A population based study on human papillomavirus infection and associated risk factors among women of the remote South Andaman Island, India.

BACKGROUND: Human papillomavirus (HPV) is associated with cervical cancer and cervical dysplasia worldwide. Data on HPV prevalence in a region is important because it serves as a predictor of the likelihood of the population in that particular region acquiring cervical cancer. Moreover, with the availability of effective vaccines, the public health system must be aware of the preponderance of HPV to implement the vaccine. The present study was designed to understand the prevalence of HPV and associated factors among the women of South Andaman Island. METHODS: A cross-sectional study was conducted among married women of reproductive age (18-59 years) from South Andaman District from 2018 to 2022. Cervical scrapes were collected from participants after obtaining informed written consent for HPV molecular testing (HPV DNA) such as PCR assay. Demographic data was collected using a standard questionnaire and statistical analyses were performed to determine the associated factors. RESULTS: The study showed prevalence of HPV as 5.9%(95% CI: 3.9-7.9) and prevalence of HR-HPV16 was 4.1% (95% CI 2.6 - 5.5) and HR-HPV18 prevalence was 1.8(95% CI: 0.6-3). The independent factors associated the HPV positivity were age above 55 years, menopause, post-menopausal bleeding, blood-stained vaginal discharge and loss of weight. Age was associated with all HPV infections among the South Andaman women. CONCLUSIONS: HPV 16 was reported as the predominant high risk HPV type circulating among women of South Andaman. Cervical cancer and precancerous lesions were significantly associated with HPV positivity and High risk HPV 16. Based on the knowledge of the risk factors associated with HPV, implementation of stronger public health awareness and prophylactic HPV vaccination is crucial among the women of this remote island.

Potent Rifampicin derivatives can clear MRSA infections at single low doses when concomitantly dosed with Vancomycin.

For a number of years, antimicrobial resistance (AMR) has been a critical issue for humanity. Drug discovery efforts have been very limited and the spread of bacterial pathogens has over-run our traditional arsenal of antibiotics. Bacteria can involve to evade compounds that can halt their rapid growth. The authors have discovered a potent macrocycle derivative that when dosed concomitantly with the standard of care (SOC) antibiotic vancomycin, can clear methicillin resistant Staphylococcus aureus (MRSA) infections. In addition, we have probed the lead compounds in Salmonella typhimurium bacterial strains. In vitro, in vivo, and ADME data have been included to stress the virtues of this new antibiotic.

Distribution of Human Papillomavirus Genotypes among the Women of South Andaman Island, India.

BACKGROUND: Human Papillomavirus (HPV) causes various types of cancer in both men and women. Woman with HPV infection has a risk of developing invasive cervical cancer. Globally, HPV 16 and 18 were predominant. This study aims to find the distribution of various HPV types in South Andaman. METHODS: A cross-sectional study was conducted among women in South Andaman, where cervical scrapes were collected after collecting written informed consent. Detection of HPV genotypes was carried out by using a PCR assay. Further, sequencing analysis was performed using MEGA11 to identify various genotypes in this territory. RESULT: Of these 1000 samples, 32 were positive for HR-HPV 16, and four were positive for HR-HPV 18. Fifteen HPV genotypes were detected using molecular evolutionary analysis. Six cases were identified with multiple genotypes. The most prevalent genotype is HPV 16 which belongs to Lineage-A and sub-lineage A2. HPV 18 identified in South Andaman belonged to the lineage A1 to A5. DISCUSSION: Various HPV types were identified among women in South Andaman. Global burden of cervical cancer associated with various HPV sub-lineages. HPV-16 A1 sub-lineage was globally widespread, whereas sub-lineages A1, A2 and D1 prevailed in South Andaman. CONCLUSIONS: HR-HPV identified in this study enlightens the importance of HPV vaccination among women in remote places. These findings will help to strengthen public health awareness programs and prevention strategies for women in remote areas.

