Tag: nevin manimala

In Vivo. 2024 Jul-Aug;38(4):1690-1697. doi: 10.21873/invivo.13619.

ABSTRACT

BACKGROUND/AIM: Chronic obstructive pulmonary disease (COPD) is a major public health concern, affecting over 200 million people worldwide in 2019. The prevalence of COPD has risen by 40% from 1990 to 2010 and continued to increase by 13% from 2010 to 2019, causing over 3 million deaths globally in 2019, ranking it as the third leading cause of death. This study explored how daily weather changes relate to the number of COPD-related emergency department (ED) visits.

MATERIALS AND METHODS: We collected data on daily COPD-related ED visits in 2017 in Pécs along with corresponding meteorological data to analyze this connection.

RESULTS: High diurnal temperature range (DTR) and day-to-day variability in dew point were linked to a 4.5% increased risk of more COPD-related ED visits. Notably, DTR had a stronger impact on males, contributing to a 6.3% increase, while dew point variability significantly affected males with an odds ratio (OR) of 1.083. (OR=1.083). Stratifying by age revealed heightened risks for those aged 30-39 (43.5% increase) and 50-59 (7.6% increase). Females aged 30-39 and 50-59 faced elevated risks of 42.7% and 9.1%, respectively, whereas males aged 60-69 showed a 9.8% increase.

CONCLUSION: Our findings highlight the influence of weather variations on COPD-related ED visits, with nuanced effects based on age and sex.

PMID:38936910 | DOI:10.21873/invivo.13619

In Vivo. 2024 Jul-Aug;38(4):1875-1881. doi: 10.21873/invivo.13642.

ABSTRACT

BACKGROUND/AIM: The purpose of the current study was to compare the vascular endothelial growth factor-A (VEGF-A) levels in the aqueous humor of patients with primary open angle glaucoma (POAG) and non-glaucomatous eyes and reveal any potential statistically significant correlations.

PATIENTS AND METHODS: This was an observational cross-sectional study. Aqueous humor samples (50-100 μl) were collected under aseptic conditions, from the anterior chamber at the start of glaucoma or cataract surgery. The levels of VEGF-A were measured using a multiplex bead-based immunoassay.

RESULTS: Aqueous humor samples were obtained from 76 participants: 39 with POAG and 36 with age-related cataracts as controls. VEGF-A levels were significantly elevated in the POAG group (166.37±110.04 pg/ml, p=0.011) compared to the control group (119.02±49.09 pg/ml). The receiver operating characteristic (ROC) analysis showed that VEGF-A had significant prognostic ability for POAG (AUC=0.67; p=0.006). An optimal cut-off for VEGF-A was found to be 148.5 pg/ml with a sensitivity of 54%, specificity of 81.1%, positive prognostic value (PPV) of 75% and negative prognostic value (NPV) of 62.5%. Logistic regression analysis showed that after adjusting for sex and age, patients with VEGF-A higher than 148.5 pg/ml had almost 10 times greater likelihood for POAG.

CONCLUSION: VEGF-A is elevated in patients with POAG and can potentially have a prognostic ability for these patients.

PMID:38936903 | DOI:10.21873/invivo.13642

In Vivo. 2024 Jul-Aug;38(4):2031-2040. doi: 10.21873/invivo.13661.

ABSTRACT

BACKGROUND/AIM: Overactive bladder (OAB) has recently been recognized as an independent risk factor for falls and fractures. This study aimed to predict fracture risk in female patients with OAB symptoms.

PATIENTS AND METHODS: We assessed and compared the fracture risk in newly diagnosed female patients with OAB to those without OAB using the Fracture Risk Assessment Tool (FRAX), and investigated the relationship between fracture risk and OAB severity.

RESULTS: The present single-center, cross-sectional study included 177 female participants (79 with OAB, 98 without OAB). The OAB group was older (p=0.033) and shorter (p=0.010) compared to the non-OAB group. Compared to the non-OAB group, the OAB group had more patients with hypertension (p<0.001) and diabetes mellitus (p=0.011), as well as higher risks for major fractures (non-OAB group: 15.2±13.2%; OAB group: 23.6±14.1%; p<0.001) and hip fractures (non-OAB group: 6.3±11.0%; OAB group: 10.6±10.0%; p=0.007). In addition, those with moderate/severe OAB had the most significantly elevated risks for both major fractures (non-OAB group: 15.2±13.2%, mild-OAB: 17.6±12.5%, moderate/sever-OAB: 26.4±14.0%; p<0.001) and hip fractures (non-OAB group: 6.3±11.0%, mild-OAB: 6.5±7.6%, moderate/sever-OAB: 12.5±10.4%; p<0.001). Among the OAB symptoms, nocturia had the strongest correlation with fracture risk (major fracture, ρ=0.534; hip fracture, ρ=0.449; all p<0.001).

