Tag: nevin manimala

JAMA Cardiol. 2025 May 7. doi: 10.1001/jamacardio.2025.0945. Online ahead of print.

ABSTRACT

IMPORTANCE: Innate immunity, particularly neutrophil activation, plays a crucial role in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). The potential of calprotectin, a biomarker of neutrophil activation, as a mechanistically informed biomarker for ASCVD in an ethnically diverse population requires further investigation.

OBJECTIVE: To examine the prospective association between circulating calprotectin and ASCVD in a diverse, population-based cohort while also exploring calprotectin’s mechanistic contributions to ASCVD in vitro.

DESIGN, SETTING, AND PARTICIPANTS: Circulating calprotectin was measured in plasma collected from 2412 participants during phase 2 of the Dallas Heart Study, a multiethnic, population-based cohort study. The median follow-up after plasma collection was 8 years.

MAIN OUTCOMES AND MEASURES: Associations with future ASCVD events (defined as first nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or death from a cardiovascular cause) were assessed using Cox proportional hazards models, adjusted for known cardiovascular disease risk factors as well as high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT).

RESULTS: Higher calprotectin levels were associated with older age, male sex, Black race, hypertension, diabetes, and smoking history. Individuals with higher calprotectin had higher hemoglobin A1c, very low-density lipoprotein cholesterol, and triglycerides, and lower high-density lipoprotein cholesterol and cholesterol efflux capacity. Log-transformed calprotectin levels were associated with an increased risk of ASCVD events over 8 years (hazard ratio [HR], 1.98 per log increase [95% CI, 1.54-2.53]). This association remained statistically significant after adjusting for prior ASCVD and traditional risk factors (HR, 1.61 [95% CI, 1.22-2.13]) and hs-CRP, NT-proBNP, and hs-cTnT (HR, 1.43 [95% CI, 1.04-1.96]). Higher calprotectin also correlated with higher coronary artery calcium scores (P < .001). In vitro studies revealed that calprotectin impaired coronary endothelial integrity, diminished nitric oxide production, and fostered endothelial to mesenchymal transition, providing potential mechanisms for ASCVD progression.

CONCLUSIONS AND RELEVANCE: The findings suggest that calprotectin may serve as a mechanistically informed biomarker for ASCVD, independent of traditional and contemporary cardiovascular risk factors and biomarkers. However, its clinical utility warrants further evaluation.

PMID:40332890 | DOI:10.1001/jamacardio.2025.0945

Int J Mol Sci. 2025 Apr 19;26(8):3883. doi: 10.3390/ijms26083883.

ABSTRACT

The adaptation of the body when exposed to a lower-than-usual temperature is a challenge that involves neuro-endocrine-immune mechanisms and affects the pharmacokinetics and/or pharmacodynamics of drugs taken before or after cold exposure. The experiments presented in this study clearly show differences in the analgesic effect of an exogenously introduced model substance (C-terminal fragment of calcium-binding protein, spermatid-specific 1) before and after cold exposure compared to its effect at an ambient temperature. The model substance used for the experiments is an octapeptide, TDIFELLK, which was synthesized via standard solid-phase peptide synthesis. Preliminary studies proved TDIFELLK’s analgesic activity. The ANOVA analysis performed showed statistically significant differences in the pain thresholds, measured by a paw pressure test, in 109 rats distributed among 14 groups and subjected to cold exposure according to different set-ups. Cold exposure immediately after TDIFELLK administration appears to enhance its analgesic effect, while cold exposure before administration reduces the effect. In some of the set-ups, antagonists of the most significant for analgesia receptors, i.e., opioid, cannabinoid, and serotonergic, were also introduced. The results showed that cold exposure had a modulating influence on the effect of the exogenously administered substances. The modulating effect was manifested differently depending on whether the intake occurred before or after cold exposure. The results also showed that the interaction with individual mediator systems was also subjected to differences depending on intake occurring before and after cold exposure.

PMID:40332811 | DOI:10.3390/ijms26083883

Insects. 2025 Mar 26;16(4):346. doi: 10.3390/insects16040346.

