Tag: nevin manimala

Invest Ophthalmol Vis Sci. 2025 Apr 1;66(4):44. doi: 10.1167/iovs.66.4.44.

ABSTRACT

PURPOSE: The lacrimal gland (LG) is the major source of aqueous tears, and insufficient LG secretion leads to aqueous-deficient dry eye (ADDE) disease. To provide a foundational description of LG’s protein expression patterns, we prepared protein extracts of LGs from a wild-type and an ADDE mouse model and analyzed the proteome by quantitative mass spectrometry.

METHODS: LGs were isolated from an ADDE mouse model, male non-obese diabetic (NOD) mice and control wild-type BALB/c mice (n = 6 each). Protein samples were prepared in urea-based lysis buffer and protein concentrations determined by the BCA method. The equivalent of 200 µg protein were tryptically digested and analyzed by nanoflow liquid chromatography tandem mass spectrometry (LC-MS/MS). Proteins were identified and quantified using the PEAKS X bioinformatics suite. Downstream differential protein expression analysis was performed using the MS-DAP R package. Selected significantly differentially expressed and detected proteins were subjected to spatial expression analysis using immunohistochemistry.

RESULTS: Cumulatively, the LC-MS/MS-based proteomics analyses of the murine LG samples identified a total of 31,932 peptide sequences resulting in 2617 protein identifications at a 1% false discovery rate at the peptide and protein level. Principal component analysis (PCA) and hierarchical cluster analysis revealed a separation of NOD and BALB/c samples. Overall, protein diversity was consistently higher in NOD samples. After applying global peptide filter criteria and peptide-to-protein rollup, 1750 remaining proteins were subjected to differential expression analysis using the MSqRob algorithm, which identified 580 proteins with statistically significant expression differences. Data are available via ProteomeXchange with identifier PXD060937. At the cellular level, the up- and downregulation of select proteins were confirmed by immunohistochemistry.

CONCLUSIONS: Our data suggest that chronic inflammation leads to significant alterations in the LG proteome. Ongoing studies aim to identify potentially unique, inflammation-induced proteins that could be amenable to pharmacological modulation.

PMID:40244610 | DOI:10.1167/iovs.66.4.44

Invest Ophthalmol Vis Sci. 2025 Apr 1;66(4):48. doi: 10.1167/iovs.66.4.48.

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the neuroprotective effects of delivering nerve growth factor (NGF) to retinal ganglion cells (RGCs) through adeno-associated virus serotype 2 (AAV2) carrying a neuronal-specific human synapsin (hSyn) promoter.

METHODS: AAV2-hSyn-NGF was injected intravitreally in three glaucoma models: optic nerve crush (ONC), microbead-induced ocular hypertension (MB), and genetic glaucoma model (DBA). Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) determined the optimal injection concentration of AAV vector. Flow cytometry monitored immune responses. Transduction efficiency was quantified using green fluorescent protein (GFP) co-localization with RGC-specific marker RNA-binding protein with multiple splicing (RBPMS). The RGCs’ density, retinal nerve fiber density, ganglion cell complex thickness, and positive scotopic threshold response (pSTR) were measured to assess structural and functional outcomes of the RGCs. Non-parametric Mann-Whitney U tests or Kruskal-Wallis tests were utilized to ascertain the statistical significance (P < 0.05).

RESULTS: The optimal concentration of AAV vector for intravitreal injection was determined to be 1 × 1010 vector particles (VPs) per eye. The use of the hSyn promoter significantly enhanced targeting specificity to RGCs, resulting in a transduction efficiency of 46.64% ± 2.18%. Administration of AAV2-hSyn-NGF effectively preserved the RGCs’ density, nerve fiber layer integrity, and the thickness of ganglion cell complex, while maintaining the RGCs’ function across three glaucoma models. Furthermore, this gene delivery system did not elicit detectable immune responses or structural damage to the retina.

CONCLUSIONS: The AAV2-hSyn-NGF gene therapy offers a safe and effective neuroprotective strategy for RGCs across multiple glaucoma models, making it a promising candidate for future clinical trials in patients with glaucoma.

