Nevin Manimala

Transbound Emerg Dis. 2021 Nov 9. doi: 10.1111/tbed.14387. Online ahead of print.

ABSTRACT

Host immune response and virulence factors are key to disease susceptibility. However, there are no known association studies of human leukocyte antigen (HLA) class I and II alleles with chikungunya virus (CHIKV) infection in the Latin American population. Here we aimed to identify HLA alleles present in patients with CHIKV infection versus healthy controls as well as the allelic association with the clinical spectrum of the disease. We conducted a cross-sectional analysis of a community cohort and included patients aged 18 years and older with serologically confirmed CHIKV infection. HLA typing of HLA-A, HLA-B, and HLA-DRB1 alleles was performed. Two-by-two tables were used to establish associations between allele presence and clinical characteristics. Data from 65 patients with confirmed CHIKV infection were analyzed for HLA typing. CHIKV infection was significantly associated with the presence of HLA-A*68 (p = 0.005; odds ratio [OR]: 8.90; 95% confidence interval [CI]: 1.88-42.13), HLA-B*35 (p = 0.03; OR: 2.01; 95% CI: 1.06-3.86), HLA-DRB*01 (p<0.001; OR: 5.70; 95% CI: 1.95-16.59), HLA-DRB1*04 (p<0.001; OR: 7.37; 95% CI: 3.33-16.30), and HLA-DRB1*13 (p = 0.004; OR: 3.75; 95% CI: 1.50-9.39) alleles in patients versus healthy subjects. A statistically significant relationship was found between the presence of a rash on the face or abdomen and the presence of HLA-DRB1*04 (p = 0.028; OR: 3.2; 95% CI: 1.11-9.15 and p = 0.007; OR: 4.33; 95% CI: 1.45-12.88, respectively). Our study demonstrated that, in our cohort, HLA type I and type II alleles are associated with CHIKV infection, and an HLA type II allele is associated with dermatological symptoms. Further research is needed to establish a path for future investigation of genes outside the HLA system to improve knowledge of the pathophysiology of CHIKV infection and its host-pathogen interaction. This article is protected by copyright. All rights reserved.

PMID:34752688 | DOI:10.1111/tbed.14387

Immun Inflamm Dis. 2021 Nov 9. doi: 10.1002/iid3.564. Online ahead of print.

ABSTRACT

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is highly expressed by lymphocytes at skin sites affected by alopecia areata (AA). Variations in MCP-1 as well as in methylene-tetrahydrofolate reductase (MTHFR), a key enzyme related to many inflammatory pathologies, have been associated with several autoimmune disorders. This study was designed to test a possible association between MCP-1 and MTHFR variations and altered expression of their genes and the risk of AA.

METHODS: Blood samples of patients (60) suffering from AA as well as healthy subjects (60) were collected. Gene expression levels of MCP-1 and MTHFR were evaluated by real-time reverse-transcription polymerase chain reaction analysis. Moreover, MCP-1 rs1024611 (A-2518G) and MTHFR rs1801133 (C677T) polymorphisms were genotyped by using polymerase chain reaction-restriction fragment length polymorphism assays.

RESULTS: In contrast to MCP-1, the MTHFR gene expression was found to be significantly higher in patients than in controls. Further stratification of the patients revealed that polymorphic genotypes in MCP-1 (AG + GG) and MTHFR (CT + TT) could significantly alter gene expression levels. Elevation of MCP-1 expression was significantly associated with the total number of variant MCP-1 and MTHFR alleles. However, no statistically significant difference was noticed in the genotypic distribution of MCP-1 and MTHFR variations between patients and controls.

CONCLUSION: In summary, despite MCP-1 rs1024611 and MTHFR rs1801133 variations are not associated with AA risk, they may implicate the disease pathogenesis by influencing MCP-1 activity.

PMID:34752683 | DOI:10.1002/iid3.564

Macromol Rapid Commun. 2021 Nov 9:e2100632. doi: 10.1002/marc.202100632. Online ahead of print.

