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International audience; Introduction: This study aimed to assess if an interference effect could blunt the neuromuscular gains induced by a same-session combined rehabilitation in hemodialysis (HD) patients. Methods: Patients exercised twice a week, for 16 weeks, over their HD sessions. They were either always trained with resistance and endurance exercises (continuous training, “CONT”) or alternatively with 1 week of resistance alternated with 1 week of endurance (discontinuous training, “DISC”). Adherence and workload were continuously recorded. Short Physical Performance Battery (SPPB) score, one-leg balance test, and handgrip and quadriceps strength were evaluated before and after training intervention. Results: Adherence to both programs was high (>90%). SPPB score had significantly improved (CONT: +1.5 point, DISC: +1.2 pt, p < 0.001), like one-leg balance test (CONT: +3.7 s, DISC: +5.5 s, p < 0.05), handgrip strength of exercised (CONT: +5.5 kg, DISC: +5.6 kg, p < 0.001) and of nonexercised arm (CONT: +4.4 kg, DISC: +2.8 kg, p < 0.01) as well as maximal quadriceps strength (+22 N·m for dominant and +29 N·m for nondominant leg in both groups, p < 0.001) bearing no difference between the trainings. Conclusion: Same-session combined training does not induce an interference effect in HD patients and temporal separation of exercises does not optimize strength gains. These practical data may be relevant for clinicians and practitioners to alternate endurance and resistance exercises.

Background Malnutrition in chronic obstructive pulmonary disease (COPD) patients is more prevalent during times of exacerbation. Fat-free mass index (FFMI), calf circumference (CC), and adductor muscle pollicis thickness (AMPT) can be used to identify reduced muscle mass and have been found to be good predictors of clinical outcomes in other conditions, but they have not been investigated in COPD. Therefore, this study evaluated low muscle mass as predictor of malnutrition, prolonged length of stay (LOS), and in-hospital death in COPD patients. Methods This prospective cohort study was carried out in hospitalized patients with COPD exacerbation. Malnutrition diagnosis was performed by Subjective Global Assessment, and muscle mass was assessed by FFMI, calculated using fat-free mass from bioelectrical impedance, CC, and AMPT. Clinical outcomes (LOS and in-hospital death) were collected from records. Results One hundred seventy-six patients were included (68.2 ± 10.4 years old, 56.2% women); 74.2% were classified as Global Initiative of Chronic Obstructive Lung Disease 2 or 3 and 58.2% as malnourished. The median LOS was 11 (7-19) days, and the incidence of death was 9.1%. Low FFMI and CC predicted malnutrition (low CC: odds ratio [OR], 4.6; 95% CI, 2.2-9.7 and low FFMI: OR, 8.8; 95% CI, 3.7-20.8) and were associated with prolonged LOS (low CC: OR, 2.3; 95% CI, 1.1-4.6 and low FFMI: OR, 2.5; 95% CI, 1.3-4.8). Conclusion Simple, inexpensive, and noninvasive parameters of muscle mass-FFMI and CC-are good predictors of malnutrition and prolonged LOS in COPD patients experiencing exacerbation.

Background Subjective Global Assessment (SGA) is the reference method to identify hospital malnutrition. The Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition (AND-ASPEN) proposed a more objective consensus, but studies regarding its validity are still scarce. This study aimed to evaluate the concurrent and predictive validity of the AND-ASPEN Consensus. Methods Prospective cohort conducted with hospitalized adult and elderly patients. At admission, general data were collected and patients were evaluated by SGA and AND-ASPEN with and without handgrip strength (HGS) for nutrition diagnoses. Patients were followed up for collection of outcomes-length of hospital stay (LOS), in-hospital death, readmission, and mortality within 6 months after being discharged. Concurrent and predictive validity were tested. Results Six hundred patients (55.7 ± 14.8 years, 51.3% males) were evaluated. The median of LOS was 10.0 (5.018.0) days and in-hospital mortality was 2.7%. SGA identified 34.0% and AND-ASPEN 34.6% of patients as malnourished. AND-ASPEN had substantial agreement with SGA (κ = 0.690) and satisfactory accuracy (AUC = 0.85; 95% CI, 0.810.88). Malnutrition defined by AND-ASPEN predicted about 1.4 times higher risk of prolonged LOS (95% CI, 1.2-1.6) and hospital readmission (95% CI, 1.2-1.8), besides 5.0 times higher risk of hospital death (95% CI, 1.3-18.8) and 6 months' death (95% CI, 2.6-9.9), in an adjusted analysis. The validity of AND-ASPEN without HGS was also satisfactory. Conclusion AND-ASPEN can be used for malnutrition diagnoses, even without HGS because it has satisfactory concurrent and predictive validity.

