Advancing posaconazole quantification analysis with a new reverse-phase HPLC method in its bulk and marketed dosage form.

Introduction: Posaconazole is a widely used antifungal drug, and its accurate quantification is essential for quality control and assessment of its pharmaceutical products. This study aimed to develop and validate a reverse-phase high-performance liquid chromatography (HPLC) analytical method for quantifying Posaconazole in bulk and dosage form. Methods: The HPLC method was developed and validated based on International Conference on Harmonisation (ICH) guidelines. The developed method was then applied to quantify Posaconazole in a marketed tablet formulation. The method's specificity, linearity, precision, accuracy, robustness, and stability were evaluated. Results: The developed HPLC method showed good linearity over a 2-20 µg/mL concentration range. The percentage recovery of Posaconazole from the bulk and marketed formulations was found to be 99.01% and 99.05%, respectively. The intra-day and inter-day precisions were less than 1%, and the method was stable under different conditions. The HPLC method was successfully applied to quantify Posaconazole in the marketed formulation. Conclusion: The developed and validated HPLC method is reliable and efficient for analyzing Posaconazole in bulk and dosage forms. The method's accuracy, precision, specificity, linearity, robustness, and stability demonstrate its effectiveness. The method can be used for the quality control and assessment of Posaconazole-containing pharmaceutical products.

Association Between AMH Levels and Fertility/Reproductive Outcomes Among Women Undergoing IVF: A Retrospective Study.

Background: Anti-mullerian hormone (AMH) is a marker for predicting ovarian response to gonadotropin stimulation. It plays an important role in ovarian primordial follicle recruitment and dominant follicle selection. Therefore, the present study evaluated the AMH levels and their association with fertility/reproductive outcomes among women undergoing IVF. Methods: A retrospective study was conducted on 665 women in GarbhaGudi Institute of Reproductive Health and Research in India from October 2018 to 2019. Subjects were divided into ≥1.1 and ≤1.1 AMH level groups. Data on age, luteinizing hormone; LH (mIU/L), follicle-stimulating hormone values; FSH (mIU/ml), LH value, oocytes retrieved, and oocytes fertilization were collected. AMH category was considered as the primary explanatory variable. Independent sample t-test and chi-square tests were performed. The p<0.05 was considered statistically significant. Results: Couple's age, FSH values (mIU/ml), number of large follicles, matured oocytes, fertilized oocytes, and cleaved embryos were statistically significant (p<0.001) among subjects with ≥1.1 AMH values. Percentage of women with successful embryo transfer was slightly higher among AMH category 1.1 (p=0.09). Fertilization rate (86.67±20.08 vs. 83.64±21.39, p=0.18) and clinical pregnancy rate (43.38% vs. 36.36%, p=0.19) were slightly higher among women with AMH level of ≥1.1 as compared to AMH of <1.1. Live birth rate was slightly higher among women with AMH level of 1.1 (25.85% vs. 22.22%, p=0.45). Also, the number of fertilized oocytes was associated with clinical pregnancy rate (aOR=1.20, 95%CI 1.09-1.33). Conclusion: Women with ≥1.10 serum AMH levels had more number of retrieved oocytes, good oocyte quality, increased embryo transfer, and fertilization rates.

Preventable contributors to the neonatal healthcare-associated infections: a uni-center analytical study from South India.

BACKGROUND: Globally, neonatal healthcare-associated infections (HAIs) are known to cause high mortality. HAIs is a preventable condition related to the healthcare environment. The current study explored the contributors to neonatal HAIs in one of the largest tertiary care referral hospitals in South India. METHODS: Neonates from December 2016 to June 2018 were observed for the occurrence of healthcare-associated infections and compared with the matched control group. Various observations on neonatal demography, maternal contributors, and medical procedures were made and recorded to explore and analyse the contributors to neonatal HAIs. Univariate and multivariate analysis was carried out to find the contributors. The Odds ratio with 95% CI was also computed and reported. RESULTS: Bloodstream infection (83%) was prevalent among neonates; the maternal contributor was only preterm labor (Odds ratio of 11.93; 95% CI; 6.47-21.98; p<.05) to acquire HAIs. On univariate analysis, mechanical ventilation for > 3days duration, NIV for > five days, and PICC line insertion procedure were significant (p<0.05) contributors to neonatal HAIs. IV cannulation for more than three times in four consecutive days was found in 100(85%) neonates considered being associated with neonatal HAIs. On multivariate analysis, NIV, PICC line, preterm labor, and low birth weight were significant (p<0.05) contributors to neonatal HAIs. CONCLUSION: The increased duration of invasive and non-invasive therapeutic devices and catheters contributes to neonatal HAIs. Neonates are acquiring bloodstream infections; low birth weight (LBW) neonates are more susceptible to acquiring HAIs.

