Instead of tissue-based detection, blood-based tumor mutation burden (bTMB) is becoming an alternative promising alternate to predict the response of immune checkpoint inhibitor in cancers, especially non-small-cell lung cancer. Although bTMB is more convenient and less invasive, many evidences identified its limited predictive ability and less accurate discrimination of candidates to receive immunotherapy. Several ways of adjustments have been applied to improve the clinical usefulness of bTMB, such as setting restriction for threshold of allele frequency to exclude some unwanted mutations. But many questions remained to be explored such as the number and the type of mutations that should be incorporated into the bTMB estimation. This viewpoint summarized the current attempts to modify bTMB and provided granular aspects that have implications for further enhancement of bTMB’s predictive capability.

MCPH1, otherwise known as the microcephalin gene (*607117) and protein, is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The Microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptide. There is a strong connection between mutations of the MCPH1 and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains which means smaller size, varying levels of mental retardation, delayed speech and poor language skills, individuals with mild microcephaly and normal intelligence notwithstanding. In this case, a fetus with novel homozygous mutation of the MCPH1 gene ((c.348del)), whose parents were recessive heterozygous for (c.348del), displayed severe microcephaly at 22 weeks of gestation. Due to the effect on splice sites in introns, this mutation causes forming of dysfunctional proteins which lack crucial domains of the C-terminus. Our findings portray an association between the new MCPH1 mutation ((c.348del)) and the clinical features of autosomal recessive primary microcephaly (MCPH) contributing to a broader spectrum related to these pathologies.

The Center for Disease Control and Prevention and the World Health Organization issued a practical approach and Global Action Plan to control the threatening emerging antibacterial resistance. One of the main basis of this plan is the Antimicrobial Stewardship Program (ASPs). This study aimed to evaluate community pharmacists’ awareness and perception towards antimicrobial resistance and ASPs in Jordan. Thus, a qualitative study was conducted through in-depth interviews with twenty community pharmacists. Convienience sampling was used in the study. Qualitative analysis of the data yielded four themes and eleven sub-themes. All the respondents showed good understanding about the causes of antimicrobial resistance. The most important causes reported by them was the non-restricted prescription of antimicrobials. Most of the pharmacists believed that they are competent to provide ASPs, however, they believed that there are several barriers against the implementation of ASPs in community pharmacies in Jordan. Barriers demonstrated by the pharmacists, including organizational obstacles, resources obstacles, and personal obstacles. As a conclusion, this study revealed several barriers against the implementation of ASPs in community pharmacies in Jordan. Incorporating ASPs in the community pharmacy settings requires proper pharmacist training, several academic disciplines team efforts, and good pharmacy practice of antimicrobial guidelines.

(1) Background: the NGS based mutational study of hereditary cancer genes is crucial to design tailored prevention strategies in subjects with different hereditary cancer risk. The ease of amplicon-based NGS library construction protocols contrasts with the greater uniformity of enrichment provided by capture-based protocols and so with greater chances for detecting larger genomic rearrangements and copy-number variations. Capture-based protocols, however, are characterized by a higher level of complexity of sample handling, extremely susceptible to human bias. Robotics platforms may definitely help dealing with these limits, reducing hands-on time, limiting random errors and guaranteeing process standardization. (2) Methods: We implemented and validated the complete automation of the SOPHiA GENETICS’ CE-IVD Hereditary Cancer Solution™ (HCS) libraries preparation workflow on the Hamilton’s STARlet platform. (3) Results: We demonstrate that this automated workflow, used for more than 1000 samples achieved the same performances of manual setup in terms of coverages and reads uniformity, with extremely lower variability of reads mapping rate onto the regions of interest. (4) Conclusions: This automated solution offers same reliable and affordable NGS data, but with the essential advantages of a flexible, automated and integrated framework, minimizing possible human errors and depicting a laboratory’s walk-away scenario.

Background: During the COVID-19 pandemic some family physicians were overburdened and experienced difficulties reaching vulnerable patients and meeting the increased need for psycho-social support. This randomized controlled trial (RCT) tested whether a primary healthcare (PHC) based community health worker (CHW) intervention could tackle psychosocial suffering due to physical distancing measures in patients with limited social networks. Methods: CHWs provided 8 weeks of tailored psychosocial support to the intervention group. Control group patients received ‘care as usual’. The impact on feelings of emotional support, social isolation, social participation, anxiety and fear of COVID-19 were measured longitudinally using a face-to-face survey to determine their mean change from baseline. Self-rated change in psychosocial health at 8 weeks was determined. Results: We failed to find a significant effect of the intervention on the prespecified psychosocial health measures. However, the intervention did lead to significant improvement in self-rated change in psychosocial health. Conclusions: This study confirms partially the existing evidence on the effectiveness of CHW in-terventions as a strategy to address mental health in PHC in a COVID context. Further research is needed to elaborate the implementation of CHWs in PHC to reach vulnerable populations during and after health crises.

The aim of this study was to analyze surgical and refractive outcomes of XEN glaucoma implant (Allergan, an Abbvie company, Irvine, CA, USA), a minimally invasive surgical device for the treatment of refractory glaucoma. A retrospective chart review of eyes that received XEN Gel Stent placement from December 2014 to October 2019 was conducted. Intraocular pressure (IOP) change, best corrected visual acuity (BCVA), change in glaucoma medications, frequency of slit lamp revision procedures, and frequency of secondary glaucoma surgeries were the primary outcomes. Seventy-two subjects were included in the study: 32 (44%) males and 40 (56%) females. The mean follow-up time was 26.87 ± 15.33 months. The mean IOP before surgery was 24.82 ± 8.03 mmHg and decreased to 17.45 ± 5.84 mmHg at the end of the study, MD = -7.48, CI95 [-10.04; -4.93], p < 0.001. The mean decrease from baseline was 23%. Before surgery BCVA was 0.38±0.30 and at the end of the follow-up period it had improved to 0.47±0.37, MD = 0.09, CI95 [0.04; 0.13], p < 0.001. Additional procedures (fluorouracil injection, Bleb needling) were performed in 11/72 patients (15%). Further glaucoma surgery was necessary for 23.9%% of the patients. Implantation of XEN Gel Stent is both safe and effective for lowering IOP in refractory glaucoma patients.

Doxorubicin, a member of the anthracycline family, is a common anticancer agent often used as a first line treatment for the wide spectrum of cancers. Doxorubicin-based chemotherapy, although effective, is associated with serious side effects, such as irreversible cardiotoxicity or nephrotoxicity. Those often life-threatening adverse risks, responsible for the elongation of the patients' recuperation period and increasing medical expenses, have prompted the need for creating novel and safer drug delivery systems. Among many proposed concepts, polymeric nanocarriers are shown to be a promising approach, allowing for controlled and selective drug delivery simultaneously enhancing its activity towards cancerous cells and reducing toxic effects on healthy tissues. This article is a chronological examination of the history of the work progress on polymeric nanostructures, designed as efficient doxorubicin nanocarriers, with the emphasis on the main achievements of 2010-2020. Numerous publications have been reviewed to provide an essential summation of the nanopolymer types and their essential properties, mechanisms towards efficient drug delivery, as well as active targeting stimuli-responsive strategies that are currently utilized in the doxorubicin transportation field.

Following the first triple-drug MDA for lymphatic filariasis in Samoa in 2018, unexpected persistence of Mf-positivity in 18 (15%) of 121 antigen-positive persons was observed in a nationwide household survey 1-2 months later, raising concerns about MDA efficacy. In 2019, a monitored treatment study was done before and 7 days after directly observed weight-based treatment. Mf presence and density were evaluated using 1 mL membrane filtered venous blood, and 60uL thick blood films on slides prepared from venous or fingerprick blood. All 14 participants were still Mf positive on filters from venous blood pre-treatment samples, but two were negative by slide made from the same samples. Mf were cleared completely by day 7 in 12 of 13 participants followed up, and by day 30 in the remaining participant. Filtered blood using EDTA samples (to reduce clumping of Mf) is preferred over slides alone for improving the likelihood of detecting Mf and estimating their density. The triple-drug MDA strategy was effective at clearing Mf by day 30 when given and taken at the correct dose.

Despite advances in understanding of the molecular pathogenesis of glioma, outcomes remain dismal. Developing successful treatments for glioma requires faithful in vivo disease modeling and rigorous preclinical testing. Murine models, including xenograft, syngeneic, and genetically engineered models, are used to study gliomagenesis, identify methods of tumor progression, and test novel treatment strategies. Since the discovery of highly recurrent isocitrate dehydrogenase (IDH) mutations in lower-grade gliomas, there is increasing emphasis on effective modeling of IDH mutant brain tumors. Improvements in preclinical models that capture the phenotypic and molecular heterogeneity of gliomas are critical for the development of effective new therapies. Herein, we explore the current status, advancements, and challenges with contemporary murine glioma models.

This observational study aims to depict the impact of gender and socio-economic issues on the health status of Italian Orthopaedic patients during the COVID-19 lockdown. An Ad Hoc ques-tionnaire was developed and online administered. The following data were extracted from the questionnaire: age, body mass index (BMI), education level, distance from hospital, orthopaedic disease, concomitant medical comorbidities, living status (with/without cohabitants) and physical activity level (according to Tegner Activity Scale). The impact of the COVID-19 lockdown was studied analyzing differences related to the above-mentioned parameters. A significant increase of the call number to general practitioner and to the orthopaedic surgeon was observed during the COVID-lockdown, especially in patients with higher education level. Nonetheless, a reduced compliance in drugs assumption was observed in patients with higher education level during lockdown (p=0.007). Almost all the analyzed items were significantly in-fluenced by the distance between patient’s domicile and the nearest hospital. However, no sig-nificant differences were observed comparing pre-COVID to COVID lockdown. In the present study patients’ gender and education level revealed a significant impact on the social behavior during the COVID lockdown, compared with the pre-COVID period.

We aimed to assess awareness, knowledge, and attitudes of healthy pregnant women towards human papillomavirus (HPV), to estimate factors associated with a positive attitude towards HPV immunization and to assess the uptake of the vaccine among their children. A cross-sectional study was conducted at the University Clinic of Gynecology and Obstetrics, Belgrade, Serbia among pregnant women attending their regular gynecological check-ups at the 12th gestational week. Knowledge about HPV and HPV vaccine was assessed using a specifically designed 12-item and 5-item questionnaires. Out of total 265 included women, 79.3% had heard of HPV, and 37.5% knew that HPV vaccine exists. HPV vaccine knowledge score was associated with higher odds for a positive attitude towards vaccination of both female (OR = 4.10, 95% CI 1.50-11.29) and male (OR = 3.71, 95% CI 1.52-9.01) child. The number of children (OR = 1.32, 95% CI 1.04-1.67) and high vaccine knowledge score (OR = 1.64 95% CI 1.13-2.39) were independent predictors associated with willingness to vaccinate child against HPV. The gynecologist was the preferable point of reference for information seeking about the HPV vaccine. Despite relatively high HPV awareness and knowledge among pregnant women in Serbia, about one-third of them are HPV vaccine aware, and are willing to vaccinate their children against HPV.

Proper treatment of infectious air could potentially mitigate the spread of airborne viruses such as porcine reproductive and respiratory syndrome virus (PRRSV). The objective of this research is to test the effectiveness of ultraviolet (UV) in inactivating aerosolized PRRSV, specifically, four UV lamps, UV-A (365 nm, both fluorescent and LED-based), "excimer" UV-C (222 nm), and germicidal UV-C (254 nm), were tested. The two UV-C lamps effectively irradiated fast-moving PRRSV aerosols with short treatment times (<2 s). One-stage and two-stage UV inactivation models estimated the UV doses needed for target percentage (%) reductions on PRRSV titer. UV-C (254 nm) dose needed for 3-log (99.9%) reduction was 0.521 and 0.0943 mJ/cm2, respectively, based on one-stage and two-stage models. An order of magnitude lower UV-C (222 nm) doses were needed for a 3-log reduction, i.e., 0.0882 and 0.048 mJ/cm2, based on one-stage and two-stage models, respectively. However, the cost of 222-nm excimer lamps is still economically prohibitive for scaling-up trials. The UV-A (365 nm) lamps could not reduce PRRSV titers for tested doses up to 4.11 mJ/cm2. Pilot-scale or farm-scale testing of UV-C on PRRSV aerosols simulating barn ventilation rates are recommended based on its effectiveness and reasonable costs comparable to HEPA filtration.

