Characterization of a unique Sikkimese yak population of India: a multivariate approach.

Native Sikkimese yak in Sikkim state of India is a pastoral treasure being raised through centuries-old transhumance practices and has evolved in response to natural and man-made selection. Currently, the population of Sikkimese yak is at risk with about five thousand total headcounts. Characterization is essential for taking appropriate decisions for conservation of any endangered population. In an attempt to phenotypically characterize the Sikkimese yaks, this study recorded phenotypic morphometric traits information, viz., body length (LG), height at withers (HT), heart girth (HG), paunch girth (PG), horn length (HL), horn circumference (HC), distance between horns (DbH), ear length (EL), face length (FL), face width (FW), and tail length with switch (TL), on 2154 yaks of both sexes. Multiple correlation estimation highlighted that HG and PG, DbH and FW, and EL and FW were highly correlated. Using principal component analysis, LG, HT, HG, PG, and HL were found to be the most important traits for phenotypic characterization of Sikkimese yak animals. Discriminant analysis based on different locations of Sikkim hinted at the existence of two separate clusters, however, broadly, phenotypic uniformity could be observed. Subsequent genetic characterization can offer greater insights and can pave the way for future breed registration and conservation of the population.

User involvement throughout development of technology to support diabetes foot care: a case illustration of the devices for dignity PPIE model.

The successful development and implementation of any healthcare technology requires input from multiple stakeholders including clinical leads, trust information technology directorates as well as project management and procurement. In this process however, a key stakeholder that is often overlooked is the patient.This paper illustrates the crucial importance of patient involvement to avoid poor design and poor uptake of technology and subsequently poor health outcomes.To highlight this, we share a case example evidencing involvement of people with lived experience of foot ulcers resulting from Diabetic foot neuropathy throughout identification of unmet technology needs, design requirements for the device and iterative device development and evaluation.

A tool for evaluating novel osteoarthritis therapies using multivariate analyses of human cartilage-synovium explant co-culture.

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-h 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.

'Your mascara is running'.

Chromhidrosis is a rare disorder, which can have significant psychosocial consequences for patients, particularly when it affects the face, as it can be mistaken for scarring, dirt or erroneous make-up application. Chromhidrosis can be divided into apocrine, eccrine and pseudo subtypes. We present a case of apocrine chromhidrosis localized to the bilateral cheek area. Click https://www.wileyhealthlearning.com/#/online-courses/9c761d0a-20de-4709-a57d-36be93cf64e1 for the corresponding questions to this CME article.

Zinc finger protein-440 promotes cartilage degenerative mechanisms in human facet and knee osteoarthritis chondrocytes.

OBJECTIVES: To investigate the role of zinc finger protein 440 (ZNF440) in the pathophysiology of cartilage degeneration during facet joint (FJ) and knee osteoarthritis (OA). METHODS: Expression of ZNF440 in FJ and knee cartilage was determined by immunohistochemistry, quantitative (q)PCR, and Western blotting (WB). Human chondrocytes isolated from FJ and knee OA cartilage were cultured and transduced with ZNF440 or control plasmid, or transfected with ZNF440 or control small interfering RNA (siRNA), with/without interleukin (IL)-1ß. Gene and protein levels of catabolic, anabolic and apoptosis markers were determined by qPCR or WB, respectively. In silico analyses were performed to determine compounds with potential to inhibit expression of ZNF440. RESULTS: ZNF440 expression was increased in both FJ and knee OA cartilage compared to control cartilage. In vitro, overexpression of ZNF440 significantly increased expression of MMP13 and PARP p85, and decreased expression of COL2A1. Knockdown of ZNF440 with siRNA partially reversed the catabolic and cell death phenotype of human knee and FJ OA chondrocytes stimulated with IL-1ß. In silico analysis followed by validation assays identified scriptaid as a compound with potential to downregulate the expression of ZNF440. Validation experiments showed that scriptaid reduced the expression of ZNF440 in OA chondrocytes and concomitantly reduced the expression of MMP13 and PARP p85 in human knee OA chondrocytes overexpressing ZNF440. CONCLUSIONS: The expression of ZNF440 is significantly increased in human FJ and knee OA cartilage and may regulate cartilage degenerative mechanisms. Furthermore, scriptaid reduces the expression of ZNF440 and inhibits its destructive effects in OA chondrocytes.

Sequencing identifies a distinct signature of circulating microRNAs in early radiographic knee osteoarthritis.