Evaluation of Use of RPMI Medium to Preserve Cell Morphology for Pleural/Peritoneal Fluid Cytology.

Introduction: Cytologic evaluation is the best way to detect the presence of malignancy in body cavity fluids. Roswell Park Memorial Institute (RPMI) medium or RPMI 1640 is used in cell culture, tissue culture, and also to improve the cellularity and morphology of CSF cytology specimens. Objectives: To determine whether RPMI medium can be used to preserve cell morphology in pleural/peritoneal effusion samples. Method and Material: The study was conducted on 30 pleural/peritoneal fluid samples received routinely during 2 months for diagnostic purposes in our department. The samples were divided into four parts. One-fourth of the sample was directly refrigerated and the other fourth was at room temperature. In the other two parts, an equal volume of RPMI media was added, and one was kept at room temperature and the other refrigerated. These cytospin-prepared Giemsa-stained smears were examined for cell morphology, cellularity, and occurrence of bacterial colonies at 24 h, 48 h, 72 h, and 1 week, respectively. Result: Refrigerated RPMI medium is the best preservative for pleural/peritoneal samples; however, samples with RPMI at room temperature were equivalent/even worse than the simple refrigerated sample.

Basaloid squamous cell carcinoma of anal canal with adenoid cystic pattern and liver metastasis: A rare case report.

Anal malignancies are rare, and of these squamous cell carcinoma and basaloid squamous cell carcinoma are the most common types. Anal basaloid squamous carcinoma (BSC) can show a variety of patterns including unusual variants with cribriform areas resembling adenoid cystic carcinoma (ACC). BSC is reported more frequently in elderly females. Although the histopathology of BSC is characteristic, its cytomorphology is rarely described in the anorectal region. Due to overlapping morphological features, it is challenging to distinguish between ACC and BSC. Immunohistochemistry (IHC) is mandatory for this distinction and definite diagnosis, as it is a highly aggressive tumor with a tendency for distant metastasis. An interesting and rare case of BSC with ACC-pattern arising in the anal canal with liver metastasis in a middle-aged male is reported here. The aim is to highlight its cytological features, correlation with histology, IHC and its differential diagnoses.

Cationic biopolymer decorated Asiatic Acid and Centella asiatica extract incorporated liposomes for treating early-stage Alzheimer's disease: An In-vitro and In-vivo investigation.

Background: Asiatic acid (AA) is a naturally occurring triterpenoid derivative of Centella asiatica (CA) with neuroprotective effect. The study aimed to design an ideal oral drug delivery system to treat Alzheimer's disease (AD) and develop chitosan-embedded liposomes comprising an extract of CA (CLCAE) and compare them with the chitosan-coated liposomes of asiatic acid (CLAA) for oral delivery to treat the initial phases of AD.  Methods: The solvent evaporation technique was used to develop CLCAE and CLAA, optimised with the experiment's design, and was further evaluated. Results: Nuclear magnetic resonance (NMR) studies confirmed coating with chitosan. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) indicated the successful formation of CLCAE and CLAA. Differential scanning colorimetry (DSC) confirmed the drug-phospholipid complex. Furthermore, the rate of  in vitro release of CLCAE and CLAA was found to be 69.43±0.3 % and 85.3±0.3 %, respectively, in 24 h.  Ex vivo permeation of CLCAE and CLAA was found to be 48±0.3 % and 78±0.3 %, respectively. In the Alcl3-induced AD model in rats, disease progression was confirmed by Y-maze, the preliminary histopathology evaluation showed significantly higher efficacy of the prepared liposomes (CLCAE and CLAA) compared to the Centella asiatica extract (CAE) and they were found to have equivalent efficacy to the standard drug (rivastigmine tartrate). The considerable increase in pharmacodynamic parameters in terms of neuronal count in the CLAA group indicated the protective role against Alcl3 toxicity and was also confirmed by assessing acetylcholine (Ach) levels. The pharmacokinetic study, such as C max, T max, and area under curve (AUC) parameters, proved an increase in AA bioavailability in the form of CLAA compared to the pure AA and CLCAE forms. Conclusion: The preclinical study suggested that CLAA was found to have better stability and an ideal oral drug delivery system to treat AD.

