The clinical manifestations and pregnancy outcomes of COVID-19 infection at a tertiary care hospital.

Objective: To evaluate clinical presentation and pregnancy outcomes in pregnant women with Covid-19 infection in our local tertiary care from lower middle-income country. Methods: A retrospective study was conducted at Obstetrics & Gynecology department, Sheikh Saeed Memorial Hospital (SSMH) of The Indus Hospital and Health Network (IHHN) from March 2020 to August 2021. Data of 422 admitted pregnant women with COVID-19 infection was retrieved for demographic and clinical information, laboratory tests, pregnancy outcome, and neonatal outcomes on RED-Cap and analyzed on SPSS 26. Univariate and multivariable logistic regression analyses were performed to estimate odds ratios (OR) for symptomology with categorical variables and feto-maternal outcome. Results: Of the total 422 pregnant women, 24.4% were symptomatic, 74.7% exhibiting mild symptoms. Largely reported symptoms were fever (71.8%), cough (36.9%) and body ache (35.0%); while odds of symptomatic COVID-19 infection was less in educated pregnant women (OR 0.3; 95% CI 0.1-0.9) compared to uneducated. Amongst maternal comorbidities, odds of having symptomatic COVID-19 infection were 3.8 times (95% CI 1.1-13.0) in women with chronic hypertension and 5.5 times (95% CI 2.9-10.4) in women with diabetes. Symptomatic women had significantly greater incidence of miscarriages (p= 0.009), PPROM (p= 0.001), preterm birth (p= 0.000), preeclampsia (p= 0.000), placental abruption (p= 0.006) and maternal ICU admission (p= 0.000) than asymptomatic patients. Still birth was higher (6.4% vs 1.3%, p-value= 0.013) in symptomatic group. The odds of having severe maternal outcome were higher (OR=3.5; 95% CI 1.9-6.0) in symptomatic pregnant women. Conclusion: Majority of pregnant women were asymptomatic. Symptomatic women with COVID-19 infection had an increased risk of adverse feto-maternal outcome.

Regulation of gut bacteria in silkworm (Bombyx mori) after exposure to endogenous cadmium-polluted mulberry leaves.

Soil cadmium (Cd) pollution presents a severe pollution burden to flora and fauna due to its non-degradability and transferability. The Cd in the soil is stressing the silkworm (Bombyx mori) out through a soil-mulberry-silkworm system. The gut microbiota of B.mori are reported to shape host health. However, earlier research had not reported the effect of endogenous Cd-polluted mulberry leaves on the gut microbiota of B.mori. In the current research, we compared the phyllosphere bacteria of endogenous Cd-polluted mulberry leaves at different concentrations. The investigation of the gut bacteria of B.mori fed with the mulberry leaves was done to evaluate the impact of endogenous Cd- polluted mulberry leaves on the gut bacteria of the silkworm. The results revealed a dramatic change in the gut bacteria of B.mori whereas, the changes in the phyllosphere bacteria of mulberry leaves in response to an increased Cd concentration were insignificant. It also increased the α-diversity and altered the gut bacterial community structure of B. mori. A significant change in the abundance of dominant phyla of gut bacteria of B.mori was recorded. At the genus level, the abundance of Enterococcus, Brachybacterium and Brevibacterium group related to disease resistance, and the abundance of Sphingomonas, Glutamicibacter and Thermus related to metal detoxification was significantly increased after Cd exposure. Meanwhile, there was a significant decrease in the abundance of the pathogenic bacteria Serratia and Enterobacter. The results demonstrated that endogenous Cd-polluted mulberry leaves caused perturbations in the gut bacterial composition of B.mori, which may driven by Cd content rather than phyllosphere bacteria. A significant variation in the specific bacterial community indicated the adaptation of B. mori gut for its role in heavy metal detoxification and immune function regulation. The results of this study help to understand the bacterial community associated with endogenous Cd-polluted resistance in the gut of B.mori, which proves to be a novel addition in describing its response in activating the detoxification mechanism and promoting its growth and development. This research work will help to explore the other mechanisms and microbiota associated with the adaptations to mitigate the Cd pollution problems.

