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Objective: This study aimed to examine the association of loneliness and social isolation on cognition over a 3-year follow-up period in middle- and older-aged adults.Methods: Data from a Spanish nationally representative sample were analyzed (n = 1691; aged 50 years or older). Loneliness, social isolation, and cognition (immediate recall, delayed recall, verbal fluency, forward digit span, backward digit span, and a composite cognitive score) were assessed both at baseline and at follow-up. Adjusted generalized estimating equations models were performed.Results: Loneliness was significantly associated with lower scores in the composite cognitive score, immediate and delayed recall, verbal fluency, and backward digit span (B = -0.14 to B = -3.16; P < .05) and with a more rapid decline from baseline to follow-up in two out of six cognitive tests. Higher social isolation was associated with lower scores in the composite cognitive score, verbal fluency, and forward digit span (B = -0.06 to B = -0.85; P < .05). The effect of loneliness and social isolation on cognition remained significant after the exclusion of individuals with depression.Conclusions: Both loneliness and social isolation are associated with decreased cognitive function over a 3-year follow-up period. The development of interventions that include the enhancement of social participation and the maintenance of emotionally supportive relationships might contribute to cognitive decline prevention and risk reduction. [ABSTRACT FROM AUTHOR]

Background: The positive-intraoperative-cultures-type prosthetic joint infection (PIOC-PJI) is considered when surgical cultures yield microorganisms in presumed aseptic arthroplasty revisions. Herein we assess the risk factors for failure in the largest cohort of PIOC-PJI patients reported to date.Methods: A retrospective, observational, multicenter study was performed during 2007-2017. Surgeries leading to diagnose PIOC-PJI included only one-stage procedures with either complete or partial prosthesis revision. Failure was defined as recurrence caused by the same microorganism.Results: 203 cases were included (age 72 years, 52% females). Coagulase-negative staphylococci (n = 125, 62%) was the main etiology, but some episodes were caused by virulent bacteria (n = 51, 25%). Prosthesis complete and partial revision was performed in 93 (46%) and 110 (54%) cases, respectively. After a median of 3.4 years, failure occurred in 17 episodes (8.4%, 95%CI 5.3-13.1). Partial revision was an independent predictor of failure (HR 3.63; 95%CI 1.03-12.8), adjusted for gram-negative bacilli (GNB) infection (HR 2.68; 95%CI 0.91-7.89) and chronic renal impairment (HR 2.40; 95%CI 0.90-6.44). Treatment with biofilm-active antibiotics (rifampin/fluoroquinolones) had a favorable impact on infections caused by staphylococci and GNB.Conclusion: Overall prognosis of PIOC-PJI is good, but close follow-up is required in cases of partial revision and in infections caused by GNB. [ABSTRACT FROM AUTHOR]

Objective: To assess whether higher adherence to the traditional Mediterranean diet (MedDiet) was associated with lower consumption of ultra-processed foods (UPF) and lower free sugar intake.Design: Cross-sectional analysis of baseline information among participants in the SENDO project, a Spanish paediatric cohort. Dietary information was collected through a semi-quantitative FFQ. Food items were classified according to the NOVA classification. Adherence to the MedDiet was evaluated through the KIDMED index.Setting: Spain.Participants: Three hundred eight-six children (52 % boys) with a mean age of 5·3 years old (sd 1·0) were included in the analysis.Results: 74·4 % of the children had moderate adherence to the MedDiet (mean KIDMED score: 5·9 points; sd 1·7) and overall, 32·2 % of the total energy intake came from UPF. Each two additional points in the KIDMED score was associated with 3·1 % (95 % CI 2·1, 4·0) lower energy intake from UPF. Compared to those with low adherence to the MedDiet, children with medium and high adherence reported 5·0 % (95 % CI 2·2, 7·7) and 8·5 % (95 % CI 5·2, 11·9) lower energy intake from UPF, respectively. We also found that 71·6 % of the variability in free sugar intake was explained by the variability in UPF consumption.Conclusions: Adherence to the traditional MedDiet was inversely associated with energy intake from UPF. Furthermore, most of the variability in free sugar intake was explained by the variability of UPF consumption. Public health strategies are needed to strengthen the adherence to the MedDiet in pre-schoolers while regulating the production, marketing and advertising of UPF. [ABSTRACT FROM AUTHOR]

Introduction: To assess the risk of occurrence and potential determinants of metabolic disorders in adult patients treated with second-generation antipsychotics (SGAs) under real-world practice conditions.Methods: MEDLINE, EMBASE, and PsycInfo were searched in July 2019 from database inception. We included population-based, longitudinal, comparative studies that report the results of the outcomes of interest for adult participants, including diabetes, ketoacidosis, hyperosmolar hyperglycemic state, weight gain/obesity, dyslipidemia, hypertension, and metabolic syndrome. Two reviewers independently extracted data on the study design, study quality, and study outcomes.Results: We included 40 studies. Most studies showed that clozapine and olanzapine were associated with an increased likelihood of developing diabetes, while the results for risperidone and quetiapine were mixed. Although less well studied, ziprasidone and aripiprazole appeared to not be associated with the occurrence of diabetes. Information on antipsychotic-induced weight gain/obesity is extremely scarce. Regarding dyslipidemia, aripiprazole was not associated with an increased likelihood of developing dyslipidemia, clozapine was associated with an increased likelihood of developing dyslipidemia, and risperidone, olanzapine, quetiapine, and ziprasidone showed mixed results. Two studies suggested an association between ziprasidone and the occurrence of hypertension. Several studies found that the occurrence of a metabolic disorder acted as a risk factor for the development of other metabolic disorders. We did not find information on brexpiprazole, cariprazine, or lurasidone, and data on any long-acting SGA were lacking.Conclusion: Although there are relevant differences among SGAs concerning the risk of metabolic disorders, it appears that none of the SGAs included in our review are fully devoid of these disturbances. [ABSTRACT FROM AUTHOR]

Background: Invasive fusariosis (IF) affects mostly severely immunocompromised hosts and is associated with poor outcome. Since Fusarium species exhibit high MICs for most antifungal agents, this could explain the poor prognosis. However, a clear-cut correlation between MIC and outcome has not been established.Objective: To evaluate the correlation between MIC and outcome (6 week death rate) in patients with IF.Methods: We performed a multicentre retrospective study of patients with IF who received treatment and had MIC levels determined by EUCAST or CLSI for the drug(s) used during treatment. We compared the MIC50 and MIC distribution among survivors and patients who died within 6 weeks from the diagnosis of IF.Results: Among 88 patients with IF, 74 had haematological diseases. Primary treatment was monotherapy in 52 patients (voriconazole in 27) and combination therapy in 36 patients (liposomal amphotericin B + voriconazole in 23). The MIC50 and range for the five most frequent agents tested were: voriconazole 8 mg/L (range 0.5-64), amphotericin B 2 mg/L (range 0.25-64), posaconazole 16 mg/L (range 0.5-64), itraconazole 32 mg/L (range 4-64), and isavuconazole 32 mg/L (range 8-64). There was no difference in MIC50 and MIC distribution among survivors and patients who died. By contrast, persistent neutropenia and receipt of corticosteroids were strong predictors of 6 week mortality.Conclusions: Our study did not show any correlation between MIC and mortality at 6 weeks in patients with IF. [ABSTRACT FROM AUTHOR]

Background: The semantic variant of primary progressive aphasia (svPPA) is characterized by a progressive loss of semantic knowledge impairing the ability to name and to recognize the meaning of words.Objective: We aimed to evaluate the immediate and short-term effect of errorless learning speech therapy on the naming and recognition of commonly used words in patients with svPPA.Methods: Eight participants diagnosed with svPPA received 16 sessions of intensive errorless learning speech therapy. Naming and word comprehension tasks were evaluated at baseline, immediately postintervention, and at follow-up after 1, 3, and 6 months. These evaluations were performed using two item sets (a trained list and an untrained list).Results: In the naming tasks, patients showed a significant improvement in trained items immediately after the intervention, but that improvement decayed progressively when therapy ended. No improvements were found either in trained comprehension or in untrained tasks.Conclusion: Errorless learning therapy could improve naming ability in patients with svPPA. This effect may be due to the relative preservation of episodic memory, but the benefit is not maintained over time, presumably because there is no consolidation. [ABSTRACT FROM AUTHOR]