ABSTRACT

In this work, a block copolymer (BCP) consisting of poly((butyl methacrylate-co-benzophenone methacrylate-co-methyl methacrylate)-block-(2-hydroxyethyl methacrylate)) (P(BMA-co-BPMA-co-MMA)-b-P(HEMA)) was prepared by a two-step atom-transfer radical polymerization (ATRP) procedure. The obtained molecular weight of the BCP was 55100 g mol^-1 featuring a poly(HEMA) content of 10 mol-% and about 10 mol-% of the benzophenone methacrylate as UV cross-linker within the statistical copolymer segment. BCP membranes were fabricated applying the self-assembly and non-solvent induced phase separation (SNIPS) process from a ternary solvent mixture of tetrahydrofuran (THF), 1,4-dioxane, and dimethylformamide (DMF); (2:1:1 in mass). The presence of a porous top layer of the integral asymmetric membrane featuring pores of about 30 nm was confirmed via scanning electron microscopy (SEM). UV-mediated cross-linking protocols for the nanoporous membrane were adjusted to maintain the open and isoporous top layer of the stabilized membrane. The swelling capability of the non-cross-linked and cross-linked BCP membranes was investigated in water, water/ethanol mixture (1:1), and pure ethanol using atomic force microscopy (AFM), proving a stabilizing effect of the UV cross-linking on the porous structures. Finally, the influence of the herein described cross-linking protocols on water-flux measurements for the obtained membranes was explored. As a result, an increased swelling resistance for all tested solvents was found, leading to an increased water flux compared to the pristine membrane. The herein established UV-mediated cross-linking protocol is expected to pave the way to a new generation of porous and stabilized membranes within the fields of separation technologies. This article is protected by copyright. All rights reserved.

PMID:34752668 | DOI:10.1002/marc.202100632

Mycoses. 2021 Nov 9. doi: 10.1111/myc.13392. Online ahead of print.

ABSTRACT

BACKGROUND: Onychomycosis is a difficult-to-treat fungal nail infection whose treatment can involve systemic or topical antifungal approaches.

OBJECTIVES: To assess the efficacy and safety of terbinafine 10% nail lacquer in distal lateral subungual onychomycosis (DLSO).

PATIENTS/METHODS: Patients with mild-to-moderate DLSO were randomised (3:3:1) to receive double-blind topical terbinafine 10% (n = 406) or its vehicle (n = 410) administered once daily for 4 weeks and then once weekly for 44 weeks, or open-label topical amorolfine 5% (n = 137) for 48 weeks, with a 12-week follow-up period. The primary efficacy endpoint, complete cure rate at Week 60, was a composite of negative potassium hydroxide (KOH) microscopy, negative culture for dermatophytes and no residual clinical involvement of the target big toenail.

RESULTS: Complete cure rates at Week 60 in the terbinafine, vehicle and amorolfine groups were 5.67%, 2.20% and 2.92%, respectively (odds ratio (OR) vs vehicle = 2.68; 95% confidence intervals (CI): 1.22-5.86; p = .0138). Statistically significant differences in responder (negative KOH and negative culture and ≤10% residual clinical involvement) and mycological cure rates (negative KOH and negative culture) at Week 60 were obtained between terbinafine and vehicle. Terbinafine was well-tolerated with no systemic adverse reactions identified; the most common topical adverse reactions were erythema and skin irritation.

CONCLUSIONS: Terbinafine 10% nail lacquer was an effective treatment for mild-to-moderate onychomycosis improving both clinical and mycological criteria compared with vehicle. Furthermore, there may be some benefits compared to the currently available topical agent, amorolfine 5%. Treatment was well-tolerated and safe.

PMID:34752667 | DOI:10.1111/myc.13392

Magn Reson Med. 2021 Nov 9. doi: 10.1002/mrm.29065. Online ahead of print.

ABSTRACT

PURPOSE: Before MR fingerprinting (MRF) can be adopted clinically, the derived quantitative values must be proven accurate and repeatable over a range of T₁ and T₂ values and temperatures. Correct assessment of accuracy and precision as well as comparison between measurements can only be performed when temperature is either controlled or corrected for. The purpose of this study was to investigate the temperature dependence of T₁ and T₂ MRF values and evaluate the accuracy and repeatability of temperature-corrected relaxation values derived from a B₁ -corrected MRF-fast imaging with steady-state precession implementation using 2 different dictionary sizes.

METHODS: The International Society of MR in Medicine/National Institute of Standards and Technology phantom was scanned using an MRF sequence of 2 different lengths, a variable flip angle T₁ , and a multi-echo spin echo T₂ at 14 temperatures ranging from 15°C to 28°C and investigated with a linear regression model. Temperature-corrected accuracy was evaluated by correlating T₁ and T₂ times from each MRF dictionary with reference values. Repeatability was assessed using the coefficient of variation, with measurements taken over 30 separate sessions.

RESULTS: There was a statistically significant fit of the model for MRF-derived T₁ and T₂ and temperature (p < 0.05) for all the spheres with a T₁ > 500 ms. Both MRF methods showed a strong linear correlation with reference values for T₁ (R² = 0.996) and T₂ (R² = 0.982). MRF repeatability for T₁ values was ≤1.4% and for T₂ values was ≤3.4%.

CONCLUSION: MRF demonstrated relaxation times with a temperature dependence similar to that of conventional mapping methods. Temperature-corrected T₁ and T₂ values from both dictionaries showed adequate accuracy and excellent repeatability in this phantom study.

