Category: Nevin Manimala

Iran J Immunol. 2024 Dec 3;21(4). doi: 10.22034/iji.2024.100817.2710. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical features of SARS-CoV-2 infection vary, ranging from asymptomatic cases to pneumonia, and other serious complications. Some populations have been observed to be at higher risk for severe disease and death compared to other ethnical groups.

OBJECTIVE: To evaluate two parameters of the innate immune system, that play a significant role in viral immunity.

METHODS: In samples of peripheral blood from sixteen patients with severe COVID-19, ten with asymptomatic to mild illness, and fifteen healthy subjects, the percentage of NK and NKT cells, the expression of different NK cell receptors and the blood levels of pro-inflammatory cytokines were tested.

RESULTS: We observed that patients with severe COVID-19 showed significantly lower frequencies of both CD56dim and CD56bright NK cells compared to patients with mild illness or healthy controls. Furthermore, patients with severe manifestation of COVID-19 exhibited an aberrant expression of the natural cytotoxicity receptors NKp30, NKp44 and NKp46. Similarly, NK cells from these patients showed statistically significant differences in the expression of various killer immunoglobulin-like receptors (KIRs) in the two main cell subsets (CD56bright, CD56dim) compared to controls or patients with mild disease. Moreover, patients with severe illness displayed decreased frequency of NKT cells (defined as CD3+CD56+) and elevated blood levels of the cytokines IL-6 and IL-8.

CONCLUSION: This study suggests that the abnormal features of NK and NKT cells observed in patients with severe SARS-CoV-2 infection may play an important role in the outcome of this infectious disease in various population groups.

PMID:39624905 | DOI:10.22034/iji.2024.100817.2710

Hip Int. 2024 Dec 3:11207000241302471. doi: 10.1177/11207000241302471. Online ahead of print.

ABSTRACT

INTRODUCTION: Various techniques have been described for restoring leg length and offset during total hip arthroplasty (THA). We herein describe a novel “Quartered Head Technique” (QHT) involving a series of femoral osteotomies.

METHODS: 124 hips were included in the analysis. An anterolateral approach was used in all cases. Leg length, and offset were assessed intraoperatively and reproduced using the QHT. A leg-length discrepancy (LLD) of <6 mm was chosen as acceptable based on previously published literature. Postoperative pelvic radiographs were assessed by two independent observers to ensure inter-observer reliability.

RESULTS: The mean absolute postoperative difference in leg length from the contralateral leg was +3.58 mm. 84% of patients had LLD within ±6 mm of the contralateral limb. Mean absolute postoperative difference in offset from the contralateral leg was +3.88 mm. 90% of patients were within ±6 mm offset of the contralateral limb. There was no statistical difference noted between observer measurement.

CONCLUSIONS: The QHT provides a simple, inexpensive, yet effective method of maintaining femoral leg length and offset during total hip arthroplasty.

PMID:39624855 | DOI:10.1177/11207000241302471

Front Pharmacol. 2024 Nov 18;15:1505926. doi: 10.3389/fphar.2024.1505926. eCollection 2024.

ABSTRACT

BACKGROUND: Epimedium total flavonoids (EF) have been recommended to be one of the effective components in Traditional Chinese Medicine (TCM) for the treatment of primary osteoporosis (POP) in China. Due to the lack of evidence-based medical evidence on the efficacy and safety of EF for the treatment of POP, the current systematic review and meta-analysis was carried out aimed at evaluating the curative effects and safety profile of EF treatment for POP in order to provide decision making references for clinical research.

METHODS: The PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, Wanfang, and VIP databases were searched from the date of inception to 11 August 2024. The outcomes of effectiveness and safety of included studies were collected to conduct meta-analysis or systematic review.

RESULTS: A total of 6 RCTs were included in this study, involving 838 participants. Overall, our results revealed that the experimental group (EG) had comparable results of efficacy to the control group (CG). The lumbar vertebra bone mineral density (BMD) was statistically different compared to the CG (MD = 0.03; 95% CI: 0.01, 0.04; p = 0.0003), but the clinical significance deserved consideration because the 95% CI nearly crossed the invalid line. The femoral neck BMD was neither statistically different nor clinically different between two groups (MD = 0.00; 95% CI: 0.01, 0.02; p = 0.67). The total complication rates were comparable among the two groups (RR = 0.68; 95% CI: 0.39, 1,19; p = 0.18). The quality of the evidence of the present study was judged as moderate and low based on the GRADE analysis.