PMID:40244606 | DOI:10.1167/iovs.66.4.48

Dent Med Probl. 2025 Apr 17. doi: 10.17219/dmp/192096. Online ahead of print.

ABSTRACT

The hyoid bone exhibits potential sex-based variations and is implicated in the severity of obstructive sleep apnea (OSA). Sex-specific comparisons are lacking. The present meta-analysis aimed to address this gap.The Embase, MEDLINE and Web of Science databases were searched. The inclusion criteria were as follows: studies that reported the measurements of the hyoid bone-mandibular plane distance (HMP), demonstrated in cephalometric imaging (CEPH) in patients with OSA of both sexes, involving a polysomnography (PSG) examination with the apnea-hypopnea index (AHI), as well as information on the body mass index (BMI) and age. The exclusion criteria comprised reviews, meta-analyses and case reports. The risk of bias was assessed with the use of the Scottish Intercollegiate Guidelines Network (SIGN) checklist. Statistical analysis was conducted using Comprehensive Meta-Analysis software (CMA) and IBM SPSS Statistics for Windows.Seven observational studies with 718 adult patients (515 males and 203 females) met the inclusion criteria. The mean HMP value was 20.5 ±3.8 mm, with a significant difference observed between males (21.6 ±3.3 mm) and females (17.8 ±3.7 mm) (p < 0.00001). The correlation between HMP and AHI was significantly stronger in females – 2.5 times higher than in males (r = 0.423 vs. r = 0.167, respectively).Although a standard range of the hyoid bone position for healthy adults and elderly individuals is currently lacking, sex significantly affects the anatomical variation of the hyoid mandibular position in patients with OSA. It is crucial to identify distinct OSA endotypes by sex to ensure accurate diagnosis and treatment planning, which could lead to sex-specific therapeutic strategies.

PMID:40244603 | DOI:10.17219/dmp/192096

JAMA Netw Open. 2025 Apr 1;8(4):e255359. doi: 10.1001/jamanetworkopen.2025.5359.

ABSTRACT

IMPORTANCE: Digital health care services expanded with the COVID-19 pandemic. Disparities in telehealth, telemedicine, and telemonitoring use remain understudied.

OBJECTIVE: To examine associations between individual-level characteristics and digital health care use and if these associations differ by county-level social vulnerability.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was an online survey that included a nonprobability sample of US adults aged 18 years or older who resided in 871 counties in the least or most vulnerable quartiles of the Minority Health Social Vulnerability Index (MHSVI), an indicator of county-level social vulnerability. The study was conducted between February and August 2022, and data were analyzed from August 2023 to August 2024.

EXPOSURES: Participant characteristics and MHSVI county-level social vulnerability.

MAIN OUTCOMES AND MEASURES: Self-reported use of telehealth, telemedicine, and telemonitoring. Multivariable logistic regression models were fit to examine associations between sociodemographic, health, and technology factors and each service use, overall and stratified by MHSVI.

