Antimicrobial resistance (AMR) is one of the major leading causes of death around the globe. Present treatment pipelines are insufficient to overcome the critical situation. Prominent biofilm forming human pathogens which have the ability to thrive in infection sites using adaptive features results in biofilm persistence. This is a challenge due to involvement of unknown pathways for which therapeutic targets are still unknown. In regard to this developing newer and effective treatment options using edge cutting technologies in medical research is the need of time. The reasons underlying the adaptive features in biofilm persistence have been centred on different metabolic and physiological aspects. The high tolerance levels against antibiotics direct researchers to search for novel bioactive molecules that can help combat the problem. In view of this, the present review outlines the focuses on a possible opportunity of different strategies which are in testing pipeline can thus be developed into products ready to use.

CASP assessments primarily rely on comparing predicted coordinates with experimental reference structures. However, errors in the reference structures can potentially reduce the accuracy of the assessment. This issue is particularly prominent in cryoEM-determined structures, and therefore, in the assessment of CASP15 cryoEM targets, we directly utilized density maps to evaluate the predictions. A method for ranking the quality of protein chain predictions based on rigid fitting to experimental density was found to correlate well with the CASP assessment scores. Overall, the evaluation against the density map indicated that the models are of high accuracy although local assessment of predicted side chains in a 1.52 Å resolution map showed that side-chains are sometimes poorly positioned. The top 136 predictions associated with 9 protein target reference structures were selected for refinement, in addition to the top 40 predictions for 11 RNA targets. To this end, we have developed an automated hierarchical refinement pipeline in cryoEM maps. For both proteins and RNA, the refinement of CASP15 predictions resulted in structures that are close to the reference target structure, including some regions with better fit to the density. This refinement was successful despite large conformational changes and secondary structure element movements often being required, suggesting that predictions from CASP-assessed methods could serve as a good starting point for building atomic models in cryoEM maps for both proteins and RNA. Loop modeling continued to pose a challenge for predictors with even short loops failing to be accurately modeled or refined at times. The lack of consensus amongst models suggests that modeling holds the potential for identifying more flexible regions within the structure.

Objective: To examine the effect of uterine arterial (UtA) blood flow changes after tadalafil treatment for fetal growth restriction (FGR) using two-dimensional (2D) phase-contrast magnetic resonance imaging (PC-MRI). Design: Prospective, controlled study. Setting: Single tertiary center. Population or Sample: Fourteen pregnant women with FGR aged 20–44 years and at ≥20 weeks’ gestation were recruited between May 2019 and July 2020. Methods: They underwent 2D PC-MRI for UtA blood flow measurement 3 days after diagnosis. They were compared with 14 gestational age (GA)-matched healthy pregnant women (control group). Six patients in the FGR group received tadalafil at 20 mg twice daily after the first MRI until delivery. They underwent a second MRI 1 week later and were compared with 6 of the 14 GA-matched healthy pregnant women. Main Outcome Measures: Total UtA blood/body surface area Results: The median total UtA blood/body surface area was 420 mL/min/m 2 (290–494) in the FGR group and 547 mL/min/m 2 (433–681) in the control group (p=0.01). Percent increases of blood flow in the FGR and control groups were significantly different at 68.8% (51–75) and 18.8% (16–57), respectively (p<0.01). Both intraobserver reproducibility (r=0.997, p<0.01; intraclass correlation coefficients (ICC), 0.997) and interobserver reproducibility (r=0.997, p<0.01; ICC, 0.998) were high. Conclusions: UtA blood flow in pregnant women with FGR was significantly lower than that in healthy pregnant women. Tadalafil may improve UtA blood flow, thereby improving placental function in pregnant patients with FGR.