BACKGROUND Malnourished patients present impairment of functionality due to loss of strength and muscle mass. However, the validity of handgrip strength (HGS) in identifying malnutrition and its association with clinical outcomes in hospitalized patients requires investigation. AIMS Evaluate the accuracy of HGS in identifying malnutrition, its association with clinical outcomes, and the change in HGS in the first 2 weeks of hospitalization. METHODS A prospective cohort study with adult/elderly patients. Subjective Global Assessment (SGA) was applied in the first 48 hours for malnutrition diagnosis, and HGS was measured in this moment and after 7 and 14 days of hospital admission. HGS

OBJECTIVES: The Accreditation Council for Graduate Medical Education requires residents to participate in scholarship and requires residency programs to provide an environment within which residents can acquire skills related to scholarly activities. However, consensus on the definition of scholarship and structure of program environments does not yet exist. We designed and implemented a content expert program (CEP) in 2015, in which each resident worked with a faculty advisor to develop a longitudinal scholarly activity linked to a core area of practice and, in doing so, became the department's “content expert.” We hypothesized that the CEP would significantly increase the number of scholarly outputs per resident. METHODS: The CEP was structured around an oversight committee composed of key faculty members, which guided development of CEP projects through regular meetings and formative feedback. Each resident generated one or more scholarly outputs from their content area. Outputs were categorized into educational, operational, research, and miscellaneous domains and further identified as intradepartmental, interdepartmental, or interdisciplinary collaborations. The number of outputs was compared to the baseline number of scholarly activities per resident at the study program using a Mann–Whitney U test. RESULTS: A total of 187 scholarly outputs were generated by 76 residents, which equated to 31.2 outputs per year, or 2.5 outputs per resident. This was a significant increase compared to the program baseline of one output per resident (p = 0.003). Eighteen distinct types of outputs spanned four major categories. Of the outputs, 37 were interdepartmental, 42 were interdisciplinary, and 32 were intradepartmental. CONCLUSIONS: The CEP proved to be a sustainable way to significantly increase scholarly activity and additionally improved collaborative efforts. With the appropriate structure and willing faculty in place, such a program can enhance the practical education provided by residency programs.

Chondrocytes in osteoarthritic (OA) cartilage acquire a hypertrophic-like phenotype, where Hedgehog (Hh) signaling is pivotal. Hh overexpression causes OA-like cartilage lesions, whereas its downregulation prevents articular destruction in mouse models. Mutations in EVC and EVC2 genes disrupt Hh signaling, and are responsible for the Ellis-van Creveld syndrome skeletal dysplasia. Since Ellis-van Creveld syndrome protein (Evc) deletion is expected to hamper Hh target gene expression we hypothesized that it would also prevent OA progression avoiding chondrocyte hypertrophy. Our aim was to study Evc as a new therapeutic target in OA, and whether Evc deletion restrains chondrocyte hypertrophy and prevents joint damage in an Evc tamoxifen induced knockout (EvccKO) model of OA. For this purpose, OA was induced by surgical knee destabilization in wild-type (WT) and EvccKO adult mice, and healthy WT mice were used as controls (n = 10 knees/group). Hypertrophic markers and Hh genes were measured by qRT-PCR, and metalloproteinases (MMP) levels assessed by western blot. Human OA chondrocytes and cartilage samples were obtained from patients undergoing knee joint replacement surgery. Cyclopamine (CPA) was used for Hh pharmacological inhibition and IL-1 beta as an inflammatory insult. Our results showed that tamoxifen induced inactivation of Evc inhibited Hh overexpression and partially prevented chondrocyte hypertrophy during OA, although it did not ameliorate cartilage damage in DMM-EvccKO mice. Hh pathway inhibition did not modify the expression of proinflammatory mediators induced by IL-1 beta in human OA chondrocytes in culture. We found that hypertrophic—IHH—and inflammatory—COX-2—markers co-localized in OA cartilage samples. We concluded that tamoxifen induced inactivation of Evc partially prevented chondrocyte hypertrophy in DMM-EvccKO mice, but it did not ameliorate cartilage damage. Overall, our results suggest that chondrocyte hypertrophy per se is not a pathogenic event in the progression of OA., This work was financially supported by grants from the Instituto de Salud Carlos III [PI20/00349, PI16/00065, PI18/00261] and Fondo Europeo de Desarrollo Regional (FEDER); and by the Spanish Ministry of Science and Innovatin (MICINN) [SAF-2013-43365-R and SAF2016-75434-R] to VLR-P. AL and PG were funded by Fundación Conchita Rábago.