CONCLUSION: Patients with severe OAB, and particularly severe nocturia, should be closely monitored with timely and aggressive symptom management; however, an interventional study incorporating the management of OAB symptoms is required to confirm whether the proactive management of OAB symptoms reduces the risk of fractures in older females.

PMID:38936892 | DOI:10.21873/invivo.13661

In Vivo. 2024 Jul-Aug;38(4):1740-1749. doi: 10.21873/invivo.13624.

ABSTRACT

BACKGROUND/AIM: To date, therapeutic options for T-cell acute lymphoblastic leukemia (T-ALL) remain very limited. This study evaluated the efficacy of monotherapies and combination therapies including a selective BCL-2 inhibitor for T-ALL cell lines, namely Jurkat, CCRF-CEM, and Loucy.

MATERIALS AND METHODS: Loucy is an early T-precursor ALL (ETP-ALL) cell line characterized by an immature phenotype, whereas Jurkat and CCRF-CEM are late T-cell progenitor ALL (LTP-ALL) cell lines. Monotherapy was conducted with venetoclax, cytarabine, bendamustine, or azacytidine, whereas combination therapy was performed with venetoclax plus cytarabine, venetoclax plus bendamustine, or venetoclax plus azacytidine. Cell viability assay was conducted after 48 h using Trypan blue and the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). Statistical analysis for evaluating synergistic interactions between anticancer drugs was performed by using the SynergyFinder Plus and drc R package.

RESULTS: Adding venetoclax to cytarabine, bendamustine, or azacitidine achieved an additive effect, with Loewe synergic scores ranging from -10 to 10 in Jurkat and CCRF-CEM. Conversely, the combination of venetoclax and cytarabine displayed an additive effect (Loewe synergic score: 8.45 and 5.82 with MTS and Trypan blue assays, respectively), whereas venetoclax plus bendamustine or azacitidine exhibited a synergistic effect (Loewe synergic score >10 with MTS assay) in Loucy. Remarkably, the Bliss/Loewe score revealed that the combination of venetoclax and bendamustine was the most synergistic, yielding a score of 13.832±0.55.

CONCLUSION: The combination of venetoclax and bendamustine demonstrated the greatest synergistic effect in suppressing ETP-ALL cell proliferation. Further studies are warranted to determine the mechanisms for the synergism between venetoclax and bendamustine in high-risk T-ALL.

PMID:38936885 | DOI:10.21873/invivo.13624

ESMO Open. 2024 Jun 26;9(7):103604. doi: 10.1016/j.esmoop.2024.103604. Online ahead of print.

ABSTRACT

BACKGROUND: Low muscle mass (MM) predicts unfavorable outcomes in cancer. Protein intake supports muscle health, but oncologic recommendations are not well characterized. The objectives of this study were to evaluate the feasibility of dietary change to attain 1.0 or 2.0 g/kg/day protein diets, and the preliminary potential to halt MM loss and functional decline in patients starting chemotherapy for stage II-IV colorectal cancer.

PATIENTS AND METHODS: Patients were randomized to the diets and provided individualized counseling. Assessments at baseline, 6 weeks, and 12 weeks included weighed 3-day food records, appendicular lean soft tissue index (ALSTI) by dual-energy X-ray absorptiometry to estimate MM, and physical function by the Short Physical Performance Battery (SPPB) test.

RESULTS: Fifty patients (mean ± standard deviation: age, 57 ± 11 years; body mass index, 27.3 ± 5.6 kg/m²; and protein intake, 1.1 ± 0.4 g/kg/day) were included at baseline. At week 12, protein intake reached 1.6 g/kg/day in the 2.0 g/kg/day group and 1.2 g/kg/day in the 1.0 g/kg/day group (P = 0.012), resulting in a group difference of 0.4 g/kg/day rather than 1.0 g/kg/day. Over one-half (59%) of patients in the 2.0 g/kg/day group maintained or gained MM compared with 44% of patients in the 1.0 g/kg/day group (P = 0.523). Percent change in ALSTI did not differ between groups [2.0 g/kg/day group (mean ± standard deviation): 0.5% ± 4.6%; 1.0 g/kg/day group: -0.4% ± 6.1%; P = 0.619]. No differences in physical function were observed between groups. However, actual protein intake and SPPB were positively associated (β = 0.37; 95% confidence interval 0.08-0.67; P = 0.014).

