Summary Osteoarthritis (OA) may result from intrinsic inflammation related to metabolic disturbance. Obesity-associated inflammation is triggered by lipopolysaccharide (LPS) derived from the gut ...microbiota. However, the relationship between gut microbiota, LPS, inflammation, and OA remain unclear. Objective To evaluate the associations between gut microbiota, systemic LPS levels, serum and local inflammatory profiles, and joint damage in a high fat/high sucrose diet induced obese rat model. Methods 32 rats were randomized to a high fat/high sucrose diet (diet-induced obese (DIO), 40% fat, 45% sucrose, n = 21) or chow diet group (12% fat, 3.7% sucrose n = 11) for 28 weeks. After a 12-week obesity induction period, DIO animals were stratified into Obesity Prone (DIO-P, top 33% by change in body mass, n = 7), and Obesity Resistant groups (DIO-R, bottom 33%, n = 7). At sacrifice, joints were scored using a Modified Mankin Criteria. Blood and synovial fluid analytes, serum LPS, and fecal gut microbiota were analyzed. Results DIO animals had greater Modified Mankin scores than chow animals ( P = 0.002). There was a significant relationship ( r = 0.604, p = 0.001) between body fat, but not body mass, and Modified Mankin score. Eighteen synovial fluid and four serum analytes were increased in DIO animals. DIO serum LPS levels were increased compared to chow ( P = 0.031). Together, Lactobacillus species (spp.) and Methanobrevibacter spp. abundance had a strong predictive relationship with Modified Mankin Score ( r2 = 0.5, P < 0.001). Conclusions Increased OA in DIO animals is associated with greater body fat, not body mass. The link between gut microbiota and adiposity-derived inflammation and metabolic OA warrants further investigation.
the National Overactive BLadder Evaluation (NOBLE) Program was initiated to better understand the prevalence and burden of overactive bladder in a broad spectrum of the United States population.
to ...estimate the prevalence of overactive bladder with and without urge incontinence in the US, assess variation in prevalence by sex and other factors, and measure individual burden.
US national telephone survey using a clinically validated interview and a follow-up nested study comparing overactive bladder cases to sex- and age-matched controls.
noninstitutionalized US adult population.
a sample of 5,204 adults >/=18 years of age and representative of the US population by sex, age, and geographical region.
prevalence of overactive bladder with and without urge incontinence and risk factors for overactive bladder in the US. In the nested case-control study, SF-36, CES-D, and MOS sleep scores were used to assess impact.
the overall prevalence of overactive bladder was similar between men (16.0%) and women (16.9%), but sex-specific prevalence differed substantially by severity of symptoms. In women, prevalence of urge incontinence increased with age from 2.0% to 19% with a marked increase after 44 years of age, and in men, increased with age from 0.3% to 8.9% with a marked increase after 64 years of age. Across all age groups, overactive bladder without urge incontinence was more common in men than in women. Overactive bladder with and without urge incontinence was associated with clinically and significantly lower SF-36 quality-of-life scores, higher CES-D depression scores, and poorer quality of sleep than matched controls.
the NOBLE studies do not support the commonly held notion that women are considerably more likely than men to have urgency-related bladder control problems. The overall prevalence of overactive bladder does not differ by sex; however, the severity and nature of symptom expression does differ. Sex-specific anatomic differences may increase the probability that overactive bladder is expressed as urge incontinence among women compared with men. Nonetheless, overactive bladder, with and without incontinence, has a clinically significant impact on quality-of-life, quality-of-sleep, and mental health, in both men and women.
Increased levels of pro-inflammatory cytokines are associated with the release of degradative enzymes leading to osteoarthritis (OA) development. Although physical exercise (PE) is generally ...recognized as beneficial for OA symptoms, excessive training workload and eccentric muscular exercise have increased OA risk. Here, we investigated the effects of excessive exercise workload and exercise type on systemic inflammation and knee joint OA.
Mice were divided into five groups: sedentary (SED), uphill training (TRU), downhill training (TRD), excessive uphill training (ETU), and excessive downhill training (ETD) for an 8-week training intervention protocol.