RESULTS: Of the 5444 participants who were included in this study, 2927 were female (53.77%), 798 were non-Hispanic Black or African American (14.66%), 838 were Hispanic or Latino (15.39%), 3542 were non-Hispanic White (65.06%); the mean (SE) age was 45.4 (0.2) years. Overall, 2754 participants used telehealth (50.59%), 1609 used telemedicine (29.56%), and 854 used telemonitoring (15.69%). Being English nonproficient (adjusted odds ratio [aOR], 1.54; 95% CI, 1.23-1.92) and having had in-person health care visits (aOR, 4.71; 95% CI, 3.93-5.63) were associated with higher odds of using telehealth, whereas not having a primary care clinician was associated with lower odds (aOR, 0.68; 95% CI, 0.59-0.78). Similar findings were documented for telemedicine and telemonitoring use. Education was associated with higher odds of digital health care use in MHSVI most vulnerable counties (telehealth: aOR, 1.18; 95% CI, 1.06-1.32; telemedicine: aOR, 1.18; 95% CI, 1.05-1.33), whereas individuals who did not self-identify as heterosexual (telehealth: aOR, 1.47; 95% CI, 1.10-1.97; telemedicine: aOR, 1.57; 95% CI, 1.16-2.11; telemonitoring: aOR, 1.54; 95% CI, 1.02-2.31) and those who self-reported fair or poor mental health (telehealth: aOR, 1.29; 95% CI, 1.03-1.61) had higher odds of digital service use in the least vulnerable counties. Self-identifying as Black or African American or Hispanic was associated with high odds of telehealth (Black or African American: aOR, 1.41; 95% CI, 1.17-1.70; Hispanic or Latino: aOR, 1.41; 95% CI, 1.17-1.70), telemedicine (Black or African American: aOR, 1.44; 95% CI, 1.18-1.76; Hispanic or Latino: aOR, 1.27; 95% CI, 1.04-1.54), and telemonitoring (Black or African American: aOR, 1.40; 95% CI, 1.11-1.78; Hispanic or Latino: aOR, 1.46; 95%CI, 1.16-1.84) use overall, but these associations varied across MHSVI strata.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US adults from MHSVI most and least vulnerable counties, digital health care use varied by participant characteristics. Some traditionally underserved groups self-reported higher use of digital health care. Differing associations between individual-level characteristics and digital health care use by county-level social vulnerability reflect the importance of place-based disadvantage indicators. Eliminating digital health care use disparities is important as it represents a complementary avenue to access health care for underserved populations.

PMID:40244585 | DOI:10.1001/jamanetworkopen.2025.5359

JAMA Netw Open. 2025 Apr 1;8(4):e255522. doi: 10.1001/jamanetworkopen.2025.5522.

ABSTRACT

IMPORTANCE: Crossmatched packed red blood cells (pRBC) that are not transfused result in significant waste of this scarce resource. Efficient utilization should be part of a patient blood management strategy.

OBJECTIVE: To develop and validate a prediction model to identify surgical patients at high risk of intraoperative pRBC transfusion.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study used hospital registry data from 2 quaternary hospital networks from January 2016 to June 2021 (development: Montefiore Medical Center [MMC], Bronx, New York), June 2021 to February 2023 (internal validation: MMC), and January 2008 to June 2022 (external validation: Beth Israel Deaconess Medical Center [BIDMC], Boston, Massachusetts). Participants were patients aged 18 years or older undergoing surgery.

MAIN OUTCOME AND MEASURES: The outcome was intraoperative transfusion of 1 or more pRBC units. Based on a priori-defined candidate predictors, stepwise backward regression was applied to develop a computational model of independent predictors for intraoperative pRBC transfusion.

RESULTS: The development and validation cohorts consisted of 816 618 patients (273 654 at MMC: mean [SD], age 57.5 [17.2] years; 161 481 [59.0%] female; 542 964 at BIDMC: mean [SD] age, 56.0 [17.1] years; 310 272 [57.1%] female). Overall, 18 662 patients (2.3%) received at least 1 unit of pRBC. The final model contained 24 preoperative predictors: nonambulatory surgery; American Society of Anesthesiologists physical status; international normalized ratio; redo surgery; emergency surgery or surgery outside of regular working hours; estimated surgical duration of at least 120 minutes; surgical complexity; liver disease; hypoalbuminemia; thrombocytopenia; mild, moderate, or severe anemia; and surgery type. The area under the receiver operating characteristic curve (AUC) was 0.93 (95% CI, 0.92-0.93), suggesting high predictive accuracy and generalizability. Positive predictive value (PPV) and negative predictive value (NPV) were 8.9% (95% CI, 8.7%-9.2%) and 99.7% (95% CI, 99.7%-99.7%), respectively, with increased predictive values for operations with a higher a priori risk of pRBC transfusion. The model’s performance was confirmed in internal and external validation. The prediction tool outperformed the established Transfusion Risk Understanding Scoring Tool (AUC, 0.64 [0.63-0.64]; PPV, 2.6% [95% CI, 2.5%-2.6%]; NPV, 99.2% [95% CI, 99.1%-99.3%]) (P < .001) and was noninferior to 3 machine learning-derived scores.