Background: Limb-girdle muscular dystrophy recessive 1 calpain3-related (LGMDR1), previously known as LGMD2A, is a disease caused by mutations in the CAPN3 gene. It is characterized by progressive weakness and muscle degeneration. Frizzled related protein (FRZB), upregulated in LGMDR1, was identified as a key regulator of the crosstalk between Wnt and integrin signalling pathways. FRZB gene silencing showed a recovery in the expression of some of the costamere protein levels in myotubes.Results: Here, we performed a comprehensive characterization of Frzb-/- mice muscles to study the absence of Frzb in skeletal muscle and eventual links with the molecular characteristics of LGMDR1 patient muscles. Frzb-/- mice showed reduced muscle size and strength. Gait analysis showed that Frzb-/- mice moved more slowly but no impaired regeneration capacity was observed after muscle injury. Additionally, Frzb-/- mice muscle showed an increased number of mesoangioblasts. Lack of Frzb gene in Frzb-/- mice and its increased expression in LGMDR1 patients, showed contrary regulation of Rora, Slc16a1, Tfrc and Capn3 genes. The reciprocal regulation of Frzb and Capn3 genes further supports this axis as a potential target for LGMDR1 patients.Conclusions: Our data confirm a role for Frzb in the regulation of Rora, Slc16a1, Tfrc, and Capn3 genes in muscle cells. In vivo, reduced muscle strength and gait in the Frzb-/- mice are intriguing features. The reciprocal relationship between FRZB and CAPN3 further supports a key role for this axis in patients with LGMDR1. [ABSTRACT FROM AUTHOR]

A lack of reliable laryngeal thermal injury models precludes laryngeal burn wound healing studies and investigation of novel therapeutics. We hypothesize that a swine laryngeal burn model can allow for laryngeal burn evaluation over time. Twelve Yorkshire crossbreed swine underwent tracheostomy and endoscopically directed laryngeal burns using heated air (150-160°C). Swine larynges were evaluated and sectioned/stained at 12 hours, 1, 3, 7, 14, and 21 days. A board-certified veterinary pathologist assessed anatomic regions (left and right: epiglottis, true/false vocal folds, and subglottis) using a nine criteria histological injury scoring scale. Six swine were euthanized at scheduled endpoints, three prematurely (airway concerns), and three succumbed to airway complications after 16 to 36 hours. Endoscopic and gross examination from scheduled endpoints revealed massive supraglottic edema and tissue damage, particularly around the arytenoids, extending transglottically. Swine from premature endpoints had comparatively increased edema throughout. Microscopic evaluation documented an inverse relationship between injury severity score and time from injury. Inflammation severity decreased over time, nearly resolving by 14 days. Neutrophils predominated early with histiocytes appearing at 3 days. Granulation tissue appeared at 3 days, and early epiglottic and/or subglottic fibrosis appeared by 7 days and matured by 14 days. Edema, abundant initially, decreased by day 3 and resolved by day 7. This approach is the first to provide longitudinal analysis of laryngeal thermal injuries, reflecting some of the first temporal wound healing characteristic data in laryngeal thermal injuries and providing a platform for future therapeutic studies. [ABSTRACT FROM AUTHOR]

Purpose: Individuals with X-linked myotubular myopathy (XLMTM) who survive infancy require extensive supportive care, including ventilator assistance, wheelchairs and feeding tubes. Half die before 18 months of age. We explored respiratory support and associated mortality risk in RECENSUS, particularly among patients ≤5 years old who received respiratory support at birth; this subgroup closely matches patients in the ASPIRO trial of gene therapy for XLMTM.Design: RECENSUS is an international, retrospective study of patients with XLMTM. Descriptive and time-to-event analyses examined survival on the basis of age, respiratory support, tracheostomy use, predicted mutational effects and life-sustaining care.Results: Outcomes for 145 patients were evaluated. Among 126 patients with respiratory support at birth, mortality was 47% overall and 59% among those ≤5 years old. Median survival time was shorter for patients ≤5 years old than for those >5 years old (2.2 years (IQR 0.7-5.6) vs 30.2 years (IQR 19.4-30.2)). The most common cause of death was respiratory failure (66.7%). Median survival time was longer for patients with a tracheostomy than for those without (22.8 years (IQR 8.7-30.2) vs 1.8 years (IQR 0.2-not estimable)). The proportion of patients living without a tracheostomy was 50% at age 6 months and 28% at age 2 years. Median survival time was longer with provision of life-sustaining care than without (19.4 years (IQR 3.1-not estimable) vs 0.2 years (IQR 0.1-2.1)).Conclusions: High mortality, principally due to respiratory failure, among patients with XLMTM ≤5 years old despite respiratory support underscores the need for early diagnosis, informed decision-making and disease-modifying therapies.Trial Registration Number: NCT02231697. [ABSTRACT FROM AUTHOR]

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Objective: To compare response to rituximab (RTX) between adult patients positive for myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies.Methods: We prospectively studied adult patients with MOG or AQP4 antibodies who received RTX under an individualized dosing schedule adapted to the biological effect of RTX monitored by memory B-cell measurement. Memory B cells were counted monthly and when relapse occurred. The biological effect of RTX was considered significant with <0.05% memory B cells in peripheral blood lymphocytes.Results: In 16 patients with MOG antibodies and 29 with AQP4 antibodies, mean follow-up was 19 (range = 9-38) and 38 (13-79) months. Under RTX, 10 relapses occurred in 6 of 16 (37.5%) patients with MOG antibodies, and 13 occurred in 7 of 29 (24%) with AQP4 antibodies. The median time of relapse after the most recent infusion was 2.6 (0.6-5.8) and 7 (0.8-13) months, respectively (p < 0.001). Memory B cells had reemerged in 2 of 10 (20%) relapses in patients with MOG antibodies and 12 of 13 (92.5%) with AQP4 antibodies (p < 0.001).Interpretation: In AQP4 antibody-associated disorder, relapse mostly occurs when the biological effect of RTX decreases, which argues for treatment efficacy. In MOG antibody-associated disorder, the efficacy of RTX is not constant, because one-third of patients showed relapse despite an effective biological effect of RTX. In this subpopulation, memory B-cell depletion was unable to prevent relapse, which was probably caused by different immunological mechanisms. These findings should be used to improve treatment strategies for MOG antibody-associated disorder. ANN NEUROL 2020;87:256-266. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the current study is to assess, using new technologies, the interaction of four monthly silicone hydrogel contact lenses on the ocular surface and the comfort over 15 days of use.Methods: Prospective cross-over, randomized and double-masked study including four materials (lotrafilcon-B, samfilcon-A , comfilcon-A and filcom-V3). Clinical examination was performed in the following order: tear meniscus height, first break-up of the tear film, the average time of all tear film breakup incidents, bulbar redness, limbal redness (Keratograph 5M ,Oculus, Germany); central corneal thickness (Pentacam, Oculus, Germany), thermography values (FLIR A325; FLIR Systems Inc., USA), and slit-lamp evaluations, including ocular surface staining. Finally, subjective comfort was obtained from Contact Lens Dry Eye Questionnaire-8.Results: The impact of contact lens wear on the ocular surface didn't show statistically significant changes over time except for corneal and conjunctival staining grades on day 15 compared to day 1 for the comfilcon A group (P = .003 and P = .01, respectively). Contact lens stability and impact on the ocular surface during contact lens wear didn't show statistically significant changes over time except in the case of the comfilcon A material with respect to the irritation item (P = .01).Conclusions: These results suggest that the impact of monthly silicone hydrogel contact lens materials on the ocular surface after and during contact lens wear, contact lens stability over time, and subjective comfort did not reveal any significant changes over 15 days of use for any of the materials. [ABSTRACT FROM AUTHOR]