Breast cancer is the most commonly diagnosed cancer in women worldwide. Approximately, 70 % of breast cancer patients express hormone receptors (HR) (Luminal subtype). Adjuvant endocrine treatments are the standard of care in HR+/HER2- breast cancer. Over time, about 50% of those patients develop endocrine resistance and metastatic breast cancer. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacy increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic breast cancer patients. CDKi blocks kinases 4/6 ATP-binding domain preventing G1/S cell cycle transition. Despite this, not all patients respond to CDKi and those who respond, finally develop resistance to combination therapy. Different studies, in tumour tissue or cell lines, have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. In the last few years, liquid biopsy has contributed relevant information to this knowledge. Liquid biopsy can be performed in real-time, non-invasively and be repeated whenever needed. Circulating tumour material are potential prognostic markers in metastatic luminal breast cancer to determine patient prognosis, monitor disease and treatment selection. The objective of this review is to outline the different studies carried out in HR+ metastatic breast cancer patients treated with CDKi plus endocrine therapy using liquid biopsy approaches looking for possible resistance mechanisms.

Colorectal cancer is a major threat to the society causing the death through metastasis to several patients with stage IV. Computational tools provide a relatively quick procedure in order to evaluate several molecules for their drug activity. Prenylated flavonoids are well known for their anticancer properties even in colon cancer. Here, we provided altered structures of chalcones, based on theoretical studies that are showing better binding affinities to several colon cancer related proteins. Using molecular docking and dynamics, alongside with density function theory and ADMET studies we are representing two new derivatives of Xanthohumol prenylated flavonoids having promising results against this disease.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a rare and potentially life-threatening systemic drug reaction with skin involvement. We present the unusual case of DRESS in a 16-year-old male that was treated with TMP-SMX for acne and was initially misdiagnosed with Steven Johnson Syndrome. Our case serves as an example to healthcare providers treating adverse drug reactions to having a high clinical suspicion for DRESS as delay in diagnosis and treatment can result in disseminated disease and higher patient mortality risk.

: This paper presents a couple of meal monitoring systems for senile dementia patients by using electronic weight and temperature sensors. These monitoring systems enable to convey the information of the amount of meal taken by the patients in real-time via wireless communication networks onto the mobile phones of their families or nurses in charge. Thereby, the nurses can easily spot the most desperate patient to take care of while the families can have relief to see the crucial information for survival of their parents at least three times a day. Meanwhile, the senile dementia patients tend to suffer the burn of their tongues because they can hardly recognize the temperature of hot meals served and therefore avoid the burn of tongues. This phenomenon can be discarded by utilizing the meal temperature monitoring system which displays alarm to the patients when the meal temperature is above the reference. These meal monitoring systems can be easily implemented by utilizing low-cost sensor chips and Arduino UNO boards so that elder-care hospitals and nursing homes can afford to exploit them with no additional cost. Hence, we believe that the proposed monitoring systems would be a potential solution to provide a great help and relief not only for the professional nursing nurses working in elder-care hospitals and nursing homes, but also for the families of the dementia patients.

Telecommuting is a flexible form of work that has progressively spread over the last 40 years and which has been strongly encouraged by the measures to limit the Covid19 pandemic. There is still limited evi-dence on the effects it has on workers' health. In this survey we invited 905 workers of companies that made a limited use of telework to fill out a questionnaire to evaluate: Intrusive leadership of managers (IL), the request for work outside traditional hours (OFF-TAJD), workaholism (BWAS), effort / reward imbalance (ERI), happiness and common mental issues (CMIs), anxiety and depression, assessed by the Goldberg scale (GADS). The interaction between these variables has been studied by structural equation modeling (SEM). Intrusive leadership and working after hours were significantly associated with occu-pational stress. Workaholism is a relevant moderator of this interaction: intrusive leadership significantly increased the stress of workaholic workers. Intrusive leadership and overtime work were associated with reduced happiness, anxiety and depression. These results indicate the need to guarantee the right to disconnect, to limit the effect of the OFF-TAJD. In addition to this, companies should implement policies to prevent intrusive leadership and workaholism.

1) Background: Fetal Growth Restriction (FGR) has been associated with adverse perinatal outcomes and epigenetic modifications that impact gene expression leading to permanent changes of fetal metabolic pathways and thereby influence development of disease in childhood and adult life. Both clinical and experimental studies showed that maternal nutrition during pregnancy is critical since malnutrition adversely affects fetal growth and physiology. In this study, we investigated the result of maternal food restriction on liver protein expression in Wistar male newborn pups. (2) Materials & methods: Pups born to food restricted mothers were subdivided to FGR and non-FGR groups. Livers of control, FGR and non-FGR groups were analyzed using quantitative proteomics. (3) Results: In total 6665 proteins were profiled. Of these, 451 and 751 were differentially expressed in FGR and non-FGR vs. control respectively, whereas 229 were common between the two groups. Bioinformatics analysis of the differentially expressed proteins (DEPs) in FGR vs. control revealed: induction of the super-pathway of cholesterol biosynthesis and inhibition of thyroid hormone metabolism, fatty acid beta oxidation and apelin liver signaling pathway. In the DEPs of non-FGR vs. control groups there was inhibition of thyroid hormone metabolism, fatty acid beta oxidation and apelin liver signaling pathway as well. (4) Conclusion: This study demonstrates the impact of prenatal food restriction on the proteomic liver profile of FGR and non-FGR offspring underlying the importance of both prenatal adversities and birth weight on liver dependent postnatal disease.

The gut microbiome is important in the homeostasis of gut health and has pivotal roles in digestion, immune regulation, and metabolic processes. The gut microbiome has been implicated in range of diseases and there is a rapidly growing understanding of this ecosystem’s importance in inflammatory bowel disease. We have yet to identify a single microbe that causes either ulcerative colitis or pouchitis, however, perturbations in the gut microbiome are associated with disease states. Importantly, we can manipulate the gut microbiome using dietary interventions, medications, and faecal microbiota transplantation. This review will summarise our knowledge of gut microbiome therapies in ulcerative colitis and pouchitis.

Background: Inadequate meibomian glands (MGs) secretion can lead to dry eye signs and symptoms. Tear film lipid layer (TFLL) secreted by MGs protects and prevents rapid evaporation of tear film. Our purpose was to assess TFLL alteration and function in patients with evaporative dry eye (EDE) using tear interferometry after optimal pulse light technology (OPT) intense pulsed light (IPL). Methods: This prospective randomized examiner-masked sham- controlled study included 86 participants (142 eyes) with DED. IPL or sham procedure was performed on day 0, 21, and 42. Ocular Surface Disease Index (OSDI), non-invasive breakup time (NITBUT), interferometric fringe pattern determined TFLL quality, fluorescein staining (FS), and meibum gland (MG) were assessed at day 0, 21, 42 and 3-month. Results: At 3-month, TFLL, NITBUT, MG drop-out, MG quality, MG expressibility, FS and OSDI improved significantly (P<0.05) in the IPL group, while the sham group had no significant improvements. All DE parameters significantly correlated with the improvement in TFLL following IPL treatment. Additionally, artificial tears usage was significantly less in the IPL group from D-42 onwards. Conclusion: IPL treatment demonstrated the ability to improve TFLL quality and clinically reduced sign and symptoms of DED thereby reducing the frequency of artificial tears usage.

The COVID-19 pandemic has contributed to mental health problems worldwide. Nurses are particularly prone to stress because they directly care for individuals with suspected or confirmed cases of COVID-19. The aim of this study is to explore the association between the mental health promotion strategies used by nurses during the coronavirus disease (COVID-19) outbreak and their symptoms of depression, anxiety, and stress, and to compare the strategies and symptoms of mental health nurses and non-mental health nurses. Cross-sectional study was conducted with a sample of 821 nurses. Portuguese nurses demonstrated high symptoms of depressive symptoms, stress, and anxiety. Healthy eating, physical activity, rest between shifts, maintaining social contacts, verbalizing feelings/emotions, and spending less time searching for information about COVID-19 are associated with better mental health. Mental health nurses have less depression, anxiety, and stress, and use more strategies to promote mental health than other nurses. We consider it important to promote nurses’ mental health literacy by encouraging them to develop skills and strategies aimed at improving their resilience and ability to deal with difficult situations while caring for the population.

Background The high incidence of diverticulitis and hemorrhoidal proctitis episodes in the population imposes an important healthcare and economic burden. Aim To determine the association between intake of certain plant foods and diverticulitis and hemorrhoidal proctitis episodes. Methods Case-control study with quantitative food frequency questionnaire focusing on selected plant foods and derived products. These were grouped by main chemical components into: ethanol, caffeine/theine/theobromine, capsaicin, alliin, acids, eugenol, and miscellaneous foods like curcumin. We quantified intake according to 24-h recall, either on a 1-4 scale (no intake, low, moderate, high intake) or as the number of units consumed (e.g. cups of tea/coffee, n of oranges or lemons); this value was multiplied by the number of reported intake days per week (1-7). Overall intake was expressed as a continuous variable obtained by successively multiplying the score for each food category, and the result was transformed into a common logarithm (range 0.3 to 27.7). Cases and controls were compared using the chi-squared test, student’s t test, odds ratio (OR) and 95% confidence interval (CI), and predictive analysis (multiple logistic regression). Results The sample included 410 cases and 401 controls, who were similar in mean age and gender distribution. The mean score for overall intake of included plant foods was 6.3 points (standard deviation [SD] 4.5), and this was significantly higher in cases (8.5 points, SD 5.3) than in controls (4.1 points, SD 1.2; p < 0.001). Overall intake was similar in cases presenting diverticulitis or hemorrhoidal proctitis. Cases had 13 times the odds of being in the upper quartile for overall intake (> 7 points) compared to controls (OR 13.2, 95% CI 8.3 to 20.8, p < 0.001). Predictive logistic regression models showed that the chemical food group most closely associated with diverticulitis and hemorrhoidal proctitis was capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids. The OR for age was near the null value. Neither alliin nor miscellaneous food groups showed any association. Conclusions High, frequent consumption of some plant foods and derived products increases the risk of presenting symptoms of diverticulitis and hemorrhoidal proctitis.

The functioning of the parents’ emotional sphere is very important to a child’s mental and physical health. This study focused on investigating the association between mothers’ emotional intelligence (EI) and paediatric type I diabetes (T1DM) disease management in their children. We hypothesized that mothers’ EI is associated with T1DM outcomes. Mothers of children with T1DM aged 6-12 years were surveyed. One hundred and thirty-four mothers, the main caregivers of their diabetic children, provided measures of EI and completed a demographic questionnaire. The primary indicator of diabetes management was haemoglobin A1c (HbA1c; the main form of glycosylated haemoglobin). EI scales and subscales were associated with glycaemic management indices. Logistic regression analysis was applied for the assessment of the association between parents’ EI and their paediatric with T1DM disease management. The analysis demonstrated a statistically significant correlation between T1DM management and mothers’ ability to understand and control own emotions, to transform their own negative emotions into positive and to control own negative emotions. Mothers’ EI scales and subscales of understanding and regulating their own emotions, subscales of transforming their own negative emotions into positive ones and controlling their own negative emotions were statistically reliable predictors of glycaemic control in children with T1DM.

BACKGROUND: To present a new method of urethral pressures examination, and to evaluate diagnostic capabilities of three dimensional profilometry , as an alternative to classical urethral profile (UPP) .Using four channel catheters and dedicated software global urethral pressures image is obtained. The method eliminates the main limitation of classical urethral profilometry where the catheter orientation determines the pressures picture limited to only one point in the uretral circumference while we observed even 50% differences in pressure measures depending on the point of measurement. METHODS: This is a preliminary study containing method presentation and analisys of the use in varied clinical cases of either healthy patients and patients with LUTS. The article includes technique and equipment decription, full evaluation of selected cases, including three dimensional urethral pressures distribution graphics. RESULTS AND CONCLUSIONS:Three dimensional profilometry compared to classical technique is comparable regarding the time, cost, technical difficulty and patient discomfort. At the same time we obtain much more data on the urethral pressures and its distribution.The results are easy for interpretation due to 3D movable graphics created automatically through the dedicated software.

