Category: Nevin Manimala

PLoS One. 2022 Aug 3;17(8):e0272327. doi: 10.1371/journal.pone.0272327. eCollection 2022.

ABSTRACT

BACKGROUND: Interstitial lung disease (ILD) is the most important pulmonary manifestation of connective tissue diseases (CTDs) since it is associated with high morbidity and mortality. However, there is uncertainty on what constitutes the optimal treatment options from a variety of competing interventions. The aim of the overview is to summarize existing evidence of the effectiveness and harm of pharmacological therapies for adults with CTD-ILD.

METHODS: A literature search will be conducted in MEDLINE, the Cochrane Database of Systematic Reviews, DARE, the Centre for Reviews and Dissemination Health Technology Assessment database, Epistemonikos.org, KSR Evidence, and PROSPERO. We will search for systematic reviews with or without meta-analysis that examine pharmacological treatment for CTD-ILD. Updated supplemental search will also be undertaken to identify additional randomized controlled trials. The primary outcomes will be changes in lung function measures and adverse events. The methodological quality of the included reviews will be assessed using the AMSTAR 2 tool. The overall quality of the evidence will be evaluated using the GRADE rating. Summarized outcome data extracted from systematic reviews will be described in narrative form or in tables. For each meta-analysis we will estimate the summary effect size by use of random-effects and fixed-effects models with 95% confidence intervals, the between-study heterogeneity expressed by I², and the 95% prediction interval. If feasible, given sufficient data, network meta-analysis will be conducted to combine direct and indirect evidence of class and agent comparisons.

DISCUSSION: While many factors are crucial in selecting an appropriate treatment for patients with CTD-ILD, evidence for the efficacy and safety of a drug is essential in guiding this decision. Thus, this overview will aid clinicians in balancing the risks versus benefits of the available therapies by providing high-quality evidence to support informed decision-making and may contribute to future guideline development.

SYSTEMATIC REVIEW REGISTRATION: MedRxiv: DOI 10.1101/2022.01.25.22269807 PROSPERO: CRD42022303180.

PMID:35921316 | DOI:10.1371/journal.pone.0272327

Int J Med Educ. 2022 Jul 29;13:205-214. doi: 10.5116/ijme.62d2.8497.

ABSTRACT

OBJECTIVE: To assess the reliability and construct validity of a French version of the Jefferson Scale of Empathy-Students.

METHODS: A cross-sectional study was performed among undergraduate medical students in Tunisia. A total of 833 students completed a French version of the JSE-S using convenience sampling. To identify the internal consistency aspect of the reliability, Cronbach’s alpha coefficient was computed. Moreover, to assess the construct validity, the sample was randomly divided into two groups. Data from the first group (n=415) were subjected to exploratory factor analysis (EFA), with principal axing factoring (PAF) and oblimin rotation, to re-examine the underlying factor structure of the scale. Data from the second group (n=419) were used for confirmatory factor analysis (CFA) to confirm its latent variable structure. Some goodness-of-fit indices were used to assess the hypothesized model. Gender groups were compared using a t-test to check the known-group validity.

RESULTS: Reliability analysis reported an acceptable level of internal consistency, with an overall Cronbach’s alpha of 0.78 (95% CI [0.75,0.80]). EFA identified a two-factor structure, accounting for 27.4% of the total variance. The two-factor model produced good fit indices when item correlated errors were considered (χ²/df = 1.95, GFI = 0.92, CFI = 0.90, PCFI = 0.79, PGFI = 0.73 and RMSEA = 0.04). Female students had a statistically significant higher empathy scores than male students (t ₍₈₃₀₎ = – 4.16, p < .001).

CONCLUSIONS: The findings support the construct validity and reliability of a French version of the JSE for medical students. This instrument appears to be useful for investigating empathy among French-speaking populations.

PMID:35920177 | DOI:10.5116/ijme.62d2.8497

Soft Matter. 2022 Aug 3. doi: 10.1039/d2sm00935h. Online ahead of print.

