Behavioral Alterations Research Articles

Phosphatidic acid is involved in regulation of autophagy in neurons in vitro and in vivo.

Major depressive disorder (MDD) is a common and severe psychiatric disease, which does not only lead to variety of neuropsychiatric symptoms, but unfortunately in a relatively large proportion of cases also to suicide. The pathogenesis of MDD still requires definition. We have previously shown that ceramide is increased in the blood plasma of patients with MDD. In mouse models of MDD, which are induced by treatment with corticosterone or application of chronic unpredictable stress, increased blood plasma ceramide also increased and caused an inhibition of phospholipase D in endothelial cells of the hippocampus and reduced phosphatidic acid levels in the hippocampus. Here, we demonstrated that corticosterone treatment of PC12 cells resulted in reduced cellular autophagy, which is corrected by treatment with phosphatidic acid. In vivo, treatment of mice with corticosterone or chronic unpredictable stress also reduced autophagy in hippocampus neurons. Autophagy was normalized upon i.v. injection of phosphatidic acid in these mouse models of MDD. In an attempt to identify targets of phosphatidic acid in neurons, we demonstrated that corticosterone reduced levels of the ganglioside GM1 in PC-12 cells and the hippocampus of mice, which were normalized by treatment of cells or i.v. injection of mice with phosphatidic acid. GM1 application also normalized autophagy in cultured neurons. Phosphatidic acid and GM1 corrected stress-induced alterations in behavior, i.e., mainly anxiety and anhedonia, in experimental MDD in mice. Our data suggest that phosphatidic acid may regulate via GM1 autophagy in neurons.

Training Protocol for Nellore Cattle in Respirometry Flow Trials Using Non-Ventilated Facial Mask.

Training is instrumental in identifying and selecting cattle that exhibit greater cooperation with experimental conditions required in flow respirometry assays, like restraint and the use of a valved facial mask. In our study, a tailored training protocol for Nellore cattle facilitated their participation in flow respirometry assays with a valved facial mask. Over 127 days, 30 entire Nellore males, weighing 450 ± 25 kg and averaging 32 ± 2 months, underwent training from May to September 2022. The regimen involved gradually altering the animals' environment and providing positive reinforcement, divided into three phases. Physiological and behavioral responses to containment routines and facial mask use were meticulously assessed. Principal component analyses revealed dissimilarity patterns among the animals. Animals classified as less reactive showed increased acceptance of handling, reduced reactions to weighing, and greater tolerance of the facial mask. In the final phase, the least reactive animals tolerated wearing a valved mask for extended periods without notable changes in respiratory rate. The training protocol effectively identified and selected Nellore cattle displaying enhanced cooperation with restraint and mask use during flow respirometry assays, without apparent behavioral or physiological alterations.

Locomotor and gait changes in the LPS model of neuroinflammation are correlated with inflammatory cytokines in blood and brain.

Lipopolysaccharide (LPS) challenge in mice has been used to identify the mechanisms and therapeutics for neuroinflammation. In this study, we aimed to comprehensively evaluate the behavioral changes including locomotion, exploration, and memory, correlating them with a panel of thirteen inflammatory cytokines in both blood and brain.We found that acute LPS administration (0.83 mg/Kg i.p.) reduced body weight, food intake, and glucose levels compared to the saline-injected mice, concomitant with decreased activity in home cage monitoring. Locomotion was significantly reduced in Open Field, Introduced Object, and Y-Maze tests. Decreased exploratory behavior in the Y-Maze and Introduced Object tests was noticed, by measuring the number of arms explored and object interaction time, respectively. Additionally, in rotarod, LPS administration led to a significant decrease in the distance achieved, while in the MouseWalker, LPS led to a reduction in average velocity.LPS induced a decrease in microglia ramification index in the motor cortex and the striatum, while surprisingly a reduction in microglia number was observed in the motor cortex.The concentrations of thirteen cytokines in the blood were significantly altered, while only CXCL1, CCL22, CCL17, G-CSF, and IL-12p40 were changed in the brain. Correlations between cytokine levels in blood and brain were found, most notably for CCL17 and CCL22. TGFβ was the only one with negative correlations to other cytokines. Correlations between cytokines and behavior changes were also disclosed, especially for CCL17, CCL22, G-CSF, and IL-6 and negatively for TGFβ and IL-10.In summary, our study employing acute LPS challenge in mice has revealed a comprehensive profile of behavioral alterations alongside significant changes in inflammatory cytokine levels, both in peripheral blood and brain tissue. These findings contribute to a deeper understanding of the interplay between inflammation and behavior, with possible implications for identifying prognostics and therapeutic targets for neuroinflammatory conditions.