Knee Osteoarthritis (KOA) is a chronic disease characterized by progressive disability and joint pain. Meniscus chondrocytes apoptosis is the main cause of reduced chondrocyte number and self-repair function. The purpose of this study was to investigate the role of miR-27b-3p in KOA.In this study, we found that the expression of miR-27b-3p was downregulated in cultured IL-1β treated chondrocyte and cartilage tissues in KOA. KOA overexpression evidently reduced IL-1β induced chondrocyte apoptosis and caspase-3 and caspase-9 expression.The upregulated iNOS and COX-2 mRNA and proteins expression was also inhibited by miR-27b-3p mimics. The expression of nitric oxide, PGE2, TNF-α and IL-6 was also inhibited by miR-27b-3p mimics. The target gene of miR-27b-3p was confirmed to be BDNF. TrkB/CREB pathway was proved to be the downstream pathway of miR-27b-3p/BDNF axis.The apoptotic cell percentage and nitric oxide, PGE2, TNF-α and IL-6 expression was induced by BDNF+IL-1β. This induction was inhibited by miR-27b-3p mimics. The cartilage tissues stained with safranin O results showed miR-27b-3p greatly decreased KOA induced cartilage degradation. The expression of BDNF、TrkB and p-CREB was inhibited by len-miR-27b-3p. MiR-27b-3p also reduced the expression of TNF-α、IL-6 and Bax, and increased Bcl-2 expression. These results indicated miR-27b-3p could applied to inhibit the development of KOA and miR-27b-3p/BDNF/TrkB/CREB pathway could serve as novel treatment target to handle KOA.

(1) Background: Research has shown that thoughts about pain are important for the management of chronic pain in children. In order to monitor changes in thoughts about pain over time and evaluate the efficacy of treatments, we need valid and reliable measures. The aims of this study were to develop a questionnaire to assess a child’s concept of pain and to evaluate its psychometric properties; (2) Methods: This is a cross-sectional, two-phase, mixed-method study. A total of 324 individuals aged 8 to 17 years old responded to the newly created questionnaire. The Survey of the Concept of Pain (SOCOPA) was calibrated using the Rasch model. The chi-square test was used for the fit statistics. Underfit and overfit of the model were determined and a descriptive analysis of infit and outfit was conducted to identify who responded erratically. Internal consistency was measured using the Person Separation Index (PSI); (3) Results: Fit to the Rasch model was good. Suitable targeting indicated which items were simple to answer; Person Fit identified 9.56% children who responded erratically; PSI=0.814; (4) Conclusions: The findings suggest that SOCOPA is a measure of a child’s concept of pain that is easy to administer and respond to. It has a good fit and a good internal consistency.

Background: Care home residents have complex healthcare needs but may have faced barriers to accessing hospital treatment during the first wave of the COVID-19 pandemic. Objective: To examine trends in the number of hospital admissions for care home residents during the first months of the COVID-19 outbreak. Methods: Retrospective analysis of a national linked dataset on hospital admissions for residential and nursing home residents in England between 20 January 2020 and 28 June 2020, compared to the corresponding period in 2019. Elective and emergency admission rates, normalised to the time spent in care homes across all residents, were derived across the first three months of the pandemic between 1 March and 31 May and primary admissions reasons for this period were compared across years. Results: Hospital admission rates rapidly declined during early March 2020 and remained substantially lower than in 2019 until the end of June. Between March and May, 2,960 admissions from residential homes (16.2%) and 3,295 admissions from nursing homes (23.7%) were for suspected or confirmed COVID-19. Rates of other emergency admissions decreased by 36% for residential and by 38% for nursing home residents. Emergency admissions for acute coronary syndromes fell by 42% and 28% and emergency admissions for stroke fell by 16% and 24% for residential and nursing home residents, respectively. Elective admission rates declined by 64% for residential and by 61% for nursing home residents. Conclusions: This is the first study showing that care home residents’ hospital use declined during the first wave of COVID-19, potentially resulting in substantial unmet health need that will need to be addressed alongside ongoing pressures from COVID-19.

The spillover of a virus from one host species to another requires both molecular and ecological risk factors to align. While extensive research both before and after the emergence of SARS-CoV-2 in 2019 implicates horseshoe bat as the significant reservoir genus for the new coronavirus, it remains unclear why it emerged at this time. One massive disruption to human-animal contact in 2019 is linked to the on-going African swine fever virus (ASFV) pandemic. This began in Georgia in 2007 and was introduced to China in 2018. Pork is the major meat source in the Chinese diet. Severe fluctuations in the pork market prior to December 2019, may have increased the transmission of zoonotic pathogens, including severe acute respiratory syndrome–related coronaviruses, from wildlife to humans, wildlife to livestock and non-local animals to local animals. The major production and consumption regions for pork are geographically separated in China. The dramatic shortage of pork following restrictions of pig movement and culling resulted in price increases, leading to alternative sources of meat and unusual animal and meat movements nationwide often involving wildlife and thus greatly increased opportunities for human-Sarbecovirus contacts. Pork prices were particularly high in southern provinces (Guangdong, Guangxi, Fujian, Jiangxi, Hunan, and Hubei), where wildlife is farmed on different scales and more frequently consumed. Shandong experienced the biggest losses in pork production (~1.7 million metric tons), which is also the largest mink farming province. Hence, human exposure to SARS-CoV-2 from wildlife or infected animals are more likely to have taken place in 2019, when China was experiencing the worst effects of the ASFV pandemic.

L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. However, while the binding mechanisms of L-17 to the SERT and 5-HT1A receptor were similar to fluoxetine and WAY100135, its interacting with 5-HT3 receptor might be substantially different from this of granisetron. Acute administration of L-17 led to dose-dependent inhibition of firing activity of 5-HT neurons of the dorsal raphe nucleus. This inhibition was partially reversed by subsequent administration of WAY100135. Based on both in silico and in vivo electrophysiology assessments, we suggest that L-17 is a potent 5-HT reuptake inhibitor and a putative partial agonist of 5-HT1A receptors. As such, L-17 in particular and thiadiazine derivatives, in general, might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardioprotective properties, it can be useful in affective illness developing due to the general medical condition, such as post-stroke and post-myocardial infarction (MI) depression.

Fire-related deaths are issues for forensic pathologists particularly in ascertaining if death occurred before or during fire. The authors highlight a unique bronchiolar epithelial cytological clue (nuclear heat-induced elongation) determined by active inhalation of hot gases and fumes, not yet described in the literature at distal small airways level.

BACKGROUND AND PURPOSE—Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, the metformin therapy reducing the metabolic distress and the inflammatory burden, could lead to reduction of MACE in ACAS patients with pre-diabetes. In this setting, microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture and worse prognosis in normoglycemics (NG) vs. pre-diabetics metformin users (PDMU) vs. pre-diabetics non metformin users (PDNMU). However, the aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG vs. PDMU vs. PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. METHODS—The study included 234 patients with ACAS divided in NG (n 125), PDNMU (n 73) and PDMU (n 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from plasma samples of the patients from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG vs. PDMU vs. PDNMU. RESULTS—prediabetics vs. NG had over-inflammation (p<0.05) and over expressed miR 24 and miR 27 at baseline. At 2 years of follow-up PDNMU vs. NG, PDMU vs. NG and PDNMU vs. PDMU over-expressed inflammatory markers and miR 24, miR 27, miR 100, miR 126 and miR 133 (p<0.05). Finally, at follow-up end we observed a significant difference about MACE comparing PDNMU vs. NG (n 27 (36.9%) vs. n 8 (6.4%); p<0.05), PDNMU vs. PDMU (n 27 (36.9%) vs. n 6 (16.6%); p <0.05), and PDMU vs. NG (n 6 (16.6%) vs. n 8 (6.4%); p<0.05). Admission glucose values (HR 1.020, CI 95% [1.001-1.038], p 0.029), atheromatous carotid plaque (HR 5.373, CI 95% [1.251-11.079], p 0.024), and miR 24 (HR 3.842, CI 95% [1.768-19.222], p 0.011) predicted MACE at 2 years of follow-up. CONCLUSIONS—Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU vs. PDMU after endarterectomy. MiR24, hyperglycemia and atheromatous plaque could predict MACE at 2 years of follow-up.

Growing evidence from neurodegenerative disease research supports an early pathogenic role for mitochondrial dysfunction in affected neurons that precedes morphological and functional deficits. Resulting oxidative stress and respiratory malfunction contribute to neuronal toxicity and may enhance the vulnerability of neurons to continued assault by aggregation-prone proteins. Consequently, targeting mitochondria with antioxidant therapy may be a non-invasive, inexpensive, and viable means of strengthening neuronal health and slowing disease progression, thereby extending quality of life. We review the pre-clinical and clinical findings available to date of the natural bioactive phenol resveratrol and two synthetic mitochondrial-targeted antioxidants MitoQ and SkQ.

Urinary and fecal incontinence as well as skin pressure injury are common healthcare problems in nursing home; however, these prevalence and related risk factors were not well understood in the Japanese special elderly nursing home settings. We surveyed the prevalence of urinary, fecal and double incontinence, and skin pressure injury among the elderly living in special elderly nursing home in Japan. A nationwide cross-sectional epidemiological survey was conducted with a total of 4,881 residents. The prevalence of urinary, fecal and double incontinence was 82.9%, 68.9% and 64.9%, respectively. Skin pressure injury was found in 283 residents (283/4881, 5.8%). Age, Care-Needs level, loss of voiding desire, and fecal incontinence were significant risk factors for urinary incontinence. Residential period, Care-Needs level, loss of voiding and defecation desires, and urinary incontinence were significant risk factors for fecal incontinence. Only male sex was a significant risk factor for skin pressure injury. Our study revealed continence status and the prevalence of pressure skin injury among older adult residents who receive an end-of-life care in special nursing homes in Japan. Further studies should be conducted to examine whether recovery of urinary and fecal sensations improves continence status.

The original purpose of this article was to modify the original SIR equations to allow for a direct source of infection (without which the original equations would have no solutions unless one starts with an already infected population) and also to see to what extent one could obtain multiple outbreaks of an infectious disease. In the course of developing the basic ideas several other factors arose to take prominent roles.Perhaps one of the more salient factors is the point that choosing an arbitrary time to change conditions from say a lock-down for the population to a less stringent social behavior, such as allowing partial or complete opening of businesses and schools, etc. should be based on knowledge of the disease and its evolution. Such decisions are usually made by politicians who have less than full information concerning the consequences of their actions. Several examples are given to illustrate these points.

Substances that can modify the androgen receptor pathway in humans and animals are entering the environment and food chain with the proven ability to disrupt hormonal systems and leading to toxicity and adverse effects on reproduction, brain development, and prostate cancer, among others. State-of-the-art databases with experimental data of human, chimp, and rat effects by chemicals have been used to build machine learning classifiers and regressors and evaluate these on independent sets. Different featurizations, algorithms, and protein structures lead to dif- ferent results, with deep neural networks (DNNs) on user-defined physicochemically-relevant features developed for this work outperforming graph convolutional, random forest, and large featurizations. The results show that these user-provided structure-, ligand-, and statistically-based features and specific DNNs provided the best results as determined by AUC (0.87), MCC (0.47), and other metrics and by their interpretability and chemical meaning of the descriptors/features. In addition, the same features in the DNN method performed better than in a multivariate logistic model: validation MCC = 0.468 and training MCC = 0.868 for the present work compared to evalu- ation set MCC = 0.2036 and training set MCC = 0.5364 for the multivariate logistic regression on the full, unbalanced set. Techniques of this type may improve AR and toxicity description and predic- tion, improving assessment and design of compounds. Source code and data are available at https://github.com/AlfonsoTGarcia-Sosa/ML

There is a huge need to search for new treatment options and potential biomarkers of therapeutic response to antidepressant treatment. Depression and metabolic syndrome often coexist while pathophysiological overlap, including microbiota changes, may play a role. The aim of the study is to assess the effect of probiotic supplementation on symptoms of depression, anxiety and stress, metabolic parameters, inflammation and oxidative stress markers, and faecal microbiota in adult patients with depressive disorders depending on the co-occurance of MetS. The trial will be a four-arm, parallel group, prospective, randomized, double-blind, controlled design that will include 200 participants and will last 20 weeks. The probiotic preparation will contain Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175. We will assess the level of depression, anxiety and stress, quality of life, blood pressure, body mass index and waist circumference, white blood cells count, serum levels of C-reactive protein, HDL cholesterol, triglicerides, fasting glucose, faecal microbiota composition and the level of some faecal microbiota metabolites, as well as inflammation markers and oxidative stress parameters in serum. The trial may establish a safe and easy-to-use treatment option as an adjunct in a subpopulation of depressive patients only partially responsive to pharmacologic treatment. (ClinicalTrials.gov identifier: ).