OBJECTIVE: MicroRNAs act locally and systemically to impact osteoarthritis (OA) pathophysiology, but comprehensive profiling of the circulating miRNome in early vs late stages of OA has yet to be conducted. Sequencing has emerged as the preferred method for microRNA profiling since it offers high sensitivity and specificity. Our objective was to sequence the miRNome in plasma from 91 patients with early [Kellgren-Lawrence (KL) grade 0 or 1 (n = 41)] or late [KL grade 3 or 4 (n = 50)] symptomatic radiographic knee OA to identify unique microRNA signatures in each disease state. DESIGN: MicroRNA libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the Illumina NextSeq 550. Counts were produced for microRNAs captured in miRBase and for novel microRNAs. Statistical, bioinformatics, and computational biology approaches were used to refine and interpret the final list of microRNAs. RESULTS: From 215 differentially expressed microRNAs (FDR < 0.01), 97 microRNAs showed an increase or decrease in expression in ≥85% of samples in the early OA group as compared to the median expression in the late OA group. Increasing this threshold to ≥95%, seven microRNAs were identified: hsa-miR-335-3p, hsa-miR-199a-5p, hsa-miR-671-3p, hsa-miR-1260b, hsa-miR-191-3p, hsa-miR-335-5p, and hsa-miR-543. Four novel microRNAs were present in ≥50% of early OA samples and had 27 predicted gene targets in common with the prioritized set of predicted gene targets from the 97 microRNAs, suggesting common underlying mechanisms. CONCLUSION: Sequencing of well-characterized patient cohorts produced unbiased profiling of the circulating miRNome and identified a unique panel of 11 microRNAs in early radiographic knee OA.

TAT-Beclin-1 induces severe synovial hyperplasia and does not protect from injury-induced osteoarthritis in mice.

OBJECT: Autophagy maintains cartilage homeostasis and is compromised during osteoarthritis (OA), contributing to cartilage degeneration. We sought to determine if D-isomer TAT-Beclin-1, a potent inducer of autophagy, could attenuate post-traumatic OA in mice. METHODS: 10-week-old mice underwent destabilization of the medial meniscus (DMM) surgery to induce post-traumatic OA, or sham surgery (control), and injected intra-articularly with D-isomer TAT-Beclin-1 (0.5-2 mg/kg) or PBS 1 week post-surgery for up to 9 weeks. Mice were sacrificed at 2 or 10 weeks post-surgery. Knee joint sections were evaluated by histopathology for cartilage degeneration and synovitis, and immunostaining for key markers of autophagy (LC3B), cell proliferation (nuclear Ki67), activated fibroblasts (αSMA), and cells of hematopoietic origin (CD45). RESULTS: All D-isomer TAT-Beclin-1-treated DMM mice had no difference in the degree of cartilage degeneration compared to PBS-injected DMM mice. Surprisingly, all D-isomer TAT-Beclin-1-treated mice exhibited substantial synovial hyperplasia, with increased cellularity and ECM deposition (fibrosis-like phenotype), as compared to PBS-injected mice. Synovial effects of D-isomer TAT-Beclin-1 were dose- and injection frequency-dependent. An increased percentage of cells positive for LC3B and nuclear Ki67 were found in the synovial intima early after injection, which persisted after frequent injections. CONCLUSIONS: D-isomer TAT-Beclin-1 did not attenuate cartilage degeneration, but rather induced synovial hyperplasia associated with increased expression of key markers of autophagy and cell proliferation and a fibrosis-like phenotype, independent of markers of fibroblast activation or persistent hematopoietic-origin cell infiltration. These data suggest that, if not tissue-targeted, caution should be taken using autophagy activators due to diverse cellular responses in the joint.

Influence of Calcium Scaling on Corrosion Behavior of Steel and Aluminum Alloys.

Calcium scaling is a serious problem encountered in the oil and gas industry because it is common that brines produced alongside oil and gas exhibit high concentrations of calcium ions, among others, which is expensive to remedy. The precipitation of calcium salts on the internal wall of the pipelines may occur because of the physical and chemical changes as fluids are produced from downhole to surface facilities. Although different researchers have address scaling and corrosion in the oil and gas industry, there are few reports in the literature relating the corrosion and scaling phenomena simultaneously. Despite there being indications that scales may produce corrosion problems, affecting the mechanical integrity of the infrastructure, there is minimal research in the literature addressing such relations. Previous studies presented aluminum alloys as excellent and reliable materials for applications in the petroleum industry, such as drilling activities. In this work, we evaluate the corrosion behavior of steel and aluminum alloys under highly scaling environments using supersaturated brines. Our results show that the presence of calcium carbonate and calcium sulfate as a scaling environment increases the corrosion rates for aluminum alloys and carbon steel; however, the same environments do not affect the corrosion behavior of stainless steel.

