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The article refers also to the standards of treating the dissection of the interior carotid artery which still arouse controversies.Introduction of the definition and classification of chronic kidney disease (CKD) according to the KDOQI guidelines in 2002 served as a turning point in nephrology. On one hand, the new definition has allowed for the standardization of terminology, on the other hand, however, it has led to a rapid growth in CKD diagnoses. Another issue is the strengthening of the assumption, that diagnosis of CKD is associated with further progressive kidney dysfunction until reaching the end stage renal disease (ESRD). Clinical practice, however, provides evidence that not all patients diagnosed with CKD reach ESRD and eventually require renal replacement therapy (RRT), and in many cases CKD does not progress.

The aim of the study was to assess practical information for a clinician provided by eGFR and its changes during the follow-up of a patient as regards the RRT prognosis and mortality risk.

The study group consisted of patients with CKD treated in the regional outpatient clinic. Progression was assessed by determininer, eGFR below 45 ml/min/ 1.73m2 was associated with a significantly higher mortality risk (p=0.036). Moreover, the groups with the fastest and with improved eGFR were characterized by the highest mortality.

The baseline eGFR was not a significant predictor of future renal outcomes (ESRD, RRT). However, eGFR below 45 ml/min/ 1.73m2 was associated with a significantly higher mortality risk (p=0.036). Moreover, the groups with the fastest and with improved eGFR were characterized by the highest mortality.Hypercalcemia (HCM) is predominantly caused by primary hyperparathyroidism (PHPT) or malignancy. It's incidence varies from 0.17% to 4.74%. Its numerous manifestations include renal symptoms.

The aim of the study was to assess the incidence and etiology of hypercalcemia in patients hospitalized at the Department of Nephrology of the Warsaw Military Institute, as well as to evaluate its impact on renal function.

In this cross-sectional study patients admitted to the Nephrology Department of the Warsaw Military Institute between January 2017 and December 2018 were retrospectively screened for presence of HCM, defined as total calcium level or corrected calcium level in case of hypoalbuminemia >10.2 mg/dl, measured at least twice. Each patient's medical history as well as other laboratory findings were subsequently analyzed in order to establish the etiology of hypercalcemia.

Among 3062 hospitalisations (1993 patients) at The Department, 96 patients had elevated calcium level of which 36 were identified d medications having hypercalcemizing effect. Kidney injury is dependent on the severity of hypercalcemia.

Hypercalcemia is a rare disorder among Nephrology Department patients, which primary etiology is malignancy and medications having hypercalcemizing effect. Kidney injury is dependent on the severity of hypercalcemia.Fibroblast Activation Protein (FAP) is a cell surface glycoprotein expressed exclusively by myofibroblastic cells in areas of active tissue remodeling. Role of FAP expression by smooth muscle cells in atherosclerotic plaque and possible role in plaque rupture resulting in acute coronary syndromes remains unclear.

The aim of our study was to analyze FAP expression by smooth muscle cells in sections of human coronary arteries without atherosclerosis and with atherosclerotic plaque. Additionally, FAP expression in human atherosclerotic plaque was compared with other markers of activated smooth muscle cells.

Hybrid cells (cF19) producing anti human FAP were grown in suspension. A crude anti-human FAP IgG have been obtained in 4 consecutive days process. Monoclonal anti-human FAP antibody were used with immunochemistry staining and immunofluorescence to identify FAP distribution in human atherosclerotic plaque in normal coronary arteries without atherosclerosis from heart transplant patients and in coronary arteries from patients with advanced atherosclerotic plaques.

Analysis of FAP expression in human coronary vessels showed absence of FAP in sections without atherosclerosis and expression of FAP in human atherosclerotic plaque. Immunofluorescence staining of advanced atherosclerotic plaque showed distinct distribution of FAP expression in advanced atherosclerotic plaque as compared with other markers of activated vascular smooth muscle cells.

FAP is expressed in advanced atherosclerotic plaque. Comparison of FAP expression with other markers of activated myocytes suggests that FAP may identify different specific subpopulation of activated smooth muscle cells in atherosclerotic plaque.

FAP is expressed in advanced atherosclerotic plaque. Comparison of FAP expression with other markers of activated myocytes suggests that FAP may identify different specific subpopulation of activated smooth muscle cells in atherosclerotic plaque.

SARS-CoV-2 and its related COVID-19 are now affecting people worldwide. The pandemic, started at the end of 2019 and spread in Europe and all over the world at the beginning of the 2020, is the biggest threat to the health and to the economy of all countries, since the time of Spanish Flu. A global effort is being made to counter the virus with social distancing and restrictions, but our habits and behavior have dramatically been modified. Hospital activity has changed, and Plastic Surgery is affected as well as other disciplines.

Our work describes the impact of the pandemic on a Plastic Surgery Unit in a tertiary care hospital and estimates the possible consequences in the near future. Elective procedures and consultations have been postposed and rescheduled, but we ensured treatment for life-threatening conditions and offered the best therapy, complying with the new safety standard to protect the patients and the healthcare providers. Media helped in keeping in touch the people, ensuring continuity in education and circulation of the data about SARS-CoV-2 research.

We don't know yet what the overall cost of the crisis will be on the global economy and on the National Health Systems. Definitely, it will be a big challenge to face, both for the Governments, for the people, as for healthcare providers. However, to date, we should remind our responsibilities as doctors, as we can contribute with our efforts and our knowledge to ensure continuity of care and research.

COVID, COVID-19, Italy, Outbreak, Pandemic, Plastic Surgery, SARS-Cov-2.