Longer-Term Assessment of Azithromycin for Reducing Childhood Mortality in Africa.

BACKGROUND: The MORDOR I trial (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) showed that in Niger, mass administration of azithromycin twice a year for 2 years resulted in 18% lower postneonatal childhood mortality than administration of placebo. Whether this benefit could increase with each administration or wane owing to antibiotic resistance was unknown. METHODS: In the Niger component of the MORDOR I trial, we randomly assigned 594 communities to four twice-yearly distributions of either azithromycin or placebo to children 1 to 59 months of age. In MORDOR II, all these communities received two additional open-label azithromycin distributions. All-cause mortality was assessed twice yearly by census workers who were unaware of participants' original assignments. RESULTS: In the MORDOR II trial, the mean (±SD) azithromycin coverage was 91.3±7.2% in the communities that received twice-yearly azithromycin for the first time (i.e., had received placebo for 2 years in MORDOR I) and 92.0±6.6% in communities that received azithromycin for the third year (i.e., had received azithromycin for 2 years in MORDOR I). In MORDOR II, mortality was 24.0 per 1000 person-years (95% confidence interval [CI], 22.1 to 26.3) in communities that had originally received placebo in the first year and 23.3 per 1000 person-years (95% CI, 21.4 to 25.5) in those that had originally received azithromycin in the first year, with no significant difference between groups (P = 0.55). In communities that had originally received placebo, mortality decreased by 13.3% (95% CI, 5.8 to 20.2) when the communities received azithromycin (P = 0.007). In communities that had originally received azithromycin and continued receiving it for an additional year, the difference in mortality between the third year and the first 2 years was not significant (-3.6%; 95% CI, -12.3 to 4.5; P = 0.50). CONCLUSIONS: We found no evidence that the effect of mass administration of azithromycin on childhood mortality in Niger waned in the third year of treatment. Childhood mortality decreased when communities that had originally received placebo received azithromycin. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02047981.).

Independence of clinical events committees: A consensus statement from clinical research organizations.

BACKGROUND: Randomized clinical trials are the gold standard to assess the causal relationship between an intervention and subsequent outcomes, also known as clinical endpoints. In order to limit bias, central clinical events committees (CEC) are established to ensure consistent event reporting across participating centers, as well as complete and accurate ascertainment of endpoints. However, defining independence is challenging. METHODS: This consensus statement was generated by teleconferences and electronic communications among clinical research organizations from the United States, Europe and Australia. This document does not constitute regulatory guidance. RESULTS: An independent CEC is defined when the adjudicators are not primarily involved in designing, funding, sponsoring, organizing, conducting, analyzing or regulating the clinical trial for which they serve as an adjudicator, beyond their role as CEC member. Moreover, independence requires absence of conflicts of interest with the steering committee, sponsor, grant giver, manufacturer, coordinating center, other independent committees, core laboratories, medical monitor, safety physician, participating clinical sites, statistician or data manager, regulatory agencies or authorities, which could influence (or be perceived to influence) a member's objectivity in evaluating trial data. Such conflicts of interest include financial benefits, directing or advisory role (paid or unpaid), decision-making position, as well as being a direct relative. An independent adjudicator has no other role within a clinical trial. CONCLUSIONS: This consensus statement presents a standardized definition of an independent CEC to be considered by clinical research organizations, manufacturers, and investigators. In addition, it provides recommendations on best practices for implementation of an independent CEC.

Clinical events classification (CEC) in clinical trials: Report on the current landscape and future directions - proceedings from the CEC Summit 2018.

