Nevin Manimala

Bone. 2021 Sep 18:116208. doi: 10.1016/j.bone.2021.116208. Online ahead of print.

ABSTRACT

BACKGROUND: Bone mineral density (BMD) loss and fat gain is common in people living with HIV (PLWH), particularly after initiating combination antiretroviral therapy (cART). Given the close metabolic interaction between bone and fat, we tested the hypotheses that changes in bone-derived hormones are associated with fat accumulation and changes in fat-derived hormones are associated with BMD loss following cART initiation.

METHODS: HIV-seropositive subjects (n=15) initiating fixed dose cART of tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/FTC/EFV) underwent dual x-ray absorptiometry (DXA) assessment pre-cART and again 12-months post-cART initiation. DXA-derived measurements included BMD at the lumbar spine, femoral neck, total hip, and trochanter and the trunk and total fat. Serum undercarboxylated osteocalcin (ucOCN), sclerostin, lipocalin-2, leptin, and adiponectin were measured pre and post-cART. Spearman’s rank-order correlations assessed the cross-sectional associations between hormones and bone and fat mass pre- and post-cART. Linear regression models adjusting for baseline bone or fat mass assessed the association between hormone change and BMD/fat changes following cART initiation.

RESULTS: ucOCN (p=0.04) and lipocalin-2 (p=0.03) increased post-cART while sclerostin, leptin, and adiponectin remained unchanged. BMD significantly decreased post-cART at all skeletal sites. Trunk and total fat increased post-cART but not significantly, while weight and BMI remained unchanged. In models adjusting for baseline BMD and fat mass, change in ucOCN was negatively associated with change in trunk (p=0.008) and total fat (p=0.01) and the change in leptin was positively associated with change in total hip (p=0.03) and trochanteric BMD (p=0.02).

CONCLUSION: The current study demonstrates bone-fat crosstalk in cART initiating PLWH.

PMID:34547525 | DOI:10.1016/j.bone.2021.116208

J Sport Health Sci. 2021 Sep 18:S2095-2546(21)00103-4. doi: 10.1016/j.jshs.2021.09.006. Online ahead of print.

ABSTRACT

OBJECTIVE: Participation in sports is associated with many benefits to all aspects of health; however, it also come with the risk of injury, particularly concussions. Self-disclosure and care-seeking following a concussion are especially important due to the lack of outwardly visible signs and/or symptoms. While recent research has explored factors affecting concussion disclosure, utilization of isolated methodologies limits the ability to contextualize how disclosure or non-disclosure occurs. Therefore, the purpose of this study was to describe the factors and expectations of National Collegiate Athletic Association (NCAA) athletes that may influence concussion disclosure.

METHODS: This mixed-methods convergent parallel research study included 25 NCAA Division I athletes representing 13 sports, all of whom completed a concussion education session with pre-/post-test surveys and a semi-structured interview. Eligible athletes were at least 18 years old and on an NCAA roster. The surveys focused on previous concussion-related disclosure behaviors, knowledge, attitudes, beliefs, norms, and intentions toward disclosing concussion. Interviews focused on the athletes’ experiences related to concussion disclosure. Survey data were analyzed using descriptive statistics and Mann-Whitney U tests. Interviews were analyzed using a Consensual Qualitative Research (CQR) tradition.

RESULTS: Participants had high concussion knowledge (median = 46), positive attitudes (median = 38), strong beliefs (median = 13), and high intentions to disclose concussion symptoms (median = 7). None of the constructs differed by participant gender. Although quantitative findings were mostly positive, interview data highlighted factors that may explain why some participants are successful in disclosing concussions and why others may find disclosure difficult. Educational efforts, sport culture, and medical professional presence were the primary facilitators discussed by participants. Stigma, pressure, and a lack of team support were perceived as disclosure barriers.

CONCLUSION: The context in which concussion disclosure occurs, or does not occur, is vital to the success of educational interventions. Interventions must prioritize stakeholder and team-based perspectives on concussion to establish a network supportive to disclosure.

PMID:34547482 | DOI:10.1016/j.jshs.2021.09.006

Osteoarthritis Cartilage. 2021 Sep 18:S1063-4584(21)00910-9. doi: 10.1016/j.joca.2021.09.007. Online ahead of print.

ABSTRACT

OBJECTIVE: There is a need to incorporate multiple tissues into in vitro OA models to evaluate novel therapeutics. This approach is limited by inherent donor variability. We present an optimized research tool: a human OA cartilage-synovium explant co-culture model (OA-EXM) that employs donor-matched lower and upper limit response controls combined with statistical approaches to address variability. Multiple rapid read-outs allow for evaluation of therapeutics while cataloguing cartilage-synovium interactions.