PMID:34752644 | DOI:10.1002/mrm.29065

Scand J Psychol. 2021 Nov 9. doi: 10.1111/sjop.12780. Online ahead of print.

ABSTRACT

The fifth version of Wechsler Intelligence Scale for Children is designed to measure five distinct aspects of intelligence, incorporating a new fluid reasoning index to the four indexes of the previous fourth version. Several factor analyses, however, have failed to support the fifth factor. The Scandinavian version is the only national version not showing clear superiority for the five-factor solution in the Manual. In the present study, we analyze WISC-V protocols from a clinical sample of 237 children tested with the new Scandinavian version. We perform six confirmatory factor analyses (CFA) testing three hierarchical-, two bifactor-, and one correlated candidate factor models. The study shows that the three-factor model does not fit the data, and that all four- and five-factor models showed good fit. The four-factor bifactor model was somewhat better than the five-bifactor and hierarchical models, but the correlated five-factor model was the superior model. Finding support for five-factors in a clinical sample representative of those most probable to be tested with the test, strengthen the claim that also the Scandinavian version measure a distinct fluid factor as intended by the test owners, and thus that clinicians may use the index scores as their main level of analysis. Review of previous CFAs show that the choice of statistical methods for CFA, bifactor or hierarchical/correlated, influence whether second order factor models are better than g-factor models.

PMID:34752640 | DOI:10.1111/sjop.12780

J Athl Train. 2021 Nov 1;56(11):1224-1231. doi: 10.4085/1062-6050-0494.20.

ABSTRACT

CONTEXT: Secondary schools that offer school-sponsored athletic events should follow best-practice guidelines to provide policies that promote student health and safety.

OBJECTIVE: To assess emergency preparedness from the perspective of athletic administrators (AAs) in Iowa secondary schools.

DESIGN: Cross-sectional study.

SETTING: Online survey.

PATIENTS OR OTHER PARTICIPANTS: Ninety-eight AAs from Iowa completed the survey (age = 45.33 ± 10.22 years, years as an AA = 9.37 ± 8.14, years in current role = 7.72 ± 7.09).

MAIN OUTCOME MEASURES(S): The 6-section survey contained with questions about access to athletic trainers (ATs), emergency action plans (EAPs), cardiopulmonary resuscitation (CPR), automated external defibrillators (AEDs), concussions, heat illness, and other general policies. Descriptive statistics (percentages and frequencies) were reported. Relative risk was calculated to compare schools with and those without access to ATs (P < .05).

RESULTS: Most respondents (76.5%, n = 75/98) reported their school had access to a licensed AT. The majority had a written EAP (83.3%, n = 70/84), but fewer than half (39.2%, n = 31/79) reviewed it annually and fewer than 10% (n = 6/85) reported practicing it each year. All respondents (100%, N = 78/78) stated they had an AED on campus. All respondents (N = 77/77) indicated that they were familiar with the Iowa High School Athletic Association’s (IHSAA’s) concussion policy and had a concussion guideline in place. Many respondents (95.9%, n = 71/74) described being familiar with the IHSAA’s heat illness policy, but more than half (62.1%, n = 41/66) noted they did not have a heat illness policy in place at their school.

CONCLUSIONS: Most respondents indicated their school had access to ATs, followed the state-mandated concussion guidelines, and had an AED. Although participants reported having written EAPs in place, levels of annual EAP review and practice were low. These results suggest that schools would benefit from educational opportunities to improve safety policies.

PMID:34752627 | DOI:10.4085/1062-6050-0494.20

J Athl Train. 2021 Nov 1;56(11):1180-1187. doi: 10.4085/1062-6050-0578.20.

ABSTRACT

CONTEXT: Anterior knee pain (AKP) is ubiquitous in early career military members and exacerbated during functional tasks required during military duties. Therefore, it is important to understand the risk of this condition among male and female tactical athletes in diverse military occupations.

OBJECTIVE: To assess sex and occupation with respect to the AKP risk in military members.

DESIGN: Descriptive epidemiology study.

SETTING: United States Armed Forces.

PATIENTS OR OTHER PARTICIPANTS: All military members diagnosed with anteropatellar or retropatellar pain, patellar instability, or knee tendinopathy on their initial encounter from 2006 to 2015.

MAIN OUTCOME MEASURE(S): The Defense Medical Epidemiology Database was queried for the number of individuals with AKP. Relative risk (RR) and χ2 statistics were calculated in the assessment of sex and occupational category. Regressions were calculated to determine associations between service branch, sex, and AKP across time.