The objective of this cross-sectional study was to evaluate the frequency, impact, and management of sexual dysfunction associated with commonly prescribed antidepressants available in psychiatry outpatient clinics in Spain. We recruited 2163 adult patients who had undergone treatment with antidepressants for at least 8 weeks and had a history of normal sexual functioning before the prescription of the antidepressant, except for mildly impaired libido. We used the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SALSEX) for evaluating the frequency and tolerance of sexual dysfunction and whether this side effect was spontaneously reported. Overall, 79% patients showed sexual dysfunction, as indicated by a total score ≥ 3 on the PRSexDQ-SALSEX; 64% showed moderate-severe sexual dysfunction, with no differences between men and women on these outcomes. In the multivariate logistic regression analysis, treatment with a serotonergic antidepressant and having a severe clinical state of psychiatric illness were the factors associated with the highest likelihood of presenting with sexual dysfunction. Sexual dysfunction was spontaneously reported by 838 (41%) of the 2066 evaluable patients for this outcome. Among patients with sexual dysfunction, this condition was poorly tolerated by 22% of the patients, with these frequencies being significantly higher in men than in women. The most frequently used strategies employed by the psychiatrists in our study for dealing with sexual dysfunction were switching to another antidepressant (34%) and waiting for spontaneous resolution (33%). In conclusion, our results indicate that despite being a well-known, long-standing side effect of antidepressants, sexual dysfunction continues to be extremely common in patients receiving antidepressants, especially serotonergic ones, potentially jeopardizing treatment success in a substantial proportion of patients. There are important sex differences in the reporting and tolerance of sexual dysfunction that require further investigation. [ABSTRACT FROM AUTHOR]

Cannabinoid type-1 (CB1 ) receptors are widely distributed in the brain and play important roles in astrocyte function and the modulation of neuronal synaptic transmission and plasticity. However, it is currently unknown how CB1 receptor expression in astrocytes is affected by long-term exposure to stressors. Here we examined CB1 receptors in astrocytes of ethanol (EtOH)-exposed adolescent mice to determine its effect on CB1 receptor localization and density in adult brain. 4-8-week-old male mice were exposed to 20 percent EtOH over a period of 4 weeks, and receptor localization was examined after 4 weeks in the hippocampal CA1 stratum radiatum by pre-embedding immunoelectron microscopy. Our results revealed a significant reduction in CB1 receptor immunoparticles in astrocytic processes of EtOH-exposed mice when compared with controls (positive astrocyte elements: 21.50 ± 2.80 percent versus 37.22 ± 3.12 percent, respectively), as well as a reduction in particle density (0.24 ± 0.02 versus 0.35 ± 0.02 particles/μm). The majority of CB1 receptor metal particles were in the range of 400-1200 nm from synaptic terminals in both control and EtOH. Altogether, the decrease in the CB1 receptor expression in hippocampal astrocytes of adult mice exposed to EtOH during adolescence reveals a long lasting effect of EtOH on astrocytic CB1 receptors. This deficiency may also have negative consequences for synaptic function. [ABSTRACT FROM AUTHOR]

Background: Increased plasma free fatty acids (FFAs) impair insulin sensitivity in dairy cows via unknown mechanisms. In nonruminants, saturated FFAs upregulate the hepatic synthesis and secretion of ceramide, which inhibits insulin action.Objective: We aimed to determine whether an increase in plasma FFAs promotes hepatic and plasma ceramide accumulation in dairy cows.Methods: Six nonpregnant, nonlactating Holstein cows were used in a study with a crossover design and treatments consisting of intravenous infusion of either saline (control) or triacylglycerol emulsion (TG; 20 g/h) for 16 h. The feeding level was set at 120% of energy requirements. Blood was collected at regular intervals and liver was biopsied at 16 h. Ceramides, monohexosylceramides (Glc/Gal-Cer), lactosylceramides (LacCer), and sphingomyelins (SMs) in plasma and liver were profiled. Hepatic expression of ceramide synthases was determined. Data were analyzed with the use of mixed models, regressions, and Spearman rank correlations.Results: After 16 h of infusion, plasma FFA concentrations were >5-fold and liver triacylglycerol concentrations were 4-fold greater in TG cows, relative to control. Plasma total and very long-chain ceramide (e.g., C24:0-ceramide) concentrations increased ∼4-fold in TG over control by hour 16 of infusion, while C16:0-ceramide were not modified by TG. Infusion of TG increased plasma Glc/Gal-Cer (e.g., C16:0-Glc/Gal-Cer, 4-fold by hour 16) relative to control, but did not alter LacCer or SM concentrations. Hepatic ceramide concentrations increased with TG relative to control (e.g., C24:0-ceramide by 1.7-fold). Hepatic expression of ceramide synthase 2 was 60% greater after TG infusion compared with the control. Circulating ceramides were related to circulating FFA and hepatic triacylglycerol concentrations (e.g., C24:0-ceramide, ρ = 0.73 and 0.80, respectively; P < 0.001).Conclusion: Hepatic ceramide synthesis is associated with elevations in circulating FFAs and hepatic triacylglycerol during the induction of hyperlipidemia in dairy cows. This work supports the emerging evidence for the role of ceramide during hepatic steatosis and insulin antagonism in cows. [ABSTRACT FROM AUTHOR]

Background: Preclinical results showing therapeutic effect and low toxicity of metronomic chemotherapy with cyclophosphamide (Cy) + celecoxib (Cel) for mammary tumors encouraged its translation to the clinic for treating advanced breast cancer patients (ABCP).Patients and Methods: A single-arm, mono-institutional, non-randomized, phase II, two-step clinical trial (approved by Bioethics Committee and Argentine Regulatory Authority) was designed. Patients received Cy (50 mg po.d) + Cel (200 mg p.o.bid). Patient eligibility criteria included: ABCP who progressed to anthracyclines, taxanes and capecitabine, ≤4 chemotherapy schemes, with good performance status. Several pro- and anti-angiogenic molecules and cells were determined as biomarkers. Informed consent was signed by all patients. Primary endpoint was clinical benefit (CB).Results: Twenty patients were enrolled. Main clinical outcomes were prolonged disease stabilization and partial remission in 10/20 and 1/20 patients, respectively. CB was 55 %, and time to progression (TTP) was 21.1 weeks. Median TTP in patients who achieved CB was 35.6 weeks, and mean overall survival was 44.20 weeks. There were no grade 3/4 toxicities associated with treatment. Circulating endothelial cells (CECs) increased at the time of progression in patients who showed CB (P = 0.014). Baseline CECs and circulating endothelial progenitor cells showed marginal associations with TTP. Serum VEGF decreased (P = 0.050), sVEGFR-2 increased (P = 0.005) and VEGF/sVEGFR-2 ratio decreased during treatment (P = 0.041); baseline VEGF and VEGF/sVEGFR-2 were associated with TTP (P = 0.035 and P = 0.030, respectively), while sVEGFR-2 did not.Conclusions: Treatment was effective, showing low toxicity profile and excellent tolerability. The combination had anti-angiogenic effect. Increased levels of CEC could be useful for detecting progression. Baseline VEGF and VEGF/sVEGFR-2 values could be useful as early predictors of response.Trial Registration: ANMAT#4596/09. [ABSTRACT FROM AUTHOR]

Background: Lightly touching the tip of the index finger on an external surface reduces the postural sway during upright standing due to the additional somatosensory information provided by the touch to the postural control system. But when the individuals apply more force, it provides more mechanical support. However, because most of the studies investigated only two levels of force, whether the control mechanisms of postural sway are affected by the different force levels was unknown.Research Question: To examine the influence of the magnitude of force (up to 1, 2, 4, 6 or 8 N) applied to the touch bar on the mechanisms used to control the postural sway during quiet standing with eyes open or closed.Methods: Ten young right-handed adults stood for 35 s on a force platform, with feet apart, while touched a rigid bar with different force levels with eyes open or closed. The amplitude and velocity of the center of pressure and its components, Rambling and Trembling trajectories, respectively, related to more supraspinal and spinal control mechanisms, were assessed.Results: The touch reduced all trajectories, mainly of the Rambling component and with closed eyes. There was a floor effect of the touch force as amplitudes and velocities were minimal at 4 N of force.Significance: The component of postural sway under the supraspinal neural control is more affected by different force magnitudes applied to the touch bar. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections. An RSV-A genotype (ON1) that contains a 72-nt duplication was reported in 2012 and has since extended worldwide.Methods: We analyzed 345 respiratory samples obtained between 2003 and 2014 to assess the relevance of ON1 infections. Nucleotidic and deduced amino acid sequences from viruses detected in San Luis Potosí and sequences previously reported were analyzed.Results: RSV ON1 was detected in 105 samples. The earliest case of ON1 infection was detected in November 2009, almost 1 year prior to detection of this virus in Canada. Amino acid sequence analysis of the duplication region showed the presence of Y273N and L274P substitutions in RSV GA2 viruses that, when combined, resulted in 4 different GXXSPSQ sequence motifs at positions 272-278. Three of these motifs were present in both the original and duplicated regions of ON1 strains. Additional signature amino acid substitutions were observed in ON1 strains that have the different sequence motifs.Conclusions: ON1 strains include viruses that appear to be the result of at least 3 independent duplication events. Molecular data of strains from diverse geographical regions should help define the frequency and implications of this evolution mechanism. [ABSTRACT FROM AUTHOR]

