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.

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.

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.

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.

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.

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.

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.

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.

Neuropathic pain in end-stage hip and knee osteoarthritis: differential associations with patient-reported pain at rest and pain on activity.

OBJECTIVE: We investigated whether pain at rest and pain on activity were differentially associated with neuropathic pain scores in individuals with end-stage hip and knee OA. DESIGN: Study participants were 843 patients with hip or knee OA scheduled for total joint arthroplasty. In pre-surgery questionnaires, measures of socio-demographics, health status, medication use, neuropathic pain (painDETECT), pain at rest and pain on activity (WOMAC pain items), depression (HADS) and pain catastrophizing (PCS) were collected. Multivariable linear regression models were estimated for men and women separately to examine the association between neuropathic pain scores (outcome) and study measures, entered in blocks. RESULTS: Sample mean age was 65.1 years (SD: 9.6); 57.1% were women. Mean painDETECT scores were significantly higher (P ≤Ö¹ 0.001) for women (11.2 ± 6.6 out of 38) than men (9.3 ± 7.0), with 35.6% of women and 27.7% of men meeting cut-offs for possible or likely neuropathic pain. In the final regression model for women, the coefficients for both types of pain were statistically significant, although the coefficient for pain at rest was 1.6 times greater than that for pain on activity. For men, only pain at rest was significantly associated with neuropathic pain scores. CONCLUSIONS: Findings support that possible neuropathic pain is experienced by a notable proportion of patients with end-stage hip and knee OA and is more strongly associated with pain at rest than pain on activity, particularly in men. Clinical presentation of pain at rest may warrant more thorough evaluation for potential neuropathic pain and have implications for appropriate pain management.

Low dose mycophenolate mofetil versus cyclophosphamide in the induction therapy of lupus nephritis in Nepalese population: a randomized control trial.

BACKGROUND: The management of proliferative lupus nephritis (LN) comprises timely and coordinated immunosuppressive therapy. This study aimed to evaluate and compare the effectiveness and safety profile of low dose mycophenolate mofetil (MMF) and cyclophosphamide (CYC) in induction therapy of LN in Nepalese population. METHODS: We conducted a prospective, open-label, randomized trial over a period of one and half years. Forty-nine patients with class III to V lupus nephritis were enrolled, out of which 42 patients (21 in each group) could complete the study. CYC was given intravenously as a monthly pulse and MMF was administered orally in the tablet form in the maximum daily dose of 1.5 g in two divided doses. RESULTS: The mean age of the patients was 25.43 ± 10.17 years with female to male ratio of 7.3:1. Mean baseline serum creatinine was 1.58 ± 1.38 mg/dL and eGFR was 62.38 ± 26.76 ml/min/1.73m2. Mean 24-h urinary protein was 4.35 ± 3.71 g per 1.73 m2 body surface area. At 6 months, serum creatinine (mg/dL) decreased from 1.73 to 0.96 in CYC and from 1.24 to 0.91 in the MMF group with improvement in eGFR (ml/min/1.73 m2) from 60.33 to 88.52 in CYC and from 64.42 to 89.09 in MMF group. Twenty-four-hour urinary protein (gm/1.73m2) reduced from 4.47 to 0.94 in CYC and from 4.5 to 0.62 in the MMF group. Primary end point was achieved in higher percentage of patients with MMF than CYC (28.6% vs. 19%) while equal proportion of patients (67% in each group) achieved secondary end point in both groups. Number of non-responders was higher in CYC group than in the MMF group (14.3% vs. 4.8%). There was no difference in the rate of achievement of secondary end point in both CYC and MMF groups (3.16 vs. 3.05 months). The occurrence of adverse events was higher in the CYC than in MMF group (56 vs. 15 events). CONCLUSION: Present study has concluded that MMF, used in relatively lower dose, is equally effective in inducing remission with reduction of proteinuria and improvement of kidney function with lesser adverse events than CYC in the induction therapy of proliferative lupus nephritis. TRIAL REGISTRATION: Retrospectively registered to ClinicalTrials.gov PRS. NCT03200002 (Registered date: June 28, 2017).

Therapeutic drug monitoring of antitubercular agents for disseminated Mycobacterium tuberculosis during intermittent haemodialysis and continuous venovenous haemofiltration.