DESIGN: 48-hour human explant cultures were sourced from OA knee arthroplasties. An OA-like cartilage-synovium co-culture baseline was established relative to donor-matched upper limit supraphysiological pro-inflammatory cytokine and lower limit OA cartilage or synovium alone controls. 100 nM dexamethasone treatment validated possible “rescue effects” within the OA-EXM dual tissue environment. Gene expression, proteoglycan loss, MMP activity, and soluble protein concentrations were analyzed using blocking and clustering methods.

RESULTS: The OA-EXM demonstrates the value of the co-culture approach as the addition of OA synovium increases OA cartilage proteoglycan loss and expression of MMP1, MMP3, MMP13, CXCL8, CCL2, IL6, and PTGS2, but not to the extent of supraphysiological stimulation. Conversely, OA cartilage does not affect gene expression or MMP activity of OA synovium. Dexamethasone shows dual treatment effects on synovium (pro-resolving macrophage upregulation, protease downregulation) and cartilage (pro-inflammatory, catabolic, and anabolic downregulation), and decreases soluble CCL2 levels in co-culture, thereby validating OA-EXM utility.

CONCLUSIONS: The OA-EXM is representative of late-stage OA pathology, captures dual interactions between cartilage and synovium, and combined with statistical strategies provides a rapid, sensitive research tool for evaluating OA therapeutics.

PMID:34547432 | DOI:10.1016/j.joca.2021.09.007

Biol Psychol. 2021 Sep 18:108190. doi: 10.1016/j.biopsycho.2021.108190. Online ahead of print.

ABSTRACT

Interoception and homeostatic/allostatic control are intertwined branches of closed-loop brain-body interactions (BBI). Given their importance in mental and psychosomatic disorders, establishing computational assays of BBI represents a clinically important but methodologically challenging endeavor. This technical note presents a novel approach, derived from a generic computational model of homeostatic/allostatic control that underpins (meta)cognitive theories of affective and psychosomatic disorders. This model views homeostatic setpoints as probability distributions (“homeostatic beliefs”) whose parameters determine regulatory efforts and change dynamically under allostatic predictions. In particular, changes in homeostatic belief precision, triggered by anticipated threats to homeostasis, are thought to alter cerebral regulation of bodily states. Here, we present statistical procedures for inferring homeostatic belief precision from measured bodily states and/or regulatory (action) signals. We analyze the inference problem, derive two alternative estimators of homeostatic belief precision, and apply our method to simulated data. Our proposed approach may prove useful for assessing BBI in individual subjects.

PMID:34547398 | DOI:10.1016/j.biopsycho.2021.108190

J Allergy Clin Immunol. 2021 Sep 18:S0091-6749(21)01402-0. doi: 10.1016/j.jaci.2021.08.027. Online ahead of print.

ABSTRACT

BACKGROUND: The epithelium is increasingly recognized as a pathologic contributor to asthma and its phenotypes. Although delayed wound closure by asthmatic epithelial cells is consistently observed, underlying mechanisms remain poorly understood, partly due to difficulties in studying dynamic physiologic processes involving polarized multilayered cell systems. Although Type-2 immunity has been suggested to play a role, the mechanisms by which repair is diminished are unclear.

OBJECTIVE: To develop and utilize primary multilayered polarized epithelial cell systems, derived from asthmatic patients, to evaluate cell migration in response to wounding under Type-2 and untreated conditions.

METHODS: A novel wounding device for multilayered polarized cells, along with time-lapse live cell/real-time confocal imaging were evaluated under IL-13 and untreated conditions. The influence of inhibition of the Type-2 enzyme, 15 lipoxygenase (15LO1), on the process was also addressed. Cell migration patterns were analyzed by high dimensional Frequency Modulated Möbius for statistical comparisons.

RESULTS: IL-13 stimulation negatively impacts wound healing by altering the Total speed, directionality and acceleration of individual cells. Inhibition 15LO1 partially improved the wound repair through improving Total speed.

CONCLUSIONS: Migration abnormalities contributed to markedly slower wound closure of IL-13 treated cells, which was modestly reversed by 15LO1 inhibition, suggesting its potential as an asthma therapeutic target. These novel methodologies offer new ways to dynamically study cell movements and identify contributing pathologic processes.

PMID:34547368 | DOI:10.1016/j.jaci.2021.08.027

Cancer Med. 2021 Sep 21. doi: 10.1002/cam4.4238. Online ahead of print.

ABSTRACT

BACKGROUND: Although primary splenic lymphoma (PSL) is rare, it ranks first among splenic primary malignant cancers, and the incidence of lymphoma of spleen has gradually increased in recent years. However, the efficacy of surgery for PSL has not been clinically verified by large sample data, which has affected the formulation of relevant guidelines.