This study is devoted to studying Bacillus thuringiensis antigens and their insecticide activity as critical feature in bacterial differentiation. 190 samples were examined for flagellar antigenicity as well as the insecticidal activity exhibited. From a serological perspective, 122 isolates (64.2%) were attributed to 8 H-serogroups, including 3 non-typeable and 65 unverified. The dominant serotype was H3abc (82% frequency); H6 was less frequent (8.5%). The other 6 serotypes accounted for a low frequency of occurrence (up to 1.5%). Of the 190 isolates tested, 125 (65.8%) formed bipyramidal and 63 (33.2%) represented spherical inclusions. All H3abc isolates contained bipyramidal inclusions. The same applied to H8ab and H7 isolates. Insecticide activity was noted in 70.1% of populations. 128 samples were toxic to both species (Bombyx mori, Aedes sp.). Another 3 samples were toxic only to B. mori, and 2 for Aedes sp. Of the samples that showed toxicity for both species, 97.6% belonged to bipyramidal paraspore inclusions (H3abc). All H7 samples were toxic to two insect species. Monotoxic B. thuringiensis against Aedes sp. were found only among organisms producing spherical parasporal inclusions in the cell. Examples of such microorganisms include an isolate of H4ab/43 serotype.

A pediatric case with disseminated Burkitt lymphoma presenting with facial soft tissue swelling and dental pain

Urethral caruncle treated with topical estrogen ointment.Yeshey Dorjey11.Consultant Obstetricians and Gynecologist, Phuentsholing General Hospital, Chukha, Bhutan yesheydorjey@gmail.com

Background: Alteration of mitochondrial viability by induction of mitochondrial permeability transition (mPT) brings about mitochondrial-mediated apoptosis. D. oliveri is a medicinal plant traditionally used for the management of certain ailments including tumours. Purpose: Investigating effects of Methanol Fraction of D. oliveri Leaves (MFDO) on mitochondrial-mediated apoptosis. Methods: Twenty-four male rats (70-90 g) were grouped into 4 according to intraperitoneal treatments (14 days): control (distilled water), 50, 100 and 200 mg/kg MFDO. The mitochondrial ATPase and DNA fragmentation were assayed by spectrophotometry. Apoptotic biomarkers were assayed by immunohistochemistry. Caspases-3 and -9 were assessed using ELISA. GC-MS was employed to identify compounds in MFDO. Results: MFDO exhibited in vitro antioxidant properties through inhibition of DPPH and ferric radicals. There was induction of mPT by 50, 100 and 200 mg/kg MFDO relative to control. Furthermore, MFDO inhibited mLPO and enhanced mATPase relative to control. Expression of Bax, p53 and cytochrome c proteins were up-regulated, while Bcl-2 protein expression was down-regulated. Caspase-3 and -9 activities were enhanced, and DNA fragmentation was induced. GC-MS of MFDO revealed the presence of apoptosis-inducing compounds. Conclusion: MFDO induces mitochondrial-mediated apoptosis via alteration of rats liver mitochondrial viability. MFDO is therefore relevant for drug development against diseases.

TITLE: Pancreatic Lymphangioma: A Case Report and Review of LiteratureType: Case ReportShort Title: Pancreatic LymphangiomaCorresponding author :Dr. Khurram Khaliq BhinderResident Radiologist,Shifa International Hospital,Islamabad, Pakistan.kkbhinder@yahoo.com

Background: Prior research has yielded mixed results regarding the impact of acarbose intake on glycemic markers. To provide a more comprehensive analysis, a systematic review and meta-analysis was performed to compile data from various randomized controlled trials (RCTs) examining the effects of acarbose intake on fasting blood sugar (FBS), insulin, hemoglobin A1C (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR) in adults. Methods: To identify relevant literature up to April 2023, a comprehensive search was conducted on various scholarly databases, including PubMed, Web of Science, and Scopus databases. The effect size of the studies was evaluated using a random-effects model to calculate the weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity between studies was assessed using Cochran’s Q test and I2. Results: This systematic review and meta-analysis included a total of 101 RCTs with a total of 107 effect sizes. The effect sizes for FBS in milligrams per deciliter (mg/dl), insulin in picomoles per liter (pmol/l), hemoglobin A1C (HbA1c) in percentage (%), and homeostasis model assessment of insulin resistance (HOMA-IR) were 92, 46, 80, and 22, respectively. The pooled analysis indicated that acarbose intake resulted in significant decreases in FBS (p=0.018), insulin (p<0.001), HbA1c (p<0.001), and HOMA-IR (p<0.001). Conclusion: The findings of this systematic review and meta-analysis suggest that acarbose intake can potentially lead to significant improvements in glycemic indices by decreasing the levels of FBS, HbA1c, and insulin. However, larger and more rigorously designed studies are still needed to further evaluate and strengthen this association.

