Pseudogamy is a reproductive system in which females rely on the sperm of males to activate their oocytes, generally parasitizing males of other species, but do not use the sperm DNA. The nematode Mesorhabditis belari uses a specific form of pseudogamy, where females produce their own males as a source of sperm. Males develop from rare eggs with true fertilization, while females arise by gynogenesis. Males thus do not contribute their genome to the female offspring. Here, we explored the diversity of reproductive mode within the Mesorhabditis genus and addressed species barriers in pseudogamous species.

To this end, we established a collection of over 60 Mesorhabditis strains from soil and rotting vegetal matter. We found that males from pseudogamous species displayed a reduced size of their body, male tail and sperm cells compared to males of sexual Mesorhabditis species, as expected for males that face little competition. Using rDNA sequences and crosses, we could define 11 auto-pseudogamous biological of species barrier.

We established a collection of sexual and pseudo-sexual species which offer an ideal framework to explore the origin and consequences of transition to asexuality. Our results demonstrate that speciation occurs in the pseudogamous state. Whereas genomic conflicts are responsible for hybrid incompatibility in sexual species, we here reveal that centrosomes constitute key organelles in the establishment of species barrier.

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent diseases worldwide. Episodes of acute exacerbations of COPD (AECOPD) are associated with disease severity and progression. Although substantial progress has been made in understanding the dynamics of AECOPD, little is known about the sputum microbiome of AECOPD in the Chinese population.

In this study, we characterized the sputum microbiomes from sputum specimens collected from healthy controls (n = 10), stable (n = 4), AECOPD (n = 36), and recovery (n = 18) stages by sequencing the V3-V4 region of the 16S rRNA gene with a HiSeq sequencer.

Streptococcus was the most dominant genus among all the different types of sputum. A random forest model was developed to identify bacterial taxa that differentiate AECOPD samples from others. Most of the top predictors, except Pseudomonas, were less abundant in AECOPD samples. We also developed random forest models to differentiate subtypes of AECOPD based on blood eosinophil counts, the frequency of AECOPD, and sputum eosinophils. Bacterial taxa associated with Pasteurellaceae, Fusobacterium, Solobacterium, Haemophilus, Atopobium, Corynebacterium and Streptococcus, were enriched in the sputum microbiomes of eosinophilic AECOPD. Random forest models also demonstrate that a total of 2 bacterial OTUs were needed to differentiate frequent from non-frequent AECOPDs, and 23 OTUs were enough to accurately predict sputum-eosinophilic (sputum eosinophilic concentration ≥ 3%) AECOPD.

This study expanded our understanding of the sputum microbiome associated with different subtypes and clinical status of patients with AECOPD in a Chinese cohort, which provides insights into novel and more targeted management of the different subtypes of AECOPD.

This study expanded our understanding of the sputum microbiome associated with different subtypes and clinical status of patients with AECOPD in a Chinese cohort, which provides insights into novel and more targeted management of the different subtypes of AECOPD.

Recently, left bundle branch area pacing (LBBAP) has been shown to be feasible. However, the right ventricular (RV) implantation site for LBBAP remains elusive. We believe that the RV implantation site should be located at the posteromedial basal septum, and in this paper, we propose a new method to help guide lead implantation. The aim of this study is to demonstrate the feasibility of the proposed method.

The RV implantation site was positioned by a combination of a nine-grid system on fluoroscopy and the use of intracardiac echocardiogram (ICE) and then verified by ICE.

Fifteen patients were enrolled for LBBAP using our method. The acute success rate was 86.7% (13/15), which demonstrated that our method is useful for assisting with lead implantation. According to ICE, the distance between the implantation site and apex (the front) and the distance between the implantation site and tricuspid annulus (the back) were 44.9 ± 10.7 and 33.2 ± 10.4 mm, respectively, and the ratio of the front and the back whod for assisting with lead implantation. It is feasible and safe to use a nine-grid system combined with ICE for LBBAP.

Our preliminary results indicate that the posteromedial basal septum could be seen as the implantation site for LBBAP. As a technique for LBBAP, ICE is a useful method for assisting with lead implantation. It is feasible and safe to use a nine-grid system combined with ICE for LBBAP.

Among eukaryotic organisms, alternative splicing is an important process that can generate multiple transcripts from one same precursor messenger RNA, which greatly increase transcriptome and proteome diversity. This process is carried out by a super-protein complex defined as the spliceosome. Specifically, splicing factor 1/branchpoint binding protein (SF1/BBP) is a single protein that can bind to the intronic branchpoint sequence (BPS), connecting the 5′ and 3′ splice site binding complexes during early spliceosome assembly. The molecular function of this protein has been extensively investigated in yeast, metazoa and mammals. However, its counterpart in plants has been seldomly reported.

To this end, we conducted a systematic characterization of the SF1 gene family across plant lineages. In this work, a total of 92 sequences from 59 plant species were identified. Phylogenetic relationships of these sequences were constructed, and subsequent bioinformatic analysis suggested that this family likely originated from an ancient gene transposition duplication event. Most plant species were shown to maintain a single copy of this gene. Furthermore, an additional RNA binding motif (RRM) existed in most members of this gene family in comparison to their animal and yeast counterparts, indicating that their potential role was preserved in the plant lineage.

Our analysis presents general features of the gene and protein structure of this splicing factor family and will provide fundamental information for further functional studies in plants.

