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Aquatic ecosystems world-wide are being irreversibly altered, suggesting that new and innovative management strategies are necessary to improve ecosystem function and sustainability. In river ecosystems degraded by dams environmental flows and selective withdrawal (SWD) infrastructure have been used to improve habitat for native species. Yet, few studies have quantified nutrient and food web export subsidies from upstream reservoirs, despite their potential to subsidize downstream riverine food webs. We sampled nutrient, phytoplankton, and zooplankton concentrations in outflows from the Shasta-Keswick reservoir complex in Northern California over a 12-month period to understand how SWD operation and internal reservoir conditions interact to influence subsidies to the Sacramento River. We found that nutrients, phytoplankton, and zooplankton were continuously exported from Shasta Reservoir to the Sacramento River and that gate operations at Shasta Dam were important in controlling exports. Further, our results indicate that gate operations and water-export depth strongly correlated with zooplankton community exports, whereas internal reservoir conditions (mixing and residence time) controlled concentrations of exported zooplankton biomass and chlorophyll a. These results demonstrate that reservoirs can be an important source of nutrient and food web subsidies and that selective withdrawal infrastructure may provide a valuable management tool to control ecosystem-level productivity downstream of dams.

Drivers of phytoplankton and zooplankton dynamics vary spatially and temporally in estuaries due to variation in hydrodynamic exchange and residence time, complicating efforts to understand controls on food web productivity. We conducted approximately monthly (2012–2019; n = 74) longitudinal sampling at 10 fixed stations along a freshwater tidal terminal channel in the San Francisco Estuary, California, characterized by seaward to landward gradients in water residence time, turbidity, nutrient concentrations, and plankton community composition. We used multivariate autoregressive state space (MARSS) models to quantify environmental (abiotic) and biotic controls on phytoplankton and mesozooplankton biomass. The importance of specific abiotic drivers (e.g., water temperature, turbidity, nutrients) and trophic interactions differed significantly among hydrodynamic exchange zones with different mean residence times. Abiotic drivers explained more variation in phytoplankton and zooplankton dynamics than a model including only trophic interactions, but individual phytoplankton–zooplankton interactions explained more variation than individual abiotic drivers. Interactions between zooplankton and phytoplankton were strongest in landward reaches with the longest residence times and the highest zooplankton biomass. Interactions between cryptophytes and both copepods and cladocerans were stronger than interactions between bacillariophytes (diatoms) and zooplankton taxa, despite contributing less biovolume in all but the most landward reaches. Our results demonstrate that trophic interactions and their relative strengths vary in a hydrodynamic context, contributing to food web heterogeneity within estuaries at spatial scales smaller than the freshwater to marine transition.

Estuaries are among the most productive of aquatic ecosystems. Yet the collective understanding of patterns and drivers of primary production in estuaries is incomplete, in part due to complex hydrodynamics and multiple controlling factors that vary at a range of temporal and spatial scales. A whole-ecosystem experiment was conducted in a deep, pelagically dominated terminal channel of the Sacramento-San Joaquin Delta (California, USA) that seasonally appears to become nitrogen limited, to test whether adding calcium nitrate would stimulate primary productivity or increase phytoplankton density. Production did not respond consistently to fertilization, in part because nitrate and phytoplankton were dispersed away from the manipulated area within 1–3 days. Temporal and spatial patterns of gross primary production were more strongly related to stratification and light availability (i.e., turbidity) than nitrogen, highlighting the role of hydrodynamics in regulating system production. Similarly, chlorophyll was positively related not only to stratification but also to nitrogen—with a positive interaction—suggesting stratification may trigger nutrient limitation. The average rate of primary production (4.3 g O2 m−2 d−1), metabolic N demand (0.023 mg N L−1 d−1), and ambient dissolved inorganic nitrogen concentration (0.03 mg N L−1) indicate that nitrogen can become limiting in time and space, especially during episodic stratification events when phytoplankton are isolated within the photic zone, or farther upstream where water clarity increases, dispersive flux decreases, and stratification is stronger and more frequent. The role of hydrodynamics in organizing habitat connectivity and regulating physical and chemical processes at multiple temporal and spatial scales is critical for determining resource availability and evaluating biogeochemical processes in estuaries.