COVID, COVID-19, Italy, Outbreak, Pandemic, Plastic Surgery, SARS-Cov-2.We present our experience with pediatric ABO-incompatible liver transplantation in India. Data of patients 64 requiring plasmapheresis. All 8 patients survived without rejection/biliary issues. Mean (range) of post-transplant hospital stay was 19.1 (13-22) d and follow-up period was 38.1 (7.1-84.4) mo. Pediatric ABO-incompatible liver transplantation can be successfully performed using plasmapheresis with optimal immune-suppression and vigilant post-op monitoring.We report on 16 children with ingestion of magnetic foreign bodies, who were identified by a medical record review of our hospital data for the time period between January, 2017 and May, 2018. Digestive tract wall was sandwiched in 13 (75%) children and 11 (74%) had gaptic intestinal perforation.Pediatric Advanced Life Support (PALS) guidelines are updated every five years and the new 2020 guidelines were issued recently. We briefly review the important changes in terms of rates of rescue breaths, timing of epinephrine, resuscitation in septic shock, use of extracorporeal therapies, and the new component in the chain of survival - recovery.

The IAP last published the guidelines "Comprehensive Management of Diarrhea" in 2006 and a review in 2016. The WHO in 2002 and the Government of India in 2004 recommended low osmolarity rehydration solution (LORS) as the universal rehydration solution for all ages and all forms of dehydration. However, the use of LORS in India continues to be unacceptably low at 51%, although awareness about ORS has increased from a mere 14% in 2005 to69% in 2015. Availability of different compositions of ORS and brands in market added to the confusion.

The Indian Academy of Pediatrics constituted a panel of experts from the fields of pediatrics, pediatric gastroenterology and nutrition to update on management of dehydration in children with particular reference to LORS and issue a current practice guideline. The committee met twice at CIAP HQ to review all published literature on the aspect. Brief presentations were made, followed by discussions. The draft paper was circulated by email. All relevant inputs and suggestioncare providers across all systems of medicine. LORS can also be useful in managing dehydration in non-diarrheal illness. More research is required to modify ORS further to make it safe and effective in neonates, severe acute malnutrition, renal failure, cardiac and other co-morbidities. There is an urgent need to discourage production and marketing all forms of ORS not in conformity with WHO approved LORS, under a slogan "One India, one ORS".

Though psychogenic non-epileptic seizures (PNES) are seen commonly during evaluation of children and adolescents with epilepsy, the literature regarding developmental changes in PNES is limited.

Literature search was conducted in PubMed. Key search terms included Pseudoseizure* OR PNES OR [(non-epileptic or nonepileptic or psychogenic or non-epileptic attack disorder) AND (seizure*)], resulting in 3,236 articles. Filters included human, ages 1-18 years, English language and last 15 years (2004-2019), resulting in 533 articles. We reviewed 33 articles, which included 19 articles that involved children (1-18 years), with 10 or more children with PNES in their study group. 21 articles obtained in cross references that were outside the filter setting (including time frame and age range) were also reviewed, for a total of 54 articles.

Majority of the studies were retrospective. We detail clinical features, predisposing factors and appropriate workup for children and adolescents with possible PNES. There is no consensus regarding frequency of psychiatric comorbidities in children with PNES. No controlled trials of treatment of PNES in children are available, but cognitive behavioral therapy is the consensus for adult PNES. Outcome appears to be better in children with PNES.

There is a need for be long-term prospective studies to document various clinical features and outcome of pediatric and adolescent PNES, and also the comorbid conditions.

There is a need for be long-term prospective studies to document various clinical features and outcome of pediatric and adolescent PNES, and also the comorbid conditions.

To study the vaccine-induced measles specific immunoglobulin G (IgG) response in children aged 4-12 years immunized with two doses of measles containing vaccine in infancy.

This cross-sectional study was done in a tertiary care centre for a period of 18 months from January, 2017. Measles specific IgG levels were assessed using ELISA technique in 80 children of age 4-12 years, [mean (SD) age, 7.5 (2065)] who had received two doses of measles vaccine in infancy. Measles-specific IgG levels >11 NTU were considered protective.

Protective levels of measles specific IgG were found in 86.4%. Significant association was found between negative immune response to measles vaccine and low socioeconomic status (P=0.03), under-nutrition (P=0.001), anemia (P=0.03), lack of exclusive breast feeding till 5 months of age (P=0.007) and higher parity (P=0.002).

Less than one-seventh of children immunized with two doses of measles vaccine in infancy had measles-specific IgG below protective levels at the average age of 7.5 yr. Lack of exclusive breast feeding till 5 months of age, under-nutrition and anemia were the associated factors.

Less than one-seventh of children immunized with two doses of measles vaccine in infancy had measles-specific IgG below protective levels at the average age of 7.5 yr. Lack of exclusive breast feeding till 5 months of age, under-nutrition and anemia were the associated factors.

Primary immunodeficiency disorders are genetically heterogeneous immune disorders with a wide range of infectious and non-infectious manifestations.

To describe a single-center experience of primary immunodeficiency disorders.

Retrospective analysis from January 2015 to January 2020.

Tertiary care children's hospital.

One hundred and twelve children (<18 years) diagnosed with primary immunodeficiency disorders.

Diagnostic spectrum, clinical features, and outcome.

The median (IQR) age of the first clinical manifestation and lag time in diagnosis was 10 (27) and 11 (18) months, respectively. Twenty-seven children (24%) were diagnosed during their first presentation. Thirty-six (32%) children had phagocytic disorders, 20 (17.8%) had combined/cellular defects, 18 (16%) had predominant antibody deficiencies and 17 (15%) had disorders of immune dysregulation. Non-infectious manifestations were seen in 54 (48%). Eight children underwent hematopoietic stem cell transplantation, 44 (39%) children were on antimicrobial prophylaxis and supportive therapy, 36 (32%) were lost to follow-up and 24 (21%) children died.