ETD group had increased pro-inflammatory cytokines in serum, vastus lateralis (VL), and vastus medialis (VM) muscles, while ETU group mice had increased cytokine levels in the VL and VM. Total knee joint OARSI score were more significant in ETD group compared to SED and TRU groups. They were also more meaningful for the medial tibial plateau of ETD group compared to SED group. MMP-3 and cleaved Caspase-3 were higher in the ETD group than the SED and TRU group, while Adamts-5 was higher in the ETD group than the SED group. TRU group had increased PRG-4 levels compared to ETU and ETD group. ETD group had decreased total bone volume, trabecular bone volume, and cortical thickness compared to SED group.
Excessive downhill training induced a chronic pro-inflammatory state in mice and was associated with early signs of cartilage and bone degeneration that are clinical indicators of knee OA.
This study examined whether changes in driving patterns-driving cessation and reduction-have negative consequences for the depressive symptoms of older Americans and whether these consequences are ...mitigated for people with a spouse who drives.
The project used data from 3 waves of the Asset and Health Dynamics Among the Oldest Old (AHEAD) study. Depressive symptoms were assessed with an abbreviated Center for Epidemiologic Studies-Depression scale. Using 2 models, the project examined how driving cessation and reduction that occurred between Waves 1 and 2 contributed to increases in depressive symptoms between Waves 2 and 3. The first model included the entire sample (N = 5,239), and the second model focused on drivers only (n = 3,543). A third model added interaction terms to the analysis to consider whether respondents who stopped driving but had a spouse who drove were less at risk of worsening depressive symptoms.
Respondents who stopped driving had greater risk of worsening depressive symptoms. Drivers who restricted their driving distances before the study began also had greater risk of worsening depressive symptoms, but seemingly less so than the respondents who stopped driving altogether. For respondents who stopped driving, having a spouse available to drive them did not mitigate the risk of worsening symptoms.
Changes in driving patterns can be deleterious for older people's depressive symptoms. Initiatives for assisting older people should focus on strategies that help them retain driving skills, that prepare them for the possible transition from driver to ex-driver, and that ensure that they have access to mental health therapies if driving changes are imminent.
Agri-environment schemes are an increasingly important tool for the maintenance and restoration of farmland biodiversity in Europe but their ecological effects are poorly known. Scheme design is ...partly based on non-ecological considerations and poses important restrictions on evaluation studies. We describe a robust approach to evaluate agri-environment schemes and use it to evaluate the biodiversity effects of agri-environment schemes in five European countries. We compared species density of vascular plants, birds, bees, grasshoppers and crickets, and spiders on 202 paired fields, one with an agri-environment scheme, the other conventionally managed. In all countries, agri-environment schemes had marginal to moderately positive effects on biodiversity. However, uncommon species benefited in only two of five countries and species listed in Red Data Books rarely benefited from agri-environment schemes. Scheme objectives may need to differentiate between biodiversity of common species that can be enhanced with relatively simple modifications in farming practices and diversity or abundance of endangered species which require more elaborate conservation measures.
Distinct patient characteristics have been proposed for ischaemic stroke in the anterior versus posterior circulation. However, data on functional outcome according to stroke territory in patients ...with acute stroke treatment are conflicting and information on outcome predictors is scarce. In this retrospective study, we analysed functional outcome in 517 patients with stroke and thrombolysis and/or thrombectomy treated at the University Hospital Zurich. We compared clinical factors and performed multivariate logistic regression analyses investigating the effect of outcome predictors according to stroke territory. Of the 517 patients included, 80 (15.5%) suffered a posterior circulation stroke (PCS). PCS patients were less often female (32.5% vs. 45.5%, p = 0.031), received thrombectomy less often (28.7% vs. 48.3%, p = 0.001), and had lower median admission NIHSS scores (5 vs. 10, p < 0.001) as well as a better median three months functional outcome (mRS 1 vs. 2, p = 0.010). Predictors for functional outcome were admission NIHSS (OR 0.864, 95% CI 0.790-0.944, p = 0.001) in PCS and age (OR 0.952, 95% CI 0.935-0.970, p < 0.001), known symptom onset (OR 1.869, 95% CI 1.111-3.144, p = 0.018) and admission NIHSS (OR 0.840, 95% CI 0.806-0.876, p < 0.001) in ACS. Acutely treated PCS and ACS patients differed in their baseline and treatment characteristics. We identified specific functional outcome predictors of thrombolysis and/or thrombectomy success for each stroke territory.
