Tag: nevin manimala

Hum Reprod. 2022 Jan 28;37(2):366-383. doi: 10.1093/humrep/deab254.

ABSTRACT

STUDY QUESTION: Is there a shared genetic or causal association of endometriosis with asthma or what biological mechanisms may underlie their potential relationships?

SUMMARY ANSWER: Our results confirm a significant but non-causal association of endometriosis with asthma implicating shared genetic susceptibility and biological pathways in the mechanisms of the disorders, and potentially, their co-occurrence.

WHAT IS KNOWN ALREADY: Some observational studies have reported a pattern of co-occurring relationship between endometriosis and asthma; however, there is conflicting evidence and the aetiology, as well as the underlying mechanisms of the relationship, remain unclear.

STUDY DESIGN, SIZE, DURATION: We applied multiple statistical genetic approaches in the analysis of well-powered, genome-wide association study (GWAS) summary data to comprehensively assess the relationship of endometriosis with asthma. Endometriosis GWAS from the International Endogene Consortium (IEC, 17 054 cases and 191 858 controls) and asthma GWAS from the United Kingdom Biobank (UKB, 26 332 cases and 375 505 controls) were analysed. Additional asthma data from the Trans-National Asthma Genetic Consortium (TAGC, 19 954 cases and 107 715 controls) were utilized for replication testing.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We assessed single-nucleotide polymorphism (SNP)-level genetic overlap and correlation between endometriosis and asthma using SNP effect concordance analysis (SECA) and linkage disequilibrium score regression analysis (LDSC) methods, respectively. GWAS meta-analysis, colocalization (GWAS-PW), gene-based and pathway-based functional enrichment analysis methods were applied, respectively, to identify SNP loci, genomic regions, genes and biological pathways shared by endometriosis and asthma. Potential causal associations between endometriosis and asthma were assessed using Mendelian randomization (MR) methods.

MAIN RESULTS AND THE ROLE OF CHANCE: SECA revealed significant concordance of SNP risk effects across the IEC endometriosis and the UKB asthma GWAS. Also, LDSC analysis found a positive and significant genetic correlation (rG = 0.16, P = 2.01 × 10-6) between the two traits. GWAS meta-analysis of the IEC endometriosis and UKB asthma GWAS identified 14 genome-wide significant (Pmeta-analysis < 5.0 × 10-8) independent loci, five of which are putatively novel. Three of these loci were consistently replicated using TAGC asthma GWAS and reinforced in colocalization and gene-based analyses. Additional shared genomic regions were identified in the colocalization analysis. MR found no evidence of a significant causal association between endometriosis and asthma. However, combining gene-based association results across the GWAS for endometriosis and asthma, we identified 17 shared genes with a genome-wide significant Fisher’s combined P-value (FCPgene) <2.73 × 10-6. Additional analyses (independent gene-based analysis) replicated evidence of gene-level genetic overlap between endometriosis and asthma. Biological mechanisms including ‘thyroid hormone signalling’, ‘abnormality of immune system physiology’, ‘androgen biosynthetic process’ and ‘brain-derived neurotrophic factor signalling pathway’, among others, were significantly enriched for endometriosis and asthma in a pathway-based analysis.

LARGE SCALE DATA: The GWAS for endometriosis data were sourced from the International Endogen Consortium (IEC) and can be accessed by contacting the consortium. The GWAS data for asthma are freely available online at Lee Lab (https://www.leelabsg.org/resources) and from the Trans-National Asthma Genetic Consortium (TAGC).

LIMITATIONS, REASONS FOR CAUTION: Given we analysed GWAS datasets from mainly European populations, our results may not be generalizable to other ancestries.

WIDER IMPLICATIONS OF THE FINDINGS: This study provides novel insights into mechanisms underpinning endometriosis and asthma, and potentially their observed relationship. Findings support a co-occurring relationship of endometriosis with asthma largely due to shared genetic components. Agents targeting ‘selective androgen receptor modulators’ may be therapeutically relevant in both disorders. Moreover, SNPs, loci, genes and biological pathways identified in our study provide potential targets for further investigation in endometriosis and asthma.