Congenital defects of phagocyte function, followed by combined/cellular defects are the commonest primary immune deficiencies (PIDs) identified in southern India. Long lag time in diagnosis and high mortality in our cohort emphasizes the need for early diagnosis and early referral.

Congenital defects of phagocyte function, followed by combined/cellular defects are the commonest primary immune deficiencies (PIDs) identified in southern India. Long lag time in diagnosis and high mortality in our cohort emphasizes the need for early diagnosis and early referral.

The purpose of this study was to translate the Pediatric assessment scale for severe feeding Problems (PASSFP) into Turkish and investigate its validity and reliability.

The study included Turkish translation of the PASSFP, and investigating its reliability and criterion validity in relation with Children's eating behavior questionnaire (CEBQ).

Cronbach Alpha reliability of T-PASSFP was 0.79, and of its subscales, i.e. Form A and B, were 0.67, and 0.73, respectively. Test-retest correlation was 0.99 for the scale and Form A, and 0.94 for Form B. There were positive correlations between total scale and Enjoyment of food and Food fussiness subscales of CEBQ. Form A had positive relationships with Food responsiveness, Enjoyment of food, and Food fussiness subscales. Form B had positive correlations with Enjoyment of food and negative correlations with Slowness in eating subscales.

The Turkish PASSFP is valid and reliable in evaluating feeding in children with neurodevelopmental disorders. Form A is applied for all children, and Form B is used for partially or totally oral-fed children.

The Turkish PASSFP is valid and reliable in evaluating feeding in children with neurodevelopmental disorders. Form A is applied for all children, and Form B is used for partially or totally oral-fed children.

To determine seroprotective titres for diphtheria, pertussis, tetanus and measles in children with nephrotic syndrome who had received essential immunization.

Children (2-18 years) with steroid sensitive nephrotic syndrome (SSNS) or steroid-resistant nephrotic syndrome (SRNS) who were in disease remission and had received essential childhood immunization were included. Anti-diphtheria, anti-pertussis, anti-tetanus and anti-measles antibody titres were measured.

Seventy-six (40 with SSNS; 36 with SRNS) children with mean (SD) age 7.54 (3.96) years were enrolled. The time elapsed since last vaccination was >5 years in 68.4% patients. The seroprotection rates for diphtheria, tetanus, pertussis, and measles were 86.8%, 93.4%, 31.6% and 77.6% respectively; lower in SRNS subjects compared to SSNS. Robust seroprotection titers (1.0 IU/mL) for diphtheria were seen in 23.8% SSNS and 17.9% SRNS; P=0.04, and for tetanus in 69.3% SSNS and 43.8% of SRNS subjects; P=0.03, respectively.

Children with nephrotic syndrome especially those with SRNS have lower seroprotective titers for diphtheria, tetanus, pertussis and measles, necessitating a booster dose of DPT/DT/Td and MR/MMR.

Children with nephrotic syndrome especially those with SRNS have lower seroprotective titers for diphtheria, tetanus, pertussis and measles, necessitating a booster dose of DPT/DT/Td and MR/MMR.

To compare the efficacy of intravenous acetaminophen and intravenous diclofenac sodium in the management of skeletal vaso-occlusive crisis among children with sickle cell disease.

Single blind randomized controlled trial.

Tertiary care hospital.

104 children with sickle cell disease and skeletal vaso-occlusive crisis.

Intravenous acetaminophen at 10mg/kg/dose 8 hourly and intravenous diclofenac sodium at 1mg/kg/dose 8 hourly in 11 ratio.

Reduction in pain score (50%), number of doses needed to relieve pain after 24 hours of drug administration and decrease in pain score at 1 hour.

A 50% reduction in pain score was seen in 35 (77.3%) and 10 (21.7%) children among acetaminophen and diclofenac sodium groups respectively (RR, 95% CI 3.6; 2.02-6.33, P< 0.001). The mean (SD) fall in pain score at 1 hour was significantly higher among intervention arm as compared to control arm [1.51 (0.5) and 1.06 (0.5); P<0.001]. Eight (17.4%) patients developed local phlebitis at the site of infusion among diclofenac group.

Intravenous acetaminophen is a better alternative to intravenous diclofenac in children with skeletal vaso-occlusive crisis.

Intravenous acetaminophen is a better alternative to intravenous diclofenac in children with skeletal vaso-occlusive crisis.

To compare seroprotection rates and the anti-HBs titers following primary immunization with double strength (20 µg) recombinant hepatitis B virus (rHBV) vaccine administered intramuscularly (IM) in a 3-dose (0, 1 and 6 months) vs 4-dose (0, 1, 2 and 6 months) schedule in HIV-infected children receiving antiretroviral therapy (ART). An accelerated 3-dose schedule (0, 1, 2 months) within the 4-dose group was also compared.

Randomized controlled trial.

Pediatric ART clinic of a tertiary hospital in Delhi from November, 2017 to April, 2019.

Fifty (25 per group) HIV-infected children aged 18 months - 12 years receiving ART for at least 6 months who had not received any prior dose of HBV vaccine, and were anti-HBs negative.

Group 1 received 20 µg of rHBV vaccine IM (in deltoid muscle) at 0, 1, and 6 months, and group 2 received 20 µg the same vaccine at 0, 1, 2 and 6 months.