Limited Health Literacy and Hearing Loss Among Older Adults.

BACKGROUND: Effective communications between health care providers and patients are critical for high-quality health care. OBJECTIVE: This study sampled adults age 65 years and older to explore (1) characteristics associated with limited health literacy (LHL) and (2) medical costs and gaps in care based on health literacy, hearing loss, and hearing aid use status. METHODS: The study included 19,223 adults age 65 years and older who completed a health survey that was linked to his or her medical claims that were generated after medical care provided in the year prior to survey completion. Health literacy, hearing loss, and hearing aid use were assessed through self-reports. Health literacy was coded as limited and adequate. Hearing loss and hearing aid use were coded into five categories: no hearing loss, unaided mild, aided mild, unaided severe, and aided severe hearing loss. KEY RESULTS: Seven percent reported LHL and 41% reported hearing loss. Hearing loss, especially unaided severe, was associated with LHL, as were memory loss, depression, loneliness, older age, and male gender. People with aided severe hearing loss and LHL had higher annual medical costs than those with adequate health literacy. Similarly, those with no hearing loss and LHL had higher annual medical costs than those with adequate health literacy. CONCLUSIONS: Unaided mild, aided severe, and unaided severe hearing loss were positively associated with LHL, although the association was reduced among hearing aid users. Specifically, aided mild or severe hearing loss had lower odds of LHL, compared to unaided mild or severe hearing loss, respectively. We also observed that people with both hearing loss and LHL were more likely to have higher medical costs. Continued focus on solutions to address both LHL and hearing loss remains warranted. [HLRP: Health Literacy Research and Practice. 2020;4(2):e129-e137.] PLAIN LANGUAGE SUMMARY: Health survey and medical claims data were used for this study. Hearing loss, especially unaided severe, was associated with limited health literacy, as were memory loss, depression, loneliness, older age, and male gender. Those with both limited health literacy and hearing loss had the highest medical costs. Health literacy and hearing loss can affect health care communications, warranting further study.

Factors associated with unsuccessful return-to-work following work-related upper extremity injury.

BACKGROUND: Returning to work following occupational injury is a key outcome for both workers' compensation boards and injured workers. Predictive factors for returning remain unclear. AIMS: To describe factors associated with unsuccessful return-to-work (RTW) in a hand injury population to identify target areas through which occupational rehabilitation programmes can help injured workers achieve successful RTW outcomes. METHODS: Demographic data, functional, pain and psychosocial scores were recorded for injured workers discharged between April 2011 and September 2015 from a multidisciplinary upper extremity treatment programme. The primary outcome of RTW status was assessed at programme discharge. Bivariate analyses and multivariable logistic regression were used to identify factors associated with being unable to RTW. RESULTS: Of 872 participants who met the inclusion criteria, 65% were male and the mean age was 46 (standard deviation [SD] 11) years. In unadjusted bivariate analyses, the group with an unsuccessful RTW outcome had higher mean baseline pain, catastrophizing and QuickDASH scores; a higher baseline prevalence of depression, and reported a high level of pain more frequently than those who were working at discharge. In the adjusted logistic regression model, not working at baseline, higher QuickDASH score and presence of depression at baseline were independently associated with unsuccessful work status outcome. CONCLUSIONS: Negative baseline work status, greater self-reported functional disability and presence of depression were associated with greater odds of unsuccessful RTW following a workplace upper extremity injury. Integrating mental healthcare provision with occupational rehabilitation is a potential programmatic approach to improve RTW.

Geographic and Seasonal Variation of Vitamin D: A Retrospective Study in Two Centers of Nepal.

BACKGROUND: Vitamin D deficiency is a common problem in many countries throughout the world. This study aimed at understanding the status of vitamin D deficiency in relation to age, gender, geography and season among relatively bigger numbers of population residing in central and western regions of Nepal. METHODS: This retrospective cross-sectional study was carried out by reviewing the records of vitamin D tests in two centers of Nepal- namely united reference laboratories at Pokhara and Chitwan Medical College at Chitwan. A total of 3320 individuals who were tested for clinical suspicion of vitamin D deficiency over a period of one year were included in the study. RESULTS: Mean vitamin D level was 18.7 ng/mL. Majority of subjects tested for vitamin D were females (71.36 %) with female to male ratio of 2.49:1. Hypovitaminosis D (≤ 30 ng/mL) was found in 84.5% subjects and was moderate to severely deficit (less than 10 ng/mL) in 25.9% of subjects. Status of hypovitaminosis D was found to be less in ≥50 years (79.9%) than the younger subjects (89.9% in ≤18 years and 87.0% in 19-49 years age group). Vitamin D deficiency was found lower in hills districts (80.8% vs 89.7% in the plains), which was found to be more pronounced during winter through summer seasons as compared to fall season. CONCLUSIONS: Population residing in plain areas and summer, spring and winter season are found to have increased problem of Hypovitaminosis D. It is also found to be common among younger children and female of reproductive age group. We have also found out the increased problem of hypovitaminosis D among population residing in the plain areas than in the hills especially in the summer, spring and winter season.

