Comparison of different diagnostic modalities for isolation of Mycobacterium Tuberculosis among suspected tuberculous lymphadenitis patients

Tuberculosis is a communicable disease with high morbidity and mortality rates in developing countries. The study's primary objective is to compare conventional methods such as acid-fast bacillus (AFB) culture and microscopy with rapid diagnostic methods. The secondary objective is to compare histopathological and microbiological findings in suspected patients with tubercular lymphadenitis. A total of 111 samples (August 2018 to September 2019) of lymph nodes were processed for AFB microscopy, AFB cultures, drug-susceptibility testing (DST), histopathology, and Xpert Mycobacterium Tuberculosis (MTB)/resistance to Rifampin (RIF) assays. Out of 111 lymph node samples, 6 (5.4%) were positive for AFB smear microscopy, 84 (75.6%) were positive for AFB culture, 80 (70.7%) were positive on Gene Xpert, and 102 (91.8%) were indicative of tuberculosis for histopathology studies. Mycobacteria growth indicator tube (MGIT) culture positivity was 84 (75.6%) higher than solid Lowenstein-Jensen (LJ) culture 74 (66.6%). Positive cultures underwent phenotypic DST. Two cases were Multidrug-resistant (MDR) on DST, while three cases were Rifampicin resistant on Gene Xpert. The sensitivity of Genexpert was (62%) against the conventional AFB culture method. The poor performance of conventional lymphadenitis diagnostic methods requires early and accurate diagnostic methodology. Xpert MTB/RIF test can help in the treatment of multidrug-resistant TB cases. Nonetheless, rapid and conventional methods should be used for complete isolation of Mycobacterium tuberculosis.

Epidemiological, clinical and evolutionary aspects of hypotrophic newborns at term at the Mother and Child University Hospital of N'Djamena

Introduction: Hypotrophy is a public health problem in developing countries. Its etiology is multifactorial and it may be associated with high morbidity and mortality. The objective of this study was to describe the epidemiological, clinical and evolutionary profile of hypotrophic newborns at term. Methodology: this was a prospective, descriptive and analytical study conducted in the neonatology department of the MCUH of N'Djamena from 01/06/2018 to 31/05/2019. It involved 109 hypotrophic newborns at term hospitalized. Results: The frequency of hypotrophy was 7.8%, the risk factors were: housewife status (81.7%), low level of education (67%), poor pregnancy follow-up (59.7%), malaria (40.4%), urogenital infections (22%) and anemia (22%) during pregnancy. Hypotrophy was harmonious in 58.7% of cases, the sex ratio was 1.14 and visible congenital malformations were observed in 12.7% of cases. The main reasons for hospitalization were neonatal infections (64.2%), perinatal asphyxia (14.7%) and hypothermia (11.9%). Lethality was 16.5% and associated with multiparity, poor pregnancy follow-up, vaginal delivery, home delivery, pathological Apgar score, notion of resuscitation, existence of malformation, respiratory distress and perinatal asphyxia. Conclusion: Better monitoring of pregnancy, use of family planning by couples, delivery in an institutionalized setting, and reinforcement of the technical platform of the neonatology department will reduce neonatal morbidity and mortality related to hypotrophy.

Identification of Hub Genes Associated with Immune Infiltration in Cardioembolic Stroke by Whole Blood Transcriptome Analysis

Cardioembolic stroke (CS) is the most common type of ischemic stroke in the clinic, leading to high morbidity and mortality worldwide. Although many studies have been conducted, the molecular mechanism underlying CS has not been fully grasped. This study was aimed at exploring the molecular mechanism of CS using comprehensive bioinformatics analysis and providing new insights into the pathophysiology of CS. We downloaded the public datasets GSE58294 and GSE16561. Differentially expressed genes (DEGs) were screened via the limma package using R software. CIBERSORT was used to estimate the proportions of 22 immune cells based on the gene expression profiling of CS patients. Using weighted gene correlation network analysis (WGCNA) to cluster the genes into different modules and detect relationships between modules and immune cell types, hub genes were identified based on the intersection of the protein-protein interaction (PPI) network analysis and WGCNA, and their clinical significance was then verified using another independent dataset GSE16561. Totally, 319 genes were identified as DEGs and 5413 genes were clustered into nine modules using WGCNA. The blue module, with the highest correlation coefficient, was identified as the key module associated with stroke, neutrophils, and B cells naïve. Based on the PPI analysis and WGCNA, five genes (MCEMP1, CLEC4D, GPR97, TSPAN14, and FPR2) were identified as hub genes. Correlation analysis indicated that hub genes had general association with infiltration-related immune cells. ROC analysis also showed they had potential clinical significance. The results were verified using another dataset, which were consistent with our analysis. Five crucial genes determined using integrative bioinformatics analysis might play significant roles in the pathophysiological mechanism in CS and be potential targets for pharmaceutic therapies.