Pathogen spectrum of Hand, foot and mouth disease (HFMD) has substantially changed in the past decade. How do the co-circulating pathogens interact and the coronavirus disease 2019 (COVID-19) intervene the incidence of HFMD remain unclear. Here, we evaluated the virus-virus interaction (VVI) of EVs using Spearman’s Correlation in Nanchang, China. And the impact of COVID-19 intervention on HFMD incidence was estimated using seasonal autoregressive integrated moving average (ARIMA) models. Enterovirus (EV) serotypes were determined by RT-PCR. From 2019 to 2022, 1321 (57.5%) out of 2296 HFMD cases were EV-positive, in which coxsackievirus A6 (CVA6) and CVA16 were the major pathogens, accounting for 34.0%-59.6% and 14.9%-31.4%, respectively. Our analyses provide strong statistical support for the existence of VVIs among enteroviruses, in which CVA6 negatively interacted with CVA16 and EV-A71, and positive VVI between CVA16 and EV-A71 was observed. While CVA6 has a (albeit inconsistent) seasonal pattern in Nanchang, typically peaking in fall-winter months before COVID-19 epidemic, CVA16 and EV-A71 contemporaneously peaks around May, supporting the epidemiological VVIs among these strains. During the COVID-19 epidemic, the seasonal HFMD epidemic peak was restrained, indicating the COVID-19 intervention had mitigated EV transmission. Moreover, we first figured out the serotypes from other enteroviruses, among them CVA4, CVA2, CVA5 and CVB3 were the major agents accounting for 34.8%, 23.9%, 23.9% and 10.9%, respectively. Taken together, CVA6 and CVA16 were currently the most predominant pathogens negatively interacted with each other in Nanchang, while NPIs of COVID-19 outbreaks interfered the interactions by mitigating their incidence and transmission.

Kidney injury is common in patients with Coronavirus Disease-19 (COVID-19). In this study, 49 patients with Omicron associated kidney injury were included, 38 of whomperformed renal biopsy. Patients were divided into 2 groups: Group A for patients developing kidney injury afterSARS-CoV-2 infection and Group B for patients with aggravated renal insufficiency after SARS-CoV-2 infection. The clinical, pathological and prognostic characteristicsof the patients and theirC3 levels were observed.In our center, the clinical diagnoses of patients with COVID-19 associated kidney injury were mainly acute kidney injury(AKI), chronic kidney disease(CKD) and nephrotic syndrome(NS); while the pathological diagnoses were mainly IgA nephropathy(IgAN)、focal segmental glomerulosclerosis(FSGS) and membranous nephritis(MN).80% of COVID-19 associated nephropathy (COVAN) patients had normal serum C3 complement level, and a few patients had increased or decreased C3 level. In renal tissue, C3 deposits were observed in 68.4% of patients.29% of patients experienced deterioration of renal function after treatment, but no patients developed to end-stage renal disease (ESRD). Among all of them, one case presenting with thrombotic microangiopathy (TMA) had a more severe renal pathological lesion and poorer prognosis. We observed differences of clinical and pathological features of patients with COVID-19associated kidney injury between races, regions and virus variants. Asian patients with Omicron associated kidney injury have milder kidney injury and a better renal prognosis.

