Genetic association of novel SNPs in HK-1 (rs201626997) and HK-3 (rs143604141) with type 2 diabetes mellitus in Bangladeshi population.

BACKGROUND: Hexokinase, a key enzyme in glycolysis, has isoforms like HK-1, HK-2, HK-3, and Glucokinase. Unpublished exome sequencing data showed that two novel polymorphisms in HK-1 rs201626997 (G/T) and HK-3 rs143604141 (G/A) exist in the Bangladeshi population. We investigated the possible relationship of these SNPs with T2DM. MATERIALS AND METHODS: Peripheral blood samples from the study participants were used to isolate their genomic DNA. An allele-specific PCR was standardized that can discriminate between the wild-type and mutant-type alleles of HK-1 (rs201626997) and HK-3 (rs143604141) polymorphisms. The data was analyzed by SPSS for statistics. RESULTS: We performed allele-specific PCR for 249 diabetic patients and 195 control samples. For HK-1 (rs201626997), 24 (5.4%) have a mutant allele, and for HK-3 (rs143604141), 25 (5.6%) are mutant. There is no significant relationship between the individuals' disease condition and the HK-1 polymorphism (P value 0.537). But the GA genotype of the HK-3 rs143604141 pertains to an increased risk of diabetes (P value 0.039). HK-3 rs143604141 polymorphism has a moderate correlation (P value 0.078, OR, 3.11, 95% CI, 0.88-10.94) with a family diabetic history. Both polymorphisms showed no significant correlation with gender or BMI. However, hexokinase-1 polymorphism significantly related with diastolic blood pressure (P value 0.048). CONCLUSION: This study will help us to easily detect the polymorphisms of HK-1 (rs201626997) and HK-3 (rs143604141) in different populations of the world. Further studies with a greater number of participants and more physiological information are required to better understand the underlying genetic causes of T2DM susceptibility in Bangladesh.

Prevalence of dermatological manifestations due to face mask use and its associated factors during COVID-19 among the general population of Bangladesh: A nationwide cross-sectional survey.

Following the worldwide COVID-19 pandemic, individuals have begun to take preventive measures to avoid exposure. Among the precautionary measures, facemask was mostly emphasized. This study aimed to determine the prevalence of dermatological symptoms linked with face mask usage and explore other associated factors. This cross-sectional survey was conducted throughout all eight divisions of Bangladesh. 1297 people were approached using a fixed-step procedure on a random route sample where 803 fulfilled the inclusion criteria. The overall prevalence of dermatological manifestation in this study was 40.85%. The common dermatological manifestations due to facemasks use were acne (26%), allergy symptoms (24%), traumatic symptoms (24%), and other symptoms (26%). Two important frequently reported risk factors were previous history of skin diseases and obesity. Females were more likely to have acne (CI: 1.199, 3.098; p = .007) and allergy issues (CI: 1.042, 2.359; p = .031). N95 and KN95 masks were more likely to produce allergic symptoms, while surgical mask users were more likely to develop acne. Acne was prevalent more than twice (CI: 1.42, 4.26; p = 0.001) in persons with a COVID-19 infection history. Further exploration is required to find out the reason. Surgical mask users reported more complaints than other types of masks, and prolonged use caused more skin symptoms. Modifications in the pattern of facemask usage and planning for work recesses might also be advised to provide for a pause from uninterrupted facemask use.

Prevalence of dermatological, oral and neurological problems due to face mask use during COVID-19 and its associated factors among the health care workers of Bangladesh.

BACKGROUND: When caring for COVID-19 patients, using personal protective equipment (PPE) may significantly lower the risk of infection of health care workers (HCWs). However, adverse responses due to PPE use have been observed during the 2003 SARS pandemic. This study will highlight the different adverse reactions caused by face mask use, one of the essential components of PPE in the HCWs, and identify the factors associated with these problems. METHODS: This cross-sectional survey was conducted between September and October 2021. 404 HCWs were selected by snowball sampling from four randomly selected healthcare facilities of Bangladesh. Trained volunteers collected data by face-to-face interview using a pretested structured questionnaire. Data were analyzed using STATA (v.16) and summarized using frequency and relative frequency. Later, the chi-square test was used to explore bivariate relationships, and the binary logistic regression model was fit to identify the predictors. RESULTS: The majority of the respondents were 26-36 years (70.30%), male (69.80%), and doctors (74.50%). 48.76% of the respondents had unfavorable skin responses beneath the face masks; female gender, physicians, professionals working more than 32 hours a week, wearing N95, and more than one mask were predictors of skin problem. 28.47% and 60.15% of all participants suffered from some form of oral and neurological problems, respectively. CONCLUSION: Face mask use sequelae, especially skin, oral and neurological problems, are prevalent among health care workers. Therefore, necessary precautionary measures should be taken to safeguard our frontlines.

International Summit on Laparoscopic Pancreatic Resection (ISLPR) "Coimbatore Summit Statements".