IMPORTANCE: Clinical events adjudication is pivotal for generating consistent and comparable evidence in clinical trials. The methodology of event adjudication is evolving, but research is needed to develop best practices and spur innovation. OBSERVATIONS: A meeting of stakeholders from regulatory agencies, academic and contract research organizations, pharmaceutical and device companies, and clinical trialists convened in Chicago, IL, for Clinical Events Classification (CEC) Summit 2018 to discuss key topics and future directions. Formal studies are lacking on strategies to optimize CEC conduct, improve efficiency, minimize cost, and generally increase the speed and accuracy of the event adjudication process. Major challenges to CEC discussed included ensuring rigorous quality of the process, identifying safety events, standardizing event definitions, using uniform strategies for missing information, facilitating interactions between CEC members and other trial leadership, and determining the CEC's role in pragmatic trials or trials using real-world data. Consensus recommendations from the meeting include the following: (1) ensure an adequate adjudication infrastructure; (2) use negatively adjudicated events to identify important safety events reported only outside the scope of the primary endpoint; (3) conduct further research in the use of artificial intelligence and digital/mobile technologies to streamline adjudication processes; and (4) emphasize the importance of standardizing event definitions and quality metrics of CEC programs. CONCLUSIONS AND RELEVANCE: As novel strategies for clinical trials emerge to generate evidence for regulatory approval and to guide clinical practice, a greater understanding of the role of the CEC process will be critical to optimize trial conduct and increase confidence in the data generated.

Identification of Selective BRD9 Inhibitor via Integrated Computational Approach.

Bromodomain-containing protein 9 (BRD9), a member of the bromodomain and extra terminal domain (BET) protein family, works as an epigenetic reader. BRD9 has been considered an essential drug target for cancer, inflammatory diseases, and metabolic disorders. Due to its high similarity among other isoforms, no effective treatment of BRD9-associated disorders is available. For the first time, we performed a detailed comparative analysis among BRD9, BRD7, and BRD4. The results indicate that residues His42, Gly43, Ala46, Ala54, Val105, and Leu109 can confer the BRD9 isoform selectivity. The predicted crucial residues were further studied. The pharmacophore model's features were precisely mapped with some key residues including, Gly43, Phe44, Phe45, Asn100, and Tyr106, all of which play a crucial role in BRD9 inhibition. Docking-based virtual screening was utilized with the consideration of the conserved water network in the binding cavity to identify the potential inhibitors of BRD9. In this workflow, 714 compounds were shortlisted. To attain selectivity, 109 compounds were re-docked to BRD7 for negative selection. Finally, four compounds were selected for molecular dynamics studies. Our studies pave the way for the identification of new compounds and their role in causing noticeable, functional differences in isoforms and between orthologues.

Susceptibility pattern of Mycobacterium tuberculosis over a period of five years at Indus Hospital and Health Network, Karachi, Pakistan.

Objective: To determine the susceptibility pattern and frequency of isolation of multidrug, pre-extensively drug and extensively drug resistant TB in a tertiary care hospital in Karachi, Pakistan. Method: A cross-sectional study was designed. Samples received in the lab were processed for growth and sensitivity testing of Mycobacterium tuberculosis. Isolation of MTB was done on Mycobacteria growth indicator tube (MGIT) followed by identification using MPT64. Samples were than evaluated for drug sensitivity against first and second-line antimycobacterial drugs. Statistical analysis was performed using SPSS version 24.0. Results: Of the 20014 samples received, 23.1% were identified as Mycobacterium tuberculosis. Drug sensitivity testing was performed on 95.9% isolates. Fifty-two percent samples were from males and 48% female patients. The study found statistically non-significant relationship between gender and likelihood of disease with drug-resistant (DR)-MTB organisms. The rate of isolation of MDR-TB was highest (43%) among ages 25-55 years and previously treated patients compared to newly diagnosed patients (62% vs 36%). Among MTB positive samples, 91.5% were pulmonary while 8.5% were extrapulmonary samples. Extrapulmonary samples were more likely to be sensitive to antimycobacterial drugs. The highest resistance was observed against Isoniazid (pulmonary=58%; extrapulmonary=12.7%), Rifampicin (pulmonary=58.7%; extrapulmonary=8.2%), and Levofloxacin (pulmonary=29.2%; extrapulmonary=20%). Conclusion: A considerable number of drug resistant tuberculosis cases were identified in the present study. It is essential to develop further strategies to reduce the spread of this disease.