Antibiotic overprescribing is a global challenge contributing to rising levels of antibiotic resistance and mortality. We test a novel approach to antibiotic stewardship. Capitalising on the concept ...of "wisdom of crowds", which states that a group's collective judgement often outperforms the average individual, we test whether pooling treatment durations recommended by different prescribers can improve antibiotic prescribing. Using international survey data from 787 expert antibiotic prescribers, we run computer simulations to test the performance of the wisdom of crowds by comparing three data aggregation rules across different clinical cases and group sizes. We also identify patterns of prescribing bias in recommendations about antibiotic treatment durations to quantify current levels of overprescribing. Our results suggest that pooling the treatment recommendations (using the median) could improve guideline compliance in groups of three or more prescribers. Implications for antibiotic stewardship and the general improvement of medical decision making are discussed. Clinical applicability is likely to be greatest in the context of hospital ward rounds and larger, multidisciplinary team meetings, where complex patient cases are discussed and existing guidelines provide limited guidance.
Objectives. Although a number of authors have proposed that older volunteers should benefit in terms of better health and well-being, few researchers have examined the issue empirically to see ...whether this is true. The purpose of this article is to build on this literature by empirically examining the association between volunteering and mortality among older adults. Methods. Using data from a nationally representative sample, we use Cox proportional hazards regression to estimate the effects of volunteering on the rate of mortality among persons aged 65 and older. Results. We find that volunteering has a protective effect on mortality among those who volunteered for one organization or for forty hours or less over the past year. We further find that the protective effects of volunteering are strongest for respondents who report low levels of informal social interaction and who do not live alone. Discussion. We discuss the possibility that the curvilinear relationship we observe between volunteering and mortality is due to a combination of factors, including self-identity, role strain, and meaningfulness. Other research using more precise data is needed to determine whether these ideas are supportable.
Summary Osteoarthritis (OA) in obese individuals is often attributed to joint loading. However, a subtype of OA, Metabolic OA, may be due to obesity-related intrinsic factors but remains to be ...evaluated experimentally against a known OA progression model. Objective To evaluate if obesity contributes to OA onset using a high fat/high sucrose diet-induced obesity (DIO) model with anterior cruciate ligament-transected rats (ACL-X). Methods Sprague Dawley rats ( n = 33) consumed high fat/high sucrose or chow diets for 12 weeks, were randomized to one of three groups: a unilateral ACL-X group, sham surgery group, or naïve non-surgical group. These animals were followed for an additional 16 weeks. At sacrifice, body composition, knee joint Modified Mankin scores, and 27 serum and synovial fluid cytokines and adipokines were measured. Results Experimental limbs of obese ACL-X, obese Sham, and lean ACL-X animals had similar Modified Mankin scores that were greater than those obtained from lean Sham and naïve animals. Obese contralateral limbs had similar OA damage as ACL-X and Sham limbs of obese and ACL-X limbs of lean animals. Obese contralateral limb Modified Mankin scores had a strong correlation ( r = 0.75, P < 0.001) with body fat percentage. Serum leptin and synovial fluid IP10/CXCL10 best described Modified Mankin scores in contralateral limbs of obese animals. Conclusions Mechanical factors produced OA damage in experimental limbs, as expected. Interestingly, OA damage in obese contralateral limbs was similar to mechanically perturbed limbs, suggesting that obesity may induce OA in a non-mechanical manner.
The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not ...only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes.
We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 10-100 RNA copies/μL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments.
DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance.
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