Background: Neurological disorders are the leading cause disability in Australia and the world. Combating the perceived difficulty of neurology or “neurophobia” and improving physician education is a key component in addressing this problem. We aim to conduct the first study to identify whether neurophobia exists in medical students and junior doctors in an Australian population and try to identify factors that may contribute to this in this population. Methods: A 24 question online validated survey was distributed via email broadcast to all medical students and junior doctors at a metropolitan tertiary care centre in Australia. Responses were collected over 6 weeks with weekly reminder emails for 4 weeks after the initial invitation email. Results: 114 medical students and junior doctors participated in the study. Participants perceived neurology as the most difficult medical speciality compared to 10 other medical specialties (p=0.001). The top three factors contributing to this perceived difficulty were: a lack of understanding of neuroanatomy, lack of diagnostic certainty and lack of clinical exposure. 65% of the participants stated that they had too little planned teaching in neurology with only 36% of the participants having performed a neurology rotation during medical school. Conclusion: The prevalence of neurophobia in this Australian cohort of medical students and junior doctors is consistent with previous findings from around the world. This concerning finding requires further examination into the contributing factors in order to created trials of targeted interventions in order to resolve this.

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta that progressively grows till the rupture. Treatment is typically recommended when the diameter is more than 5 cm. The EVAR (Endovascular aneurysm repair) is a mininvasive procedure that involves the placement of an expandable stent graft within the aorta to treat aortic disease without operating directly on the aorta. For years, stent grafts' essential design was based on metallic stent frames to support the fabric. More recently, a polymer-based technology has been proposed as an alternative method to seal AAA. This review underlines the two platforms that are based on a polymer technology: 1)the polymer-filled endobags, so-called Endovascular Aneurysm Sealing (EVAS) with Nellix stent graft; and 2)the O-ring EVAR polymer-based proximal neck sealing device, so-called Ovation stent graft. Polymer characteristics for this particular aim, clinical applications, and durability results are summarized and commented critically. The platform that embraced the concept of inflating endobags filled with polymer to exclude the aneurysmal sac was not successful because of the lack of an adequate proximal fixation. The platform that used polymer to create a circumferential sealing of the aneurysmal neck has proven safe and effective.

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

Background: We aimed to study the frequency, management, and outcomes of patients with blunt pancreatic trauma. Methods: We reviewed the medical records for all patients admitted with pancreatic injuries between 2011 and 2017 at the only level 1 trauma center in the country. Results: There were 71 patients admitted with pancreatic trauma (0.6% of trauma admissions and 3.4% of abdominal injury admissions) with a mean age of 31 years. Sixty-two patients had pancreatic injury grade I-II and 9 had grade III-IV. Thirty-eight percent had GCS <9 and 73% had ISS >16. The level of pancreatic enzymes was significantly proportional to the grade of injury. Over half of patients required a laparotomy, of them 12 patients had an intervention on the pancreas. Eight patients developed complications related to pancreatic injuries ranging from pancreatitis to pancreatico-cutaneous fistula while 35% developed hemorrhagic shock. Mortality was 31% and regardless of the grade of injury, the mortality was associated with high ISS, low GCS and presence of hemorrhagic shock. Conclusion: Pancreatic injuries following blunt trauma are rare and the injured subjects are usually young male. However, most injuries are of low-grade severity. This study shows that shock, higher ISS and lower GCS are associated with worse in-hospital out-comes. Non-operative management may suffice in patients with lower grade injuries, which may not be the case in patients with higher grade injuries unless carefully selected

Glioma accounts for 80% of all malignant brain tumors and is the most common adult primary brain tumor. Age is an important factor affecting the development of cancer as somatic mutations accumulate with age. In this study, we aimed to analyze the significance of age-related non-silent somatic mutations in glioma prognosis. Histological tumor grade depends on age at diagnosis in patients with IDH1, TP53, ATRX, and EGFR mutations. The hierarchical clustering of patients was dominantly separated by IDH1 and EGFR mutations. Furthermore, patients with IDH1 mutation were dominantly separated by TP53 and ATRX double mutation and its double wildtype counterpart. Patients with the double mutation showed poorer prognosis than those with the double wild type genotype. In conclusion, among the many somatic mutations, those in IDH1, TP53, ATRX, and EGFR are important for glioma classification based on histological grade. Patients with EGFR mutation had the poorest prognosis, whereas those with only IDH1 mutation showed the best prognosis.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Aim. The purpose of the work was the development of a machine learning model for diagnosing the stage of liver fibrosis in patients with chronic viral hepatitis C according to the data of routine clinical examination. Materials and methods. A total of 1240 patients with chronic viral hepatitis C was examined. A set of data obtained from 689 patients balancing by the stage of liver fibrosis was used for developing and testing machine learning models. 9 routine clinical parameters were selected as the most important predictors for determining the likelihood of liver fibrosis the 3–4 stages presence: age, height, weight and body mass index of the patient, the number of platelets in the clinical blood test, levels of alanine transaminase, aspartate transaminase, gamma-glutamyltransferase, and total bilirubin in a biochemical blood test. Results. The accuracy of the developed method for determining the 3–4 stages of liver fibrosis in patients with chronic viral hepatitis C in comparison with the «gold standard» of diagnosis (liver biopsy) was 80.56% (95% CI: 69.53–88.94%), sensitivity — 66.67%, specificity — 94.44%. Conclusion. The developed method is an alternative to more expensive and geographically inaccessible studies. The method does not require the purchase of additional equipment or software, as well as additional laboratory tests, when used in real clinical practice. The introduction of the method into clinical practice can help to solve the problem of low material and territorial availability of diagnostic tests and allow determining the stage of liver fibrosis in patients with chronic viral hepatitis C.

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

Background We intend to examine whether the COVID-19 outbreak influences medical decision-making (MDM) among Non-COVID patients. Method We recruit 287 patients who admit to ER department due to cardiovascular complaints. Anxiety level was measured using three questionnaires (GAD-7, Beck Inventory, and the cardiac anxiety questionnaire). A fourth survey was designed to assess MDM considerations. Results 64% of patients were male (median age 54). Almost half of the patients were found to have moderate to severe levels of anxiety.79.3% of patients reported that the outbreak influenced their MDM. 44.5% of patients sought medical care 2-3 from the onset of symptoms. Coronary artery disease was found in only 26 patients (9.1%). Almost half of the patients stated that they would have gone earlier if not for the current pandemic. Conclusion Non-COVID patients seeking medical care had a high anxiety level that directly affected decision-making and put them at unnecessary risk.

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

Background: Australia’s healthcare system is complex and fragmented which can create challenges in healthcare, particularly in rural and remote areas. Aboriginal people experience inequalities in healthcare treatment and outcomes. This study aimed to investigate barriers and enablers to accessing healthcare services for Aboriginal people living in rural and remote Australia. Methods: Semi-structured interviews were conducted with healthcare delivery staff and stakeholders recruited through snowball sampling. The communities were selected for their high proportion of Aboriginal people and geographical representation (coastal, rural, and border). Thematic analysis identified barriers and enablers. Results: Thirty-one interviews were conducted (n =5 coastal, n=13 remote, and n=13 border) and six themes identified: 1) Improved coordination of healthcare services; 2) Better communication between services and patients; 3) Trust in services and cultural safety; 4) Importance of prioritizing health services by Aboriginal people; 5) Importance of reliable, affordable and sustainable services; 6) Distance and transport availability. These themes were often present as both barriers and enablers to healthcare access for Aboriginal people. They were also present across the healthcare system and within all three communities. Conclusions: This study describes a pathway to better healthcare outcomes for Aboriginal Australians by providing insights into ways to improve access.

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognizing symptoms do not readily trigger an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate self-care management and quality of life changes on patients with heart failure and assessed by a pilot study, for three months, to sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p<.001) and emergency admission (IRR 4.24; p<.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assign-ment_group=-.881; p<.001) and in the quality of life (βSlope. Assignment_group=1.739; p<.001). This study supports that a nurse-led program on symptom recognition and fluid restriction can have a positive impact on self-care behaviours and quality of life in patients with heart failure.

The prevalence of food allergy has increased in recent years, especially in children. Food allergen avoidance and symptomatic drugs in case of an allergic reaction remain the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanuts, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes.

The aim of this article was to examine if there are position-specific differences in the morphological characteristics of sub-elite female football players and to establish normative standards for this level of female football players. The morphological features of 101 sub-elite female football players (age: 21.8±2.7 years) were assessed. Twenty anthropometric sites were used in the measurements of body composition and somatotype. The average value of body fat percentage was 20.8±5.7%. The somatotype of the overall group was 4.0–2.4–2.1. Positional significant (p ≤ 0.05) differences were found between goalkeepers and outfield players in morphological characteristics. Goalkeepers were taller, heavier, possessed the highest body fat percentage and showed higher values for all skinfolds, breadth, girth and length measurements. However, there were very few practically worthwhile differences between the outfield positions. Positional groups did not differ (p ≤ 0.05) in somatotype characteristics either. The study suggests that at sub-elite level there are mainly differences between goalkeepers and outfield players, but outfield players are homogeneous when comparing morphological characteristics. These results may serve as normative values for future comparisons regarding the morphological characteristics of female football players.

Background: The use of technology in paediatrics is increasing, and new health technology will change the way in which paediatric care is delivered in the future. This review is part of the Royal College of Paediatrics and Child Health Paediatrics 2040 project, which is developing a credible vision for the future of paediatrics in the UK. Aims: To summarise the impact of health technology on the delivery of paediatric care over the last ten years. To learn from existing technology use and make recommendations for future implementation. Methods: A search strategy was developed and two databases (Cochrane Library and PubMed) were systematically searched in August 2019 for relevant publications in English. Searches were limited to papers published between January 2009 and August 2019 (with further rapid review of papers published between September 2019 and November 2020). We included papers that studied young people up to the age of 24 or on those providing care for this population. A thematic synthesis of the data from the included studies was undertaken using seven domains of paediatric care. Results: 128 studies were included, grouped by domain of care. Most included studies were defined as digital (n=55) or communication (n=37). Studies looked at the different types of health technology used within different domains of care, including secondary and tertiary care (n=39), public health and prevention (n=29), and community (n=20). Studies were assessed on delivery of care outcomes using positive, negative, mixed and no effect. The most common outcomes reported were adherence and satisfaction. Discussion: This review highlights the growing importance of technology in delivering paediatric care. Six themes emerged: the importance of clear guidelines, continuity of care, confidentiality and privacy, digital poverty, using a personalised approach, and using technology to supplement rather than replace. In future, technology development should involve the end user throughout the design process.

There is an increasing interest in revisiting plants for drug discovery proving scientifically their role as remedies. Pistacia lentiscus (PL) is a wild-growing shrub rich in terpenoids, which are pharmacological appealing. The more recurrent components in the oil are represented by α-pinene, terpinene, caryophyllene, limonene, and myrcene. High concentration of polyphenols enriches the extracts. PL-extracts showed in vitro and in animal model strong anti-inflammatory and anti-oxidative activities. The anti-inflammatory activity mainly occurs due to inhibition of NF-kB pathway or directly toward the proinflammatory cytokines, or arachidonic acid cascade against COX-2 and LOX. The antimicrobial activity of PL essential oil and extracts includes among others Staphylococcus aureus, Escherichia coli, periodontal bacteria and Candida sp.. In conclusion, the biological properties, and particularly the anti-inflammatory and anti-microbial capacity, propose PL as a new safe pharmaceutical agent.