Endometrial stromal cells treated by tumor necrosis factor-α stimulate macrophages polarized toward M2 via interleukin-6 and monocyte chemoattractant protein-1.

AIM: This study aimed to investigate the effects of endometrial stromal cells (ESC)-derived interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 on macrophage polarization in endometriosis. METHODS: Macrophage polarization was measured in eutopic endometrium of control participants ('normal endometrium'), eutopic endometrium of patients with endometriosis ('eutopic endometrium') and ectopic endometrium of endometriosis patients ('ectopic endometrium') by immunohistochemical staining. Expression of IL-6 and MCP-1 were measured in the eutopic and ectopic endometrium through enzyme-linked immunosorbent assays. Expression of CD163 was measured in human acute monocytic leukemia (THP-1) cell-derived macrophages that were treated with conditional medium induced by tumor necrosis factor (TNF)-α, TNF-α + anti-IL-6 or TNF-α + anti-MCP-1 via flow cytometry. RESULTS: The ratio of CD163+/CD68+ macrophages in the normal endometrium was higher than that in the eutopic endometrium, while differences between the eutopic and ectopic endometrium were not statistically significant. IL-6 and MCP-1 exhibited enhanced expression in the ectopic endometrium group and decreased expression in the eutopic endometrium group. TNF-α could promote the expression of ESC-derived IL-6 and MCP-1. Intervention with TNF-α-induced conditioned medium resulted in the upregulation of CD163 in THP-1 cells, while conditional medium induced with IL-6 and MCP-1 neutralizing antibodies decreased the proportion of CD163+ macrophages significantly. CONCLUSION: In endometriosis patients, the macrophages of the eutopic endometrium polarize toward M1 compared with the normal endometrium, and those of the ectopic endometrium were mainly M2-polarized. Under the action of TNF-α, ESC-derived IL-6 and MCP-1 could stimulate peritoneal macrophages toward M2-polarization, which could modulate endometriosis.

Prevalence and Trends of Hepatitis C, Hepatitis B, and Human Immunodeficiency Viruses Over Half a Decade Among Healthy Blood Donors Across Sindh, Pakistan.