Impact of COVID-19 on non-COVID intensive care unit service utilization, case mix and outcomes: A registry-based analysis from India.

Background: Coronavirus disease 2019 (COVID-19) has been responsible for over 3.4 million deaths globally and over 25 million cases in India. As part of the response, India imposed a nation-wide lockdown and prioritized COVID-19 care in hospitals and intensive care units (ICUs). Leveraging data from the Indian Registry of IntenSive care, we sought to understand the impact of the COVID-19 pandemic on critical care service utilization, case-mix, and clinical outcomes in non-COVID ICUs.  Methods: We included all consecutive patients admitted between 1 st October 2019 and 27 th September 2020. Data were extracted from the registry database and included patients admitted to the non-COVID or general ICUs at each of the sites. Outcomes included measures of resource-availability, utilisation, case-mix, acuity, and demand for ICU beds. We used a Mann-Whitney test to compare the pre-pandemic period (October 2019 - February 2020) to the pandemic period (March-September 2020). In addition, we also compared the period of intense lockdown (March-May 31 st 2020) with the pre-pandemic period. Results: There were 3424 patient encounters in the pre-pandemic period and 3524 encounters in the pandemic period. Comparing these periods, weekly admissions declined (median [Q1 Q3] 160 [145,168] to 113 [98.5,134]; p=0.00002); unit turnover declined (median [Q1 Q3] 12.1 [11.32,13] to 8.58 [7.24,10], p<0.00001), and APACHE II score increased (median [Q1 Q3] 19 [19,20] to 21 [20,22] ; p<0.00001). Unadjusted ICU mortality increased (9.3% to 11.7%, p=0.01519) and the length of ICU stay was similar (median [Q1 Q3] 2.11 [2, 2] vs. 2.24 [2, 3] days; p=0.15096). Conclusion: Our registry-based analysis of the impact of COVID-19 on non-COVID critical care demonstrates significant disruptions to healthcare utilization during the pandemic and an increase in the severity of illness.

Assessment of knowledge, attitude and practices among dental practitioners on methods of infection control while carrying out dental procedures during novel coronavirus (COVID-19) pandemic.

INTRODUCTION: dental procedures produce bio-aerosols that can carry the highly contagious COVID-19 virus. Hence, the entire dental care team has to follow the current COVID-19 related infection control protocols. The study aims to assess the knowledge, attitude, and practices associated with infection control methods during dental procedures among dental practitioners during the COVID-19 pandemic in India. METHODS: the online questionnaire consisted of four sections namely, demographic details, eight questions on knowledge, four questions on attitude and eight questions on the practice of dentists during COVID-19 pandemic. One point was attributed for a correct response and zero point for an incorrect response. The study used descriptive statistics and binary logistic regression models in Jamovi 1.8.1 to establish relationships between knowledge, attitude, and practices among dental professionals and their demographic characteristics. RESULTS: among 384 dentists, 294 (76.6%) were aware of the hand hygiene methods, 372 dentists (96.9%) were aware of the Personal Protective Equipment (PPE), 343 dentists (89.3%) recorded the body temperature of the patients. One hundred and thirty eight (138) dentists (35.9%) did not use rubber dam and 158 dentists (41.1%) were not aware of the four-handed dentistry. Among the study participants, 57.8% displayed adequate knowledge, 63.8% possessed good attitude and 93.5% followed good practices on COVID-19 appropriate infection control measures during dental procedures. The mean knowledge, attitude, and practice scores were found to be 6.61, 2.04, and 3.38 respectively. Based on multivariable binary logistic regression analysis, it is observed that males (aOR: 0.55, 95% CI 0.35-0.87; p=0.011) have a lower likelihood of having a good knowledge when compared with females after adjusting for the other independent variables in the model. Also, individuals with higher qualifications (aOR: 0.57, 95% CI 0.36-0.92; p=0.022) appear to have lower likelihood of having good knowledge on COVID-19 infection control methods during dental procedure. CONCLUSION: the study concludes that participants possess sound knowledge, attitude and practice on hand hygiene, PPE, patient triage and waiting area modifications at the workplace. However, poor response was noted on the use of rubber dam, remote telephonic screening and four-handed dentistry practice.