Background: Patent foramen ovale (PFO) is the correlation with migraine headaches, cryptogenic stroke. The transcatheter closure of PFO has been proven effective preventing cryptogenic stroke (CS), it is necessary to determine the structure of PFO associated with CS. This study aimed to detect the morphological and function of PFO by using transesophageal echocardiography (TEE) and contrast transthoracic echocardiography (c-TTE) to assess the morphology of PFO associated with CS, and seek out the high-risk factors of PFO for CS. Methods: 113 test patients who suffered CS combining with PFO and 117 control patients diagnosed PFO without stroke were enrolled. The structure of PFO were detected by TEE and c-TTE. The following parameters were measured by TEE: the length and height of the PFO tunnel during Valsalva, the presence of atrial septal aneurysm (ASA), the angle between inferior vena cava (IVC) and PFO, and thickness of septum secundum, and the severity of right-to-left (RLS) was tested by c-TTE. The differences structure of PFO between the test patients and controls were compared, and the correlation between the PFO parameters and CS in test group was analyzed. Based on logistic analyses, we sought out the high-risk factor of PFO for CS. Results: The patients of test group were older than that of control group (56 [48-67.5] years vs 42 [31-51] years, P < 0.001). The height of the PFO during Valsalva (2.5[2-3] mm vs 2.1[1.6-2.8] mm, P = 0.022) were found to be greater in test group than those in control group. The length of the PFO during Valsalva (13.03 ± 4.18 mm vs 11.35 ± 3.84, P = 0.002) were found to be greater in test group than those in control group. The low-angle PFO( the angle between IVC and PFO ≤ 10°) was more common in patients with CS than those in control (48 (42.5%) vs 13 (11.1%)， P＜0.001). Besides, the occurrence rate of ASA in test group is more frequently compared with control group (20 (18%) vs 9(8%), P =0.022). RLS III during Valsalva in test group (85 (75.2%)) was significantly higher than that in control group (70 (59.8%)). RLS II during Valsalva in the without CS group (36 (30.8%)) was significantly higher than that in the CS group (18 (15.9%)). There was no difference between the two groups for RLS I during Valsalva and all grades of RLS at rest. There was no significant difference regarding the thickness of septum secundum as well. Multivariate analysis showed that the length of the PFO during Valsalva, the presence of ASA, RLS III during Valsalva, and the low-angle PFO were independently relevant factors for CS. Conclusions: The relation between PFO and CS is multifactorial. The length of the PFO tunnel, the low-angle PFO, RLS III during Valsalva and the presence of ASA were the greater risk for CS, The TEE combined with c-TEE may help in identifying PFO that is of high risk for CS and screening out the patients for transcatheter closure of PFO.

A document by Arjun Basnet. Click on the document to view its contents.

Background: Ventricular Tachycardia is a life threating arrhythmia with large admission rate. In this analysis, we aim to investigate the impact of anemia in patients admitted due to ventricular tachycardia in terms of mortality, length of stay and total hospital charges. Methods: This is an analysis of the National Inpatient Sample Database of the years 2016-2020. Patients admitted with a primary diagnosis of ventricular tachycardia, with or without a secondary diagnosis of anemia were identified using the ICD-CM codes. The primary outcome was mortality. Secondary outcomes were length of stay and resources utilization. Multivariate logistic analysis was performed, and outcomes were adjusted by age, gender, race, Charlson comorbidity index, hospital location, size, region, teaching status and insurance. Data was considered statistically significant with p-value <0.05. Results: Among 221720 patients who had a primary diagnosis of ventricular tachycardia, 17.56% had anemia. Adjusted mortality was significantly different in patients with secondary diagnosis of any anemia with odds ratio 1.95, p value < 0.001, 95% Confidence Interval 1.73 – 2.2. In terms of Length of Stay, patients with anemias of any type stayed 3.09 more days in the hospital, p value < 0.001, 95% Confidence Interval 2.78 - 3.41. Patients with anemia also had an increase on their total hospital charges by 61507.92, p value < 0.001, 95% Confidence Interval 53771.36 - 69244.48. Conclusion: Patients with anemia had 1.95 higher mortality rate, stayed 3.09 more days in the hospital and had a total hospital cost higher by 61507.92$. Anemia can be a risk marker within patients admitted with ventricular tachycardia, more studies needed to investigate if the treatment of anemia improves the outcome.