Anti-HBs titers and proportion of responders in 3-dose vs 4-dose group at seventh and twelfth month and at third month after an accelerated 3-dose schedule.

Median (IQR) anti-HBs titers at the seventh month were significantly higher in group 2 [225.7 (151-300) IU/L] compared to group 1 [138.2 (35.2-250) IU/L], but were comparable at the 12th month. Seroprotection rates were comparable between group 2 and group 1 at 7th month (96% vs 80%; P=0.19) and 12th month (96% vs 88%; P=0.61). The proportion of good responders were also comparable between the groups at 7th month and 12th month (both P=0.29). Accelerated 3-dose schedule achieved comparable anti-HBs titers [179.9 (130.6-250) IU/L] and seroprotection rate (92%) one month after completion of schedule to the standard 3-dose + schedule.

A 3-dose double strength recombinant HBV vaccine schedule offers comparable seroprotection to 4-dose schedule for HIV-infected children receiving ART.

A 3-dose double strength recombinant HBV vaccine schedule offers comparable seroprotection to 4-dose schedule for HIV-infected children receiving ART.Snakebite is a neglected tropical disease that inflicts severe socioeconomic burden on developing countries by primarily affecting their rural agrarian populations. India is a major snakebite hotspot in the world, as it accounts for more than 58,000 annual snakebite mortalities and over three times that number of morbidities. The only available treatment for snakebite is a commercially marketed polyvalent antivenom, which is manufactured exclusively against the 'big four' Indian snakes. In this review, we highlight the influence of ecology and evolution in driving inter- and intra-specific venom variations in snakes. We describe the repercussions of this molecular variation on the effectiveness of the current generation Indian antivenoms in mitigating snakebite pathologies. We highlight the disturbing deficiencies of the conventional animal-derived antivenoms, and review next-generation recombinant antivenoms and other promising therapies for the efficacious treatment of this disease.

To determine the effectiveness of systemic pharmacotherapeutic interventions compared to placebo in burning mouth syndrome (BMS) randomized controlled trials (RCTs) based on the core outcome domains recommended by the Initiative on Methods, Measurement, andPain Assessmentin Clinical Trials (IMMPACT).

A systematic literature review of RCTs, concerning systemic pharmacotherapeutic interventions for BMS, published from January 1994 through October 2019, and meta-analysis was performed.

Fourteen RCTs (n=734 participants) were included. Of those, nine were eligible for the quantitative assessment due to the availability/homogeneity of data for at least one of the IMMPACT domains. Pain intensity was the only domain reported in all RCTs. Weighted mean changes in pain intensity, based on visual analogue scale (ΔVAS), were reported in three RCTs at 6±2weeks and only one RCT at 10+ weeks follow-ups. Quantitative assessment, based on ΔVAS, yielded very low evidence for the effectiveness of alpha-lipoic acid and clonazepam, low evidence for effectiveness of trazodone and melatonin, and moderate evidence for herbal compounds.

Based on the RCTs studied, variable levels of evidence exist that suggest that select pharmacological interventions are associated with improved symptoms. However, the underreporting of IMMPACT domains in BMS RCTs restricts the multidimensional assessment of systemic interventions outcomes. Standardized outcome measures need to be applied to future RCTs to improve understanding of intervention outcomes.

Based on the RCTs studied, variable levels of evidence exist that suggest that select pharmacological interventions are associated with improved symptoms. However, the underreporting of IMMPACT domains in BMS RCTs restricts the multidimensional assessment of systemic interventions outcomes. Standardized outcome measures need to be applied to future RCTs to improve understanding of intervention outcomes.Symmetric proteins are currently of interest as they allow creation of larger assemblies and facilitate the incorporation of metal ions in the larger complexes. Recently this was demonstrated by the biomineralization of the cadmium-chloride nanocrystal via the Pizza designer protein. However, the mechanism behind this formation remained unclear. Here, we set out to investigate the mechanism driving the formation of this nanocrystal via truncation, mutation, and circular permutations. In addition, the interaction of other biologically relevant metal ions with these symmetric proteins to form larger symmetric complexes was also studied. The formation of the initial nanocrystal is shown to originate from steric strain, where His 58 induces a different rotameric conformation on His 73, thereby distorting an otherwise perfect planar ring of alternating cadmium and chlorine ions, resulting in the smallest nanocrystal. Similar highly symmetric complexes were also observed for the other biological relevant metal ions. However, the flexibility of the coordinating histidine residues allows each metal ion to adopt its preferred geometry leading to either monomeric or dimeric β-propeller units, where the metal ions are located at the interface between both propeller units. These results demonstrate that symmetric proteins are not only interesting to generate larger assemblies, but are also the perfect scaffold to create more complex metal based assemblies. Such metal protein assemblies may then find applications in bionanotechnology or biocatalysis.

Nanoparticles can improve the bioavailability of bioactive compounds. Concomitant intake of food can affect pharmacokinetic profiles by altering dissolution, absorption, metabolism, and elimination behavior. Studies on the effects of food and its supplements on the bioavailability of bioactives in nanoformulations are few. In this study, the effects of typical food (milk, sugar, high-fat diet, and regular kibble) and a widely consumed probiotic [Bifidobacterium lactis Bb-12® (Bb-12)] on the bioavailability of curcumin in four formulations [simply suspended curcumin (Cur-SS) and curcumin in nanoemulsions (Cur-NEs), in single-walled carbon nanotubes (Cur-SWNTs), and in nanostructured lipid carriers (Cur-NLCs)] were investigated.