Background The present study aimed to assess the effect of a healthy diet, enriched or not with pecan nuts or extra-virgin olive oil, on the lipid profile of patients with stable coronary artery disease (CAD). Methods This was a randomised clinical trial conducted for 12 weeks with patients aged between 40 and 80 years with stable CAD for more than 60 days. Individuals were randomised into groups [control group (CG) with 67 patients, pecan nut group (PNG) with 68 patients and olive oil group (OOG) with 69 patients]. The CG was prescribed a healthy diet according to the nutritional guidelines; the PNG was prescribed the same healthy diet plus 30 g day-1 of pecan nuts; and the OOG was prescribed a healthy diet plus 30 mL day-1 of extra-virgin olive oil. Results In total, 204 subjects were submitted to an intention-to-treat analysis. After adjustment for baseline values and type of statin used, there was no difference regarding low-density lipoprotein (LDL)-cholesterol (primary outcome), high-density lipoprotein (HDL)-cholesterol, LDL-cholesterol/HDL-cholesterol ratio and HDL-cholesterol/triglycerides ratio according to groups. However, the PNG exhibited a significant reduction in non-HDL-cholesterol levels [PNG: 114.9 (31) mg dL-1 ; CG: 127 (33.6) mg dL-1 ; OOG: 126.6 (37.4) mg dL-1 ; P = 0.033] and in the total cholesterol/HDL-cholesterol ratio [PNG: 3.7 (0.7); CG: 4.0 (0.8); OOG: 4.0 (0.8); P = 0.044] compared to the CG and OOG. Conclusions Supplementing a healthy diet with 30 g day-1 of pecan nuts for 12 weeks did not improve LDL-cholesterol levels but may improve other lipid profile markers in patients with stable CAD.

The potential involvement of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC) has been previously reported. While several clinical studies show a higher incidence of CC and a lower survival rate in diabetics, others report no association. Our own experience indicates that diabetes does not seem to worsen the prognosis once the tumor is present. Despite this controversy, there are no wide‐spectrum molecular studies that delve into the impact of T2DM‐related mechanisms in colon carcinogenesis. Here, we present a transcriptomic and proteomic profiling of paired tumor and normal colon mucosa samples in a cohort of 42 CC patients, 23 of which have T2DM. We used gene set enrichment and network approaches to extract relevant pathways in diabetics, referenced them to current knowledge, and tested them using in vitro techniques. Through our transcriptomics approach, we identified an unexpected overlap of pathways overrepresented in diabetics compared to nondiabetics, in both tumor and normal mucosa, including diabetes‐related metabolic and signaling processes. Proteomic approaches highlighted several cancer‐related signaling routes in diabetics found only in normal mucosa, not in tumors. An integration of the transcriptome and proteome analyses suggested the deregulation of key pathways related to colon carcinogenesis which converged on tumor initiation axis TEAD/YAP‐TAZ as a potential initiator of the process. In vitro studies confirmed upregulation of this pathway in nontumor colon cells under high‐glucose conditions. In conclusion, T2DM associates with deregulation of cancer‐related processes in normal colon mucosa adjacent to tissue which has undergone a malignant transformation. These data support that in diabetic patients, the local microenvironment in normal colon mucosa may be a factor driving field cancerization promoting carcinogenesis. Our results set a new framework to study links between diabetes and colon cancer, including a new role of the TEAD/YAP‐TAZ complex as a potential driver.