Our analysis presents general features of the gene and protein structure of this splicing factor family and will provide fundamental information for further functional studies in plants.

Left-sided portal hypertension (LSPH) is an extremely rare clinical syndrome, and it is the only form of curable portal hypertension. It is primarily caused by pancreatic disease, and is associated with complications that cause spleen vein compression. Specific symptoms are often lacking, rendering it difficult to diagnose. Splenectomy is the main treatment for cases complicated by variceal bleeding, and the effects of treatment primarily depend on the condition of the primary disease.

The patient was a 29-year-old woman who was admitted to the hospital for repeated hematemesis and black stool. She had been misdiagnosed with pancreatic cancer 7 years prior. Combined imaging and endoscopic examination indicated varicose gastric fundus veins, a pancreatic mass, and enlarged peripancreatic lymph nodes. Laboratory investigations revealed reduced erythrocyte, platelet, and leukocyte counts, the interferon gamma release assay was positive, and liver function was normal. Abdominal exploration, splenectomy, varics and more advantageous therapy for LSPH, especially in cases caused by mechanical compression.An amendment to this paper has been published and can be accessed via the original article.

The extraesophageal manifestations of gastroesophageal reflux disease (GERD) are more difficult to manage than the typical symptoms. The efficacy of high-dose and standard-dose proton pump inhibitors against these atypical symptoms is not yet established.

In this single center, randomized, open-label study, patients with GERD received rabeprazole for 8 weeks, either 20 mg once daily (standard-dose group) or 20 mg twice daily (high-dose group). Patients were assessed before treatment and at weeks 4 and 8 with a 5-graded scale questionnaire consisting of 2 typical symptoms (heartburn and acid regurgitation) and 8 atypical symptoms (chest pain, cough, globus, wheezing, laryngopharyngitis, hoarseness, belching, and dysphagia). Sufficient improvement of reflux symptoms was defined as ≥50% reduction from the initial questionnaire score.

Final analyses included 35 patients in the standard-dose group and 38 patients in the high-dose group. The rate of sufficient improvement for typical symptoms was significantlClinicalTrials.gov Protocol Registration and Results system ID NCT04001400 ). This study was registered on June 26, 2019 – Retrospectively registered.

Maximum oxygen uptake is an established measurement of diagnosing chronic heart failure and underlies various central and peripheral factors. However, central and peripheral factors are little investigated, because they are usually measured invasively. The aim of this study was to compare non-invasively measured central and peripheral factors of oxygen uptake between patients with chronic heart failure and healthy controls.

Ten male patients with heart failure with reduced ejection fraction (62 ± 4 years; body mass index 27.7 ± 1.8 kg/m

; ejection fraction 30 ± 4%) and ten male healthy controls (59 ± 3 years; body mass index 27.7 ± 1.3 kg/m

) were tested for blood pressure, heart rate, stroke volume, cardiac output, and cardiac power output (central factors) as well as muscle oxygen saturation of the vastus lateralis and biceps brachii muscle (peripheral factors) during an incremental cycling test. Stroke volume and muscle oxygen saturation were non-invasively measured by a bioreactance analysis and neath chronic heart failure and healthy controls. Therefore, it is promising to measure both types of factors in patients with chronic heart failure to optimize the diagnosis and therapy.

Although the etiology of pouchitis remains unknown, inflammatory cytokines are significantly associated with the pathogenesis of pouchitis. The cytokine responses that characterize inflammatory bowel diseases (IBD) are key pathogenic components of the disease. Although cytokine profiles in the colonic mucosa have been investigated in experimental colitis models or IBD patients, cytokine profiles in the ileal mucosa at colectomy have been rarely assessed.

To assess the relationship between pouchitis and T helper (Th) cytokines in the ileal mucosa collected at the time of colectomy and pouch construction.

This retrospective study involved 68 consecutive patients from January 2004 to May 2011 who underwent ileal pouch-anal anastomosis for ulcerative colitis. Samples were obtained from the terminal ileum of resected specimens at time of total colectomy or subtotal colectomy. mRNA expression levels of Th cytokines (IFN-γ, IL-23A, IL-5, IL-13 and IL-17A) were determined.

Forty of 68 patients (58.8%) developed pouchitis. There was no association between IL-23A expression levels and incidence of pouchitis (p =0.301). Patients with elevated IFN-γ had a significantly higher incidence of pouchitis compared with low IFN-γ patients (p = 0.043). Univariate analysis demonstrated a total dose of prednisolone > 7000 mg administered before colectomy (p = 0.04) and high IFN-γ expression (p = 0.02) were significant risk factors for pouchitis onset. In multivariate analysis, elevated IFN-γ messenger(m)RNA levels were significantly associated with pouchitis onset (p = 0.03).

IFN-γ expression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.

IFN-γ expression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.

Gene co-expression networks (GCNs) are powerful tools that enable biologists to examine associations between genes during different biological processes. With the advancement of new technologies, such as single-cell RNA sequencing (scRNA-seq), there is a need for developing novel network methods appropriate for new types of data.

We present a novel sparse Bayesian factor model to explore the network structure associated with genes in scRNA-seq data. Latent factors impact the gene expression values for each cell and provide flexibility to account for common features of scRNA-seq high proportions of zero values, increased cell-to-cell variability, and overdispersion due to abnormally large expression counts. From our model, we construct a GCN by analyzing the positive and negative associations of the factors that are shared between each pair of genes.