Introduction: The European Respiratory Society Oscillometry Taskforce identified that clinical correlates of bronchodilator responses are needed to advance oscillometry in clinical practice. The understanding of bronchodilator-induced oscillometry changes in preterm lung disease is poor. Here we describe a comparison of bronchodilator assessments performed using oscillometry and spirometry in a population born very preterm and explore the relationship between bronchodilator-induced changes in respiratory function and clinical outcomes. Methods: Participants aged 6-23 born ≤32 (N=288; 132 with bronchopulmonary dysplasia) and ≥37 weeks’ gestation (N=76, term-born controls) performed spirometry and oscillometry. A significant bronchodilator response (BDR) to 400mcg salbutamol was classified according to published criteria. Results: A BDR was identified in 30.9% (n=85) of preterm-born individuals via spirometry and/or oscillometry, with poor agreement between spirometry and oscillometry definitions (k=0.26; 95%CI 0.18 to 0.40, p<0.001). Those born preterm with a BDR by oscillometry but not spirometry had increased wheeze (33% vs 11%, p=0.010) and baseline resistance (Rrs 5 z-score mean difference (MD)= 0.86, 95%CI 0.07 to 1.65, p=0.025), but similar spirometry to the group without a BDR (FEV 1 z-score MD= -0.01, 95%CI -0.66 to 0.68, p>0.999). Oscillometry was more feasible than spirometry (95% vs 85% (FEV 1), 69% (FVC), p<0.001), however being born preterm did not affect test feasibility. Conclusion: In the preterm population, oscillometry is a feasible and clinically useful supportive test to assess the airway response to inhaled salbutamol. Changes measured by oscillometry reflect related but distinct physiological changes to that measured by spirometry and thus these tests should not be used interchangeably.

Objective: identify the epidemiological characteristics of children with bronchiolitis hospitalized in pediatric intensive care units of a public emergency hospital. Methods: this quantitative cross-sectional study collected data from electronic medical records using a semi-structured instrument with items regarding sociodemographic and clinical characteristics of children with bronchiolitis hospitalized in the pediatric intensive care unit from April 2018 to April 2020. Results: a total of 73 children were included. Most children were under six months old (56.16%) and male (60.27%), and the most frequent causative agent of bronchiolitis was viral (75.34%). Children under invasive mechanical ventilation tended to have severe acute respiratory syndrome as a complication (p = 0.022) and death as an outcome (p = 0.001). Conclusions: prematurity, male gender, low weight, age below six months, and congenital heart disease were associated with severe bronchiolitis, which may progress to acute respiratory failure or severe acute respiratory syndrome. Mechanical ventilation reduced mortality and improved the clinical condition of children with bronchiolitis, especially in severe cases.

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene typically cause severe health complications in multiple organ systems, including the respiratory and gastrointestinal systems. Certain CFTR mutations, however, cause milder clinical phenotypes which may delay confirmatory diagnosis and treatment. Moreover, rare CFTR variants are not studied frequently or approved for genotype specific CFTR modulator therapies, creating further disadvantage. Herein, we describe a personalized medicine approach for a CF patient with three CFTR variants and mild clinical disease to aid in the diagnosis of CF and development of an optimized treatment plan. This strategy relied on the synergistic combination of advanced genetic analyses, patient-derived models of CFTR function and modulation, and personalized clinical care delivery. Whole Exome Sequencing revealed three compound heterozygous CFTR variants: c.2249C>T (p.P750L), c.1408G>A (p.V470M), and c.1251C>A (p.N417K). The CFTR channel function and nature of protein defects for both V470M and N417K mutations are not previously characterized. Patient-derived intestinal organoid models demonstrated residual CFTR channel activity, with improvement in channel function following treatment with the CFTR modulators. / n vitro studies in heterologous model system demonstrated that P750L has the features of Class II CFTR mutations, whereas V470M/N417K exhibited characteristics of Class II, III, and IV mutations, with all three variants responding to the combination modulator therapy of elexacaftor, tezacaftor, and ivacaftor (ETI) and showing functional rescue to near-wild-type CFTR levels. The laboratory data was then utilized to inform patient care, including off-label prescription of ETI. Following 18 months of ETI therapy, significant improvements were noted in key clinical outcomes, including sweat chloride, nutritional parameters, and respiratory and gastrointestinal symptoms. This study demonstrates a personalized medicine approach across clinical and laboratory domains used to care for CF patients with atypical symptoms and/or rare CFTR mutations.

A Kempe chain in a colored graph is a maximal connected component containing at most two colors. Kempe chains have played an important role historically in the study of the Four Color Problem. Some methods of systematically applying Kempe chain color exchanges have been studied by Alfred Errera and Weiguo Xie. A map constructed by Errera represents an important counterexample to some implementations of these methods. Using the ideas of Irving Kittell, we determine all colorings of the Errera map which form such a counterexample and describe how to color them individually. We then extend our results from the Errera map to a family of graphs containing the Errera map in a specific way. Being able to color this family of graphs appears to address many cases which prove difficult for the previous systematic color exchange methods.

