Impact of combined management strategies of monensin and virginiamycin in high energy diets on ruminal fermentation and nutrients utilization.

Feed additives such as monensin (MON) and virginiamycin (VM) are commonly utilized in feedlot diets to enhance rumen fermentation. Nevertheless, the precise effects of combining MON and VM during specific feedlot periods and the advantages of this combination remain unclear. This study was designed to investigate the effects of withdrawal of MON when associated with VM during the adaptation and finishing periods on ruminal metabolism, feeding behavior, and nutrient digestibility in Nellore cattle. The experimental design was a 5 × 5 Latin square, where each period lasted 28 days. Five rumen-cannulated Nellore yearling bulls were used (414,86 ± 21,71 kg of body weight), which were assigned to five treatments: (1) MON during the entire feeding period; (2) VM during the entire feeding period; (3) MON + VM during the adaptation period and only VM during the finishing period 1 and 2; (4) MON + VM during the entire feeding period; (5) MON + VM during the adaptation and finishing period 1 and only VM during the finishing period 2. For the finishing period 1, animals fed T3 had improved potential degradability of dry matter (p = 0.02). Cattle fed T3 and T5 had the highest crude protein degradability when compared to animals receiving T2 (p = 0.01). Animals fed T2 and T3 had reduced the time (p < 0.01) and area under pH 6.2 (p = 0.02). Moreover, animals fed T4 had greater population of protozoa from the genus Diplodinium (p = 0.04) when compared to those from animals fed T2, T3 and T5. For the finishing period 2, animals fed T3 had greater starch degradability when compared to animals receiving T4 and T5 (p = 0.04). Animals fed T3, T4 and T5 had increased the duration of time in which pH was below 5.6 (p = 0.03). The area under the curve for ruminal pH 5.2 and pH 5.6 was higher for the animals fed T3 (p = 0.01), and the area under pH 6.2 was higher for the animals fed T3 and T5 (p < 0.01) when compared to animals receiving T2. There is no substantial improvement on the rumen fermentation parameters by the concurrent utilization of MON and VM molecules, where the higher starch and protein degradability did not improve the rumen fermentation.

More is not always better, sometimes it is just more.

Not available.

CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma.

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.

New Insights into the Pro-Inflammatory and Osteoclastogenic Profile of Circulating Monocytes in Osteoarthritis Patients.

Osteoarthritis (OA) is a degenerative condition of the articular cartilage with chronic low-grade inflammation. Monocytes have a fundamental role in the progression of OA, given their implication in inflammatory responses and their capacity to differentiate into bone-resorbing osteoclasts (OCLs). This observational-experimental study attempted to better understand the molecular pathogenesis of OA through the examination of osteoclast progenitor (OCP) cells from both OA patients and healthy individuals (25 OA patients and healthy samples). The expression of osteoclastogenic and inflammatory genes was analyzed using RT-PCR. The OA monocytes expressed significantly higher levels of CD16, CD115, TLR2, Mincle, Dentin-1, and CCR2 mRNAs. Moreover, a flow cytometry analysis showed a significantly higher surface expression of the CD16 and CD115 receptors in OA vs. healthy monocytes, as well as a difference in the distribution of monocyte subsets. Additionally, the OA monocytes showed a greater osteoclast differentiation capacity and an enhanced response to an inflammatory stimulus. The results of this study demonstrate the existence of significant differences between the OCPs of OA patients and those of healthy subjects. These differences could contribute to a greater understanding of the molecular pathogenesis of OA and to the identification of new biomarkers and potential drug targets for OA.

Acute Effects of In-Hospital Resistance Training on Clinical Outcomes in Patients Undergoing Total Knee Arthroplasty: A Randomized Controlled Trial.

