Nevin Manimala

J Nat Prod. 2023 Oct 31. doi: 10.1021/acs.jnatprod.3c00794. Online ahead of print.

ABSTRACT

Four new natural chemical entities, including 2-hydroxy-α-truxillic acid (2), (3R,4S)-2,2-dimethyl-3-hydroxy-4-(1-angeloyloxy)-6-acetyl-7-methoxychromane (3), N-tricosanoyltyramine (4), and grandifolamide (5), were isolated along with 11 known compounds (1, 6–15) from the aerial parts of Ageratina grandifolia. The chemical structures were elucidated using chemical derivatization and HR-MS, NMR, and DFT-calculated chemical shifts, combined with DP4+ statistical analysis. It was found that 2 decomposed into its biogenetic precursor, o-coumaric acid, upon standing at room temperature for a few weeks. 3,5-Diprenyl-4-hydroxyacetophenone (8), O-methylencecalinol (10), encecalin (11), and encecalinol (12) bound to calmodulin (CaM) with higher affinity than chlorpromazine, a well-known CaM inhibitor. Molecular dynamics studies revealed that the complexes of these compounds with CaM remained stable during the simulation. Altogether these results revealed the therapeutic and research tool potential of compounds 8, 10, 11, and 12.

PMID:37906816 | DOI:10.1021/acs.jnatprod.3c00794

Andes Pediatr. 2022 Dec;93(6):860-867. doi: 10.32641/andespediatr.v93i6.3923.

ABSTRACT

The insulin microinfuser with integrated system (SAPT) for patients with type 1 Diabetes Mellitus (T1D) is included in the national financial protection system for high-cost treatments.

OBJECTIVE: To describe the initial and first-year metabolic outcomes and epidemiological and nutritional characteristics of T1D pediatric patients treated with SAPT.

PATIENTS AND METHOD: Retrospective, descriptive and analytical study of clinical records from 2017 to 2019, of 12 patients with T1D users of SAPT, attended in a referral hospital.

VARIABLES: age at program entry, time of evolution of the disease, type of insulin treatment and type of glucose monitoring (capillary: sample or Continuous Glucose Monitoring [CGM]) at program entry, cause of application to the program, nutritional status, rural or urban origin, educational level of the main guardian, HbA1c at application and in the last month of each quarter after SAPT installation, over a 12-month period. HbA1c analysis was venous sample by High-Performance Liquid Chromatography and follow-up was capillary sample by Latex Particle Agglutination Inhibition.

RESULTS: The median variables at 12 months of treatment were Total Daily Dose (TDD) 0.74, %Basal (%B) 49%, Time In Range (TIR) 39%, Time Below Range (TBR) 1%, and HbA1c 7.7%. The sensor usage time was met in all cases and only half of them achieved a correct execution of hyperglycemia and hypoglycemia treatment. Inadvertent severe hypoglycemia was the main cause of application to the program.

CONCLUSION: TDD and %B increased, approaching physiological requirement, although without statistical significance, which could be attributed to the administra tion of adequate insulin with lower risk of hypoglycemia due to predictive suspension and CGM. TIR presented a favorable increase, although not significant, nor reaching the target range, attributable to the short observation time, difficulties in understanding and execution of our patients, and the learning process of the treating clinical team. SAPT was effective in hypoglycemia management and effective in improving HbA1c.

PMID:37906803 | DOI:10.32641/andespediatr.v93i6.3923

Andes Pediatr. 2022 Dec;93(6):826-831. doi: 10.32641/andespediatr.v93i6.4271.

ABSTRACT

Unfractionated heparin (UFH) is the most widely used anticoagulant in hospitalized patients. The therapeutic range (TR) was defined in adults according to the prolongation of the activated Partial Thromboplastin Time (aPTT). However, the recommendation is to maintain a therapeutic range with anti-factor Xa assay (antiFXa). As this technique is more complex to perform and less available, it is recommended to make local correlation curves of aPTT with antiFXa.

OBJECTIVE: to determine the correlation between the values of aPTT and antiFXa in patients treated with UFH.

PATIENTS AND METHOD: 52 patients between 2 days to 14 years of age hospitalized in the Pediatric Critical Patient Unit were recruited. They received treatment with UFH in continuous infusion for at least 24 hours. aPTT and antiFXa tests were performed according to the moment of anticoagulation. To evaluate the concordance of the levels of aPTT with those of antiFXa, the Kappa statistical coefficient of Landis and Koch was used.