WHAT IS KNOWN AND OBJECTIVE: There is a lack of data regarding therapeutic drug monitoring (TDM) of antitubercular agents in the setting of continuous venovenous haemofiltration (CVVH). We describe TDM results of numerous antitubercular agents in a critically ill patient during CVVH and haemodialysis. CASE SUMMARY: A 49-year-old man was initiated on treatment for disseminated Mycobacterium tuberculosis. During hospital admission, the patient developed critical illness and required renal replacement therapy. TDM results and pharmacokinetic calculations showed adequate serum concentrations of rifampin, ethambutol and amikacin during CVVH and of rifampin, pyrazinamide, ethambutol and levofloxacin during intermittent haemodialysis. WHAT IS NEW AND CONCLUSION: The presence of critical illness and renal replacement therapy can induce pharmacokinetic changes that may warrant vigilant TDM to ensure optimal therapy. To our knowledge, this is the first report to describe TDM for several antitubercular agents during CVVH in a critically patient with disseminated M. tuberculosis.

Systemic inflammation and painful joint burden in osteoarthritis: a matter of sex?

OBJECTIVE: We investigated the association between serum levels of C-reactive protein (CRP) and the extent of multijoint pain among individuals with hip/knee osteoarthritis (OA) and determined whether the association differs by sex. DESIGN: Serum CRP and cartilage oligomeric matrix protein (COMP) were determined by enzyme-linked immunosorbent assay (ELISA) in 189 individuals (101 female, 88 male) scheduled for total hip/knee arthroplasty for OA. Patients indicated on a homunculus all painful joints; a summed count was derived. A series of negative binomial regression models was used to investigate the cross-sectional association between painful joint count (outcome) and serum CRP concentrations, adjusting for age, sex, body mass index (BMI), comorbidity count and COMP. An interaction between sex and these biomarkers was tested. RESULTS: Mean age: 66 among women, 65 among men. Women had higher mean joint count (3.7 vs 2.5, P < 0.01; 4+ joint count reported by 37% women, 25% men). Median CRP concentration was higher in women (15.4 mg/l vs 9.3, P = 0.07). From adjusted analyses, the effects of both ln(CRP) and ln(COMP) were modified by sex (P < 0.05). Increasing ln(CRP) was associated with greater painful joint count among women, but not men. CONCLUSIONS: There may be a dose-response association between painful joint burden in OA and systemic inflammation, and it appears the association is sex-specific, which may in part explain inconsistent findings in the literature. Our results underline the importance of showing sex-specific associations in OA, especially when studying the influence of inflammation.

Stage-specific differences in secretory profile of mesenchymal stromal cells (MSCs) subjected to early- vs late-stage OA synovial fluid.

OBJECTIVE: Although, mesenchymal stromal cells (MSCs) are being clinically investigated for their use in osteoarthritis (OA), it is unclear whether their postulated therapeutic properties are equally effective in the early- and late-stages of OA. In this study we investigated MSC cytokine secretion post-exposure to synovial fluid (SF), obtained from early- vs late-stage knee OA patients to justify a potential patient stratification strategy to maximize MSC-mediated treatment effects. METHOD: Subjects were recruited and categorized into early- [Kellgren-Lawrence (KL) grade I/II, n = 12] and late-stage (KL-III/IV, n = 12) knee OA groups. SF samples were obtained, and their proteome was tested using multiplex assays, after 3-days culture, with and without MSCs. SFs cultured without MSCs were used as a baseline to identify MSC-secreted factors into SFs cultured with MSCs. Linear mixed-effect models and non-parametric tests were used to identify alterations in the MSC secretome during exposure to OA SF (3-days). MSCs cultured for 3-days in 0.5% fetal bovine serum (FBS)-supplemented medium were used to compare SF results with culture medium. RESULTS: Following exposure to OA SF, the MSC secretome contained proteins that are involved in tissue repair, angiogenesis, chemotaxis, matrix remodeling and the clotting process. However, chemokine (C-X-C motif) ligand-8 (CXCL8; chemoattractant), interleukin-6 (IL6) and chemokine (C-C motif) ligand 2 (CCL2) were elevated in the MSC-secretome in response to early- vs late-stage OA SF. CONCLUSION: Early- vs late-stage OA SF samples elicit a differential MSC secretome response, arguing for stratification of OA patients to maximize MSC-mediated therapeutic effects.

Is there a connection between postprandial hyperglycemia and IGT related sensory nerve dysfunction?

