Summary
A study was conducted to evaluate the effects of three energy supply (E) levels low (L), medium (M), high (H), both pre‐partum (PRE) and post‐partum (POST), and their interactions on ...metabolic parameters and energy balance (EB) in dairy cows of three breeds. In both phases, E levels applied to a total of 81 multiparous cows of breeds Simmental (SI), Brown Swiss (BS) and Holstein–Friesian (HF; n = 27 for each breed) were 75%, 100% and 125% of recommendations of the German Society of Nutrition Physiology, using a 3 × 3 factorial arrangement of treatments. During the pre‐calving period, serum concentrations of non‐esterified fatty acids (NEFA) were higher for LPRE cows, and glucose concentrations were elevated for HPRE cows. During the lactation period, NEFA concentrations were greatest for treatment LPOST. Mean concentrations of β‐hydroxybutyrate (BHB) were highest for cows of the LPOST treatment, intermediate for MPOST and lowest for HPOST. Glucose concentrations were lower for LPOST cows. SI cows had lower BHB concentrations both pre‐ and post‐calving and higher glucose concentrations during early lactation than the other breeds. BHB concentration POST was highest for BS cows. Restricted feeding PRE resulted in a better energy status of cows fed above energy requirements POST (EPRE × EPOST interaction). HF cows had a higher EB pre‐calving, whereas SI cows had a less negative EB during early lactation, compared with the other breeds respectively. Correlations of serum NEFA, BHB and glucose concentrations with EB were strongest during the transition period. Results suggest that controlling energy intake during the dry period might be advantageous for the energy status of dairy cows after calving, whereas energy restriction in early lactation leads to metabolic stress. Evidence is provided of a clear relationship between EB and the blood metabolites NEFA and BHB, especially in the transition period.
Myofibroblasts are fibroblasts that express certain features of smooth muscle differentiation. Increased numbers of myofibroblasts and mast cells are frequently found together in a wide variety of ...settings, such as normal wound repair and scleroderma skin, which suggests that mediators produced by the mast cells could play a role in the regulation of myofibroblast differentiation and function. We used a human mast cell line, HMC-1, to determine if mast cells can induce normal human dermal fibroblasts to differentiate into functional myofibroblasts in vitro. We monitored the differentiation process by assaying two properties of the myofibroblast phenotype: expression of α-smooth muscle actin and functional capacity to contract a collagen matrix. In both a simple coculture system and in a skin-equivalent culture system, HMC-1 cells induced α-smooth muscle actin expression by fibroblasts. HMC-1 cells also stimulated fibroblast contraction of collagen gels, and the relative amount of contraction was dependent upon the number of HMC-1 cells present. To characterize the individual contributions made by specific mast cell products, we examined the effects of histamine, tumor necrosis factor α, and tryptase. Histamine induced a clear increase in α-smooth muscle actin expression, but it did not appear to stimulate fibroblast contraction. Tumor necrosis factor α had no effect in either assay. Purified human tryptase induced α-smooth muscle actin expression, and blocking the proteolytic activity of tryptase with specific inhibitors reduced that response. Tryptase inhibitors also eliminated the ability of HMC-1 cells to stimulate fibroblast contraction, suggesting that tryptase secreted by the HMC-1 cells may be one of the active mast cell mediators.
Abstract Background Persistent inflammation is associated with adverse health outcomes, but its impact on mortality has not been investigated previously among hip fracture patients. This article aims ...to investigate the influence of changes in levels of cytokines in the 2 months after a hip fracture repair on 5‐year mortality. Methods This is a prospective cohort study from the Baltimore Hip Studies (BHS) with 191 community‐dwelling older men and women (≥65 years) who had recently undergone surgical repair of an acute hip fracture, with recruitment from May 2006 to June 2011. Plasma interleukin‐6 (IL‐6), soluble tumor necrosis factor alpha receptor1 (sTNFα‐R1), and interleukin‐1 receptor agonist (IL‐1RA) were obtained within 22 days of admission and at 2 months. All‐cause mortality over 5 years was determined. Logistic regression analysis tested the associations between the cytokines' trajectories and mortality over 5 years, adjusted for covariates (age, sex, education, body mass index, lower extremity physical activities of daily living, and Charlson comorbidity index). Results High levels of IL‐6 and sTNFα‐R1 at baseline with small or no decline at 2 months were associated with higher odds of 5‐year mortality compared with those with lower levels at baseline and greater decline at 2 months after adjustment for age, and other potential confounders (OR = 4.71, p = 0.01 for IL‐6; OR = 15.03, p = 0.002 for sTNFα‐R1). Similar results that failed to reach significance were found for IL‐1RA (OR = 2.40, p = 0.18). Those with higher levels of cytokines at baseline with greater decline did not have significantly greater mortality than the reference group, those with lower levels at baseline and greater decline. Conclusion Persistent elevation of plasma IL‐6 and sTNFα‐R1 levels within the first 2 months after hospital admission in patients with hip fracture is associated with higher 5‐year mortality. These patients may benefit from enhanced care and earlier intensive interventions to reduce the risk of death.