ABSTRACT

After eight generations of laboratory selection with β-cypermethrin, a P. okadai strain was cultivated that displayed a 10.04-fold increase in resistance (RS) relative to the susceptible strain (SS), with an estimation of heritability (h²) of 0.34. Compared with the SS, the developmental duration of the eggs was significantly prolonged (p < 0.05); however, the pupal stage duration was shorter, with no statistically significant difference. Moreover, the levels of GSTs, CarEs, and CYP450 activity were notably higher in the RS than in the SS. In addition, the level of CarE and CYP450 activity in the RS was significantly higher in the midgut (MG), fat body (FB), and Malpighian tubules (MTs) compared to the SS; however, the GSTs showed no statistically significant difference in the MTs. These results suggest that P. okadai‘s resistance to β-cypermethrin could be selected rapidly and the decreases in the intrinsic rate of increase (r) observed in the RS are likely due to mutations in the detoxification enzyme genes under the strong selection pressure exerted by β-cypermethrin. The increased activity of GSTs, CarEs, and CYP450 was associated with β-cypermethrin resistance in the RS of P. okadai. The data reported herein provide a foundation for future studies on the mechanisms responsible for β-cypermethrin resistance in P. okadai.

PMID:40332797 | DOI:10.3390/insects16040346

Int J Mol Sci. 2025 Apr 21;26(8):3904. doi: 10.3390/ijms26083904.

ABSTRACT

Severe immune effector cell-associated neurotoxicity syndrome (ICANS) occurs in about 30% of all patients with large B-cell lymphoma (LBCL) who are treated with axicabtagene ciloleucel (axi-cel). There are currently limited treatment strategies other than the standard corticosteroids, and it is essential to find additional therapies to manage severe ICANS. We conducted a retrospective study of neurologic outcomes among patients who received axi-cel for LBCL from May 2015 to February 2019. We identified patients who developed severe ICANS and were treated with glucocorticoids followed by intravenous immunoglobulin (IVIG) (n = 9) or glucocorticoids alone (n = 10). There was no statistically significant difference in the time to resolution (TTR) of severe ICANS between groups; however, patients in the IVIG had more severe grades of ICANS with a lower performance status at baseline. The cumulative steroid days were 11.2 in the IVIG arm and 13.5 in the glucocorticoids-only arm. The use of IVIG for severe ICANS after axi-cel therapy was tolerable and safe and is generally recommended in the CAR-T setting in patients with hypogammaglobinemia. The use of IVIG as a potential therapeutic agent for severe ICANS can be further explored in future prospective studies.

PMID:40332772 | DOI:10.3390/ijms26083904

J Forensic Odontostomatol. 2025 Apr 30;43(1):19-32. doi: 10.5281/zenodo.15044914.

ABSTRACT

Sexual dimorphism is an important biological factor for sex estimation from skeletal remains in medicolegal identification. This study aimed to determine using a discriminant function analysis, whether specific maxillary linear and angular measurements performed in cone-beam computed tomography (CBCT) images may be useful to determine the sex in a Colombian population. The sample consisted of 212 CBCT scans acquired from 86 males and 126 females. The protocol included the assessment of 23 parameters, of which 16 were bilateral and seven were non-bilateral. An intra-observer variability test was performed to ensure data reliability and unpaired t tests were applied to determine between-group differences. Significant predictor variables were subjected to univariate and multivariate discriminant function analyses. A total of five non-bilateral and 14 bilateral measures were statistically significant. Univariate discriminant analyses produced a mean percentage of correct prediction after cross-validation ranging from 55.20% to 72.60% for non-bilateral and from 58.70% to 73.10% for bilateral maxillary variables. The association of variables in the multivariate models increased the percentages of correct sex prediction even after cross-validation up to 77.80% for non-bilateral and up to 77.40% for bilateral maxillary measurements. It was concluded that CBCT measurement of maxillary bone parameters may be applied as a complementary technique to discriminate the sex from human remains through discriminant function analysis methods in the Colombian population.

PMID:40332765 | DOI:10.5281/zenodo.15044914

J Forensic Odontostomatol. 2025 Apr 30;43(1):11-18. doi: 10.5281/zenodo.15031141.

ABSTRACT

BACKGROUND: Despite the surging crime rates and diverse operating methods, identifying the perpetrators and suspects is challenging. Incorporating forensic odontology has expanded the scope of forensics. Over the years, saliva has become the hallmark of forensics. This study aimed to develop a scale for assessing the knowledge and awareness about the role of saliva in forensic odontology. The scale was developed sequentially according to the qualitative research methodology: formation of a conceptual framework, systematic development of an item pool and refinement of an item pool (focus group discussion, cognitive interviewing and pretesting). Then, the validity and reliability of the scale were tested.