Simulation studies demonstrate that our methodology has high power in identifying gene-gene associations while maintaining a nominal false discovery rate. In real data analyses, our model identifies more known and predicted protein-protein interactions than other competing network models.

Simulation studies demonstrate that our methodology has high power in identifying gene-gene associations while maintaining a nominal false discovery rate. In real data analyses, our model identifies more known and predicted protein-protein interactions than other competing network models.

Microbiomes can have profound impacts on host biology and evolution, but to date, remain vastly understudied in spiders despite their unique and diverse predatory adaptations. This study evaluates closely related species of spiders and their host-microbe relationships in the context of phylosymbiosis, an eco-evolutionary pattern where the microbial community profile parallels the phylogeny of closely related host species. Using 16S rRNA gene amplicon sequencing, we characterized the microbiomes of five species with known phylogenetic relationships from the family Theridiidae, including multiple closely related widow spiders (L. hesperus, L. mactans, L. geometricus, S. grossa, and P. tepidariorum).

We compared whole animal and tissue-specific microbiomes (cephalothorax, fat bodies, venom glands, silk glands, and ovary) in the five species to better understand the relationship between spiders and their microbial symbionts. This showed a strong congruence of the microbiome beta-diversity of the whole spiders, cephalothorax, venom glands, and silk glands when compared to their host phylogeny. Our results support phylosymbiosis in these species and across their specialized tissues. The ovary tissue microbial dendrograms also parallel the widow phylogeny, suggesting vertical transfer of species-specific bacterial symbionts. By cross-validating with RNA sequencing data obtained from the venom glands, silk glands and ovaries of L. hesperus, L. geometricus, S. grossa, and P. tepidariorum we confirmed that several microbial symbionts of interest are viably active in the host.

Together these results provide evidence that supports the importance of host-microbe interactions and the significant role microbial communities may play in the evolution and adaptation of their hosts.

Together these results provide evidence that supports the importance of host-microbe interactions and the significant role microbial communities may play in the evolution and adaptation of their hosts.

Favism is characterized as acute anemia, due to Glucose-6-phosphate dehydrogenase (G6PD) deficiency as a result of fava beans intake. It is associated with paleness, jaundice, and hemoglobinuria. In this study, signs, symptoms and therapeutic findings of the patients with hemolysis due to G6PD deficiency were investigated in Shahid Madani Hospital of Khorramabad, Lorestan.

This is a single-center cross-sectional descriptive study that was conducted on all children with G6PD deficiencyinduced hemolysis.

308 children (64.3% male and 35.7% female) were included in this study. The most common complaint was jaundice (82.5%) and the most common cause of hemolysis was the intake of fava bean (85.7%). 68% of the children were treated with hydration/fluid therapy. Blood transfusion was conducted in 36.36% of the cases and the mean of blood administered was 18.9 cc/kg.

In this study, hydration therapy was performed in most of the children presenting favism. Also, the incorrect calculation of the amount of blood needed for transfusion has increased the frequency of blood transfusions and prolonged hospitalization time.

In this study, hydration therapy was performed in most of the children presenting favism. Also, the incorrect calculation of the amount of blood needed for transfusion has increased the frequency of blood transfusions and prolonged hospitalization time.

This study aimed to evaluate the antidiabetic and antihyperlipidemic effects of Asteriscus graveolens.

Asteriscus graveolens (Asteraceae) is a medicinal plant widely used by the Moroccan population to treat various diseases including diabetes.

This work aimed to assess the capacity of flavonoids extracted from Asteriscus graveolens (FEE) to improve diabetes mellitus and dyslipidemia in normal and STZ-induced diabetic rats.

Flavonoids were extracted from A. graveolens using the Soxhlet apparatus and using different organic solvents. Normal and streptozotocin-induced diabetic rats were treated orally by the extract of A. graveolens at a dose of 10 mg/kg. The oral treatment during 15 days was used to evaluate the effect of the flavonoids extracted from A. graveolens on blood glucose level and lipid profile in normal and diabetic rats. The oral glucose tolerance test as well as the analysis of histopathological examination of liver was performed. The antioxidant activity of FEE was also assessed by the method of trapping of free radical 2,2-diphenyl-1 picrylhydrazyl (DPPH), in order to estimate the mechanisms of action involved by FEE to improve hyperglycemia and lipid profile in normal and diabetic rats.

FEE reduced serum glucose concentrations in both normal and diabetic rats and exhibited in the last group lowering total cholesterol and triglycerides effects as well as improvement of the HDL-cholesterol serum level. In addition, a remarkable influence on glucose tolerance was also noticed after FEE treatment. Moreover, FEE was able to improve histopathological status of liver and possess a potential antioxidant effect in vitro.

In conclusion, this study demonstrates the hypoglycemic and antihyperlipidemic effects of FEE in rats supporting then its traditional use for the management of diabetes.

In conclusion, this study demonstrates the hypoglycemic and antihyperlipidemic effects of FEE in rats supporting then its traditional use for the management of diabetes.

Multiple myeloma (MM) is a malignant disease manifested by the clonal proliferation of atypical plasma cells. Macrophage inhibitory factor (MIF) is one of the pleiotropic regulators in various biological and cellular processes. Mannose-binding lectin (MBL) is a crucial protein involved in the lectin pathway of the immune system.

We aimed to assess whether variants of MIF and MBL2 genes are associated with MM among a Turkish population.

