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1.
bioRxiv ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38659887

RESUMO

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brain's volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing. To unravel the stunning diversity of a complex visual system, a careful mapping of the neural architecture matched to tools for targeted exploration of that circuitry is essential. Here, we report a new connectome of the right optic lobe from a male Drosophila central nervous system FIB-SEM volume and a comprehensive inventory of the fly's visual neurons. We developed a computational framework to quantify the anatomy of visual neurons, establishing a basis for interpreting how their shapes relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity, and expert curation, we classified the ~53,000 neurons into 727 types, about half of which are systematically described and named for the first time. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron type catalog. Together, this comprehensive set of tools and data unlock new possibilities for systematic investigations of vision in Drosophila, a foundation for a deeper understanding of sensory processing.

2.
ACS Catal ; 14(7): 4379-4394, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38633402

RESUMO

Many enzymes display non-Arrhenius behavior with curved Arrhenius plots in the absence of denaturation. There has been significant debate about the origin of this behavior and recently the role of the activation heat capacity (ΔCP⧧) has been widely discussed. If enzyme-catalyzed reactions occur with appreciable negative values of ΔCP⧧ (arising from narrowing of the conformational space along the reaction coordinate), then curved Arrhenius plots are a consequence. To investigate these phenomena in detail, we have collected high precision temperature-rate data over a wide temperature interval for a model glycosidase enzyme MalL, and a series of mutants that change the temperature-dependence of the enzyme-catalyzed rate. We use these data to test a range of models including macromolecular rate theory (MMRT) and an equilibrium model. In addition, we have performed extensive molecular dynamics (MD) simulations to characterize the conformational landscape traversed by MalL in the enzyme-substrate complex and an enzyme-transition state complex. We have crystallized the enzyme in a transition state-like conformation in the absence of a ligand and determined an X-ray crystal structure at very high resolution (1.10 Å). We show (using simulation) that this enzyme-transition state conformation has a more restricted conformational landscape than the wildtype enzyme. We coin the term "transition state-like conformation (TLC)" to apply to this state of the enzyme. Together, these results imply a cooperative conformational transition between an enzyme-substrate conformation (ES) and a transition-state-like conformation (TLC) that precedes the chemical step. We present a two-state model as an extension of MMRT (MMRT-2S) that describes the data along with a convenient approximation with linear temperature dependence of the activation heat capacity (MMRT-1L) that can be used where fewer data points are available. Our model rationalizes disparate behavior seen for MalL and previous results for a thermophilic alcohol dehydrogenase and is consistent with a raft of data for other enzymes. Our model can be used to characterize the conformational changes required for enzyme catalysis and provides insights into the role of cooperative conformational changes in transition state stabilization that are accompanied by changes in heat capacity for the system along the reaction coordinate. TLCs are likely to be of wide importance in understanding the temperature dependence of enzyme activity and other aspects of enzyme catalysis.

3.
J Neurol ; 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38583105

RESUMO

OBJECTIVE: The aim of this study was to explore the relation of language functional MRI (fMRI)-guided tractography with postsurgical naming decline in people with temporal lobe epilepsy (TLE). METHODS: Twenty patients with unilateral TLE (9 left) were studied with auditory and picture naming functional MRI tasks. Activation maxima in the left posterobasal temporal lobe were used as seed regions for whole-brain fibre tractography. Clinical naming performance was assessed preoperatively, 4 months, and 12 months following temporal lobe resection. Volumes of white matter language tracts in both hemispheres as well as tract volume laterality indices were explored as moderators of postoperative naming decline using Pearson correlations and multiple linear regression with other clinical variables. RESULTS: Larger volumes of white matter language tracts derived from auditory and picture naming maxima in the hemisphere of subsequent surgery as well as stronger lateralization of picture naming tract volumes to the side of surgery correlated with greater language decline, which was independent of fMRI lateralization status. Multiple regression for picture naming tract volumes was associated with a significant decline of naming function with 100% sensitivity and 93% specificity at both short-term and long-term follow-up. INTERPRETATION: Naming fMRI-guided white matter language tract volumes relate to postoperative naming decline after temporal lobe resection in people with TLE. This can assist stratification of surgical outcome and minimize risk of postoperative language deficits in TLE.