The purpose of this evaluation is to determine the effect of intensive, interactive training on hospital workers’ preparedness for special pathogen cases by utilizing the Frontline Facility Special Pathogens Training Course created by New York

Theranostics covers combination of diagnostic and therapeutic techniques for various cancers throughout body using suitable drug combination. This review covers well-known treatment of thyroid cancer and pheochromocytoma with I-131 compounds and also new radiopharmaceuticals for prostatic cancer and pancreatic cancer. Of particular, new trends toward patient outcome has been focused. A recent clinical study highlighted the ability of alpha-radiotherapy with high LET to overcome treatment resistance to beta--particle therapy. The theranostics will become an ever-increasing part of clinical nuclear medicine these days.

Caesarean scar ectopic pregnancy (CSEP) is an uncommon form of ectopic pregnancy. This review defines types of CSEP, discusses pathophysiology, clinical presentation and diagnosis and compares common treatment options and outcomes. The pathophysiology is not yet fully understood. One third of patient are asymptomatic. In symptomatic patients vaginal bleeding and pelvic pain which is usually misdiagnosed as threatened or missed abortion. The main principles of treatment for CSEP are early diagnose, quick management, and maintain reproductive function as much as possible. Up to date; no consensus or guidelines for the treatment and management of CSEP. Management of CSEP depends on the clinical presentation and gestational age. Significant controversy exists regarding management, for this reason, several factors should be considered including age of the patient, myometrial thickness, clinical symptoms, hemodynamic status, fertility preservation.

Tissue engineering and regenerative medicine has gradually evolved as a promising therapeutic strategy to the modern healthcare of the aging and diseased population. In this study, we developed a novel nano-fibrous scaffold and verified its application in the critical bone defect regeneration. The metformin-incorporated nano-gelatin/hydroxyapatite fibers (NGF) was produced by electrospinning, cross-linked, and then characterized by XRD and FTIR. Cytotoxicity, cells adhesion, cell differentiation, and quantitative osteogenic gene and protein expression were analyzed by bone marrow stem cells from rat. Rat forearm critical bone defect model was performed for the in vivo study. The nano-gelatin/hydroxyapatite fibers (NGF) were characterized by their porous structures with proper interconnectivity without significant cytotoxic effects; the adhesion of bone marrow stem cells on the nano-gelatin/hydroxyapatite fibers (NGF) could be enhanced. The osteogenic gene and protein expression were upregulated. Post implantation, the new regenerated bone in bone defect was well demonstrated in the NGF samples. We demonstrated that the metformin-incorporated nano-gelatin-hydroxyapatite fibers greatly improved healing potential on the critical sized bone defect. Although metformin-incorporated nano-gelatin/hydroxyapatite fibers had advantageous effectiveness during bone regeneration, further validation is required before it can be applied to clinical applications.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiological agent of the current pandemic worldwide. The pathological condition induced by this pathogen is known as COVID-19 disease. SARS-CoV-2 associated pandemic has been defined as a “public health emergency of international concern” by the International Health Regulation Emergency Committee of the World Health Organization. To date, considerable efforts are in progress to develop more advanced strategies against SARS-CoV-2. Despite the numerous scientific studies published, our knowledge regarding this pathogen is still incomplete, as this virus has been identified only recently. Therefore, scientific investigation of the SARS-CoV-2 has been possible only for a short period of time and effective management of the serious forms of this disease is still lacking. Considerable efforts are in progress worldwide with the purpose to develop more advanced strategies against this pathogen. In this review, we have analyzed the structural and the biological SARS-CoV-2 characteristics and those of other well-known RNA viruses, with the aim to identify possible similarities and analogies between all these pathogens, may be a very useful approach. These infectious agents have been widely studied since several years ago and, a large series of scientific reports are available in the literature regarding this topic. Therefore, focusing on the Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Influenza viruses (IVs), we have collected their historical data, clinical manifestations, pathogenetic mechanisms and related infections. Taking advantage of the results of our research, we have assembled this narrative review, with the aim to get useful insights and lessons from HIV, HCV and IVs characteristics and, consequently, to transfer the obtained knowledge to the study of SARS-CoV-2 biology. There are well known differences between all these pathogens. In particular, they present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne pathogens, whereas HIV and HCV are bloodborne infectious agents. However, these viruses exhibit some potential common clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2. Accordingly, we have analysed and discussed the following points: 1) the biology, the pathogenesis and the clinical manifestations of SARS-CoV-2, HIV, HCV and IVs in mankind; 2) the onset and spreading of pandemics caused by respiratory viruses according to a perspective historical point of view; 3) the possible development of a persistent SARS-CoV-2 reservoir worldwide; 4) the possibility of SARS-CoV-2 reinfection/reactivation; 5) the possible involvement and impact of climatic factors in increasing the risk of SARS-CoV-2 spreading.

(1) Background: The aim of the present study was to evaluate the effect of different types of warm-ups on the strength and skin temperature of Paralympic powerlifting athletes; (2) Methods: The participants were 15 male Paralympic powerlifting athletes. It was analyzed the effects of three different types of warm-up (without warm-up (WW), traditional warm-up (TW), or stretching warm-up (SW)) on static and dynamic strength tests as well as in the skin temperature, which was monitored by thermal imaging; (3) Results: show no differences in the dynamic and static indicators of the force in relation to the different types of warm-up. No significant differences were found in relation to the Peak Torque (p = 0.055, F=4.560, η2p= 0.246 medium effect), and 1-Repetition Maximum (p = 0.139, F=3.191, η2p = 0.186, medium effect) between the different types of warm-up. In the thermographic analysis, there was a significant difference only in the Pectoral muscle clavicular portion between the TW (33.04 ± 0.71ºC) and the WW (32.51 ± 0.74ºC) (p = 0.038). The TW method also presented slightly higher values than the SW and WW in the Pectoral Muscles Sternal portion and in the Deltoid anterior portion, but with p-value &gt; 0.05; (4) Conclusions: that the types of warm-up studied do not seem to interfere with the performance of Paralympic Powerlifting athletes. However, the thermal images showed that traditional warm-up best meets the objectives expected for this preparation phase.

The COVID-19 pandemic has become a public health emergency of international concern, which may affect lifestyle habits and mental health. Based on national health profile assessments, this study investigates perceived changes of lifestyle habits in response to the COVID-19 pandemic and associations between perceived lifestyle changes and mental health in Swedish working adults. Among 5,599 individuals (50% women, 46.3 years), the majority reported no change (sitting 77%, daily physical activity 71%, exercise 69%, diet 87%, alcohol 90%, and smoking 97%) due to the pandemic. Changes were more pronounced during the first wave (April-June) compared to the second (October-December). Women, individuals <60 years, having a university degree, being white-collar workers and having unhealthy lifestyle habits at baseline had higher odds of changing lifestyle habits compared to their counterparts. Negative changes in lifestyle habits as well as more time in mentally passive sitting at home was associated with higher odds of mental ill-health (including health anxiety regarding one’s own and relatives’ health, generalized anxiety and depression symptoms, and concerns regarding employment and economy). The results em-phasize the need to support healthy lifestyle habits to strengthen the resilience in vulnerable groups of individuals to future viral pandemics, and prevent health inequalities in society.

It is known for decades that viruses from the Coronoviridae family can adapt to human-to-human transmission. In 2020, SARS-CoV-2 caused a global pandemic of unprecedented scale imposing the loss of millions of human lives and being at the heart of a global economic crisis. Thus, we overviewed key research advances generated from the identification of the etiological agent to a better understanding of its origin, evolution and factors underlying global spread. Furthermore, we analyze the scientific productivity using the PubMed database. We found that the total number of publications increased more than 8% in 2020 when compared with 2019 or the average publications per year in the previous quinquennial. Remarkably, 86,638 publications related with COVID-19 and SARS-CoV-2 were published in 2020. Furthermore, there was also an increase in 2020 of publications in other major infectious diseases, such as AIDS, tuberculosis, or malaria. This success is likely the result from the vigorous, international, collaborative, and multidisciplinary response by the research community. During 2020 it was demonstrated, that with adequate support, it is possible to boost the rate of scientific progress in infectious diseases. Sustained investment in science will be key to address existing and future pandemics as the human population increases.

The aim of the study was to examine the prevalence of suicide thoughts and -attempts during the early stage of the COVID-19 outbreak and examine factors associated with suicide thoughts in the general Norwegian population. A sample of 4527 adults living in Norway were recruited via social media. Data related to suicide thoughts and attempts, mental health variables, pandemic-related concerns and sociodemographic variables were collected. Associations with suicide thoughts were analyzed with logistic regression analysis. In the sample, 3.6 % reported suicide thoughts during the last month, while 0.2 % had attempted to commit suicide during the same period. Lower age (OR: 0.66, p < 0.001), daily alcohol use (OR: 3.29, p < 0.001), being in the risk group for COVID-19 complications (OR: 2.38, p < 0.01), and having economic concerns related to the pandemic (OR: 2.51, p < 0.001) were associated with having suicide thoughts. In addition to known risk factors, the study suggests that aspects specific to COVID-19 may be important for suicidal behaviors during the pandemic.

Exopolysaccharides or extracellular polysaccharides (EPS, sPS) represent valuable metabolite compound synthesized from red microalgae. It is a non toxic natural agent and can be applied as immunostimulant. Toxicity test of exopolysaccharides from Porphyridium has been done in-vivo using zebrafish (Danio rerio) embryonic model, or the ZET (Zebrafish Embryotoxicity Test). The administration of extracellular polysaccharide or exopolysaccharides (EPS) from microalgae Porphyridium cruentum (synonym: P. purpureum) on shrimps Litopenaeus vannamei was investigated to determine the effect of this immunostimulant on their non specific immune response and to test if this compound can be used as a protective agent for shrimp related to Vibrio infection. For immune response, exopolysaccharides was given to shrimps by immersion method on day 1 and booster on day 8. Shrimp hemocytes were taken on day 1 (EPS administration), day 7 (no treatment), day 8 (EPS booster) and day 9 (Vibrio infection) and tested for their immune response on each treatment. Result shows that the EPS is not toxic as represented by the normal embryonic development and the mortality data. In the Pacific whiteshrimps, it show an increase in values ​​of all immune parameters in line with the increasing EPS concentration, except the Differential Haemocyte Count (DHC). In detail, an increase was noted in total hemocytes (THC) value, Phagocytotic Activity (PA), Respiratory Burst (RB) in line with the EPS concentration increase. These results and other previous studies indicate that EPS from Porphyridium is safe and it enhances immune parameters in shrimp rapidly and has the ability as an immunostimulant or an immunomodulator. It is a good modulator for the non-specific immune cells of Pacific white shrimps, and it can be used as a preventive agent against vibriosis.

COVID-19 has been a global healthcare concern impacting multiple aspects of individual and community wellness. As one moves forward with different methods to reduce the infection and mortality rates, it is critical to continue to study the impact that national and local ‘social distancing’ policies have on the daily lives of individuals. The aim of this study was to examine loneliness in relation to risk assessment, measures taken against risks, concerns, and social media use, while adjusting for sociodemographic variables. The cross-sectional study collected data from 3469 individuals from USA, UK, Norway, and Australia. Loneliness was measured with the de Jong Gierveld Loneliness Scale. Multiple linear regression was used in the analysis of associations between variables. The results showed that concerns about finances were more strongly associated with social loneliness, while concerns about the future was more strongly associated with emotional loneliness. Longer daily time spent on social media was associated with higher emotional loneliness. In conclusion, pandemic-related concerns seem to affect their perceptions of loneliness. While social media can be used productively to maintain relationships, and thereby prevent loneliness, excessive use may be counterproductive.

The morbidity and mortality caused by invasive fungal infections is increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is an effective way of expanding the application of existing drugs. In the last years, various existing drugs have been shown to be useful in the prevention and treatment of the invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up to date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field.