BACKGROUND AND AIMS: To assess the risk factors for sensory nerve dysfunction in subjects with isolated impaired glucose tolerance (IGT). METHODS AND RESULTS: Seventy-two people with isolated IGT (WHO 1999 criteria) and 39 gender and age-matched healthy volunteers underwent detailed clinical and neurological assessment including quantitative sensory testing using the Neurometer device (current perception threshold measurement on four limbs at three different frequencies). Sensory nerve dysfunction was defined as at least two abnormalities on any frequencies on the upper or lower limbs. Sensory nerve dysfunction was more prevalent among subjects with IGT compared to controls (58.3 vs. 10.3%, OR: 11.23, 95%CI: 3.57-35.35). This association was not influenced by BMI, systolic and diastolic blood pressure, heart rate and autonomic neuropathy (multiple adjusted OR: 13.87, 95%CI: 3.18-60.58), but further adjustment for glycaemic measures abolished the association (OR: 1.58, 95%CI: 0.07-35.68). Assessing the components of glycaemic measures separately, the association between sensory nerve dysfunction and IGT was not affected by HbA1c (OR: 13.94, 95%CI: 1.84-105.5). It was, however, substantially attenuated by fasting plasma glucose (OR: 6.75, 95%CI: 1.33-34.27) while the significance was lost after adjustment for 120 min postload glucose level (OR: 3.76, 95%CI: 0.26-54.10). In the pooled population assessed, independent determinants of sensory nerve dysfunction were older age, 120 min glucose, higher height and cardiovascular autonomic neuropathy at near significance. CONCLUSIONS: Sensory nerve dysfunction amongst subjects with IGT was not explained by cardiovascular covariates, only by glycaemic measures. In addition to 120 min glucose, cardiovascular autonomic neuropathy at borderline significance, age, and height were the independent determinants of sensory nerve dysfunction.

The impact of inadequate health literacy on patient satisfaction, healthcare utilization, and expenditures among older adults.

Inadequate health literacy (HL) is associated with impaired healthcare choices leading to poor quality-of-care. Our primary purpose was to estimate the prevalence of inadequate HL among two populations of AARP® Medicare Supplement insureds: sicker and healthier populations; to identify characteristics of inadequate HL; and to describe the impact on patient satisfaction, preventive services, healthcare utilization, and expenditures. Surveys were mailed to insureds in 10 states. Multivariate regression models were used to identify characteristics and adjust outcomes. Among respondents (N = 7334), 23% and 16% of sicker and healthier insureds, respectively, indicated inadequate HL. Characteristics of inadequate HL included male gender, older age, more comorbidities, and lower education. Inadequate HL was associated with lower patient satisfaction, lower preventive service compliance, higher healthcare utilization and expenditures. Inadequate HL is more common among older adults in poorer health, further compromising their health outcomes; thus they may benefit from expanded educational or additional care coordination interventions.

Identification of synovial fluid microRNA signature in knee osteoarthritis: differentiating early- and late-stage knee osteoarthritis.

OBJECTIVES: This study aimed to identify circulating microRNA (miRNA) signatures in knee synovial fluid (SF) from early-stage and late-stage knee osteoarthritis (OA) patients. METHODS: miRNAs were screened by miRNA-PCR-arrays and validated by Real-time quantitative polymerase chain reaction (RT-qPCR) in SF from early-stage (Kellgren-Lawrence (KL): Grade: I/II) and late-stage OA patients (Grade: III/IV). OA cartilage or synovial explants were cultured to study the source/release of identified miRNAs. Computational-approach was utilized to predict gene/pathway targets. RESULTS: Our screening/validation analysis identified a panel of seven (out of 752) circulating miRNAs (23a-3p, 24-3p, 27a-3p, 27b-3p, 29c-3p, 34a-5p and 186-5p) that were significantly differentially expressed in late-stage vs early-stage OA-SF, irrespective of age, gender and Body Mass Index (BMI). miR-378a-5p was mostly detectable in majority of late-stage OA-SF. Cartilage explants stimulated with IL-1ß showed a significant reduction in miR-23a-3p, 27a-3p and 27b-3p expression with no significant changes in other validated miRNAs. However, IL-1ß-stimulated OA synovial explants exhibited significantly increased expression of miR-23a-3p, 24-3p, 27a-3p, 27b-3p, 29c-3p, 186-5p and 378a-5p, and release of only 23a-3p and 27b-3p in supernatants, suggesting that IL-1ß contributes to the release of 23a-3p and 27b-3p into the SF from synovium. Computational-analysis identified 2 genes (ROQUIN-1 [RC3H1] and quaking-gene [QKI]) that are targeted by six out of eight miRNAs; miR-27b-3p exhibited greatest association with RC3H1 and QKI genes. Indeed, synovial explants treated with miR-27b-3p-mimic show significant suppression of both RC3H1 and QKI genes. CONCLUSIONS: We provide first evidence of the differential expression of circulating miRNAs in early-stage vs late-stage knee OA-SF. Further, we provide source, release and genes/pathways regulated by identified miRNAs.