Objectives. The objective of this work was to determine 1-year medical outcomes, nursing home transfer, and functional change of assisted living (AL) residents and their relationship to care. ...Methods. On-site interviews and observations regarding the status and care of 2,078 residents in 193 facilities across four states were conducted; follow-up was by telephone interview with care providers. Results. Annual mortality and transfer rates were 14.4 and 21.3 per 100 residents. The probability of hospitalization and new/worsening morbidities over a standardized quarter per 100 residents was 12.7 and 22.7. Standardized change in function was notable among those who were transferred or died and small among others. Facility characteristics did not generally relate to medical outcomes and transfer, and those that related to functional change were small and occurred across multiple functions. Facilities that are affiliated with another level of care were more likely to transfer; nurse staffing was favorable for hospitalization but not transfer; and aide turnover was protective for mortality. Discussion. No single component defines “good” AL care. Predictors and outcomes are inconsistent, and effect sizes are small. Therefore, practice and policy should not focus narrowly on any one area or restrict the type of care—this being welcome news that supports diversity to accommodate individual preferences.
Summary
Persistence rates over 36 months with denosumab in patients diagnosed with osteoporosis in a real-world setting were examined, along with baseline patient characteristics predictive of ...persistence. This study represents the longest observational period with denosumab persistence and shows higher persistence rates when compared to bisphosphonates.
Introduction
The study objective was to describe long-term persistence with denosumab among patients treated for osteoporosis in a real-world setting. We also sought to examine patient characteristics predictive of persistence. Lastly, this study attempted to place the results in context by conducting a literature review of published persistence data for denosumab.
Methods
This retrospective, non-interventional study analyzed 1158 patients from a specialty community private practice to assess patient persistence with denosumab in routine care. Persistence was defined as receiving seven denosumab injections, using an 8-week permissible gap, over 36 months. Non-persistent patients were further investigated retrospectively to identify reasons for discontinuation, when available.
Results
Demographic analysis showed a population of 1158 patients with mean age 68.4 years old and baseline T-score − 2.7; nearly half of which experienced a prior osteoporosis-related fracture. In a Kaplan-Meier survival analysis, 36-month persistence overall was 50.7%. Net persistence, as defined by receiving seven injections in the allowable time frame, was 64.2% of the cohort. In a multivariate analysis, prior vertebral fractures and recent osteoporosis therapy were associated with higher persistence; age greater than 75 years was associated with non-persistence. Reasons for discontinuation were available in 91.6% of non-persistent patients and categorized to include the ten most common explanations.
Conclusion
This study to our knowledge represents the longest continuous observational period providing data on denosumab persistence in a real-world setting. The total persistence noted is quite robust when compared to bisphosphonates and is within the upper range of prior published studies of denosumab with shorter observation periods.