ABSTRACT

The encapsulation and co-encapsulation of particles in microfluidic flows is essential in applications related to single-cell analysis and material synthesis. However, the whole encapsulation process is stochastic in nature, and its efficiency is limited by the so-called Poisson limit. We here demonstrate particle encapsulation in microfluidic devices having flow-focusing geometries with efficiency up to 2-fold larger than the stochastic limit imposed by the Poisson statistics. To this aim, we exploited the recently observed phenomenon of particle train formation in viscoelastic liquids, so that particles could approach the encapsulation area with a constant frequency that was subsequently synchronised to the constant frequency of droplet formation. We also developed a simplified expression based on the experimental results that can guide optimal design of the microfluidic encapsulation system. Finally, we report the first experimental evidence of viscoelastic co-encapsulation of particles coming from different streams.

PMID:35920163 | DOI:10.1039/d2sm00935h

Hypertension. 2022 Aug 3:101161HYPERTENSIONAHA12219566. doi: 10.1161/HYPERTENSIONAHA.122.19566. Online ahead of print.

ABSTRACT

BACKGROUND: Uromodulin regulates activity of the sodium-potassium-two-chloride transporter in the loop of Henle. In adults, higher urine uromodulin levels are associated with greater rise in blood pressure (BP) in response to salt intake. We hypothesized that higher urine uromodulin levels would be associated with higher BP in children with chronic kidney disease, and that there would be an interaction of dietary sodium on this association.

METHODS: In the chronic kidney disease in children Cohort, we utilized univariable and multivariable linear regression models to evaluate the relationship between baseline spot urine uromodulin levels indexed to urine creatinine (Umod/Cr mg/g) and 24-hour mean systolic and diastolic BP, as well as baseline clinic BP. We also tested whether sodium intake (g/day) modified these relationships.

RESULTS: Among 436 participants, the median age was 12.4 years (8.9-15.2), median estimated glomerular filtration rate was 50 mL/min per 1.73 m² (36-62), and median 24-hour mean systolic BP was 112 mm Hg (104-119). The etiology of chronic kidney disease was glomerular disease in 27%. In univariable models, each 2-fold higher Umod/Cr ratio was associated with a 1.66 mm Hg (95% CI, -2.31 to -1.00) lower 24-hour mean systolic and a 1.71 mm Hg (-2.45 to -0.97) lower clinic systolic BP. However, there was no statistically significant association between Umod/Cr and either 24-hour or clinic BP in multivariable models. We did not find a significant interaction between uromodulin and sodium intake in their effect on BP (P>0.05 in all models).

CONCLUSIONS: Urine uromodulin levels are not associated with BP in the chronic kidney disease in children cohort. Further studies are needed to confirm this finding in healthy pediatric cohorts.

PMID:35920156 | DOI:10.1161/HYPERTENSIONAHA.122.19566

Acta Obstet Gynecol Scand. 2022 Aug 3. doi: 10.1111/aogs.14425. Online ahead of print.

ABSTRACT

INTRODUCTION: Obstetric anal sphincter injuries (OASIS) are severe complications to vaginal births with potentially serious long-term consequences and large impact on quality of life. The aim was to determine risk and protective factors for OASIS.

MATERIAL AND METHODS: We performed a retrospective register-based observational study. A cohort of 988 988 singleton term deliveries 2005-2016 in Sweden were included. Data from the Swedish Medical Birth Registry and Statistics Sweden were extracted to identify cases of OASIS and maternal and fetal characteristics. Modified Poisson Regression analyses were performed to assess risk factors.

RESULTS: The rate of OASIS was 3.5% (n = 34 583). Primiparity (adjusted risk ratio [aRR] 3.13, 95% CI 3.05-3.21), vacuum extraction (aRR 2.79, 95% CI 2.73-2.86), forceps (aRR 4.27, 95% CI 3.86-4.72), and high birthweight (aRR 2.61, 95% CI 2.50-2.72) were associated with a significantly increased risk of OASIS. Increasing maternal age and decreasing maternal height also increased the risk of OASIS. Obesity increased the risk of OASIS (aRR 1.04, 95% CI 1.04-1.08), if fetal birthweight was not adjusted for. Smoking (aRR 0.74, 95% CI 0.70-0.79) and low maternal education (aRR 0.87, 95% CI 0.83-0.92) were associated with a decreased frequency of reported OASIS. Previous cesarean section increased the risk of OASIS (aRR 1.41, 95% CI 1.36-1.47).