Objectives: This study was performed to estimate diagnostic accuracy of the two commercially available point-of-care tests to identify poor glycemic control defined by HbA1c levels, with HPLC as a reference. Settings: The study was carried at two locations, general medical out-patient department of a teaching medical college in Bhopal (urban), and a primary health care centre in rural area in the state of Madhya Pradesh, India.Participants: All individuals with diabetes mellitus who presented to the health care facility for assessment of glycemic control. We excluded participants who denied a written informed consent. No other exclusions were used. We compared HbA1c estimated from two index tests (Hemocue Hb501, Sweden; SD Biosensor, South Korea) from capillary blood samples with HPLC performed from venous blood, as a reference standard. Primary and secondary outcome measures: Diagnostic properties of index tests such as sensitivity, specificity, positive and negative predictive value and diagnostic accuracy for identifying poor glycemic control were primary outcome measures. Lin’s concordance correlation coefficient (CCC) was secondary outcome measure.Results: Out of 114 patients, all received reference standard, 103-Hemocue A1C test, and 110- SD Biosensor test. Overall both the index-tests had similar diagnostic accuracy estimates. The area under the Receiver Operating Curve for SDA1c device was 0.935 (95%CI 0.886-0.983), and for Hemocue device was 0.938 (95%CI 0.893-0.984). The Hemocue device HbA1c value of above 7.0 (positive) correctly predicted poor glycemic control 92% times (81.58% for SD device). There were 4 vs. 11 device failures and 14 vs. 12 failures with SD and Hemocue respectively. Ambient air temperatures were no different for the device test failures.Conclusions: Commercially available point-of-care tests evaluated in this study are comparable and an acceptable alternative to HPLC based measurements for assessment of glycemic control. Tests and device failure rates of both the index tests are similar.

Temporomandibular disorders (TMD) is a group of orofacial pain conditions which is the most common non-dental pain complaint in the maxillofacial region. Due to the complexity of the etiology and often cyclical nature of the disease, the diagnosis and management of TMD remain a challenge where consensus is still lacking in many aspects. While clinical examination is considered the most important process in the diagnosis of TMD, imaging may serve as a valuable adjunct in selected cases. Depending on the type of TMD, many treatment modalities have been proposed, ranging from conservative options to open surgical procedures. In this review, the authors discuss the present thinking in the etiology and classification of TMD, followed by the diagnostic approach and the current trend and controversies in management.

Sound evidence recognizes the microbiota as one of the major players in human health and disease, including cancer. Every human being is an holobiont, a shared human and microbial ecosystem, in which microbial composition is individually set by behaviours and environmental factors during the first years of life. Thereafter it is modulated by diet, physical activity, emotions and drugs (in particularly antibiotics and chemotherapeutics). As a consequence, a shift in medicine is needed toward a more comprehensive practice that takes into account every individual's genoma and, in addition, his or her metagenome, known as microbiome: a "microbiota revolution". As regards breast cancer (BC), a clear link between microbiota and oncogenesis is still to be confirmed. Specific microbes display unique features regulating their host niche in a number of body sites, which can result in an increased risk of cancer; in addition, gut microbiota composition plays a role in immune modulation within the intestinal barrier, affecting local and systemic inflammation, recognized drivers of cancer. Moreover, part of the bacterial gene mass inside the gut, constituting the so called “estrobolome”, influences the sexual hormonal balance and subsequentely may impact on the onset, progression and treatment of hormonal dependent cancers. Microbiota is also clearly involved in modulating the response to anticancer treatments, and above all to the emerging immunotherapy. Based on these premises, the microbiome is becoming a potential target, in order to enhance efficacy of antitumoral treatments as well as to lower their toxicity. The complex scenario that links microbiome composition to oncogenesis and response to anticancer treatments defines the frames of a new “oncobiotic” perspective.

Introduction: Despite the introduction of increasingly multifaceted diagnostic techniques and the general progress of emergency abdominal and vascular surgery, the outcome of treatment of patients with acute impaired intestinal circulation remains unsatisfactory. The non-invasive and high-resolution technique of optical coherence tomography (OCT) can be used intraoperatively to assess intestine viability and associated conditions that frequently emerge under conditions of impaired blood circulation. This study aims to demonstrate the effectiveness of multimodal (MM) OCT for intraoperative diagnostics of both the microstructure (cross-polarization OCT mode) and microcirculation (OCT angiography mode) of the small intestine wall in patients with acute mesenteric ischemia (AMI). Methods and Participants: A total of 18 patients were enrolled in the study. Nine of them suffered from AMI in segments II-III of the superior mesenteric artery (AMI group), where the ischemic segments of the intestine were examined. Nine others were operated for adenocarcinoma of the colon (control group), thus allowing areas of their normal small intestine to be examined for comparison. Data on the microstructure and microcirculation in the walls of the small intestine were obtained intraoperatively from the side of the serous membrane using the MM OCT system (IAP RAS, Russia) before bowel resection. The MM OCT data were compared with the results of histological examination. Results: The study finds that MM OCT visualized the damage to serosa, muscularis externa, and blood vessels localized in these layers in 100% of AMI cases. It also visualized the submucosa in 33.3% of AMI cases. The MM OCT image of non-ischemic (control group), viable ischemic and necrotic small intestines (AMI group) differed significantly across stratification of the distinguishable layers, the severity of intermuscular fluid accumulations and the type and density of the vasculature. Conclusion: The MM OCT diagnostic procedure optimally meets the requirements of emergency surgery. Data on the microstructure and microcirculation of the intestinal wall can be obtained simultaneously in real time without requiring contrast agent injections. The depth of visualization of the intestinal wall from the side of the serous membrane is sufficient to assess the volume of the affected tissues. However, the methodology for obtaining MM OCT data needs to be improved to minimize the motion artefacts generated in actual clinical conditions.

Anemia is a condition of decreased red blood cell number or hemoglobin concentration, or of disturbance in their function, ultimately leading to decreased oxygen transport to tissues. Many factors and diseases may lead to anemia, with wide manifestations systemically as well as orally. Therefore, a sound understanding of this condition is essential for the dental practitioner, with emphasis on alerting signs, dental management and proper communication with patient’s physician.

Polyamines are nitrogen-rich polycationic ubiquitous bioactive molecules with diverse evolutionary-conserved functions. Their activity interferes with numerous genes' expression resulting in cell proliferation and signaling modulation. The intracellular levels of polyamines are precisely controlled by evolutionary-conserved machinery. Their transient synthesis is induced by heat stress, radiation, and other traumatic stimuli in a process termed the polyamine stress response (PSR). Notably, polyamine levels decline gradually with age; and external supplementation improves lifespan in model organisms. This corresponds to cytoprotective and reactive oxygen species scavenging properties of polyamines. Paradoxically, age-associated neurodegenerative disorders are characterized by an upsurge in polyamine levels, indicating polyamine pleiotropic, adaptive, and pathogenic roles. Specifically, arginase overactivation and arginine brain deprivation have been shown to play an important role in Alzheimer’s disease (AD) pathogenesis. Here, we assert that a universal short-term PSR associated with acute stimuli is beneficial for survival. However, it becomes detrimental and maladaptive following chronic noxious stimuli, especially in an aging organism. Furthermore, we regard cellular senescence as an adaptive response to stress and suggest that PSR plays a central role in age-related neurodegenerative diseases' pathogenesis. Our perspective on AD proposes an inclusive reassessment of the causal relationships between the classical hallmarks and clinical manifestation. Consequently, we offer a novel treatment strategy predicated upon this view and suggest fine-tuning of arginase activity with natural inhibitors to preclude or halt the development of AD-related dementia.

BackgroundUnresectable pancreatic ductal adenocarcinoma (UR-PDAC) has a poor prognosis. Conversion surgery is considered a promising strategy for improving the prognosis of UR-PDAC. This study aimed to investigate the clinical benefits of conversion surgery in patients with UR-PDAC.Methods: We retrospectively evaluated patients with PDAC who were referred to our department for possible surgical resection between January 2006 and December 2019. Conversion surgery was performed only in patients with UR-PDAC who could expect R0 resection. We analyzed the prognostic factors for overall survival among patients who underwent conversion surgery. Results: Overall, 638 patients with advanced pancreatic cancer were enrolled in this study. According to resectability, resectable cancer (R) was present in 180 patients, borderline resectable cancer (BR) in 60, unresectable locally advanced cancer (UR-LA) in 252, and unresectable cancer with distant metastasis (UR-M) in 146. Conversion surgery was performed in 20 of the 398 UR cases (5.1%). The median period between the initial therapy and conversion surgery was 15.5 months. According to the RECIST evaluation, the treatment response was CR in one patient, PR in 13, SD in five, and PD in one. Downstaging was pathologically determined in all cases. According to the Evans grading system, grade I was observed in four patients (20%), grade IIb in seven (35%), III in seven (35%), and IV in two (10%). We compared the overall survival period from initial treatment among patients undergoing conversion surgery; the median overall survival durations in the conversion surgery, R, BR, UR-LA, and UR-M groups were 73.7, 32.7, 22.7, 15.7, and 8.8 months, respectively. Multivariate analysis revealed that the presence or absence of CRT and the RECIST PR/CR for the main tumor were statistically significant prognostic factors for overall survival among patients undergoing conversion surgery (p = 0.004 and 0.03, respectively).Conclusion: In UR-PDAC, it is important to perform multidisciplinary treatment, including CRT with conversion surgery.

Background: Hepatocellular carcinoma (HCC) is one of most common cancers with a high mortality rate. HBV/HCV infection is an important risk factor to trigger HCC. Therefore, developing serum biomarkers for early diagnosis is crucial to prolong survival in HCC patients. Methods: An antibody array technology was utilized to detect serum from 20 HBV-related HCC patients, 20 chronic hepatitis B patients and 20 normal population, whose results were further validated by ELISA. Results: Both antibody array and ELISA showed that ten growth factors (SCF R, GDF-15, HGF, FGF-4, IGFBP-1, PIGF, GH, GDNF, BDNF and IGF-1) were significantly differential in HCC patients when compared to the non-HCC population. Among these growth factors, the levels of SCF R, GDF-15, HGF, GH and IGF-1 showed significant correlation with hepatitis B and its severity, indicating that these growth factors may promote HCC progression by an HBV-specific mechanism. A therapy targeting these growth factors in hepatitis B patients may help to prevent the development of HCC. FGF4 and GH were found, for the first time, to be upregulated in HCC, suggesting that these two growth factors may serve as novel serum biomarkers for the early diagnosis of HCC. Conclusion: The combined detection of all the differential growth factors may improve the diagnostic accuracy of HCC.

Rapid online surveys are an important tool in tracking the public’s knowledge and perceptions during infectious disease outbreaks. In June 2020, during the early phases of COVID-19 vaccines development, a survey had been conducted, aimed at assessing attitudes and opinions about vaccination of 885 Italian adults, in addition to their vaccine literacy levels (i.e. skills of finding, understanding and using information about vaccines). In January 2021, the same questionnaire has been administered to a similar population (n=160). Interactive vaccine literacy was significantly higher than in June 2020 (mean score 3.38 vs 3.27 respectively, P=.0021). The percentage of participants willing to be vaccinated against COVID-19 was assessed by the means of either-or questions, and was equally high in both surveys (>90%), which is quite reassuring, despite metrics based on categorical scales cannot identify hesitant subjects.

Crohn’s disease is an inflammatory bowel disease whose prevalence is increasing worldwide. Among medical strategies, the dietary therapy with exclusive enteral nutrition is recommended as first line option, at least for children, because it induces clinical remission and mucosal healing. Modulen®, a polymeric TGF-β2 enriched formula, has a good palatability and is widely used. For the first time in the literature, this review outlines and discusses the clinical outcomes obtained with this therapy, as well as the potential mechanisms of action of its compounds. It can be explained by its TGF-β2 content but also by its protein and lipid composition. Further well-designed studies are required to improve our knowledge and to optimize therapeutic strategies.

