a critical role as a predictor of response to cisplatin-based HAIC in unresectable HCC.

Castleman disease (CD) rarely presents with obstructive jaundice, which poses a diagnostic and therapeutic challenge to the management of the disease. A 40-year-old man was referred to our hospital for emergent management of upper abdominal pain. An abdominal mass was removed, and the postoperative pathology showed retroperitoneum CD, which was subsequently managed by adjuvant therapy of combination chemotherapy and steroids. One month later, a biliary metal stent was placed due to the presentation of obstructive jaundice. After approximately 3 months, the patient experienced another episode of obstructive jaundice, and SpyGlass DS cholangioscopy (Boston Scientific, Natick, Mass, USA) was performed via the biliary track for biopsy, which pathologically showed biliary malignancies. Radiofrequency ablation was performed with a probe (EMcision, Montreal, Canada), and another uncovered metal stent was placed within the existing metal stent. No stent occlusion occurred during a 6-month follow-up period. In conclusion, CD rarely presents with obstructive jaundice, and a combination of radiofrequency ablation with metal stent implantation under cholangioscopy can prolong the stent patency time and the survival time of patients.

The Body Mass Index (BMI) formula has been developed by Belgian mathematician Adolphe Quetelet and published in 1840 [1] as a law of nature and society, based on statistics about the weight and height of the population of that time, the first part of the 19^th century. He called it “social physics”. From then, for nearly two centuries, the BMI had been the most important formula describing the normal relations and ratio of weight to the square of the height for humans. The problem arises if the BMI formula, developed in the first part of the 19^th century is still good today when the type of work people perform is very different? In modern times, most people are less muscular than at the time when the BMI was developed because they do not work physically as heavy as at that time. In many cases, the Body Mass index can predict mortality, morbidity and illness but not always, for example cases such as (a) the obesity paradox for some cardiovascular problems and (b) the U shape mortality paradox as well as (c) false positive obesity diagnostic in regard to people who are strong and muscular, have low body fat percentage but are classified as obese by the BMI and (d) cases where BMI is normal but people have an “obese metabolism” (e) BMI normal but high fat percentage. The objective is to develop a formula good for all body types, a formula that makes the difference between fat and non-fat body weight such as muscle and body frame and quantifies the effect of strength and fitness, which BMI does not. Another objective is to develop a formula to predict the health risks and fitness status of people, better than BMI. The first generalizations of BMI using anthropometric metrics could be found in [2], where I discuss and analyze many formulae, developed, tested, and simulated by me, using similar new methods, accounting for body shape, physical shape and body function, making the difference between muscle mass and fat, fat and non fat body weight. Nearly all formulae and methods developed and proposed in this new model are new, never published before. Many experiments published before, in highly cited papers show that grip strength and muscle strength is a predictor of health, mortality, morbidity, endocrine and metabolic disease outside the BMI and anthropometric measures. The purpose of my formula is to explain the outcome of those experiments and create a formula which predicts these experiments [21-41].

Background: Social Anxiety Disorder (SAD) is among the most common anxiety disorders worldwide with data largely emerging from the Euro-American and Pacific Rim populations. In contrast, there is a dearth of studies among the populations of Arabian Gulf countries including Oman. This study has two interrelated aims: (i) to explore the prevalence of SAD among Omani adults, and (ii) to tease out the links between sociodemographic factors and SAD in Oman. Methods: A cross-sectional study via an online survey was conducted among 1019 adult Omani nationals residing in Oman. The presence of SAD was assessed using the Arabic version of the Liebowitz Social Anxiety Scale (LSAS). Result: Nearly half the participants (45.9%, n=468) endorsed themselves as having features of SAD as defined by LSAS. In the multivariate logistic analysis, participants below 40 years of age were 1.6 times (OR=1.568, p=0.026) more likely to have SAD than those who were 40 and older. Women were 1.3 times (OR=1.348, p=0.038) more likely to endorse SAD than men. Participants who had secondary or undergraduate education were respectively 1.5 times (OR=1.45, p=0.014) and 2.5 times (OR=2.509, p<.001) to have SAD than who were postgraduates. Conclusion: The present data suggest that 45.9% of the participants reached the cut-off for case-ness in LSAS, which is high compared to reports from other populations. As online survey respondents tend to belong to similar demographics, the current results need not be representative of the Omani adult population, which calls for studies that adopt more inclusive survey methods.

The world has been highly impacted by the COVID-19 as the virus has spread to all continents – about 200 countries in total. The latest update claims about 4,000,000 confirmed cases and about 300,000 confirmed deaths owing to the COVID-19 pandemic. This probably makes the COVID-19 as the most dangerous contagious disease in the era 2000s. Apart from massive publications on this topic, there is no available qualitative analysis that describes the dynamic spreads of the COVID-19 and its impacts on healthcare and the economy. Through the system archetypes analysis, this paper explains that the dynamic spread of the COVID-19 consists of the limits to growth and the success to successful structures. The limits to growth elucidates that more symptomatic and asymptomatic patients owing to infected droplets may be bounded by self-healing and isolated treatments. The success to successful structure explains that once the COVID-19 affects the economy through the lockdown, there will be a limited fund to support the government aids and the aggregate demand. In overall, this paper gives readers simplified holistic insights into understanding the dynamic spread of the COVID-19.