CONCLUSION: EF treatment exhibited good curative effects and safety. The result was comparable to the CG, including other Chinese patent medicines and calcium and vitamin D supplements. The EF treatment was proved to be a reliable alternative option for POP.

PMID:39624844 | PMC:PMC11608984 | DOI:10.3389/fphar.2024.1505926

Front Pharmacol. 2024 Nov 18;15:1488367. doi: 10.3389/fphar.2024.1488367. eCollection 2024.

ABSTRACT

INTRODUCTION: Arylamine N-acetyltransferase 2 (NAT2) expresses a well-defined genetic polymorphism in humans that modifies drug and xenobiotic metabolism. Recent studies and genome wide association studies have reported that genetic variants of NAT2 are associated with differential risks of developing dyslipidemia and cardiometabolic disorders, suggesting a previously unrecognized role of NAT2 in pathophysiology of metabolic disorders. In support of this notion, we recently showed that human NAT2 expression is differentially regulated by glucose and insulin. Moreover, our in silico analysis showed that NAT2 is co-expressed with nuclear receptors enriched in the liver, e.g., NR1H4 (FXR) and NR1I2 (PXR), that have been previously implicated in regulation of hepatic glucose and lipid homeostasis. Identification of transcriptional regulator(s) of human NAT2 would aid in understanding novel functions that it may play in the liver. Thus, the present study was designed to investigate if NAT2 is transcriptionally regulated by hepatic nuclear receptors.

METHODS: To test this, we treated cryopreserved human hepatocytes with agonists towards four different hepatic transcription factors/nuclear hormone receptors, namely FXR (NR1H4), PXR (NR1I2), LXR (NR1H3), and PPARα (PPARA), and measured their effects on the level of NAT2 mRNA.

RESULTS: While the treatment with a FXR, PXR, or LXR agonist (i.e., GW-4064, SR-12813, or GW-3965) significantly induced their respective target genes, treatment with these agonists did not significantly alter the transcript level of NAT2 in human hepatocytes. PPARα agonist, GW-7647, treatment resulted in a statistically significant decrease in the NAT2 transcript level. However, its magnitude was marginal.

CONCLUSION: In summary, hepatic nuclear receptors we examined in the present study (FXR, PXR, LXR, and PPARα) did not significantly alter NAT2 expression in cryopreserved human hepatocytes. Additional studies are needed to identify transcriptional regulators of hepatic NAT2 expression.

PMID:39624836 | PMC:PMC11608957 | DOI:10.3389/fphar.2024.1488367

Front Endocrinol (Lausanne). 2024 Nov 18;15:1333881. doi: 10.3389/fendo.2024.1333881. eCollection 2024.

ABSTRACT

OBJECTIVE: The aim of this study was to assess the predictive capabilities of a radiomics signature obtained from arterial spin labeling (ASL) imaging in forecasting and detecting stages of kidney damage in patients with diabetes mellitus (DM), as well as to analyze the correlation between texture feature parameters and biological clinical indicators. Additionally, this study seeks to identify the imaging risk factors associated with early renal injury in diabetic patients, with the ultimate goal of offering novel insights for predicting and diagnosing early renal injury and its progression in patients with DM.

