Fixation of pfcrt chloroquine resistance alleles in Plasmodium falciparum clinical isolates collected from unrest tribal agencies of Pakistan

Plasmodium falciparum resistance to Chloroquine (CQ) is a significant cause of mortality and morbidity worldwide. There is a paucity of documented data on the prevalence of CQ-resistant mutant haplotypes of Pfcrt and Pfmdr1 genes from malaria-endemic war effected Federally Administered Tribal Areas of Pakistan. The objective of this study was to investigate the prevalence of P. falciparum CQ-resistance in this area. Clinical isolates were collected between May 2017 and May 2018 from North Waziristan and South Waziristan agencies of Federally Administrated Trial Area. Subsequently, Giemsa-stained blood smears were examined to detect Plasmodium falciparum. Extraction of malarial DNA was done from microscopy positive P. falciparum samples, and P. falciparum infections were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes). All PCR confirmed P. falciparum samples were sequenced by pyrosequencing to find out mutation in Pfcrt gene at codon K76T and in pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y. Out of 121 microscopies positive P. falciparum cases, 109 samples were positive for P. falciparum by nested PCR. Pfcrt K76T mutation was found in 96% of isolates, Pfmdr1 N86Y mutation was observed in 20%, and 11% harboured Y184F mutation. All samples were wild type for Pfmdr1 codon N1042D and D1246Y. In the FATA, Pakistan, the frequency of resistant allele 76T remained high despite the removal of CQ. However, current findings of the study suggest complete fixation of P. falciparum CQ-resistant genotype in the study area.

MiR-937-3p promotes metastasis and angiogenesis and is activated by MYC in lung adenocarcinoma

Background Non-small cell lung cancer (NSCLC) is still one of the diseases with the highest mortality and morbidity, and lung adenocarcinoma (LUAD) accounts for more than half of all NSCLC cases in most countries. miRNA can be used as a potential biological marker and treatment for lung adenocarcinoma. However, the effect of miR-937-3p to the invasion and metastasis of LUAD cells is not clear. Methods miRNA microarray is used to analyze the expression of miRNA in lung adenocarcinoma tissue. Transwell migration, Wound-healing assay and Western blot analysis are used to analyze cell migration, invasion and epithelial-mesenchymal transition (EMT) capabilities. Tube formation is used to assess angiogenesis ability. In addition, dual luciferase reporter gene detection is used to identify the potential binding between miRNA and target mRNA. In vivo experiments were performed on male NOD/SCID nude mice by tail vein injection to establish a transplanted tumor model. The CHIP experiment is used to verify the transcription factors of miRNA. Result In our study, miR-937-3p was high-regulated in LUAD cell lines and tissues, and its expression level was related to tumor progression. We found that miR-937-3p high-expression has an effect on cell invasion and metastasis. In molecular mechanism, miR-937-3p causes SOX11 reduction by directly binding to the 3′-UTR of SOX11.In addition, MYC affects miR-937-3p transcription by binding to its promoter region. Conclusions Our research shows that miR-937-3p is mediated by MYC and can control the angiogenesis, invasion and metastasis of LUAD by regulating SOX11, thereby promoting the progress of LUAD. We speculate that miR-937-3p can be used as a therapeutic target and potential biomarker for LUAD.