Stroke represents one of the most important causes of morbidity ( eighty million patients with disabling of ongoing effects of stroke at a given time, globally) and mortality (the second leading cause of death) worldwide. Innovative systems biology-based approach is likely to increase the understanding of the underpinning of acute stroke promise to enhance stroke prevention, acute treatment, and neurorehabilitation. Recent growing body of evidence with shared pathobiology with COVID-19 and the critically important role of inflammation in the context of stroke points to far-reaching consequences of acute stroke, just as in the case of COVID-19 ( post-acute event issues as well as long term issues ) . So far, stroke typically defined by late-appearing disease manifestation by the range of stroke subtypes as defined by the WHO or American Stroke Association. This definition neglects the underlying pathobiological mechanisms such as low-grade chronic inflammation and already compromised vascular system. Diseases such as stroke is hardly a simple result of a single problem, but rather a complex cascade of pathobiological processes and interactions in a complex biochemical environment. The evidence of changes in innate immunity and adaptive immunity during the index event of acute stroke and recovery over next 3-12 months can be easily elicited with simple bedside blood tests such as neutrophil-lymphocyte ratio (NLR) with well over 300 published papers including several systematic reviews and meta-analyses confirming this. Global standard operating procedures (SOP) of stroke care dictated by the national and international stroke guidelines at present. It is imperative to explore the evidence of systems biology approach in current stroke guidelines. This is likely to be a key turning point in managing stroke across the continuum (prevention, management of acute event and rehabilitation).

Abstract: Nutritional interventions have beneficial effects on certain psychiatric disorder symptomatology and common physical health comorbidities. However, studies evaluating nutritional literacy in mental health professionals (MHP) are scarce. This study aimed to assess the degree of self-rated training and literacy relating to nutrition in MHPs. We conducted a cross-sectional survey across 52-countries. Surveys were distributed via colleagues and professional societies. Data were collected regarding self-reported general nutrition knowledge, nutrition education, learning opportunities, and the tendency to recommend food supplements or specific diets in clinical practice. In total, 1056 subjects participated in the study: 354 psychiatrists, 511 psychologists, 44 psychotherapists, and 147 MHPs in-training. All participants believed the diet quality of individuals with mental disorders was poorer compared to the general population (p<0.001). The majority of the psychiatrists (74.2%) and psychologists (66.3%) reported having no training in nutrition. Nevertheless, many of them used nutrition approaches, with 58.6% recommending supplements and 43.8% recommending specific diet strategies to their patients. Only 0.8% of participants rated their education regarding nutrition as ‘very good’. Almost all (92.9%) stated they would like to expand their knowledge regarding ‘Nutritional Psychiatry’. There is an urgent need to integrate nutrition education into MHP training, ideally in collaboration with nutrition experts to achieve best practice care.

The heterogeneity of tumor infiltrating lymphocytes is not well characterized in brain metastasis. To address this, we performed a targeted analysis of immune cell subsets in brain metastasis tissues to test which immunosuppressive routes are involved in brain metastasis. We performed multiplex immunofluorescence (mIF), using commercially available validated antibodies on twenty formalin-fixed paraffin embedded whole sections. We quantitated the subsets of immune cells utilizing a targeted panel of proteins including PanCK, CD8, CD4, VISTA and Iba1, and analyzed an average of 15000 cells per sample. We classified tumours as either high (>30%) or low (<30%) tumour infiltrating lymphocytes (TILs) and found that increased TILs density correlated with survival. We next sought out to phenotype these TILs using mIF. The tumours with low TILs (n=9) had significantly higher expression of the immune-checkpoint molecule VISTA in tumor cells (p<0.01) as well as in their microenvironment (p<0.001). Contrastingly, the brain metastatic tumours with high TILs (n=8) displayed higher levels of activated microglia, as measured by Iba1 expression. Low TILs-tumours displayed CD8+ T-cells that co-express VISTA (p<0.01) significantly more compared to high TILs group, where CD8+ T-cells significantly co-express Iba1 (p<0.05). Interestingly, no definite phenotypes of CD4+ subsets were observed. These results were supported by RNA analysis of a publicly available, independent cohort. In conclusion, our work contributes to a growing understanding of the immune surveillance escape routes active in brain metastasis.

Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of leptin receptor signalling. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.

Erectile dysfunction (ED) due to diabetes mellitus remains difficult to treat despite advances in pharmacotherapeutic approaches in the field. Therefore, this study investigated the erectogenic effect of the methanolic extract of Maytenus procumbens roots on type 2 diabetes in rats. The fructose-streptozotocin model was used to induce type 2 diabetes-linked ED in male rats. The sexually active male Sprague Dawley rats were randomly divided into two major groups; normal group and high fructose fed group for 120 days. After 120 days, the high fructose fed group rats were given a single intraperitoneal injection of a freshly prepared streptozotocin solution (30 mg/kg). The diabetic ED rats were orally administered with the extract at 250 mg/kg, daily for 28 days. The serum, brain and penile tissues were removed for biochemical analysis and protein expression. Increased testosterone level, mounting frequency, reduced blood glucose level and serum fructosamine content was observed after 28 days of treatment in diabetic rats. Methanolic extract also exhibited an inhibitory effect on arginase, AChE, and ACE activities. The crude extract further downregulated proteins PDE-5, RhoA and increased expression of eNOS in the diabetic ED treated rats. The results obtained indicate that the methanolic extract of Maytenus procumbens roots ameliorates erectile dysfunction in type 2 diabetes-induced erectile dysfunction in rats.

The aim of this study was to determine whether a rowing training program improved the quantity and quality of physical activity and quality of life in female breast cancer survivors (stage I - 4.35%; II - 30.43%; III - 52.17%; and IV - 8.7%) diagnosed 6.57 ± 5.02 years previously, who had undergone a subsequent intervention (preservation 53.52%; total mastectomy 39.13% and double mastectomy 4.35%) and had a current mean age of 53.70 ± 7.88 years. The participants (N = 30) engaged in a 12-week training program, each week comprising three sessions and each session lasting 60-90 minutes. An anthropometric evaluation was performed before and after the program. The short form of the International Physical Activity Questionnaire (IPAQ-SF) and the Short Form 36 Health Survey (SF-36) were also administered. The results showed statistically significant improvements in levels of physical activity and in the dimensions of quality of life. We can conclude that a 12-week rowing training program tailored to women who have had breast cancer increases physical activity levels, leading to improved health status and quality of life.

During prolonged standing, insufficient calf muscle pumping accompanies venous stasis and hypertension in the lower legs, resulting in valve dysfunction, venous wall problems, and subsequent inflammation. Compression therapy, which includes medical compression stockings (MCS) and mechanical intermittent pneumatic compression (IPC), is one of the most effective therapeutic interventions for treating chronic venous diseases. This study aimed to investigate the safety and efficacy of IPC and MCS, and the optimal protocol of compression therapy for chronic venous disease. This crossover trial was conducted for healthy, long standing workers (>8 h daily) with leg edema and pain. Four groups were established for each visit: group A (resting after work without MCS), group B (resting after work with MCS), group C (IPC after work without MCS), and group D (IPC after work with MCS). The primary outcome was the visual analogue scale (VAS) score for leg pain. The secondary outcomes were leg volume (mL), circumference (cm), extracellular fluid/total body fluid (ECF/TBF), and extracellular water/total body water (ECW/TBW) through bioimpedance analysis. Outcomes were assessed before work (T0), after work (T1), and 60 minutes after intervention (T2). We included 39 healthy volunteers, aged 30.03±7.56 years. All four groups had significantly increased leg pain after work (T0-1) but improved 60 minutes after intervention (T1-2), particularly group C (decreased VAS by 1.9). When leg swelling was compared at T0 and T1, groups A and C showed significant increases in leg volume and circumference, indicating significant work-induced edema, whereas groups B and D showed no change or even a decrease. After interventions, leg volume and circumference significantly decreased in groups A and C, although groups B and C did not show significant improvement. The ECF/TBF and ECW/TBW of all groups decreased after interventions. Leg pain and edema after prolonged standing in healthy adults were safely and effectively improved by IPC. Although MCS also reduced leg edema immediately after work, it did not show significant improvement in leg pain at T0-1–and T1-2, nor in swelling at T1-2.

Background. Wnt-pathway proteins play a vital role in kidney development and defects in the Wnt-pathway are associated with kidney disorders. However, the knowledge on the role of Wnt/β-catenin pathway proteins in end-stage renal disease (ESRD) is limited.Aim of the study. To delineate the association of ESRD and Wnt-proteins including the agonistR-spondin 1, the transducer β-catenin and the antagonists Dickkopf-related protein 1 (DKK1) and sclerostin.Methods. Serum Wnt-pathway proteins levels were measured by ELISA, while other biochemicals were measured spectrophotometrically in 60 ESRD patients and 30 normal controls.Results. DKK1 and sclerostin were significantly higher in ESRD than in controls, and β-catenin and the catenin + R-Sponin-1 / DKK1 + sclerostin ratio, reflecting the ratio of agonist and transducer on antagonists (AT/ANTA), were significantly lower in ESRD. Logistic regression analysis showed that ESRD was significantly predicted by increased levels of DDK1 and sclerostin and lowered β-catenin (p<0.001). eGFR was significantly associated with DKK1 and sclerostin (inversely), β-catenin (positively) and the AT/ANTA ratio (r=0.468, p<0.001). DKK1 levels were significantly and positively correlated with urea, creatinine, and copper. DKK1 and sclerostin were inversely associated with hemoglobin and packet cell volume. Catenin was significantly negatively associated with copper, urea and creatinine.Conclusion. Wnt/β-catenin pathway proteins show significant alterations in ESRD, indicating significantly increased levels of antagonists and, therefore, attenuated Wnt/β-catenin pathway activity. The latter is associated with lowered eGFR and increased serum copper levels. Wnt/β-catenin pathway proteins are possible drug targets to treat ESRD or its consequences.

Outbreaks of Ebola ebolavirus (EBOV) have been associated with high morbidity and mortality. Milestones have been reached recently in the management of EBOV disease (EVD) with licensure of an EBOV vaccine and two monoclonal antibody therapies. However, neither vaccines nor therapies are available for other disease-causing filoviruses. In preparation for such outbreaks, and for more facile and cost-effective management of EVD, we seek a cocktail containing orally available and room temperature stable drugs with strong activity against multiple filoviruses. We previously showed that (bepridil + sertraline) and (sertraline + toremifene) synergistically suppress EBOV in cell cultures. Here we describe steps towards testing these combinations in a mouse model of EVD. We identified a vehicle suitable for oral delivery of the component drugs and determined that, thus formulated the drugs are equally active against EBOV as preparations in DMSO, and they maintain activity upon storage in solution for up to seven days. Pharmacokinetic (PK) studies indicated that the drugs in the oral delivery vehicle are well tolerated in mice at the highest doses tested. Collectively the data support advancement of these combinations to tests for synergy in a mouse model of EVD. Moreover, mathematical modeling based on human oral PK projects that the combinations would be more active in humans than their component single drugs.

Stroke is one of the leading cause of adult disability and the second leading cause of death worldwide. The immune system actively participates in the pathobiological process of AIS, during the index event and during the repair process despite the limited attention drawn to this aspect in the existing stroke guidelines globally. The similar clinical course and similar circulating innate and adaptive immune cell counts in AIS and COVID-19 has created a renewed interest in these easily available biomarkers innate and adaptive immunological changes in AIS with potential diagnostic, prognostic, and therapeutic implications. The current scoping review aimed to assess the significance of circulating neutrophil and lymphocyte counts and their ratio (NLR) in AIS and explore their association with post-stroke recovery trajectory. The Arksey and O'Malley methodological framework was employed to review the published papers on the neutrophil-lymphocyte ratio (NLR) and AIS in late November 2020. Only studies published in English from 2000-2020 were included in this scoping review. Fifty-three published papers were reviewed. This review's key finding is that a canonical inflammatory response occurs in AIS just as in the case of COVID-19 and neurological involvements well described in the recent literature. An excessive circulating innate immune cells (neutrophils) and reduced circulating adaptive immune cells (lymphocytes ) are associated with poorer outcomes during the acute interventions ( reperfusion therapies) as well as the recovery trajectory. Main representatives of innate and adaptive immunity follow a canonical course in AIS and COVID-19. Exaggerated circulating innate ( elevated neutrophils and elevated NLR) and reduced adaptive immune response (lymphopenia) correlate with the worse outcome in AIS and COVID-19. This scoping review's findings make the strongest case for a systems biology-based approach to the standard operating procedures in stroke care urgently.

