Category: Nevin Manimala

JAMA Netw Open. 2024 May 1;7(5):e2414322. doi: 10.1001/jamanetworkopen.2024.14322.

ABSTRACT

IMPORTANCE: Higher adherence to the Mediterranean diet has been associated with reduced risk of all-cause mortality, but data on underlying molecular mechanisms over long follow-up are limited.

OBJECTIVES: To investigate Mediterranean diet adherence and risk of all-cause mortality and to examine the relative contribution of cardiometabolic factors to this risk reduction.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included initially healthy women from the Women’s Health Study, who had provided blood samples, biomarker measurements, and dietary information. Baseline data included self-reported demographics and a validated food-frequency questionnaire. The data collection period was from April 1993 to January 1996, and data analysis took place from June 2018 to November 2023.

EXPOSURES: Mediterranean diet score (range, 0-9) was computed based on 9 dietary components.

MAIN OUTCOME AND MEASURES: Thirty-three blood biomarkers, including traditional and novel lipid, lipoprotein, apolipoprotein, inflammation, insulin resistance, and metabolism measurements, were evaluated at baseline using standard assays and nuclear magnetic resonance spectroscopy. Mortality and cause of death were determined from medical and death records. Cox proportional hazards regression was used to calculate hazard ratios (HRs) for Mediterranean diet adherence and mortality risk, and mediation analyses were used to calculate the mediated effect of different biomarkers in understanding this association.

RESULTS: Among 25 315 participants, the mean (SD) baseline age was 54.6 (7.1) years, with 329 (1.3%) Asian women, 406 (1.6%) Black women, 240 (0.9%) Hispanic women, 24 036 (94.9%) White women, and 95 (0.4%) women with other race and ethnicity; the median (IQR) Mediterranean diet adherence score was 4.0 (3.0-5.0). Over a mean (SD) of 24.7 (4.8) years of follow-up, 3879 deaths occurred. Compared with low Mediterranean diet adherence (score 0-3), adjusted risk reductions were observed for middle (score 4-5) and upper (score 6-9) groups, with HRs of 0.84 (95% CI, 0.78-0.90) and 0.77 (95% CI, 0.70-0.84), respectively (P for trend < .001). Further adjusting for lifestyle factors attenuated the risk reductions, but they remained statistically significant (middle adherence group: HR, 0.92 [95% CI, 0.85-0.99]; upper adherence group: HR, 0.89 [95% CI, 0.82-0.98]; P for trend = .001). Of the biomarkers examined, small molecule metabolites and inflammatory biomarkers contributed most to the lower mortality risk (explaining 14.8% and 13.0%, respectively, of the association), followed by triglyceride-rich lipoproteins (10.2%), body mass index (10.2%), and insulin resistance (7.4%). Other pathways, including branched-chain amino acids, high-density lipoproteins, low-density lipoproteins, glycemic measures, and hypertension, had smaller contributions (<3%).

CONCLUSIONS AND RELEVANCE: In this cohort study, higher adherence to the Mediterranean diet was associated with 23% lower risk of all-cause mortality. This inverse association was partially explained by multiple cardiometabolic factors.

PMID:38819819 | DOI:10.1001/jamanetworkopen.2024.14322

J Vis. 2024 May 1;24(5):17. doi: 10.1167/jov.24.5.17.

ABSTRACT

What is the link between eye movements and sensory learning? Although some theories have argued for an automatic interaction between what we know and where we look that continuously modulates human information gathering behavior during both implicit and explicit learning, there exists limited experimental evidence supporting such an ongoing interplay. To address this issue, we used a visual statistical learning paradigm combined with a gaze-contingent stimulus presentation and manipulated the explicitness of the task to explore how learning and eye movements interact. During both implicit exploration and explicit visual learning of unknown composite visual scenes, spatial eye movement patterns systematically and gradually changed in accordance with the underlying statistical structure of the scenes. Moreover, the degree of change was directly correlated with the amount and type of knowledge the observers acquired. This suggests that eye movements are potential indicators of active learning, a process where long-term knowledge, current visual stimuli and an inherent tendency to reduce uncertainty about the visual environment jointly determine where we look.

PMID:38819805 | DOI:10.1167/jov.24.5.17

Clin Infect Dis. 2024 May 31:ciae235. doi: 10.1093/cid/ciae235. Online ahead of print.

ABSTRACT

BACKGROUND: Analytical treatment interruption (ATI) is the gold standard in HIV research for assessing the capability of new therapeutic strategies to control viremia without antiretroviral treatment (ART). The viral setpoint is commonly used as endpoint to evaluate their efficacy. However, in line with recommendations from a consensus meeting, to minimize the risk of increased viremia without ART, trials often implement short ATI phases and stringent virological ART restart criteria. This approach can limit the accurate observation of the setpoint.