Implementing an intensive care registry in India: preliminary results of the case-mix program and an opportunity for quality improvement and research.

Background: The epidemiology of critical illness in India is distinct from high-income countries. However, limited data exist on resource availability, staffing patterns, case-mix and outcomes from critical illness. Critical care registries, by enabling a continual evaluation of service provision, epidemiology, resource availability and quality, can bridge these gaps in information. In January 2019, we established the Indian Registry of IntenSive care to map capacity and describe case-mix and outcomes. In this report, we describe the implementation process, preliminary results, opportunities for improvement, challenges and future directions. Methods: All adult and paediatric ICUs in India were eligible to join if they committed to entering data for ICU admissions. Data are collected by a designated representative through the electronic data collection platform of the registry. IRIS hosts data on a secure cloud-based server and access to the data is restricted to designated personnel and is protected with standard firewall and a valid secure socket layer (SSL) certificate. Each participating ICU owns and has access to its own data. All participating units have access to de-identified network-wide aggregate data which enables benchmarking and comparison. Results: The registry currently includes 14 adult and 1 paediatric ICU in the network (232 adult ICU beds and 9 paediatric ICU beds). There have been 8721 patient encounters with a mean age of 56.9 (SD 18.9); 61.4% of patients were male and admissions to participating ICUs were predominantly unplanned (87.5%). At admission, most patients (61.5%) received antibiotics, 17.3% needed vasopressors, and 23.7% were mechanically ventilated. Mortality for the entire cohort was 9%.  Data availability for demographics, clinical parameters, and indicators of admission severity was greater than 95%. Conclusions: IRIS represents a successful model for the continual evaluation of critical illness epidemiology in India and provides a framework for the deployment of multi-centre quality improvement and context-relevant clinical research.

Effect of newborn's admission to intensive care unit on "quality of life" of mother: an Indian perspective.

BACKGROUND: Newborn hospitalized in the neonatal intensive care unit (NICU) raises a mother's risk of reduced health-related quality of life (QoL). We explored the contributors inducing stress among mothers related to NICU. METHODOLOGY: One hundred thirty-five mothers, whose newborn has completed 48 hours of NICU stay, were interviewed using parental stress scale: neonatal intensive care unit and SF-36 health survey questionnaire for further assessment. RESULTS: The look and behavior of the baby were predominant contributor to the decreased QoL among mothers (p= <.001). A moderate negative association between parental stresses related to the NICU environment and their QoL ρ  = -.467 was observed. CONCLUSION: It is required to look back at the interiors of the Intensive Care Unit (ICU), the duration provided for the mother and child's physical bonding, the unnecessary noise of the alarms and the jungle of wires around the baby to optimize the QoL of mothers. The further policy requires focusing on building a relation of the mother and child, especially when a child needs supportive care.

Atrial fibrillation associated genetic variation near PITX2 gene increases the risk of preeclampsia.