Fasting treatment and sugar co-ingestion can significantly enhance the bioavailability of curcumin in Cur-NEs and Cur-SWNTs, respectively. Compared with the fasting treatment, co-ingestion with regular kibble reduced the absorption of curcumin in Cur-NEs and Cur-SWNTs. Ingesting milk along with Cur-NE is also not recommended. The mechanisms behind these phenomena were briefly discussed. This study revealed for the first time that the intestinal colonization of Bb-12 reduces the bioavailability of curcumin and this reduction can be attenuated by nanoformulations SWNTs and NLCs, but not NEs. The reason for this difference was the protective effects of the former two nanoformulations against curcumin degradation by Bb-12 according to in vitro experiments.

Dietary status (including supplementary probiotics) can dramatically influence the bioavailability of curcumin in nanoformulations. © 2021 Society of Chemical Industry.

Dietary status (including supplementary probiotics) can dramatically influence the bioavailability of curcumin in nanoformulations. © 2021 Society of Chemical Industry.

Emerging oncogenes were reportedly linked to the complicated subtypes and pathogenesis of clinical gliomas. Herein, we first comprehensively explored the potential correlation between growth-arrest-specific two family genes (GAS2, GAS2L1, GAS2L2, GAS2L3) and gliomas by bioinformatics analysis and cellular experiments.

Based on the available datasets of TCGA (The Cancer Genome Atlas), CGGA (Chinese Glioma Genome Atlas), and Oncomine databases, we performed a series of analyses, such as gene expression, survival prognosis, DNA methylation, immune infiltration, and partner enrichment. We also utilized two glioma cell lines to conduct the colony formation and wound-healing assay.