OBJECTIVE: The aim of the study is to evaluate the acute responses, in the in-hospital setting, of intensive elastic resistance training on physical function, pain, psychosocial variables, and inflammatory markers in patients undergoing total knee arthroplasty. DESIGN: In a randomized controlled trial, 40 patients with total knee arthroplasty (≥55 yrs) were assigned to either (1) the intervention group (elastic resistance strengthening) or (2) a control group (conventional protocol). Patients performed three sessions in the hospital at 24, 48, and 72 hrs after total knee arthroplasty. Outcome measures included: self-administered physical function, pain intensity, kinesiophobia, catastrophizing, self-efficacy, range of motion, perceived change, test timed up and go, knee joint effusion, isometric strength, pressure pain thresholds, and inflammatory markers (levels of procalcitonin and C-reactive protein). RESULTS: The mixed analysis of variance model showed a significant group*time interaction in favor of the intervention group with a large effect size for kinesiophobia (ηp 2 = 0.308, P < 0.001), catastrophizing (ηp 2 = 0.242, P < 0.001), and passive range of motion flexion (ηp 2 = 0.167, P < 0.001) and a moderate effect size for physical function (ηp 2 = 0.103, P = 0.004), pain intensity (ηp 2 = 0.139, P < 0.001), timed up and go (ηp 2 = 0.132, P = 0.001), self-efficacy (ηp 2 = 0.074, P = 0.016), active range of motion flexion (ηp 2 = 0.121, P = 0.002), levels of procalcitonin (ηp 2 = 0.099, P = 0.005), and C-reactive protein (ηp 2 = 0.106, P = 0.004). CONCLUSIONS: Three sessions of intensive elastic resistance training improve physical function, perceived pain, psychosocial variables, and inflammatory markers during the hospitalization period after total knee arthroplasty.

Shortening the adaptation of Nellore cattle to high-concentrate diets using only virginiamycin as sole feed additive negatively impacts ruminal fermentation and nutrient utilization.

Feedlot cattle are usually adapted to high-concentrate diets containing sodium monensin (MON) in more than 14 days. However, considering that the dry matter intake DMI is usually lower during adaptation when compared to the finishing period, the use of MON during adaptation may decrease even further the DMI, and virginiamycin (VM) may be an alternative. This study was designed to investigate the effects of shortening the adaptation length from 14 to 9 or 6 days on ruminal metabolism, feeding behavior, and nutrient digestibility of Nellore cattle fed high-concentrate diets containing only VM as the sole feed additive. The experimental design was a 5 × 5 Latin square, where each period lasted 21 days. Five 17 mo-old Nellore yearling bulls were used (415 ± 22 kg of body weight), which were assigned to five treatments: (1) MON (30 mg/kg) and adaptation for 14 days; (2) MON (30 mg/kg) + VM (25 mg/kg) and adaptation for 14 days; (3) VM (25 mg/kg) and adaptation for 14 days; (4) VM (25 mg/kg) and adaptation for 9 days, and (5) VM (25 mg/kg) and adaptation for 6 days. A quadratic effect for adaptation length when only VM was fed was observed for mean pH (P = 0.03), duration of pH below 5.2 (P = 0.01) and 6.2 (P = 0.01), where cattle consuming VM adapted for 9 days had higher mean pH and shorter period of pH below 5.2 and 6.2. Cattle that consumed only MON had a lower concentration of butyrate (P = 0.02) and a higher concentration of propionate (P = 0.04) when compared to those consuming VM and adapted for 14 days. As the adaptation length decreased for animals consuming only VM, the rumen degradability of dry matter (P < 0.01), neutral detergent fiber (P < 0.01), and starch (P < 0.01) decreased; however, protozoa numbers of Entodinium and total protozoa increased. It is not recommended to shorten the adaptation length of these animals to either 6 or 9 days without negatively impacting nutrient disappearance and ruminal fermentation patterns.

Feedlot performance, rumen and cecum morphometrics of Nellore cattle fed increasing levels of diet starch containing a blend of essential oils and amylase or monensin.