OBJECTIVE To understand the drivers of body skin discomfort and to validate a new index to assess its severity. This index should be sensitive enough to capture changes in response to treatment. METHODS Previous consumer studies suggested seven potential main dimensions behind skin discomfort. Four of them refer to self-declarations (stinging, itching, warming and tightening), whereas three can be assessed by a dermatologist (skin dryness, redness and desquamation). Intensity and frequency or extent of these items were measured using 0-9 ordinal scales. To generate the data for validation of a new index based on the 7 items, a group of 49 subjects complaining of skin discomfort was followed up for 5 weeks: 1-week without product application to check reproducibility, followed by 4 weeks of treatment to evaluate sensitivity to change. Items not significantly reported at baseline or with changes because of treatment not sufficiently correlated with the overall change measured by the index were discarded. A control group of 49 subjects presenting no discomfort at all was also included to check the capacity of our index to discriminate both groups. The final index (Body Skin Discomfort Index, BSDI) was normalized to facilitate the clinical interpretation of the results. RESULTS After discarding warming and skin redness, the BSDI is finally a five-dimension score calculated as follows: (TI + TF + SI + SF + ItI + ItF + DI + DE + DqI + DqE) 9 9/90 where T, S, It, D and Dq refer to tightness, stinging, itching, dryness, desquamation respectively, and I, F or E refers to intensity, frequency or extent. The final BSDI score displayed a good capacity to discriminate people with skin discomfort from people with 'normal skin', a good reproducibility (intraclass coefficient correlation ICC = 0.85) and a good sensitivity to detect change because of treatment (Difference vs. Baseline of 2.63 on a 0-9 scale). CONCLUSION The developed index, BSDI, is a reliable way to address the measurement issue of the multidimensional skin discomfort syndrome. It thus should simplify the evaluation of cosmetic products effect and helps to compare products dedicated to body cleansing.

Bananas and plantains (Musa spp.) are among the most important crops in the world providing staple food for hundreds of millions of people. However, banana production has been devastated by fungal infestations caused by Fusarium oxysporum f. sp. cubense (Foc). Despite the fact that there is very little known on the role of microbial metabolites in the molecular mechanism of Foc infections, it has been proposed that the toxins fusaric acid and beauvericin produced by Foc play an important role during pathogenesis. The aim of this contribution was to study the toxic components of culture filtrates (CF) of Foc and to isolate the extracellular microbial metabolites involved in the plant response. An in vitro bioassay was used to evaluate the production of phytotoxic metabolites as well as the specificity of culture from a strain of Foc belonging to VCG 01210 (race 1). A host‐specific CF was obtained and the phytotoxic compounds characterized as fusaric acid, beauvericin and fumonisin B1. Despite the presence of these nonspecific toxins, a water‐soluble extract from the CF induced protection to the main phytotoxic fraction, measured by lesion area. This hydrophilic fraction induced a fast and strong response of just jasmonic acid (JA)‐dependent defence genes rather than salicylic acid (SA)‐ and ethylene (ET)‐response genes in resistant cultivars. Extracellular proteins isolated from CF of Foc provide an important source for further investigations on the molecular basis of the interaction between Foc and banana.

Oxidative damage is an important contributor to the morphological and functional changes in osteoporotic bone. Aging increases the levels of reactive oxygen species (ROS) that cause oxidative stress and induce osteoblast apoptosis. ROS modify several signaling responses, including mitogen-activated protein kinase (MAPK) activation, related to cell survival. Both parathyroid hormone (PTH) and its bone counterpart, PTH-related protein (PTHrP), can regulate MAPK activation by modulating MAPK phosphatase-1 (MKP1). Thus, we hypothesized that PTHrP might protect osteoblasts from ROS-induced apoptosis by targeting MKP1. In osteoblastic MC3T3-E1 and MG-63 cells, H2 O2 triggered p38, JNK, ERK and p66Shc phosphorylation, and cell apoptosis. Meanwhile, PTHrP (1-37) rapidly but transiently increased ERK and Akt phosphorylation without affecting p38, JNK, or p66Shc activation. H2 O2 -induced p38 and ERK phosphorylation and apoptosis were both decreased by pre-treatment with specific kinase inhibitors or PTHrP (1-37) in both osteoblastic cell types. These dephosphorylating and prosurvival actions of PTHrP (1-37) were prevented by a phosphatase inhibitor cocktail, the phosphatase MKP1 inhibitor sanguinarine or a MKP1 siRNA. PTHrP (1-37) promptly enhanced MKP1 protein and gene expression and MKP1-dependent catalase activity in osteoblastic cells. Furthermore, exposure to PTHrP (1-37) adsorbed in an implanted hydroxyapatite-based ceramic into a tibial defect in aging rats increased MKP1 and catalase gene expression in the healing bone area. Our findings demonstrate that PTHrP counteracts the pro-apoptotic actions of ROS by a mechanism dependent on MKP1-induced dephosphorylation of MAPKs in osteoblasts.