CONCLUSION: Individualized nutrition counselling positively impacted protein intake. However, 2.0 g/kg/day was not attainable using our approach in this population, and group contamination occurred. Increased protein intake suggested positive effects on MM and physical function, highlighting the potential for nutrition to attenuate MM loss in patients with cancer. Nonetheless, muscle anabolism to any degree is clinically significant and beneficial to patients. Larger trials should explore the statistical significance and clinical relevance of protein interventions.

PMID:38935990 | DOI:10.1016/j.esmoop.2024.103604

Animal. 2024 Jun 4;18(7):101211. doi: 10.1016/j.animal.2024.101211. Online ahead of print.

ABSTRACT

Feed efficiency is an important trait of dairy production. However, assessing feed efficiency is constrained by the associated cost and difficulty in measuring individual feed intake, especially on pastures. The objective of this study was to investigate short-term feed efficiency traits of herbage-fed dairy cows and screening of potential biomarkers (n = 238). Derived feed efficiency traits were ratio-based (i.e., feed conversion ratio (FCR) and N use efficiency (NUE)) or residual-based (i.e., residual feed intake (RFI), residual energy intake (REI), and residual N intake (RNI)). Thirty-eight Holstein and 16 Swiss Fleckvieh dairy cows underwent a 7-d measurement period during mid- and/or late-lactation. The experimental data (n = 100 measurement points) covered different lactational and herbage-fed system situations: mid-lactation grazing (n = 56), late-lactation grazing (n = 28), and late-lactation barn feeding (n = 16). During each measuring period, the individual herbage intake of each cow was estimated using the n-alkane marker technique. For each cow, biomarkers representing milk constituents (n = 109), animal characteristics (n = 13), behaviour, and activity (n = 46), breath emissions (n = 3), blood constituents (n = 35), surface, and rectal temperature (n = 29), hair cortisol (n = 1), and near-infrared (NIR) spectra of faeces and milk (n = 2) were obtained. The relationships between biomarkers and efficiency traits were statistically analysed with univariate linear regression and for NIR spectra using partial least squares regression with feed efficiency traits. The feed efficiency traits were interrelated with each other (r: -0.57 to -0.86 and 0.49-0.81). The biomarkers showed varying R² values in explaining the variability of feed efficiency traits (FCR: 0.00-0.66, NUE: 0.00-0.74, RFI: 0.00-0.56, REI: 0.00-0.69, RNI: 0.00-0.89). Overall, the feed efficiency traits were best explained by NIR spectral characteristics of milk and faeces (R²: 0.25-0.89). Biomarkers show potential for predicting feed efficiency in herbage-fed dairy cows. NIR spectra data analysis of milk and faeces presents a promising method for estimating individual feed efficiency upon further validation of prediction models. Future applications will depend on the ability to improve the robustness of biomarkers to predict feed efficiency in a greater variety of environments (locations), managing conditions, feeding systems, production intensities, and other aspects.

PMID:38935984 | DOI:10.1016/j.animal.2024.101211

Obstet Gynecol. 2024 Jun 27. doi: 10.1097/AOG.0000000000005660. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the relationship between changes in Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) enrollment during pregnancy from 2016 to 2019 and rates of adverse pregnancy outcomes in U.S. counties in 2019.

METHODS: We conducted a serial, cross-sectional ecologic study at the county level using National Center for Health Statistics natality data from 2016 to 2019 of nulliparous individuals eligible for WIC. The exposure was the change in county-level WIC enrollment from 2016 to 2019 (increase [more than 0%] vs no change or decrease [0% or less]). Outcomes were adverse pregnancy outcomes assessed in 2019 and included maternal outcomes (ie, gestational diabetes mellitus [GDM], hypertensive disorders of pregnancy, cesarean delivery, intensive care unit [ICU] admission, and transfusion) and neonatal outcomes (ie, large for gestational age [LGA], small for gestational age [SGA], preterm birth, and neonatal intensive care unit [NICU] admission).