The International Summit on Laparoscopic Pancreatic Resection (ISLPR) was held in Coimbatore, India, on 7th and 8th of October 2016 and thirty international experts who regularly perform laparoscopic pancreatic resections participated in ISPLR from four continents, i.e., South and North America, Europe and Asia. Prior to ISLPR, the first conversation among the experts was made online on August 26th, 2016 and the structures of ISPLR were developed. The aims of ISPLR were; i) to identify indications and optimal case selection criteria for minimally invasive pancreatic resection (MIPR) in the setting of both benign and malignant diseases; ii) standardization of techniques to increase the safety of MIPR; iii) identification of common problems faced during MIPR and developing associated management strategies; iv) development of clinical protocols to allow early identification of complications and develop the accompanying management plan to minimize morbidity and mortality. As a process for interactive discussion, the experts were requested to complete an online questionnaire consisting of 65 questions about the various technical aspects of laparoscopic pancreatic resections. Two further web-based meetings were conducted prior to ISPLR. Through further discussion during ISPLR, we have created productive statements regarding the topics of Disease, Implementation, Patients, Techniques, and Instrumentations (DIPTI) and hereby publish them as "Coimbatore Summit Statements".

Physicochemical characterization of 9-aminocamptothecin in aqueous solutions.

The present manuscript provides a detailed physicochemical and thermodynamic characterization of 9-aminocamptothecin (9AC) which can be used as a tool to develop novel formulation strategies for optimum pharmacological activity. The pKa of 9AC was determined to be 2.43 at 37°C, while the basicity of quinoline nitrogen of 9AC was found to decrease with increasing temperature due to a positive enthalpy of deprotonation of 10.36 kJ mol(-1). The equilibrium solubility as well as the intrinsic solubility of the drug was found to increase with increasing temperature and decreasing pH. The enthalpies of solution of unionized and ionized forms of 9AC obtained from isothermal and iso-pH equilibrium solubility measurements were found to be 36.01 and 24.72 kJ mol(-1), respectively. Equilibrium hydrolysis studies revealed the hydrolytic susceptibility of 9AC with only 14% of active lactone species remaining at physiological pH 7.4. The intrinsic partition coefficient log P of the free base, 9AC-lactone, was estimated to be 1.28 (a characteristic of molecules suitable for oral absorption). The estimated pKa and log P values of 9AC, combined with its increased solubility at lower pH, are features that can be utilized to develop novel drug delivery systems to optimize the antitumor activity of 9AC.

Physicochemical characterization, solubilization, and stabilization of 9-nitrocamptothecin using pluronic block copolymers.

Solid-state properties and physicochemical characteristics of 9-nitrocamptothecin (9NC) were investigated with a view of molecular and bulk level understanding of its poor aqueous solubility and hydrolytic instability that prevent efficient drug delivery and pharmacological activity. 9NC bulk drug substance was found to be a nonhygroscopic, yellowish crystalline solid with long rectangular prism-shaped particle morphology and a sharp melting point at 264°C. Hydrolysis of 9NC-lactone occurs above pH 4, whereas complete conversion of lactone to carboxylate was recorded above pH 8. At saturated conditions, appreciable concentrations of 9NC-lactone were detected at pH as high as 11. 9NC undergoes oxidation in the presence of dimethyl sulfoxide with formation of 9NC-N-oxide. The total solubility of lactone and carboxylate forms of 9NC in deionized water was found to be less than 5 µg/mL, whereas the solubility of 9NC-lactone in aqueous acidic media was determined to be approximately 2.5 µg/mL. Incorporation of 10% pluronic copolymers P123, F127, and F68 in 10 mM HCl increased 9NC solubility by 13-fold, eightfold, and fivefold, respectively. The thermodynamic stability of drug-loaded pluronic micelles was evaluated under isothermal variable volume conditions and found F127, among all poloxamers, to offer the best hydrolytic protection efficacy for 9NC.

Kinetic and thermodynamic studies of 9-aminocamptothecin hydrolysis at physiological pH in the presence of human serum albumin.

As a first step towards improving the aqueous stability of 9-aminocamptothecin (9AC), a detailed kinetic and thermodynamic investigation of the hydrolysis reaction of 9AC was carried out, using a first derivative absorption spectrophotometry technique. It was found that 9AC-lactone decayed with a half-life of 25 min in PBS at pH 7.4 and 310.15K. The activation energy (Ea) associated with the hydrolysis of 9AC-lactone was 87.3 ± 3.8 kJmol(-1), whereas the positive enthalpy and entropy values of the 9AC-lactone hydrolysis reaction indicated that the reaction is endothermic and entropically driven. Similarly to other camptothecin analogs, except for SN38, the activation energy for 9AC-lactone hydrolysis in the presence of Human Serum Albumin (HSA) was about 10 kJmol(-1) lower than that determined in plain PBS, whereas the equilibrium 9AC-lactone concentration was decreased in the presence of HSA as compared to that in plain PBS. The lower Ea for 9AC hydrolysis in presence of HSA fully explained the shift of lactone-carboxylate equilibrium towards the carboxylate form with only 4% of active 9AC-lactone remaining in the presence of HSA under physiological conditions. Finally, affinity studies of several camptothecin analogs with HSA, showed that the association constants of the lactone species with HSA are similar and pointed out that the superior stability of the SN38 over the other two analogs (9AC and 9-nitrocamptothecin) is not due to the higher affinity of lactone toward HSA, but it is rather due to the lower affinity of the SN38-carboxylate toward HSA.