Understanding the impact of the COVID-19 outbreak on vulnerable populations in Malaysia through an ethical lens: A study of non-state actors involved in aid distribution

Background: Globally, vulnerable populations have been disproportionately affected by the COVID-19 pandemic and subsequent responses, such as lockdown measures and mass vaccinations. Numerous ethical challenges have arisen at different levels, be it at the policy-making level or on the ground. For example, policymakers have to contain a highly contagious disease with high morbidity using scarce resources, while minimizing the medium- to long-term social and economic impacts induced by containment measures. This study explores the impact of COVID-19 on vulnerable populations in Malaysia by using an intersectional framework that accounts for overlapping forms of marginalization. Methods: This study utilizes in-depth qualitative data obtained from 34 individuals and organizations to understand the impact of the COVID-19 outbreak on vulnerable populations in Malaysia. We utilize four principles of ethics to guide our coding and interpretation of the data – namely beneficence, non-maleficence, justice and autonomy. We utilize a frequency analysis to roughly understand the types of ethical issues that emerged. Using hermeneutic content analysis (HCA), we then explore how the principles interact with each other. Results: Through the frequently analysis, we found that although beneficence was very prevalent in our dataset, so was a significant amount of harm – as perpetuated through injustice, the removal or lack of autonomy and maleficence. We also unearthed a worrying landscape of harm and deep systemic issues associated with a lack of support for vulnerable households – further exacerbated during the pandemic. Conclusions: Policy recommendations for aid organizations and society to mitigate these ethical problems are presented, such as long overdue institutional reforms and stronger ethical practices rooted in human rights principles, which government agencies and aid providers can then use in the provision of aid to vulnerable populations.

Machine Learning-Based Approaches for Prediction of Patients’ Functional Outcome and Mortality after Spontaneous Intracerebral Hemorrhage

Spontaneous intracerebral hemorrhage (SICH) has been common in China with high morbidity and mortality rates. This study aims to develop a machine learning (ML)-based predictive model for the 90-day evaluation after SICH. We retrospectively reviewed 751 patients with SICH diagnosis and analyzed clinical, radiographic, and laboratory data. A modified Rankin scale (mRS) of 0–2 was defined as a favorable functional outcome, while an mRS of 3–6 was defined as an unfavorable functional outcome. We evaluated 90-day functional outcome and mortality to develop six ML-based predictive models and compared their efficacy with a traditional risk stratification scale, the intracerebral hemorrhage (ICH) score. The predictive performance was evaluated by the areas under the receiver operating characteristic curves (AUC). A total of 553 patients (73.6%) reached the functional outcome at the 3rd month, with the 90-day mortality rate of 10.2%. Logistic regression (LR) and logistic regression CV (LRCV) showed the best predictive performance for functional outcome (AUC = 0.890 and 0.887, respectively), and category boosting presented the best predictive performance for the mortality (AUC = 0.841). Therefore, ML might be of potential assistance in the prediction of the prognosis of SICH.

Recovery of Recombinant Canine Distemper Virus That Expresses CPV-2a VP2: Uncovering the Mutation Profile of Recombinant Undergoing 50 Serial Passages In Vitro