Feed additives used in finishing diets improve energy efficiency in ruminal fermentation, resulting in increased animal performance. However, there is no report evaluating the effect of BEO associated with exogenous α-amylase in response to increased starch content in feedlot diets. Our objective was to evaluate increasing levels of starch in the diet associated with a blend of essential oils plus amylase or sodium Monensin on performance, carcass characteristics, and ruminal and cecal morphometry of feedlot cattle. 210 Nellore bulls were used (initial body weight of 375 ± 13.25), where they were blocked and randomly allocated in 30 pens. The experiment was designed in completely randomized blocks in a 3 × 2 factorial arrangement: three starch levels (25, 35, and 45%), and two additives: a blend of essential oils plus α-amylase (BEO, 90 and 560 mg/kg of DM, respectively) or sodium Monensin (MON, 26 mg/kg DM). The animals were fed once a day at 08:00 ad libitum and underwent an adaptation period of 14 days. The diets consisted of sugarcane bagasse, ground corn, soybean hulls, cottonseed, soybean meal, mineral-vitamin core, and additives. The animals fed BEO35 had higher dry matter intake (P = 0.02) and daily weight gain (P = 0.02). The MON treatment improved feed efficiency (P = 0.02). The treatments BEO35 and BEO45 increased hot carcass weight (P < 0.01). Animals fed BEO presented greater carcass yield (P = 0.01), carcass gain (P < 0.01), rib eye area gain (P = 0.01), and final rib eye area (P = 0.02) when compared to MON. The MON25 treatment improved carcass gain efficiency (P = 0.01), final marbling (P = 0.04), and final subcutaneous fat thickness (P < 0.01). The use of MON reduced the fecal starch% (P < 0.01). Cattle-fed BEO increased rumen absorptive surface area (P = 0.05) and % ASA papilla area (P < 0.01). The MON treatment reduced the cecum lesions score (P = 0.02). Therefore, the use of BEO with 35 and 45% starch increases carcass production with similar biological efficiency as MON; and animals consuming MON25 improve feed efficiency and reduce lesions in the rumen and cecum.

Withdrawal of sodium monensin when associated with virginiamycin during adaptation and finishing periods on feedlot performance, feeding behavior, carcass, rumen, and cecum morphometrics characteristics of Nellore cattle.

Feed additives such as monensin (MON) and virginiamycin (VM) are widely used in feedlots diets to maximize rumen fermentation. However, the knowledge about the effects of MON and VM combinations in specifics feedlot periods and the benefits of this association are still unclear. This study aimed to evaluate the effects of withdrawal of MON when associated with VM during the adaptation and finishing periods on feedlot performance of Nellore cattle. The experiment was designed as a completely randomized block replicated six times (four animals/pen) in which 120 Nellore bulls (378.4 ± 24.4 kg) were allocated in 30 pens and fed for 112 days according to the following treatments: (T1) MON during the entire feeding period; (T2) VM during the entire feeding period; (T3) MON+VM during the adaptation period and only VM during the finishing period 1 and 2; (T4) MON+VM during the entire feeding period; (T5) MON+VM during the adaptation and finishing period 1 and only VM during the finishing period 2. After 112 days on feed, no treatment effect was observed for DMI (P ≥ 0.12). However, bulls fed T5 had greater (P = 0.05) final BW and ADG when compared to T1, T2, and T4. Cattle from T3 and T5 groups presented heavier HCW (P = 0.05) than that fed T1, T2, and T4. Nellore bulls fed T1 and T5 had lower (P < 0.01) DMI variation than those receiving T2. The withdrawal of MON when associated with VM during the final third of the feedlot period improved overall final BW, ADG, and HCW when compared to bulls fed either MON or VM, but did not positively impact feedlot performance when compared to cattle that had MON withdrawn at the end of the adaptation period.

Lenalidomide plus R-GDP (R2-GDP) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Final Results of the R2-GDP-GOTEL Trial and Immune Biomarker Subanalysis.

PURPOSE: New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma. PATIENTS AND METHODS: In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29). RESULTS: After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells. CONCLUSIONS: R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.

Relationships of the Microbial Communities with Rumen Epithelium Development of Nellore Cattle Finished in Feedlot Differing in Phenotypic Residual Feed Intake.