Alkyl-substituted N-methylaryl-N'-aryl-4-aminobenzamides: A new series of small molecule inhibitors for Wip1 phosphatase.

The wild-type p53 induced phosphatase 1 (Wip1), a member of the serine/threonine-specific PP2C family, is overexpressed in numerous human cancers. Wip1 dephosphorylates p53 as well as several kinases (such as p38 MAPK, ATM, Chk1, and Chk2) in the DNA damage response pathway that are responsible for maintaining genomic stability and preventing oncogenic transformation. As a result, Wip1 is an attractive target for synthetic inhibitors that could be further developed into therapeutics to treat some cancers. In this study, we report a series of alkyl-substituted N-methylaryl-N'-aryl-4-aminobenzamides and their inhibitory activity of the Wip1 phosphatase. A straightforward synthetic route was developed to synthesize the target compounds from commercially available starting materials. Three different portions (R1, R2, R3) of the core scaffold were extensively modified to examine structure-activity relationships. This study revealed interesting trends about a new molecular scaffold to inhibit Wip1.

Maternal Mortality in the Remote Islands of India-Unraveling the Conundrum.

Introduction: Reduction in maternal mortality has been a top priority in low- and lower middle-income countries of Asia-Pacific region. India, being one of them, has a major responsibility of reducing maternal mortality especially in light of the commitment on the part of the Sustainable Development Goals. Despite massive efforts and availability of technology needed to avert maternal deaths, the maternal mortality ratio (MMR) in India continues to be high especially in remote areas. This study aims at collecting the MMR data and analyzing in the context of island infrastructure. Material and Methods: This was a hospital-based cross-sectional study. The records of maternal deaths from January 2010 to December 2019 were collected from the medical record section and analyzed. Results: The MMR was estimated to be 95.63 per 100,000 live births. Majority of the patients were multigravida (82%) in the age group of 21 to 30 years (75%). Around 64% of them were referred cases. Majority (86%) of the deaths occurred in the postpartum period. Hemorrhage was the leading direct cause of maternal deaths (35.7%) followed by hypertensive disorders of pregnancy (HDP) (21.4%). Conclusion: Most maternal deaths are preventable. Early detection of high-risk pregnancies and early referral of such patients to a well-equipped center is the key to curb the catastrophe of mortality. Adopting methods like qSOFA (quick sequential organ failure assessment) for identifying patients requiring intensive care and miniPIERS (Preeclampsia Integrated Estimate of RiSk) model for predicting adverse outcome in HDP is the need of hour. More efforts should be made to retain the specialists in the islands.

Maternal Near Miss: Unraveling Our Experience in the Tertiary Care Hospital of Andaman and Nicobar Islands.

CONTEXT: Women who survive life-threatening complications related to pregnancy and delivery have many common aspects with those who die of such complications. This similarity brought forward the near miss concept in maternal health. Analysis of the similarities, differences, and the relationship between these two groups of women provide a complete assessment of quality of maternal health care. AIMS: The aim of this study is to assess the baseline indices of maternal near miss (MNM) and analyze the quality of care at a tertiary care center in Andaman and Nicobar Islands. SETTINGS AND DESIGN: Facility-based, cross-sectional study. SUBJECTS AND METHODS: The study was conducted for a period of 18 months from January 1, 2015, to August 31, 2016. Cases, who met the World Health Organization (WHO) criteria of severe obstetric morbidity, were included and followed up during their hospital stay and till their discharge or death. Quality of maternal health care was assessed through the WHO near-miss criteria and criterion-based clinical audit methodology. STATISTICAL ANALYSIS USED: Descriptive statistics using mean and percentages and Student's t-test were used. RESULTS: Among 4720 women who delivered in our hospital, there were 4677 live births, 52 patients were near miss, and there were 9 maternal deaths. The MNM incidence ratio was 11.11%, the MNM mortality ratio was 5.77, and the mortality index 14.75%. The most common cause of maternal morbidity was hemorrhage followed by hypertensive disorders. CONCLUSIONS: Improving referral systems, effective use of critical care, and evidence-based interventions can potentially reduce severe maternal outcomes.