RESULTS: Among 1,945,914 deliveries from 3,120 U.S. counties, the age-standardized rate of WIC enrollment decreased from 73.1 (95% CI, 73.0-73.2) per 100 live births in 2016 to 66.1 (95% CI, 66.0-66.2) per 100 live births in 2019, for a mean annual percent change decrease of 3.2% (95% CI, -3.7% to -2.9%) per year. Compared with individuals in counties in which WIC enrollment decreased or did not change, individuals living in counties in which WIC enrollment increased had lower rates of maternal adverse pregnancy outcomes, including GDM (adjusted odds ratio [aOR] 0.71, 95% CI, 0.57-0.89), ICU admission (aOR 0.47, 95% CI, 0.34-0.65), and transfusion (aOR 0.68, 95% CI, 0.53-0.88), and neonatal adverse pregnancy outcomes, including preterm birth (aOR 0.71, 95% CI, 0.56-0.90) and NICU admission (aOR 0.77, 95% CI, 0.60-0.97), but not cesarean delivery, hypertensive disorders of pregnancy, or LGA or SGA birth.

CONCLUSION: Increasing WIC enrollment during pregnancy at the county level was associated with a lower risk of adverse pregnancy outcomes. In an era when WIC enrollment has decreased and food and nutrition insecurity has increased, efforts are needed to increase WIC enrollment among eligible individuals in pregnancy.

PMID:38935972 | DOI:10.1097/AOG.0000000000005660

JMIR Form Res. 2024 Jun 27;8:e58551. doi: 10.2196/58551.

ABSTRACT

BACKGROUND: Urinary incontinence (UI) affects millions of women with substantial health and quality-of-life impacts. Supervised pelvic floor muscle training (PFMT) is the recommended first-line treatment. However, multiple individual and institutional barriers impede women’s access to skilled care. Evidence suggests that digital health solutions are acceptable and may be effective in delivering first-line incontinence treatment, although these technologies have not yet been leveraged at scale.

OBJECTIVE: The primary objective is to describe the effectiveness and safety of a prescribed digital health treatment program to guide PFMT for UI treatment among real-world users. The secondary objectives are to evaluate patient engagement following an updated user platform and identify the factors predictive of success.

METHODS: This retrospective cohort study of women who initiated device use between January 1, 2022, and June 30, 2023, included users aged ≥18 years old with a diagnosis of stress, urgency, or mixed incontinence or a score of >33.3 points on the Urogenital Distress Inventory Short Form (UDI-6). Users are prescribed a 2.5-minute, twice-daily, training program guided by an intravaginal, motion-based device that pairs with a smartphone app. Data collected by the device or app include patient-reported demographics and outcomes, adherence to the twice-daily regimen, and pelvic floor muscle performance parameters, including angle change and hold time. Symptom improvement was assessed by the UDI-6 score change from baseline to the most recent score using paired 2-tailed t tests. Factors associated with meeting the UDI-6 minimum clinically important difference were evaluated by regression analysis.

RESULTS: Of 1419 users, 947 met inclusion criteria and provided data for analysis. The mean baseline UDI-6 score was 46.8 (SD 19.3), and the mean UDI-6 score change was 11.3 (SD 19.9; P<.001). Improvement was reported by 74% (697/947) and was similar across age, BMI, and incontinence subtype. Mean adherence was 89% (mean 12.5, SD 2.1 of 14 possible weekly uses) over 12 weeks. Those who used the device ≥10 times per week were more likely to achieve symptom improvement. In multivariate logistic regression analysis, baseline incontinence symptom severity and maximum angle change during pelvic floor muscle contraction were significantly associated with meeting the UDI-6 minimum clinically important difference. Age, BMI, and UI subtype were not associated.

CONCLUSIONS: This study provides real-world evidence to support the effectiveness and safety of a prescribed digital health treatment program for female UI. A digital PFMT program completed with visual guidance from a motion-based device yields significant results when executed ≥10 times per week over a period of 12 weeks. The program demonstrates high user engagement, with 92.9% (880/947) of users adhering to the prescribed training regimen. First-line incontinence treatment, when implemented using this digital program, leads to statistically and clinically substantial symptom improvements across age and BMI categories and incontinence subtypes.

PMID:38935967 | DOI:10.2196/58551

JMIR Bioinform Biotechnol. 2022 Dec 22;3(1):e42243. doi: 10.2196/42243.

ABSTRACT

BACKGROUND: The emergence of SARS-CoV-2 variants with mutations associated with increased transmissibility and virulence is a public health concern in Ontario, Canada. Characterizing how the mutational patterns of the SARS-CoV-2 genome have changed over time can shed light on the driving factors, including selection for increased fitness and host immune response, that may contribute to the emergence of novel variants. Moreover, the study of SARS-CoV-2 in the microcosm of Ontario, Canada can reveal how different province-specific public health policies over time may be associated with observed mutational patterns as a model system.