CONCLUSIONS AND RELEVANCE: In this prognostic study of surgical patients, the Transfusion Forecast Utility for Surgical Events (TRANSFUSE) model for predicting intraoperative pRBC transfusion was developed and validated. The instrument can be used independently of machine learning infrastructure availability to inform preoperative pRBC orders and to minimize waste of nontransfused red blood cell units.

PMID:40244584 | DOI:10.1001/jamanetworkopen.2025.5522

JAMA Netw Open. 2025 Apr 1;8(4):e255532. doi: 10.1001/jamanetworkopen.2025.5532.

ABSTRACT

IMPORTANCE: The COVID-19 pandemic has been associated with risk factors for cognitive decline, such as bereavement and SARS-CoV-2 infection.

OBJECTIVE: To examine whether the COVID-19 pandemic and pandemic-related exposures are associated with cognitive function among middle-aged women.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data from the Nurses’ Health Study II, an ongoing study of registered nurses in the US. The present study focused on women aged 51 to 76 years who completed 2 to 8 objective cognitive assessments both prior to (October 1, 2014, to February 29, 2020) and during the COVID-19 pandemic (March 1, 2020, to September 30, 2022). Statistical analyses were performed from January 2023 to January 2025.

EXPOSURE: COVID-19 pandemic.

MAIN OUTCOMES AND MEASURES: Two standardized (ie, z-scored) composite cognitive scores (psychomotor speed and attention, learning and working memory) and a global score constituted the primary outcomes. Higher scores indicated better cognitive function. Cognitive function was assessed using the Cogstate Brief Battery, a computer-administered cognitive test battery. Participants completed cognitive assessments every 6 to 12 months.

RESULTS: A total of 5191 women (mean [SD] age at first cognitive assessment, 63.0 [4.8] years) completed both prepandemic and during-pandemic measures, contributing 23 678 cognitive assessments. After adjustment for age at cognitive assessment, educational level for both participants and their parents, cognitive test practice effects, and comorbidities (eg, diabetes, hypertension), no difference in cognitive function was observed between assessments taken during vs before the pandemic (psychomotor speed and attention: β = -0.01 SD [95% CI, -0.05 to 0.02 SD]; learning and working memory: β = 0.00 SD [95% CI, -0.03 to 0.03 SD]; global score: β = 0.00 SD [95% CI, -0.03 to 0.02 SD]). Among 4456 participants who responded to the COVID-19 substudy (ie, surveys about pandemic-related events), those with a history of SARS-CoV-2 infection (164 [3.7%]) or post-COVID-19 conditions (PCC; 62 [1.4%]), at a median (IQR) 20.0 (18.5-22.1) months after initial infection, had reduced cognitive function compared with women without infection or PCC; however, these differences did not reach statistical significance, and the wide CIs suggested considerable uncertainty.

CONCLUSIONS AND RELEVANCE: This cohort study of middle-aged women found that the COVID-19 pandemic and pandemic-related events were not associated with cognitive decline up to 2.5 years after the onset of the pandemic. Future studies are needed to examine the long-term implications of SARS-CoV-2 infection and PCC for cognitive function.

PMID:40244583 | DOI:10.1001/jamanetworkopen.2025.5532

JAMA Oncol. 2025 Apr 17. doi: 10.1001/jamaoncol.2025.0522. Online ahead of print.

ABSTRACT

IMPORTANCE: Effective treatment of locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) cancer remains a challenge.

OBJECTIVE: To compare the efficacy and safety of atezolizumab plus trastuzumab plus capecitabine and oxaliplatin chemotherapy (XELOX) vs trastuzumab plus XELOX in Chinese patients with locally advanced human epidermal growth factor receptor 2 (ERBB2; formerly HER2)-positive GC or adenocarcinoma of the GEJ.

DESIGN, SETTING, AND PARTICIPANTS: This was an open-label phase 2 randomized clinical trial conducted at 8 study sites in China. Patient recruitment started on February 25, 2021, and this study is ongoing as participants are still being actively followed up. Chinese patients eligible for surgery with locally advanced ERBB2-positive GC or adenocarcinoma of the GEJ were included. Data were analyzed from March 2021 to October 2023.