Most educational systems across the world have migrated to remote learning modality as a measure against the spread of the coronavirus disease 2019 (COVID-19). This phenomenon is causing a lot of difficulties especially as voiced out by students in the context of developing countries. This paper attempts to describe the difficulties in remote learning of university students in the Philippines in the wake of the COVID-19 crisis. Following a mainly qualitative research design, this study surveyed a pool of purposively and conveniently selected students currently enrolled in a tertiary institution. The result of the content analysis revealed the following categories of difficulties in remote learning: unstable internet connectivity; inadequate learning resources; electric power interruptions; vague learning contents; overloaded lesson activities; limited teacher scaffolds; poor peer communication; conflict with home responsibilities; poor learning environment; financial related problems; physical health compromises; and mental health struggles. Based on the result, cogent recommendations are discussed at the end of the study.

Ecosystem metabolism is a key ecological attribute and easy to describe, but quantifying metabolism in estuaries is challenging. Properly scaling measurements through time and space requires consideration of hydrodynamics and mixing water from heterogeneous sources, making any estimation uncertain. Here, we compared three methods for modeling ecosystem metabolism in a portion of the Sacramento-San Joaquin Delta. Metabolism estimates based on laboratory incubations, continuous in situ buoys, and an oxygen isotope approach all indicated the system was net heterotrophic, and calculated rates were comparable in magnitude when averaged over the 2-month study. Daily metabolic rates based on in situ buoys were the most variable, likely due to horizontal and vertical advection and poor portrayal of the dissolved oxygen budget. After temporally averaging in situ buoy estimates or smoothing the dissolved oxygen time series for tidal effects, rates were more comparable to the other methods, which may be necessary to account for tidal advection and unbalanced contributions from subhabitats within the metabolic footprint. Incubation-based rates represent the finest temporal and spatial scale and only account for pelagic processes, which may explain why incubation-based rates were lower than the other two methods. The oxygen isotope method provided temporally and spatially integrated rates that were bracketed by the other two methods and may be a valuable tool in systems matching the model requirements. Because uncertainty arises in each method from a number of assumptions and scaling calculations, the resolution of metabolic rates in estuaries is likely coarser and more variable than in other aquatic ecosystems.

In the Western United States, volcanic spring-fed rivers are anticipated to become increas-ingly more important for salmonids and other native fishes, as these rivers will retain coldwater habitats as the climate warms. Despite this, little is known about the hydro-biogeochemical interactions within these ecosystems. A review of existing literature on spring-fed rivers, coupled with a decade of research on volcanic spring-fed rivers of northern California, finds that these systems are exceptionally productive and exhibit stable environmental conditions. These unique conditions stem from hydrogeologic processes typical of young volcanic terrains. Aquatic macrophytes, com-mon to some nutrient-rich spring-fed systems, play a disproportionate role in hydrologic and geo-morphic processes by facilitating ecological interactions and velocity conditions that improve juvenile salmonid growth. We find that volcanic spring-fed rivers are also resilient to climate change, due not only to their ability to dampen water temperature changes through deep groundwater flow but also because of their nutrient-driven high ecosystem productivity, which may enable coldwater species to metabolically compensate for marginal increases in water temperature. Understanding the fundamental geomorphic and ecological differences between these rare ecosystems and their numerically dominant runoff rivers is essential for developing long-term conservation strategies for coldwater species under a rapidly changing climate.