We analyzed the MIF-173G/C (rs755622) and MBL2 codon 54A/B (rs1800450) variants in 200 patients with MM and 200 healthy control subjects using a polymerase chain reaction (PCR) followed by restriction endonuclease digestion. There was also an evaluation of the patients undergoing autologous stem-cell transplantation (ASCT) for these variants.

AA and BB genotypes of MBL2 codon 54A/B increased in the patients as compared to the controls (p=0.008, p=0.001, respectively). The subjects carrying AA and BB genotypes of MBL2 were at high risk of development of susceptibility to MM by 7.377 and 8.812 times, respectively. The distribution of MBL2 codon 54A/B alleles was similar between the groups (p>0 .05). There was no statistical difference between the patients and controls in the genotype and allele frequencies of the MIF-173G/C variant (p>0 .05). The patients undergoing ASCT, MBL2 codon54A/B AA and BB genotypes also showed association with increased risk for MM (p=0.004, p=0.001, respectively).

As far as we know, this is the first report of the study on an association between these variants and MM in our population. Our results indicate that the MBL2 codon 54A/B variant may be associated with susceptibility to MM.</p>.

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To investigate the effect of smoking and alcohol intake on the association between betel nut chewing and each metabolic abnormality.

Betel nut chewing has been associated with metabolic syndrome.

Whether the association is affected by tobacco or alcohol use is not clarified so far.

We made a cross-sectional study using 6,657 military males, aged 18-50 years in eastern Taiwan in 2013-2014. Metabolic syn-drome was defined according to the International Diabetes Federation ethnic criteria for Asians. The population was classified as non-betel nut chewers (N =5,749), current chewers with both tobacco and alcohol use (N =615), and current chewers without tobacco and/or alcohol use (N =293). Multiple logistic regressions analyses were stepwise adjusted for the confounders including alcohol and tobacco use to de-termine the associations of betel chewing with the metabolic abnormalities.

As compared with the non-current chewers, the current chewers with both tobacco/alcohol use and those without had higher and 1.87 (1.42-2.45), respectively, p =0.76).

Our findings suggest that tobacco smoking but not alcohol intake could increase the relationship of betel nut chewing with metabolic syndrome, which is likely mediated by a synergic effect on increasing serum triglycerides levels.

Our findings suggest that tobacco smoking but not alcohol intake could increase the relationship of betel nut chewing with metabolic syndrome, which is likely mediated by a synergic effect on increasing serum triglycerides levels.

Anxiety and oxidative stress are the common disorders prevailing in the modern age. Many new pyrazoline derivatives have been synthesized and patented, but there is still continuous research in progress to explore antidepressant and antioxidant potential of pyrazoline scaffold.

The present work was carried out to synthesize, characterize and evaluate the pharmacological potential of 1,3,5-Pyrazoline derivatives.

Ten new 1,3,5-Pyrazoline derivatives were synthesized and characterized by IR, 1HNMR and mass spectral techniques. The synthesized pyrazoline derivatives were investigated for their in vivo antidepressant activity by Tail Suspension Test (TST) and in vitro antioxidant activity by FRAP and DPPH assay methods. The docking studies and in silico ADME and toxicity characteristics were also evaluated.

Among the synthesized analogues, IVh showed the highest antidepressant activity with a significant reduction in the duration of immobility. The compound IVh emerged as the most potent antioxidant compound due to the presence of an electron releasing hydroxyl group. Docking studies of most potent compounds revealed good interaction points with the MAO-A enzyme. The compounds were found to obey Lipinski’s Rule of Five and displayed the least in silico toxicity profile.

The synthesized compounds were found to possess great potential in decreasing the duration of immobility in Swiss albino mice and scavenging free radicals. These compounds may serve as new leads for further drug exploration.

The synthesized compounds were found to possess great potential in decreasing the duration of immobility in Swiss albino mice and scavenging free radicals. These compounds may serve as new leads for further drug exploration.

Pre-eclampsia contributes significantly to both maternal and perinatal morbidities and mortalities. One of the identified pathophysiology of pre-eclampsia is deranged serum lipid profile of which some components have been found to be elevated early in pregnancy in women destined to develop pre-eclampsia.

To compare the serum fasting lipid profiles of pre-eclamptic primigravidas with normal primigravidas at week 20, 28 ad 34.

We conducted a nested case-control study at Obafemi Awolowo University, Ile-Ife between November 2016 and April 2018. A cohort of 290 primigravidas was recruited at week 20 and followed up until delivery. Serum fasting lipid profiles were quantified at weeks 20, 28 and 34 for all participants. Twenty four women that developed pre-eclampsia were compared with 48 women that had normal pregnancy. Data were analysed with SPSS version 22. We used a linear mixed-effect regression model with random intercept and slope. Significance was established using p<0.05.

Serum lipid profiles showed average weekly increase in both groups. Primigravidas that developed pre-eclampsia had a weekly increase of 0.2(SE0.14) mmol/l in serum total cholesterol more than those with normal pregnancies.(p<0.001) Serum low density lipoprotein also showed a differential weekly increase of 0.1(SE0.05)mmol/l in primigravidas that developed pre-eclampsia over primigravidas with normal pregnancies.(p<0.001).

The average weekly increase in serum total cholesterol and low density lipoprotein were higher significantly in primigravidas that developed pre-eclampsia when compared to the control group. These findings depicted an association between serum lipid profile and pre-eclampsia among the primigravidas.</P>.