OBJECTIVES: SNP rs2200733 located near PITX2 gene is associated with the risk of atrial fibrillation. Preeclamptic women are at increased risk of developing cardiovascular disease like atrial fibrillation. Whether this translates into an association between SNP rs2200733 and preeclampsia is not known. Therefore, we determined the association of SNP rs2200733 (C/T) with the risk of preeclampsia. STUDY DESIGN: A hospital based prospective case-control study involving 585 pregnant women of whom 285 were preeclamptic and 300 were normotensive. SNP rs2200733 was genotyped by PCR-RFLP method. MAIN OUTCOME MEASURES: Statistical significance of the difference in the minor allele frequency between case and control groups was determined by Fisher's exact test. RESULTS: Minor allele frequency was 21.4% among preeclamptic pregnant women and 13.7% among normotensive pregnant women (P = 0.00064; odds ratio = 1.72 (0.95 CI: 1.23-2.41). The measures of association were heterogeneous when compared after categorisation of the preeclamptic group into clinical sub-groups. The association was not significant with the eclampsia sub-group (P = 0.39) but relatively higher with the sub-group not superimposed by eclampsia (P = 0.0000048; odds ratio = 2.10 [0.95CI: 1.50-2.92]). Furthermore, the association was relatively higher with the sub-group involving intrauterine growth retardation and intrauterine death (P = 0.00017; odds ratio = 2.89 (0.95CI: 1.65-4.94)]. CONCLUSIONS: Minor allele of SNP rs2200733 is associated with the risk of preeclampsia. SNP rs220073 may represent a common risk factor that predispose women to develop both preeclampsia during pregnancy and cardiovascular disease later on.

Functional Genomic Investigation of the Molecular Biological Impact of Electron Beam Radiation in Lymphoma Cells.

PURPOSE: The biological response of electron beam radiation (EBR) in tumors remains underexplored. This study describes the molecular biological and genomic impact of EBR on tumor cells. METHODS: A mouse model bearing Dalton's lymphoma ascites cells was exposed to an 8-MeV pulsed electron beam, at a dose rate of 2 Gy/min using a microtron, a linear accelerator. The radiation-induced changes were assessed by histopathology, fluorescence-activated cell sorting, signaling pathway-focused reporter assays, and gene expression by microarray analysis. RESULTS: EBR was found to increase apoptosis and G2-M cell cycle arrest with concomitant tumor regression in vivo. The microarray data revealed that EBR induced tumor regression, apoptosis, and cell cycle arrest mediated by p53, PPAR, and SMAD2/3/4 signaling pathways. Activation of interferon regulatory factor and NFkB signaling were also found upon EBR. Chemo-genomics exploration revealed the possibility of drugs that can be effectively used in combination with EBR. CONCLUSION: For the first time, an 8-MeV pulse EBR induced genomic changes, and their consequence in molecular and biological processes were identified in lymphoma cells. The comprehensive investigation of radiation-mediated responses in cancer cells also revealed the potential therapeutic features of EBR.

Amelioration Effect of Zinc and Iron Supplementation on Selected Oxidative Stress Enzymes in Liver and Kidney of Cadmium-Treated Male Albino Rat.

Cadmium (Cd) is a highly toxic, nonessential heavy metal with many industrial uses that can contribute to a well-defined spectrum of diseases in animals as well as in humans. The present study examines the effect of zinc (Zn) and iron (Fe) supplementation on oxidative stress enzymes in Cd-treated rats. Wistar strain male albino rats were treated with cadmium chloride (CdCl2) at a dose of 1/10(th) LD50/48 h, that is, 22.5 mg/kg body weight for 7, 15, and 30 days (d) time intervals. The 15d Cd-treated rats were divided into three groups. The first group received Zn (12 mg/kg), second group Fe (40 mg/kg) alone, and third group supplemented with both Zn and Fe and observed for 7, 15, and 30d. After the specific time intervals, rats were decapitated and oxidative stress enzymes like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed in liver and kidney. Simultaneously lipid peroxidation (LPO) levels were also measured. A significant elevation in LPO levels with decreased activity levels of CAT, SOD, GPx, and GST were observed during Cd intoxication. With Zn and/or Fe supplementation, a significant reversal in the oxidative stress enzymes was observed. Our study reveals that combination of Zn and Fe supplementation is effective in detoxifying the Cd body burden from the test tissues.

Small cell neuroendocrine carcinoma of the cervix: a rare entity.

Small cell carcinoma of the cervix is a rare and a very aggressive tumour. Once being considered to be a rare type of squamous cell carcinoma, evidence has proven that most of the tumours express one or more markers of neuroendocrine differentiation. The behaviour of this rare malignancy is different from that of squamous cell carcinomas, with a high propensity for nodal and distant metastases. Hence, there is a need to highlight this histopathological entity.