Introduction: Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson’s disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and to discuss mechanisms proposed by authors. Method: A search on the literature was performed on PubMed up to December 2023 using the following key words: Parkinson’s disease AND exercise, exercise therapy, neurological rehabilitation AND brain-derived neurotrophic factor, brain-derived neurotrophic factor/blood, brain-derived neurotrophic factor/cerebrospinal fluid AND randomized clinical trial, intervention study. Only randomized clinical trials comparing an exercise intervention to treatment as usual, usual care (UC), sham intervention, or no intervention were included. Results: A meta-analysis of BDNF outcomes with pooled data from five trials (N = 216 participants) resulted in a significant standardized mean difference (SMD) of 1.20 [95% CI 0.53 to 1.87; Z = 3.52, p = 0.0004, I2 = 77%], favoring exercise using motorized treadmill, Speedflex machine, rowing machine, and non-specified exercise. Significant improvements were found in Unified Parkinson’s Disease Rating Scale (UPDRS), UPDRS-III, 6 Minute Walk Test (6MWT), and Berg Balance Scale (BBS). Methodological quality of trials was categorized as “good” in three trials, “fair” in one trial, and “poor” in one trial. Conclusion: Key results of this systematic review are that exercise therapy is effective in raising serum BDNF levels and seems effective in alleviating PD motor symptoms. Exercise therapy confers neuroplastic effects on Parkinson brain, mediated, in part, by BDNF.

Abstract Background Stroke survivors show deteriorated physical functioning and physical activity levels. Physical activity levels of stroke survivors are generally low. It is increasingly recognized that physical activity is a multidimensional construct that cannot be captured in a single outcome. In-depth insight into multidimensional physical activity patterns may guide the development and timing of targeted rehabilitation interventions. This longitudinal cohort study explored how multidimensional physical activity outcomes develop during recovery in the subacute phase after stroke and if changes in physical activity were correlated to recovery of lower limb motor function. Methods Patients were recruited during inpatient rehabilitation. At 3, 12, and 26 weeks post-onset, motor function was measured by the Fugl-Meyer Lower Extremity Assessment (FMA-LE). Physical activity was measured with the Activ8 accelerometer in multiple outcomes: counts per minute during walking (CPMwalking; a measure of Intensity), number of active bouts (Frequency), mean length of active bouts (Distribution) and % of waking time in upright positions (Duration). Generalized estimating equations (GEE) were used to study changes in physical activity over time and the relation with the change in lower limb motor recovery. Results Thirty-nine patients (age 56 ± 9, 77% male, 89% ischemic stroke) were included. GEE models showed a significant main effect of time for PA Intensity (+ 13%, p = 0.007) and Duration (+ 64%, p = 0.012) between 3 and 12 weeks. Motor function did not show a significant effect in all PA models across the 3 timepoints (p > 0.020). A significant interaction effect of time × motor function was observed (p

Abstract Background Smoothness is commonly used for measuring movement quality of the upper paretic limb during reaching tasks after stroke. Many different smoothness metrics have been used in stroke research, but a ‘valid’ metric has not been identified. A systematic review and subsequent rigorous analysis of smoothness metrics used in stroke research, in terms of their mathematical definitions and response to simulated perturbations, is needed to conclude whether they are valid for measuring smoothness. Our objective was to provide a recommendation for metrics that reflect smoothness after stroke based on: (1) a systematic review of smoothness metrics for reaching used in stroke research, (2) the mathematical description of the metrics, and (3) the response of metrics to simulated changes associated with smoothness deficits in the reaching profile. Methods The systematic review was performed by screening electronic databases using combined keyword groups Stroke, Reaching and Smoothness. Subsequently, each metric identified was assessed with mathematical criteria regarding smoothness: (a) being dimensionless, (b) being reproducible, (c) being based on rate of change of position, and (d) not being a linear transform of other smoothness metrics. The resulting metrics were tested for their response to simulated changes in reaching using models of velocity profiles with varying reaching distances and durations, harmonic disturbances, noise, and sub-movements. Two reaching tasks were simulated; reach-to-point and reach-to-grasp. The metrics that responded as expected in all simulation analyses were considered to be valid. Results The systematic review identified 32 different smoothness metrics, 17 of which were excluded based on mathematical criteria, and 13 more as they did not respond as expected in all simulation analyses. Eventually, we found that, for reach-to-point and reach-to-grasp movements, only Spectral Arc Length (SPARC) was found to be a valid metric. Conclusions Based on this systematic review and simulation analyses, we recommend the use of SPARC as a valid smoothness metric in both reach-to-point and reach-to-grasp tasks of the upper limb after stroke. However, further research is needed to understand the time course of smoothness measured with SPARC for the upper limb early post stroke, preferably in longitudinal studies.