STUDY FUNDING/COMPETING INTEREST(S): National Health and Medical Research Council (NHMRC) of Australia (241,944, 339,462, 389,927, 389,875, 389,891, 389,892, 389,938, 443,036, 442,915, 442,981, 496,610, 496,739, 552,485, 552,498, 1,026,033 and 1,050,208), Wellcome Trust (awards 076113 and 085475) and the Lundbeck Foundation (R102-A9118 and R155-2014-1724). All researchers had full independence from the funders. Authors do not have any conflict of interest.

PMID:35472084 | DOI:10.1093/humrep/deab254

J Am Acad Orthop Surg. 2022 Apr 25. doi: 10.5435/JAAOS-D-21-01169. Online ahead of print.

ABSTRACT

INTRODUCTION: Fragility fractures are an enduring source of morbidity in the elderly with unfortunate frequency and rising costs. Although the predominant cause of fractures is generally understood to be falls, the exact stratification of the causes of fractures presenting to the emergency department has not yet been described in the literature. We sought out to stratify the primary products associated with fractures in the elderly, further describing the anatomic location of the fracture and setting of injury.

METHODS: We queried the National Electronic Injury Surveillance System database for all fractures in patients older than 65 years from January 1, 2000, to December 31, 2019. We analyzed demographic data, patient disposition, anatomic fracture location, and injury setting for the top 20 causes of fractures. Trends, proportions and distributions were analyzed using descriptive statistics.

RESULTS: A total of 901,418 visits to the Emergency Department were reviewed. Of these, 216,657 (24%) were found to have fractures. The top 20 causes for fractures accounted for a total of 173,557 (19%) fractures. The average age in our population was 80.1 years (SD 8.7). Women constituted most of the patients (127,753 [74%]). Flooring (58,347 [33.6%]) was the most common product associated with the cause of fractures, with stairs/steps (29,804 [17.2%]) and bed/bed frames (19,004 [10.9%]) being the second and third most common, respectively. Lower extremity fractures (97,195 [56%]) were more common than upper extremity fractures (63,899 [37%]). The lower trunk (pelvis, femoral neck, and lower spine) was the most common anatomic location of fractures reported (64,132 [37.0%]). Most fractures occurred either at home (113,158 [65.2%]) or at a public setting (31,162 [18.0%]).

CONCLUSIONS: Most products associated with fractures among mature adults were related to flooring, stairs, or bedding. This study offers a detailed understanding on the common products associated with fractures in mature adults and aids in discussing preventive measures for lowering fracture risk with patients, communities, and healthcare systems.

PMID:35472060 | DOI:10.5435/JAAOS-D-21-01169

Spine (Phila Pa 1976). 2022 Apr 21. doi: 10.1097/BRS.0000000000004374. Online ahead of print.

ABSTRACT

STUDY DESIGN: Prospective cohort study.

OBJECTIVE: To evaluate whether sagittal and spinopelvic alignment correlate with preoperative patient-reported outcomes (PROs) in degenerative lumbar spondylolisthesis (DLS) with spinal stenosis.

SUMMARY OF BACKGROUND DATA: Positive global sagittal balance and spinopelvic malalignment are strongly correlated with symptom severity in adult spinal deformity, but this correlation has not been evaluated in DLS.

METHODS: Patients were enrolled in the Canadian Spine Outcomes Research Network (CSORN) prospective DLS study at 7 centres between January 2015 and May 2018. Correlation was assessed between the following preoperative PROs: Oswestry Disability Index (ODI), numeric rating scale (NRS) leg pain and NRS back pain and the following preoperative sagittal radiographic parameters SS, PT, PI, SVA, LL, TK, T1SPI, T9SPI, and PI-LL. Patients were further divided into groups based on spinopelvic alignment: Group 1 PI-LL<10°; Group 2 PI-LL≥10° with PT < 30°; and Group 3 PI-LL≥10° with PT≥30°. Preoperative PROs were compared among these 3 groups and were further stratified by those with SVA<50 mm and SVA≥50 mm.