Commonalities of platelet dysfunction in heart failure with preserved ejection fraction and underlying comorbidities.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a lack of a specific targeted treatment and a complex, partially unexplored pathophysiology. Common comorbidities associated with HFpEF are hypertension, atrial fibrillation, obesity and diabetes. These comorbidities, combined with advanced age, play a crucial role in the initiation and development of the disease through the promotion of systemic inflammation and consequent changes in cardiac phenotype. In this context, we suggest platelets as important players due to their emerging role in vascular inflammation. This review provides an overview of the role of platelets in HFpEF and its associated comorbidities, including hypertension, atrial fibrillation, obesity and diabetes mellitus, as well as the impact of age and sex on platelet function. These major HFpEF-associated comorbidities present alterations in platelet behaviour and in features linked to platelet size, content and reactivity. The resulting dysfunctional platelets can contribute to further increase inflammation, oxidative stress and endothelial dysfunction, suggesting an active role of these cells in the initiation and progression of HFpEF. Recent evidence shows that reduced platelet count and elevated mean platelet volume are associated with worsening heart failure in HFpEF patients. However, the specific mechanisms by which platelets contribute to HFpEF development and progression are still largely unexplored, with only a few studies investigating platelet function in HFpEF. We discuss the limited yet significant body of research investigating platelet function in HFpEF, emphasizing the need for more comprehensive studies. Additionally, we explore the potential mechanisms through which platelets may influence HFpEF, such as their interactions with the vascular endothelium and the secretion of bioactive molecules like cytokines, chemokines and RNA molecules. These interactions and secretions may play a role in modulating vascular inflammation and contributing to the pathophysiological landscape of HFpEF. The review underscores the necessity for future research to elucidate the precise contributions of platelets to HFpEF, aiming to potentially identify novel therapeutic targets and improve patient outcomes. The evidence presented herein supports the hypothesis that platelets are not merely passive bystanders but active participants in the pathophysiology of HFpEF and its comorbidities.

Cacna1c deficiency in forebrain glutamatergic neurons alters behavior and hippocampal plasticity in female mice

CACNA1C, coding for the α1 subunit of L-type voltage-gated calcium channel (LTCC) Cav1.2, has been associated with multiple psychiatric disorders. Clinical studies have revealed alterations in behavior as well as in brain structure and function in CACNA1C risk allele carriers. These findings are supported by rodent models of Cav1.2 deficiency, which showed increased anxiety, cognitive and social impairments as well as a shift towards active stress-coping strategies. These behavioral alterations were accompanied by functional deficits, such as reduced long-term potentiation (LTP) and an excitation/inhibition (E/I) imbalance. However, these preclinical studies are largely limited to male rodents, with few studies exploring sex-specific effects. Here, we investigated the effects of Cav1.2 deficiency in forebrain glutamatergic neurons in female conditional knockout (CKO) mice. CKO mice exhibited hyperlocomotion in a novel environment, increased anxiety-related behavior, cognitive deficits, and increased active stress-coping behavior. These behavioral alterations were neither influenced by the stage of the estrous cycle nor by the Nex/Neurod6 haploinsufficiency or Cre expression, which are intrinsically tied to the utilization of the Nex-Cre driver line for conditional inactivation of Cacna1c. In the hippocampus, Cav1.2 inactivation enhanced presynaptic paired-pulse facilitation without altering postsynaptic LTP at CA3-CA1 synapses. In addition, CA1 pyramidal neurons of female CKO mice displayed a reduction in dendritic complexity and spine density. Taken together, our findings extend the existing knowledge suggesting Cav1.2-dependent structural and functional alterations as possible mechanisms for the behavioral alterations observed in female Cav1.2-Nex mice.

Rising global temperatures and its impact on sleep behavior of male redheaded bunting (Emberiza bruniceps).