Abstract Background The cause of smoothness deficits as a proxy for quality of movement post stroke is currently unclear. Previous simulation analyses showed that spectral arc length (SPARC) is a valid metric for investigating smoothness during a multi-joint goal-directed reaching task. The goal of this observational study was to investigate how SPARC values change over time, and whether SPARC is longitudinally associated with the recovery from motor impairments reflected by the Fugl-Meyer motor assessment of the upper extremity (FM-UE) in the first 6 months after stroke. Methods Forty patients who suffered a first-ever unilateral ischemic stroke (22 males, aged 58.6 ± 12.5 years) with upper extremity paresis underwent kinematic and clinical measurements in weeks 1, 2, 3, 4, 5, 8, 12, and 26 post stroke. Clinical measures included amongst others FM-UE. SPARC was obtained by three-dimensional kinematic measurements using an electromagnetic motion tracking system during a reach-to-grasp movement. Kinematic assessments of 12 healthy, age-matched individuals served as reference. Longitudinal linear mixed model analyses were performed to determine SPARC change over time, compare smoothness in patients with reference values of healthy individuals, and establish the longitudinal association between SPARC and FM-UE scores. Results SPARC showed a significant positive longitudinal association with FM-UE (B: 31.73, 95%-CI: [27.27 36.20], P

Introduction: Physical exercise is receiving increasing interest as an augmentative non-pharmacological intervention in Parkinson’s disease (PD). This pilot study primarily aimed to quantify individual response patterns of motor symptoms to alternating exercise modalities, along with non-motor functioning and blood biomarkers of neuroplasticity and neurodegeneration. Materials & Methods: People with PD performed high-intensity interval training (HIIT) and continuous aerobic exercise (CAE) using a crossover single-case experimental design. A repeated assessment of outcome measures was conducted. The trajectories of outcome measures were visualized in time series plots and interpreted relative to the minimal clinically important difference (MCID) and smallest detectable change (SDC) or as a change in the positive or negative direction using trend lines. Results: Data of three participants were analyzed and engaging in physical exercise seemed beneficial for reducing motor symptoms. Participant 1 demonstrated improvement in motor function, independent of exercise modality; while for participant 2, such a clinically relevant (positive) change in motor function was only observed in response to CAE. Participant 3 showed improved motor function after HIIT, but no comparison could be made with CAE because of drop-out. Heterogeneous responses on secondary outcome measures were found, not only between exercise modalities but also among participants. Conclusion: Though this study underpins the positive impact of physical exercise in the management of PD, large variability in individual response patterns to the interventions among participants makes it difficult to identify clear exercise-induced adaptations in functioning and blood biomarkers. Further research is needed to overcome methodological challenges in measuring individual response patterns.

Fatigue is a common complaint and a disabling symptom among patients following transient ischemic attack (TIA) or minor stroke. In patients with stroke, decreased cardiorespiratory fitness (CRF) is believed to be related to increased severity of post-stroke fatigue (PSF). However, this association between PSF and CRF in patients with TIA or minor stroke has been less investigated, and currently there is no proven treatment for PSF. We aimed to determine the association between PSF and CRF in patients with TIA or minor stroke and to find out whether this association was distorted by confounders. A cross-sectional association study was conducted among a total of 119 patients with TIA or minor stroke. PSF was measured by the Fatigue Severity Scale (FSS) and CRF was quantified by maximal exercise capacity (V̇O2max). The FSS showed a significant association with V̇O2max (ß = −0.061, SE: 0.022; p = 0.007). This association was confounded by anxiety (ß = −0.044, SE: 0.020; p = 0.028) and depression (ß = −0.030, SE: 0.022; p = 0.177) as measured by the subscales of the Hospital Anxiety and Depression Scale (HADS). After controlling for HADS scores on depression and anxiety, the univariate relationship between V̇O2max and FSS was no longer significant. These results suggest that the association between PSF and CRF in patients with TIA or minor stroke is weak and significantly confounded by the factors of depression and anxiety.