RESULTS: From 2006 to 2015, a total of 151 263 enlisted and 14 335 officer service members were diagnosed with AKP. Enlisted females had an incidence rate of 16.7 per 1000 person-years compared with enlisted males’ incidence rate of 12.7 per 1000 person-years (RR = 1.32; 95% CI = 1.30, 1.34; P < .001) across all AKP diagnoses. Female officers had an incidence rate of 10.7 per 1000 person-years; male officers had an incidence rate of 5.3 per 1000 person-years (RR = 2.01; 95% CI = 1.94, 2.09). Differences in risk were also noted across military occupations for both enlisted and officer service members (P values < .05).

CONCLUSIONS: Sex and military occupation were salient factors for the AKP risk. Evaluating training requirements and developing intervention programs across military occupations could serve as a focus for future research aiming to decrease the incidence of chronic knee pain.

PMID:34752626 | DOI:10.4085/1062-6050-0578.20

J Anim Sci. 2021 Nov 9:skab330. doi: 10.1093/jas/skab330. Online ahead of print.

ABSTRACT

A total of 360 weanling barrows (Line 200 ×400, DNA, Columbus NE; initially 5.6 ± 0.03 kg) were used in a 42-d study to evaluate yeast-based pre- and probiotics (Phileo by Lesaffre, Milwaukee, WI) in diets with or without pharmacological levels of Zn on growth performance and antimicrobial resistance (AMR) patterns of fecal Escherichia coli. Pens were assigned to 1 of 4 dietary treatments with 5 pigs per pen and 18 pens per treatment. Dietary treatments were arranged in a 2 × 2 factorial with main effects of yeast-based pre- and probiotics (none vs. 0.10% ActiSaf Sc 47 HR+, 0.05% SafMannan, and 0.05% NucleoSaf from d 0 to 7, then concentrations were lowered by 50% from d 7 to 21) and pharmacological levels of Zn (110 vs. 3,000 mg/kg from d 0 to 7, and 2,000 mg/kg from d 7 to 21 with added Zn provided by ZnO). All pigs were fed a common diet from d 21 to 42 post-weaning. There were no yeast ×Zn interactions or effects from yeast additives observed on any response criteria. From d 0 to 21, and 0 to 42, pigs fed pharmacological levels of Zn had increased (P < 0.001) ADG and ADFI. Fecal samples were collected on d 4, 21, and 42 from the same three pigs per pen for fecal dry matter (DM) and AMR patterns of E. coli. On d 4, pigs fed pharmacological levels of Zn had greater fecal DM (P = 0.043); however, no differences were observed on d 21 or 42. E. coli was isolated from fecal samples and the microbroth dilution method was used to determine the minimal inhibitory concentrations (MIC) of E. coli isolates to 14 different antimicrobials. Isolates were categorized as either susceptible, intermediate, or resistant based on Clinical and Laboratory Standards Institute (CLSI) guidelines. The addition of pharmacological levels of Zn had a tendency (P = 0.051) to increase the MIC values of ciprofloxacin; however, these MIC values were still well under the CLSI classified resistant breakpoint for Ciprofloxacin. There was no evidence for differences (P > 0.10) for yeast additives or Zn for AMR of fecal E. coli isolates to any of the remaining antibiotics. In conclusion, pharmacological levels of Zn improved ADG, ADFI, and all isolates were classified as susceptible to ciprofloxacin although the MIC of fecal E. coli tended to be increased. Thus, the short-term use of pharmacological levels of Zn did not increase antimicrobial resistance. There was no response observed from live yeast and yeast extracts for any of the growth, fecal DM, or AMR of fecal E. coli criteria.

PMID:34752618 | DOI:10.1093/jas/skab330

Biostatistics. 2021 Nov 9:kxab037. doi: 10.1093/biostatistics/kxab037. Online ahead of print.

ABSTRACT

Multimorbidity constitutes a serious challenge on the healthcare systems in the world, due to its association with poorer health-related outcomes, more complex clinical management, increases in health service utilization and costs, but a decrease in productivity. However, to date, most evidence on multimorbidity is derived from cross-sectional studies that have limited capacity to understand the pathway of multimorbid conditions. In this article, we present an innovative perspective on analyzing longitudinal data within a statistical framework of survival analysis of time-to-event recurrent data. The proposed methodology is based on a joint frailty modeling approach with multivariate random effects to account for the heterogeneous risk of failure and the presence of informative censoring due to a terminal event. We develop a generalized linear mixed model method for the efficient estimation of parameters. We demonstrate the capacity of our approach using a real cancer registry data set on the multimorbidity of melanoma patients and document the relative performance of the proposed joint frailty model to the natural competitor of a standard frailty model via extensive simulation studies. Our new approach is timely to advance evidence-based knowledge to address increasingly complex needs related to multimorbidity and develop interventions that are most effective and viable to better help a large number of individuals with multiple conditions.

PMID:34752610 | DOI:10.1093/biostatistics/kxab037