GAS2L3 gene was highly expressed in glioma tissues compared to normal brain tissues (p<0.05). We further observed the relationship between the high expressed GAS2L3 and poor clinical prognosis of brain low-grade glioma (LGG) cases in our Cox proportional hazard model (hazard ratio [HR]=0.1715, p<0.001). Moreover, DNA hypometh family genes, especially GAS2L3, in the clinical prognosis and possible functional mechanisms of glioma, which gives a novel insight into the relationship between GAS2L3 and LGG.We report an unique case of a patient who showed coexistence of three nevus lipomatosus cutaneus superficialis (NLCS) with typical, cutaneous adenolipoma (AL)-like, and dermal spindle cell lipoma (SCL)-like histopathological features. A 53-year-old woman presented with a 20-year history of skin-colored and slightly elevated nodules. These lesions were separately located on the lateral side (lesion 1) and medial side (lesion 2) of her left buttock and on her right thigh (lesion 3). Microscopically, all were ill-defined dermal lesions with some subcutaneous involvement and were mostly composed of mature adipocytes. The adipocytes formed small aggregates around blood vessels in the upper dermis. Lesions 1, 2, and 3 were diagnosed as NLCS, and additional features were recognized in lesions 2 and 3. Lesion 2 revealed eccrine glands and ducts amongst the lipomatous component, as seen in cutaneous AL. Lesion 3 had scattered CD34-positive spindle cells, which is representative of dermal SCL. These appearances were considered to be on the morphological spectrum of NLCS. In all three lesions, CD34-positive cells proliferated between the upper dermal blood vessels and their peripheral mature adipocytes. This pathological finding could be principal in NLCS and might be associated with its pathogenesis.In vertebrates, the mineralocorticoid receptor (MR) is a steroid-activated nuclear receptor (NR) that plays essential roles in water-electrolyte balance and blood pressure homeostasis. It belongs to the group of oxo-steroidian NRs, together with the glucocorticoid (GR), progesterone (PR), and androgen (AR) receptors. Classically, these oxo-steroidian NRs homodimerize and bind to specific genomic sequences to activate gene expression. NRs are multi-domain proteins, and dimerization is mediated by both the DNA (DBD) and ligand binding domains (LBDs), with the latter thought to provide the largest dimerization interface. However, at the structural level, the dimerization of oxo-steroidian receptors LBDs has remained largely a matter of debate and, despite their sequence homology, there is currently no consensus on a common homodimer assembly across the four receptors, that is, GR, PR, AR, and MR. Here, we examined all available MR LBD crystals using different computational methods (protein common interface database, proteins, interfaces, structures and assemblies, protein-protein interaction prediction by structural matching, and evolutionary protein-protein interface classifier, and the molecular mechanics Poisson-Boltzmann surface area method). A consensus is reached by all methods and singles out an interface mediated by helices H9, H10 and the C-terminal F domain as having characteristics of a biologically relevant assembly. Interestingly, a similar assembly was previously identified for GRα, MR closest homolog. Alternative architectures that were proposed for GRα were not observed for MR. These data call for further experimental investigations of oxo-steroid dimer architectures.SimBit is a general purpose, high performance forward-in-time population genetics simulator. SimBit can simulate a wide variety of selection scenarios (any selection and dominance coefficients variation, any epistatic interaction, any spatial and temporal changes of selection scenario, etc.), demographic scenarios (any changes in patch sizes, migration rates, realistic demography dependent on fecundity, hard vs. soft selection, exponential vs. logistic growth, gametic or zygotic dispersion, etc.) and mating systems (cloning and selfing rates, hermaphrodites or males and females). SimBit can also track QTLs (with hyperdimensional phenotypes, explicit fitness landscape, plasticity, developmental noise, etc.). Finally, SimBit can simulate multiple species with their ecological relationships. SimBit comes with a R wrapper that simplifies the management of an entire research project from the creation of a grid of parameters and corresponding inputs, running simulations and gathering outputs for analysis. SimBit's performance was extensively benchmarked in comparison to SLiM, Nemo and SFS_CODE, varying population size, recombination rate, mutation rate, and the number of loci. I also reproduced simulations from previous studies, benchmarked QTLs and coalescent tree recording techniques. SimBit was most often the highest performing program with the only notable exception of SLiM outperforming SimBit in scenarios with few loci and low genetic diversity.Immunity against different Mycobacteria species targeting the lung requires distinctly different pulmonary immune responses for bacterial clearance. Many parameters of acquired and regulatory immune responses differ quantitatively and qualitatively from immunity during infection with Mycobacteria species. Nontuberculosis Mycobacteria species (NTM) Mycobacterium avium- (M avium), Mycobacterium abscessus-(M abscessus), and the Mycobacteria species Mycobacterium tuberculosis-(Mtb). Herein, we discuss the potential implications of acquired and regulatory immune responses in the context of animal and human studies, as well as future directions for efforts to treat Mycobacteria diseases.Cholesterotic fibrous histiocytoma is a particularly rare variant of dermatofibroma that is distinguished histopathologically by the presence of prominent cholesterol deposits within the lesion. We report the case of a 54-year-old male with poorly controlled hyperlipidemia who presented with a firm violaceous papule on the right shin, diagnosed as a cholesterotic fibrous histiocytoma. We also review and summarize the existing literature on this uncommon entity.Ferroelectric spin crossover (SCO) behavior is demonstrated to occur in the cobalt(II) complex, [Co(FPh-terpy)2 ](BPh4 )2 ⋅3ac (1⋅3 ac; FPh-terpy=4'-((3-fluorophenyl)ethynyl)-2,2'6',2-terpyridine) and is dependent on the degree of 180° flip-flop motion of the ligand's polar fluorophenyl ring. Single crystal X-ray structures at several temperatures confirmed the flip-flop motion of fluorobenzene ring and also gave evidence for the SCO behavior with the latter behavior also confirmed by magnetic susceptibility measurements. The molecular motion of the fluorobenzene ring was also revealed using solid-state 19 F NMR spectroscopy. Thus the SCO behavior is accompanied by the flip-flop motion of the fluorobenzene ring, leading to destabilization of the low spin cobalt(II) state; with the magnitude of rotation able to be controlled by an electric field. This first example of spin-state conversion being dependent on the molecular motion of a ligand-appended fluorobenzene ring in a SCO cobalt(II) compound provides new insight for the design of a new category of molecule-based magnetoelectric materials.Tadpoles of the Vampire tree frog Rhacophorus vampyrus differ substantially from other rhacophorid tadpoles, by having profound modifications in external morphology. The morphological peculiarities of this species likely correlate with their arboreal microhabitat and strict oophagous diet. In this work, we examine buccal and musculoskeletal anatomy and compare them to other rhacophorid and egg-eating larvae. The shape and arrangement of cartilages of the lower jaw are unique among tadpoles, and the lack of a palatoquadrate suspensorium is only known in the distantly related macrophagous tadpoles of the dicroglossid Occidozyga baluensis. The cranial musculature is massive, and the morphology of several mandibular, hyoid, and abdominal muscles could be related to the ingestion and transit of large eggs. In the buccal cavity, conspicuous aspects are the absence of ridges and papillae, and the development of a unique glandular zone in the buccal floor. Finally, observations of the skeletal support of keratinized mouthparts allow us to present a topography-based hypothesis of homology of the conspicuous fangs of these tadpoles.Amniotic eggs are multifunctional structures that enabled early tetrapods to colonize the land millions of years ago, and are now the reproductive mode of over 70% of all terrestrial amniotes. Eggshell morphology is at the core of animal survival, mediating the interactions between embryos and their environment, and has evolved into a massive diversity of forms and functions in modern reptiles. These functions are critical to embryonic survival and may serve as models for new antimicrobial and/or breathable membranes. However, we still lack critical data on the basic structural and functional properties of eggs, particularly of reptiles. Here, we first characterized egg shape, shell thickness, porosity, and mineralization of eggs from 91 reptile species using optical images, scanning electron microscopy, and micro computed tomography, and collected data on nesting ecology from the literature. We then used comparative analyses to test hypotheses on the selective pressures driving their evolution. We hypothesized that eggshell morphology has evolved to protect shells from physical damage and desiccation, and, in support, found a positive relationship between thickness and precipitation, and a negative relationship between porosity and temperature. Although mineralization varied extensively, it was not correlated with nesting ecology variables. Ancestral state reconstructions show thinning and increased porosity over evolutionary time in squamates, but the opposite in turtles and crocodilians. Egg shape, size, porosity and calcification were correlated, suggesting potential structural or developmental tradeoffs. This study provides new data and insights into the morphology and evolution of reptile eggs, and raises numerous questions for additional research.Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and one of the leading causes of cancer associated death worldwide. This is due to the highly resistant nature of this malignancy and the lack of effective treatment options for advanced stage HCC patients. The hyperactivity of PI3K/Akt and Ras/Raf/MEK/ERK signaling pathways contribute to the cancer progression, survival, motility, and resistance mechanisms, and the interaction of these two pathways are responsible for the regulation of cancer cell growth and development. Therefore, it is vital to design and develop novel therapeutic options for HCC treatment targeting these hyperactive pathways. For this purpose, novel series of trans-indole-3-ylacrylamide derivatives originated from the lead compound, 3-(1H-indole-3-yl)-N-(3,4,5-trimethoxyphenyl)acrylamide, have been synthesized and analyzed for their bioactivity on cancer cells along with the lead compound. Based on the initial screening, the most potent compounds were selected to elucidate their effects on cellular signaling activity of HCC cell lines. Cell cycle analysis, immunofluorescence, and Western blot analysis revealed that lead compound and (E)-N-(4-tert-butylphenyl)-3-(1H-indole-3-yl)acrylamide induced cell cycle arrest at the G2/M phase, enhanced chromatin condensation and PARP-cleavage, addressing induction of apoptotic cell death. Additionally, these compounds decreased the activity of ERK signaling pathway, where phosphorylated ERK1/2 and c-Jun protein levels diminished significantly. Relevant to these findings, the lead compound was able to inhibit tubulin polymerization as well. To conclude, the novel trans-indole-3-ylacrylamide derivatives inhibit one of the critical pathways associated with HCC which results in cell cycle arrest and apoptosis in HCC cell lines.

