Sustained Exposure to the Widely Used Herbicide Atrazine: Altered Function and Loss of Neurons in Brain Monoamine Systems

The widespread use of atrazine (ATR) and its persistence in the environment have resulted in documented human exposure. Alterations in hypothalamic catecholamines have been suggested as the mechanistic basis of the toxicity of ATR to hormonal systems in females and the reproductive tract in males. Because multiple catecholamine systems are present in the brain, however, ATR could have far broader effects than are currently understood. Catecholaminergic systems such as the two major long-length dopaminergic tracts of the central nervous system play key roles in mediating a wide array of critical behavioral functions. In this study we examined the hypothesis that ATR would adversely affect these brain dopaminergic systems. Male rats chronically exposed to 5 or 10 mg/kg ATR in the diet for 6 months exhibited persistent hyperactivity and altered behavioral responsivity to amphetamine. Moreover, when measured 2 weeks after the end of exposure, the levels of various monoamines and the numbers of tyrosine hydroxylase-positive (TH(+)) and -negative (TH(−)) cells measured using unbiased stereology were reduced in both dopaminergic tracts. Acute exposures to 100 or 200 mg/kg ATR given intraperitoneally to evaluate potential mechanisms reduced both basal and potassium-evoked striatal dopamine release. Collectively, these studies demonstrate that ATR can produce neurotoxicity in dopaminergic systems that are critical to the mediation of movement as well as cognition and executive function. Therefore, ATR may be an environmental risk factor contributing to dopaminergic system disorders, underscoring the need for further investigation of its mechanism(s) of action and corresponding assessment of its associated human health risks

Evaluation of mesoscale convective systems in South America using multiple satellite products and an object‐based approach

In this study, an object-based verification method was used to reveal the existence of systematic errors in three satellite precipitation products: Tropical Rainfall Measurement Mission (TRMM), Climate Prediction Center Morphing Technique (CMORPH), and Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks (PERSIANN). Mesoscale convective systems (MCSs) for the austral summer 2002–2003 in the La Plata river basin, southeastern South America, were analyzed with the Contiguous Rain Area (CRA) method. Errors in storms intensity, volume, and spatial location were evaluated. A macroscale hydrological model was used to assess the impact of spatially shifted precipitation on streamflows simulations. PERSIANN underestimated the observed average rainfall rate and maximum rainfall consistent with the detection of storm areas systematically larger than observed. CMORPH overestimated the average rainfall rate while the maximum rainfall was slightly underestimated. TRMM average rainfall rate and rainfall volume correlated extremely well with ground observations whereas the maximum rainfall was systematically overestimated suggesting deficiencies in the bias correction procedure to filter noisy measurements. The preferential direction of error displacement in satellite-estimated MCSs was in the east-west direction for CMORPH and TRMM. Discrepancies in the fine structure of the storms dominated the error decomposition of all satellite products. Errors in the spatial location of the systems influenced the magnitude of simulated peaks but did not have a significant impact on the timing indicating that the system's response to precipitation was mitigating the effect of the errors.Fil: Demaria, E. M. C.. University Of Arizona; Estados UnidosFil: Rodriguez, D. A.. Centro de Previsao de Tempo e Estudos Climaticos. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Ebert, E. E.. Centre for Australian Weather and Climate Research; AustraliaFil: Salio, Paola Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmosfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmosfera; ArgentinaFil: Su, F.. University of Washington; Estados UnidosFil: Valdes, J. B.. University Of Arizona; Estados Unido