METHODS: We analyzed viral dynamics in 235 people with HIV from 3 trials, examining virological criteria during ATI phases. Time-related (eg time to rebound, peak, and setpoint) and viral load magnitude-related criteria (peak, setpoint, and time-averaged AUC [nAUC]) were described. Spearman correlations were analyzed to identify (1) surrogate endpoints for setpoint and (2) optimal virological ART restart criteria mitigating the risks of ART interruption and the evaluation of viral control.

RESULTS: Comparison of virological criteria between trials showed strong dependencies on ATI design. Similar correlations were found across trials, with nAUC the most strongly correlated with the setpoint, with correlations >0.70. A threshold >100 000 copies/mL for 2 consecutive measures is requested as a virological ART restart criterion.

CONCLUSIONS: Our results are in line with recommendations and emphasize the benefits of an ATI phase >12 weeks, with regular monitoring, and a virological ART restart criterion of 10 000 copies/mL to limit the risk for patients while capturing enough information to keep nAUC as an optimal proxy to the setpoint.

PMID:38819800 | DOI:10.1093/cid/ciae235

J Sep Sci. 2024 Jun;47(11):e2400164. doi: 10.1002/jssc.202400164.

ABSTRACT

Oxaliplatin (L-OHP), a third-generation platinum-based anti-tumor drug, finds widespread application in the first-line treatment of metastatic colorectal cancer. Despite its efficacy, the drug’s usage is curtailed by a litany of side effects, with L-OHP-induced peripheral neuropathy (OIPN) being the most debilitating. This condition can be classified into varying degrees of severity. Employing serum metabolomics, a high-sensitivity, high-throughput technique, holds promise as a method to identify biomarkers for clinical assessment and monitoring of OIPN patients across different severity levels. In our study, we analyzed serum metabolites in patients with different OIPN levels using ultra-performance liquid chromatography-high resolution mass spectrometry. By employing statistical analyses and pathway enrichment studies, we aimed to identify potential biomarkers and metabolic pathways. Our findings characterized the serum metabolic profiles of patients with varying OIPN levels. Notably, pathway analysis revealed a significant correlation with lipid metabolism, amino acid metabolism, and energy metabolism. Multivariate statistical analysis and receiver operator characteristic curve evaluation pointed to anhalamine and glycochenodeoxycholic acid as potential biomarkers for OIPN C and A, which suggest that serum metabolomics may serve as a potent tool for exploring the metabolic status of patients suffering from diverse diseases and for discovering novel biomarkers.

PMID:38819794 | DOI:10.1002/jssc.202400164

Rheumatol Ther. 2024 May 31. doi: 10.1007/s40744-024-00676-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Psoriatic arthritis (PsA) is associated with increased cardiovascular (CV) risk and mortality. Aortic stiffness measured by carotid-femoral pulse wave velocity (cfPWV) has been shown to predict CV risk in the general population. The present study aimed to examine cfPWV values of patients with PsA compared to healthy controls and to evaluate associations of cfPWV with patient- and disease-associated characteristics, as well as with an established traditional CV prediction score of the European Society of Cardiology (Systemic Coronary Risk Evaluation; SCORE), for the first time.

METHODS: cfPWV and SCORE were evaluated in patients with PsA and healthy controls, along with clinical and laboratory disease parameters. Differences in cfPWV measurements between the two groups and associations of cfPWV with patient- and disease-associated characteristics were statistically evaluated.

RESULTS: A total of 150 patients with PsA (PSOCARD cohort) and 88 control subjects were recruited. cfPWV was significantly higher in the PsA group compared to controls, even after adjustment for confounders (p_adj = 0.034). Moreover, cfPWV was independently associated with disease duration (r = 0.304, p = 0.001), age (rho = 0.688, p < 0.001), systolic arterial pressure (rho = 0.351, p < 0.001), glomerular filtration rate (inverse: rho = – 0.264, p = 0.001), and red cell distribution width, a marker of major adverse CV events (MACE) (rho = 0.190, p = 0.02). SCORE revealed an elevated CV risk in 8.73% of the patients, whereas cfPWV showed increased aortic stiffness and end-organ disease in 16.00% of the same cohort.

CONCLUSIONS: In the largest cfPWV/PsA cohort examined to date, patients with PsA exhibited increased aortic stiffness compared to healthy controls. PsA duration was the most important independent disease-associated predictor of increased aortic stiffness, next to traditional CV risk factors. cfPWV measurements may help identify subclinical end-organ disease and abnormal aortic stiffness and thus assist CV risk classification in PsA.

PMID:38819779 | DOI:10.1007/s40744-024-00676-z

Braz J Microbiol. 2024 May 31. doi: 10.1007/s42770-024-01397-9. Online ahead of print.