4.
Cell Death Dis ; 15(4): 246, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575601

RESUMO

Parkinson's disease (PD) is a debilitating neurodegenerative disease characterized by the loss of midbrain dopaminergic neurons (DaNs) and the abnormal accumulation of α-Synuclein (α-Syn) protein. Currently, no treatment can slow nor halt the progression of PD. Multiplications and mutations of the α-Syn gene (SNCA) cause PD-associated syndromes and animal models that overexpress α-Syn replicate several features of PD. Decreasing total α-Syn levels, therefore, is an attractive approach to slow down neurodegeneration in patients with synucleinopathy. We previously performed a genetic screen for modifiers of α-Syn levels and identified CDK14, a kinase of largely unknown function as a regulator of α-Syn. To test the potential therapeutic effects of CDK14 reduction in PD, we ablated Cdk14 in the α-Syn preformed fibrils (PFF)-induced PD mouse model. We found that loss of Cdk14 mitigates the grip strength deficit of PFF-treated mice and ameliorates PFF-induced cortical α-Syn pathology, indicated by reduced numbers of pS129 α-Syn-containing cells. In primary neurons, we found that Cdk14 depletion protects against the propagation of toxic α-Syn species. We further validated these findings on pS129 α-Syn levels in PD patient neurons. Finally, we leveraged the recent discovery of a covalent inhibitor of CDK14 to determine whether this target is pharmacologically tractable in vitro and in vivo. We found that CDK14 inhibition decreases total and pathologically aggregated α-Syn in human neurons, in PFF-challenged rat neurons and in the brains of α-Syn-humanized mice. In summary, we suggest that CDK14 represents a novel therapeutic target for PD-associated synucleinopathy.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Sinucleinopatias , Animais , Humanos , Camundongos , Ratos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Neurônios Dopaminérgicos/metabolismo , Mesencéfalo/metabolismo , Doenças Neurodegenerativas/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Sinucleinopatias/metabolismo , Sinucleinopatias/patologia
5.
iScience ; 27(4): 109415, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38523789

RESUMO

Brain organoids derived from human pluripotent stem cells are a promising tool for studying human neurodevelopment and related disorders. Here, we generated long-term cultures of cortical brain organoid slices (cBOS) grown at the air-liquid interphase from regionalized cortical organoids. We show that cBOS host mature neurons and astrocytes organized in complex architecture. Whole-cell patch-clamp demonstrated subthreshold synaptic inputs and action potential firing of neurons. Spontaneous intracellular calcium signals turned into synchronous large-scale oscillations upon combined disinhibition of NMDA receptors and blocking of GABAA receptors. Brief metabolic inhibition to mimic transient energy restriction in the ischemic brain induced reversible intracellular calcium loading of cBOS. Moreover, metabolic inhibition induced a reversible decline in neuronal ATP as revealed by ATeam1.03YEMK. Overall, cBOS provide a powerful platform to assess morphological and functional aspects of human neural cells in intact minimal networks and to address the pathways that drive cellular damage during brain ischemia.

6.
Spinal Cord Ser Cases ; 10(1): 15, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514608

RESUMO

STUDY DESIGN: Anonymous online survey OBJECTIVES: To investigate the priorities, needs and willingness to adopt nerve stimulation devices for managing neurogenic bladder and bowel function in people with spinal cord injury (SCI) living in Australia. SETTING: Online survey of people living with SCI in Australia. METHODS: This anonymous online survey used Qualtrics and was advertised via standard communication channels, such as advocacy groups representing the SCI community in Australia, social media, attending SCI sporting events and by word-of-mouth. RESULTS: Responses from 62 individuals (32% female, 68% male) were included. Bladder emptying through urethra without catheter was the highest priority for bladder function. Reducing time required for bowel routines and constipation were the top priorities regarding bowel function. The highest concern for internal/implanted devices was the 4% chance of device surgical removal, while wearing wires under the clothes was the main concern for external devices. 53% of respondents were willing to trial an implanted nerve stimulation device, while 70% would trial an external device to improve and gain independence in bladder and bowel function. CONCLUSION: The findings of this study highlighted the potential role in which nerve stimulation can have in addressing bladder and bowel dysfunction in people with SCI, and have also identified that there was a need for Australian physiotherapists to evaluate their role in bladder and bowel dysfunction. Results from this study can help guide further research in nerve stimulation devices for bladder and bowel dysfunction in people with SCI. SPONSORSHIP: n/a.