UEDVT still remains an underdiagnosed entity due to a significant percentage of patients who remain asymptomatic. The etiology of UEDVT is overwhelmingly attributed to secondary causes including but not limited to central venous access devices and malignancy. Treatment modalities include anticoagulation, catheter directed thrombolysis, percutaneous mechanical thrombectomy or a multimodality approach along with the management of underlying etiology. We describe a case of a female with breast cancer, who came with left UEDVT and CVC malfunction and was successfully treated using the ClotTriever system to maintain continuous intravenous access.

Background: It has been reported that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers while a study done in MD Anderson found that obesity and adult weight gain are independent risk factors for CML however no study evaluated the role of obesity in the disease progression while more studies investigate the impact of translocation types. Method: We conducted a retrospective analysis of the files of 37 patients being treated in our center for CML in chronic phase (CMP-CP) with known BCR-ABL1 breakpoints, Results: patients’ management and response assessment was done based on ELN 2013 guidelines. Analysis is done based on two main groups, obese vs normal BMI, and then based on BCR-ABL1 transcripts: e13a2 vs e14a2. Although the number of cases is limited, in the patient-cohort studied an e14a2 BCR-ABL1 transcript type / normal body weight was associated with an inferior outcome when compared to e13a2 transcript / obesity groups Conclusion: our finding suggest the need to enlarge the series to better evaluate a potential role of altered metabolism and/or specific transcripts in the response to TKI in CML.

COVID-19 pandemic represents an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease are still urgently needed.A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of initial symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention. In analogy with other respiratory viral infections, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain, fever and control inflammation. Non-steroidal antinflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in these conditions and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of ACE2 protein levels (the receptor used by SARS-CoV2 to enter host airways cells), the risk of bacterial superinfections and masking of disease symptoms. As a consequence, the use of NSAIDs was, and is, strongly discouraged while the alternative adoption of paracetamol is still preferred.On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may produce an oxidative imbalance which could be detrimental in COVID-19 clinical outcomes.

Breast cancer is the leading cause of cancer deaths worldwide in women. This aggressive tumour can be categorized into two main groups: in situ and infiltrative, with the latter being the most common malignant lesions. The current use of Magnetic Resonance Imaging (MRI) was shown to provide highest sensitivity in the detection and discrimination between benign vs. malignant lesions, when interpreted by expert radiologists. In this article, we present the prototype of a Computer-Aided Detection/Diagnosis (CAD) system that could provide valuable assistance to the radiologist for the discrimination between in situ and infiltrating tumours. The system consists of two main processing levels: 1) Localization of possibly tumoral regions of interest (ROIs) through an iterative procedure based on intensity values (ROI Hunter) followed by a deep-feature extraction and classification method for false-positive rejection; 2) Characterization of the selected ROIs and discrimination between in situ and invasive tumour, consisting of Radiomics feature extraction and classification through a machine-learning algorithm. The CAD system was developed and evaluated using a DCE-MRI image database, containing at least one confirmed mass per image, as diagnosed by an expert radiologist. When evaluating the accuracy of the ROI Hunter procedure with respect to the radiologist-drawn boundaries, sensitivity to mass detection was found to be 75%. The AUC of the ROC curve for discrimination between in situ and infiltrative tumors was 0.70.

The prospective study enrolled 144 patients after surgical treatment of biliary atresia in early infancy. We analyze the immediate effectiveness of the surgery and the age-related structure of complications in the up to 16-year follow-up. The immediate 2-year survival rate after the surgery constituted 49.5%. At the time of this writing, 17 of the patients have celebrated their 10th birthdays with good quality of life and no indications for LT. The obtained results underscore the critical importance of surgical correction of BA by Kasai surgery during the first 60 days of life and subsequent dynamic follow-up of the patients for the purpose of the early detection and timely correction of possible complications.