INTRODUCTION: Pakistan has a high prevalence of viral hepatitis and these transfusion-transmitted illnesses (TTIs) pose a major hazard to the health of patients who need blood transfusions, which has a negative impact on the affordability and accessibility of safe blood products in underfunded or less strengthened healthcare systems. While selecting a donor for blood donation, he/she must be healthy enough to donate 500 mL of whole blood, but some of them who were considered the healthiest community were caught to be reactive while getting screened for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV), which reflects the true prevalence of these illnesses in this specific population. OBJECTIVE:  To study the seroprevalence and trends of HBV, HCV, and HIV in healthy blood donors of Sindh, Pakistan. SUBJECTS AND METHODS:  Blood donated by healthy donors from Sindh, collected from January 2018 to December 2022, was tested by enzyme-linked immunosorbent assay (ELISA) or chemiluminescent immunoassay (CLIA) at 185 blood centers running under the umbrella of Sindh Blood Transfusion Authority Pakistan (SBTA). RESULTS:  The results of serological screening tests for HBV, HCV, and HIV performed from January 2018 to December 2022 revealed a continuously increasing trend of all infections. The total number of blood donations in the blood banks across the province showed a progressive increase from 22,822 donors in 2018 to 937,039 donors in 2022, which is 14.21% of the total increase. Among 4,199,195 donors screened from the said period, 3,821,268 (91%) were replacement donors while only 3,77,927 (9%) were voluntary donors. Among them 3,870,598 (92.2%) were males and only 3,285,97 (7.8%) were females, whereas with regard to donors' age, most of them i.e. 2,664,648 (63%), fall in the 29-39 years age group. Overall, from 2018 to 2022, out of a total of 4,199,195 individuals screened, 81,266 (1.94%) tested positive for HCV, 71,688 (1.7%) tested positive for HBV, and 6,711 (0.15%) tested positive for HIV. The total number of positive cases across all three infections was 159,665 (3.80%). The overall average seroprevalence of hepatitis B surface antigen (HBsAg), anti-HCV, and anti-HIV among blood donors of 185 blood banks, for five years, was 2.78%, 3.82%, 3.65%, 4.15%, and 4.04%, respectively. CONCLUSION:  The study highlights a concerning increase in the prevalence of HCV, HBV, and HIV among blood donors in Sindh, Pakistan, over the five-year period. It underscores the importance of continued surveillance, prevention, and intervention strategies to address these infections. The recommendations include the promotion of voluntary blood donors and screening of donated blood through a highly sensitive screening assay (nucleic acid testing). There should be centralized blood collection systems having better personnel and equipment, and non-remunerated voluntary blood donations must be strongly encouraged. All these, however, require strong political commitment and multisector engagement with comprehensive policy implementation.

Knowledge, attitude, and practice of artificial intelligence among medical students in Sudan: a cross-sectional study.

Introduction: In this cross-sectional study, the authors explored the knowledge, attitudes, and practices related to artificial intelligence (AI) among medical students in Sudan. With AI increasingly impacting healthcare, understanding its integration into medical education is crucial. This study aimed to assess the current state of AI awareness, perceptions, and practical experiences among medical students in Sudan. The authors aimed to evaluate the extent of AI familiarity among Sudanese medical students by examining their attitudes toward its application in medicine. Additionally, this study seeks to identify the factors influencing knowledge levels and explore the practical implementation of AI in the medical field. Method: A web-based survey was distributed to medical students in Sudan via social media platforms and e-mail during October 2023. The survey included questions on demographic information, knowledge of AI, attitudes toward its applications, and practical experiences. The descriptive statistics, χ2 tests, logistic regression, and correlations were analyzed using SPSS version 26.0. Results: Out of the 762 participants, the majority exhibited a basic understanding of AI, but detailed knowledge of its applications was limited. Positive attitudes toward the importance of AI in diagnosis, radiology, and pathology were prevalent. However, practical application of these methods was infrequent, with only a minority of the participants having hands-on experience. Factors influencing knowledge included the lack of a formal curriculum and gender disparities. Conclusion: This study highlights the need for comprehensive AI education in medical training programs in Sudan. While participants displayed positive attitudes, there was a notable gap in practical experience. Addressing these gaps through targeted educational interventions is crucial for preparing future healthcare professionals to navigate the evolving landscape of AI in medicine. Recommendations: Policy efforts should focus on integrating AI education into the medical curriculum to ensure readiness for the technological advancements shaping the future of healthcare.

Focal Seizures in a Child Receiving Terbutaline Sulfate: A Case Report.

Terbutaline sulfate is a beta-adrenergic receptor agonist. More specific for B2 receptors, it is used as a bronchodilator in asthma. Its known side effects can include dizziness, tremors, and tachycardia. However, seizures are not among the commonly reported side effects. This is the case of a five-month-old girl who presented with focal seizures after the intake of terbutaline sulfate syrup. Other causes of the seizures were excluded through history and investigations, including an EEG and electrolyte panel. The seizures stopped on cessation of the terbutaline sulfate with no recurrence, leading us to believe that the focal seizures were an adverse effect of the terbutaline sulfate. A high index of suspicion for drug-related adverse effects should therefore be kept for a child with new onset focal seizures.