Assuntos
Traumatismos da Medula Espinal , Bexiga Urinária , Humanos , Masculino , Feminino , Defecação , Austrália , Inquéritos e Questionários , Traumatismos da Medula Espinal/complicações
7.
J Neurotrauma ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38468543

RESUMO

Brief exposure to repeated episodes of low inspired oxygen, or acute intermittent hypoxia (AIH), is a promising therapeutic modality to improve motor function after chronic, incomplete spinal cord injury (SCI). Although therapeutic AIH is under extensive investigation in persons with SCI, limited data are available concerning cardiorespiratory responses during and after AIH exposure despite implications for AIH safety and tolerability. Thus, we recorded immediate (during treatment) and enduring (up to 30 min post-treatment) cardiorespiratory responses to AIH in 19 participants with chronic SCI (>1 year post-injury; injury levels C1 to T6; American Spinal Injury Association Impairment Scale A to D; mean age = 33.8 ± 14.1 years; 18 males). Participants completed a single AIH (15, 60-sec episodes, inspired O2 ≈ 10%; 90-sec intervals breathing room air) and Sham (inspired O2 ≈ 21%) treatment, in random order. During hypoxic episodes: (1) arterial oxyhemoglobin saturation decreased to 82.1 ± 2.9% (p < 0.001); (2) minute ventilation increased 3.83 ± 2.29 L/min (p = 0.008); and (3) heart rate increased 4.77 ± 6.82 bpm (p = 0.010). Considerable variability in cardiorespiratory responses was found among subjects; some individuals exhibited large hypoxic ventilatory responses (≥0.20 L/min/%, n = 11), whereas others responded minimally (<0.20 L/min/%, n = 8). Apneas occurred frequently during AIH and/or Sham protocols in multiple participants. All participants completed AIH treatment without difficulty. No significant changes in ventilation, heart rate, or arterial blood pressure were found 30 min post-AIH p > 0.05). In conclusion, therapeutic AIH is well tolerated, elicits variable chemoreflex activation, and does not cause persistent changes in cardiorespiratory control/function 30 min post-treatment in persons with chronic SCI.

8.
Res Vet Sci ; 171: 105204, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38471347

RESUMO

The bioactivities of two commercially available probiotics and one chemical disinfectant were tested against strains of Vibrio parahaemolyticus (VPAHPND) and V. harveyi. This study aimed to determine shrimp pathogenic Vibrios' in vitro and in vivo sensitivities to commercial probiotics and a chemical disinfectant. The probiotics and disinfectant were tested first in vitro, followed by the in vivo trials. Results showed that upon administration of probiotics either through diet or adding into the tank water, the survivability of shrimp was increased during challenge with VPAHPND and V. harveyi. Also, the disinfectant was tested against the same pathogens and showed positive bactericidal effects at 2500 ppm and 5000 ppm. The present findings suggest that adding probiotics to the rearing water or the shrimp feeds effectively prevents infection by lowering the load of pathogenic bacteria. In comparison, the effectiveness of the disinfectant (PUR) depends on its appropriate concentration and timing of application. It is not only limited to rearing water but is also applicable for decontaminating pond liners, tanks, and other paraphernalia.