MATERIALS AND METHODS: In total, 42 healthy volunteers (Group A); 68 individuals with diabetes (Group B) who exhibited microalbuminuria, defined by a urinary albumin-to-creatinine ratio (ACR)< 30 mg/g and an estimated glomerular filtration rate (eGFR) within the range of 60-120 mL/min/1.73m²; and 53 patients with diabetic nephropathy (Group C) were included in the study. ASL using magnetic resonance imaging (MRI) at 3.0T was conducted. The radiologist manually delineated regions of interest (ROIs) on the ASL maps of both the right and left kidney cortex. Texture features from the ROIs were extracted utilizing MaZda software. Feature selection was performed utilizing a range of methods, such as the Fisher coefficient, mutual information (MI), probability of classification error, and average correlation coefficient (POE + ACC). A radiomics model was developed to detect early diabetic renal injury, extract imaging risk factors associated with early diabetic renal injury, and examine the relationship between significant texture feature parameters and biological clinical indicators. Patients with DM and kidney injury were followed prospectively. The study utilized seven machine learning algorithms to develop a detective radiomics model and a comprehensive predictive model for assessing the progression of kidney damage in patients with DM. The diagnostic efficacy of the models in detecting variations in diabetic kidney damage over time was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Empower (R) was used to establish a correlation between clinical biological indicators and texture feature metrics. Statistical analysis was conducted using R, Python, MedCalc 15.8, and GraphPad Prism 8.

RESULTS: A total of 367 texture features were extracted from the ROIs in the kidneys and refined based on selection criteria using MaZda software across groups A, B, and C. The renal blood flow (RBF) values of the renal cortex in groups A, B, and C exhibited a decreasing trend, with values of 256.458 ± 54.256 mL/100g/min, 213.846 ± 52.109 mL/100g/min, and 170.204 ± 34.992 mL/100g/min, respectively. There was a positive correlation between kidney RBF and eGFR (r = 0.439, P<0.001). The negative correlation between RBF and various clinical parameters including urinary albumin-to-creatinine ratio (UACR), body mass index (BMI), diastolic blood pressure (DBP), blood urea nitrogen (BUN), and serum creatinine (SCr) was investigated. Through the use of a least absolute shrinkage and selection operator (LASSO) regression model, the study identified the eight most significant texture features and biological indicators, namely GeoY, GeoRf, GeoRff, GeoRh, GeoW8, GeoW12, S (0, 4) Entropy, and S (5, -5) Entropy. Spearman correlation analysis revealed associations between imaging markers in early diabetic patients with kidney damage and factors such as age, systolic blood pressure (SBP), Alanine Transaminase (ALT), Aspartate Amino Transferase (AST) albumin, uric acid (UA), microalbuminuria (UMA), UACR, 24h urinary protein, fasting blood glucose (FBG), two hours postprandial blood glucose (P2BG), and HbA1c. The study utilized ASL imaging as a detection model to identify renal injury in patients with DM across different stages, achieving a sensitivity of 85.1%, specificity of 65.5%, and an AUC of 0.865. Additionally, a comprehensive prediction model combining imaging labels and biological indicators, with the naive Bayes machine learning algorithm as the best model, demonstrated an AUC of 0.734, accuracy of 0.74, and precision of 0.43.

CONCLUSION: ASL imaging sequences demonstrated the ability to accurately detect alterations in kidney function and blood flow in patients with DM. Strong associations were observed between renal blood flow values in ASL imaging and established clinical biomarkers. These values show promise in detecting early microstructural changes in the kidneys of diabetic patients. Utilizing image markers in conjunction with clinical indicators was effective in identifying early renal dysfunction and its progression in individuals with DM. Furthermore, the integration of imaging texture feature parameters with clinical biomarkers holds significant potential for predicting early renal damage and its progression in patients with diabetes.

PMID:39624821 | PMC:PMC11608948 | DOI:10.3389/fendo.2024.1333881

Front Endocrinol (Lausanne). 2024 Nov 18;15:1501818. doi: 10.3389/fendo.2024.1501818. eCollection 2024.

ABSTRACT

PURPOSE: here is a general consensus that an inverse relationship exists between vitamin D status and body mass index (BMI) in overweight and obese individuals, leading to the hypothesis that vitamin D deficiency may contribute to the development of unfavorable metabolic phenotypes. However, evidence from non-obese adults remains limited. This study measured energy metabolism in non-obese adults using a metabolic chamber and explored its association with vitamin D status.

METHODS: Sixty-nine healthy adults (mean age = 22.8 years, mean BMI = 20.7 kg/m²) participated in this cross-sectional study. Participants were categorized into vitamin D-deficient, insufficient, and sufficient groups based on the Chinese classification for total 25(OH)D levels (WS/T 677-2020). They performed typical daily activities in a metabolic chamber, where their baseline lipid profile, 24-hour energy expenditure, and substrate oxidation were measured.