ABSTRACT

Bacterial Cellulose (BC) offers a wide range of applications across various industries, including food, biomedical, and textiles, owing to its distinctive properties. Its unique 3D reticulated network of cellulose nanofibers, imparts excellent mechanical qualities, a high water-holding capacity, and thermal stability. Additionally, it possesses remarkable biocompatibility, biodegradability, high crystallinity, and purity. These attributes have offered significant interest in BC within both academic and industrial sectors. However, BC production is associated with high costs due to the use of expensive growth media and low yields. The study reports the potential of our indigenous isolate, Komagataeibacter saccharivorans BC-G1, as BC producer. Statistical optimization of BC production was carried out using Placket-Burman design and Central composite design, by selecting different parameters. Eight significant factors such as temperature, pH, glucose, yeast, peptone, acetic acid, incubation time and % inoculum were studies using ANOVA-based response surface methodology. Results showed that BC yield (8.5 g/L) with 1.8-fold after optimization of parameters. Maximum cellulose production (8.5 ± 1.8 g/L) was obtained using 2% glucose, 0.3% yeast extract, 0.3% peptone, 0.75% (v/v) acetic acid at pH 7.0 for 10 days of incubation with 4% inoculum at 25 °C under static culture. Main effect graph showed incubation time and acetic acid concentration as the most significant parameters affecting BC production in our study. The physicochemical characterization of produced BC was done using FTIR, XRD and SEM techniques.

PMID:38819773 | DOI:10.1007/s42770-024-01397-9

3D Print Med. 2024 May 31;10(1):18. doi: 10.1186/s41205-024-00220-3.

ABSTRACT

BACKGROUND: Ulnar shortening osteotomy (USO) has demonstrated good outcomes for patients with ulnar impaction syndrome. To minimize complications such as non-union, precise osteotomy and firm fixation are warranted. Despite various ulnar shortening systems have been developed, current technology does not meet all needs. A considerable portion of patients could not afford those designated USO systems. To tackle this challenge, our team reported successful results in standardized free-hand predrilled USO technique. However, it is still technical demanding and requires sufficient experience and confidence to excel. Therefore, our team designed an ulnar shortening system based on our free-hand technique principle, using metal additive manufacturing technology. The goal of this study is to describe the development process and report the performance of the system.

METHODS: Utilizing metal additive manufacturing technology, our team developed an ulnar shortening system that requires minimal exposure, facilitates precise cutting, and allows for the easy placement of a 3.5 mm dynamic compression plate, available to patients at zero out-of-pocket cost. For performance testing, two surgeons with different levels of experience in ulnar shortening procedures were included: one fellow-trained hand and wrist surgeon and one senior resident. They performed ulnar shortening osteotomy (USO) using both the free-hand technique and the USO system-assisted technique on ulna sawbones, repeating each method three times. The recorded parameters included time-to-complete-osteotomy, total procedure time, chip diameter, shortening length, maximum residual gap, and deviation angle.

RESULTS: For the hand and wrist fellow, with the USO system, the time-to-complete osteotomy was significantly reduced. (468.7 ± 63.6 to 260.0 ± 5 s, p < 0.05). Despite the preop goal was shortening 3 mm, the average shortening length was significantly larger in the free-hand group (5 ± 0.1; 3.2 ± 0.2 mm, p < 0.05). Both maximum residual gap and deviation angle reported no statistical difference between the two techniques for the hand surgeon. As for the senior resident, the maximum residual gap was significantly reduced, using the USO system (2.9 ± 0.8; 0.4 ± 0.4 mm, p = 0.02). Between two surgeons, significant larger maximum residual gap and deviation angle were noted on the senior resident doctor, in the free-hand technique group, but not in the USO system group.

CONCLUSION: The developed USO system may serve as a valuable tool, aiding in reliable and precise cutting as well as fixation for patients undergoing ulnar shortening osteotomy with a 3.5 mm dynamic compression plate, even for less experienced surgeons. The entire process, from concept generation and sketching to creating the CAD file and final production, serves as a translatable reference for other surgical scenarios.

PMID:38819766 | DOI:10.1186/s41205-024-00220-3

J Clin Monit Comput. 2024 May 31. doi: 10.1007/s10877-024-01177-8. Online ahead of print.