RESULTS: A conceptual framework was developed based on five constructs, which included forensic sciences, forensic odontology, crime investigations, salivary analysis and forensic genetics. A pool of 28 items was designed based on existing literature and refined through a focus group discussion involving the target audience and expert panellists. After validation by cognitive interview and pretesting, the scale was condensed into a pool of 23 items. Statistical analysis revealed a Cronbach’s alpha of 0.8 (good reliability) and kappa value of 0.79, indicating a strong level of agreement.

CONCLUSION: The Salivary Analysis for Forensic Evidence scale is a valid and reliable tool that consolidates all possible constructs involved in assessing the role of saliva in forensic odontology.

PMID:40332764 | DOI:10.5281/zenodo.15031141

J Forensic Odontostomatol. 2025 Apr 30;43(1):2-10. doi: 10.5281/zenodo.15046145.

ABSTRACT

In forensics, dental age estimation is crucial, and literature has many methods for estimating dental age. London Atlas of Human Tooth Development and eruption method was developed on British and Bangladeshi populations in 2010, and there are likely to be differences between other populations. Malaysian children have not yet been extensively tested for the method’s applicability despite its universal acceptance and reliability. This research aimed to test the applicability of The London Atlas of human tooth development and eruption in children of the Malaysian population aged 4 to 16.99 years old. The study sample included 523 panoramic radiographs of healthy patients who had attended the Dental Paediatrics Department Hospital Tunku Azizah, Malaysia, between May 2019 and December 2019. The intra- and inter-observer errors were analysed by taking 53 radiographs and evaluating them over 14 days using the interclass correlation and Cohen’s Kappa index. A paired t-test was used to compare chronological and estimated age ANOVA F-tests were used to establish if the difference is statistically significant between chronological and estimated age. The range of age estimation fell within a year due to the mean absolute difference of 0.60 years. The mean age for estimated age was 9.31±3.18 for the overall sample, 9.06±3.09 for males, and 9.60±3.27 for females. Paired t-test analysis showed the mean difference between chronological and estimated age of -0.0365 and was not statistically significant (p=0.240). The result also showed no statistically significant difference between the sexes. The difference between the chronological and estimated age was underestimated within minimal range, 0.002 years in males and 0.08 years in females. The London Atlas of human tooth development and eruption showed high accuracy in Malaysian children.

PMID:40332763 | DOI:10.5281/zenodo.15046145

Obes Surg. 2025 May 7. doi: 10.1007/s11695-025-07886-6. Online ahead of print.

ABSTRACT

BACKGROUND: Conversional bariatric surgeries (CBS) are performed using laparoscopic and robotic techniques, but comprehensive data comparing these approaches remains scarce.

OBJECTIVE: To compare the indications and outcomes of laparoscopic versus robotic CBS.

METHODS: The MBSAQIP database was retrospectively analyzed from 2020 to 2022, comparing laparoscopic and robotic CBS. Primary outcomes were 30-day serious complications and mortality.

RESULTS: Of 72,189 CBS procedures, 75.4% were laparoscopic and 24.6% robotic. Mean age and BMI were similar between groups. The most common indications for both approaches were reflux, weight regain, and inadequate weight loss, with reflux being more prevalent in robotic CBS (38.3% vs 33.2%). Sleeve-to-bypass was the most common procedure in both groups (35.8% laparoscopic, 44.2% robotic). Robotic CBS had longer mean operative times (165.4 vs 121.7 min, p < 0.001) and slightly longer hospital stays (1.7 vs 1.6 days, p < 0.001). The rate of serious complications was slightly higher for robotic CBS, though not statistically significant (6.5% vs 6.1%, p = 0.08). Robotic CBS had higher rates of leak (0.9% vs 0.7%, p = 0.071), reoperation (2.8% vs 2.6%, p = 0.138), and readmission (6.7% vs 5.4%, p < 0.001). Mortality rates were similar (0.1% for both, p = 0.942).

CONCLUSIONS: Both laparoscopic and robotic CBS show similar safety profiles with comparable mortality rates. However, robotic CBS was associated with longer operative times, slightly longer hospital stays, and higher readmission rates. These findings suggest that the choice between approaches should consider individual patient factors and institutional expertise.

PMID:40332741 | DOI:10.1007/s11695-025-07886-6

Curr Med Sci. 2025 May 7. doi: 10.1007/s11596-025-00056-w. Online ahead of print.