RESULTS: A two-way ANOVA (seasonality × 25(OH)D) revealed no statistically significant differences in total energy expenditure, resting energy expenditure, sleeping energy expenditure, walking energy expenditure, carbohydrate oxidation rate, or fat oxidation rate among the three groups (p > 0.05). These results remained consistent even after adjusting for fat-free mass. Although statistically significant correlations were found between 25(OH)D status and certain lipid profile markers (i.e., total cholesterol, high-density lipoprotein, and free fatty acid) (p < 0.05), these correlations were weak, with Pearson’s correlation coefficients below 0.3.

CONCLUSIONS: Total 25(OH)D status does not affect energy metabolism in young, healthy, non-obese adults. Along with existing evidence, this suggests that low 25(OH)D status is more likely a consequence of unfavorable metabolic phenotypes rather than a contributing factor.

CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn, identifier ChiCTR-IIR-17010604.

PMID:39624819 | PMC:PMC11608976 | DOI:10.3389/fendo.2024.1501818

Front Endocrinol (Lausanne). 2024 Nov 18;15:1461103. doi: 10.3389/fendo.2024.1461103. eCollection 2024.

ABSTRACT

INTRODUCTION: Turner syndrome (TS) is associated with significant neuropsychological challenges, and screening is recommended at key transition stages. Our goal was to describe the institutional experience of formal neuropsychological assessments in TS and assess differences by karyotype.

METHODS: Data were abstracted by retrospective chart review of completed assessments between January 1, 2019, and October 31, 2022, referred from the newly established multidisciplinary clinic, and descriptive statistical analyses were presented (SAS V9.4).

RESULTS: Of 114 patients, 38 (33%) had completed neuropsychological assessment at a median age of 11.3 years (IQR 6.5-14.9). Median full-scale IQ (FSIQ) was lower in those with a 45,X karyotype compared with other karyotypes (p = 0.027) but did not meet statistical significance at the adjusted significance level for multiple comparisons. Lower median non-verbal IQ [performance intelligence quotient (PIQ)] relative to verbal IQ (VIQ) was observed. Diagnoses of attention-deficit hyperactivity disorder (ADHD) (26%) and anxiety disorder (26%) were common followed by specific learning disorder (mathematics; 18%) and autism spectrum disorder (16%).

DISCUSSION: The prevalence of neuropsychological abnormalities in our diverse clinic underscores the importance of early and routine neuropsychological testing in TS.

PMID:39624818 | PMC:PMC11608949 | DOI:10.3389/fendo.2024.1461103

Front Endocrinol (Lausanne). 2024 Nov 18;15:1461865. doi: 10.3389/fendo.2024.1461865. eCollection 2024.

ABSTRACT

OBJECTIVE: This study aimed to assess the viability of a multivariate regression model utilizing ultrasound findings and serum markers for predicting thyroid cancer metastasis.

METHODS: A retrospective analysis of 98 thyroid patients admitted from January 2022 to October 2022 was conducted to categorize them into a metastasis group (n=20) and a non-metastasis group (n=78) based on postoperative pathological results. Both groups underwent ultrasound examination and serum marker testing. Correlative analysis was performed to explore the association between various indicators and thyroid cancer metastasis. A multivariate regression model was developed, and receiver operating characteristic (ROC) curves were used to assess the predictive value of ultrasound findings, serum markers, and their combination for thyroid cancer metastasis.

RESULTS: Statistically significant differences were found in the levels of ultrasound findings and serum markers between the two groups. Nodule boundaries, presence or absence of halos, margins, lobulation, capsular invasion, surface smoothness, nodule aspect ratio, uric acid, total cholesterol, triglyceride, and LDL cholesterol levels were predictors of metastasis in thyroid cancer. The AUC value of 0.950 for the prediction of thyroid cancer metastasis by ultrasound signs combined with serologic indicators was significantly higher than 0.728 and 0.711 predicted by ultrasound signs or serologic indicators alone.