Characteristics and Health Outcomes Associated With Hearing Loss and Hearing Aid Use Among Older Adults.

Background: This study recruited older adults to explore physical and psychosocial conditions and other health outcomes associated with hearing loss (HL) and hearing aid use. Method: Survey data were used to categorize 20,244 participants into five groups: no HL, unaided mild HL, aided mild HL, unaided severe HL, and aided severe HL. Results: Individuals with unaided severe HL were more likely to report poor-fair self-rated health and were less likely to leave the home, or exercise 4 to 7 days per week, while there were no such associations for those with aided mild or severe HL. In addition, those with aided hearing were less likely to report depression, low social support, or mobility limitations. Discussion: In several instances, hearing aid use reduced associations between HL and negative psychosocial and physical characteristics, and health outcomes. More research using longitudinal study designs is needed to better understand the true implications of these findings.

Comparative analyses of published cost effectiveness models highlight critical considerations which are useful to inform development of new models.

Background: Comparative analyses of published cost effectiveness models provide useful insights into critical issues to inform the development of new cost effectiveness models in the same disease area.Objective: The purpose of this study was to describe a comparative analysis of cost-effectiveness models and highlight the importance of such work in informing development of new models. This research uses genotypic antiretroviral resistance testing after first line treatment failure for Human Immunodeficiency Virus (HIV) as an example.Method: A literature search was performed, and published cost effectiveness models were selected according to predetermined eligibility criteria. A comprehensive comparative analysis was undertaken for all aspects of the models.Results: Five published models were compared, and several critical issues were identified for consideration when developing a new model. These include the comparator, time horizon and scope of the model. In addition, the composite effect of drug resistance prevalence, antiretroviral therapy efficacy, test performance and the proportion of patients switching to second-line ART potentially have a measurable effect on model results. When considering CD4 count and viral load, dichotomizing patients according to higher cost and lower quality of life (AIDS) versus lower cost and higher quality of life (non-AIDS) status will potentially capture differences between resistance testing and other strategies, which could be confirmed by cross-validation/convergent validation. A quality adjusted life year is an essential outcome which should be explicitly explored in probabilistic sensitivity analysis, where possible.Conclusions: Using an example of GART for HIV, this study demonstrates comparative analysis of previously published cost effectiveness models yields critical information which can be used to inform the structure and specifications of new models.

Brucellosis in India: results of a collaborative workshop to define One Health priorities.

Brucellosis is an important zoonosis worldwide. In livestock, it frequently causes chronic disease with reproductive failures that contribute to production losses, and in humans, it causes an often-chronic febrile illness that is frequently underdiagnosed in many low- and middle-income countries, including India. India has one of the largest ruminant populations in the world, and brucellosis is endemic in the country in both humans and animals. In November 2017, the International Livestock Research Institute invited experts from government, national research institutes, universities, and different international organizations to a one-day meeting to set priorities towards a "One Health" control strategy for brucellosis in India. Using a risk prioritization exercise followed by discussions, the meeting agreed on the following priorities: collaboration (transboundary and transdisciplinary); collection of more epidemiological evidence in humans, cattle, and in small ruminants (which have been neglected in past research); Economic impact studies, including cost effectiveness of control programmes; livestock vaccination, including national facilities for securing vaccines for the cattle population; management of infected animals (with the ban on bovine slaughter, alternatives such as sanctuaries must be explored); laboratory capacities and diagnostics (quality must be assured and better rapid tests developed); and increased awareness, making farmers, health workers, and the general public more aware of risks of brucellosis and zoonoses in general. Overall, the meeting participants agreed that brucellosis control will be challenging in India, but with collaboration to address the priority areas listed here, it could be possible.

Factors associated with job satisfaction among graduate nursing faculties in Nepal.