The structure-activity profile of mercaptobenzamides' anti-HIV activity suggests that thermodynamics of metabolism is more important than binding affinity to the target.

Mercaptobenzamide thioesters and thioethers are chemically simple HIV-1 maturation inhibitors with a unique mechanism of action, low toxicity, and a high barrier to viral resistance. A structure-activity relationship (SAR) profile based on 39 mercaptobenzamide prodrug analogs exposed divergent activity/toxicity roles for the internal and terminal amides. To probe the relationship between antiviral activity and toxicity, we generated an improved computational model for the binding of mercaptobenzamide thioesters (SAMTs) to the HIV-1 NCp7 C-terminal zinc finger, revealing the presence of a second low-energy binding orientation, hitherto undisclosed. Finally, using NMR-derived thiol-thioester exchange equilibrium constants, we propose that thermodynamics plays a role in determining the antiviral activity observed in the SAR profile.

Synthesis of Fmoc-Protected ( S, S)- trans-Cyclopentane Diamine Monomers Enables the Preparation and Study of Conformationally Restricted Peptide Nucleic Acids.

An efficient synthesis of Fmoc-protected ( S, S)- trans-cyclopentane PNA ( tcypPNA) monomers starting from mono-Boc-protected ( S, S)-1,2-cyclopentanediamine is reported. A general synthetic strategy was developed so that tcypPNA monomers with each nucleobase can be made in sufficient quantity and purity for use in solid-phase peptide synthesis (SPPS). The newly synthesized monomers were then successfully incorporated into 10-residue PNA oligomers using standard Fmoc chemistry for SPPS. The different tcypPNAs allow different positions in the sequence to be conformationally constrained with ( S, S)- trans-cyclopentane to determine the effects on binding to complementary DNA.

Chemical Features Important for Activity in a Class of Inhibitors Targeting the Wip1 Flap Subdomain.

The wild-type p53 induced phosphatase 1, Wip1 (PP2Cδ), is a protein phosphatase 2C (PP2C) family serine/threonine phosphatase that negatively regulates the function of the tumor suppressor p53 and several of its positive regulators such as ATM, Chk1, Chk2, Mdm2, and p38 MAPK. Wip1 dephosphorylates and inactivates its protein targets, which are critical for cellular stress responses. Additionally, Wip1 is frequently amplified and overexpressed in several human cancer types. Because of its negative role in regulating the function of tumor suppressor proteins, Wip1 has been identified as a potential therapeutic target in various types of cancers. Based on a recently reported Wip1 inhibitor (G-1), we performed an extensive structure-activity relationship (SAR) analysis. This led us to interesting findings in SAR trends and to the discovery of new chemical analogues with good specificity and bioavailability.

Probing Mercaptobenzamides as HIV Inactivators via Nucleocapsid Protein†7.

Human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein 7 (NCp7), a zinc finger protein, plays critical roles in viral replication and maturation and is an attractive target for drug development. However, the development of drug-like molecules that inhibit NCp7 has been a significant challenge. In this study, a series of novel 2-mercaptobenzamide prodrugs were investigated for anti-HIV activity in the context of NCp7 inactivation. The molecules were synthesized from the corresponding thiosalicylic acids, and they are all crystalline solids and stable at room temperature. Derivatives with a range of amide side chains and aromatic substituents were synthesized and screened for anti-HIV activity. Wide ranges of antiviral activity were observed, with IC50 values ranging from 1 to 100 µm depending on subtle changes to the substituents on the aromatic ring and side chain. Results from these structure-activity relationships were fit to a probable mode of intracellular activation and interaction with NCp7 to explain variations in antiviral activity. Our strategy to make a series of mercaptobenzamide prodrugs represents a general new direction to make libraries that can be screened for anti-HIV activity.