Canine distemper and canine parvoviral enteritis are infections caused by the canine distemper virus (CDV) and canine parvovirus type 2 (CPV-2), respectively. They are two common infectious diseases that cause high morbidity and mortality in affected dogs. Combination vaccines have been broadly used to protect dogs from infections of CDV, CPV-2, and other viruses. VP2 is the most abundant protein of the CPV-2 capsid. It elicits potent immunity in animals and, therefore, is widely used for designing subunit antigen-based vaccines. In this study, we rescued a recombinant CDV (QN vaccine strain) using reverse genetics. The recombinant CDV (rCDV-VP2) was demonstrated to express stably the VP2 in cells for at least 33 serial passages in vitro. Unfortunately, a nonsense mutation was initially identified in the VP2 open reading frame (ORF) at passage-34 (P34) and gradually became predominant in rCDV-VP2 quasispecies with passaging. Neither test strip detection nor indirect immunofluorescence assay demonstrated the expression of the VP2 at P50. The P50 rCDV-VP2 was subjected to next-generation sequencing, which totally identified 17 single-nucleotide variations (SNVs), consisting of 11 transitions and 6 transversions. Out of the 17 SNVs, 1 and 9 were identified as nonsense and missense mutations, respectively. Since the nonsense mutation arose in the VP2 ORF as early as P34, an earlier rCDV-VP2 progeny should be selected for the vaccination of animals in future experiments.

Usefulness of Serial Multiorgan Point-of-Care Ultrasound in Acute Heart Failure: Results from a Prospective Observational Cohort

Background and Objectives: Acute heart failure (AHF) is a common disease and a cause of high morbidity and mortality, constituting a major health problem. The main purpose of this study was to determine the impact of multiorgan ultrasound in identifying pulmonary hypertension (PH), a major prognostic factor in patients admitted due to AHF, and assess whether there are significant changes in the venous excess ultrasonography (VE × US) score or femoral vein Doppler at discharge. Materials and Methods: Patients were evaluated with a standard protocol of lung ultrasound, echocardiography, inferior vena cava (IVC) and hepatic, portal, intra-renal and femoral vein Doppler flow patterns at admission and on the day of discharge. Results: Thirty patients were enrolled during November 2021. The mean age was seventy-nine years (Standard Deviation–SD 13.4). Seven patients (23.3%) had a worsening renal function during hospitalization. Regarding ultrasound findings, VE × US score was calculated at admission and at discharge, unexpectedly remaining unchanged or even worsened (21 patients, 70.0%). The area under the curve for the lung score was 83.9% (p = 0.008), obtaining a cutoff value of 10 that showed a sensitivity of 82.6% and a specificity of 71.4% in the identification of intermediate and high PH. It was possible to monitor significant changes between both exams on the lung score (16.5 vs. 9.3; p < 0.001), improvement in the hepatic vein Doppler pattern (2.4 vs. 2.1; p = 0.002), improvement in portal vein Doppler pattern (1.7 vs. 1.4; p = 0.023), without significant changes in the intra-renal vein Doppler pattern (1.70 vs. 1.57; p = 0.293), VE × US score (1.3 vs. 1.1; p = 0.501), femoral vein Doppler pattern (2.4 vs. 2.1; p = 0.161) and IVC collapsibility (2.0 vs. 2.1; p = 0.420). Conclusions: Our study results suggest that performing serial multiorgan Point-of-Care ultrasound can help us to better identify high and intermediate probability of PH patients with AHF. Currently proposed multi-organ, venous Doppler scanning protocols, such as the VE × US score, should be further studied before expanding its use in AHF patients.

Osteopontin as a Tumor Marker in Ovarian Cancer

Introduction: Ovarian cancer is associated with high morbidity and mortality. This is due to the nonspecific symptoms and no effective screening methods. Currently CA 125 is used as a tumor biomarker for the diagnosis of ovarian cancer, but it has its own limitations. So, there is need for other tumor biomarkers for the diagnosis of ovarian cancer. To determine the diagnostic test characteristics of plasma osteopontin (OPN) in detecting ovarian malignancy and comparing its performance with carbohydrate antigen-125 (CA 125). Methods: This is a prospective cross-sectional diagnostic test evaluation. Women with adnexal mass detected by clinical or radiological examination were enrolled as suspected cases. Women who presented with other gynecological conditions were enrolled as controls. OPN and CA 125 levels were measured in all enrolled subjects. Results: Among 106 women enrolled, 26 were ovarian cancer, 31 had benign ovarian masses and 49 were controls. Median plasma CA 125 levels were higher in subjects with ovarian cancer (298 U/ml; IQR 84-1082 U/ml vs. 37.5U/ml; IQR 17.6-82.9U/ml; P<0.001).CA 125 sensitivity, specificity, positive and negative likelihood ratios were 88.5%, 61.3%,2.10 and 0.19 respectively. Median plasma OPN levels were higher in subjects with ovarian cancer (63.1 ng/ml; IQR 39.3-137 ng/ml vs. 27ng/ml; IQR 20-52ng/ml; P=0.001). Sensitivity, specificity, positive and negative likelihood ratios of OPN were 50%,87%,2.58 and 0.62, respectively. Conclusion: OPN levels were higher in ovarian cancer than in the benign ovarian mass and had better specificity than CA125. OPN can better differentiate between benign and malignant ovarian mass as compared to CA125.