AIM: To assess whether surgery can enhance the prognosis PSL patients.

METHODS: Extracted the data of patients with PSL from The Surveillance, Epidemiology, and End Results (SEER) database, and divided the patients into surgery and non-surgery group. Kaplan-Meier curves and log-rank tests were used to compare the overall survival (OS) and cancer-specific survival (CSS). The propensity score matching (PSM) was used to match the data, then compared the OS and CSS again. The COX proportional hazard regression model was used for univariate and multivariate analysis. Finally, we performed subgroup analysis in different Ahmann stages.

RESULTS: A sum of 2207 patients with PSL were enrolled, of which 1062 (48.1%) patients received surgery, and 1145 (51.9%) patients did not undergo surgery. Overall, patients in the surgery group had better OS and CSS. After the propensity scores matching, surgery was not statistically significant in OS and CSS. In the subgroup analysis, surgery was a protective factor for the OS and CSS in Ahmann I/II. However, surgery was no statistical significance in OS and CSS in Ahmann III. In patients with Ahmann Ⅰ/Ⅱ SMZL, surgery was a protective factor for OS and CSS. In patients with Ahmann Ⅲ SMZL, surgery was also statistically significant of OS and CSS.

CONCLUSIONS: Surgery can significantly improve the prognosis of patients with Ahmann Ⅰ/Ⅱ primary splenic lymphoma, but there was no survival difference in the Ahmann Ⅲ patients with or without surgery. For patients with SMZL, surgery was effective for improving OS and CSS.

PMID:34547191 | DOI:10.1002/cam4.4238

J Parasitol. 2021 Sep 1;107(5):770-777. doi: 10.1645/20-102.

ABSTRACT

Cryptosporidium spp. have been identified in a wide range of hosts, such as humans and domestic and wild animals, while less information about the prevalence of Cryptosporidium spp. in pet hamsters is documented. A total of 351 dwarf winter white Russian hamsters’ fecal specimens were collected from 6 pet markets from the cities of Luzhou and Ziyang in Sichuan province in the southwestern part of China. The prevalence of Cryptosporidium spp. determined with nested-PCR amplification of the partial small-subunit (SSU) rRNA gene was 39.32% (138/351). The highest prevalence of Cryptosporidium spp. was in pet market 5 (79.49%, 62/78), followed by pet market 6 (38.64%, 17/44). The lowest prevalence of Cryptosporidium spp. was observed in pet market 3 (14.89%, 7/47). Statistically significant differences in the prevalence of Cryptosporidium spp. were observed among different pet markets (χ2 = 76.386, df = 5, P < 0.05), and a further post hoc test revealed that only pet market 5 was significantly different from other pet markets. Molecular analysis showed that 4 different Cryptosporidium species or genotypes were identified: Cryptosporidium parvum (n = 127), Cryptosporidium chipmunk genotype III (n = 6), Cryptosporidium andersoni (n = 4), and Cryptosporidium wrairi (n = 1). The identification of Cryptosporidium spp. was further tested with the 60-kDa glycoprotein (GP60) gene, and the positive rate was 29.7% (41/138). This is the first molecular report on Cryptosporidium spp. infection in dwarf winter white Russian hamsters in China. With C. parvum and C. andersoni being identified in both humans and pet hamsters, these findings suggest that pet hamsters may be potential reservoirs of zoonotic Cryptosporidium species and subtypes.

PMID:34547101 | DOI:10.1645/20-102

JAMA. 2021 Sep 7;326(9):839-850. doi: 10.1001/jama.2021.11559.

ABSTRACT

IMPORTANCE: School and classroom allergens and particles are associated with asthma morbidity, but the benefit of environmental remediation is not known.

OBJECTIVE: To determine whether use of a school-wide integrated pest management (IPM) program or high-efficiency particulate air (HEPA) filter purifiers in the classrooms improve asthma symptoms in students with active asthma.

DESIGN, SETTING, AND PARTICIPANTS: Factorial randomized clinical trial of a school-wide IPM program and HEPA filter purifiers in the classrooms was conducted from 2015 to 2020 (School Inner-City Asthma Intervention Study). There were 236 students with active asthma attending 41 participating urban elementary schools located in the Northeastern US who were randomized to IPM by school and HEPA filter purifiers by classroom. The date of final follow-up was June 20, 2020.

INTERVENTIONS: The school-wide IPM program consisted of application of rodenticide, sealing entry points, trap placement, targeted cleaning, and brief educational handouts for school staff. Infestation was assessed every 3 months, with additional treatments as needed. Control schools received no IPM, cleaning, or education. Classroom portable HEPA filter purifiers were deployed and the filters were changed every 3 months. Control classrooms received sham HEPA filters that looked and sounded like active HEPA filter purifiers. Randomization was done independently (split-plot design), with matching by the number of enrolled students to ensure a nearly exact 1:1 student ratio for each intervention with 118 students randomized to each group. Participants, investigators, and those assessing outcomes were blinded to the interventions.