INTERVENTIONS: Eligible patients were enrolled and randomly assigned 1:1 to perioperative treatment with either atezolizumab plus trastuzumab plus XELOX (arm A) or trastuzumab plus XELOX (arm B) for 3 neoadjuvant cycles (3 weeks per cycle) and 5 adjuvant cycles.

MAIN OUTCOMES AND MEASURES: The primary efficacy end point was the pathological complete response (pCR) rate following completion of neoadjuvant therapy and surgery.

RESULTS: In total, 42 patients were screened and randomly assigned to arm A (n = 21) or arm B (n = 21). The median (range) ages were 61 (33-72) years and 65 (49-72) years in arm A and arm B, respectively, and 39 patients (93%) were male. The pCR rate was significantly higher in arm A (8 [38%]) than arm B (3 [14%]; difference, 23.8%; 90% CI, 1.3-44.7). Age younger than 65 years, male sex, and intestinal Lauren classification were significantly associated with a better pCR rate in arm A. Median event-free survival, disease-free survival, and overall survival were not reached. Based on the same way of interpretation, major pathologic response should be statistically significantly different between the 2 arms, while other outcome measures remained not significantly different. The incidence of treatment-emergent adverse events was 100% (21 of 21) and 100% (21 of 21) in arms A and B, respectively; grade 3 or higher TEAEs, 57% (12 of 21) and 67% (14 of 21), respectively; and serious TEAEs, 29% (6 of 21) and 10% (2 of 21), respectively.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, add-on atezolizumab to trastuzumab plus XELOX therapy demonstrated promising efficacy in this patient population, and no new safety concerns were raised.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04661150.

PMID:40244574 | DOI:10.1001/jamaoncol.2025.0522

Int J Gynaecol Obstet. 2025 Apr 17. doi: 10.1002/ijgo.70168. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the ovarian reserve and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes after various laparoscopic approaches in infertile patients with endometriomas and suspected compromised ovarian reserve, and the operated and non-operated/healthy ovaries were also compared, aiming to determine the most appropriate laparoscopic approach for each patient.

METHODS: A total of 132 infertile patients with endometriomas and suspected compromised ovarian reserve (anti-Müllerian hormone [AMH] <2.0 ng/mL or antral follicle count [AFC] <8) were treated by various laparoscopic approaches at the Sir Run Run Shaw Hospital from January 2021 to December 2023, followed by IVF/ICSI. Patients were divided into three groups-group A (n = 33) received anhydrous alcohol instillation, group B (n = 65) underwent fenestration/coagulation, and group C (n = 34) underwent ovarian cystectomy. The clinical characteristics, ovarian reserve, and IVF/ICSI outcomes were evaluated among the three groups. The operated side and non-operated/healthy side in patients undergoing initial surgery were also compared.

RESULTS: The proportion of bilateral endometriomas was higher in group A (63.6%, 21/33) than in group B (40.0%, 26/65) and group C (32.4%, 11/34) (P = 0.023). There was no statistically significant difference in serum AMH in group A before and after surgery (median 1.32 [0.84-1.86 ng/mL] vs. 1.13 [0.59-1.86 ng/mL], P = 0.098). However, significant postoperative decreases were observed in groups B (median 1.30 [0.97-1.76 ng/mL] vs. 0.91 [0.50-1.23 ng/mL], P = 0.009) and C (median 1.52 [1.02-1.81 ng/mL] vs. 1.15 [0.76-1.67 ng/mL], P = 0.006). In group C, the follicle-stimulating hormone/luteinizing hormone ratio also increased postoperatively (median 1.75 [1.33-2.50] vs. 2.29 [1.84-3.61], P = 0.005), while no significant differences were seen in groups A (median 1.72 [1.56-2.80] vs. 2.89 [1.89-3.54], P = 0.096) and B (median 2.14 [1.67-2.82] vs. 2.37 [1.83-3.03], P = 0.189). The clinical pregnancy rate was significantly higher in group A than in group C (60.6%, 20/33 vs. 36.4%, 12/33; P = 0.042), but not significantly different between groups A and B (60.6%, 20/33 vs. 46.9%, 30/64; P = 0.143) or groups B and C (P = 0.220). Compared with the control group, there was a statistically significant difference in preoperative AFC in the group anhydrous ethanol instillation side (median 4.0 [2.0-5.0] vs. 2.0 [0.75-3.25], P < 0.001), the group fenestration/coagulation side (median 2.0 [0-3.0] vs. 2.0 [0.75-3.25], P < 0.001), and the group ovarian cystectomy side (median 2.0 [0-4.0] vs. 2.0 [0.75-3.25], P = 0.003), with no significant differences among the three groups themselves. Compared with the control group, significant differences were also observed between the group fenestration/coagulation side (median 2.0 [1.0-3.75] vs. 2.0 [1.0-3.0], P = 0.014) and the group ovarian cystectomy side (median 2.0 [1.0-4.0] vs. 2.0 [1.0-3.0], P = 0.040), in the 15-20 mm follicles, while no significant differences were found in the group anhydrous ethanol instillation side (median 3.0 [2.0-5.0] vs. 2.0 [1.0-3.0], P = 0.108).

