Tag: pubmed

Elife. 2024 Dec 18;13:RP97709. doi: 10.7554/eLife.97709.

ABSTRACT

The mis-folding and aggregation of intrinsically disordered proteins (IDPs) such as α-synuclein (αS) underlie the pathogenesis of various neurodegenerative disorders. However, targeting αS with small molecules faces challenges due to the lack of defined ligand-binding pockets in its disordered structure. Here, we implement a deep artificial neural network-based machine learning approach, which is able to statistically distinguish the fuzzy ensemble of conformational substates of αS in neat water from those in aqueous fasudil (small molecule of interest) solution. In particular, the presence of fasudil in the solvent either modulates pre-existing states of αS or gives rise to new conformational states of αS, akin to an ensemble-expansion mechanism. The ensembles display strong conformation-dependence in residue-wise interaction with the small molecule. A thermodynamic analysis indicates that small-molecule modulates the structural repertoire of αS by tuning protein backbone entropy, however entropy of the water remains unperturbed. Together, this study sheds light on the intricate interplay between small molecules and IDPs, offering insights into entropic modulation and ensemble expansion as key biophysical mechanisms driving potential therapeutics.

PMID:39693390 | DOI:10.7554/eLife.97709

J Gerontol A Biol Sci Med Sci. 2024 Dec 18:glae293. doi: 10.1093/gerona/glae293. Online ahead of print.

ABSTRACT

The population of older adults is exponentially expanding. Alongside aging comes the onset of chronic disease, decline of functional capacity, and reduced quality of life. Thus, this population increase will stress the capacity and financial viability of health and long-term care systems. Developing pre-clinical models for age-related functional decline is imperative to advancing therapies that extend healthspan and prolong independence. Previously in a cross-sectional study, we established a powerful composite scoring system we termed CFAB (comprehensive functional assessment battery). CFAB measures physical function and exercise capacity using well-validated determinants to measure overall motor function, fore-limb strength, four-limb strength/endurance, aerobic capacity, and volitional exercise/activity rate. In the current work, we used CFAB to track cohorts of male and female C57BL/6 mice over the lifespan (measuring CFAB at 6, 12, 18, 24, and 28 months of age). Overall, we found statistically significantly declining function as the mice aged, with some differences between males and females in trajectory and slope. We also determined that body mass changes presented differently between sexes, and tracked body composition (fat percentage, using magnetic resonance imagery) in females. In a subset of mice, we tracked in vivo contractile physiology noting declines in plantar flexor maximum isometric torque. In summary, our data suggest that males and females declined at different rates. We confirmed the efficacy of CFAB to track longitudinal changes in exercise capacity and physical fitness in both males and females, further validating the system to track age-related functional decline.

PMID:39693388 | DOI:10.1093/gerona/glae293

J Sports Sci. 2024 Dec 17:1-9. doi: 10.1080/02640414.2024.2440676. Online ahead of print.

ABSTRACT

The aim was to estimate national temporal trends in muscular fitness for French youth between 1999 and 2023. Data were obtained from five cross-sectional studies on 53,314 children and adolescents (age range: 6-16 years). Lower- and upper-body strength were assessed by standing broad jump (SBJ) and handgrip strength (HGS). BMI z-scores (BMIz) were calculated using WHO growth curves. We found a statistically significant negligible decline in SBJ performance (standardised effect size (ES) trend per decade [95%CI]: -0.08 [-0.10, -0.07] or -2.1 cm [95%CI: -2.4, -1.8]) and a statistically significant negligible improvement in HGS (ES trend per decade [95%CI]: 0.11 [0.08, 0.13]) or 0.6 kg [(95%CI: 0.4, 0.8]). We found evidence of significant increases in distributional variability and asymmetry, with poorer trends in the low performers (<25^th percentile) and better trends in the high performers (>75^th percentile) compared to the average performers. Our data suggest negligible trends in mean SBJ and HGS, coupled with increased distributional variability and asymmetry. Trends were not uniform across the population distribution with data suggesting an increase over time in the gap between low and high performers. These results reinforce the importance of interventions and programmes aiming at improving muscular fitness specifically in children and adolescents with low muscular strength.

PMID:39690442 | DOI:10.1080/02640414.2024.2440676

Retrovirology. 2024 Dec 17;21(1):22. doi: 10.1186/s12977-024-00656-9.