The objective of this study was to examine the relationships among ruminal microbial community, rumen morphometrics, feeding behavior, feedlot performance, and carcass characteristics of Nellore cattle, classified by residual feed intake (RFI). Twenty-seven Nellore yearling bulls with an initial body weight (BW) of 423.84 ± 21.81 kg were fed in feedlot for 107 d in individual pens to determine the RFI phenotype. Bulls were categorized as high RFI (>0.5 SD above the mean, n = 8), medium RFI (±0.5 SD from the mean, n = 9), and low RFI (<0.5 SD below the mean, n = 10). At harvest, whole rumen content samples were collected from each bull to evaluate ruminal microbial community, including bacteria and protozoa. The carcass characteristics were determined by ultrasonography at the beginning and at the end of the experimental period, and behavior data were collected on d 88. As a result of ranking Nellore bulls by RFI, cattle from low-RFI group presented lesser daily dry matter intake (DMI), either in kilograms (p < 0.01) or as percentage of BW (p < 0.01) than high-RFI yearling bulls, resulting in improved gain:feed (G:F). However, variables, such as average daily gain (ADG), final BW, hot carcass weight (HCW) and other carcass characteristics did not differ (p > 0.05) across RFI groups. The eating rate of either dry matter (DM )(p = 0.04) or neutral detergent fiber (NDF) (p < 0.01) was slower in medium-RFI yearling bulls. For ruminal morphometrics an RFI effect was observed only on keratinized layer thickness, in which a thinner layer (p = 0.04) was observed in low-RFI Nellore yearling bulls. Likewise, Nellore yearling bulls classified by the RFI did not differ in terms of Shannon's diversity (p = 0.57) and Chao richness (p = 0.98). Our results suggest that the differences in feed efficiency of Nellore bulls differing in phenotypic RFI should be attributed to metabolic variables other than ruminal microorganisms and epithelium, and deserves further investigation.

Long-term outcome of cementless total hip arthroplasty with threaded Tropic® acetabular cup and Corail® femoral stem.

This study investigates the clinical and radiological results of a tapered femoral stem (Corail®) and uncemented threaded acetabular cups (Tropic®) and in addition an analysis of the complications and retrieved implants was conducted. Between January 1990 and September 1998, 301 total hips arthroplasties in 268 patients were implanted. 78 patients (87 hips) had died and 9 patients (12 hips) had been lost to follow-up, leaving at the time of the latest follow-up 180 patients (202 hips). The mean age at surgery was 56,1 (27-75) years. Of the 154 unrevised hips, the median Harris and Merle d'Aubigne and Postel hip scores were 83,3 points and 15,3 points respectively at the latest follow-up. The median follow-up time was 16.9 years (10,4-25). No femoral component was revised for aseptic loosening ; osteolysis was observed in the 9,5% of the implants (13 stems). 48 hips (23%) were revised and 27 cups (56,2%) needed revision surgery because of massive polyethylene wear. Pelvic osteolysis was found out in 80 cups (58,8%). 87 hips (63,9%) showed signs of a progressive wear of the liner, more than 2mm in 48 hips. Kaplan-Meier survivorship analysis at 15 years follow-up was 81.2% with revision for any reason (85.8% for mechanical or radiographic loosening). High rates of polyethylene wear and the high prevalence of pelvic osteolysis are serious matters in these types of implants with high rates of revision at 15 years follow-up so we decided to abandon the concept of a threaded cup design in favor of a press-fit acetabular cup.

Role of peroxiredoxin 6 in the chondroprotective effects of microvesicles from human adipose tissue-derived mesenchymal stem cells.

BACKGROUND: Osteoarthritis (OA) is a joint disease characterized by cartilage degradation, low-grade synovitis and subchondral bone alterations. In the damaged joint, there is a progressive increase of oxidative stress leading to disruption of chondrocyte homeostasis. The modulation of oxidative stress could control the expression of inflammatory and catabolic mediators involved in OA. We have previously demonstrated that extracellular vesicles (EVs) present in the secretome of human mesenchymal stem cells from adipose tissue (AD-MSCs) exert anti-inflammatory and anti-catabolic effects in OA chondrocytes. In the current work, we have investigated whether AD-MSC EVs could regulate oxidative stress in OA chondrocytes as well as the possible contribution of peroxiredoxin 6 (Prdx6). METHODS: Microvesicles (MV) and exosomes (EX) were isolated from AD-MSC conditioned medium by differential centrifugation with size filtration. The size and concentration of EVs were determined by resistive pulse sensing. OA chondrocytes were isolated from knee articular cartilage of advanced OA patients. 4-Hydroxynonenal adducts, IL-6 and MMP-13 were determined by enzyme-linked immunosorbent assay. Expression of Prdx6 and autophagic markers was assessed by immunofluorescence and Western blotting. Prdx6 was downregulated in AD-MSCs by transfection with a specific siRNA. RESULTS: MV and to a lesser extent EX significantly reduced the production of oxidative stress in OA chondrocytes stimulated with IL-1ß. Treatment with MV resulted in a dramatic upregulation of Prdx6. MV also enhanced the expression of autophagy marker LC3B. We downregulated Prdx6 in AD-MSCs by using a specific siRNA and then MV were isolated. These Prdx6-silenced MV failed to modify oxidative stress and the expression of autophagy markers. We also assessed the possible contribution of Prdx6 to the effects of MV on IL-6 and MMP-13 production. The reduction in the levels of both mediators induced by MV was partly reverted after Prdx6 silencing. CONCLUSION: Our results indicate that EVs from AD-MSCs regulate the production of oxidative stress in OA chondrocytes during inflammation. Prdx6 may mediate the antioxidant and protective effects of MV.The translational potential of this article: This study gives insight into the protective properties of EVs from AD-MSCs in OA chondrocytes. Our findings support the development of novel therapies based on EVs to prevent or treat cartilage degradation.