Background: Multiple factors can account for surgical complexity during laparoscopic partial nephrectomy (LPN); severe adhesion of perirenal fat (PRF) is a crucial one. Consequent renal decapsulation can deem renorrhaphy a very challenging task. We propose a novel technique (synthetic renal capsule tailoring [SYRCT]) to facilitate renorrhaphy in decapsulated kidneys and suggest early decapsulation as a safe option in cases with severe PRF.Materials and Methods: We retrospectively analyzed perioperative results of this novel technique performed in cases with severe PRF. All cases were classified as high grade in the Mayo Adhesive Probability (MAP) score.Results: A total of six cases were performed with the SYRCT technique. All patients were male with a mean age of 70 years (62-76 years) and mean body mass index of 30 kg/m2 (23.66-33.86). Of the six cases, five were T1a and 1 T1b. Mean tumor size was 2.83 cm (range 1.2-6 cm). Mean operative time was 121 minutes (range 74-150 minutes); mean warm ischemia time was 17.2 minutes (range 13-25 minutes). Mean operative bleeding was 128 mL (range 50-250 mL). Mean hospital stay was 2.3 days. There were no surgical complications greater or equal to Clavien II.Conclusion: Performing complete renal decapsulation with subcapsular dissection and SYRCT in cases with high MAP score and severe PRF is safe and reproducible. Using this novel technique, we were able to obtain perioperative results comparable to the ones we found in LPN with normal PRF. [ABSTRACT FROM AUTHOR]

Background: Accurately determining renal function is essential for clinical management of HIV patients. Classically, it has been evaluated by estimating glomerular filtration rate (eGFR) with the MDRD-equation, but today there is evidence that the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has greater diagnostic accuracy. To date, however, little information exists on patients with HIV-infection. This study aimed to evaluate eGFR by CKD-EPI vs. MDRD equations and to stratify renal function according to KDIGO guidelines.Methods: Cross-sectional, single center study including adult patients with HIV-infection.Results: Four thousand five hundred three patients with HIV-infection (864 women; 19%) were examined. Median age was 45 years (IQR 37-52), and median baseline creatinine was 0.93 mg/dL (IQR 0.82-1.05). A similar distribution of absolute measures of eGFR was found using both formulas (p = 0.548). Baseline median eGFR was 95.2 and 90.4 mL/min/1.73 m2 for CKD-EPI and MDRD equations (p < 0.001), respectively. Of the 4503 measurements, 4109 (91.2%) agreed, with a kappa index of 0.803. MDRD classified 7.3% of patients as "mild reduced GFR" who were classified as "normal function" with CKD-EPI. Using CKD-EPI, it was possible to identify "normal function" (>90 mL/min/1.73 m2) in 73% patients and "mild reduced GFR" (60-89 mL/min/1.73 m2) in 24.3% of the patients, formerly classified as >60 mL/min/1.73 m2 with MDRD.Conclusions: There was good correlation between CKD-EPI and MDRD. Estimating renal function using CKD-EPI equation allowed better staging of renal function and should be considered the method of choice. CKD-EPI identified a significant proportion of patients (24%) with mild reduced GFR (60-89 mL/min/1.73 m2). [ABSTRACT FROM AUTHOR]

Background: C-met and its ligand, hepatocyte growth factor (HGF) have been associated with the resistance mechanism of EGFR-TKIs. HGF was evaluated as a clinical-marker of response in NSCLC patients treated with afatinib.Methods: Sixty-six patients with stage IIIB/IV lung adenocarcinoma and progression to any-line chemotherapy received afatinib 40 mg/day. Mutational EGFR and HER2 status were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Serum HGF content was measured by ELISA before and 2 months after the start of treatment. HGF levels were assessed with the objective response rate (ORR), progression-free-survival (PFS), and overall survival (OS). This trial was registered on ClinicalTrials.gov: NCT01542437.Results: Fifty patients (75 %) were EGFR mutation positive. Response was achieved in 59 % of all patients and 78 % of EGFR mutated patients. Median PFS was 10 [95 % CI 6.8-13.1] and 14.5 months [10.9-18.9] for all and EGFR mutated patients, respectively. Median OS was 22.8 [17.5-28.1] and 32.4 months [18.3-46.6] for all and EGFR mutated patients, respectively. Patients with reduced serum HGF levels had improved ORR (75 % vs 44 %; p = 0.011), PFS (15.1 [2.9-27.3] vs 6.5 months [3.9-9.1]; p = 0.005) and OS (NR vs 14.5 months [7.8 - 21.3] p = 0.007). A reduction in serum HGF levels was an independent factor associated with longer PFS (HR 0.40; p = 0.021) and OS (HR 0.31; p = 0.006) in all and EGFR mutated patients.Conclusions: A reduction in serum HGF levels was associated with improved outcomes in patients treated with afatinib. These results suggest HGF might have a role as a mechanism of resistance to EGFR-TKIs. HGF could represent a potential therapeutic target to prevent or reverse resistance particularly in EGFR mutated patients. [ABSTRACT FROM AUTHOR]

Aims: To test the screening performance of urinary ethyl glucuronide (EtG) under routine clinical conditions in a sample of alcohol-dependent outpatients, comparing it against urinary ethanol, self reports and clinical judgment.Methods: A cross-sectional study under routine conditions was conducted in February 2015, where 613 consecutive urinary samples, provided by 188 outpatients with alcohol use disorders, were analyzed for ethanol and EtG (cut-off level = 500 ng/ml). Clinical variables such as the presence of aversive medication, comorbidities and clinician judgment were also collected. The discrepancy between the number of alcohol and EtG positives was recorded. A logistic regression analysis including clinical variables was conducted to assess for predictors of EtG positivity.Results: Urinary alcohol yielded 9 positives (1.5% of all urine samples) belonging to 8 patients. EtG yielded 136 positives (22% of all urine samples) belonging to 74 patients. Of these, 93.4% (127 of 136) were negative for alcohol. All urinary alcohol positives resulted in EtG positives. The clinician judged 48 samples from 26 patients as belonging to not abstinent patients and 550 samples from 178 patients as belonging to abstinent patients. She was unsure in 15 samples from 15 patients. When comparing it against EtG as the gold standard, the area under the curve was 0.592. Self reports were extremely unreliable in this study, with only 5 patients reporting drinking in a total of 6 urine samples. In the logistic regression model, only aversive medications (OR 2.1, 95% CI 1.3-3.3) and clinician judgment (OR 2, 95% CI 1.4-2.9) resulted in significant effects.Conclusions: EtG performed largely better than ethanol for urine screening in alcohol outpatients, detecting an extra 20.4% (125 out of 613) of positives. It means that for each alcohol-positive sample, there were 15 EtG-positive samples. Although better than ethanol, clinician judgment was also not performed efficiently. If routinely implemented in the screening of alcohol outpatients, EtG might bring relevant changes that merit further research. [ABSTRACT FROM AUTHOR]

Background: Residual depressive symptoms are associated with a poor prognosis for relapse or recurrence and are recognized as impeding factors of functionality. Recovery to the pre-depression level of functioning should be the goal of treatment.Aim: To evaluate outcomes in depressed outpatients treated with escitalopram regarding response, recovery, residual symptoms, functionality and ability to work over 48 weeks.Method: 3278 outpatients were evaluated at weeks 8, 24 and 48. A simple questionnaire was used to rate severity of illness, impairment of functionality, treatment response, tolerability, presence and severity of residual symptoms, whether remission with residual symptoms or recovery was achieved, and to what degree the patient was able to work.Results: Data over the full 48-week period were available for 75.8% of patients, for whom treatment response was rated as "very good" or "good" in 81%. However, only 42% of the completing patients achieved recovery without residual symptoms, while 41% were rated as remitters with residual symptoms. Lack of energy/motivation was the most common reported residual symptom and was present in 23.5% of patients at study end. Concentration difficulties were present in 15.8% and impaired sleep in 13.9% of patients. Complete inability to work decreased from 36% at baseline to 9% at week 48, while full-time working capacity increased from 37% to 62%.Limitations: Non-controlled observational real life study using simple ratings rather than established rating scales.Conclusion: <50% of patients completing a one-year antidepressant treatment regimen were rated as being symptomatically fully recovered, and ≈50% still reported functional deficits. [ABSTRACT FROM AUTHOR]