An Unusual Case of Phagocytic Histiocytes on Peripheral Blood Smear of a Patient With Methicillin-Resistant Staphylococcus aureus (MRSA) Endocarditis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of the immune system that may rapidly progress into life-threatening complications. There is uncontrolled activation of histiocytes and phagocytic macrophages, resulting in excess secretions of cytokines that manifest into systemic hyperinflammation affecting several organs. HLH may present as primary due to underlying familial or genetic causes or as secondary due to underlying conditions such as malignancies, infections, or autoimmune disorders. This case is of a seven-year-old girl who developed culture-proven MRSA infective endocarditis. She received sensitivity-tailored antimicrobial treatment. Initially unremarkable, but later her peripheral blood smear showed the presence of large histiocyte-like cells showing hemophagocytic activity of moderate grade (two to five histiocytes with hemophagocytosis/slide) on the feathered edge of the slide. Peripheral film findings triggered further workup for HLH. Her condition later deteriorated, requiring high-dependency unit care. This case highlights the significance of maintaining a high index of suspicion with subsequent laboratory work in cases that develop cardinal diagnostic criteria for clinical manifestations of HLH. It also emphasizes reviewing the feathered edges of blood smears to prevent overlooking important morphological findings.

Epigenetic modulation by targeting bromodomain containing protein 9 (BRD9): Its therapeutic potential and selective inhibition.

The bromodomain-containing protein 9, a component of the SWI/SNF chromatin remodeling complex, functions as an 'epigenetic reader' selectively recognizing acetyl-lysine marks. It regulates chromatin structure and gene expression by recruitment of acetylated transcriptional regulators and by modulating the function of remodeling complexes. Recent data suggests that BRD9 plays an important role in regulating cellular growth and it has been suggested to drive progression of several malignant diseases such as cervical cancer, and acute myeloid leukemia. Its role in tumorigenesis suggests that selective BRD9 inhibitors may have therapeutic value in cancer therapy. Currently, there has been increasing interest in developing small molecules that can specifically target BRD9 or the closely related bromodomain protein BRD7. Available chemical probes will help to clarify biological functions of BRD9 and its potential for cancer therapy. Since the report of the first BRD9 inhibitor LP99 in 2015, numerous inhibitors have been developed. In this review, we summarized the biological roles of BRD9, structural details and the progress made in the development of BRD9 inhibitors.

Prognostic Significance of Nucleated RBCs in Predicting Mortality Among ST-Elevation Myocardial Infarction Patients Admitted to the ICU.