RESULTS: 105 samples were collected from 52 patients. The overall concordance was 0.452 (moderate correlation). In patients aged < 1 month (n = 40), a considerable correlation was evident (r = 0.617); in those from 1 month to < 6 months (n = 18) and 6 months – < 12 months with aPTT < 120 seconds (n = 11), also showed a considerable correlation (r = 0.636 and 0.615, respec tively), while in those aged > 12 months (n = 37) with aPTT < 120 seconds, a moderate correlation was evident (r = 0.454).

CONCLUSION: In our population, there is a moderate correlation between the values of aPTT and antiFXa.

PMID:37906799 | DOI:10.32641/andespediatr.v93i6.4271

Andes Pediatr. 2022 Dec;93(6):807-814. doi: 10.32641/andespediatr.v93i6.3807.

ABSTRACT

Coronavirus 2 (SARS-CoV-2) infection has spread rapidly. In pediatrics, a condition similar to shock is described named multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). The mechanisms of cardiological involvement are not clear.

OBJECTIVE: To describe cardiological in volvement and inflammatory markers in hospitalized patients with MIS-C in a tertiary hospital.

PATIENTS AND METHOD: Observational, retrospective study in children under 15 years of age with MIS-C. Demographic, clinical, and laboratory variables were collected from an electronic plat form, including troponin, B-type natriuretic peptide (proBNP), ultrasound, and electrocardio gram. Patients with / without cardiological involvement (CCC / SCC) were compared. GraphPad QuickCalcs© 2018 Software was used for statistical analysis, considering p < 0.05.

RESULTS: Thir teen patients diagnosed with MIS-C, 9 males, median age 9.5 years. All presented with fever and abdominal pain, adding one or more of the following symptoms: vomiting, exanthema, diarrhea, altered mucous membranes and/or edema. Five patients had hemodynamic compromise, 9/13 were categorized as CCC. Troponins were elevated 4.1 times in CCC (p < 0.05), median ProBNP CCC 6940 pg/ml vs 921 pg/ml in SCC (p < 0.05), median Ferritin CCC 482 vs 154 ng/ml in SCC (p < 0.01), platelets CCC 106,000 vs SCC 207,000/mm3 (p < 0.05). Echocardiogram showed pe ricardial effusion (N = 6), mild systolic dysfunction (N = 4), moderate dysfunction (N = 1) and coronary alterations (N = 3). In the ECG, 3 patients presented transient repolarization disturbance and 1 first-degree atrioventricular block. None required support with extracorporeal membrane oxygenation, with no deaths.

CONCLUSION: cardiological involvement in hospitalized children with MIS-C is frequent. Our series showed nonspecific and transitory symptoms, and hemodynamic compromise which responded early to medical treatment, with a favorable evolution. The markers in CCC patients were troponin, ProBNP, ferritin, and thrombocytopenia. The most frequent ul trasound finding was pericardial effusion. The importance of both clinical and laboratory cardio logical evaluation in these patients is evident.

PMID:37906797 | DOI:10.32641/andespediatr.v93i6.3807

Rev Med Chil. 2023 Feb;151(1):32-41. doi: 10.4067/s0034-98872023000100032.

ABSTRACT

BACKGROUND: Long-term outcomes of Off-Pump Coronary Artery Bypass Grafting (OPCAB) as an alternative to the traditional Coronary Artery Bypass Grafting (CABG) technique with cardiopulmonary bypass (CPB) are not well defined.

AIM: To compare 10-year survival of isolated OPCAB versus CABG with CPB.

MATERIAL AND METHODS: Analysis of information obtained from databases, clinical records and surgical protocols of patients treated with isolated CABG between January 2006 and November 2008 at a Regional Hospital. Of 658 isolated CABG, 192 (29.2%) were OPCAB and 466 (79.9%) CPB. Propensity Score Matching (PSM) was performed to compare both groups. After PSM, two groups of 192 cases were obtained. Mortality data was obtained from the Chilean public identification service. Ten-year survival was calculated and compared with Kaplan-Meier and log-rank methods.

RESULTS: Follow-up data was obtained in all cases. No statistically significant differences were found when comparing 10-year survival between OPCAB versus CPB (78.6% and 80.2% respectively, p 0.720). There was also no statistical difference in cardiovascular death free survival (90.1% with CPB versus 89.1% OPCAB, p 0.737). Survival was comparable when analyzing subgroups with diabetes mellitus, left ventricular dysfunction or chronic kidney disease, among others.