Wearable devices that obtain transdermal alcohol concentration (TAC) could become valuable research tools for monitoring alcohol consumption levels in naturalistic environments if the TAC they produce could be converted into quantitatively-meaningful estimates of breath alcohol concentration (eBrAC). Our team has developed mathematical models to produce eBrAC from TAC, but it is not yet clear how a variety of factors affect the accuracy of the models. Stomach content is one factor that is known to affect breath alcohol concentration (BrAC), but its effect on the BrAC-TAC relationship has not yet been studied.

We examine the BrAC-TAC relationship by having two investigators participate in four laboratory drinking sessions with varied stomach content conditions (i) no meal, (ii) half and (iii) full meal before drinking, and (iv) full meal after drinking. BrAC and TAC were obtained every 10 min over the BrAC curve.

Eating before drinking lowered BrAC and TAC levels, with greater variability in TAC across person-device pairings, but the BrAC-TAC relationship was not consistently altered by stomach content. The mathematical model calibration parameters, fit indices, and eBrAC curves and summary score outputs did not consistently vary based on stomach content, indicating that our models were able to produce eBrAC from TAC with similar accuracy despite variations in the shape and magnitude of the BrAC curves under different conditions.

This study represents the first examination of how stomach content affects our ability to model estimates of BrAC from TAC and indicates it is not a major factor.

This study represents the first examination of how stomach content affects our ability to model estimates of BrAC from TAC and indicates it is not a major factor.A set of novel hydrazone derivatives were synthesized and analyzed for their biological activities. The compounds were tested for their inhibitory effect on the phosphorylating activity of the protein kinase CK2, and their antioxidant activity was also determined in three commonly used assays. The hydrazones were evaluated for their radical scavenging against the DPPH, ABTS and peroxyl radicals. Several compounds have been identified as good antioxidants as well as potent protein kinase CK2 inhibitors. Most hydrazones containing a 4-N(CH3 )2 residue or perfluorinated phenyl rings showed high activity in the radical-scavenging assays and possess nanomolar IC50 values in the kinase assays.

Placenta accreta spectrum (PAS) is a condition often resulting in severe maternal morbidity. Scheduled delivery by an experienced team has been shown to improve maternal outcomes; however, the benefits must be weighed against the risk of iatrogenic prematurity. The aim of this study is to investigate the rates of emergency delivery seen for antenatally suspected PAS and compare the resulting outcomes in the 15 referral centers of the International Society for PAS (IS-PAS).

Fifteen centers provided cases between 2008 and 2019. The women included were divided into two groups according to whether they had a planned or an emergency cesarean delivery. Delivery was defined as "planned" when performed at a time and date to suit the team. All the remaining cases were classified as "emergency". Maternal characteristics and neonatal outcomes were compared between the two groups according to gestation at delivery.

In all, 356 women were included. Of these, 239 (67%) underwent a planned delivery and 117 (33%) an emate expertise and resources are available, to defer delivery in women with no significant antenatal bleeding and no risk factors for pre-term birth until >36

weeks can be considered to improve fetal outcomes. Further studies are needed to investigate this fully.