Abstract Background The growing societal and economic impact of Alzheimer’s disease (AD) is further compounded by the present lack of disease-modifying interventions. Non-pharmacological intervention approaches, such as exercise, have the potential to be powerful approaches to improve or mitigate the symptoms of AD without added side effects or financial burden associated with drug therapies. Various forms and regiments of exercise (i.e., strength, aerobic, multicomponent) have been reported in the literature; however, conflicting evidence obscures clear interpretation of the value and impact of exercise as an intervention for older adults with AD. The primary objective of this review will be to evaluate the effects of exercise interventions for older adults with AD. In addition, this review will evaluate the evidence quality and synthesize the exercise training prescriptions for proper clinical practice guidelines and recommendations. Methods This systematic review and meta-analysis will be carried out by an interdisciplinary collective representing clinical and research stakeholders with diverse expertise related to neurodegenerative diseases and rehabilitation medicine. Literature sources will include the following: Embase, PsychINFO, OVID Medline, and Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily. Inclusion criteria are participants with late onset AD and structured exercise interventions with prescribed duration, frequency, and intensity. The primary outcome of this study will center on improved or sustained cognitive functioning. Secondary outcomes will include institutionalization-related outcomes, ability in activities of daily living, mood and emotional well-being, quality of life, morbidity, and mortality. Analysis procedures to include measurement of bias, data synthesis, sensitivity analysis, and assessment of heterogeneity are described in this protocol. Discussion This review is anticipated to yield clinically meaningful insight on the specific value of exercise for older adults with AD. Improved understanding of diverse exercise intervention approaches and their specific impact on various health- and function-related outcomes is expected to guide clinicians to more frequently and accurately prescribe meaningful interventions for those affected by AD. Systematic review registration PROSPERO CRD42020175016 .

Cassia alata L. (Gelinggang) one of the plants known as medicinal plants, especially for the treatment of skin diseases. The purpose of this study was to determine the type of secondary metabolites using phytochemical tests, toxicity with the BSLT method and antioxidant properties against DPPH radicals from the extract of the Gelinggang leaves. The results of the study showed extracts of Gelinggang leaves containing alkaloids, triterpenoids, steroids, and quinones. Based on the results of toxicity and antioxidant tests showed that Gelinggang leaves extract was very toxic to Artemia salina shrimp and it was a strong antioxidant against DPPH radicals with LC50 and IC50 were 28.84 ppm and 73.57 ppm, respectively. Keywords: Gelinggang, Cassia alata L., toxicity, antioxidants, DPPH

Background The evidence for rehabilitation interventions poststroke lack sufficient robustness. However, variation in treatment effects across countries have been given little attention. Objective To compare two identically protocolized trials conducted in different western countries in order to identify factors that may have caused variation in secondary trial outcomes. Methods Comparative study based on individual patient data (N = 129) from two randomized controlled trials, conducted in hospitals and rehabilitation facilities in the Netherlands (N = 66) and Australia (N = 63). Patients with stroke and their caregivers were randomly allocated to an 8-week caregiver-mediated exercises intervention (N = 63; 31 Australian and 32 Dutch) or to a control group (N = 66; 32 Australian and 34 Dutch). Patient characteristics, compliance, usual care and process measures were compared across countries. We examined if study setting significantly moderated the trial outcomes: Hospital Anxiety and Depression Scale, Fatigue Severity Scale and General Self-Efficacy Scale, measured at 8- and 12 weeks follow-up. In addition, we explored if factors that were significantly different across countries caused variation in these trial outcomes. Results Most patients suffered an ischemic stroke, were in the subacute phase and participated with their partner. Dutch patients were younger (P = 0.005) and had a lower functional status (P = 0.001). Australian patients were recruited earlier poststroke (PConclusions The present study highlighted important clinical differences across countries whilst using an identical study protocol. The observed differences could result in a different potential for recovery and variation in treatment effects across trials. We argue that we can proceed faster to evaluating interventions within international pragmatic trials.