ABSTRACT

BACKGROUND: Human T-cell Lymphotropic Virus type-1 (HTLV-1) infection is associated with serious disorders, including Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In addition to sexual, vertical, parenteral, and blood transfusion, organ/tissue transplantation is considered as a transmission route of HTLV infection. Given the substantial risk of HTLV-1 transmission and the subsequent development of HAM/TSP (approximately 40%) in kidney transplant recipients, pre-transplant donor screening is crucial. The present study aimed to investigate the prevalence of HTLV-1 in potential organ/tissue donors referred to the Iranian Tissue Bank and Research Center (ITBRC).

MATERIALS AND METHODS: The study population was potential organ and/or tissue donors referred to ITBRC between 2014 and 2021, including two groups of brain death (potential donors of organs and/or tissues) and circulatory death donors (potential tissue donors from Iranian Legal Medicine Organization). Initial screening was performed using enzyme-linked immunosorbent assay (ELISA), and positive cases were confirmed for HTLV-1 infection with polymerase chain reaction (PCR).

RESULTS: 111 out of 3,814 donors were positive for HTLV-1 (3%). The rate of positive tests between 2014 and 2017 was 6%, which was significantly higher than the positive tests percentage between 2017 and 2021 with 0.5% (P-value < 0.001). The rate of test positivity in females was 4% compared to 2% in males (P-value = 0.001). Furthermore, individuals diagnosed with brain death exhibited a significantly lower likelihood of HTLV-1 infection (0.2%) compared to cases with circulatory death (4%) (P-value < 0.001).

CONCLUSION: Considering the contraindication of organ/tissue donation from donors with HTLV-1 positive test, these findings give an insight into the prevalence of HTLV-1 among potential organ/tissue donors in Iran. Moreover, the higher prevalence of HTLV-1 infection in circulatory death donors from Iranian Legal Medicine Organization urges for cautious evaluation in these donors.

PMID:39690425 | DOI:10.1186/s12977-024-00656-9

Clin Diabetes Endocrinol. 2024 Dec 18;10(1):49. doi: 10.1186/s40842-024-00210-8.

ABSTRACT

AIMS: The ICMR INDIAB-17 study revealed a diabetes prevalence of 11.4% in India, emphasizing the need for effective treatment for glycemic control. A Phase IV study was conducted to evaluate the safety and efficacy of a Fixed Dose Combination (FDC) of Remogliflozin, Metformin and Vildagliptin (RMV) in Type 2 Diabetes Mellitus (T2DM) patients uncontrolled on Metformin plus SGLT2 inhibitor or Metformin plus DPP4 inhibitor dual therapy.

METHODS: A total of 215 patients (mean age: 46.4 years; 64% male, 36% female) were enrolled across multiple centers in India. The study population included patients with a baseline HbA1c ≥ 8% at the time of screening. The primary objective was to assess safety based on treatment-emergent adverse events (TEAEs), while the secondary. aim was to evaluate effectiveness in terms of glycemic (HbA1c, fasting plasma glucose, postprandial glucose) and extra-glycemic measures (renal and lipid parameters). Statistical analysis was conducted using paired t-tests and the Wilcoxon signed-rank test for within-group comparisons, and the Bonferroni correction was applied to adjust for multiple comparisons. Effectiveness was evaluated at baseline, week 12, and week 24.

RESULTS: The study demonstrated statistically significant reductions in mean HbA1c levels from baseline to both week 12 and week 24 (p < 0.00001). At 24, weeks, 45.1% of patients achieved target HbA1c levels of ≤ 7%. Significant reduction was also observed in fasting plasma glucose (FPG) and postprandial glucose (PPG) levels. Renal parameters remained stable or improved, and lipid profile parameters, including LDL-C and triglycerides, showed favorable changes. Adverse events of special interest, including hypoglycemia and urinary tract infections, were reported in 4.7% of patients, with no serious adverse event recorded.

CONCLUSIONS: The twice daily triple FDC of RMV was well tolerated, safe and effective in patients with Type 2 Diabetes Mellitus uncontrolled on dual drug therapy of Metformin plus SGLT2i or Metformin plus DPP4i. The treatment led to significant improvements in glycemic control and other metabolic parameters over 24 weeks, without compromising renal function or causing serious adverse events.

TRIAL REGISTRATION: CTRI, CTRI/2022/05/042581. Registered 17 May 2022, https//ctri.nic.in/Clinicaltrials/rmaindet.php? trialid=68,757&EncHid=36127.16500&modid=1&compid=19.