Background The nucleated red blood cells (NRBCs) are a readily available hematological parameter with potential for risk stratification for mortality. Therefore, our objective was to assess the predictive significance of NRBCs for ICU mortality among ST-elevation myocardial infarction (STEMI) patients admitted to an ICU. Additionally, we aimed to compare the predictive capacity of NRBCs with that of the acute physiology and chronic health evaluation (APACHE) II score and the sequential organ failure assessment (SOFA) score. Methodology This descriptive cross-sectional study was conducted in the ICU of the National Institute of Cardiovascular Diseases (NICVD) in Karachi, Pakistan, from the 1st of February to the 30th of June, 2023. We included adult patients (≥18 years) diagnosed with STEMI who were subsequently admitted to the ICU. NRBCs were assessed in all patients over up to five days at 24-hour intervals, and the highest NRBC levels were used for the final analysis. Furthermore, the APACHE II score and the SOFA score were also documented. Patients were monitored throughout their ICU stay, and any adverse events or complications, such as re-intubation, bleeding necessitating transfusion, requirement for renal replacement therapy, arrhythmias, re-infarction, and mortality, were recorded. Results This study included 151 patients, of whom 97 (64.2%) were male, with an average age of 61.1 ± 10.7 years. Patients with positive NRBCs had higher mean SOFA scores (7.4 ± 2.9 vs. 5.4 ± 2.6; p < 0.001) and APACHE II scores (14.6 ± 6.3 vs. 12.6 ± 5.5; p = 0.037) compared to those with negative NRBCs. The culprit vessel showed greater mean stenosis (%) in patients with positive NRBCs (98.8 ± 3.0% vs. 96.8 ± 5.7%; p = 0.004). Post-procedure thrombolysis in myocardial infarction (TIMI) flow grade III was lower in patients with positive NRBCs (77.8% vs. 91.8% for positive vs. negative NRBCs, respectively). Moreover, patients with positive NRBCs experienced significantly higher mortality rates (63% vs. 8.2%; p < 0.001), a higher occurrence of arrhythmias (35.2% vs. 19.6%; p = 0.034), and an increased requirement for vasopressors/inotropic support (96.3% vs. 71.1%; p < 0.001) compared to those with negative NRBCs. NRBCs demonstrated superior discriminatory ability compared to the SOFA and APACHE II scores, with an area under the curve of 0.818 (95% CI: 0.738-0.899) for NRBCs, 0.774 (95% CI: 0.692-0.857) for SOFA, and 0.707 (95% CI: 0.613-0.801) for APACHE II. Positive NRBCs exhibited a sensitivity of 81.0% and a specificity of 81.7% in predicting ICU mortality. Conclusion In conclusion, positive NRBCs emerge as a robust and reliable prognostic indicator, strongly associated with an elevated risk of ICU mortality in STEMI patients. Moreover, the predictive power of positive NRBCs surpasses that of both SOFA and APACHE II scoring systems.

Prediction of Phytochemicals for Their Potential to Inhibit New Delhi Metallo ß-Lactamase (NDM-1).

The effectiveness of all antibiotics in the ß-lactam group to cure bacterial infections has been impaired by the introduction of the New Delhi Metallo-ß-lactamase (NDM-1) enzyme. Attempts have been made to discover a potent chemical as an inhibitor to this enzyme in order to restore the efficacy of antibiotics. However, it has been a challenging task to develop broad-spectrum inhibitors of metallo-ß-lactamases. Lack of sequence homology across metallo-ß-lactamases (MBLs), the rapidly evolving active site of the enzyme, and structural similarities between human enzymes and metallo-ß-lactamases, are the primary causes for the difficulty in the development of these inhibitors. Therefore, it is imperative to concentrate on the discovery of an effective NDM-1 inhibitor. This study used various in silico approaches, including molecular docking and molecular dynamics simulations, to investigate the potential of phytochemicals to inhibit the NDM-1 enzyme. For this purpose, a library of about 59,000 phytochemicals was created from the literature and other databases, including FoodB, IMPPAT, and Phenol-Explorer. A physiochemical and pharmacokinetics analysis was performed to determine possible toxicity and mutagenicity of the ligands. Following the virtual screening, phytochemicals were assessed for their binding with NDM-1using docking scores, RMSD values, and other critical parameters. The docking score was determined by selecting the best conformation of the protein-ligand complex. Three phytochemicals, i.e., butein (polyphenol), monodemethylcurcumin (polyphenol), and rosmarinic acid (polyphenol) were identified as result of pharmacokinetics and molecular docking studies. Furthermore, molecular dynamics simulations were performed to determine structural stabilities of the protein-ligand complexes. Monodemethylcurcumin, butein, and rosmarinic acid were identified as potential inhibitors of NDM-1 based on their low RMSD, RMSF, hydrogen bond count, average Coulomb-Schrödinger interaction energy, and Lennard-Jones-Schrödinger interaction energy. The present investigation suggested that these phytochemicals might be promising candidates for future NDM-1 medication development to respond to antibiotic resistance.

Different Shapes Of Megakaryocytes In Essential Thrombocythemia.