Background Exercise training may affect the blood levels of brain-derived neurotrophic factor (BDNF), but meta-analyses have not yet been performed comparing pre- and post-intervention BDNF concentrations in patients with multiple sclerosis (PwMS). Objective To perform a meta-analysis to study the influence of exercise on BDNF levels and define components that modulate them across clinical trials of exercise training in adults living with multiple sclerosis (MS). Method Five databases (PubMed, EMBASE, Cochrane Library, PEDro database, CINAHL) were searched up to June 2021. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 13 articles in the meta-analysis, including 271 subjects. To investigate sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. We performed the meta-analysis to compare pre- and post-exercise peripheral levels of BDNF in PwMS. Results Post-exercise concentrations of serum BDNF were significantly higher than pre-intervention levels (Standardized Mean Difference (SMD): 0.33, 95% CI: [0.04; 0.61], p-value = 0.02). Meta-regression indicated that the quality of the included studies based on the PEDro assessment tool might be a source of heterogeneity, while no significant effect was found for chronological age and disease severity according to the expanded disability status scale. Conclusion This systematic review and meta-analysis shows that physical activity increases peripheral levels of BDNF in PwMS. More research on the effect of different modes of exercise on BDNF levels in PwMS is warranted.

We often interact with our environment through manual handling of objects and exploration of their properties. Object properties (OP), such as texture, stiffness, size, shape, temperature, weight, and orientation provide necessary information to successfully perform interactions. The human haptic perception system plays a key role in this. As virtual reality (VR) has been a growing field of interest with many applications, adding haptic feedback to virtual experiences is another step towards more realistic virtual interactions. However, integrating haptics in a realistic manner, requires complex technological solutions and actual user-testing in virtual environments (VEs) for verification. This review provides a comprehensive overview of recent wearable haptic devices (HDs) categorized by the OP exploration for which they have been verified in a VE. We found 13 studies which specifically addressed user-testing of wearable HDs in healthy subjects. We map and discuss the different technological solutions for different OP exploration which are useful for the design of future haptic object interactions in VR, and provide future recommendations.

Background: Proprioception is important for regaining motor function in the paretic upper extremity after stroke. However, clinical assessments of proprioception are subjective and require verbal responses from the patient to applied proprioceptive stimuli. Cortical responses evoked by robotic wrist perturbations and measured by electroencephalography (EEG) may be an objective method to support current clinical assessments of proprioception.Objective: To establish whether evoked cortical responses reflect proprioceptive deficits as assessed by clinical scales and whether they predict upper extremity motor function at 26 weeks after stroke.Methods: Thirty-one patients with stroke were included. In week 1, 3, 5, 12, and 26 after stroke, the upper extremity sections of the Erasmus modified Nottingham Sensory Assessment (EmNSA-UE) and the Fugl-Meyer Motor Assessment (FM-UE) and the EEG responses (64 channels) to robotic wrist perturbations were measured. The extent to which proprioceptive input was conveyed to the affected hemisphere was estimated by the signal-to-noise ratio (SNR) of the evoked response. The relationships between SNR and EmNSA-UE as well as SNR and time after stroke were investigated using linear regression. Receiver-operating-characteristic curves were used to compare the predictive values of SNR and EmNSA-UE for predicting whether patients regained some selective motor control (FM-UE > 22) or whether they could only move their paretic upper extremity within basic limb synergies (FM-UE ≤ 22) at 26 weeks after stroke.Results: Patients (N = 7) with impaired proprioception (EmNSA-UE proprioception score < 8) had significantly smaller SNR than patients with unimpaired proprioception (N = 24) [EmNSA-UE proprioception score = 8, t(29) = 2.36, p = 0.03]. No significant effect of time after stroke on SNR was observed. Furthermore, there was no significant difference in the predictive value between EmNSA-UE and SNR for predicting motor function at 26 weeks after stroke.Conclusion: The SNR of the evoked cortical response does not significantly change as a function of time after stroke and differs between patients with clinically assessed impaired and unimpaired proprioception, suggesting that SNR reflects persistent damage to proprioceptive pathways. A similar predictive value with respect to EmNSA-UE suggests that SNR may be used as an objective predictor next to clinical sensory assessments for predicting motor function at 26 weeks after stroke.