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Vortioxetine is approved for the treatment of Major Depressive Disorder (MDD). However, the safety of this drug in a large group of populations is still unclear. Thus, we have tried to analyze the risk profile of vortioxetine.

The data related to the risk profile of vortioxetine has been extracted from Pub-Med from January 2014 to May 2019. The adverse drug reactions (ADRs) have been categorized into a listed and unlisted categories as per Summary of product characteristics (SmPC) of the innovator. Further, unlisted ADRs have been analyzed as per Naranjo Scale.

The galactorrhea, hyperprolactinemia, glycolimia, exacerbation of anxiety, weight gain, edema, excessive itching, petechiae, and ecchymoses have been observed with the use of vortioxetine and falls under the unlisted category. Further, the causality assessment results have shown probable relation between vortioxetine and galactorrhea, hyperprolactinemia, edema, excessive itching, ecchymoses, and petechiae. The weight gain, glycolimia and exacerbation of anxiety have a possible relationship with vortioxetine. The common ADRs observed with the use of vortioxetine are nausea, diarrhea, constipation, vomiting, pruritus including pruritus generalized, abnormal dreams, and dizziness.

In conclusion, more data is required to establish the strong relationship between vortioxetine and reported unlisted ADRs.

In conclusion, more data is required to establish the strong relationship between vortioxetine and reported unlisted ADRs.Adult neurogenesis consists in the generation of newborn neurons from neural stem cells taking place in the adult brain. In mammals, this process is limited to very few areas of the brain, and one of these neurogenic niches is the subgranular layer of the dentate gyrus (DG) of the hippocampus. Adult newborn neurons are generated from quiescent neural progenitors (QNPs), which differentiate through different steps into mature granule cells (GCs), to be finally integrated into the existing hippocampal circuitry. In animal models, adult hippocampal neurogenesis (AHN) is relevant for pattern discrimination, cognitive flexibility, emotional processing and resilience to stressful situations. Imaging techniques allow to visualize newborn neurons within the hippocampus through all their stages of development and differentiation. In humans, the evidence of AHN is more challenging, and, based on recent findings, it persists through the adulthood, even if it declines with age. Whether this process has an important role in human brain function and how it integrates into the existing hippocampal circuitry is still a matter of exciting debate. Importantly, AHN deficiency has been proposed to be relevant in many psychiatric disorders, including mood disorders, anxiety, post-traumatic stress disorder and schizophrenia. This review aims to investigate how AHN is altered in different psychiatric conditions and how pharmacological treatments can rescue this process. In fact, many psychoactive drugs, such as antidepressants, mood stabilizers and atypical antipsychotics (AAPs), can boost AHN with different results. In addition, some non-pharmacological approaches are discussed as well.

The deterioration of cognitive and motor functions and activities of daily living is common in Alzheimer’s dementia.

The purpose of this study was to investigate the correlation and the strength of the relationship between cognitive function and motor function and activities of daily living after a diagnosis of Alzheimer’s disease dementia.

Sixty-three patients with mild to moderate Alzheimer’s disease dementia in a community setting of South Korea were examined for cognitive and motor functions, and functional levels. The test or measures used for cognitive function were the Mini-Mental State Examination (MMSE), Global Deterioration Scale (GDS), and Clinical Dementia Rating (CDR). The 10-meter walking test (10MWT), Berg Balance Scale (BBS), and Timed Up and Go Test (TUG) were used to examine motor function, while the Modified Barthel Index (MBI) and Katz Index (KI) were used to examining activities of daily living.