RRAM technology relying on transitional metal oxides (namely OxRAM) is about to reach the industrial stage. Nevertheless the physical-based understanding of the material and process implications at device and circuit levels is still not completely clear, hindering the full industrial exploitation of the OxRAM technology. In this context, this article presents a multi-scale methodology that connects the microscopic material properties to the electrical behavior of OxRAM devices at the circuit level. Microscopic models describing OxRAM operation (i.e., forming, resistive switching) and variability (e.g., cycle-to-cycle, RTN) will be reviewed and used for the development of compact models that will allow investigating the potential of this technology at the circuit level. An overview of some innovative applications involving OxRAM will be finally presented.

Introduction: Mild ophthalmoparesis can be seen in oculopharyngeal muscular dystrophy (OPMD). Methods: Orthoptic analysis included assessment of phoria/tropia, eye excursion, saccades, pursuit, stereoacuity, and Hess–Lancaster screen test. Video-oculography included fixation, horizontal and vertical saccades, and pursuit. Results: Orthoptic abnormalities were: tropia (4 of 6); abnormal eye excursion (4 of 6, 78% involved lateral or superior rectus muscles); abnormal horizontal or vertical saccades (2 of 6); abnormal pursuit (0 of 6); abnormal stereoacuity (2 of 6); and pathological Hess–Lancaster screen (4 of 6). Video-oculographic abnormalities were present for: fixation (1 of 6); saccade latency (1 of 6); horizontal pursuit (3 of 6); and vertical pursuit (0 of 6). For horizontal saccades, mean velocity, peak velocity, and gain were pathological in 5 of 6, 5 of 6 (61% of pathological mean and peak velocities involved abducting eye movements), and 3 of 6, respectively. For vertical saccades, mean velocity, peak velocity, and gain were pathological in 4 of 6, 4 of 6 (53% involved upward movements), and 3 of 6, respectively. Conclusion: The data indicate preferential involvement of lateral and (to a lesser degree) superior rectus muscles in OPMD. Muscle Nerve 52: 554–558, 2015

Objective Otologic complaints may place a significant burden on emergency departments (EDs) in the United States; however, few studies have comprehensively examined this discrete patient population. We aim to identify utilization of EDs by patients with primary otologic complaints.

Telaprevir and boceprevir, the two first hepatitis C virus (HCV) NS3 protease inhibitors (PIs), considerably increase rates of sustained virologic response in association with pegylated interferon and ribavirin in chronic HCV genotype 1 infections. The 30 first patients treated by telaprevir or boceprevir including anti-HCV therapies since 2011 in Marseille University hospitals, France, were monitored. HCV loads and plasmatic concentrations of telaprevir and boceprevir were determined on sequential blood samples. HCV NS3 protease gene population sequencing was performed at baseline of treatment and in case of treatment failure. Fifteen patients (including 7 co-infected with HIV) received telaprevir and the other 15 patients (including 4 co-infected with HIV) received boceprevir. At baseline, HCV NS3 protease from six patients harbored amino acid substitutions associated with PI-resistance. Treatment failure occurred at week 12 for 7 patients. Amino acid substitutions associated with PI-resistance were observed in six of these cases. HCV NS3 R155K and T54A/S mutants, all of genotype 1a, were found from four patients. Median (interquartile range) plasma concentrations were 3,092 ng/ml (2,320-3,525) for telaprevir and 486 ng/ml (265-619) for boceprevir. For HIV-HCV co-infected patients, median concentrations were 3,162 ng/ml (2,270-4,232) for telaprevir and 374 ng/ml (229-519) for boceprevir. Plasma drug concentration monitoring revealed undetectable concentrations for two patients at week 4, and probable non-adherence to therapy for another patient. These findings indicate that routine HCV NS3 protease sequencing and plasma PI concentration monitoring might be helpful to characterize cases of therapy failure, at a cost dramatically low compared to that of anti-HCV therapy.

Fibrosing mediastinitis (FM), also called sclerosing mediastinitis or mediastinal fibrosis, is a rare disease characterized by excessive fibrotic reaction in the mediastinum and may compromise the airway, the great vessels and other mediastinal structures, with a morbidity directly related to the location and extent of fibrosis. The cause is not always known but is often the result of a granulomatous disease, most often the histoplasmosis. We report a 43-year-old woman with a history of tuberculosis infection 23 years ago. She attended the pulmonology clinic for cough and dyspnea. Physical examination revealed jugular venous distention at 90°. In computed tomography scan of the chest with contrast (c/c), we observed a mediastinal nodal cast provoking cava compression and obliteration of main and intermediary right lobar bronchus. The pathological examination was FM.