Intracerebral hemorrhage during the pandemic- Learning from experience

Worldwide stroke care was affected by COVID 19 pandemic and the majority of the literature was on ischemic stroke. Intracerebral hemorrhage (ICH) accounts for about one-fourth of strokes worldwide and has got high mortality and morbidity. We aimed to study the effect of the Pandemic on ICH outcomes and flow metrics during the first wave compared to the pre-pandemic period and how that experience was made used in managing ICH during the second wave. Ours was a single-center observational study, where consecutive patients with non-COVID spontaneous ICH aged more than 18 years who presented within 24 hours of last seen normal were included in the study. We selected the months of June, July, and August in 2021 as the second wave of the pandemic, the same months in 2020 as the first wave of the pandemic, and the same months in 2019 as the pre-pandemic period. We compared the 3-month functional outcomes, in hospital mortality and workflow metrics during the three time periods. We found poor three-month functional outcomes and higher hospital mortality during the first wave of the COVID 19 pandemic, which improved during the second wave. In-hospital time metrics measured by the door to CT time which was delayed during the first wave improved to a level better than the pre-pandemic period during the second wave. ICH volume was more during the first and second waves compared to the pre-pandemic period. Other observations of our study were younger age during the second wave and higher baseline systolic BP at admission during both pandemic waves. Our study showed that functional outcomes and flow metrics in ICH care improved during the second wave of the pandemic through crucial re-organization of hospital stroke workflows. We are sharing this experience because we may have to do further rearrangements in future as the upcoming times are challenging due to new variants emerging.

Duration of immunity against COVID-19 after vaccination in Indian subcontinent

Coronavirus disease (COVID-19) continues to be a major health concern leading to substantial mortality and morbidity across the world. Vaccination is effective in reducing the severity and associated mortality. Data pertaining to the duration of immunity, antibody waning and the optimal timing of booster dose administration is limited. In this cross-sectional study, we assessed the antibody levels in healthcare workers who were fully vaccinated after obtaining Institutional ethics committee approval and informed consent. Whole blood was collected and enumeration of S1/S2 neutralizing antibody levels was carried out using LIAISON SARS-COV-2 S1/S2 IgG assay. A total of 1636 individuals who were vaccinated with Covaxin or Covishield were included. Of these, 52% were males with a median age of 29 years. Diabetes and Hypertension was noted in 2.32% (38/1636) and 2.87% (47/1636) of the individuals. Spike neutralizing antibodies were below the detectable range (<15 AU/ml) in 6.0% (98/1636) of the individuals. Decline in neutralizing antibody was seen in 30% of the individuals above 40 years of age with comorbidities (diabetes and hypertension) after 6 months. These individuals may be prioritized for a booster dose at 6 months.

Maternally transferred monoclonal antibodies protect neonatal mice from herpes simplex virus-induced mortality and morbidity

Neonatal herpes simplex virus (HSV) infections often result in significant mortality and neurological morbidity despite antiviral drug therapy. Maternally-transferred HSV-specific antibodies reduce the risk of clinically-overt neonatal HSV (nHSV), but this observation has not been translationally applied. Using a neonatal mouse model, we tested the hypothesis that passive transfer of HSV-specific human monoclonal antibodies (mAbs) can prevent mortality and morbidity associated with nHSV. The mAbs were expressed in vivo by vectored immunoprophylaxis, or administered in vivo following recombinant expression in vitro. Through these maternally-derived routes or through direct administration to pups, diverse mAbs to HSV glycoprotein D protected against neonatal HSV-1 and HSV-2 infection. Using in vivo bioluminescent imaging, both pre- and post-exposure mAb treatment significantly reduced viral load. Administration of mAb also reduced nHSV-induced behavioral morbidity, as measured by anxiety-like behavior. Together these studies support the notion that HSV-specific mAb-based therapies may prevent or improve HSV infection outcomes in neonates.