Association of gene polymorphism in detoxification enzymes and urinary 8-OHdG levels in traffic policemen exposed to vehicular exhaust.

CONTEXT: With rapid economic growth and massive development of transportation, the number of automobiles has greatly increased. Traffic police are the one of the vulnerable groups predominantly exposed to vehicular exhaust during traffic control. OBJECTIVE: The present study is aimed to study the relation between occupational exposure to vehicular exhaust and oxidative stress (OS) in traffic police. We investigated the levels of 8- hydroxydeoxyguanosine (8-OHdG), one of the most sensitive biomarkers for measuring OS and the association between polymorphisms in Cytochrome P450 (CYP) and Glutathione S-Transferase (GST) genes that are known to play a significant role in the activation and detoxification of xenobiotics. MATERIALS AND METHODS: 148 non smoking male traffic policemen and 135 control subjects were selected for this study. The 8-OHdG levels were analyzed by liquid chromatography with electrochemical detection method. Gene polymorphism was detected by multiplex PCR and RFLP method. RESULTS: 8-OHdG levels were found to be increased in traffic police with increase in the years of service in traffic control (p = 0.02) when compare to the controls. The results showed a significant increase in urinary 8-OHdG levels in mutated CYP1A1m1 (p < 0.007) and null GSTM1 (p < 0.01) genotypes. However the genotype frequencies of CYP1A1 m2 and GSTT1 genes did not vary in both exposed and control groups. CONCLUSION: Our study suggests that exposure to vehicular exhaust over a period of time increases oxidative stress and subsequently induces oxidative DNA damage in traffic policemen. Preventive and therapeutic strategies may be considered for traffic policemen to minimize the adverse effects due to vehicular exposure.

The spectroscopic (FTIR, FT-Raman, NMR and UV), first-order hyperpolarizability and HOMO-LUMO analysis of methylboronic acid.

The solid phase FTIR and FT-Raman spectra of methylboronic acid (MBA) have been recorded in the regions 400-4000 and 50-4000 cm(-1), respectively. The spectra were interpreted interms of fundamentals modes, combination and overtone bands. The structure of the molecule was optimized and the structural characteristics were determined by density functional theory (B3LYP) and HF method with 6-311++G(d,p) as basis set. The vibrational frequencies were calculated for most stable conformer and were compared with the experimental frequencies, which yield good agreement between observed and calculated frequencies. The infrared and Raman spectra were also predicted from the calculated intensities. (1)H and (13)C NMR spectra were recorded and (1)H and (13)C nuclear magnetic resonance chemical shifts of the molecule were calculated using the gauge independent atomic orbital (GIAO) method. UV-visible spectrum of the compound was recorded in the region 200-400 nm and the electronic properties HOMO and LUMO energies were calculated by time-dependent TD-DFT approach. Mulliken charges of the MBA molecule was also calculated and interpreted. The geometric parameters, energies, harmonic vibrational frequencies, IR intensities, Raman intensities and absorption wavelengths were compared with the available experimental data of the molecule.

Giant cell tumor of tendon sheath mimicking pyogenic granuloma in the index finger pulp: a case report.

We report a 75-year-old man who presented with a painless friable mass in the index finger pulp mimicking pyogenic granuloma. Complete excision of the mass was done. The radiological and the histopathological findings suggested giant cell tumor of the tendon sheath. The patient had no recurrence at the end of a two-year follow-up. This unusual clinical presentation of the giant cell tumor of the tendon sheath was our study base and adds up to its variant presentation in the literature.

Sternal traction: simple technique to prevent tamponade/compression of the heart.

Routine closure of the sternum after cardiovascular surgery sometimes causes severe cardiac depression because of tamponade, leading to cardiogenic shock. We describe a full-thickness chest wall traction suture taken parasternally and tied to an intravenous fluid stand. Upward (outward) traction is applied to the anterior chest while the sternum is primarily closed, which allows physiologic improvement equivalent to delayed sternal closure. It is a safe and easily reproducible technique.