Assuntos
Penaeidae , Probióticos , Vibrioses , Vibrio parahaemolyticus , Animais , Vibrioses/prevenção & controle , Vibrioses/veterinária , Penaeidae/microbiologia , Probióticos/farmacologia , Necrose/veterinária , Água
9.
Brain Spine ; 4: 102773, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38465280

RESUMO

Introduction: TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on mortality is about 10% across all ages. Amantadine hydrochloride is one of the most commonly prescribed medications for patients undergoing inpatient neurorehabilitation who have disorders of consciousness.6 It is a dopamine (DA) receptor agonist and a N-Methyl-D-aspartate (NMDA) receptor antagonist via dopamine release and dopamine reuptake inhibition. The current study will synthesize the current available evidence and show the effect of Amantadine in functional improvement after TBI. Research question: Does Amantadine have an effect on functional improvement of TBI patients? Material and methods: This systematic review included all randomized placebo-controlled trials that compare the use of Amantadine versus placebo for functional improvement of patients after TBI. Outcome measures included DRS, GCS and/or GOS scores. Results: Three studies with a total of 281 patients were included in the quantitative analyses. GRADE assessments show that there was a high certainty of evidence for functional improvement in terms of DRS scores. Discussion and conclusion: Evidence of this review show that the use of Amantadine may have a beneficial effect on functional outcome in moderate to severe traumatic brain injuries among adult patients. Given the still-limited body of knowledge, more relevant studies must be made exploring the impact of Amantadine therapies on promoting functional recovery within the brain injury rehabilitation care continuum, with the goals of achieving larger sample sizes and establishing the early- or later-treatment beneficial effects.

10.
Environ Res ; 250: 118376, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38354891

RESUMO

Antibiotic mycelial dreg (AMD) has been categorized as hazardous waste due to the high residual hazardous contaminants. Inappropriate management and disposal of AMD can cause potential environmental and ecological risks. In this study, the potential of pleuromutilin mycelial dreg (PMD) as a novel feedstock for preparing tetracycline hydrochloride (TC) adsorbent was explored to achieve safe management of PMD. The results suggested that residual hazardous contaminants were completely eliminated after pyrolysis. With the increase of pyrolysis temperature, the yields, H/C, O/C, (O + N)/C, and pore size in PMD-derived biochars (PMD-BCs) decreased, while BET surface area and pore volume increased, resulting in the higher stability of the PMD-BCs prepared from higher temperatures. The TC adsorption of the PMD-BCs increased from 27.3 to 46.9 mg/g with the increase of the pyrolysis temperature. Surprisingly, pH value had a strong impact on the TC adsorption, the adsorption capacity of BC-450 increased from 6.5 to 71.1 mg/g when the solution pH value increased from 2 to 10. Lewis acid-base interaction, pore filling, π-π interaction, hydrophobic interaction, and charge-assisted hydrogen bond (CAHB) are considered to drive the adsorption. This work provides a novel pathway for the concurrent detoxification and reutilization of AMD.

12.
Sci Total Environ ; 917: 170478, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38301780

RESUMO

Denitrifying woodchip bioreactors (DBRs) are an established nitrate mitigation technology, but uncertainty remains on their viability for phosphorus (P) removal due to inconsistent source-sink behaviour in field trials. We investigated whether iron (Fe) redox cycling could be the missing link needed to explain P dynamics in these systems. A pilot-scale DBR (Aotearoa New Zealand) was monitored for the first two drainage seasons (2017-2018), with supplemental in-field measurements of reduced solutes (Fe2+, HS-/H2S) and their conjugate oxidised species (Fe3+/SO42-) made in 2021 to constrain within-reactor redox gradients. Consistent with thermodynamics, the dissolution of Fe3+(s) to Fe2+(aq) within the DBR sequentially followed O2, NO3- and MnO2(s) reduction, but occurred before SO42- reduction. Monitoring of inlet and outlet chemistry revealed tight coupling between Fe and P (inlet R2 0.94, outlet R2 0.85), but distinct dynamics between drainage seasons. In season one, outlet P exceeded inlet P (net P source), and coincided with elevated outlet Fe2+, but at ⁓50 % lower P concentrations relative to inlet Fe:P ratios. In season 2 the reactor became a net P sink, coinciding with declining outlet Fe2+ concentrations (indicating exhaustion of Fe3+(s) hydroxides and associated P). In order to characterize P removal under varying source dynamics (i.e. inflows vs in-situ P releases), we used the inlet Fe vs P relationship to estimate P binding to colloidal Fe (hydr)oxide surfaces under oxic conditions, and the outlet Fe2+ concentration to estimate in-situ P releases associated with Fe (hydr)oxide reduction. Inferred P-removal rates were highest early in season 1 (k = 0.60 g P m3 d-1; 75-100 % removal), declining significantly thereafter (k = 0.01 ± 0.02 g P m3 d-1; ca. 3-67 % removal). These calculations suggest that microbiological P removal in DBRs can occur at comparable magnitudes to nitrate removal by denitrification, depending mainly on P availability and hydraulic retention efficiency.