Evaluation of Risk Factors for Preterm Birth Outcome in Gujarat, India

Background: Preterm birth (PTB) is a leading cause of neonatal survival complications, mortality, and morbidity worldwide. In India 35% of all neonatal deaths are due to PTB with 36th global ranking, hence, India's healthcare sector has been working towards reducing the rate of PTB effectively. Objective: This study aimed to assess the risk factors such as environmental and pathophysiological causes associated with preterm birth in the population of Gujarat, India. Materials and Methods: In this study, multivariate random sampling was performed and systematically 200 pregnant mothers [PTB <37 weeks (N=100), Full-term >37 weeks (N=100)] were chosen after excluding mothers with vaginal infection, multiple gestations, fetal anomalies, non-cephalic presentation, cesarean delivery, and pregnancy with Mullerian anomalies. Statistical analysis was performed by Chi-square test, and variables with p-value <0.05 were considered statistically significant. Results: Out of all the variables, maternal age below 20 years, extreme BMI, high blood pressure during pregnancy, maternal health complications, medication and doctor's consultation were highly significant (p < 0.0001). Furthermore, variables like type of area, diet, education, Hb levels below 9 g/dL and above 13 g/dL and blood-group of the mother were also significantly associated with PTB outcome (p < 0.05). Among the sub-categories of PTB (extreme-, very-, moderate/late- PTB), maternal age, Hb level and the past obstetric outcome showed very high significance (p < 0.0001). Conclusion: For the prediction of birth outcome, mother's internal physiological and lifestyle factors need to be taken into consideration, and mothers at risk priorly can be screen out, followed by proper healthcare assistance to decrease the preterm birth rate and its consequences. Key words: Preterm birth, maternal age, blood pressure, past obstetric outcome, risk factors

CARTOGRAPHY AND MAPPING FOR PRECISION HEALTH: REVIEW OF ESSENTIAL ELEMENTS FOR DISEASE MAPPING

A well-developed healthcare system, decent access to clean water and sanitation, and programmes to eliminate poverty and build modern infrastructure are essential components to create healthier Malaysia's population. Non-communicable diseases currently account for most of the mortality and morbidity, although communicable diseases such as dengue fever, avian flu and covid-19 still pose a threat. The World Health Organization (WHO) identified COVID-19 is a rare pneumonia disease that originated in Wuhan, on January 12, 2020, before it became an outbreak in all countries including Malaysia. The requirement of a precise mapping and Cartography for the accurate disease mapping and data management are crucial due to a precise map gives higher resolution of the data and for more specific data analysis, interpretation and decision making process. In Malaysia, there no specific report on precise mapping for health applications, and it is therefore this paper is to identify the potential criteria and factors needed for precise health mapping applications. A precise health mapping is essential to create a precise risk map towards the surveillance and signal detection, predicting future risk, targeted interventions, and understanding disease phenomena.

Arterial Embolization of Polycystic Kidneys for Heterotopic Transplantation

Introduction: The purpose of this study was to evaluate the efficacy of polycystic kidney embolization, performed to reduce kidney volume before heterotopic kidney transplantation, as this technique could be an alternative to pretransplant nephrectomy. Materials and Methods: All patients who underwent pretransplant embolization of polycystic kidneys were included in a prospective register from June 2014 to February 2020. All patients underwent computed tomography (CT) scan with volumetric reconstruction (OsiriX, Bernex, Switzerland) before embolization and were then followed up at 3 and 6 months after embolization. Primary outcome was percentage of kidney volume reduction. Secondary outcomes were 30 day mortality and morbidity. Results: Thirty-one embolizations performed on 29 patients (medium age = 55.6; 62.1% male) were included between June 2014 and February 2020. All patients were under dialysis before embolization (9 peritoneal dialysis and 20 hemodialysis). Technical success was observed in 96.8% of cases. Mean procedural time was 65 minutes (range = 35–106 minutes) and mean length of in-hospital stay was 3.8 days (range = 3–6 days). A volume reduction allowing a kidney transplant was obtained for 28 patients (96.5%). The mean volume reduction was 39.9% (range = 6.01–68.2). The main observed complication was postembolization pain in 10 cases (32.2%). One patient needed complementary nephrectomy due to insufficient volume reduction. Twenty-three patients (79.3%) received renal transplant during follow-up with a mean delay of 19.5 month (range = 4–54). Conclusion: Polycystic kidney embolization is an effective and safe minimally invasive technique. It can be proposed as the first-choice technique for kidney transplant recipients as an alternative to pretransplantation nephrectomy.