We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011-June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 μg/mL and 0.5 μg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2-5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1-5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications. [ABSTRACT FROM AUTHOR]

Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6 months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs.Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6 months post-intervention, using 95 % confidence intervals. A linear multilevel regression will be used to adjust the model.Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance.Trial Registration: ClinicalTrials.gov: NCT02210442 . [ABSTRACT FROM AUTHOR]

Introduction: Research on the emotional impact of tobacco-warning images (TWIs) has not evaluated the role of context (ie, cigarette packs) as a modulator of the emotional response to TWIs. The objective of the present study was to identify the influence of the cigarette package brand on the emotional impact of TWIs that cover 30% of cigarette packs in smokers and nonsmokers using a specific methodology for the study of emotion.Methods: The participants included 95 smokers and 111 nonsmokers who observed three TWIs under two conditions: TWIs that covered 30% of cigarette packs and TWIs alone, without brands. Additionally, 18 pictures from the International Affective Picture System were presented as comparison stimuli and to reduce the effect of habituation. The Self-Assessment Manikin was used to assess valence, arousal, and dominance dimensions.Results: TWIs that covered 30% of cigarette packs were evaluated as least aversive, with lower ratings of arousal and higher ratings of dominance in both groups. Differences in the valence, arousal, and dominance dimensions were found between groups. Smokers rated TWIs that covered 30% of cigarette packs as less aversive and more arousing and gave them lower dominance scores compared with nonsmokers.Conclusion: The results suggest that cigarette packages modulate the emotional impact of TWIs, especially in smokers, and the minimum size of TWIs (ie, 30% of the front and back of the package) is not sufficiently large to generate an emotional impact associated with avoidance behavior.Implications: Cigarette packages modulate the emotional impact of TWIs, especially in smokers. The cigarette package itself is an appetitive context that captures the attention of the observer and decreases the aversive emotional response to the TWIs. The minimum size of TWIs (ie, 30% of the front and back of the package) is not sufficiently large to generate an emotional impact associated with avoidance behavior. [ABSTRACT FROM AUTHOR]

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The aim of this study is to compare the effect of conventional bread and a whole grain bread on appetite and energy intake, satiety and satiety gut-hormones. A randomized controlled crossover pilot study was carried out in 11 university students (age: 18.7 ± 0.9 years; body mass index: 22.7 ± 2.7 kg/m(2)). Participants consumed two different mid-morning cereal-based snacks, including a conventional or whole grain bread. Two testing days were completed, including satiety questionnaires, blood sampling and consumption of standardized breakfast, mid-morning test-snacks and ad libitum lunch. Several gut-hormones were analysed and satiation was assessed using Visual Analogue Scale scores. The consumption of whole grain bread increased satiety perception, decreased the remained energy intake during the testing day, and decreased the postprandial response of peptide YY, compared with conventional bread (p < 0.005). These data suggest that the consumption of whole grain bread might be a useful strategy to improve satiety. [ABSTRACT FROM AUTHOR]

Seventy-two postmenopausal osteoporotic women having more than one nontraumatic vertebral crush fracture were studied. Thirty-six of them, aged 68.8 +/- 1.2 years (18 +/- 4 YSM-years since menopause), were treated with 100 IU/day of salmon calcitonin i.m. plus 500 mg of elemental calcium for 10 days each month. The remaining 36 patients, aged 69.6 +/- 1.4 years (19 +/- 3 YSM), were given only 500 mg of elemental calcium for 10 days each month. All patients underwent clinical and analytical evaluation every 3 months. Radiological evaluation, assessment of vertebral deformities, and metacarpal radiogrammetry were done every 6 months. Densitometric measurements of total and regional bone mass were made every 12 months. At 24 months, the calcitonin group showed a 60% reduction in the number of new fractures and the group receiving only calcium had a 45% increase (P < 0.001). The incidence of vertebral fractures was 0.07 per patient-year in the group treated with calcitonin and 0.45 per patient-year in the group treated with calcium (P < 0.001). At 2 years, the calcitonin group showed a 12% increase in cortical bone mass on metacarpal radiogrammetry, a 16% increase in the axial skeleton on trunk densitometry, a 3.5% increase in total body bone mineral content, a 30.7% increase in pelvic bone mineral content, and a 6.2% increase in arm bone mineral content (all P < 0.001). In the group treated with calcium alone there was a loss of bone mass in every region. These findings suggest that salmon calcitonin is effective in the treatment of osteoporosis and show that it acts on cortical and trabecular bone. [ABSTRACT FROM AUTHOR]

Seventy-two eugonadal women, mean age 39 +/- 4 years, with a z score for total body bone mineral content (BMC) of less than -1.5 (mean -1.80 +/- 0.12) were selected from a previous screening study of normal values of total body and regional BMC in women using dual-energy X-ray absorptiometry. The women were distributed into two groups: 36 women undergoing treatment with 1 g/day of elemental calcium in the form of calcium pidolate and 36 women not treated. One year later, total body BMC, regional BMC in arms, legs and trunk, 24-hour urinary calcium excretion (Ca 24 hour), fasting urinary calcium/creatinine ratio, and serum tartrate-resistant acid phosphatase concentration were measured in both groups. There was a significant increase in total body and regional BMC (P < 0.001) in the group taking calcium pidolate. The increase was greater in arms and legs (2.5%) than in trunk (1.7%), being 2.6% for total body BMC. The z score increased from -1.81 +/- 0.13 to -1.52 +/- 0.12 (16%, P < 0.001). The corporal index did not change, and total body BMC corrected for fat-free body mass increased by 6.7% (P < 0.001). These changes were accompanied by an increase in 24-hour urinary calcium excretion and a decrease in urinary calcium/creatinine ratio and serum tartrate-resistant acid phosphatase concentration (P < 0.05 for all). There was a correlation between cumulative calcium dose at the end of treatment and gain in total body BMC (r2 = 0.925, P < 0.001). The untreated group showed no changes.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

Background: Zika virus infection during pregnancy can cause serious birth defects, which include brain and eye abnormalities. The clinical importance of detection of Zika virus RNA in amniotic fluid is unknown.Objective: The purpose of this study was to describe patterns of Zika virus RNA testing of amniotic fluid relative to other clinical specimens and to examine the association between Zika virus detection in amniotic fluid and Zika-associated birth defects. Our null hypothesis was that Zika virus detection in amniotic fluid was not associated with Zika-associated birth defects.Study Design: We conducted a retrospective cohort analysis of women with amniotic fluid specimens submitted to Colombia's National Institute of Health as part of national Zika virus surveillance from January 2016 to January 2017. Specimens (maternal serum, amniotic fluid, cord blood, umbilical cord tissue, and placental tissue) were tested for the presence of Zika virus RNA with the use of a singleplex or multiplex real-time reverse transcriptase-polymerase chain reaction assay. Birth defect information was abstracted from maternal prenatal and infant birth records and reviewed by expert clinicians. Chi-square and Fisher's exact tests were used to compare the frequency of Zika-associated birth defects (defined as brain abnormalities [with or without microcephaly, but excluding neural tube defects and their associated findings] or eye abnormalities) by frequency of detection of Zika virus RNA in amniotic fluid.Results: Our analysis included 128 women with amniotic fluid specimens. Seventy-five women (58%) had prenatally collected amniotic fluid; 42 women (33%) had amniotic fluid collected at delivery, and 11 women (9%) had missing collection dates. Ninety-one women had both amniotic fluid and other clinical specimens submitted for testing, which allowed for comparison across specimen types. Of those 91 women, 68 had evidence of Zika virus infection based on detection of Zika virus RNA in ≥1 specimen. Testing of amniotic fluid that was collected prenatally or at delivery identified 39 of these Zika virus infections (57%; 15 [22%] infections were identified only in amniotic fluid), and 29 infections (43%) were identified in other specimen types and not amniotic fluid. Among women who were included in the analysis, 89 had pregnancy outcome information available, which allowed for the assessment of the presence of Zika-associated birth defects. Zika-associated birth defects were significantly (P<.05) more common among pregnancies with Zika virus RNA detected in amniotic fluid specimens collected prenatally (19/32 specimens; 59%) than for those with no laboratory evidence of Zika virus infection in any specimen (6/23 specimens; 26%), but the proportion was similar in pregnancies with only Zika virus RNA detected in specimens other than amniotic fluid (10/23 specimens; 43%). Although Zika-associated birth defects were more common among women with any Zika virus RNA detected in amniotic fluid specimens (ie, collected prenatally or at delivery; 21/43 specimens; 49%) than those with no laboratory evidence of Zika virus infection (6/23 specimens; 26%), this comparison did not reach statistical significance (P=.07).Conclusion: Testing of amniotic fluid provided additional evidence for maternal diagnosis of Zika virus infection. Zika-associated birth defects were more common among women with Zika virus RNA that was detected in prenatal amniotic fluid specimens than women with no laboratory evidence of Zika virus infection, but similar to women with Zika virus RNA detected in other, nonamniotic fluid specimen types. [ABSTRACT FROM AUTHOR]