CONCLUSION: This study suggests that laparoscopic anhydrous ethanol treatment prior to IVF/ICSI in infertile patients with ovarian endometrioma and suspected compromised ovarian reserve may be superior to fenestration/coagulation and ovarian cystectomy.

PMID:40244566 | DOI:10.1002/ijgo.70168

Acta Otolaryngol. 2025 Apr 17:1-6. doi: 10.1080/00016489.2025.2485435. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease with varying patterns across regions.

OBJECTIVE: This study aims to investigate the clinical and histopathological features of CRSwNP in Xizang, a high-altitude region in China.

MATERIALS AND METHODS: We retrospectively analyzed the histopathological features of CRSwNP patients from Shanghai and Xizang who underwent functional endoscopic sinus surgery (FESS) between 2017 and 2024. Polyp tissue samples were assessed, and statistical analyses compared features between the two regions in CRSwNP, eosinophilic CRSwNP (eCRSwNP), and noneosinophilic CRSwNP (neCRSwNP) patients.

RESULTS: Twenty-eight patients from Xizang and 35 from Shanghai were analyzed. All Shanghai patients were Han Chinese, and all Xizang patients were Tibetan. Compared to Shanghai, Tibetan patients had significantly lower rates of smoking and asthma. Overall inflammation levels in Xizang were lower, while eosinophil counts were lower in eCRSwNP patients. Neutrophil infiltration, mucosal ulceration, and squamous metaplasia were higher in Xizang patients, while neCRSwNP patients exhibited more neutrophil infiltration and less subepithelial edema.

CONCLUSIONS: The study revealed that Tibetan patients with CRSwNP have lower eosinophilic inflammation but higher neutrophil infiltration and squamous metaplasia compared to Shanghai patients, indicating the impact of high-altitude environments on inflammatory patterns.

PMID:40244564 | DOI:10.1080/00016489.2025.2485435

Indian J Ophthalmol. 2025 Apr 17. doi: 10.4103/IJO.IJO_962_24. Online ahead of print.

ABSTRACT

This meta-analysis evaluates optical coherence tomography angiography (OCTA) results in macular telangiectasia (MacTel) type 2, a rare retinal condition marked by vascular abnormalities. We analyzed 26 studies for OCTA findings in MacTel type 2. We examined parameters like best corrected visual acuity (BCVA), foveal avascular zone (FAZ), and superficial and deep capillary plexus densities. The pooled mean BCVA was 0.37 log of minimum angle of resolution (20/50). FAZ enlargement was observed, with a pooled mean FAZ size of 0.39 mm2. Foveal deep vascular density (FDVD) and parafoveal superficial vascular density (PSVD) were significantly reduced (P = 0.021 and P < 0.001, respectively). Parafoveal deep vascular density (PDVD) and foveal superficial vascular density (FSVD) did not decrease significantly (P = 0.067 and 0.114, respectively). MacTel type 2 has unique OCTA characteristics, including reduced FDVD, PSVD, and enlarged FAZ. However, FSVD and PDVD did not statistically decrease in patients. Future studies using more parameters are required to expand our understanding.

PMID:40244563 | DOI:10.4103/IJO.IJO_962_24