CONCLUSIONS: In our series, OPBAB has a comparable 10-year survival with CABG with CPB.

PMID:37906744 | DOI:10.4067/s0034-98872023000100032

JCO Clin Cancer Inform. 2023 Sep;7:e2300132. doi: 10.1200/CCI.23.00132.

ABSTRACT

Waterfall plots have gained popularity as a visualization tool to present antitumor activity of treatments in oncology, especially for phase I and II trials. The typical waterfall plot in oncology is a bar plot with each bar representing the best percent tumor size reduction from baseline for a patient sorted in descending order along the x-axis. As new therapies are routinely developed in combination with standard of care or other investigational treatments, waterfall plot comparison between combination therapy and monotherapy may facilitate development decisions in addition to overall response rate or duration of response. However, waterfall plots are often assessed heuristically in practice with lack of statistical rigor. In this work, we examine the correspondence between the waterfall plot and the empirical cumulative distribution function. We demonstrate how to derive key summary statistics directly from the waterfall plot. Using real examples from published waterfall plots, we show how comparisons of waterfall plots can elucidate clinically meaningful information, such as treatment effect patterns in progression-free survival and overall survival.

PMID:37906725 | DOI:10.1200/CCI.23.00132

West Afr J Med. 2023 Oct 31;40(10):1086-1095.

ABSTRACT

INTRODUCTION: Various factors influence the expression of dental anxiety (DA) among patients. Knowledge of these factors may aid the management of mandibular third molar (M3) dis-impaction patients.

AIM: The study aimed to determine the predictive and relative factors of DA among Mandibular third molar (M3) dis-impaction patients at the Aminu Kano Teaching Hospital (AKTH), Kano, Nigeria.

METHODOLOGY: The study was a cross-sectional type conducted at the Oral Surgery clinic of AKTH, Kano among M3 dis-impaction patients between September 2016 and August 2017. Biodata and information on the past dental history of the participants were collected and recorded. The level of anxiety of participants was assessed with the Modified Dental Anxiety Scale (MDAS). Data were analyzed using Statistical Package for Social Sciences (SPSS) for windows (IBM SPSS statistic version 23). The significance level in the study was set at p ≤ 0.05.

RESULTS: One hundred and sixteen patients comprising 62(55.2%) males and 54(44.8%) females were recruited. The sample’s median age was 27 years and the majority of the participants were students (n=49,42.2%). The participants’ MDAS scores ranged from 5 to 22 with a median score of 11. Females (median MDAS score of 12.50) were significantly (p<0.0001) more anxious than males (median MDAS score of 9.00). Bivariate analysis showed statistically significant differences in DA of the categories of the following independent variables – gender (p<0.0001), ethnicity (p=0.041), occupational status (p=0.044), previous surgical extraction experience (p=0.006), previous bad dental treatment experience (p<0.0001) and history of postponement of dental treatment due to anxiety(p<0.0001). Binary logistic regression analysis with these variables as independent predictors of DA showed that only gender (p=0.013) and previous surgical extraction experience (p=0.042) had statistically significant odds of predicting dental anxiety among the patients. Females had significantly higher odds of being anxious than males [adjusted odds ratio (OR) = 4.180, 95% Confidence Interval (CI)=1.359 to 12.852] and patients with previous surgical extraction experience had higher odds of being anxious than those without surgical extraction experience [adjusted OR=3.65, 95% CI=1.02 to 13.03].

CONCLUSION: The predictors of DA in the study are female gender and previous surgical extraction experience. These and other DA-related factors such as patients’ occupation and previous bad dental treatment experiences should be considered preoperatively to identify and manage anxious M3 dis-impaction patients.

PMID:37906714

J Phys Chem A. 2023 Oct 31. doi: 10.1021/acs.jpca.3c05078. Online ahead of print.

ABSTRACT

In this study, mixed carbonyl and nitrous oxide complexes with Rh⁺ were studied by mass-selective infrared photodissociation spectroscopy in a molecular beam. The infrared spectra, recorded in the region of the CO and N₂O N═N stretches, were assigned and interpreted with the aid of simulated spectra of low-energy structural isomers. Clear evidence of an inner coordination shell of four ligands is observed. The observed vibrational structure can be understood on the basis of local mode vibrations in the two ligands. However, there is also evidence of multiple low-lying isomers and cooperative binding effects between the two ligands. In particular, σ donation from directly coordinated nitrous oxide ligands drives more classical carbonyl bonding than has been observed in pure carbonyl complexes. The observed fragmentation branching ratios following resonant infrared absorption are explained by simple statistical and energetic arguments, providing a contrast with those of equivalent Au⁺ complexes.