Impact and Outcomes of a Pediatric Robotic Urology Mini-Fellowship

Introduction: In order to support practicing pediatric surgeons and urologists to safely and effectively incorporate robotic surgery into their practice, we established a 5-day mini-fellowship program with a mentor, preceptor and proctor at our institution. This study was designed to report our experience with the pediatric robotic mini-fellowship (PRM) and to evaluate the impact this course had on the participants' practice.Methods: The mini-fellowship training at our institution is provided in two modules, including upper and lower urinary tract surgery, over a 5-day period. The one to one teacher-to-attendee experience included tutorial sessions, hands-on inanimate, and animate skills training, clinical case observations and video discussions. Participants were asked to complete a detailed questionnaire on their practice patterns before and after the PRM.Results: Between 2012 and 2018, a total of 29 national and international pediatric surgeons and urologists underwent robotic renal and bladder surgery training. Twenty-six fellows (90%) completed the surveys, all of which were included for analysis. The median age at the time of fellowship was 43 years (32–63), and participants had practiced urology for a median of 76 months (3–372). All of them had a laparoscopic background, with a median experience of 120 months (12–372), and an average of 454 (± 703) laparoscopic procedures performed, including the years of training. The most common primary goals of participants were to understand the concept of robotic surgery and its applications (38.5%), and to practice in the wet lab to shorten their learning curve (38.5%). After PRM completion, 24 graduates (92%) felt likely to incorporate robotic surgery into their practice, of which 15 (58%) actually started a robotic program at their home institution. At 24 months after PRM completion, the overall number of surgeries performed with a robotic approach (RA) by these 15 participants was 478 with an average of 32 (± 44) procedures per fellow, of which 109 (23%) were extirpative (nephrectomy, partial nephrectomy, etc.), and 369 (77%) reconstructive procedures (pyeloplasty, ureteral reimplantation, etc.). Before PRM, the same 15 participants performed 844 procedures with a laparoscopic approach (LA), of which 527 (62.4%) were extirpative, and 317 (37.6%) were reconstructive surgeries. These data mark a significant switch in indications for minimally invasive surgery (MIS) in pediatric urology. The rise in the number of reconstructive procedures (37.6% LA vs. 77% RA) has shown that robotic surgery has undoubtedly facilitated the performance of more challenging procedures in a minimally invasive fashion.Conclusion: The success of a mini-fellowship program relies on the commitment of expert faculty to serve as tutorial instructors and proctors. In addition, a completely outfitted robotic laboratory with access to dry and wet lab is indispensable. A 5-day intensive PRM appears to enable postgraduate surgeons to successfully incorporate the robotic platform into their practice and to advance the complexity of minimally invasive procedures, allowing for more challenging surgeries, such as reconstructive urology

The Prevalence of Fatigue Following Deep Brain Stimulation Surgery in Parkinson's Disease and Association with Quality of Life

Fatigue is a common and disabling nonmotor symptom seen in Parkinson's disease (PD). While deep brain stimulation surgery (DBS) improves motor symptoms, it has also been associated with non-motor side effects. To date no study has utilized standardized instruments to evaluate fatigue following DBS surgery. Our objective was to determine the prevalence of fatigue following DBS surgery in PD its impact on quality of life and explore predictive factors. We recruited 44 PD subjects. At least one year following DBS placement, we administered the Fatigue Severity Scale (FSS), the Parkinson's Disease Questionnaire (PDQ-39), the Beck Depression Inventory, the Beck Anxiety Inventory, the UPDRS, and a neuropsychological battery. Fifty-eight percent of subjects had moderate to severe fatigue. Fatigue was significantly associated with quality of life, depression, and anxiety. Depression preoperatively was the only predictive factor of fatigue. Fatigue is common following DBS surgery and significantly impacts quality of life

Deterministic observability calculations for zero-dimensional models of lithium–sulfur batteries

Among the various energy storage technologies under development, the lithium‑sulfur (Li–S) battery has considerable promise due to its higher theoretical energy density, small environmental footprint, and low projected costs. One of the main challenges posed by Li–S is the need for a battery management system (BMS) that can accommodate the system's complex multi-step redox behaviours; conventional approaches for lithium-ion batteries do not transfer. Most existing approaches rely on equivalent circuit network models, but there is growing interest in ‘zero-dimensional’ electrochemical models which can potentially give insights into the relative polysulfide species concentrations present at any given time. To be useful for state estimation, a model must be ‘observable’: it must be possible to uniquely determine the internal state through observation of the system's behaviour over time. Previous studies have assessed observability using numerical methods, which is an approximation. This study derives an analytic expression for the observability criterion, which allows greater confidence in the results. The analytic observability criterion is then validated against a numerical comparator. A zero-dimensional model from the literature is translated into an ordinary differential equation (ODE) form to define the state variables matrix A, the output matrix C, and subsequently the observability matrix O. These are compared to simulated numerical equivalents. In addition, the sensitivity of the numerical process has been demonstrated. The results have the potential to offer greater confidence in conclusions around observability, which in turn gives greater confidence in the effects of any algorithms based on them.This work was funded by the European Commission under grant agreement 814471, and the Innovate UK under grant TS/R013780/1