PMID:39690416 | DOI:10.1186/s40842-024-00210-8

Int Urol Nephrol. 2024 Dec 18. doi: 10.1007/s11255-024-04326-9. Online ahead of print.

ABSTRACT

INTRODUCTION: The positive effect of varicocelectomy on sperm parameters (sperm morphology, concentration, motility) and fertility and pregnancy rates has been proven. Although various techniques have been defined for varicocele treatment, varicocelectomy with the pulling technique was first defined in 2017. The aim of this retrospective study is to compare the effectiveness and reliability of subinguinal microsurgical varicocelectomy with the “pulling” technique and conventional subinguinal varicocelectomy.

METHODS: A total of 841 patients who underwent subinguinal microsurgical varicocelectomy using the “pulling” or conventional technique between January 2015 and January 2024 were examined retrospectively. Patients with missing and/or inaccessible data, who were using empirical treatments, were excluded from the study. Demographic data, laboratory and imaging results, and peroperative and postoperative 3rd and 6th month semen analysis results of the remaining 231 patients were evaluated.

RESULTS: The mean age of 231 patients who underwent varicocelectomy was 31.1 ± 5.5 years. 202 of the patients (87.4%) were primary infertile. Conventional technique was applied to 124 (53.7%) of the 231 patients, while pulling technique was applied to 107 (46.3%) patients. No significant difference was found between the demographic and clinical data of the patients. The median number of ligated pampiniform plexus veins in the patient group who underwent pulling technique was statistically significantly less than that in the patient group that underwent the conventional method (4 vs 5, p = 0.03). In all patients who underwent varicocelectomy, semen volume, spermatozoa concentration, and progressive motile spermatozoa proportion increased significantly in the postoperative period (p = 0.002, p = 0.006, p = 0.001, respectively). No significant change was found in the proportion of spermatozoa with normal morphology (p = 0.617). The changes in semen analysis data from the preoperative period to the third and sixth postoperative months after varicocelectomy with conventional and pulling techniques were compared. No significant difference was found between the two techniques.

CONCLUSION: Subinguinal microsurgical varicocelectomy with the “pulling” technique may be a safe and effective treatment option with fewer vein ligations compared to the standard surgical method.

PMID:39690399 | DOI:10.1007/s11255-024-04326-9

Surg Radiol Anat. 2024 Dec 17;47(1):36. doi: 10.1007/s00276-024-03541-4.

ABSTRACT

INTRODUCTION: The evolving curricula in medical education have significantly reduced the time allocated for learning and clinically correlating anatomical facts. This has led to noticeable gaps in the anatomical knowledge observed by specialists while training junior residents and is being extensively documented in the literature.

MATERIALS AND METHODS: The descriptive, cross-sectional, questionnaire-based study was conducted online by sharing the questionnaire via e-mail, WhatsApp, and Telegram to institutes across all Indian states and union territories where postgraduate radiodiagnosis courses are offered.

RESULTS: The survey had a predominant response from radiodiagnosis residents belonging to the female gender (53.8%), pursuing MD (83.2%), from final year (43.4%), and from private (58%) institutes. 98% of the residents encountered challenges interpreting radiological images, 89% had no formal training in anatomy during residency, and 59% felt a lack of confidence regarding the human anatomy knowledge required for radiodiagnosis. 91.5% of the residents believe that a short human anatomy posting would significantly improve their radiological reporting skills, and 94% expressed interest in attending workshops or seminars to enhance their knowledge of human anatomy for radiological practice. A standardized curriculum for human anatomy training during the radiodiagnosis residency program is needed for the current period, as 90% of the respondents agreed.

CONCLUSION: To bolster future radiologists’ diagnostic acumen, an enhanced anatomical education within radiodiagnosis residency programs in India is indeed necessary. Implementing structured training programs, incorporating interactive workshops, and leveraging advanced technological tools can significantly bridge knowledge gaps among residents.

PMID:39690295 | DOI:10.1007/s00276-024-03541-4

Spine Deform. 2024 Dec 17. doi: 10.1007/s43390-024-01018-3. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the impact of different positions of adolescent idiopathic scoliosis (AIS) patients and examiners on the angle of trunk rotation (ATR) measured during the forward bending test (FBT) with Scoliometer.

METHODS: Adolescents who had come to the hospital for outpatient were recruited. Considering the location of the subject and the examiner, four postural combinations of ATR were measured. After measuring ATR, the subject underwent radiographic measurements for diagnosis of AIS. Mann-Whitney test was used for the inter-group reliability test in two examiners, and the Kruskal-Wallis test was used to measure intra-group differences in ATR for the four positions. The receiver operating characteristic curve and area under the curve were used to evaluate the diagnostic performance of ATR in AIS measured by different postures. Preplanned sensitivity analyses of the primary outcome were performed by subgroup.