PMID:37906705 | DOI:10.1021/acs.jpca.3c05078

Epidemiol Health. 2023 Oct 24:e2023095. doi: 10.4178/epih.e2023095. Online ahead of print.

ABSTRACT

OBJECTIVES: Inhalation exposure to humidifier disinfectants has resulted to various types of health damages in Korea. To determine the epidemiological correlation necessary for presuming the legal causation, we aimed to develop a method to synthesize the entire evidence.

METHODS: Epidemiological and toxicological studies are systematically reviewed. Target health problems are selected by criteria such as frequent complaints of claimants. Relevant epidemiologic studies are reviewed and the risk of bias and confidence level of the total evidence are evaluated. Toxicological literature reviews are conducted on a line of evidence comprising hazard information, animal studies, and mechanistic studies. The confidence levels for evidence-based toxicological effects and source-to-outcome pathways are synthesized to classify the toxicological evidence levels for the causality between humidifier disinfectant exposure and health effects. Finally, the levels of epidemiological and toxicological evidence are synthesized.

RESULTS: Under the Special Act revised in 2020, if the history of exposure and the disease occurred/worsened after exposure were approved, and the epidemiological correlation between the exposure and disease was verified, the legal causation is presumed unless the company proves the evidence against it. The epidemiological correlation can be verified through epidemiological investigations, health monitoring, cohort investigations and toxicological studies. It is not simply as statistical correlation as understood in judicial precedents, but a general causation established by the evidence as a whole, i.e., through weight-of-the-evidence approach.

CONCLUSION: The weight-of-the-evidence approach differs from the conclusive single study approach and this systematic evidence integration can be used in presumption of causation.

PMID:37905312 | DOI:10.4178/epih.e2023095

Cureus. 2023 Sep 29;15(9):e46178. doi: 10.7759/cureus.46178. eCollection 2023 Sep.

ABSTRACT

Introduction It has been discovered that low levels of thiamine reserves in the body are related to diabetes mellitus (DM) because thiamine directly influences carbohydrate metabolism. Therefore, the purpose of this study was to assess several metabolic variables and blood thiamine levels in patients with type 1 and type 2 DM and compare them with those in a control group of healthy individuals. Methods This case-control study was conducted at multiple diabetic outpatient centers in Karachi. A total of 90 participants, who were divided into three groups, each containing 30 individuals, were chosen using a convenient non-probability sampling technique. Group A served as the control group and consisted of healthy, non-diabetic individuals. Groups B and C contained subjects with type 1 and type 2 DM, respectively. Descriptive analysis was reported as mean standard deviation, whereas gender and comorbidities were expressed as frequencies and percentages. The chi-square test and Pearson’s correlation coefficient were used to determine the associations of the variables with type 1 DM, type 2 DM, and controls. Results The study results revealed statistically significant differences between controls, type 1 and type 2 DM, in the means of blood glucose levels and all lipid profiles, such as glycated hemoglobin (HbA1c), fasting blood sugar (FBS), random blood sugar (RBS), serum thiamine, triglycerides (p < 0.001), high-density lipoprotein (HDL) (p = 0.014), and total cholesterol (p = 0.013). Furthermore, it was shown that among the control group, type 1 and type 2 DM, HbA1c, and FBS were insignificantly correlated with thiamine levels, whereas the HbA1c and FBS of the combined diabetic groups were significantly correlated with the thiamine level (r = 0.465, p < 0.001) and (r = 0.360, p = 0.005), respectively, where ‘r’ is the Pearson correlation coefficient. Additionally, HbA1c and FBS in the combined three groups were significantly correlated with the thiamine level (r = -0.626, p < 0.001) and (r = -0.561, p < 0.001), respectively. Conclusion This study concluded that patients with type 1 and type 2 DM had significantly higher levels of FBS, RBS, HbA1c, triglycerides, and total cholesterol than controls. Furthermore, both type 1 and type 2 DM patients’ serum thiamine and HDL levels were observed to be considerably lower than those of controls. Additionally, among both types of DM and controls, there was a strong correlation between FBS and HbA1c. Therefore, we recommend that serum thiamine levels be routinely monitored in diabetic patients, and thiamine supplementation should be considered to avoid complications, especially vascular complications of DM.

PMID:37905298 | PMC:PMC10613325 | DOI:10.7759/cureus.46178