Qiguiyin Decoction Improves Multidrug-Resistant Pseudomonas aeruginosa Infection in Rats by Regulating Inflammatory Cytokines and the TLR4/MyD88/NF-κB Signaling Pathway

Pseudomonas aeruginosa (PA), a Gram-negative bacterium, has a high detection rate in hospital-acquired infections. Recently, the frequent appearance of multidrug-resistant (MDR) PA strain with high morbidity and mortality rates has aggravated the difficulty in treating infectious diseases. Due to its multiple resistance mechanisms, the commonly used antibiotics have gradually become less effective. Qiguiyin decoction (QGYD) is a clinically experienced prescription of Chinese herbal medicine, and its combined application with antibiotics has been confirmed to be effective in the clinical treatment of MDR PA infection, which could be a promising strategy for the treatment of drug-resistant bacterial infections. However, the mechanism of QGYD restoring antibiotics susceptibility to MDR PA remains unclear. In the present study, we investigated the effects of QGYD and levofloxacin (LEV) singly or in combination on MDR PA-induced pneumonia rat models. Further analysis was carried out in the serum differential expression profiles of inflammatory cytokines by cytokine antibody array. Besides, the lung TLR4/MyD88/NF-κB signaling pathway was detected by RT-qPCR. Our results showed that based on the treatment of MDR PA-infected rat model with LEV, the combination of QGYD improved the general state and immune organ index. Furthermore, it moderately increased the expressions of proinflammatory cytokines including IL-1β, IL-6, and TNF-α in the early stage of infection and decreased their release rapidly in the later stage, while regulated the same phase change of anti-inflammatory cytokine IL-10. In addition, the adhesion molecule ICAM-1 was significantly downregulated after QGYD combined with LEV treatment. Moreover, the mRNA expressions of TLR4, MyD88, NF-κB, and ICAM-1 were significantly downregulated. These results indicated that the mechanism of QGYD restoring LEV susceptibility to MDR PA was related to its regulation of inflammatory cytokines and the TLR4/MyD88/NF-κB signaling pathway, which provides theoretical support for the clinical application of QGYD combined with LEV therapy to MDR PA infection.

Notoginsenoside R1 Facilitated Wound Healing in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

Diabetic ulcers bring about high morbidity and mortality in patients and cause a great economic burden to society as a whole. Since existing treatments cannot fulfil patient requirements, it is urgent to find effective therapies. In this study, the wound healing effect of topical notoginsenoside R1 (NR1) treatment on diabetic full-thickness wounds in type II diabetes mellitus (T2DM) was induced by the combination of a high-fat diet and streptozotocin (STZ) injection. NR1 significantly increased the wound closure rate, enhanced extracellular matrix (ECM) secretion, promoted collagen growth, increased platelet endothelial cell adhesion molecule-1 (CD31) expression, and decreased cleaved caspase-3 expression. RNA-Seq analysis identified ECM remodeling and inflammation as critical biological processes and Timp1 and Mmp3 as important targets in NR1-mediated wound healing. Further experiments showed that NR1-treated wounds demonstrated higher expression of tissue inhibitor of metalloproteinase 1 (TIMP1) and transforming growth factor-β1 (TGFβ1) and lower expression of matrix metallopeptidase 9 (MMP9), matrix metallopeptidase 3 (MMP3), interleukin-1β (IL-1β), and interleukin-6 (IL-6) than diabetic wounds. These investigations promote the understanding of the mechanism of NR1-mediated diabetic wound healing and provide a promising therapeutic drug to enhance diabetic wound healing.