Essential thrombocytopenia is the myeloproliferative neoplasm associated with the JAK2/CALR/MPL mutation. It is characterized by an increase in thrombocytes and abnormal megakaryocytes. WHO established the diagnostic criteria for diagnosing the myeloproliferative disorder, which is the combination of molecular, clinical, and histological findings. The appearance of megakaryocytes on bone marrow biopsy is the distinguishing feature to identify myeloproliferative neoplasm, and this short review would like to emphasize the presentation of megakaryocytes in bone marrow biopsy.

Assessing Tumor Size by MRI and Pathology in Type I Endometrial Carcinoma to Predict Lymph Node Metastasis.

Introduction Lymphatic spread is the most common route of spread of endometrial carcinoma, and the most frequently involved lymph nodes are those of the external iliac group. MRI is one of the best imaging tools for the preoperative evaluation of patients with endometrial carcinoma. The objective of the current study is to analyze the relationship between tumor size and lymph node metastasis in patients with type I endometrial carcinoma. Methods This is a prospective observational study performed in the Department of Obstetrics and Gynaecology at Liaquat National Hospital, Karachi, Pakistan. The duration of the study was from January 2020 to January 2021. During this period, 86 patients with biopsy-proven type I endometrial carcinoma were selected. Tumor size was measured by MRI. All participants underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic lymphadenectomy. Histopathological evaluation was performed according to the College of American Pathologists (CAP) protocols, and staging was performed using the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system. Lymph nodes were considered positive or negative, irrespective of their number. Result Of the 86 patients, 25 (29.1%) had positive lymph node metastasis. The mean tumor size with positive lymph node metastasis by MRI and histopathology was 7.86 cm and 10.21 cm, respectively. Tumor size determined by MRI and histopathology was significantly associated with lymph node metastasis (p < 0.01 and p < 0.01, respectively). Tumor size was positively correlated with lymph node metastasis (r = 0.715). The cutoff value of >6.5 cm by MRI was established as the statistically significant differentiator of lymph node metastasis. The calculated sensitivity and specificity were 88% and 90.16%, respectively, with an area under the curve (AUC) of 0.920. The cutoff value of >8 cm by histopathology was established as the statistically significant differentiator of lymph node metastasis. The calculated sensitivity and specificity were 80% and 88.52%, respectively, with an AUC of 0.907. Conclusion Our results showed that lymph node metastasis in patients with type I endometrial carcinoma can be predicted by tumor size. This may help incorporate adequate surgical skills and management plans in the treatment course of type I endometrial carcinoma.

Changing Trends Of Multidrug Resistant Bacteria: A Six Year Experience From A Tertiary Care Hospital.

BACKGROUND: There is a continuous increase in the number of bacteria showing resistance to various antibiotics, limiting the treatment options for infections. The objective of this study was to assess the trend in resistance pattern of multi drug resistant organisms over a period of 6 years. METHODS: A retrospective study was conducted in Indus Hospital and Health Network, Karachi, Pakistan from January 2014 to December 2019. Multidrug resistant organisms were isolated from various samples and the data of corresponding patients were extracted from electronic medical record. The patients of all age groups and either gender was included. Specimens were inoculated on Sheep Blood Agar, chocolate agar and MacConkey agar. Organisms were identified and antibiotic susceptibility testing was performed according to Clinical Laboratory Standard Institute guidelines. RESULTS: In 34628 cases, 5159 (14.8%) were isolated as MDR organisms. Out of these 44.2% were Gram negative, while 55.7% were Gram-positive bacteria. The highest MDR trend was observed for A. baumannii (0-70%) followed by MRSA (0-64%) P. aeruginosa (0-16%) Enterococcus (0-10%) CRE (2.8-5.8%). CONCLUSIONS: The continuous rising trend of multidrug resistant organisms has been observed during the period of our study. Therefore, there is an imperative need of constant monitoring and firm adherences to infection control strategies to avoid spread of MDR organisms.