How stable are visions for protected area management? Stakeholder perspectives before and during a pandemic

Envisioning processes enable protected area managers to chart a course for future management to reach desired goals, but unexpected changes that could affect future visions are not usually considered. The global COVID-19 pandemic provided an opportunity to explore changes in stakeholder visions, the values that underpin the visions, and their perceptions of landscape changes and the underlying drivers (e.g. climate change, mass tourism and demographic trends). Through a mixed-methods approach in this post-evaluation study, we gathered comparative data on these issues from stakeholders in the Sierra de Guadarrama National Park, Spain, between July 2019 (pre-pandemic) and October 2020 (mid-pandemic). Our qualitative analysis demonstrates that pre-pandemic, differences in visions for protected area management were largely spurred by different perceptions of drivers of change, rather than differences in values or perceived landscape changes, which were similar across different vision themes. One year later, in the midst of the COVID-19 pandemic, the majority of stakeholders reported that their values, visions and perceptions of drivers did not change despite this large-scale disturbance. Of the 20%-30% of stakeholders that did report changes, visions generally shifted towards greater prioritization of biodiversity and nature conservation as a result of heightened perceptions of the impacts of drivers of change associated with an increase in the numbers of park visitors. These drivers included mass tourism, mountain recreation, lack of environmental awareness, and change in values and traditions. Our findings reinforce the importance of adaptive and inclusive management of protected areas, including enhancing transparency and communications regarding factors driving change in the landscape, and integration of local and traditional knowledge and stakeholder perceptions of changes and drivers. Furthermore, management plans integrating stakeholder values have the potential to stay relevant even in the face of wildcard events such as a pandemic. To enhance the relevancy of visions and scenarios in conservation and land-use planning, scenario planning methodologies should more strongly consider different potential disturbances and how drivers of change in the near and far future can be affected by wildcard events such as a pandemic. A free Plain Language Summary can be found within the Supporting Information of this article.Peer reviewe

Development and early diagnosis of critical illness myopathy in COVID-19 associated acute respiratory distress syndrome.

BACKGROUND The COVID-19 pandemic has greatly increased the incidence and clinical importance of critical illness myopathy (CIM), because it is one of the most common complications of modern intensive care medicine. Current diagnostic criteria only allow diagnosis of CIM at an advanced stage, so that patients are at risk of being overlooked, especially in early stages. To determine the frequency of CIM and to assess a recently proposed tool for early diagnosis, we have followed a cohort of COVID-19 patients with acute respiratory distress syndrome and compared the time course of muscle excitability measurements with the definite diagnosis of CIM. METHODS Adult COVID-19 patients admitted to the Intensive Care Unit of the University Hospital Bern, Switzerland requiring mechanical ventilation were recruited and examined on Days 1, 2, 5, and 10 post-intubation. Clinical examination, muscle excitability measurements, medication record, and laboratory analyses were performed on all study visits, and additionally nerve conduction studies, electromyography and muscle biopsy on Day 10. Muscle excitability data were compared with a cohort of 31 age-matched healthy subjects. Diagnosis of definite CIM was made according to the current guidelines and was based on patient history, results of clinical and electrophysiological examinations as well as muscle biopsy. RESULTS Complete data were available in 31 out of 44 recruited patients (mean [SD] age, 62.4 [9.8] years). Of these, 17 (55%) developed CIM. Muscle excitability measurements on Day 10 discriminated between patients who developed CIM and those who did not, with a diagnostic precision of 90% (AUC 0.908; 95% CI 0.799-1.000; sensitivity 1.000; specificity 0.714). On Days 1 and 2, muscle excitability parameters also discriminated between the two groups with 73% (AUC 0.734; 95% CI 0.550-0.919; sensitivity 0.562; specificity 0.857) and 82% (AUC 0.820; CI 0.652-0.903; sensitivity 0.750; specificity 0.923) diagnostic precision, respectively. All critically ill COVID-19 patients showed signs of muscle membrane depolarization compared with healthy subjects, but in patients who developed CIM muscle membrane depolarization on Days 1, 2 and 10 was more pronounced than in patients who did not develop CIM. CONCLUSIONS This study reports a 55% prevalence of definite CIM in critically ill COVID-19 patients. Furthermore, the results confirm that muscle excitability measurements may serve as an alternative method for CIM diagnosis and support its use as a tool for early diagnosis and monitoring the development of CIM