Understanding Bacteriophage Tail Fiber Interaction with Host Surface Receptor: The Key "Blueprint" for Reprogramming Phage Host Range.

Bacteriophages (phages), as natural antibacterial agents, are being rediscovered because of the growing threat of multi- and pan-drug-resistant bacterial pathogens globally. However, with an estimated 1031 phages on the planet, finding the right phage to recognize a specific bacterial host is like looking for a needle in a trillion haystacks. The host range of a phage is primarily determined by phage tail fibers (or spikes), which initially mediate reversible and specific recognition and adsorption by susceptible bacteria. Recent significant advances at single-molecule and atomic levels have begun to unravel the structural organization of tail fibers and underlying mechanisms of phage-host interactions. Here, we discuss the molecular mechanisms and models of the tail fibers of the well-characterized T4 phage's interaction with host surface receptors. Structure-function knowledge of tail fibers will pave the way for reprogramming phage host range and will bring future benefits through more-effective phage therapy in medicine. Furthermore, the design strategies of tail fiber engineering are briefly summarized, including machine-learning-assisted engineering inspired by the increasingly enormous amount of phage genetic information.

The sex and gender dimensions of COVID-19: A narrative review of the potential underlying factors.

Multiple lines of evidence indicate that the male sex is a significant risk factor for severe disease and mortality due to coronavirus disease 2019 (COVID-19). However, the precise explanation for the discrepancy is currently unclear. Immunologically, the female-biased protection against COVID-19 could presumably be due to a more rapid and robust immune response to viruses exhibited by males. The female hormones, e.g., estrogens and progesterone, may have protective roles against viral infections. In contrast, male hormones, e.g., testosterone, can act oppositely. Besides, the expression of the ACE-2 receptor in the lung and airway lining, which the SARS-CoV-2 uses to enter cells, is more pronounced in males. Estrogen potentially plays a role in downregulating the expression of ACE-2, which could be a plausible biological explanation for the reduced severity of COVID-19 in females. Comorbidities, e.g., cardiovascular diseases, diabetes, and kidney disorders, are considered significant risk factors for severe outcomes in COVID-19. Age-adjusted data shows that males are statistically more predisposed to these morbidities-amplifying risks for males with COVID-19. In addition, many sociocultural factors and gender-constructed behavior of men and women impact exposure to infections and outcomes. In many parts of the world, women are more likely to abide by health regulations, e.g., mask-wearing and handwashing, than men. In contrast, men, in general, are more involved with high-risk behaviors, e.g., smoking and alcohol consumption, and high-risk jobs that require admixing with people, which increases their risk of exposure to the infection. Overall, males and females suffer differently from COVID-19 due to a complex interplay between many biological and sociocultural factors.

Nucleic Acid Vaccine Platform for DENGUE and ZIKA Flaviviruses.

Dengue virus and Zika virus are mosquito-borne, single-stranded, positive-sense RNA viruses that belong to the Flaviviridae family. Both the viruses are closely related and have similarities with other flaviviruses. Dengue virus (DENV) causes a severe febrile illness with fever, joint pain, and rash leading to a life-threatening condition in severe cases. While Zika virus (ZIKV) primarily causes mild fever, it can be passed from a pregnant mother to her fetus, resulting in severe birth defect microcephaly and even causing a rare autoimmune disease-Guillain-Barre syndrome. To date, there are no approved DENV and ZIKA vaccines available, except a Dengue vaccine (Dengvaxia, Sanofi Pasteur Inc., Lyon, France) recently approved to be used only for 9-16 years of age groups living in endemic areas and having a previous record of confirmed dengue infection. There are several potential vaccine candidates in the clinical trials based on multiple vaccine platforms, such as live attenuated, subunit, nucleic acid, and viral vector-based vaccines. In the current review, we have focused exclusively on the nucleic acid vaccine platform and discussed the progress of all the DNA/RNA vaccine candidates under preclinical and clinical studies for DENV and ZIKA viruses. Additionally, we have described a brief history of the emergence of these flaviviruses, major structural similarities between them, prominent vaccine targets, and the mechanism of virus entry and infection.

Genetic counseling in the context of Bangladesh: current scenario, challenges, and a framework for genetic service implementation.

With the advancements in genetics and genomics in the twenty-first century, genetic services have become an integral part of medical practices in high-income and upper-middle-income countries. However, people living in low and lower-middle-income countries (LICs and LIMCs), including Bangladesh, are rather underprivileged in receiving genetic services. Consequently, genetic disorders are emerging as a significant public health concern in these countries. Lack of expertise, high expense, the dearth of epidemiological data, insufficiently updated medical education system, poor infrastructure, and the absence of comprehensive health policies are the main factors causing people living in these countries not having access to genetic services. In this article, the authors took benefit from their professional experience of practicing medical genetics in the area and reviewed existing literature to provide their opinions. Particularly, it reviews the current knowledge of genetic disorders' burden and their causative factors in Bangladesh. It focuses on why providing genetic services is challenging in the context of the country's cultural and religious sentiment. Finally, it proposes a physician-academician collaborative framework within the existing facility that aims to tackle the challenges. Such a framework could also be useful for other LICs and LMICs to address the challenges associated with providing genetic services.

Genetic and reproductive consequences of consanguineous marriage in Bangladesh.