The Potential of Shortening the Adaptation of Nellore Cattle to High-Concentrate Diets Using Only Virginiamycin as Sole Feed Additive.

Feedlot cattle are usually adapted to high-concentrate diets containing sodium monensin (MON) in more than 14 days. However, for finishing diets with lower energy content, the use of MON during adaptation may hold dry matter intake (DMI), and virginiamycin (VM) may be an alternative. This study was designed to determine the potential of shortening the adaptation of Nellore cattle to high-concentrate diets using only VM as a sole feed additive relative to feedlot performance, feeding behavior, and ruminal and cecum morphometrics. The experiment was designed as a completely randomized block replicated six times (four animals/pen) in which 120 Nellore bulls (390.4 ± 19.0 kg) were fed in 30 pens for 111 days according to the following treatments: (1) MON and adaptation for 14 days (MON14), (2) MON + VM and adaptation for 14 days (MONVM14), (3) VM and adaptation for 14 days (VM14), (4) VM and adaptation for 9 days (VM9), and (5) VM and adaptation for 6 days (VM6). At the end of the adaptation, 30 animals (n = 1 per pen) were randomly slaughtered for rumen and cecum evaluations. The remaining 90 bulls were harvested at the end of the study. No effects of treatments were observed (P < 0.10) for final body weight, average daily gain (ADG), and hot carcass weight (HCW). Cattle fed VM14 presented a greater (P ≤ 0.03) DMI, expressed as percent of body weight (BW), than animals fed either MON14 or MONVM14; however, cattle fed either MON14 or MONVM14 improved (P ≤ 0.02) the gain-to-feed ratio (G/F) by 10.4 or 8.1%, respectively, when compared to bulls fed VM14. Bulls fed VM14 had smaller (P < 0.05) papillae area (0.34 vs. 0.42 cm2) and rumen absorptive surface area (28.9 vs. 33.8 cm2) than those fed MON14. The shortening of the adaptation period linearly decreased the 12th rib fat (P = 0.02) and biceps femoris fat daily gain (P = 0.02) of Nellore bulls fed only VM, which linearly decreased the final biceps femoris fat thickness (P < 0.01). Feedlot cattle fed VM as a sole feed additive should not be adapted to high-concentrate diets in less than 14 days. Regardless of either adaptation length or feed additive, feedlot cattle need at least 14 days to adapt to finishing diets.

Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial.

BACKGROUND: The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator. METHODS: Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations. RESULTS: In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival. CONCLUSIONS: In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.

Knee Extensor Muscle Strength Is More Important Than Postural Balance for Stair-Climbing Ability in Elderly Patients with Severe Knee Osteoarthritis.