The article discusses a study aimed at evaluating the validity and reliability of the Confusion Assessment Method-Intensive Care Unit (CAM-ICU) and Intensive are Delirium Screening Checklist (ICDSC) for delirium assessment in patients with mild or moderate traumatic brain injury (TBI). It suggests further studies aimed at developing specific tools to discriminate between delirium and other acute cognitive dysfunction in critically ill TBI patients.

Objective: To evaluate the effectiveness of Health-E You/Salud iTu, a mobile health application (app), on increasing knowledge, self-efficacy and contraception use among Latina adolescents, its impact on visit quality, and app satisfaction.Study Design: This study used cluster-randomized controlled trial (CRCT) of 18 school-based health centers (SBHCs). Prior to the visit, intervention participants received the patient-centered contraceptive decision-making support app and controls answered sexual health questions on iPads. Participants completed a previsit questionnaire and 3 follow-up surveys (48 hours, 3-, and 6-months) after the recruitment visit (where intervention participants completed the app). Differences in adolescents' contraceptive knowledge, self-efficacy, and use over the 6-month follow-up were assessed by generalized mixed effects regression models.Results: A total of 1,360 Latina adolescents participated; 57.2% responded to the 48-hour survey, 50.1% to the 3-month, 49.7% to the 6-month, and 42.3% to both the 3- and 6-month surveys. Health-E You users' demonstrated significant increases in pre-post knowledge (p < 0.001). Intervention participants who completed the follow-up survey reported greater increases in mean self-efficacy from baseline (23.2 intervention vs. 22.5 controls) to 6 months (26.1 vs. 23.4; b = 1.58, 95% CI 0.38-2.77, p = 0.01), and greater increases in non-barrier contraceptive use from baseline (29% intervention vs. 30% controls) to 3 months (63% vs. 45%; OR = 3.29, 95% CI 1.04-10.36, p = 0.04) and 6 months (63% vs. 44%; OR = 5.54, 95% CI 1.70-18.06, p = 0.005). Providers and adolescents reported high app satisfaction and stated it improved visit quality.Conclusions: While data suggest that Health-E You improved outcomes, findings must be interpreted cautiously. Intervention participants had higher baseline sexual activity rates, more recruitment visits for pregnancy testing, emergency contraception or birth control, and lower completion rates of follow-up surveys than controls.Implications: Despite declines in adolescent pregnancy in the United States, Latinas continue to have disproportionately high rates compared to white females. The Health-E You app may be an effective support tool for both adolescents and providers in SBHCs, and possibly other clinical settings, across the country to increase contraceptive use and thereby decrease unintended pregnancies. It could potentially reduce disparities in adolescent pregnancies and create more efficient visit time spent between clients and their providers. [ABSTRACT FROM AUTHOR]

Background: Severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency (ADA-SCID) is a rare and life-threatening primary immunodeficiency.Methods: We treated 50 patients with ADA-SCID (30 in the United States and 20 in the United Kingdom) with an investigational gene therapy composed of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a self-inactivating lentiviral vector encoding human ADA. Data from the two U.S. studies (in which fresh and cryopreserved formulations were used) at 24 months of follow-up were analyzed alongside data from the U.K. study (in which a fresh formulation was used) at 36 months of follow-up.Results: Overall survival was 100% in all studies up to 24 and 36 months. Event-free survival (in the absence of reinitiation of enzyme-replacement therapy or rescue allogeneic hematopoietic stem-cell transplantation) was 97% (U.S. studies) and 100% (U.K. study) at 12 months; 97% and 95%, respectively, at 24 months; and 95% (U.K. study) at 36 months. Engraftment of genetically modified HSPCs persisted in 29 of 30 patients in the U.S. studies and in 19 of 20 patients in the U.K. study. Patients had sustained metabolic detoxification and normalization of ADA activity levels. Immune reconstitution was robust, with 90% of the patients in the U.S. studies and 100% of those in the U.K. study discontinuing immunoglobulin-replacement therapy by 24 months and 36 months, respectively. No evidence of monoclonal expansion, leukoproliferative complications, or emergence of replication-competent lentivirus was noted, and no events of autoimmunity or graft-versus-host disease occurred. Most adverse events were of low grade.Conclusions: Treatment of ADA-SCID with ex vivo lentiviral HSPC gene therapy resulted in high overall and event-free survival with sustained ADA expression, metabolic correction, and functional immune reconstitution. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT01852071, NCT02999984, and NCT01380990.). [ABSTRACT FROM AUTHOR]

Background: Neurocognitive impairment is recognised as a risk factor for suicidal behaviour in adults. The current study aims to determine whether neurocognitive deficits also predict ongoing or emergent suicidal behaviour in young people with affective disorders.Methods: Participants were aged 12-30 years and presented to early intervention youth mental health clinics between 2008 and 2018. In addition to clinical assessment a standardised neurocognitive assessment was conducted at baseline. Clinical data was extracted from subsequent visits using a standardised proforma.Results: Of the 635 participants who met inclusion criteria (mean age 19.6 years, 59% female, average follow up 476 days) 104 (16%) reported suicidal behaviour during care. In 5 of the 10 neurocognitive domains tested (cognitive flexibility, processing speed, working memory, verbal memory and visuospatial memory) those with suicidal behaviour during care were superior to clinical controls. Better general neurocognitive function remained a significant predictor (OR=1.94, 95% CI 1.29- 2.94) of suicidal behaviour in care after controlling for other risk factors.Limitations: The neurocognitive battery used was designed for use with affective and psychotic disorders and may not have detected some deficits more specific to suicidal behaviour.Conclusion: Contrary to expectations, better neurocognitive functioning predicts suicidal behaviour during care in young people with affective disorders. While other populations with suicidal behaviour, such as adults with affective disorders or young people with psychotic disorders, tend to experience neurocognitive deficits which may limit their capacity to engage in some interventions, this does not appear to be the case for young people with affective disorders. [ABSTRACT FROM AUTHOR]

Introduction: Lifestyle-related habits have a strong influence on morbidity and mortality worldwide. This study investigates the association between a multidimensional healthy lifestyle score and all-cause mortality risk, including in the score some less-studied lifestyle-related factors.Methods: Participants (n=20,094) of the Seguimiento Universidad de Navarra cohort were followed up from 1999 to 2018. The analysis was conducted in 2019. A 10-point healthy lifestyle score previously associated with a lower risk of major cardiovascular events was applied, assigning 1 point to each of the following items: never smoking, moderate-to-high physical activity, moderate-to-high Mediterranean diet adherence, healthy BMI, moderate alcohol consumption, avoidance of binge drinking, low TV exposure, short afternoon nap, time spent with friends, and working ≥40 hours per week.Results: During a median follow-up of 10.8 years, 407 deaths were documented. In the multivariable adjusted analysis, the highest category of adherence to the score (7-10 points) showed a 60% lower risk of all-cause mortality than the lowest category (0-3 points) (hazard ratio=0.40, 95% CI=0.27, 0.60, p<0.001 for trend). In analyses of the healthy lifestyle score as a continuous variable, for each additional point in the score, a 18% relatively lower risk of all-cause mortality was observed (adjusted hazard ratio=0.82, 95% CI=0.76, 0.88).Conclusions: Adherence to a healthy lifestyle score, including some less-studied lifestyle-related factors, was longitudinally associated with a substantially lower mortality rate in a Mediterranean cohort. Comprehensive health promotion should be a public health priority. [ABSTRACT FROM AUTHOR]