BackgroundPyridoxine-dependent epilepsy (PDE) is due to biallelic variants in ALDH7A1 (PDE-ALDH7A1). ALDH7A1 encodes α-aminoadipic semialdehyde dehydrogenase in lysine catabolism. We investigated the gamma aminobutyric acid (GABA) metabolism and energy production pathways in human PDE-ALDH7A1 and its knock-out aldh7a1 zebrafish model.MethodsWe measured GABA pathway, and tricarboxylic acid cycle metabolites and electron transport chain activities in patients with PDE-ALDH7A1 and in knock-out aldh7a1 zebrafish.ResultsWe report results of three patients with PDE-ALDH7A1: low paired complex I+II and complex II+III and individual complex IV activities in muscle biopsy in patient 1 (likely more severe phenotype); significantly elevated CSF glutamate in the GABA pathway and elevated CSF citrate, succinate, isocitrate and α-ketoglutarate in the TCA cycle in patient 3 (likely more severe phenotype); and normal CSF GABA pathway and TCA cycle metabolites on long-term pyridoxine therapy in patient 2 (likely milder phenotype). All GABA pathway metabolites (γ-hydroxybutyrate, glutamine, glutamate, total GABA, succinic semialdehyde) and TCA cycle metabolites (citrate, malate, fumarate, isocitrate, lactate) were significantly low in the homozygous knock-out aldh7a1 zebrafish compared to the wildtype zebrafish. Homozygous knock-out aldh7a1 zebrafish had decreased electron transport chain enzyme activities compared to wildtype zebrafish.DiscussionWe report impaired electron transport chain function, accumulation of glutamate in the central nervous system and TCA cycle dysfunction in human PDE-ALDH7A1 and abnormal GABA pathway, TCA cycle and electron transport chain in knock-out aldh7a1 zebrafish. Central nervous system glutamate toxicity and impaired energy production may play important roles in the disease neuropathogenesis and severity in human PDE-ALDH7A1.

Background: People with Parkinson's disease (PD) experience not only motor problems but also non-motor problems that seriously impede their daily functioning and quality of life. The current pharmacologic treatment of PD is symptomatic, and alternative rehabilitation treatments, which preferably also have a disease-modifying effect and promote neuroplasticity, are needed. Recent studies suggest that high-intensity interval training (HIIT) is promising for promoting neuroplasticity in human PD, with short training time and reduced burden. Biomarkers for neuroplasticity such as brain-derived neurotrophic factor (BDNF) and neurodegeneration (including neurofilament NfL and α-synuclein) may play a role, but their response to HIIT is not well-investigated.Objectives: The aims of this study were (1) to study the effects of 4 weeks of HIIT compared with 4 weeks of continuous aerobic exercise on motor and non-motor outcomes of PD and (2) to investigate the association between HIIT, motor/non-motor performances changes, and blood biomarker levels for neuroplasticity and neurodegeneration.Study Design: Single-subject research design with alternating treatment setup (ABACA) and frequent repeated measurements was used. Each participant received different intervention conditions (B/C) interspersed with baseline periods (A, i.e., ABACA or ACABA), and frequent repeated assessment of outcome measures is done to quantify within-subject, individual response patterns with sufficient power for data analysis. Blood samples were collected once a week in the baseline and training phases (A1 and B/C) and once every 2 weeks in the washout phases (A2 and A3).Intervention: Four subjects with PD on stable dopaminergic medication, two in Hoehn–Yahr stage 1–2, and two in Hoehn–Yahr stage 2.5–3 followed an ABACA or ACABA schedule, consisting of blocks with 30-min sessions of “B” (HIIT) or 50-min sessions of “C” [continuous aerobic exercise (CAE)] 3×/week for 4 weeks, separated by baseline “A” periods of 8 weeks for a total duration of 28 weeks.Outcome Measures: Outcome measures include disease status [Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)], blood biomarkers (BDNF, Nfl, and α-synuclein), measures for functional mobility (including an activity tracker), and activities of daily living, as well as cognition, mood, biorhythm (sleeping problems), and quality of life.Data Analysis: Visual analysis of trends in level, slope, and variability in response patterns was carried out, confirmed by longitudinal regression analysis with phase (ABACA) as the independent variable.