Assuntos
Nitratos , Fósforo , Compostos de Manganês , Desnitrificação , Óxidos , Reatores Biológicos , Nitrogênio
13.
Adv Mater ; : e2312513, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38288908

RESUMO

Polymer electrolytes have received tremendous interest in the development of solid-state batteries, but often fall short in one or more key properties required for practical applications. Herein, a rigid gel polymer electrolyte prepared by immobilizing a liquid mixture of a lithium salt and poly(ethylene glycol) dimethyl ether with only 8 wt% poly(2,2'-disulfonyl-4,4'-benzidine terephthalamide) (PBDT) is reported. The high charge density and rigid double helical structure of PBDT lead to formation of a nanofibrillar structure that endows this electrolyte with stronger mechanical properties, wider temperature window, and higher battery rate capability compared to all other poly(ethylene oxide) (PEO)-based electrolytes. The ion transport mechanism in this rigid polymer electrolyte is systematically studied using multiple complementary techniques. Li/LiFePO4 cells show excellent capacity retention over long-term cycling, with thermal cycling reversibility between ambient temperature and elevated temperatures, demonstrating compelling potential for solid-state batteries targeting fast charging at high temperatures and slower discharging at ambient temperature.

14.
J Clin Sleep Med ; 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38205944

RESUMO

STUDY OBJECTIVES: This study evaluated the prevalence and correlates of insomnia in male Veterans with MST who currently receive care within a VAMC. METHODS: We evaluated cross-sectional data from a VAMC (N=138) using the following instruments: ISI, PCL-5, QIDS-SR, AUDIT-C, and a nightmare question for insomnia, PTSD, depression, and drinking, respectively. Bivariate and multivariable analyses assessed the relationship between ISI and other clinical variables. RESULTS: About 31.9% screened positive for MST. When compared to those without MST (MST-), those with MST (MST+) had a higher prevalence of insomnia (95.5% vs 81.9%), higher ISI (20±5.1 vs. 16.7±7.2, p=0.003) and PCL-5 (48.5±14.4 vs. 38.2±19.8, p=0.0008) total scores. In the multivariable models, the ISI total score was associated with the PCL-5 total score (p=0.015) in MST+ individuals and with QIDS-SR (p<0.001) in MST- individuals. CONCLUSIONS: Most Veterans with MST within the VHA had insomnia, which was associated with their underlying psychiatric comorbidity.

15.
Dev Psychopathol ; : 1-9, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38273706

RESUMO

The effects of maternal postpartum depression (PPD) on offspring emotion regulation (ER) are particularly deleterious as difficulties with ER predict an increased risk of psychopathology. This study examined the impact of maternal participation in a public health nurse (PHN)-delivered group cognitive behavioral therapy (CBT) intervention on infant ER. Mothers/birthing parents were ≥ 18 years old with an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10, and infants were < 12 months. Between 2017 and 2020, 141 mother-infant dyads were randomized to experimental or control groups. Infant ER was measured at baseline (T1) and nine weeks later (T2) using two neurophysiological measures (frontal alpha asymmetry (FAA) and high-frequency heart rate variability (HF-HRV)), and informant-report of infant temperament. Mothers were a mean of 30.8 years old (SD = 4.7), 92.3% were married/ common-law, and infants were a mean of 5.4 months old (SD = 2.9) and 52.1% were male. A statistically significant group-by-time interaction was found to predict change in HF-HRV between T1 and T2 (F(1,68.3) = 4.04, p = .04), but no significant interaction predicted change in FAA or temperament. Results suggest that PHN-delivered group CBT for PPD may lead to adaptive changes in a neurophysiological marker of infant ER, highlighting the importance of early maternal intervention.