Beer is a beverage that has been consumed worldwide for thousands of years due to social, religious, and cultural reasons; it contains polyphenolic compounds as well as phenolic acids with a potential positive effect on human health. This study aimed to explore the impact of moderate beer consumption on human health and gut microbiota diversity. Three hundred fifty-five mL of non-alcoholic beer (NAB) or alcoholic beer (AB) were consumed daily by the participants for 30 days in each study. Anthropometric measures, blood samples for biochemistry, and fecal samples for microbiota analysis were collected on Day 1 and Day 30. Microbial diversity was characterized by high-throughput sequencing of 16S rDNA libraries, and data were analyzed using the QIIME pipeline. We found that NAB and AB have effects on the composition of the gut microbiota, favoring the proliferation of Bacteroidetes with respect to Firmicutes. No increase in weight, waist, and hip parameters was observed, and the liver and lipid profile values were not modified for NAB. In addition, the consumption of NAB induced a decrease in fasting blood serum glucose and an increase in functional β cells, while, on the other hand, there was an increase in blood serum glucose and a decrease in functional β cells with the consumption of AB. In general, beer consumption neither changed anthropometric values, nor affected liver function. Although the glucose values decreased with NAB or increased with AB, they remained within the normal range. Our conclusion is that moderate consumption of NAB has a positive effect on human health via supplementation of biological active polyphenol and phenolic acids, and by enrichment of the gut microbiota diversity with beneficial bacteria, while the presence of alcohol in AB interferes with this effect. More work should be done on this topic before general conclusions are drawn. [ABSTRACT FROM AUTHOR]

There has been polarizing debate on addictive-like eating in recent years. To move toward valid definition and measurement of this construct, qualitative research describing individuals' experiences is needed. The present study explored how Brazilian men and women define and experience addictive-like eating. Interviews were conducted with 7 men and 8 women (Mage = 46.6 years, MBMI = 35.43 kg/m2) seeking treatment for addictive-like eating. Thematic analysis of interviews identified three saturated, overarching themes describing participants' conceptualizations of the (1) characteristics, (2) causal factors, and (3) consequences of addictive-like eating. Lack of control was a key characteristic of addictive-like eating described by all participants. A causal factor which most participants described was emotional eating. Consequences included emotional, interpersonal, occupational, and health-related impairments which appeared primarily related to weight gain, rather than to the pattern of addictive-like eating itself. These results are largely consistent with those of previous qualitative studies. Importantly, the symptoms described by our participants and in previous qualitative studies may be inadequately captured by existing self-report questionnaires designed to assess addictive-like eating. To address this potential limitation, we provide recommendations for assessing the full range of possible addictive-like eating symptoms. [ABSTRACT FROM AUTHOR]

Background: Drug resistance is a challenge for the global control of tuberculosis. We examined mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and in a reference laboratory.Methods: This multicentre cohort study was done in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand. We collected Mycobacterium tuberculosis isolates and clinical data from adult patients aged 16 years or older. Patients were stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing was done locally and at the Swiss National Center for Mycobacteria, Zurich, Switzerland. We examined mortality during treatment according to drug susceptibility test results and treatment adequacy in multivariable logistic regression models adjusting for sex, age, sputum microscopy, and HIV status.Findings: We obtained M tuberculosis isolates from 871 patients diagnosed between 2013 and 2016. After exclusion of 237 patients, 634 patients with tuberculosis were included in this analysis; the median age was 33·2 years (IQR 26·9-42·5), 239 (38%) were women, 272 (43%) were HIV-positive, and 69 (11%) patients died. Based on the reference laboratory drug susceptibility test, 394 (62%) strains were pan-susceptible, 45 (7%) monoresistant, 163 (26%) multidrug-resistant (MDR), and 30 (5%) had pre-extensively or extensively drug resistant (pre-XDR or XDR) tuberculosis. Results of reference and local laboratories were concordant for 513 (81%) of 634 patients and discordant for 121 (19%) of 634. Overall, sensitivity to detect any resistance was 90·8% (95% CI 86·5-94·2) and specificity 84·3% (80·3-87·7). Mortality ranged from 6% (20 of 336) in patients with pan-susceptible tuberculosis treated according to WHO guidelines to 57% (eight of 14) in patients with resistant strains who were under-treated. In logistic regression models, compared with concordant drug susceptibility test results, the adjusted odds ratio of death was 7·33 (95% CI 2·70-19·95) for patients with discordant results potentially leading to under-treatment.Interpretation: Inaccurate drug susceptibility testing by comparison with a reference standard leads to under-treatment of drug-resistant tuberculosis and increased mortality. Rapid molecular drug susceptibility test of first-line and second-line drugs at diagnosis is required to improve outcomes in patients with MDR tuberculosis and pre-XDR or XDR tuberculosis.Funding: National Institutes of Allergy and Infectious Diseases, Swiss National Science Foundation, Swiss National Center for Mycobacteria. [ABSTRACT FROM AUTHOR]

Objective: Female sex has been associated with differences in diagnostic and management of acute coronary syndrome (ACS). Our aim was to analyze sex differences in ACS with interventional management in a tertiary care hospital.Methods: Patients with ACS admitted to a Spanish tertiary care referral center were included prospectively and consecutively. All patients included in the study underwent a coronary angiography.Results: From the total cohort of 1214 patients, 290 (24%) were women. Women were older (71 ± 12.8 vs 64 ± 13.4 years, p < 0.001) and showed lower ischemic risk and higher hemorrhagic risk scores (GRACE 159 ± 45 vs 171 ± 42, p = 0.005; CRUSADE 41 ± 19 vs 28 ± 17, p < 0.001). There were no significant differences in time to coronary angiography and revascularization rates between sex groups. A lower proportion of women received high-potency antiplatelet agents (29% vs 41.3%, p = 0.004). In-hospital evolution and one-year mortality were similar between groups.Conclusions: In our population, there were no gender differences in management and prognosis of ACS. Differences in risk profile among groups could have an influence on antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Background: Efforts aimed at reducing alcohol-related harm include early detection of risky drinkers as well as detection of early relapse in patients with alcohol dependence. Ethyl glucuronide (EtG) has been proven to be a reliable biomarker for the detection of recent drinking; however, no randomized, diagnostic trial to date has tested its impact on drinking outcomes. The aim of this study was to assess, in a randomized design, the implications of EtG screening on alcohol outcomes, compared to screening with a low sensitivity biomarker such as ethanol.Methods: Alcohol dependent outpatients were randomized to either 24 weeks of continuous screening with EtG or ethanol. Patients were aware of screening methods and results. After 24 weeks, all participants were screened with EtG. Self-reports were also gathered. A logistic regression compared the rate of EtG positive results at study end between groups. Generalized estimating equations evaluated the descending monthly rate of EtG positive patients in the EtG group.Results: A total of 162 patients were randomized. During the study period, the ethanol group showed less patients with positive screens (19/64 (29.7%) vs 58/98 (59%)). After 24 weeks, the EtG group showed a greater number of patients having a negative screening test compared to ethanol subjects when they were all screened with EtG (5/62 (8.1%) vs 13/39 (33.3%)). A significant decrease in the rate of EtG positive patients was found for the first three months of the study.Conclusions: Routine screening with EtG seems to reduce drinking and improve abstinence rates in alcohol dependent outpatients. [ABSTRACT FROM AUTHOR]

In highly complex task situations (dual tasking), stressed individuals have been shown to adapt the most resource-efficient task processing strategy, accepting costs of performance. We argue that an interpretation of this behavior in terms of a stress-induced impairment of cognitive control might be too simplified. In the present study, we therefore tested whether stressed individuals are still capable to up-regulate cognitive control when instructed to adapt more resource-intensive strategies, enabling preservation of task performance. Fifty-six participants underwent either an established psychosocial stress induction protocol (Trier Social Stress Test) or a standardized control intervention. Afterwards, all participants performed a dual task in which task prioritization was systematically varied, calling for the adoption of different task processing strategies that require more or less voluntary top-down control. Although individuals of the stress group showed a pronounced stress response, as indicated by salivary cortisol, they were able to recruit more resources and to engage more voluntary top-down control when instructed to do so. This finding suggests an adaptive nature of control regulation under acute stress that reflects a compensatory capacity with the potential to account for some of the observed ostensible impairments of cognitive control. Our finding calls for careful empirical examination of whether stressed individuals cannot or do not recruit certain cognitive control functions in a given situation that will inform novel interventions to optimize performance in high-stress environments. [ABSTRACT FROM AUTHOR]