RESULTS: 320 patients (61% female) with mean age of 66.1 years were included. Mean (SD) preoperative PROs were: NRS leg pain 7.4 (2.1), NRS back pain 7.1 (2.0), and ODI 45.5 (14.5). Preoperative radiographic parameters included: SVA 27.1 (33.4) mm, LL 45.7 (13.4º), PI 57.6 (11.9), and PI-LL 11.8 (14.0º). Weak but statistically significant correlations were observed between leg pain and PT (r = -0.114) and PI (ρ = -0.130), and T9SPI with back pain (r = 0.130). No significant differences were observed among the three groups stratified by PI-LL and PT. No significant differences in PROs were observed between patients with SVA<50 mm compared to those with SVA≥50 mm.

CONCLUSIONS: Sagittal and spinopelvic malalignment does not appear to significantly influence baseline PROs in patients with degenerative lumbar spondylolisthesis.

LEVEL OF EVIDENCE: Prognostic Level II.

PMID:35472076 | DOI:10.1097/BRS.0000000000004374

Psychosom Med. 2022 Apr 27. doi: 10.1097/PSY.0000000000001087. Online ahead of print.

ABSTRACT

OBJECTIVE: Recent research identified that workplace factors play a role in the development of diabetes mellitus (DM). This study examines the longitudinal association of work-related overqualification with the incidence of DM over a 14-year follow-up period.

METHODS: We used data from the 2003 Canadian Community Health Survey linked to the Ontario Health Insurance Plan and the Canadian Institute for Health Information Discharge Abstract databases. Cox-proportional hazards regression models were performed to evaluate the relationship between overqualification and the incidence of DM.

RESULTS: Over the study period, there were 91,835 person-years of follow-up (median follow-up 13.7 years). The final sample included 7,026 respondents (mean age at baseline = 47.1; SD = 8.2; 47% female). An elevated risk of DM was associated with substantial overqualification (HR = 1.58, 95% CI: 1.01 – 2.49) after adjustment for socio-demographic, health and work variables. Additional adjustment for body mass index (BMI) and health behaviours attenuated this risk (HR = 1.30, 95% CI: 0.81 – 2.08). Underqualification was not associated with the incidence of DM in adjusted regression models. We did not observe any statistical difference in the effects of overqualification on DM risk across sex or education groups.

CONCLUSIONS: This study adds to the growing body of research literature uncovering the relationships between work exposures and DM risk. The results from the study suggest that higher BMI, and to a lesser extent health behaviours, may be mediating factors in the association between overqualification and incident DM. Further research on the association of overqualification with DM is warranted.

PMID:35472044 | DOI:10.1097/PSY.0000000000001087

Am J Hematol. 2022 Apr 26. doi: 10.1002/ajh.26581. Online ahead of print.

ABSTRACT

Iron overload is a severe general complication of hereditary anemias. Treatment with iron chelators is hampered by important side-effects, high costs and the lack of availability in many countries with high prevalence of hereditary anemias. In this phase III randomized placebo-controlled trial we assigned adults with non-transfusion-dependent hereditary anemias with mild-to-moderate iron overload to receive esomeprazole (at a dose of 40mg twice daily) or placebo for 12 months in a cross-over design. The primary end point was change of liver iron content measured by MRI. A total of thirty participants were enrolled in the trial. Treatment with esomeprazole resulted in a statistically significant reduction in liver iron content that was 0.55 mg Fe/g dw larger than after treatment with placebo (95%CI [0.05 to 1.06]; p=0.03). Median baseline liver iron content at start of esomeprazole was 4.99 versus 4.49 mg Fe/g dw at start of placebo. Mean delta liver iron content after esomeprazole treatment was -0.57 (SD 1.20) versus -0.11 mg Fe/g dw (SD 0.75) after placebo treatment. Esomeprazole was well tolerated, reported adverse events were mild and none of the patients withdrew from the study due to side effects. In summary, esomeprazole resulted in a significant reduction in liver iron content when compared to placebo in a heterogeneous group of patients with non-transfusion-dependent hereditary anemias. From an international perspective this result can have major implications given the fact that proton pump inhibitors may frequently be the only realistic therapy for many patients without access to or not tolerating iron chelators. This article is protected by copyright. All rights reserved.

PMID:35472008 | DOI:10.1002/ajh.26581

J Am Acad Orthop Surg Glob Res Rev. 2022 Apr 1;6(4). doi: 10.5435/JAAOSGlobal-D-21-00016.