BACKGROUND: Job satisfaction among nursing faculty is critical to improving quality of nursing education, producing future nurses who will contribute directly to the health of patients at a local and national level. This study explores factors associated with job satisfaction among graduate nursing faculties in different universities of Nepal. METHODS: A cross-sectional study was conducted among nursing faculty with at least one year of teaching in their respective institutions. A 36-items job satisfaction questionnaire with 6-point Likert type responses was administered online. The questionnaire was pre-tested with 30 faculties pooled from multiple institutions. Link to the final survey was sent via e-mail to 327 nursing faculties working in 39 nursing colleges. Respondents were contacted by phone as a follow up to the email to politely remind them about the survey. Data analysis was carried out with SAS University Edition software. Chi-Square test and t-test were used for simple descriptive analysis. A multivariate binary logistic regression model was used to identify the significant factors associated with nursing faculties' job satisfaction. Adjusted odds ratio was calculated and significance was considered at p ≤ 0.05 with 95% confidence interval. RESULTS: The response rate was 54.4%. After retrospective cleaning of data, usable response rate was 52.3% (n = 171). The average age of the nursing faculties was 36.8 ± 7.0 years. Based on the overall job satisfaction score, 36.8% nursing faculties were satisfied with their current job. The coefficient for Cronbach's alpha was 0.895 suggesting very good reliability of the overall measure. The significant factors associated with job satisfaction were the involvement of the faculties in decision making process related to the department (OR = 4.83) and adequate access to reference materials (OR = 2.90). CONCLUSIONS: This study suggests that nursing faculties have positive attitude towards their job but are dissatisfied with the benefits offered to them and the operating condition of their institutions. Expanding the teaching learning resources, such as reference books, subscription to journals, and continuing education opportunities for nursing faculties through participation in professional meetings would be helpful in improving the quality of nursing education in Nepal.

Reduced vitamin D levels in painful diabetic peripheral neuropathy.

AIM: Recent studies have reported an association between low vitamin D levels and diabetic peripheral neuropathy. However, many of these did not differentiate between people with painful diabetic peripheral neuropathy and those with painless diabetic peripheral neuropathy, or assess major confounding factors including sunlight exposure and daily activity. Our study addressed these limitations and evaluated vitamin D levels in people with carefully phenotyped diabetic peripheral neuropathy and controls. METHODS: Forty-five white Europeans with Type 2 diabetes and 14 healthy volunteers underwent clinical and neurophysiological assessments. People with Type 2 diabetes were then divided into three groups (17 with painful diabetic peripheral neuropathy, 14 with painless diabetic peripheral neuropathy and 14 with no diabetic peripheral neuropathy). All had seasonal sunlight exposure and daily activity measured, underwent a lower limb skin biopsy and had 25-hydroxyvitamin D measured during the summer months, July to September. RESULTS: After adjusting for age, BMI, activity score and sunlight exposure, 25-hydroxyvitamin D levels (nmol/l) (se) were significantly lower in people with painful diabetic peripheral neuropathy [painful diabetic peripheral neuropathy 34.9 (5.8), healthy volunteers 62.05 (6.7), no diabetic peripheral neuropathy 49.6 (6.1), painless diabetic peripheral neuropathy 53.1 (6.2); ANCOVAP = 0.03]. Direct logistic regression was used to assess the impact of seven independent variables on painful diabetic peripheral neuropathy. Vitamin D was the only independent variable to make a statistically significant contribution to the model with an inverted odds ratio of 1.11. Lower 25-hydroxyvitamin D levels also correlated with lower cold detection thresholds (r = 0.39, P = 0.02) and subepidermal nerve fibre densities (r = 0.42, P = 0.01). CONCLUSIONS: We have demonstrated a significant difference in 25-hydroxyvitamin D levels in well-characterized people with painful diabetic peripheral neuropathy, while accounting for the main confounding factors. This suggests a possible role for vitamin D in the pathogenesis of painful diabetic peripheral neuropathy. Further prospective and intervention trials are required to prove causality between low vitamin D levels and painful diabetic peripheral neuropathy.

Self-Reported Hearing Loss in Older Adults Is Associated With Higher Emergency Department Visits and Medical Costs.

Hearing loss is common among older adults. Thus, it was of interest to explore differences in health care utilization and costs associated with hearing loss and hearing aid use. Hearing loss and hearing aid use were assessed through self-reports and included 5 categories: no hearing loss, aided mild, unaided mild, aided severe, and unaided severe hearing loss. Health care utilization and costs were obtained from medical claims. Those with aided mild or severe hearing loss were significantly more likely to have an emergency department visit. Conversely, those with aided severe hearing loss were about 15% less likely to be hospitalized. Individuals with unaided severe hearing loss had the highest annual medical costs ($14349) compared with those with no hearing loss ($12118, P < .001). In this study, those with unaided severe hearing loss had the highest medical costs. Further studies should attempt to better understand the relationship between hearing loss, hearing aid use, and medical costs.