Background: Little is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression.Methods: Twelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered over 100min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered). Clinical measures were assessed at baseline, at 24h following each infusion, at the last acute-phase observation, and during continuation and post-continuation follow-up (acute phase remitters only).Results: Of the 12 enrollees, 5 (41.7%) remitted and 7 (58.3%) responded to ketamine treatment during the acute-phase. All five subjects who remitted during the acute-phase experienced further depressive symptom improvement during continuation-phase treatment. Four subjects lost remission status during the post-continuation phase, but all were still classified as positive treatment responders at the end of the post-continuation phase. Adverse effects were generally mild and transient during acute- and continuation-phase treatment; however, one subject developed behavioral outbursts and suicide threats during follow-up while hospitalized, and one subject died by suicide several weeks after the end of follow-up.Limitations: This was an uncontrolled feasibility study with a small sample size.Conclusions: The continuation-phase administration of ketamine at weekly intervals to patients with treatment-resistant depression who remitted during acute-phase ketamine treatment can extend the duration of depressive symptom remission. The antidepressive effect of ketamine persisted for several weeks after the end of continuation-phase treatment. Our results highlight the need for close monitoring of subjects who are at high baseline risk for suicide but do not respond clinically to ketamine. CLINICALTRIALS.Gov Identifier: NCT02094898. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic performance of gray scale transrectal ultrasound-B-mode US (BMUS), power Doppler (PDUS), and sonographic contrast (CEUS) in early imaging-based diagnosis of localized prostate cancer (PCa) and to compare the diagnostic profitability of randomized biopsy (RB), US-targeted prostate biopsy by means of PDUS and CEUS.Material and Methods: A single-center, prospective, transversal, epidemiological study was conducted from January 2010 to January 2014. We consecutively included patients who an imaging study of the prostate with BMUS, PDUS, and CEUS was performed, followed by prostate biopsy due to clinical suspicion of prostate cancer (PSA 4-20ng/mL and/or rectal exam suggestive of malignancy). The diagnostic performance of BMUS, PDUS, and CEUS was determined by calculating the Sensitivity (S), Specificity (Sp), Predictive values (PV), and diagnostic odds ratio (OR) of the diagnosis tests and, for these variables, in the population general and based on their clinical stage according to rectal exam (cT1 and cT2). PCa detection rates determined by means of a randomized 10-core biopsy scheme were compared with detection rates of CEUS-targeted (SonoVue) 2-core biopsies.Results: Of the initial 984 patients, US contrast SonoVue was administered to 179 (18.2%). The PCa detection rate by organ of BMUS/PDUS in the global population was 38% versus 43% in the subpopulation with CEUS. The mean age of the patients was 64.3±7.01years (95% CI, 63.75-64.70); mean total PSA was 8.9±3.61ng/mL (95% CI, 8.67-9.13) and the mean prostate volume was 56.2±29cc (95% CI, 54.2-58.1). The detection rate by organ of targeted biopsy with BMUS, PDUS, and CEUS were as follows: Global population (10.6, 8.2, 24.5%), stage cT1 (5.6, 4.2, 16.4%), and stage cT2 (32.4, 22.3, 43.5%). Comparing the detection rates of the CEUS-targeted biopsy and randomized biopsy, the following results were obtained: Global population (24.5% vs. 41.8%), stage cT1 (16% vs. 35%), and stage cT2 (43.5% vs. 66.6%), with a p value<0.05. Following the "core-by-core" analysis, the detection rates by core of CEUS-targeted biopsy versus randomized biopsy were: Global population (16% vs. 13%), stage cT1 (30.3% vs. 28%), and stage cT2 (48% vs. 37%), with a p value>0.05. The NNT for CEUS-targeted biopsy was 83.3.Conclusions: The low sensitivity, specificity, positive predictive and negative predictive values of gray scale-B-mode, PDUS and CEUS represent scant diagnostic performance of these variables in prostate cancer detection. Prostate cancer detection rates yielded by randomized biopsy were superior than the detection rate of targeted biopsy using B-mode, PDUS and CEUS; as a result, randomized biopsy versus CEUS-targeted biopsies cannot be excluded from biopsy strategy plans for the diagnosis of prostate cancer. [ABSTRACT FROM AUTHOR]

This study compared ground reaction forces (GRF) and lower limb two-dimensional (2D) kinematic waveforms, with and without load carriage, in military personnel walking in two different types of boots. Data were measured in 24-soldiers walking on a 10-m walkway under four randomized crossover trials: wearing two military boots (styrene-butadiene rubber midsole - SBR - 63 Shore A; and polyurethane midsole - PU - 48 Shore A); with and without a 15-kg backpack. GRF traditional parameters were evaluated by two-way ANOVAs. GRF and kinematic waveforms were assessed using a statistical parametric mapping (SPM) method (two-way ANOVA). No interaction effects were observed between footwear and load. GRF at the beginning of stance was lower while wearing the SBR boot condition compared to the PU boot condition. Load carriage increased trunk, hip, and knee flexion. The analyzed military boots did not affect movement patterns during loaded walking and the military boot with SBR midsole material reduced impact to a greater extent. The study demonstrated that the design and materials (e.g., midsole material and thickness) used in boot manufacturing can influence military boot performance. [ABSTRACT FROM AUTHOR]

Background and Objectives: Neurocognitive processes are key drivers of addictive and compulsive disorders. The current study examined whether reward-related attentional capture and cognitive inflexibility are associated with impulsive and/or compulsive personality traits, and whether these cognitive characteristics interact to predict greater compulsivity-related problems across obsessive-compulsive and drinking behaviors.Methods: One-hundred and seventy-three participants (mean age = 34.5 years, S.D = 8.4, 42% female) completed an online visual search task to measure reward-related attentional capture and its persistence following reversal of stimulus-reward contingencies. Participants also completed questionnaires to assess trait impulsivity, compulsivity, alcohol use, and obsessive-compulsive behaviors.Results: Greater reward-related attentional capture was associated with trait compulsivity, over and above all impulsivity dimensions, while greater cognitive inflexibility was associated with higher negative urgency (distress-elicited impulsivity). Reward-related attentional capture and cognitive inflexibility interacted to predict greater compulsivity-related problems among participants who reported obsessive-compulsive behaviors in the past month (n = 57) as well as current drinkers (n = 88). Follow-up analyses showed that, for OCD behaviors, this interaction was driven by an association between higher reward-related attentional capture and more problematic behaviors among cognitively inflexible participants only. For drinking, the same pattern was seen, albeit at trend level.Limitations: This study includes a non-clinical, online sample and is cross-sectional, thus its findings need to be interpreted with these limitations in mind.Conclusions: Reward-related attentional capture and cognitive flexibility are related to trait compulsivity and impulsivity (negative urgency) respectively, and interact to determine more problematic behaviors. [ABSTRACT FROM AUTHOR]

Background: In this study, an alternative and complementary method to those approaches currently used to estimate alcohol consumption by the population is described. This method, known as wastewater-based epidemiology (WBE), allows back-calculating the alcohol consumption rate in a given population from the concentrations of a selected biomarker measured in wastewater.Methods: Composite (24-h) wastewater samples were collected at the inlet of 17 wastewater treatment plants located in 13 Spanish cities for seven consecutive days in 2018. The sampled area covered 12.8% of the Spanish population. Wastewater samples were analyzed to determine the concentration of ethyl sulfate, the biomarker used to back-calculate alcohol consumption.Results: Alcohol consumption ranged from 4.5 to 46 mL/day/inhabitant. Differences in consumption were statistically significant among the investigated cities and between weekdays and weekends. WBE-derived estimates of alcohol consumption were comparable to those reported by its corresponding region in the Spanish National Health Survey in most cases. At the national level, comparable results were obtained between the WBE-derived annual consumption rate (5.7 ± 1.2 L ethanol per capita (aged 15+)) and that reported by the National Health Survey (4.7 L ethanol per capita (aged 15+)).Conclusions: This is the largest WBE study carried out to date in Spain to estimate alcohol consumption rates. It confirms that this approach is useful for establishing spatial and temporal patterns of alcohol consumption, which could contribute to the development of health care management plans and policies. Contrary to established methods, it allows obtaining information in a fast and relatively economical way. [ABSTRACT FROM AUTHOR]