Background: Health-related knowledge is among the essential factors to enable women to be aware of their rights to seek health services. However, little is known about knowledge of safe abortion care services among women of reproductive age in Ethiopia. The main purpose of the study was to assess knowledge of safe abortion care services and associated factors among women of reproductive age in Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted from April-June 2019 among 432 respondents. Bivariate statistics including correlation coefficients, student t-test, one-way analysis of variance, and linear regressions, and multiple linear regression analyses were used. A significant statistical test was determined at a 95% confidence interval and p-value <0.05. Results: About 65.5% had heard about safe abortion care services; media being the main source of information for 79.5%. The finding from an independent-sample t-test shows that the place where the respondents grew up (p< 0.006), history of past miscarriage, and previous information of abortion care service were significantly associated with the knowledge about safe abortion care services (p< 0.001). Conclusions: Women without prior health experiences and those with rural origin could be targeted for reproductive health information interventions including safe abortion care provision.

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

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

The coronavirus disease 2019 (COVID-19) has spread over the world for more than one year. COVID-19 often develops life-threatening hypoxemia. Endothelial injury caused by the viral infection leads to intravascular coagulation and ventilation-perfusion mismatch. However, besides above pathogenic mechanisms, the role of alveolar edema in the disease progression has not been discussed comprehensively. Since the exudation of pulmonary edema fluid was extremely serious in COVID-19 patients, we bring out a hypothesis that severity of alveolar edema may determine the size of poorly-ventilated area and the blood oxygen content. Treatments to pulmonary edema (alcohol-oxygen vapor therapy and fluid management) may be great helpful for reducing occurrence of severe cases. Given that late mechanical ventilation may cause mucus (edema fluid) to be blown to the deep of the small airways, oxygen therapy should be given at the early stages. The optimal time and SpO₂ threshold for oxygen therapy are also discussed.

Social isolation magnified by the restriction of movement order during the COVID-19 pandemic may lead to negative psychosocial health impact among community-dwelling older adults. We evaluated the feasibility of virtual research methods and virtual group exercises among individuals aged 60 years and over in Malaysia. Participants were recruited from the Promoting Independence in Seniors with Arthritis (PISA) pilot cohort through social media messages. A four-week course of virtual group exercise was offered. Anxiety and depression were assessed with the Hospital Anxiety and Depression Scale (HADS) during the last attended follow-up of the cohort study (pre-pandemic), pre-intervention, and post-intervention. Exercise adherence was recorded using diary with daily entries and attendance to the virtual group exercise sessions were captured daily. The outcomes of interest were changes of anxiety and depression scores from baseline to pre-intervention (pandemic-related) and post-intervention (virtual exercise related). Forty-three individuals were recruited. A significant increase in anxiety scores from baseline to pre-intervention was observed. Comparisons using repeated-measures analysis of variance between those who attendance ≥14 and &lt;14 group exercise sessions revealed no between-within subjects differences in depression scores. There was a 23% dropout rate in the post intervention survey and 60.5% of diaries were returned. This study demonstrated the feasibility of conducting research entirely virtually among older persons during the peak of global first wave of a pandemic. The pandemic has led to increased anxiety among community-dwelling older adults.

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

As medical schools cope with the consequences of the COVID-19 pandemic, a new cohort of students will be admitted in the fall. Administrators are again challenged to make unprecedented enrollment decisions without standardized exams. This challenge provides unique opportunities to support holistic admissions but also abruptly bypasses a process that has been employed since 1928. This article highlights key factors that are being considered during current medical school admission cycles, including limited opportunities to take standardized exams, heightened student anxiety, and potential exam alternatives. These factors are framed and discussed within the context of the medical college admission test (MCAT) exam.

A novel method of investigating the temperature dependent variation of aspects of the complex refractive index n* in samples in the THz range using continuous, non-polarised, synchrotron radiation is presented. The method relies on the use of ATR apparatus, and retains the advantage of minimal sample preparation, which is a feature of ATR techniques. The method demonstrates the viability of rapidly monitoring temperature reflectance whilst continuously heating or cooling samples by using a temperature variable Thermal Sample Stage. The method remains useful when the refractive index of the sample precludes attenuated total reflection study. This is demonstrated with the water reflectance experiments. The temperature dependent ATR reflectance of tissue-representative fats (lard and Lurpak® butter) was investigated with the novel approach. Both are within the ATR range of the diamond crystal in a “true” ATR mode. Lard showed no clear temperature variation between -15 0C and 24 0C at 0.7 to 1.15 THz or 1.70 to 2.25 THz. Lard can be regarded as having invariable, constant, dielectric properties within mixtures when biological substances are being assessed for temperature dependent dielectric variation within the stated THz ranges. Lurpak® butter (water content 14.7%) displayed temperature dependent reflectance features with a steady decline in reflectivity with increasing temperature. This is in line with the temperature-dependent behaviour of liquid water. There is no rapid change in reflectance, even at -20 0C, suggesting that emulsified water retains liquid-water-like THz properties at freezing temperatures.

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

Neonatal palliative care (NPC) is an integrated and holistic approach that is an integral part of the contemporary neonatal treatment delivery paradigm. It is the highest fulfillment of the notion of beneficence (doing or creating 'good') that has otherwise been neglected/underestimated by the focus of modern medicine on technology and instrumental treatments by its commitment to alleviating patient pain and quality of life. For decades, the Double-Effect Doctrine (DDE) has been used to consider and address a range of ethically questionable circumstances, often at the end of life, including euthanasia, termination of pregnancy to save maternal life, and morally justified warfare. The theory has continued to be mired in controversy as ethicists, legal scholars, theologians, and philosophers discuss the abstract concepts of moral reasoning, purpose, foresight, and other underlying moral theories. In this paper, the moral theory of DDE is discussed in its clinical application to the ethical decision-making process in neonatal palliative and end-of-life treatment, specifically 1) the administration of opioids as required for symptom control and 2) the use of palliative sedation for intractable symptom care.

Background: Tropheryma whipplei is the causative pathogen of Whipple’s disease and other acute and chronic manifestations. Children have been identified as reservoirs of this bacterium especially in low-middle income countries. No information is currently available on the dissemination of T. whipplei in Iran. Therefore, the aim of this study was to investigate the presence of T. whipplei in children with immunodeficiency. Methods: This cross-sectional study was performed from July 2018 to February 2019 in Qom province (central Iran). Stool samples were collected from immuno-compromised children. T. whipplei was tested by SYBR Green and Taq-Man Real-time PCR assays. For confirmation, sequencing of the isolated bacteria was done. Results: One hundred and 30 children with a mean age of 56.7 months were enrolled. Acute lymphocytic leukemia was the most reported immunodeficient disease (77%), followed by non-Hodgkin lymphoma and retinoblastoma. The majority of the children were undergoing chemotherapy during the study. Thirteen (10%) children had T. whipplei DNA in the collected stools. Sequencing results confirmed T. whipplei identification in all the cases. Eight out of 70 (11.4%) children under 5 years old resulted positive. Conclusion: This is the first study showing the circulation of T. whipplei among immunocompromised children in Iran. More epidemiological studies are needed to evaluate the prevalence of this pathogen in different risk groups in Iran and to increase the knowledge of its rare clinical manifestations.

RNA editing involves the insertion, deletion or substitution of single nucleotides within a RNA molecule, without altering the DNA sequence. Adenosine to inosine (A-to-I) editing consists of an RNA modification where single adenosines along the RNA sequence are converted into inosines. Such a biochemical transformation is catalyzed by enzymes belonging to the family of adenosine deaminases acting on RNA (ADARs) and occurs either co- or post-transcriptionally. Initially, the A-to-I RNA editing phenomenon was discovered and studied in messenger RNAs (mRNAs), where it can influence RNA splicing and cause the recoding of codon sequences. The employment of more powerful, high-throughput detection methods has recently revealed that A-to-I editing widely occurs in non-coding RNAs, including microRNAs (miRNAs). MiRNAs are a class of small regulatory non-coding RNAs (ncRNAs) acting as translation inhibitors, known to exert relevant roles in controlling cell cycle, proliferation, and cancer development. Indeed, a growing number of recent researches have evidenced the importance of miRNA editing in cancer biology by exploiting various detection and validation methods. Herein, we briefly overview early and currently available A-to-I miRNA editing detection and validation methods and discuss the significance of A-to-I miRNA editing in human cancer.

Cytochrome-c-oxidase (COX) subunit 4 (COX4) plays important roles in the function, assembly and regulation of COX (mitochondrial respiratory complex 4), the terminal electron acceptor of the oxidative phosphorylation (OXPHOS) system. The principal COX4 isoform, COX4-1, is expressed in all tissues, whereas COX4-2 is mainly expressed in the lungs, or under hypoxia and other stress conditions. We have previously described a patient with a COX4-1 defect with a relatively mild presentation compared to other primary COX deficiencies, and hypothesized that this could be the result of compensatory upregulation of COX4-2. To this end, COX4-1 was downregulated by shRNAs in human foreskin fibroblasts (HFF), and compared to patient's cells. COX4-1, COX4-2 and HIF-1α were detected by immunocytochemistry. The mRNA transcripts of both COX4 isoforms and HIF-1 target genes were carried out by RT-qPCR. COX activity and OXPHOS function were measured by enzymatic and oxygen consumption assays, respectively. Pathways were analyzed by CEL-Seq2 and by RT-qPCR. We demonstrate elevated COX4-2 levels in the COX4-1-deficient cells with a concomitant HIF-1α stabilization, nuclear localization and upregulated hypoxia and glycolysis pathways. We suggest that COX4-2 and HIF-1α has the are upregulated, also in normoxia as a compensatory mechanism in COX4-1 deficiency.

Background: Mucoadhesive polymers represent a major part of site-specific and localized retention strategies in oral drug delivery. Present research was designed to synthesize and characterize a novel mucoadhesive carbohydrate polymer (thiolated gum ghatti; TGG) which was further employed to fabricate mucoadhesive tablets of domperidone using an industrially viable compression coating technique. Methods: Thiolation of gum ghatti was achieved by the ester formation (esterification) between hydroxyl group and carboxyl group of gum ghatti and thioglycolic acid. Results: TGG was characterized by various physico-chemical techniques such as FTIR, XRD, SEM and DSC techniques. In rheological studies, the observed viscosities of pure gum-mucin were 45.45 and 71.75 mPas and that of thiolated gum were 78.7 and 112.58 mPas respectively in water and simulated gastric fluid. Signifi-cant increase in viscosity for thiolated gum may be attributed to increased macromolecular interactions responsible for enhanced mucoadhesive potential of thiolated gum. In-silico studies corroborate the role of mucin gum interaction and energetic stabilization for en-hanced mucoadhesion properties of thiolated gum. Ex-vivo mucoadhesion strength of gum ghatti and thiolated gum ghatti coated tablets was found to be ranging between 4.67± 0.79 to 8.99± 0.75 g and 11.76± 1.34 to 18.83± 2.07 g respectively. Conclusion: Thiolated gum ghatti may be regarded as a promising polymer for developing different mucoadhesive drug delivery systems.

Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during pre-conception, pregnancy and throughout life have been explored. The effects of inherited genetic variations and disorders, pre-existing diseases, infectious agents, hobbies, occupations, prior treatments and a host of other factors have been proposed, but none is universally applicable to all cases. Variation in the incidence and prognosis based on the age, sex, race, type of the disease, geographic area of residence and other factors are intriguing, but remains unexplained. Advances in genomic profiling, including genome‐wide gene expression, DNA copy number, and single nucleotide polymorphism [SNP] genotype may shed some light on the role of genetics in these disparities. Separate two-hit hypothesis for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis. A number of pre- and post-natal environmental conditions and exposure to infections, including a mycovirus infected Aspergillus flavus, have been suggested. The exact nature, timing, sequence of the events and mechanisms resulting in occurrence of leukemia requires further investigations. This review summarizes some of the above factors and the direction for future research on the etiology of acute leukemias.