RESULTS: Of the 63 participants suspected of having AIS included, there was no statistically significant difference (P > 0.05) observed between ATR measurements taken in different postures. Only the measurements taken by the examiner from behind the subject demonstrated diagnostic capability for AIS (AUC = 0.73 for both feet together and apart, $P<0.05$ ). There was no statistically significant difference ( $P=0.989)$ in diagnostic ability between the subjects who stood with feet together or apart. The sensitivity analysis supports the robustness of the conclusions ( $P>0.05)$ .

CONCLUSION: When the examiner measured from behind the subject, AIS can be effectively diagnosed, regardless of whether the subject is standing on feet apart or feet together. There is no difference in diagnostic ability in ATR between the two forward bending positions.

LEVEL OF EVIDENCE: Level III.

PMID:39690294 | DOI:10.1007/s43390-024-01018-3

Aesthetic Plast Surg. 2024 Dec 17. doi: 10.1007/s00266-024-04619-5. Online ahead of print.

ABSTRACT

BACKGROUND: This retrospective cohort study aimed to assess differences in surgical trauma between the inframammary fold approach and endoscopic transaxillary approach in breast augmentation surgery.

METHODS: One hundred and ninety-four patients who underwent breast augmentation using either an inframammary fold or endoscopic transaxillary approach were enrolled. All procedures were primary and bilateral cases. Patients’ demographics and indicators, such as operation duration, postoperative volume of drainage, drainage duration, length of hospital stay, and postoperative pain scores, were observed and analyzed.

RESULTS: One hundred and five patients underwent inframammary fold incisions, while the remaining 89 received transaxillary incisions. The operation duration was significantly shorter in the inframammary fold group than in the transaxillary group, while the VAS scores were significantly lower (p < 0.001). Similarly, differences in the age and fertility status between the two groups were statistically significant (p < 0.05). However, no statistically significant differences were noted in the scores of the remaining indicators (p < 0.05).

CONCLUSIONS: This research demonstrated that while patients in the endoscopic transaxillary group were typically younger, which is commonly hypothesized to result in superior results, the inframammary fold approach may offer a surgical option with reduced trauma and pain and concomitantly greater convenience and efficiency, yielding high satisfaction levels among Chinese women.

LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

PMID:39690204 | DOI:10.1007/s00266-024-04619-5

Aesthetic Plast Surg. 2024 Dec 17. doi: 10.1007/s00266-024-04616-8. Online ahead of print.

ABSTRACT

BACKGROUND: The prevalence of body dysmorphic disorder (BDD) varies across different clinical settings, with evidence indicating its notable presence not only in psychiatric environments but also in dermatology and plastic surgery. This article aims to investigate the etiological factors associated with the elevated incidence of BDD in plastic surgery outpatient settings, with the ultimate objective of enhancing the assessment process for potential cosmetic procedure candidates.

METHODS: We recruited 531 patients seeking consultations or surgeries at the Department of Plastic Surgery, Peking University Shenzhen Hospital, from October 2022 to February 2024. The Yale-Brown Obsessive-Compulsive Scale Modified for Body Dysmorphic Disorder (BDD-YBOCS) was utilized to diagnose BDD, and the Hospital Anxiety and Depression Scale (HADS) assessed psychological comorbidities. Statistical analyses included Spearman’s correlation, Kruskal-Wallis, and chi-square tests.

RESULTS: BDD was diagnosed in 11.3% of the participants, with significant variations related to gender (p = 0.042) and marital status (p = 0.026). A significant correlation was also displayed between BDD-YBOCS and HADS (Spearman’s rho = 0.266, p < 0.001). Notably, BDD prevalence was higher during the COVID-19 pandemic (13.6%) compared to post-pandemic period (3.4%) (p = 0.003).

CONCLUSION: This study elucidates the significant prevalence of body dysmorphic disorder (BDD) among patients seeking cosmetic surgery, highlighting critical demographic, psychological and environmental factors that contribute to its manifestation. Given the significant prevalence and the multifactorial nature of BDD, it is important to develop comprehensive assessment tools before cosmetic consultation that prioritize mental health alongside aesthetic considerations in the future.

LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID:39690202 | DOI:10.1007/s00266-024-04616-8