The MMSE had a positive correlation with that from the BBS (r=.338, p<.05), MBI (r=MMSE is correlated with balance by BBS and activities of daily living by MBI and KI, and MMSE, which are tests or measures for cognitive function, can be explanatory variable to explain variations in the BBS, MBI, and KI in the persons with mild to moderate Alzheimer’s dementia. It may mean that a decrease in cognitive function was found to affect motor function and activities of daily living. Based on this study, appropriate intervention approaches including physical exercise, should be considered for caring for persons with mild to moderate Alzheimer’s dementia in a community setting.Progress of modern dentistry is accelerating at a spectacular speed in the scientific, technological and clinical areas. Practical examples are the advancement in the digital field, which has guaranteed an average level of prosthetic practices for all patients, as well as other scientific developments, including research on stem cell biology. Given their plasticity, defined as the ability to differentiate into specific cell lineages with a capacity of almost unlimited self-renewal and release of trophic/immunomodulatory factors, stem cells have gained significant scientific and commercial interest in the last 15 years. Stem cells that can be isolated from various tissues of the oral cavity have emerged as attractive sources for bone and dental regeneration, mainly due to their ease of accessibility. This review will present the current understanding of emerging conceptual and technological issues of the use of stem cells to treat bone and dental loss defects. In particular, we will focus on the clinical application of stem cells, either directly isolated from oral sources or in vitro reprogrammed from somatic cells (induced pluripotent stem cells). Research aimed at further unraveling stem cell plasticity will allow to identify optimal stem cell sources and characteristics, to develop novel regenerative tools in dentistry.The challenges of viral infection have increased in recent decades due to the emergence of resistance, crossresistance and drying up of antiviral drug discovery. Many neglected tropical viruses including the chikungunya virus, dengue virus & Japanese encephalitis virus have gradually become global pathogens. This has further increased the burden of viral infection which necessitates the continuous development of antiviral therapy. The antiviral chemistry began with the development of thiosemicarbazide derived thiosemicarbazones as antiviral. Although very few thiosemicarbazides have progressed into clinical application, it still inspires antiviral development. During last 3 decades (1990-2020), several efforts have been made to develop suitable antiviral by using thiosemicarbazide scaffold. Its hybridization with other pharmacophores has been used as a strategy to enhance safety and efficacy. Cyclization and substitution of thiosemicarbazides have also been used to develop potent antiviral. With the ability to form coordinate bonds, thiosemicarbazides have been used either as metal complex or chelator against viruses. This work is an attempt to systematically review the research on the use of thiosemicarbazides as an antiviral scaffold. It also reviews the structureactivity relationship and translational suitability of thiosemicarbazide derived compounds.Naturally occurring naphthoquinones (NQs) comprising highly reactive small molecules are the subject of increasing attention due to their promising biological activities such as antioxidant, antimicrobial, apoptosis-inducing activities, and especially anticancer activity. Lapachol, lapachone, and napabucasin belong to the NQs and are in the USA in phase II clinical trials for the treatment of many cancers. This review aims to provide a comprehensive and updated overview on the biological activities of several new NQs isolated from different species of plants reported from January 2013 to January 2020, their potential therapeutic applications and their clinical significance.The need for new therapeutics and drug delivery systems has become necessary owing to the public health concern associated with the emergence of multidrug-resistant microorganisms. Among the newly discovered therapeutic agents is cefiderocol which was discovered by Shionogi Company, Japan as an injectable siderophore cephalosporin. Just like the other β-lactam antibiotics, cefiderocol exhibits antibacterial activity via cell wall synthesis inhibition, especially in Gram negative bacteria (GNB); it binds to the penicillin-binding proteins, but its unique attribute is that it crosses the periplasmic space of bacteria owing to its siderophore-like attribute; it also resists the activity of β-lactamases. Among all the synthesized compounds with the modified C-7 side chain, cefiderocol (3) presented the best and well-balanced activity against multi-drug resistant (MDR) Gram negative bacteria, including those that are resistant to carbapenem. İn this article, an overview of the recent studies on cefiderocol was presented.

Resistance of Helicobacter pylori（H. pylori） to antibiotics is increasing worldwide. In order to understand the current situation of antibiotic resistance in Nanjing and provide a reasonable basis for clinical selection of antibiotics to cure H. Pylori.

To investigate the current status of H. Pylori antibiotics resistance in Nanjing area, and analyze the primary and post-treatment antibiotic resistance of H. pylori in this area.

During the period from July 2017 to December 2019, 1533 gastric mucosal specimens from patients with positive H. pylori confirmed by breath test or rapid urease test were collected for isolation and identify H. pylori. The agar dilution method was used for antibiotic resistance test.

The result showed that the resistance rates of H. pylori to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 2.74%, 47.03%, 33.59%, 0.91%, 0.52% and 80.76%, respectively in the period of July 2017 to December 2019. The resistance rates of H. pylori (primts．.

This study is an original contribution to the gender-based perspective of measuring knowledge and practice towards COVID-19 among Saudi population.

This study investigates the existing knowledge of COVID-19 among both genders and its likely use in practice to combat COVID-19.

Cross sectional study with an online survey and data collected from all the five regions of Saudi Arabia.

A structured, self-reported validated questionnaire was developed based on the World Health Organization (WHO) general public advice towards COVID-19 prevention. This study has employed snow-ball sampling technique.

627 participants (Male n=343, 54.7%) and (Females n=284, 45.3%).

This study has found that women not only carry better knowledge, but their practicing behavior is far better than the male respondents. Females practiced their knowledge of hands hygiene more in comparison to males (86% vs 80 %, p >0.05). Female respondents were also practicing more about sneezing/coughing into their elbows as compared to males(79 % vs 71%, p < 0.05). Likewise, the practice of knowledge of staying at home to prevent infection (females 98.2 % vs males 95.5%, p > 0.05), and (females 83.2 % vs males 81.5%, p > 0.05) respectively.

This study shows that women were more compliant to the WHO public health covid-19 prevention advice than men which can decrease the chances of covid-19 infection.

This study shows that women were more compliant to the WHO public health covid-19 prevention advice than men which can decrease the chances of covid-19 infection.Azoles are a family of five-membered azacyclic compounds with relevant biological and pharmacological activity. Different subclasses of azoles are defined depending on the atomic arrangement and the number of nitrogen atoms present in the ring pyrazoles, indazoles, imidazoles, benzimidazoles, triazoles, benzotriazoles, tetrazoles and pentazoles. The complete characterization of their structure and the knowledge about their crystal packing and physical and chemical properties are of vital importance for the advancement in the design of new azole-containing drugs. In this review, we report the latest recent contributions to azole chemistry, in particular, those in which theoretical studies have been performed.

The newly emerged coronavirus SARS-CoV-2, first reported in December 2019, has infected about five and a half million people globally and resulted in nearly 9063264 deaths until the 24th of June 2020. Nevertheless, the highly contagious virus has instigated an unimaginably rapid response from scientific and medical communities.

Pioneering research on molecular mechanisms underlying the viral transmission, molecular pathogenicity, and potential treatments will be highlighted in this review. The development of antiviral drugs specific to SARS-CoV-2 is a complicated and tedious process. To accelerate scientific discoveries and advancement, researchers are consolidating available data from associated coronaviruses into a single pipeline, which can be readily made available to vaccine developers.

