Reshaping cortical activity with subthalamic stimulation in Parkinson's disease during finger tapping and gait mapped by near infrared spectroscopy

Exploration of motor cortex activity is essential to understanding the pathophysiology in Parkinson's Disease (PD), but only simple motor tasks can be investigated using a fMRI or PET. We aim to investigate the cortical activity of PD patients during a complex motor task (gait) to verify the impact of deep brain stimulation in the subthalamic nucleus (DBS-STN) by using Near-Infrared-Spectroscopy (NIRS). NIRS is a neuroimaging method of brain cortical activity using low-energy optical radiation to detect local changes in (de)oxyhemoglobin concentration. We used a multichannel portable NIRS during finger tapping (FT) and gait. To determine the signal activity, our methodology consisted of a pre-processing phase for the raw signal, followed by statistical analysis based on a general linear model. Processed recordings from 9 patients were statistically compared between the on and off states of DBS-STN. DBS-STN led to an increased activity in the contralateral motor cortex areas during FT. During gait, we observed a concentration of activity towards the cortex central area in the "stimulation-on" state. Our study shows how NIRS can be used to detect functional changes in the cortex of patients with PD with DBS-STN and indicates its future use for applications unsuited for PET and a fMRI

Return to work, work productivity loss and activity impairment in Chinese breast cancer survivors 12-month post-surgery: a longitudinal study

Introduction: Existing evidence of returning-to-work (RTW) after cancer comes predominately from Western settings, with none prospectively examined since the initial diagnostic phase. This study prospectively documents RTW-rate, time-to-RTW, work productivity loss, and activity impairment, within the first-year post-surgery among Chinese women with breast cancer (BCW) and identify potential causal co-variants. Methods: This observational longitudinal study followed 371 Chinese BCW who were employed/self-employed at the time of diagnosis at 4-week post-surgery (baseline). RTW-status and time-to-RTW were assessed at baseline (T1), 4-month (T2), 6-month (T3), and 12-month (T4) post-baseline. WPAI work productivity loss and activity impairment were assessed at T4. Baseline covariates included demographics, medical-related factors, work satisfaction, perceived work demand, work condition, RTW self-efficacy, B-IPQ illness perception, COST financial well-being, EORTC QLQ-C30 and QLQ-BR23 physical and psychosocial functioning, and HADS psychological distress. Results: A 68.2% RTW-rate (at 12-month post-surgery), prolonged delay in RTW (median = 183 days), and significant proportions of T4 work productivity loss (20%), and activity impairment (26%), were seen. BCW who were blue-collar workers with lower household income, poorer financial well-being, lower RTW self-efficacy, poorer job satisfaction, poorer illness perception, greater physical symptom distress, impaired physical functioning, and unfavorable work conditions were more likely to experience undesired work-related outcomes. Discussion: Using a multifactorial approach, effective RTW interventions should focus on not only symptom management, but also to address psychosocial and work-environmental concerns. An organizational or policy level intervention involving a multidisciplinary team comprising nurses, psychologists, occupational health professionals, and relevant stakeholders in the workplace might be helpful in developing a tailored organizational policy promoting work-related outcomes in BCW

Zircon ages in granulite facies rocks: decoupling from geochemistry above 850 °C?

Granulite facies rocks frequently show a large spread in their zircon ages, the interpretation of which raises questions: Has the isotopic system been disturbed? By what process(es) and conditions did the alteration occur? Can the dates be regarded as real ages, reflecting several growth episodes? Furthermore, under some circumstances of (ultra-)high-temperature metamorphism, decoupling of zircon U–Pb dates from their trace element geochemistry has been reported. Understanding these processes is crucial to help interpret such dates in the context of the P–T history. Our study presents evidence for decoupling in zircon from the highest grade metapelites (> 850 °C) taken along a continuous high-temperature metamorphic field gradient in the Ivrea Zone (NW Italy). These rocks represent a well-characterised segment of Permian lower continental crust with a protracted high-temperature history. Cathodoluminescence images reveal that zircons in the mid-amphibolite facies preserve mainly detrital cores with narrow overgrowths. In the upper amphibolite and granulite facies, preserved detrital cores decrease and metamorphic zircon increases in quantity. Across all samples we document a sequence of four rim generations based on textures. U–Pb dates, Th/U ratios and Ti-in-zircon concentrations show an essentially continuous evolution with increasing metamorphic grade, except in the samples from the granulite facies, which display significant scatter in age and chemistry. We associate the observed decoupling of zircon systematics in high-grade non-metamict zircon with disturbance processes related to differences in behaviour of non-formula elements (i.e. Pb, Th, U, Ti) at high-temperature conditions, notably differences in compatibility within the crystal structure