ABSTRACT

Whether to undergo bilateral total knee arthroplasty (BTKA) depends on patient and surgeon preferences. We used the National Inpatient Sample to compare temporal trends in BTKA utilization and in-hospital complication rates among TKA patients ≥50 with Medicare/Medicaid versus private insurance from 2007 to 2016. We used multivariable logistic regression to assess the association between insurance type and trends in utilization and complication rates adjusting for individual-, hospital-, and community-level covariates, using unilateral TKA (UTKA) for reference. Discharge weights were used for nationwide estimates. About 132,400 (49.5%) Medicare/Medicaid patients and 135,046 (50.5%) privately insured patients underwent BTKA. Among UTKA patients, 62.7% had Medicare/Medicaid, and 37.3% had private insurance. Over the study period, BTKA utilization rate decreased from 7.18% to 5.63% among privately insured patients and from 4.59% to 3.13% among Medicaid/Medicare patients (P trend difference <0.0001). In multivariable analysis, Medicare/Medicaid patients were less likely to receive BTKA than privately insured patients. Although Medicare/Medicaid patients were more likely to develop in-hospital complications after UTKA (adjusted odds ratio, 1.06; 95% confidence interval, 1.002 to 1.12; P = 0.04), this relationship was not statistically significant for BTKAs. In this nationwide sample of TKA patients, BTKA utilization rate was higher in privately insured patients compared with Medicare/Medicaid patients. Furthermore, privately insured patients had lower in-hospital complication rates than Medicare/Medicaid patients.

PMID:35472007 | DOI:10.5435/JAAOSGlobal-D-21-00016

Inflamm Bowel Dis. 2022 Apr 26:izac088. doi: 10.1093/ibd/izac088. Online ahead of print.

ABSTRACT

BACKGROUND: There is lack of knowledge concerning postpartum infections in women with inflammatory bowel disease (IBD). Our aim is to determine the 30-day postpartum infectious complications in women with and without IBD who have a caesarian section, normal vaginal delivery, or assisted vaginal delivery.

METHODS: We used Danish national registries to establish a study population of liveborn, singleton births from January 1, 1997, through December 31, 2015. We examined 30-day postpartum maternal infectious complications in women with and without IBD, according to the mode of delivery. Statistical models were adjusted for multiple confounders.

RESULTS: In all, 3255 women with and 207 608 without IBD had a caesarian section. Within 30 days postpartum, 4.5% of women with and 3.7% without IBD had an infectious complication. Increased infectious complications included overall infections (adjusted OR [aOR], 1.83; 95% confidence interval [CI], 1.35-2.47), infections of the gastrointestinal tract (aOR, 4.36, 95% CI 2.34-8.10), and infections of the skin and subcutaneous tissue (aOR, 4.45; 95% CI, 2.30-8.50). Other puerperal infections, urological and gynecological, and other infections were increased, although not significantly. For vaginal deliveries, 1.6% of 5771 women with IBD and 1.3% of 793 110 women without IBD had an infectious complication, and the aOR of infections of the gastrointestinal tract was 3.17 (95% CI, 1.47-6.85). There were too few outcomes to calculate the risk of infections after assisted vaginal delivery.

CONCLUSIONS: The risk of a 30-day postpartum infectious complication is increased in women with IBD. Physicians should carefully monitor their patients postpartum to prevent these adverse outcomes.

PMID:35472003 | DOI:10.1093/ibd/izac088

J Am Coll Health. 2022 Apr 26:1-4. doi: 10.1080/07448481.2022.2066976. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to identify out-of-hospital cardiac arrest characteristics for patients treated by collegiate-based emergency medical services (CBEMS) organizations.

PARTICIPANTS: CBEMS organizations provided data via the National Collegiate EMS Foundation Cardiac Arrest Data Registry.

METHODS: CBEMS organization details, patient demographics, cardiac arrest characteristics and treatments, and prehospital outcomes for cases spanning October 2007 to May 2020 were analyzed with descriptive statistics.

RESULTS: There were 65 OHCA entries. The majority were for male patients (82%) and a notable number of cases occurred in patients 45 years of age or younger (41%). Cases were frequently witnessed (71%) with high rates of bystander cardiopulmonary resuscitation (57%) and defibrillation (29%) prior to EMS arrival. Almost half of the patients (48%) had achieved return of spontaneous circulation until care was transferred to a provider of equal/higher level.