Coastal protection is crucial to human development since the ocean has many values associated with the economy, ecosystem, and culture. However, most ocean-protecting efforts are currently ineffective due to the burdens of finance, lack of appropriate management, and international cooperation regimes. For aiding bottom-up initiatives for ocean protection support, this study employed the Mindsponge Theory to examine how the public’s perceived economic and cultural values influence their willingness to support actions to protect the ocean. Analyzing the European-Union-Horizon-2020-funded dataset of 709 respondents from 42 countries, we discovered that perceived economic values have negative effects on the tendency of ocean protection supports (i.e., food, transportation, renewable energy, oil and gas, and recreation). In contrast, certain perceived cultural values can help increase the willingness to do so (i.e., mental well-being and sense of identity). However, the effects of perceived cultural values are only moderately reliable. These findings suggest that designing cultural information delivery campaigns can help promote coastal reserve supports, such as fundraisings and preserving the oceans from the community.

This paper describes a method to correct phase aberration for transcranial ultrasound.

A document by RABEL GUHAROY . Click on the document to view its contents.

1. Cyanobacterial blooms in freshwater sources are a global concern, and gaining insight into their causes is crucial for effective resource management and control. 2. In this study, we present a computational framework for the causal analysis of cyanobacterial harmful algal blooms (cyanoHABs) in Lake Kinneret. Our framework integrates Convergence Cross Mapping (CCM) and Extended CCM (ECCM) causal networks with Bayesian Network (BN) models. 3. The constructed CCM - ECCM causal networks and BN models unveil significant interactions among factors influencing cyanoHAB formation. These interactions have been validated by domain experts and supported by evidence from peer-reviewed publications. Our findings suggest that M. flos-aquae levels are influenced not only by community structure but also by nitrate, nitrite, ammonium, phosphate, oxygen, and temperature levels in the weeks preceding bloom occurrences. 4. We have demonstrated a non-parametric computational framework for the causal analysis of a multivariate ecosystem. Our framework offers a more comprehensive understanding of the underlying mechanisms driving M. flos-aquae in Lake Kinneret. It captures complex interactions and provides an explainable prediction model. By considering causal relationships, temporal dynamics, and joint probabilities of environmental factors, the proposed framework enhances our understanding of cyanoHABs in Lake Kinneret.

The segmentation of histopathological images is an important problem in the field of medical image processing. However, the high cost of manual annotation and the lack of large-scale annotated data are important factors that restrict the application of deep learning methods in this field. To overcome these challenges, we propose a two-stage weakly supervised semantic segmentation model based on pathological tissue relationships. Our framework leverages the potential relationships between various tissues in histopathological images through a similar Graph Parsing Attention Mechanism to improve segmentation performance. At the segmentation stage, we validate the effectiveness of our cyclic pseudo-mask strategy for denoising and segmentation, and further enhance segmentation performance through multi-resolution supervision. Our model exhibits advanced performance on both BCSS and LUAD histopathology datasets, demonstrating the superiority of our framework. The contribution of our paper lies in the introduction of prior knowledge about the potential relationships between tissues into the weakly supervised semantic segmentation domain, which realizes high-quality histopathological image segmentation on small sample datasets. Moreover, we propose novel strategies such as cyclic pseudo-masks and multi-resolution supervision to improve segmentation performance. Our framework has significant application value and theoretical significance, providing accurate diagnostic support for doctors.

Space medicine has developed controlled terrestrial models to investigate the impacts on human health and performance, and their application should be expanded to encompass disease conditions involving hypoxia and other factors, in order to make valuable contributions to clinical drug development. Hypoxia, a condition in which the body is deprived of adequate oxygen supply, profoundly affects human physiology at multiple levels and contributes to the pathogenesis of various diseases. Experimental exposure to hypoxic conditions has gained recognition as a valuable model for studying diseases like pulmonary hypertension, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), migraine, and kidney disease. The approach may be particularly useful in mechanism-oriented early-stage clinical studies. This review will discuss the ability to mimic or induce these conditions in a controlled laboratory setting using hypoxia, making it a valuable tool for testing the efficacy and safety of new pharmaceutical interventions.