Factors contributing to posttraumatic growth and its buffering effect in adult chidren of cancer patients undergoing treatment

This study examined relationships among demographic, clinical, and psychosocial variables in adult children of cancer patients. Two hundred and fourteen participants completed measures of posttraumatic growth (PTG), distress, posttraumatic stress disorder (PTSD) symptoms, social support, and family functioning. Significant gender differences in all PTG dimensions were found, as well as associations among PTG, gender, parental dependency, distress, PTSD, and family functioning. Social support was not a mediator in the relationship between gender and PTG. Gender, education, disease duration, dependency, distress, and family flexibility predicted PTG. Finally, PTG had amoderating effect in the relationship between distress and PTSD/social support. These results may guide psychosocial interventions in this population.Fundação para a Ciência e Tecnologia (FCT

CRTC Potentiates Light-independent timeless Transcription to Sustain Circadian Rhythms in Drosophila

Light is one of the strongest environmental time cues for entraining endogenous circadian rhythms. Emerging evidence indicates that CREB-regulated transcription co-activator 1 (CRTC1) is a key player in this pathway, stimulating light-induced Period1 (Per1) transcription in mammalian clocks. Here, we demonstrate a light-independent role of Drosophila CRTC in sustaining circadian behaviors. Genomic deletion of the crtc locus causes long but poor locomotor rhythms in constant darkness. Overexpression or RNA interference-mediated depletion of CRTC in circadian pacemaker neurons similarly impairs the free-running behavioral rhythms, implying that Drosophila clocks are sensitive to the dosage of CRTC. The crtc null mutation delays the overall phase of circadian gene expression yet it remarkably dampens light-independent oscillations of TIMELESS (TIM) proteins in the clock neurons. In fact, CRTC overexpression enhances CLOCK/CYCLE (CLK/CYC)-activated transcription from tim but not per promoter in clock-less S2 cells whereas CRTC depletion suppresses it. Consistently, TIM overexpression partially but significantly rescues the behavioral rhythms in crtc mutants. Taken together, our data suggest that CRTC is a novel co-activator for the CLK/CYC-activated tim transcription to coordinate molecular rhythms with circadian behaviors over a 24-hour time-scale. We thus propose that CRTC-dependent clock mechanisms have co-evolved with selective clock genes among different species.ope

Spermidine Promotes Human Hair Growth and Is a Novel Modulator of Human Epithelial Stem Cell Functions

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Antimicrobial management and appropriateness of treatment of urinary tract infection in general practice in Ireland

<p>Abstract</p> <p>Background</p> <p>Urinary tract infections (UTIs) are the second most common bacterial infections in general practice and a frequent indication for prescription of antimicrobials. Increasing concern about the association between the use of antimicrobials and acquired antimicrobial resistance has highlighted the need for rational pharmacotherapy of common infections in general practice.</p> <p>Methods</p> <p>Management of urinary tract infections in general practice was studied prospectively over 8 weeks. Patients presenting with suspected UTI submitted a urine sample and were enrolled with an opt-out methodology. Data were collected on demographic variables, previous antimicrobial use and urine samples. Appropriateness of different treatment scenarios was assessed by comparing treatment with the laboratory report of the urine sample.</p> <p>Results</p> <p>A total of 22 practices participated in the study and included 866 patients. Bacteriuria was established for 21% of the patients, pyuria without bacteriuria for 9% and 70% showed no laboratory evidence of UTI. An antimicrobial agent was prescribed to 56% (481) of the patients, of whom 33% had an isolate, 11% with pyuria only and 56% without laboratory evidence of UTI. When taking all patients into account, 14% patients had an isolate identified and were prescribed an antimicrobial to which the isolate was susceptible. The agents most commonly prescribed for UTI were co-amoxyclav (33%), trimethoprim (26%) and fluoroquinolones (17%). Variation between practices in antimicrobial prescribing as well as in their preference for certain antimicrobials, was observed. Treatment as prescribed by the GP was interpreted as appropriate for 55% of the patients. Three different treatment scenarios were simulated, i.e. if all patients who received an antimicrobial were treated with nitrofurantoin, trimethoprim or ciprofloxacin only. Treatment as prescribed by the GP was no more effective than treatment with nitrofurantoin for all patients given an antimicrobial or treatment with ciprofloxacin in all patients. Prescribing cost was lower for nitrofurantoin. Empirical treatment of all patients with trimethoprim only was less effective due to the higher resistance levels.</p> <p>Conclusions</p> <p>There appears to be considerable scope to reduce the frequency and increase the quality of antimicrobial prescribing for patients with suspected UTI.</p