36+0 weeks can be considered to improve fetal outcomes. Further studies are needed to investigate this fully.Nudibranch mollusks (Gastropoda Heterobranchia) are widely known for their ability to incorporate some active biochemical compounds of their prey, or even organelles and symbionts of the prey, which assured biological success of this group. At the same time, the process of nematocysts obtaining and incorporation into specific structures called cnidosacs by cladobranch mollusks remain poorly studied. This highlights a necessity of additional ultrastructural studies of cnidosac and adjacent organs in various aeolid mollusks using modern microscopic methods as they may provide new insight into the cnidosac diversity and fine-scale dynamics of nematocysts sequestration process. The present study is focused on the general and fine structure of the cnidosac area in cladobranch Aeolidia papillosa (Aeolidiidae). Specific goals of our study were to provide a detailed description of histological and ultrafine structure of epidermis, upper parts of the digestive glands and the cnidosac, its innervation and proliferation using standard histological techniques, confocal laser scanning microscopy (CLSM) and transmission electron microscopy. Our results clearly demonstrated that A. papillosa cnidosac is a much more complex structure, than it was thought, especially compared with simple cnidosacs found in flabellinids and facelinids. Using CLSM for functional morphological analysis provides a better resolution in visualization of structural elements within a cnidosac compared with traditional histological techniques. We revealed the presence of two cell types in the cnidophage zone cnidophages and interstitial cells, which differ in ultrastructure and function. Our results also document the presence of a specific cnidopore zone, lined with differentiated cuboid epithelium bearing long microvilli, which likely provides a unidirectional flow of nematocysts during kleptocnides extrusion. For the first time, occurrence of vacuoles containing protective chitinous spindles in the cnidosac epithelium was shown.Colorectal cancer is the third most common neoplasm in the world and the third leading cause of cancer-related deaths in the USA. A safer and more effective therapeutic intervention against this malignant carcinoma is called for given the limitations and toxicities associated with the currently available treatment modalities. Immuno-oncolytic or oncolytic virotherapy, the use of viruses to selectively or preferentially kill cancer cells, has emerged as a potential anticancer treatment modality. Oncolytic viruses act as double-edged swords against the tumors through the direct cytolysis of cancer cells and the induction of antitumor immunity. A number of such viruses have been tested against colorectal cancer, in both preclinical and clinical settings, and many have produced promising results. Oncolytic virotherapy has also shown synergistic antitumor efficacy in combination with conventional treatment regimens. In this review, we describe the status of this therapeutic approach against colorectal cancer at both preclinical and clinical levels. Successes with and the challenges of using oncolytic viruses, both as monotherapy and in combination therapy, are also highlighted.Cerebrovascular disease is the most common life-threatening and debilitating condition that often leads to stroke. The multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) is a key Ca2+ sensor and an important signaling protein in a variety of biological systems within the brain, heart, and vasculature. In the brain, past stroke-related studies have been mainly focused on the role of CaMKII in ischemic stroke in neurons and established CaMKII as a major mediator of neuronal cell death induced by glutamate excitotoxicity and oxidative stress following ischemic stroke. However, with growing understanding of the importance of neurovascular interactions in cerebrovascular diseases, there are clearly gaps in our understanding of how CaMKII functions in the complex neurovascular biological processes and its contributions to cerebrovascular diseases. Additionally, emerging evidence demonstrates novel regulatory mechanisms of CaMKII and potential roles of the less-studied CaMKII isoforms in the ischemic brain, which has sparked renewed interests in this dynamic kinase family. This review discusses past findings and emerging evidence on CaMKII in several major cerebrovascular dysfunctions including ischemic stroke, hemorrhagic stroke, and vascular dementia, focusing on the unique roles played by CaMKII in the underlying biological processes of neuronal cell death, neuroinflammation, and endothelial barrier dysfunction triggered by stroke. We also highlight exciting new findings, promising therapeutic agents, and future perspectives for CaMKII in cerebrovascular systems.Sympathetic nervous system plays an important role in secondary injury of diseases. Accumulating evidence has observed association between ischemic stroke and renal dysfunction, but the mechanisms are incompletely clear. In this study, we investigated whether sympathetic hyperactivity can cause the development of renal dysfunction, apoptosis, and fibrogenesis after focal cerebral infarction. To determine the renal consequences of focal cerebral ischemia, we subjected a mice model of transient middle cerebral artery occlusion (tMCAO) and examined systolic blood pressure, heart rate, renal structure and function, serum catecholamine, and cortisol levels, and the expression of active caspase-3 bcl-2, bax, and phosphorylated p38 MAPK after 8 weeks. We also analyzed the relationship between insular cortex infarction and acute kidney injury (AKI) in 172 acute anterior circulation ischemic stroke (ACIS) patients. Transient right middle cerebral artery occlusion induced sympathetic hyperactivity, renal dysfunction, upregulation of apoptosis, and fibrogenesis in kidneys of mice. Metoprolol treatment relieves the development of renal injury. Study in stroke patients demonstrated that insular cortex infarction, especially the right insular cortex infarction, is an independent risk factor of AKI. Focal cerebral ischemia in mice leads to the development of renal injury driven by sympathetic hyperactivity. Right insular cortex infarction is an independent risk factor of AKI in older patients. Understanding the brain-kidney interaction after stroke would have clinical implications for the treatment and overall patient outcome.Excessive glutamate leading to excitotoxicity worsens brain damage after SAH and contributes to long-term neurological deficits. The drug ifenprodil is a non-competitive antagonist of GluN1-GluN2B N-methyl-d-aspartate (NMDA) receptor, which mediates excitotoxic damage in vitro and in vivo. Here, we show that cerebrospinal fluid (CSF) glutamate level within 48 h was significantly elevated in aSAH patients who later developed poor outcome. In rat SAH model, ifenprodil can improve long-term sensorimotor and spatial learning deficits. Ifenprodil attenuates experimental SAH-induced neuronal death of basal cortex and hippocampal CA1 area, cellular and mitochondrial Ca2+ overload of basal cortex, blood-brain barrier (BBB) damage, and cerebral edema of early brain injury. Using in vitro models, ifenprodil declines the high-concentration glutamate-mediated intracellular Ca2+ increase and cell apoptosis in primary cortical neurons, reduces the high-concentration glutamate-elevated endothelial permeability in human brain microvascular endothelial cell (HBMEC). Altogether, our results suggest ifenprodil improves long-term neurologic deficits through antagonizing glutamate-induced excitotoxicity.Overactive bladder (OAB) is a common disorder in the general population, and the prevalence increases with age. Adults with OAB typically have a greater number of comorbid conditions, such as hypertension, depression, and dementia, compared with adults without OAB. Subsequent to an increased number of comorbidities, adults with OAB take a greater number of concomitant medications, which may increase the risk of potentially harmful drug‒drug interactions. There are two important considerations for many of the medications approved for the treatment of OAB in the USA anticholinergic burden and potential for drug‒drug interactions, notably related to cytochrome P450 (CYP) 2D6, which is responsible for the metabolism of approximately 25% of all drugs. A substantial number of drugs used for the treatment of OAB and comorbid conditions (e.g., cardiovascular and neurologic disorders) are CYP2D6 substrates or inhibitors. Furthermore, a substantial number of drugs with CYP2D6 properties also have strong anticholinergic properties.