16.
J Diabetes Sci Technol ; 18(2): 266-272, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37747075

RESUMO

BACKGROUND: Accurately identifying eating patterns, specifically the timing, frequency, and distribution of eating occasions (EOs), is important for assessing eating behaviors, especially for preventing and managing obesity and type 2 diabetes (T2D). However, existing methods to study EOs rely on self-report, which may be prone to misreporting and bias and has a high user burden. Therefore, objective methods are needed. METHODS: We aim to compare EO timing using objective and subjective methods. Participants self-reported EO with a smartphone app (self-report [SR]), wore the ActiGraph GT9X on their dominant wrist, and wore a continuous glucose monitor (CGM, Abbott Libre Pro) for 10 days. EOs were detected from wrist motion (WM) using a motion-based classifier and from CGM using a simulation-based system. We described EO timing and explored how timing identified with WM and CGM compares with SR. RESULTS: Participants (n = 39) were 59 ± 11 years old, mostly female (62%) and White (51%) with a body mass index (BMI) of 34.2 ± 4.7 kg/m2. All had prediabetes or moderately controlled T2D. The median time-of-day first EO (and interquartile range) for SR, WM, and CGM were 08:24 (07:00-09:59), 9:42 (07:46-12:26), and 06:55 (04:23-10:03), respectively. The median last EO for SR, WM, and CGM were 20:20 (16:50-21:42), 20:12 (18:30-21:41), and 21:43 (20:35-22:16), respectively. The overlap between SR and CGM was 55% to 80% of EO detected with tolerance periods of ±30, 60, and 120 minutes. The overlap between SR and WM was 52% to 65% EO detected with tolerance periods of ±30, 60, and 120 minutes. CONCLUSION: The continuous glucose monitor and WM detected overlapping but not identical meals and may provide complementary information to self-reported EO.


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , Punho , Autorrelato , Estado Pré-Diabético/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Monitoramento Contínuo da Glicose , Automonitorização da Glicemia , Glicemia , Obesidade/diagnóstico
17.
J Environ Manage ; 351: 119692, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38039589

RESUMO

Chemical contaminants, such as pesticides, pharmaceuticals and industrial compounds are ubiquitous in surface water and sediment in areas subject to human activity. While targeted chemical analysis is typically used for water and sediment quality monitoring, there is growing interest in applying effect-based methods with in vitro bioassays to capture the effects of all active contaminants in a sample. The current study evaluated the biological effects in surface water and sediment from two contrasting catchments in Aotearoa New Zealand, the highly urbanised Whau River catchment in Tamaki Makaurau (Auckland) and the urban and mixed agricultural Koreti (New River) Estuary catchment. Two complementary passive sampling devices, Chemcatcher for polar chemicals and polyethylene (PED) for non-polar chemicals, were applied to capture a wide range of contaminants in water, while composite sediment samples were collected at each sampling site. Bioassays indicative of induction of xenobiotic metabolism, receptor-mediated effects, genotoxicity, cytotoxicity and apical effects were applied to the water and sediment extracts. Most sediment extracts induced moderate to strong estrogenic and aryl hydrocarbon (AhR) activity, along with moderate toxicity to bacteria. The water extracts showed similar patterns to the sediment extracts, but with lower activity. Generally, the polar Chemcatcher extracts showed greater estrogenic activity, photosynthesis inhibition and algal growth inhibition than the non-polar PED extracts, though the PED extracts showed greater AhR activity. The observed effects in the water extracts were compared to available ecological effect-based trigger values (EBT) to evaluate the potential risk. For the polar extracts, most sites in both catchments exceeded the EBT for estrogenicity, with many sites exceeding the EBTs for AhR activity and photosynthesis inhibition. Of the wide range of endpoints considered, estrogenic activity, AhR activity and herbicidal activity appear to be the primary risk drivers in both the Whau and Koreti Estuary catchments.