CONCLUSIONS: Primiparity, instrumental delivery, and high birthweight significantly increased the risk of OASIS. Obesity, low height, increasing age, and previous cesarean section also increased the risk whereas smoking and low maternal educational level were associated with a lower OASIS rate.

PMID:35920107 | DOI:10.1111/aogs.14425

Bone Joint Res. 2022 Aug;11(8):548-560. doi: 10.1302/2046-3758.118.BJR-2021-0565.R1.

ABSTRACT

AIMS: We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism.

METHODS: Five datasets were obtained from the Gene Expression Omnibus database. Unsupervised consensus cluster analysis was used to determine new PMOP subtypes. To determine the central genes and the core modules related to PMOP, the weighted gene co-expression network analysis (WCGNA) was applied. Gene Ontology enrichment analysis was used to explore the biological processes underlying key genes. Logistic regression univariate analysis was used to screen for statistically significant variables. Two algorithms were used to select important PMOP-related genes. A logistic regression model was used to construct the PMOP-related gene profile. The receiver operating characteristic area under the curve, Harrell’s concordance index, a calibration chart, and decision curve analysis were used to characterize PMOP-related genes. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of the PMOP-related genes in the gene signature.

RESULTS: We identified three PMOP-related subtypes and four core modules. The muscle system process, muscle contraction, and actin filament-based movement were more active in the hub genes. We obtained five feature genes related to PMOP. Our analysis verified that the gene signature had good predictive power and applicability. The outcomes of the GSE56815 cohort were found to be consistent with the results of the earlier studies. qRT-PCR results showed that RAB2A and FYCO1 were amplified in clinical samples.

CONCLUSION: The PMOP-related gene signature we developed and verified can accurately predict the risk of PMOP in patients. These results can elucidate the molecular mechanism of RAB2A and FYCO1 underlying PMOP, and yield new and improved treatment strategies, ultimately helping PMOP monitoring.Cite this article: Bone Joint Res 2022;11(8):548-560.

PMID:35920104 | DOI:10.1302/2046-3758.118.BJR-2021-0565.R1

Bone Joint Res. 2022 Aug;11(8):541-547. doi: 10.1302/2046-3758.118.BJR-2021-0238.R3.

ABSTRACT

AIMS: This observational cross-sectional study aimed to answer the following questions: 1) how has nonunion incidence developed from 2009 to 2019 in a nationwide cohort; 2) what is the age and sex distribution of nonunions for distinct anatomical nonunion localizations; and 3) how high were the costs for surgical nonunion treatment in a level 1 trauma centre in Germany?

METHODS: Data consisting of annual International Classification of Diseases (ICD)-10 diagnosis codes from German medical institutions from 2009 to 2019, provided by the Federal Statistical Office of Germany (Destatis), were analyzed. Nonunion incidence was calculated for anatomical localization, sex, and age groups. Incidence rate ratios (IRRs) were determined and compared with a two-sample z-test. Diagnosis-related group (DRG)-reimbursement and length of hospital stay were retrospectively retrieved for each anatomical localization, considering 210 patients.

RESULTS: In 2019, a total of 11,840 nonunion cases (17.4/100,000 inhabitants) were treated. In comparison to 2018, the incidence of nonunion increased by 3% (IRR 1.03, 95% confidence interval (CI) 0.53 to 1.99, p = 0.935). The incidence was higher for male cases (IRR female/male: 0.79, 95% CI 0.76 to 0.82, p = 0.484). Most nonunions occurred at the pelvic and hip region (3.6/100,000 inhabitants, 95% CI 3.5 to 3.8), followed by the ankle and foot as well as the hand (2.9/100,000 inhabitants each). Mean estimated DRG reimbursement for in-hospital treatment of nonunions was highest for nonunions at the pelvic and hip region (€8,319 (SD 2,410), p < 0.001).