INTRODUCTION: This study aimed to assess the prevalence, sociodemographic factors, reproductive consequences, and heritable disease burdens associated with consanguineous marriage (CM) in Bangladesh. METHODS: A total of 7,312 families, including 3,694 CM-families, were recruited from 102 locales of 58 districts of Bangladesh. Using a standard questionnaire, we collected medical history and background sociodemographic data of these families. Family history was assessed by pedigree analysis. Fertility, mortality, secondary sex ratio, selection intensity, lethal equivalents were measured using standard methods. RESULTS: The mean prevalence of CM in our studied population was 6.64%. Gross fertility was higher among CM families, as compared to the non-CM families (p < 0.05). The rate of under-5 child (U5) mortality was significantly higher among CM families (16.6%) in comparison with the non-CM families (5.8%) (p < 0.01). We observed a persuasive rise of abortion/miscarriage and U5 mortality rates with the increasing level of inbreeding. The value of lethal equivalents per gamete found elevated for autosomal inheritances as compared to sex-linked inheritance. CM was associated with the incidence of several single-gene and multifactorial diseases, and congenital malformations, including bronchial asthma, hearing defect, heart diseases, sickle cell anemia (p < 0.05). The general attitude and perception toward CM were rather indifferent, and very few people were concerned about its genetic burden. CONCLUSION: This study highlights the harmful consequences of CM on reproductive behavior and the incidence of hereditary conditions. It essences the need for genetic counseling from premarital to postnatal levels in Bangladesh.

Umbilical Cord Blood Screening for the Detection of Common Deletional Mutations of α-Thalassemia in Bangladesh.

α-Thalassemia (α-thal) is assumed to be very prevalent in Bangladesh. We aimed to assess the prevalence of the disease in the country and provide a model for α-thal newborn screening in Bangladesh. We collected umbilical cord blood (UCB) samples from 413 unrelated newborns in Bangladesh. Demographic information, blood indices, osmotic fragility, serum iron (Fe), and zinc (Zn) levels were evaluated for all the subjects. All subjects underwent a polymerase chain reaction (PCR)-based diagnosis for α-thal status, followed by a multiplex gap-PCR-based identification of the deletion type present. Sixty-seven subjects had at least one α-thal deletion (16.22%). We observed that -α3.7 (rightward), - -SEA (Southeast Asian), -α4.2 (leftward), - -MED (Mediterranean) and - -THAI (Thailand) deletions were the most common α-globin deletions present in the country, with the -α3.7 (n = 37) and - -SEA (n = 18) being most prevalent. The osmotic fragility test (OFT) could predict the presence of α-thal deletions with over 98.0% sensitivity. Complete UCB count analysis revealed significant differences between healthy subjects and subjects with α-thal deletions. Although the iron level was almost the same (108.0 vs. 105.7 µg/dL), a reduced level of Zn (98.6 vs. 71.8 µg/dL, p < 0.01) was observed in the cord blood-derived serum of the subjects with α-thal deletions. Moreover, parental age at the time of delivery, gestational period, and birth weight was lower in the subjects with α-thal deletions. This study provides partial information on the epidemiology of α-thal in Bangladesh and describes a model for α-thal newborn screening in the country.

Chikungunya outbreak in Bangladesh (2017): Clinical and hematological findings.

INTRODUCTION: A massive outbreak of chikungunya virus (CHIKV) occurred in Bangladesh during the period of April-September 2017, and over two million people were at risk of getting infected by the virus. A prospective cohort of viremic patients was constituted and analyzed to define the clinical, hematological, and long-term aspects of this outbreak. METHODS: A 35-day long comprehensive survey was conducted in two major, neighboring cities, Dhaka and Mymensingh. One-hundred and eighty-seven laboratory-confirmed CHIKV cases were enrolled in the cross-sectional cohort study. Additionally, a smaller group of 48 chikungunya patients was monitored for post-infection effects for 12 months. RESULTS: Clinical data revealed that a combination of fever and arthralgia (oligoarthralgia and/or polyarthralgia) was the cardinal hallmark (97.9% of cases) of the infection. Hematological analysis showed that irrespective of age and sex groups, CHIKV patients had a decreased level of hemoglobin (n = 64, p < 0.01) and elevated erythrocyte sedimentation rate (n = 131, p < 0.01). Besides, a significant portion of the patients represented abnormal values for RBC (n = 38, p = 0.0005) and WBC (n = 63, p < 0.01) counts. The post-infection study revealed that children had an early recovery from the infection compared to the adults. Moreover, post-infection weakness, successive relapse of arthralgic pain, and memory problems were the most significant aftereffects, which had an impact on the daily activities of patients. CONCLUSIONS: This study represents a comprehensive overview of clinical and epidemiological features of the 2017 outbreak of CHIKV in Bangladesh as well as its chronic outcomes till the 12th month. It provides insights into the natural history of this disease, which may help to improve the management of CHIKV patients.

Arsenic hampered embryonic development: An in vivo study using local Bangladeshi Danio rerio model.

Zebrafish (Danio rerio) has appeared as a valuable and popular model species to study the developmental and toxicological impact of environmental pollutants. To get insights on the toxicological effect of arsenic on early embryonic development, a controlled breeding of local Bangladeshi zebrafish followed by comprehensive microscopic analysis was conducted to study the embryonic development after exposure to different concentrations of arsenic ranges from 4-120 h post-fertilization. Zebrafish embryos exposed to 2 mM of arsenic displayed distinguishable developmental delay compared to control. At three days post-fertilization, a distinct phenotype appears in arsenic-treated embryos, which can be characterized by dechorionated embryos, larger egg mass, pericardial edema, abnormal heart rate, and abnormal head development. Remarkably, the death rate of the arsenic-treated embryos was significantly higher compared to control. Collectively, these findings indicate that exposure to arsenic may result in abnormal embryonic development. These results suggest for proper management of the pregnant mother in the arsenic-exposed area, and may also explain the incidence of increased miscarriage/abortion rate in arsenic water drinking pregnant mother.