CONCLUSION: The multivariate regression model incorporating ultrasound findings and serum markers enhances the predictive accuracy for thyroid cancer metastasis, offering essential guidance for early prediction and intervention in a clinical setting.

PMID:39624817 | PMC:PMC11608942 | DOI:10.3389/fendo.2024.1461865

Cureus. 2024 Dec 1;16(12):e74888. doi: 10.7759/cureus.74888. eCollection 2024 Dec.

ABSTRACT

Introduction Mind The Bleep (MTB) is an online medical education organisation run by United Kingdom-based resident doctors. It represents one of a number of free-open access online medical resources (FOAMed) that have increased in popularity, especially since the COVID-19 pandemic. The surgical team of MTB works to produce high-quality surgical educational resources aimed at early postgraduate doctors. This paper provides an appraisal of the teams’ current methods of teaching and the learning points identified from these. Methods This was a retrospective mixed-method review analysing quantitative and qualitative data sources including website analytics and feedback surveys. Wilcoxon signed-rank tests were used to identify significant differences between pre- and post-session confidence levels in the subject matter. Results A total of 22 online targeted education programmes, with a total of 140 webinars were completed between November 2021 and August 2024. The total live viewership was 6733 participants with a mean of 48.1 per webinar. The total attendance including live and watched later was 10221 participants, with a mean of 73 total viewers per webinar. Of the total viewers, 4714 provided feedback (46.1%). Across all webinar series, we identified a statistically significant increase in participant-rated confidence (p<0.05). Discussion Our ability to produce consistent high-quality content is due to leveraging a near-peer teaching model and recruiting resident doctors as teachers. This method ensures cognitive congruence between participant and educator and provides doctors an opportunity to gain teaching experience. Our social media advertising has ensured wide reach. To the best of our knowledge, we provide the first large-scale breakdown of the work done by an online surgical education organisation. Limitations include a low feedback rate and feedback limited to Kirkpatrick type 1 learner reaction.

PMID:39624814 | PMC:PMC11608416 | DOI:10.7759/cureus.74888

Cureus. 2024 Dec 2;16(12):e74990. doi: 10.7759/cureus.74990. eCollection 2024 Dec.

ABSTRACT

Background The use of automatic external defibrillators (AEDs) by lay rescuers can reduce the time to defibrillation and improve survival in out-of-hospital cardiac arrest (OHCA). AEDs use voice prompts to guide users through the defibrillation process, creating a potential barrier for deaf and hard-of-hearing (HoH) individuals. The objective of this study is to assess familiarity with and concerns regarding AED use among members of these communities. Methods A 19-question Qualtrics survey was distributed to adults in the United States who self-identified as deaf or HoH. The questions included seven demographics, eight yes/no/unsure, three Likert scales, and one multiple-response question. Quantitative analysis was performed using 95% confidence intervals to compare familiarity with and concerns about AED use among deaf, HoH, and combined groups of respondents. Results Of the responses, 500 met the inclusion criteria; 130 (26%) self-identified as deaf, and 370 (74%) self-identified as HoH. Around 460 (92%) were in the 18-40 age group. AED recognition was high among both deaf (90.77%) and HoH (84.59%) respondents, though deaf respondents were less likely than HoH respondents to have seen an AED in a public place (p=0.03) or know how to safely use one (p=0.001). In both the deaf and HoH groups, the top concern regarding AED use was that AEDs were too technical or complicated (61.86% and 56.8%). Of all respondents, 36.4% reported that AEDs were not user-friendly (p=0.034). All participants identified some concerns regarding AED use in emergencies. In addition, 56.15% of deaf and 39.19% of HoH respondents were concerned that AED use is potentially dangerous (p<0.001). There was no statistically significant difference between the two groups in knowing when to use an AED or where to find more information about AEDs. Conclusion Deaf and HoH people have specific concerns about AEDs, including the safety and complexity of operating an AED and the accessibility (user-friendliness). In this study, the deaf population is less familiar with using an AED than the HoH population. Possible interventions to address concerns of the deaf and HoH communities include AED training given in American Sign Language (ASL) and updating AED designs with improved visual and non-verbal directions.

PMID:39624811 | PMC:PMC11611321 | DOI:10.7759/cureus.74990