Metabolic adaptation includes an array of concerted metabolic and endocrine events that enable dairy cows bridging the period of energy deficit at the onset of lactation. The present study evaluated ...metabolic, endocrine and reticuloruminal pH changes in 30 (25 Holstein and five Simmental) periparturient dairy cows experiencing variable lipolysis early postpartum. Cows were fed the same close-up and fresh lactation diets and kept in the same management conditions. Blood samples were collected at day 14, and day 4, relative to expected parturition, and at day 2, and day 21 postpartum, and serum metabolites and hormones related to glucose and lipid metabolism, as well as concentrations of several liver enzymes and acute phase proteins were determined. Additionally, reticuloruminal pH was monitored every 10 min over the last 3 days of the observation period. BW and milk yields were recorded and balances of energy and protein were assessed. Based on serum concentration of non-esterified fatty acids (NEFA) postpartum, cows were retrospectively classified into low (n=8), medium (n=11), and high (n=11) lipolysis groups, with NEFA levels of 0.7 mmol/l, respectively. Overall, elevated NEFA concentrations in the High group went along with a higher ratio of NEFA to cholesterol and reduced insulin sensitivity. While serum glucose, energy deficit and BW loss did not differ, cows of the High group exhibited increased lactate concentrations in the serum, compared with the Medium group. No differences in liver enzymes and acute phase proteins were evidenced among fat mobilization groups, whereas concentration of serum billirubin was lowest in the Low group after parturition. Data of milk yield and milk energy output showed no differences among groups, despite divergences in calculated energy balance and BW change postpartum. Cows of the Low group tended to increase dry matter intake but also showed longer time duration of pH below 6.0 in the reticulorumen (on average 299 min/day compared with 99 and 91 min/day for Medium and High groups, respectively). Differences in metabolic, endocrine and reticuloruminal pH responses indicate diverse metabolic adaptation strategies of early-lactation cows to cope with energy deficit postpartum.
A study was conducted to evaluate the effects of pre partum (PRE) and post partum (POST) dietary energy and nutrient supply (E) and their interactions on feed intake, performance and energy status in ...dairy cows of three breeds. In this experiment, the effects of three energy and nutrient supply levels (low (L), medium (M), high (H)), both pre-calving and post-calving, were investigated, using a 3×3 factorial arrangement of treatments. In both phases (84 days pre- and 105 days post-calving) E levels applied to a total of 81 multiparous cows of breeds Simmental (SI), Brown Swiss (BS) and Holstein-Friesian (HF; n=27 for each breed), were 75%, 100% and 125% of recommendations of the German Society of Nutrition Physiology (GfE). Dry matter intake (DMI) was restricted, if energy intake exceeded target values. Pre partum DMI and energy intake were different as designed, liveweight and body condition score (BCS) of SI cows were higher, but EB was lower, compared to BS and HF cows. Milk yield and composition were influenced by all three main experimental factors (EPRE, EPOST, breed). Energy-corrected milk yield was 25.6, 28.6 and 30.1 kg/day for LPRE, MPRE and HPRE as well as 21.5, 30.1 and 32.6 kg/day for LPOST, MPOST and HPOST, respectively. Numerically, only for milk protein content the interactions EPRE×EPOST and EPRE×breed reached significance. Impact of energy supply pre-calving was more pronounced when cows had lower energy supply post-calving and vice versa. On the other hand, milk yield response of cows to energy supply above requirements was greater for cows that were fed on a low energy level pre partum. Impact of energy level pre partum was higher for HF cows, showing that their milk production relies to a greater extent on mobilization of body reserves. Increasing energy supply pre partum led to a more negative energy balance post partum, mainly by increasing milk yield and content, whereas feed intake was slightly reduced. Increasing energy supply post partum enhanced milk yield as well as milk protein and lactose content. Calculated energy balance corresponded well with liveweight and BCS change. Response of milk yield to increasing energy supply followed the principle of diminishing returns, since energy was increasingly partitioned to body retention. Increasing energy supply pre partum enhances milk yield and content post partum, but exacerbates negative energy balance and its consequences.
ABSTRACTWe report a 40-year-old woman with onset of oligoarthritis shortly after initiating treatment with methimazole for Graves disease. Over the course of 7 years, her arthritis became ...progressively severe, leading to a diagnosis of seronegative rheumatoid arthritis. Treatment with disease-modifying antirheumatic agents and surgical intervention was contemplated. Ultrasound and magnetic resonance imaging revealed exuberant synovitis, involving right elbow and knees. Upon withdrawal of methimazole, prompt resolution of all signs and symptoms of arthritis was observed within several weeks. Following a MEDLINE search of available literature concerning antithyroid drug–induced arthritis, it is evident that this case represents the lengthiest duration of inflammatory arthropathy ever described in a patient that nonetheless was rapidly reversible with discontinuation of methimazole.
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