Extreme rainfall accompanied by strong winds hit the province of Bengkulu in the western coastal area of Sumatera Island during September 19-20, 2017, causing floods and landslides in Seluma and Central Bengkulu district. This extreme rainfall was recorded by Bengkulu Meteorological Station about 257.0 mm day−1 using rain-gauge observation. The spatial distribution of extreme rainfall cannot be seen if only using a rain-gauge observation in this location. The spatial distribution of extreme rainfall is needed to identify the impact of rainfall on landslides in large areas. The study aims to (1) develop the reconstruction of the spatial distribution of extreme rainfall using weather radar and (2) investigate the trigger that caused extreme rainfall by analyzing the synoptic-scale tropical waves. Each weather radar datum is saved in a Constant Altitude Plan Position Indicator (CAPPI). To get rainfall information, the CAPPI must be derived from Quantitative Precipitation Estimation (QPE) values. In this paper, we derived CAPPI using a Marshall-Palmer reflectivity-rain rate relationship. The result shows that rainfall formed on September 20, 2017, 21.00 UTC with total daily rainfall ranged between 176 and 247 mm in both districts and the mean of total daily rainfall has exceeded the average of monthly rainfall. The analysis of tropical waves suggests that only Kelvin waves were active and served as a possible trigger factor while the Madden-Julian Oscillation (MJO) and Equatorial Rossby (ER) waves were inactive during this extreme rainfall.

Abstract Background Animal models of exercise and Parkinson’s disease (PD) have found that the physiologic use of exercise may interact with the neurodegenerative disease process, likely mediated by brain derived neurotrophic factor (BDNF). No reviews so far have assessed the methodologic quality of available intervention studies or have bundled the effect sizes of individual studies on exercise-induced effects on BDNF blood levels in human PD. Research design and methods We searched MEDLINE, EMBASE, Cochrane Library, PsycINFO and PubMed from inception to June 2017. Results Data aggregated from two randomized controlled trials and four pre-experimental studies with a total of 100 ambulatory patients with idiopathic PD (Hoehn/Yahr ≤3) found improvements in BDNF blood concentration levels in all 6 studies (two RCTs and 4 pre-experimental studies). Pooled BDNF level change scores from the 2 RCTs resulted in a significant homogeneous summary effect size (Standardized Mean Difference 2.06, 95% CI 1.36 to 2.76), and a significant heterogeneous SES for the motor part of the UPDRS-III examination (MD -5.53, 95% CI -10.42 to -0.64). Clinical improvements were noted in all studies using a variety of outcome measures. Limitations The evidence-base consists primarily of small studies with low to moderate methodological quality. Conclusions This review provides preliminary evidence for the effectiveness of physical exercise treatments for persons with PD on BDNF blood levels. Further research is needed.

The Stockton Deep Water Ship Channel, a stretch of the tidal San Joaquin River, is frequently subject to low dissolved oxygen conditions and annually violates regional water quality objectives. Underlying mechanisms are examined here using the long-term water quality data, and the efficacy of possible solutions using time-series regression models. Hypoxia is most common during June-September, immediately downstream of where the river enters the Ship Channel. At the annual scale, ammonium loading from the Regional Wastewater Control Facility has the largest identifiable effect on year-to-year variability. The longer-term upward trend in ammonium loads, which have been increasing over 10% per year, also corresponds to a longer-term downward trend in dissolved oxygen during summer. At the monthly scale, river flow, loading of wastewater ammonium and river phytoplankton, Ship Channel temperature, and Ship Channel phytoplankton are all significant in determining hypoxia. Over the recent historical range (1983–2003), wastewater ammonium and river phytoplankton have played a similar role in the monthly variability of the dissolved oxygen deficit, but river discharge has the strongest effect. Model scenarios imply that control of either river phytoplankton or wastewater ammonium load alone would be insufficient to eliminate hypoxia. Both must be strongly reduced, or reduction of one must be combined with increases in net discharge to the Ship Channel. Model scenarios imply that preventing discharge down Old River with a barrier markedly reduces hypoxia in the Ship Channel. With the Old River barrier in place, unimpaired or full natural flow at Vernalis would have led to about the same frequency of hypoxia that has occurred with actual flows since the early 1980s.