CONCLUSION: Despite attempts to improve fracture treatment in recent years, nonunions remain a problem for orthopaedic and trauma surgery, with a stable incidence throughout the last decade.Cite this article: Bone Joint Res 2022;11(8):541-547.

PMID:35920100 | DOI:10.1302/2046-3758.118.BJR-2021-0238.R3

Blood Res. 2022 Aug 3. doi: 10.5045/br.2022.2022057. Online ahead of print.

ABSTRACT

BACKGROUND: The pathophysiology underlying primary adult immune thrombocytopenic purpura (ITP) has not yet been identified. However, many mechanisms affect the immune system, causing defective tolerance to self-platelets and megakaryocytes. Cluster of differentiation 40 (CD40) contributes to both humoral and cell-mediated immune responses.

METHODS: This case-control study was conducted to detect rs4810485G>T and rs1883832C>T polymorphisms of CD40 in Egyptian patients with persistent/chronic ITP to clarify their possible association with chronic disease evolution. This study included 50 patients with persistent/chronic ITP and 50 healthy controls. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism technique.

RESULTS: Genotyping of rs1883832 and rs4810485 revealed no statistically significant differences between the two groups. However, combined gene polymorphism genotyping showed a statistically significant difference between the two groups (P<0.01).

CONCLUSION: Our results indicate a strong association between the combined polymorphism of both genes and susceptibility to developing ITP among adult Egyptian patients. Targeting this pathway using novel therapeutic approaches is promising.

PMID:35920091 | DOI:10.5045/br.2022.2022057

J Chem Theory Comput. 2022 Aug 3. doi: 10.1021/acs.jctc.2c00393. Online ahead of print.

ABSTRACT

Present-day atomistic simulations generate long trajectories of ever more complex systems. Analyzing these data, discovering metastable states, and uncovering their nature are becoming increasingly challenging. In this paper, we first use the variational approach to conformation dynamics to discover the slowest dynamical modes of the simulations. This allows the different metastable states of the system to be located and organized hierarchically. The physical descriptors that characterize metastable states are discovered by means of a machine learning method. We show in the cases of two proteins, chignolin and bovine pancreatic trypsin inhibitor, how such analysis can be effortlessly performed in a matter of seconds. Another strength of our approach is that it can be applied to the analysis of both unbiased and biased simulations.

PMID:35920063 | DOI:10.1021/acs.jctc.2c00393

Vet Dermatol. 2022 Aug 3. doi: 10.1111/vde.13103. Online ahead of print.

ABSTRACT

BACKGROUND: Assessment of the severity of pruritus is difficult in cats, because they manifest discomfort by increased licking, increased scratching or both.

HYPOTHESIS/OBJECTIVES: Our objective was to develop and validate a feline-specific pruritus scale (VAScat).

METHODS: The scale was designed as a double Visual Analog Scale (VAS), one VAS for licking and one for scratching, with severity and behavioural descriptors. The highest score (VAS-max) on either VAS was taken as the pruritus score for each cat. Owners of 153 cats with skin diseases and of 108 healthy cats scored their pet’s pruritus using the VAScat. Ninety-six of 153 cats with skin diseases also were re-evaluated after four to eight weeks of treatment.

RESULTS: Pearson’s correlation value between VAS-licking and VAS-scratching scores was r = 0.26 (p < 0.01), and Cronbach’s alpha was 0.41. Both indexes indicated that the two scales measure different manifestations of pruritus and supported the use of a dual assessing system. Comparison with a numerical pruritus severity scale (0, absent; 1, mild; 2, moderate; 3, severe) suggested that VAS-licking and VAS-scratching scales taken alone are unsuitable for measuring absent to mild pruritus (grades 0-1), while VAS-max is (p = 0.001). VAS-licking, VAS-scratching and VAS-max all were suitable to assess higher levels of pruritus (grades 2-3, p < 0.01). The VAScat was able to measure pruritus improvement following therapy, as post-treatment scores were significantly decreased compared to pre-treatment ones (p < 0.0001).

CONCLUSIONS AND CLINICAL IMPORTANCE: The VAScat proved to be a useful tool to assess pruritus in cats and for monitoring the response to treatment for pruritus.

PMID:35920060 | DOI:10.1111/vde.13103