In order to find studies evaluating the COVID-19 virus epidemiology, repurposed drugs and potential vaccines, web searches and bibliographical bases have been used with keywords that matches the content of this revievidence and potential of possible therapeutics and small molecules with their mode of action.

Reducing the healing time of wounds can decrease the patient’s immobility time and their medical costs,leading a faster return of the patients to daily work.

To compare the effect of adipose-derived stem cells and curcumin-containing liposomal nanoparticles with phenytoin on wound healing.

After anesthesia of the rats, open skin ulcers were made by a bistoury blade.Subsequently,stem cells were re-moved from the adipose tissue of the upper border of the epididymis. Then,the originality of stem cells was confirmed by the flow cytometry. The fusion method was used to prepare the liposome;and also nanoliposomal particles were confirmed by using the DLS microscope.The percentage of recovery and the cell count was measured with IMAGEJ.The expression of genes was assessed by PCR. The number of fibro blasts was counted by immuno histo chemistry techniques.The amount of collagen was determined by Tri-chromosome staining and the number of capillaries was enumerated byH & E staining.

The expression of TGF-β1 gene, vascular number, wound healing rate and the number of fibro blasts increased significantly in adipose tissue-derived stem cells and curcumin nanoliposome groups(p<0.05);the wound surface was also decreased significantly(p<0.05).

Based on the results of our research, adipose tissue-derived stem cells and curcumin nanoliposomescan heal wounds efficiently.

Based on the results of our research, adipose tissue-derived stem cells and curcumin nanoliposomescan heal wounds efficiently.

ALDH-2 has been considered an important molecular target for the treatment of drug addiction due to its involvement in the metabolism of the neurotransmitter dopamine however, the molecular basis for the selective inhibition of ALDH-2 versus ALDH-1 should be better investigated to enable a more pragmatic approach to the design of novel ALDH-2 selective inhibitors.

In the present study, we investigated the molecular basis for the selective inhibition of ALDH-2 by the antioxidant isoflavonoid daidzin (IC50 = 0.15 μM) compared to isoform 1 of ALDH through molecular dynamics studies and semiempirical calculations of the enthalpy of interaction.

The applied methodology consisted of performing the molecular docking of daidzin in the structures of ALDH-1 and ALDH-2 and submitting the lower energy complexes obtained to semiempirical calculations and dynamic molecular simulations.

Daidzin in complex with ALDH-2 presented directed and more specific interactions, resulting in stronger bonds in energetic terms and, therefore, in enthalpic gain. Moreover, the hydrophobic subunits of daidzin, in a conformationally more restricted environment (such as the catalytic site of ALDH-2), promote the better organization of the water molecules when immersed in the solvent, also resulting in an entropic gain.

The molecular basis of selective inhibition of ALDH-2 by isoflavonoids and related compounds could be related to a more favorable equilibrium relationship between enthalpic and entropic features. The results described herein expand the available knowledge regarding the physiopathological and therapeutic mechanisms associated with drug addiction.

The molecular basis of selective inhibition of ALDH-2 by isoflavonoids and related compounds could be related to a more favorable equilibrium relationship between enthalpic and entropic features. The results described herein expand the available knowledge regarding the physiopathological and therapeutic mechanisms associated with drug addiction.Musculoskeletal tumors of the hand are a rare entity and are divided into skeletal and soft tissue tumors. Either category comprises benign and malignant or even intermediate tumors. Basic radiology allows an optimal resolution of bone and related soft tissue areas, ultrasound and more sophisticated radiologic tools such as scintigraphy, CT and MRI allow a more accurate evaluation of tumor extent. Enchondroma is the most common benign tumor affecting bone, whereas chondrosarcoma is the most commonly represented malignant neoplasm localized to hand bones. In the soft tissues ganglions are the most common benign tumors and epithelioid sarcoma is the most frequently represented malignant tumor targeting hand soft tissues. The knowledge regarding diagnostic and therapeutic management of these tumors is often deriving from small case series, retrospective studies or even case reports. Evidences from prospective studies or controlled trials are limited and for this lack of clear and supported evidences data from the medical literature on the topic are controversial, in terms of demographics, clinical presentation, diagnosis prognosis and therapy.The correct recognition of the specific subtype and extension of the tumor through first line and second line radiology is essential for the surgeon, in order to effectively direct the therapeutic decisions.

The Insall-Salvati Index (ISI) is the ratio of the patellar tendon length to the length of the patella. This ratio is the most commonly used method for evaluating patellar placement and patellofemoral imbalance. The position of the patella is important for the knee joint function and also biomechanics. The abnormal position of the patella may lead to patellofemoral malalignment and instability. Herein, we aimed to analyze the relationship between the ISI and pain, physical function, muscle strength, fall risk and postural stability in patients with primary knee osteoarthritis (OA).