Unified Synthesis of 10-Oxygenated Lycopodium Alkaloids: Impact of C10-Stereochemistry on Reactivity.

The pronounced impact of the C10 stereochemistry on the successful construction of a polycyclic Lycopodium alkaloid scaffold has been explored. A wide range of reaction conditions and functionality were investigated to control a keto sulfone Michael addition to construct the C7-C12 linkage. An unexpected, overriding impact of the C10 stereochemistry in stereoselectivity and reaction rate in the Michael addition was observed. Furthermore, divergent reactivity of a conformationally accelerated, intramolecular Mannich cyclization based on the C10 stereochemistry was discovered. The successful execution of this synthetic route resulted in the total synthesis of all three known 10-oxygenated Lycopodium alkaloids: 10-hydroxylycopodine, paniculine, and deacetylpaniculine.

Maternal mortality in andaman and nicobar group of islands: 10 years retrospective study.

CONTEXT: Maternal mortality ratio (MMR) is an indicator of effectiveness of health care facilities for women of child bearing age group. Andaman and Nicobar (A&N) group of islands are unique as they are situated 1200 km from the mainland India. Healthcare delivery for the these islands is exclusively provided and controlled by only one authority, Directorate of Health Services, A&N Islands. GB Pant Hospital, Port Blair is the only referral hospital with round the clock specialists and surgical services. AIMS: To estimate the MMR in A&N islands from 2001 to 2010, and study the causes of maternal mortality. SETTINGS AND DESIGN: Retrospective. MATERIALS AND METHODS: Data for the estimation of MMR were collected from office of Registrar of Births and Deaths, Hospital and Peripheral Health Centres. Case records of maternal deaths in GB Pant Hospital were reviewed to study the causes of death. STATISTICAL ANALYSIS USED: Proportions and Ratios. RESULTS: Ten years average MMR for the entire island was 85.42. Analysis of 30 maternal deaths in GB Pant Hospital showed that 63.3% were due to direct obstetric causes (eclampsia 30%, hemorrhage 23.33%, sepsis 6.66%, and 3.33% amniotic fluid embolism). Of the indirect causes, anemia was the commonest (16.66%). CONCLUSIONS: The MMR of A&N islands is much lower than the national average of 250. Direct obstetric causes accounted for more than half of maternal deaths 63.33%.

Enantioselective approach to quinolizidines: total synthesis of cermizine D and formal syntheses of senepodine G and cermizine C.

The formal syntheses of C5-epi-senepodine G and C5-epi-cermizine C have been accomplished through a novel diastereoselective, intramolecular amide Michael addition process. The total synthesis of cermizine D has been achieved through use of an organocatalyzed, heteroatom Michael addition to access a common intermediate. Additional key steps of this sequence include a matched, diastereoselective alkylation with an iodomethylphenyl sulfide and sulfone-aldehyde coupling/reductive desulfurization sequence to combine the major subunits. The utility of a Hartwig-style C-N coupling has been explored on functionally dense coupling partners. Diastereoselective conjugate additions to α,ß-unsaturated sulfones have been investigated, which provided the key sulfone intermediate in just six steps from commercially available starting materials. The formal syntheses of senepodine G and cermizine C have been accomplished through an intramolecular cyclization process of a N-Boc-protected piperidine sulfone.

Toward a unified approach for the lycopodines: synthesis of 10-hydroxylycopodine, deacetylpaniculine, and paniculine.

The enantioselective syntheses of 10-hydroxylycopodine, deacetylpaniculine, and paniculine have been accomplished through use of a common intermediate. Key steps in the synthetic sequence toward these lycopodium alkaloids include formation of the tricyclic core via a conformationally accelerated, intramolecular Mannich cyclization and an organocatalyzed, intramolecular Michael addition to form the C(7)-C(12) linkage.