OBJECTIVE: This study aimed to perform a comprehensive analysis of single base substitution (SBS) types, counts, and genomic locations observed in SARS-CoV-2 genomic sequences sampled in Ontario, Canada. Comparisons of mutational patterns were conducted between sequences sampled during 4 different epochs delimited by major public health events to track the evolution of the SARS-CoV-2 mutational landscape over 2 years.

METHODS: In total, 24,244 SARS-CoV-2 genomic sequences and associated metadata sampled in Ontario, Canada from January 1, 2020, to December 31, 2021, were retrieved from the Global Initiative on Sharing All Influenza Data database. Sequences were assigned to 4 epochs delimited by major public health events based on the sampling date. SBSs from each SARS-CoV-2 sequence were identified relative to the MN996528.1 reference genome. Catalogues of SBS types and counts were generated to estimate the impact of selection in each open reading frame, and identify mutation clusters. The estimation of mutational fitness over time was performed using the Augur pipeline.

RESULTS: The biases in SBS types and proportions observed support previous reports of host antiviral defense activity involving the SARS-CoV-2 genome. There was an increase in U>C substitutions associated with adenosine deaminase acting on RNA (ADAR) activity uniquely observed during Epoch 4. The burden of novel SBSs observed in SARS-CoV-2 genomic sequences was the greatest in Epoch 2 (median 5), followed by Epoch 3 (median 4). Clusters of SBSs were observed in the spike protein open reading frame, ORF1a, and ORF3a. The high proportion of nonsynonymous SBSs and increasing dN/dS metric (ratio of nonsynonymous to synonymous mutations in a given open reading frame) to above 1 in Epoch 4 indicate positive selection of the spike protein open reading frame.

CONCLUSIONS: Quantitative analysis of the mutational patterns of the SARS-CoV-2 genome in the microcosm of Ontario, Canada within early consecutive epochs of the pandemic tracked the mutational dynamics in the context of public health events that instigate significant shifts in selection and mutagenesis. Continued genomic surveillance of emergent variants will be useful for the design of public health policies in response to the evolving COVID-19 pandemic.

PMID:38935965 | DOI:10.2196/42243

JMIR Bioinform Biotechnol. 2022 Jun 17;3(1):e33186. doi: 10.2196/33186.

ABSTRACT

BACKGROUND: Long noncoding RNAs (lncRNAs) are noncoding RNA transcripts greater than 200 nucleotides in length and are known to play a role in regulating the transcription of genes involved in vital cellular functions. We hypothesized the disease process in dysferlinopathy is linked to an aberrant expression of lncRNAs and messenger RNAs (mRNAs).

OBJECTIVE: In this study, we compared the lncRNA and mRNA expression profiles between wild-type and dysferlin-deficient murine myoblasts (C2C12 cells).

METHODS: LncRNA and mRNA expression profiling were performed using a microarray. Several lncRNAs with differential expression were validated using quantitative real-time polymerase chain reaction. Gene Ontology (GO) analysis was performed to understand the functional role of the differentially expressed mRNAs. Further bioinformatics analysis was used to explore the potential function, lncRNA-mRNA correlation, and potential targets of the differentially expressed lncRNAs.

RESULTS: We found 3195 lncRNAs and 1966 mRNAs that were differentially expressed. The chromosomal distribution of the differentially expressed lncRNAs and mRNAs was unequal, with chromosome 2 having the highest number of lncRNAs and chromosome 7 having the highest number of mRNAs that were differentially expressed. Pathway analysis of the differentially expressed genes indicated the involvement of several signaling pathways including PI3K-Akt, Hippo, and pathways regulating the pluripotency of stem cells. The differentially expressed genes were also enriched for the GO terms, developmental process and muscle system process. Network analysis identified 8 statistically significant (P<.05) network objects from the upregulated lncRNAs and 3 statistically significant network objects from the downregulated lncRNAs.

CONCLUSIONS: Our results thus far imply that dysferlinopathy is associated with an aberrant expression of multiple lncRNAs, many of which may have a specific function in the disease process. GO terms and network analysis suggest a muscle-specific role for these lncRNAs. To elucidate the specific roles of these abnormally expressed noncoding RNAs, further studies engineering their expression are required.

PMID:38935964 | DOI:10.2196/33186