62 sympthomatic knees of 45 patients (aged between 40 -75 years) who were suffering from the primary knee OA according to the American College of Rheumatology criteria were included retrospectively in the study. Patients with stages II and III osteoarthritis according to the Kellgren-Lawrence (K/L) radiological grading system were included. The ISI was measured on the lateral knee radiograph in a 30° flexed posture. Visual Anal not have an effect on pain, physical function, fall risk, postural stability, and isokinetic muscle strength.Current European guidelines on chronic coronary syndromes recommend the use of low-dose aspirin (or clopidogrel if intolerance or contraindication) throughout life. However, as the risk of recurrent vascular events is high, particularly in some patients (i.e. diffuse multivessel coronary artery disease, diabetes, recurrent myocardial infarction, peripheral artery disease, or chronic kidney disease,…), these guidelines also consider that in those patients at moderate or high risk of ischemic events, but without a high bleeding risk, dual antithrombotic therapy should be considered. According to these guidelines, treatment options for dual antithrombotic therapy in combination with aspirin may include clopidogrel 75mg/daily, prasugrel 10 mg/daily, ticagrelor 60 mg bid or rivaroxaban 2.5 mg bid. Remarkably, despite the results of the clinical trials that sustain these recommendations clearly diverge, guidelines do not differentiate between them. However, although all these drugs have demonstrated a significant reduction of major cardiovascular events in patients with stable atherosclerotic disease, only the addition of rivaroxaban has been associated with a reduction of cardiovascular and overall mortality in a secondary analysis. This may be related with the fact that the activation of platelets and factor X plays a key role in the development of atherothrombosis, and, consequently, both targets should be considered for the appropriate management of these patients.

Betulinic acid (BA) is a lipophilic compound with proven beneficial results in topical inflammation. Nanogels (NG) are carriers of bioactive compounds with properties that make them good candidates to treat skin diseases.

The objective of this study was to evaluate the anti-inflammatory activity of BA carried in NG.

NG were composed of a nanoemulsion and a crosslinking agent (Carbopol 940®) applied at three concentrations (0.5, 1, and 1.5 %) and three activation times (6, 12 and 24 h). In order to select the optimal formulation, the NG were characterized mechanically and micro-structurally followed by evaluation of the BA anti-inflammatory activity in an in vivomodel of auricular edema. We determined the edema inhibition activity aspercent weight. Additionally, the anti-inflammatory activity of NG was validated through histological analysis.

The formulation with the best viscoelastic properties was the one prepared with 0.5% carbopol and 6 h of activation. Microstructural examination of this formulation showed mostly spherical structures with a mean diameter of 65 nm. From the evaluation of edema and the histological analyses, we established that the NG of BA produced 52% inhibition. In contrast, a conventional gel and freeBA produced 28% and 19% inhibition, respectively.

The NG of BA showed to be good vehicles to treat skin inflammation.

The NG of BA showed to be good vehicles to treat skin inflammation.Chemometrics is an important emerging discipline with unique charm formed by the intersection of mathematics, statistics, chemistry and computer science. The application of chemometrics in the field of pharmacy has injected fresh blood into the scientific research and clinical practice of medicine, and has provided sufficient scientific basis for drug analysis and content determination to solve the problem of cancer treatment with combined therapy in different ranges. This paper introduces the basic principles, advantages and disadvantages of several commonly used pattern recognition and multidimensional correction methods of chemometrics, reviews the application of chemometrics for efficiency enhancement and toxicity reduction in cancer treatment with combined therapy, and summarizes its development and prospects in the future.The misuse, abuse, and illicit use of prescription opioid analgesics is a global public health concern. However, there are many viable therapeutic options for the treatment of patients with chronic pain. Both intact and manipulated opioid drug products are abused by various routes such as oral, nasal, and injection which may lead to overdose, drug addiction, and even death. To combat the abuse of these medications, regulatory agencies and pharmaceutical companies are switching their interest towards developing Abuse deterrent formulations (ADFs), with the intent to deter the abuse of opioid products to a maximum extent. Thereare several manufacturing strategies implemented in an attempt to develop ADFs. An example include matrix tablets of high molecular weight polymers such as polyethylene oxide. The scalable and continuous manufacturing techniques, such as hot melt extrusion (HME), is increasingly accepted by pharmaceutical companies to advance the development and manufacturing of ADFs. The application of the HME technique in the development of ADFs may overcome the challenges of opioid analgesic formulation development and provide improved protection against misuse and abuse, while also ensuring access to safe and effective use in patients with chronic pain. This review deals with a brief overview of strategies, with emphasis on HME to deter opioid abuse, in vitrocharacterization methods, commonly used excipients in the development of ADFs, and regulatory standards to meet the requirements of ADFs.

This study aimed to fabricate hyaluronic acid (HA)/parecoxib-loaded PLGA microspheres for the treatment of temporomandibular disorders (TMD) and investigate the in vitro and in vivo effect of the microsphere system so as to solve the issues of poor drug delivery and short duration on drug concentration in conventional TMD therapy.

The microspheres were prepared by the double emulsion (w/o/w) method. Various formulations were compared in terms of particle size, drug loading rate and encapsulation rate. Scanning electron microscopy (SEM), differential Scanning Calorimetry (DSC) and FT-IR spectroscopy were performed to evaluate physicochemical properties. The drug release be-havior of microspheres and toxicity assay on synovial cells were investigated. The in vitro anti-inflammatory effect on in-flammatory markers such as IL-1β, TNF-α and COX-2 was assessed by real-time PCR. Then the in vivo therapeutic effect of microspheres was investigated using mechanically-induced rat synovitis model. Protein levels of inflammatory cytokines (IL-1β, TNF-α and COX-2) from TMJ periarticular tissues were quantified by enzyme-linked immunosorbent assay (ELISA).