Assuntos
Rios , Poluentes Químicos da Água , Humanos , Rios/química , Água/análise , Poluentes Químicos da Água/análise , Agricultura , Bioensaio , Polietileno , Monitoramento Ambiental/métodos , Sedimentos Geológicos/química
18.
Neurosurgery ; 94(1): 202-211, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37931081

RESUMO

BACKGROUND AND OBJECTIVES: No study has comprehensively examined the delivery of neurosurgical care in the Philippines, a lower-middle-income country in Southeast Asia with a total population of 109 million. We aimed to quantify the workforce, map the distribution, and characterize the clinical practice of neurosurgeons across the 17 regions and 81 provinces of the Philippines. METHODS: An online survey was sent to all fellows of the Academy of Filipino Neurosurgeons and all graduates of neurosurgical training programs in the country. Neurosurgeons who have been in active clinical practice for at least 1 year were eligible to participate. A database of Filipino neurosurgeons was generated through personal communications, correspondence with neurosurgery departments, and accessing publicly available information. The top neurosurgical procedures were identified to estimate the overall volume of neurosurgical disease. RESULTS: There are 174 neurosurgeons practicing in the Philippines or approximately one neurosurgeon for every 600 000 people. In 9 provinces, neurosurgeons were only available part-time, and 35 provinces had no neurosurgeons at all, equivalent to an underserved population of 24 million people. Among 99 survey respondents, the median numbers of neurosurgical consults and operations every month were 30 (IQR:35) and 8 (IQR:8), respectively. The top neurosurgical procedures were burr holes/craniotomy for traumatic brain injury, craniotomy for stroke, and biopsy/resection of brain tumors. There are an estimated 93 498 cases requiring essential neurosurgery every year. CONCLUSION: Although positive trends have been observed in the number, distribution, and composition of neurosurgeons in the Philippines, there remains a large workforce deficit that needs to be addressed to provide timely, quality, and affordable neurosurgical care to the entire population.


Assuntos
Neurocirurgia , Humanos , Filipinas , Neurocirurgia/educação , Neurocirurgiões , Procedimentos Neurocirúrgicos , Recursos Humanos
19.
Dev Psychol ; 60(2): 271-283, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37971827

RESUMO

The risk potentiation model of cognitive control posits that inhibitory control heightens children's risk for problematic outcomes in the context of shyness because it limits shy children's ability to engage flexibly with their environment. Although there is empirical support for the risk potentiation model, most studies have been restricted to parent report of children's outcomes and do not consider the influence of shyness and inhibitory control on other children's social behavior. In the present study, we used an actor-partner interdependence model to examine whether shyness and inhibitory control at Time 1 (N = 105, 52 girls, Mage = 3.50 years; 87% White; Mincome = between $75,000 and $100,000 in Canadian dollars) predicted children's own and their partner's observed social behavior with an unfamiliar peer at Time 2 (Mage = 4.76 years). When the child's own inhibitory control was high, the child's own shyness was negatively associated with their own approach behaviors but negatively associated with their partner's avoidance behaviors. However, when the child's own inhibitory control was low, the child's own shyness was unrelated to their own approach behaviors but positively associated with their partner's avoidance behaviors. Although inhibitory control was negatively associated with approach-related behavior for some shy children, this did not translate to more avoidance from the social partner. These results highlight the importance of examining the child's own behavior in addition to their partner's behavior when considering children's socioemotional development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Timidez , Comportamento Social , Criança , Feminino , Humanos , Pré-Escolar , Canadá , Instituições Acadêmicas , Grupo Associado
20.
Malar J ; 22(1): 348, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957702

RESUMO

BACKGROUND: The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. METHODS: Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. RESULTS: From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63). CONCLUSIONS: Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. TRIAL REGISTRATION: The study is registered at Clinical Trial.gov NCT05354258.


Assuntos
Antimaláricos , Helmintos , Malária , Animais , Humanos , Criança , Masculino , Feminino , Antimaláricos/efeitos adversos , Praziquantel/efeitos adversos , Albendazol/efeitos adversos , Administração Massiva de Medicamentos , Estações do Ano , Estudos de Viabilidade , Vitamina A/uso terapêutico , Malária/epidemiologia , Quimioprevenção/efeitos adversos , Quimioprevenção/métodos
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