MAIN OUTCOMES AND MEASURES: The primary outcome was the number of symptom-days with asthma during a 2-week period. Symptom-days were assessed every 2 months during the 10 months after randomization.

RESULTS: Among the 236 students who were randomized (mean age, 8.1 [SD, 2.0] years; 113 [48%] female), all completed the trial. At baseline, the 2-week mean was 2.2 (SD, 3.9) symptom-days with asthma and 98% of the classrooms had detectable levels of mouse allergen. The results were pooled because there was no statistically significant difference between the 2 interventions (P = .18 for interaction). During a 2-week period, the mean was 1.5 symptom-days with asthma after use of the school-wide IPM program vs 1.9 symptom-days after no IPM across the school year (incidence rate ratio, 0.71 [95% CI, 0.38-1.33]), which was not statistically significantly different. During a 2-week period, the mean was 1.6 symptom-days with asthma after use of HEPA filter purifiers in the classrooms vs 1.8 symptom-days after use of sham HEPA filter purifiers across the school year (incidence rate ratio, 1.47 [95% CI, 0.79-2.75]), which was not statistically significantly different. There were no intervention-related adverse events.

CONCLUSIONS AND RELEVANCE: Among children with active asthma, use of a school-wide IPM program or classroom HEPA filter purifiers did not significantly reduce symptom-days with asthma. However, interpretation of the study findings may need to consider allergen levels, particle exposures, and asthma symptoms at baseline.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02291302.

PMID:34547084 | DOI:10.1001/jama.2021.11559

Int J Periodontics Restorative Dent. 2021 Sep-Oct;41(5):703-710. doi: 10.11607/prd.4973.

ABSTRACT

This article evaluated the sealing capacity of single crowns made of a new zirconia (Katana STML, Kuraray Noritake) when cemented with two different cement types and two different marginal preparation types. Forty intact human anterior teeth, extracted for periodontal reasons, were used. Each sample was prepared with two margin preparations: knife-edge (KE) on one half of the tooth and chamfer (CH) on the other half. Based on the type of cement used, abutments were randomly distributed into one of two groups: Group 1 used resin cement (Panavia V5, Kuraray Noritake), and Group 2 used reinforced glass-ionomer cement (FujiCEM 2, GC). A digital workflow was utilized for crown fabrication. After the cementing procedures, samples were processed, and microleakage and scanning electron microscopic observations were made. Microleakage varied significantly depending on the type of cement combination used. Group 1 samples showed less microleakage (medians: 0.76 for CH and 0.51 for KE in Group 1, and 4.1 and 3.45 for Group 2, respectively) than Group 2 specimens; the difference was statistically significant (P < .000). KE preparation showed less microleakage than CH, although no statistically significant differences were found (P < .0558). Under microscopic observations, some samples showed internal fractures within the zirconia material. KE and CH seal the margin of zirconia crowns similarly. The resin cement system ensured better adhesion than reinforced glass-ionomer cement.

PMID:34547074 | DOI:10.11607/prd.4973

Int J Periodontics Restorative Dent. 2021 Sep-Oct;41(5):665-673. doi: 10.11607/prd.4636.

ABSTRACT

This study evaluated the influence of different implant types on (1) radiographic marginal bone levels after healing and (2) radiographic and histomorphometric tissue levels and characteristics following ligature-induced peri-implantitis. Four implant types (Standard Plus, Straumann [S]; NobelReplace Tapered, Nobel Biocare [N]; In-Kone Universal, Global D [I]; and twinKon, Global D [T]) were randomly placed in the edentulous healed mandibular ridge of six dogs (T0), for a total of 57 implants placed. After 10 weeks, a peri-implantitis was ligature-induced (T1). After 12 weeks, biopsy samples were processed for histomorphometric analysis (T2). Standardized radiographs were taken at T0, T1, and T2 for imaging analysis. Statistical analysis was performed using mixed-effects linear modeling. After healing (T1), the radiographic marginal bone level was more coronal for implants I, T, and S compared to N. Following peri-implantitis (T2), the histologic marginal bone level was more coronal for implants I, T, and S compared to N, and for implants I and T compared to S. Also at T2, the radiographic marginal bone level was more coronal at implants I, T, and S compared to N. Implant type may influence bone remodeling during healing and bone loss during the early stages of experimental peri-implantitis.

PMID:34547068 | DOI:10.11607/prd.4636