ABSTRACT

OBJECTIVE: The geriatric nutritional risk index (GNRI) is widely used for nutritional assessment. Poor nutritional status is associated with complications and poor survival in cirrhotic patients. We aimed to investigate the value of the GNRI in predicting outcomes in cirrhotic patients.

METHODS: This retrospective study included 420 cirrhotic patients from three centers between 2013 and 2017. Patients were divided into the high GNRI group (≥ 92) and low GNRI group (< 92). Overall survival (OS) in the two groups was evaluated via the Kaplan‒Meier method. Cox proportional hazards model was used to estimate the value of the GNRI in predicting outcomes. Restricted cubic spline model was used to intuitively display the dose‒response associations between the GNRI and OS. A nomogram was constructed to predict OS.

RESULTS: During the 2-year follow-up period, 58 (13.81%) patients died, and 262 (62.38%) patients experienced episodes of complications. Compared with patients in the low GNRI group, those in the high GNRI group had lower mortality rates (18.73% vs. 5.23%, P < 0.001). The GNRI was an independent predictor of OS (hazard ratio [HR] = 0.958, 95% confidence interval [CI] 0.929-0.988, P = 0.007). The GNRI was associated with the cumulative incidence of ascites (HR = 0. 954, 95% CI 0.940-0.969, P < 0.001), spontaneous bacterial peritonitis (HR = 0.928, 95% CI 0.891-0.966, P < 0.001), hepatic encephalopathy (HE; HR = 0.944, 95% CI 0.920-0.968, P < 0.001), and hepatorenal syndrome (HRS) (HR = 0.916, 95% CI 0.861-0.974, P = 0.005). Furthermore, 6 independent factors were included to construct the nomogram for OS prediction, including GNRI, age, total bilirubin, serum sodium, history of HE and HRS. The C statistics of our model were 0.83 (95% CI 0.75-0.90) and 0.80 (95% CI 0.73-0.86) at 1 and 2 years, respectively. Patients whose GNRI score decreased within 3 and 6 months had poorer outcomes (P < 0.001).

CONCLUSIONS: The lower GNRI score was associated with the higher cumulative incidence of complications and poorer OS of cirrhotic patients. The GNRI could be a helpful tool for assessing nutritional status and prognosis of these patients.

PMID:40332738 | DOI:10.1007/s11596-025-00056-w

Curr Med Sci. 2025 May 7. doi: 10.1007/s11596-025-00043-1. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate the neuroprotective effects of cholecalciferol cholesterol emulsion (CCE), a vitamin D (VD) precursor, in a murine model of acute cerebral infarction (ACI) and to elucidate the role of the Nrf2 signaling pathway in mediating these effects.

METHODS: Forty C57BL/6J mice (male and female) were divided into five groups (n = 10 per group): control, control + CCE, ACI, ACI + CCE, and ACI + CCE + ML385 (an Nrf2 inhibitor). ACI was induced by middle cerebral artery occlusion (MCAO). CCE was administered for three weeks prior to ACI induction, and ML385 was administered intravenously to inhibit Nrf2. Neurological function, brain edema, and infarct size, as well as inflammatory and apoptotic marker levels, were assessed post-ACI. Statistical analyses were conducted via one-way ANOVA and Student’s t test, with P < 0.05 considered significant.

RESULTS: Compared to ACI group, CCE significantly reduced neurological deficits, brain edema, and infarct size (P < 0.01). The ACI + CCE group presented improved short-term memory retention, as evidenced by shorter avoidance latency in shuttle avoidance tests (P < 0.01). CCE administration attenuated the expression of inflammatory markers (IL-6, MIF, Lp-PLA2) while increasing IL-10 levels (P < 0.001). Furthermore, CCE increased Nrf2 and HO-1 expression and reduced apoptosis by decreasing the Bax/Bcl-2 ratio in brain tissue (P < 0.001). ML385 abolished these neuroprotective effects, confirming the role of the Nrf2 pathway in mediating the benefits of VD.

CONCLUSION: VD, via VD receptor-mediated activation of the Nrf2/HO-1 pathway, reduces inflammation, apoptosis, and neurological damage following ACI. These findings support the therapeutic potential of VD in the treatment of ischemic stroke and highlight the importance of Nrf2 in mediating these effects.

PMID:40332737 | DOI:10.1007/s11596-025-00043-1