ABSTRACT

The Inferior Vena Cava (IVC) is commonly utilized to evaluate fluid status in the Intensive Care Unit (ICU),with more recent emphasis on the study of venous congestion. It is predominantly measured via subcostal approach (SC) or trans-hepatic (TH) views, and automated border tracking (ABT) software has been introduced to facilitate its assessment. Prospective observational study on patients ventilated in pressure support ventilation (PSV) with 2 × 2 factorial design. Primary outcome was to evaluate interchangeability of measurements of the IVC and the distensibility index (DI) obtained using both M-mode and ABT, across both SC and TH. Statistical analyses comprised Bland-Altman assessments for mean bias, limits of agreement (LoA), and the Spearman correlation coefficients. IVC visualization was 100% successful via SC, while TH view was unattainable in 17.4% of cases. As compared to the M-mode, the IVC-DI obtained through ABT approach showed divergences in both SC (mean bias 5.9%, LoA -18.4% to 30.2%, ICC = 0.52) and TH window (mean bias 6.2%, LoA -8.0% to 20.4%, ICC = 0.67). When comparing the IVC-DI measures obtained in the two anatomical sites, accuracy improved with a mean bias of 1.9% (M-mode) and 1.1% (ABT), but LoA remained wide (M-mode: -13.7% to 17.5%; AI: -19.6% to 21.9%). Correlation was generally suboptimal (r = 0.43 to 0.60). In PSV ventilated patients, we found that IVC-DI calculated with M-mode is not interchangeable with ABT measurements. Moreover, the IVC-DI gathered from SC or TH view produces not comparable results, mainly in terms of precision.

PMID:38819726 | DOI:10.1007/s10877-024-01177-8

J Assist Reprod Genet. 2024 May 31. doi: 10.1007/s10815-024-03147-0. Online ahead of print.

ABSTRACT

PURPOSE: The study aimed to analyse the relationship of the rs4986790 locus of the TLR4 gene with the overall risk of preeclampsia, including both its early and late forms.

METHODS: The study used standard genetic analysis methods such as DNA extraction, PCR amplification, and genotyping of the rs4986790 locus of the TLR4 gene to assess the association with the development of preeclampsia and peripartal stroke in 207 pregnant women from the southern regions of Kazakhstan from 2016 to 2022, of whom 103 had peripartal stroke on the background of preeclampsia (the main group) and 104 preeclampsia (comparative group).

RESULTS: The results of the study demonstrate that the AG and AG + GG genotypes at the rs4986790 locus of the TLR4 gene are significantly associated with an increased risk of developing an early form of preeclampsia. This opens up a new perspective in the identification of genetic markers that can serve as indicators of a tendency to develop preeclampsia in earlier periods of pregnancy.

CONCLUSION: It was noted that the rs4986790 locus did not show a statistically significant association with the risk of late preeclampsia. An important aspect of the study revealed the relationship of genotypes with the development of peripartal stroke on the background of preeclampsia. This study offers practical insights for creating targeted genetic screening and personalised treatments for preeclampsia, aiming to improve patient outcomes. To fully understand the molecular mechanisms underlying the identified association, additional research is required to identify deeper molecular pathways and relationships, and to develop new strategies for the prevention and treatment of preeclampsia.

PMID:38819715 | DOI:10.1007/s10815-024-03147-0

Jpn J Radiol. 2024 May 31. doi: 10.1007/s11604-024-01602-7. Online ahead of print.

ABSTRACT

PURPOSE: To investigate glymphatic system function in patients with brain tumors, including both primary and secondary tumors, using diffusion tensor imaging along perivascular spaces (DTI-ALPS).

METHODS: We retrospectively analyzed the MR DTI of 24 patients with unilateral brain tumors and compared them with age and sex-matched controls. We compared the DTI-ALPS index of the ipsi- and contralateral brain hemispheres. The region of interest was placed in the periventricular vessels adjacent to the lateral ventricles. Differences between sex, age, and kind of tumor (primary or brain metastasis) were evaluated. Correlations between DTI-ALPS index and age and the tumor’s apparent diffusion coefficient (ADC) were also investigated.

RESULTS: The DTI-ALPS index was significantly lower (p < 0.05) in the tumor-affected hemisphere (mean = 1.26 ± 0.24) than contralateral (mean = 1.43 ± 0.28). A comparison with healthy controls revealed no significant difference on the matched ipsilateral side. However, the DTI-ALPS index of the contralateral side of the patients was larger than the HC. Additionally, no statistically significant differences were found when analyzing the DTI-ALPS index vs. age, sex, and tumor entity. Additionally, we did not find a correlation between the DTI-ALPS index and patient age or tumor ADC.

CONCLUSION: The decreased DTI-ALPS index in the tumor-affected hemisphere may be related to impaired glymphatic system function. However, cancer is often a systemic disease; thus, the DTI-ALPS index from the contralateral brain hemisphere may not generally be considered as a normal control. Nonetheless, the DTI-ALPS index does not only reflect diffusion in the perivascular spaces but it can also be influenced by factors such as axonal degeneration. Therefore, it does not directly reflect brain waste clearance and changes in the index should be interpreted carefully.

PMID:38819694 | DOI:10.1007/s11604-024-01602-7