CONCLUSIONS: CBEMS organizations may be well situated to respond rapidly to on-campus OHCAs.

PMID:35472006 | DOI:10.1080/07448481.2022.2066976

PLoS Negl Trop Dis. 2022 Apr 26;16(4):e0010324. doi: 10.1371/journal.pntd.0010324. eCollection 2022 Apr.

ABSTRACT

BACKGROUND: The combination of Wolbachia-based incompatible insect technique (IIT) and radiation-based sterile insect technique (SIT) can be used for population suppression of Aedes aegypti. Our main objective was to evaluate whether open-field mass-releases of wAlbB-infected Ae. aegypti males, as part of an Integrated Vector Management (IVM) plan led by the Mexican Ministry of Health, could suppress natural populations of Ae. aegypti in urbanized settings in south Mexico.

METHODOLOGY/PRINCIPAL FINDINGS: We implemented a controlled before-and-after quasi-experimental study in two suburban localities of Yucatan (Mexico): San Pedro Chimay (SPC), which received IIT-SIT, and San Antonio Tahdzibichén used as control. Release of wAlbB Ae. aegypti males at SPC extended for 6 months (July-December 2019), covering the period of higher Ae. aegypti abundance. Entomological indicators included egg hatching rates and outdoor/indoor adult females collected at the release and control sites. Approximately 1,270,000 lab-produced wAlbB-infected Ae. aegypti males were released in the 50-ha treatment area (2,000 wAlbB Ae. aegypti males per hectare twice a week in two different release days, totaling 200,000 male mosquitoes per week). The efficacy of IIT-SIT in suppressing indoor female Ae. aegypti density (quantified from a generalized linear mixed model showing a statistically significant reduction in treatment versus control areas) was 90.9% a month after initiation of the suppression phase, 47.7% two months after (when number of released males was reduced in 50% to match local abundance), 61.4% four months after (when initial number of released males was re-established), 88.4% five months after and 89.4% at six months after the initiation of the suppression phase. A proportional, but lower, reduction in outdoor female Ae. aegypti was also quantified (range, 50.0-75.2% suppression).

CONCLUSIONS/SIGNIFICANCE: Our study, the first open-field pilot implementation of Wolbachia IIT-SIT in Mexico and Latin-America, confirms that inundative male releases can significantly reduce natural populations of Ae. aegypti. More importantly, we present successful pilot results of the integration of Wolbachia IIT-SIT within a IVM plan implemented by Ministry of Health personnel.

PMID:35471983 | DOI:10.1371/journal.pntd.0010324

J Chem Theory Comput. 2022 Apr 26. doi: 10.1021/acs.jctc.1c00548. Online ahead of print.

ABSTRACT

Despite the variety of available computational approaches, state-of-the-art methods for calculating excitation energies, such as time-dependent density functional theory (TDDFT), are computationally demanding and thus limited to moderate system sizes. Here, we introduce a new variation of constrained DFT (CDFT), wherein the constraint corresponds to a particular transition (T), or a combination of transitions, between occupied and virtual orbitals, rather than a region of the simulation space as in traditional CDFT. We compare T-CDFT with TDDFT and ΔSCF results for the low-lying excited states (S₁ and T₁) of a set of gas-phase acene molecules and OLED emitters and with reference results from the literature. At the PBE level of theory, T-CDFT outperforms ΔSCF for both classes of molecules, while also proving to be more robust. For the local excitations seen in the acenes, T-CDFT and TDDFT perform equally well. For the charge transfer (CT)-like excitations seen in the OLED molecules, T-CDFT also performs well, in contrast to the severe energy underestimation seen with TDDFT. In other words, T-CDFT is equally applicable to both local excitations and CT states, providing more reliable excitation energies at a much lower computational cost than TDDFT cost. T-CDFT is designed for large systems and has been implemented in the linear-scaling BigDFT code. It is therefore ideally suited for exploring the effects of explicit environments on excitation energies, paving the way for future simulations of excited states in complex realistic morphologies, such as those which occur in OLED materials.

PMID:35471972 | DOI:10.1021/acs.jctc.1c00548