Background: Although a cholesterol-lowering diet and the addition of plant sterols and stanols are suggested for the lipid management of children and adults with familial hypercholesterolemia, there is limited evidence evaluating such interventions in this population. Objectives: To investigate the impact of cholesterol-lowering diet and other dietary interventions on the incidence or mortality of cardiovascular disease and lipid profile of patients with familial hypercholesterolemia. Search methods: Relevant trials were identified by searching US National Library of Medicine National Institutes of Health Metabolism Trials Register and clinicaltrials.gov.gr using the following terms: diet, dietary, plant sterols, stanols, omega-3 fatty acids, fiber and familial hypercholesterolemia. Selection criteria: Randomized controlled trials evaluating the effect of cholesterol-lowering diet or other dietary interventions in children and adults with familial hypercholesterolemia were included. Data collection and analysis: Two authors independently assessed the trial eligibility and bias risk and one extracted the data, with independent verification of data extraction by a colleague. Results: A total of 17 trials were finally included, with a total of 376 participants across 8 comparison groups. The included trials had either a low or unclear bias risk for most of the parameters used for risk assessment. Cardiovascular incidence or mortality were not evaluated in any of the included trials. Among the planned comparisons regarding patients’ lipidemic profile, a significant difference was noticed for the following comparisons and outcomes: omega-3 fatty acids reduced triglycerides (mean difference [MD]: -0.27 mmol/L, 95% confidence interval [CI]: -0.47 to -0.07, p<0.01) when compared with placebo. A non-significant trend towards a reduction in subjects’ total cholesterol (MD: -0.34, 95% CI: -0.68 to 0, mmol/L, p=0.05) and low-density lipoprotein cholesterol (MD: -0.31, 95% CI: -0.61 to 0, mmol/L, p=0.05) was noticed. In comparison with cholesterol-lowering diet, the additional consumption of plant stanols decreased total cholesterol (MD: -0.62 mmol/l, 95% CI: -1.13 to -0.11, p=0.02) and low-density lipoprotein cholesterol (MD: -0.58 mmol/l, 95% CI: -1.08 to -0.09, p=0.02). The same was by plant sterols (MD: -0.46 mmol/l, 95% CI: -0.76 to -0.17, p<0.01 for cholesterol, and MD: -0.45 mmol/l, 95% CI: -0.74 to -0.16, p<0.01 for low-density lipoprotein cholesterol). No heterogeneity was noticed among the studies included in these analyses. Conclusions: Available trials confirm that the addition of plant sterols or stanols has a cholesterol-lowering effect on such individuals. On the other hand, supplementation with omega-3 fatty acids effectively reduces triglycerides and might have a role in lowering the cholesterol of patients with familial hypercholesterolemia. Additional studies are needed to investigate the effectiveness of a cholesterol-lowering diet or the addition of soya protein and dietary fibers to a cholesterol-lowering diet in familial hypercholesterolemia.

This review and meta-analysis (PROSPERO registration number: CRD42020138845) critically evaluates test-retest reliability, concurrent validity and criterion validity of different physical activity (PA) levels of three most-common used international PA questionnaires (PAQs) in national language versions of EU-28: IPAQ-SF, GPAQ, and EHIS-PAQ. In total, 4969 abstracts were read, 287 full-text articles were identified as relvant to the study objectives, and 19 studies were included in the final meta-analysis. The studies’ results and quality were evaluated using the Quality Assessment of Physical Activity Questionnaires (QAPAQ) checklist. Results indicate that only five EU-28 countries validated national language versions of selected PAQs. Meta analysis revealed that assessment of moderate-to-vigourus PA (MVPA) is the most relevant PA level outcome, since no publication bias in any of measurement properties was detected while test-retest reliability was the moderately-high (rw=0.74), and moderate for both criterion (rw=0.41) and concurrent validity (rw=0.72). Reporting of methods and results of the studies was poor with overall moderate risk of bias with total score of 0.43. In conclusion, where only self-reporting is feasible, assessment of MVPA with selected PAQs in EU-28 adult population is recommended for policymaking.

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients’ outcome. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but also might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies, as well as preliminary clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

The popularity of multiparticulate formulations (MPs) as a paediatric dosage form continues to increase. MPs comprise of multiple small units that are easy-to-swallow. Currently, MPs are commonly manufactured into unit doses that are either swallowed whole or opened prior to administration. While this is an acceptable approach, dosing is envisioned to be optimized with a ‘standard’ paediatric device which can better harness the flexible dosing potential of MPs. We evaluated a novel oral syringe (SympfinyTM) that is being developed as a tool to dispense and administer MPs to children. Forty children, 4-12 years old, received 0.5, 1.2, and 2.0 mL doses of placebo MPs using the oral syringe with spring water or a drink of choice to complete sample intake. Acceptability was recorded as those able to completely swallow the dose and participants also rated dose acceptability on a 5-point scale. The ability to completely swallow the dose decreased as dose volume increased; the smallest dose was completely swallowed by 87.5% (35/40) children, and 69.4% (27/39) of children confirmed their willingness to take the sample as a daily medicine. Larger doses, 1.2 and 2.0 mL, gave values of 55% and 57.5% for the doses completely swallowed and 58.8% and 51.72% for willingness to take the sample as a daily medicine, respectively. Use of a drink of choice showed no increase in swallowability as compared with water. The novel oral syringe being developed is an appropriate device for dispensing doses flexibly and administering neutral tasting MPs directly to the mouth in the lower dose range without the need for a co-administration vehicle in children aged 4-12 years.