Knee osteoarthritis is a chronic joint disease which damages articular cartilage. In its severe stages, it results in impairments in balance and muscle strength loss, which affect daily life activities such as walking or climbing stairs. This study sought to investigate associated factors with stair-climbing ability in this population, with special interest in measuring the relevance of postural balance for this task. Forty-four patients scheduled to undergo unilateral total knee arthroplasty were assessed. Timed up and go test, stair ascent-descent test, three different isometric strength tests (knee flexion, knee extension and hip abduction), active knee extension and flexion range of movement and static postural balance assessment were evaluated. Spearman's correlation coefficients and multiple linear regression analysis determined the strength of association between the different variables and stair-climbing time. No significant association between the stair-climbing time and static balance was found. Significant associations were found between stair-climbing time and timed up and go (r = 0.71; p < 0.0001) and maximal knee extensor strength (r = -0.52; p = 0.0003). One-year increase in age was associated with 0.15 s (95% CI 0.00 to 0.30) slower stair-climbing time. In conclusion, muscle strength is more important than postural balance for stair-climbing ability in this population.

Osteosarcoma of the Trapezium.

Osteogenic sarcoma is a malignant tumor that rarely affects the hand. When it does, it most often involves the phalanges or metacarpal heads. We present the case of a 51-year-old woman with a low-grade osteosarcoma affecting the trapezium bone of her left hand. A total trapeziectomy with partial removal of the first metatarsal, scaphoid, trapezoid, and capitate bones was performed, and no adjuvant therapy was administered. Six years after the intervention, the patient is disease-free, with excellent functionality and yearly imaging tests showing no signs of recurrence.

The condition of the contralateral knee may induce different degrees of knee extensor strength asymmetry and affect functionality in individuals with unilateral or bilateral osteoarthritis.

BACKGROUND: Loss of knee extensor strength in individuals with knee osteoarthritis (KOA) may induce inter-limb strength asymmetries and alter functionality. The aims were to analyse whether the condition of the uninvolved knee (advanced to severe KOA or no affection) may induce different degrees of knee extensor strength asymmetry in individuals with KOA and to study whether functionality may differ in cases of unilateral or bilateral KOA. METHODS: Sixty-eight subjects with advance-to-severe KOA were categorized into two groups (unilateral or bilateral KOA). The knee extensor strength ratio (KESR), and self-reported and performance-based functionality were analysed and compared. Sex and age were independent factors. One- and two-way analysis of variance assessed for significant between-group differences (95% confidence interval (CI)). RESULTS: Participants with unilateral KOA presented with 20% knee extensor strength asymmetry. The mean difference with the bilateral KOA group in terms of Knee Extensors Strength Ratio was 0.2 (95% CI 0-0.3; P = 0.021), of the Oxford Knee Scale score was 4.2 (95% CI 3.4-5.1; P = 0.037), and of the Timed Up and Go was 1.3 s (95% CI 0.5-2.2; P > 0.05). There were significant sex and age interactions (P < 0.05). CONCLUSIONS: Individuals with unilateral or bilateral KOA present with different degrees of knee extensor strength asymmetry. The non-affected knee seems to help to better develop functional tasks in cases of unilateral condition. The findings may help the design of tailored strengthening interventions in which each knee condition in individuals with KOA should be considered.

Ruminal Fermentation Pattern, Bacterial Community Composition, and Nutrient Digestibility of Nellore Cattle Submitted to Either Nutritional Restriction or Intake of Concentrate Feedstuffs Prior to Adaptation Period.

Beef cattle are key contributors to meat production and represent critical drivers of the global agricultural economy. In Brazil, beef cattle are reared in tropical pastures and finished in feedlot systems. The introduction of cattle into a feedlot includes a period where they adapt to high-concentrate diets. This adaptation period is critical to the success of incoming cattle, as they must adjust to both a new diet and environment. Incoming animals are typically reared on a variety of diets, ranging from poor quality grasses to grazing systems supplemented with concentrate feedstuffs. These disparate pre-adaptation diets present a challenge, and here, we sought to understand this process by evaluating the adaptation of Nellore calves raised on either grazing on poor quality grasses (restriction diet) or grazing systems supplemented with concentrate (concentrate diet). Given that nutrient provisioning from the diet is the sole responsibility of the ruminal microbial community, we measured the impact of this dietary shift on feeding behavior, ruminal fermentation pattern, ruminal bacterial community composition (BCC), and total tract digestibility. Six cannulated Nellore bulls were randomly assigned to two 3 × 3 Latin squares, and received a control, restriction, or concentrate diet. All cohorts were then fed the same adaptation diet to mimic a standard feedlot. Ruminal BCC was determined using Illumina-based 16S rRNA amplicon community sequencing. We found that concentrate-fed cattle had greater dry matter intake (P < 0.01) than restricted animals. Likewise, cattle fed concentrate had greater (P = 0.02) propionate concentration during the adaptation phase than control animals and a lower Shannon's diversity (P = 0.02), relative to the restricted animals. We also found that these animals had lower (P = 0.04) relative abundances of Fibrobacter succinogenes when compared to control animals during the pre-adaptation phase and lower abundances of bacteria within the Succinivibrio during the finishing phase, when compared to the control animals (P = 0.05). Finally, we found that animals previously exposed to concentrate were able to better adapt to high-concentrate diets when compared to restricted animals. Our study presents the first investigation of the impact of pre-adaptation diet on ruminal BCC and metabolism of bulls during the adaptation period. We suggest that these results may be useful for planning adaptation protocols of bulls entering the feedlot system and thereby improve animal production.

Microvesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells as a New Protective Strategy in Osteoarthritic Chondrocytes.

BACKGROUND/AIMS: Chronic inflammation contributes to cartilage degeneration during the progression of osteoarthritis (OA). Adipose tissue-derived mesenchymal stem cells (AD-MSC) show great potential to treat inflammatory and degradative processes in OA and have demonstrated paracrine effects in chondrocytes. In the present work, we have isolated and characterized the extracellular vesicles from human AD-MSC to investigate their role in the chondroprotective actions of these cells. METHODS: AD-MSC were isolated by collagenase treatment from adipose tissue from healthy individuals subjected to abdominal lipectomy surgery. Microvesicles and exosomes were obtained from conditioned medium by filtration and differential centrifugation. Chondrocytes from OA patients were used in primary culture and stimulated with 10 ng/ml interleukin(IL)-1ß in the presence or absence of AD-MSC microvesicles, exosomes or conditioned medium. Protein expression was investigated by ELISA and immunofluorescence, transcription factor-DNA binding by ELISA, gene expression by real-time PCR, prostaglandin E2 (PGE2) by radioimmunoassay, and matrix metalloproteinase (MMP) activity and nitric oxide (NO) production by fluorometry. RESULTS: In OA chondrocytes stimulated with IL-1ß, microvesicles and exosomes reduced the production of inflammatory mediators tumor necrosis factor-α, IL-6, PGE2 and NO. The downregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 would lead to the decreased PGE2 production while the effect on NO could depend on the reduction of inducible nitric oxide synthase expression. Treatment of OA chondrocytes with extracellular vesicles also decreased the release of MMP activity and MMP-13 expression whereas the production of the anti-inflammatory cytokine IL-10 and the expression of collagen II were significantly enhanced. The reduction of inflammatory and catabolic mediators could be the consequence of a lower activation of nuclear factor-κB and activator protein-1. The upregulation of annexin A1 specially in MV may contribute to the anti-inflammatory and chondroprotective effects of AD-MSC. CONCLUSIONS: Our data support the interest of AD-MSC extracellular vesicles to develop new therapeutic approaches in joint conditions.

HIV1-viral protein R (Vpr) mutations: associated phenotypes and relevance for clinical pathologies.

Over the last 30 years, research into HIV has advanced the knowledge of virus genetics and the development of efficient therapeutic strategies. HIV-1 viral protein R (Vpr) is a specialized and multifunctional protein that plays important roles at multiple stages of the HIV-1 viral life cycle. This protein interacts with a number of cellular and viral proteins and with multiple activities including nuclear transport of the pre-integration complex (PIC) to the nucleus, transcriptional activation, cell cycle arrest at G2/M transition phase and induction of cell death via apoptosis. Specifically, Vpr has been shown to control many host cell functions through a variety of biological processes and by interaction with several cellular pathways. The different functions of Vpr may enhance viral replication and impair the immune system in HIV-1 infected patients. Importantly, functional defects induced by mutations in the Vpr protein correlate with slow disease progression of HIV-infected patients. Vpr is also associated with other concomitant pathologies developed by these patients, which may lead it to be considered as a potential novel therapeutic target. This review will focus on HIV-1 Vpr, mainly on the importance of its structural mutations on the progression of HIV infection, associated phenotypes and relevance for clinical pathologies. Copyright © 2016 John Wiley & Sons, Ltd.