Anthropogenic global warming is one of the most pervasive threats to nature and biodiversity. The magnitude with which earths' temperature is rising is affecting every lifeform uniquely; however, the studies highlighting the impacts of global warming on avian sleep are scarce. To this end, the present study was aimed at analyzing the impact of global warming on sleep behavior of a nocturnal migrant, Emberiza bruniceps. For this purpose, the birds were divided into two groups (N = 15 each), subjected to high (35 ± 1°C) and low (19 ± 1°C) temperature schedule with concurrent exposure to 8L:16D (short day; SD) photoperiod followed by 13L:11D (long day; LD). The experiment continued till 7 cycles of zugunruhe (LD) in birds. The results reveal significant impact of temperature treatment on initiation and quality of zugunruhe. Temporal distribution of activity and rest varied according to the temperature provided. Focusing on rest and specifically on sleep of birds, high ambient temperatures resulted in greater sleep fragmentation (evident by increased awakenings during night), whereas low temperature created a sleep conducive environment (evident by abundance of back sleep). Besides postural differences, high temperature resulted in reduced sleep duration, sleep onset latency and circulating plasma melatonin levels in comparison with low temperature suggesting the negative impact of high temperature on different sleep attributes. Not only sleep, seasonal physiology of birds such as hyperphagia, gain in body mass, and fat stores showed significant reduction in high temperature condition. Besides behavioral and physiological alterations, high ambient temperature led to elevated expression of temperature sensitive (trpv4, trpm8, hspa8, and hsp70) genes. Enhanced expression of chrm3 (responsible for wakefulness) also affirms sleep fragmentation in response to high temperature. Thus, the study highlights the negative impact of high temperature on birds' sleep behavior and seasonal physiology.

Change in Nfkb/Nrf2/Bax Levels by High Monomeric Polyphenols Berries Extract (HMPBE) in Acute and Chronic Secondary Brain Damage.

High Monomeric Polyphenols Berries Extract (HMPBE) is a formula highly rich in polyphenols clinically proven to enhance learning and memory. It is currently used to enhances cognitive performance including accuracy, working memory and concentration. Here, we investigated for the first time the beneficial effects of HMPBE in a mouse model of acute and chronic traumatic brain injury (TBI). HMPBE, at the dose of 15 mg/kg was able to reduce histological alteration as well as inflammation and lipid peroxidation. HMPBE ameliorate TBI by improving Nrf-2 pathway, reducing Nf-kb nuclear translocation and apoptosis, and ameliorating behavioral alteration such as anxiety and depression. Moreover, in the chronic model of TBI, HMPBE administration restored the decline of Tyrosine Hydroxylase (TH) and dopamine transporter (DAT) and the accumulation of a-synuclein into the midbrain region. This finding correlates the beneficial effect of HMPBE administration with the onset of parkinsonism related to traumatic brain damage. The data may open a window for developing new support strategies to limit the neuroinflammation event of acute and chronic TBI.

8273 ACTH-Dependent Cushing's Syndrome Due To Metastatic Cervical Cancer: A Case Report

Abstract Disclosure: T.D. Bertolacini da Silva: None. V.D. Kamura: None. P.D. Buchalla: None. A.G. Simoes: None. S. Glina: None. Z.M. Campos: None. I.S. Rosa: None. P.X. Santi: None. Background: The association of dependent Cushing's ACTH Syndrome with certain types of cancer is well known, such as small cell lung cancer, enteropancreatic tumors, thymoma, thyroid cancer, however, in association with cervical cancer there are almost no cases described. Clinical Case: A 39-year women, showed about 2.5 years ago with abnormal uterine bleeding, being submitted to colposcopy with the presence of exophytic, friable and hardened lesion in the anterior region of the cervix. Biopsies revealed adenocarcinoma, endometrioid type and immunohistochemistry (IHC) positive for: Ki-67 80%, vimentin and CEA. Patient underwent initial treatment with chemotherapy and radiotherapy, losing follow-up with Oncology. After 1 year, the patient was admitted to a hospital with behavioral alteration, including suicidal ideation, muscle weakness, breast enlargement and hair growth on the face. On physical examination, there was the presence of hypertension, hyperglycemia, centripetal obesity, legs edema and hirsutism. Due to the typical symptoms, the hypothesis of Cushing's Syndrome was made and laboratory and imaging tests were requested. Initial tests: K 1.9 mmol/L (3.5-5.6 mmol/L), Na 146 mmol/L (137-145 mmol/L), TSH 0.25 uIU/mL (0.49-5.58 uIU/mL/mL), free T4 0.78 ng/dL (0.89-1.53 ng/dL), pH 7.57 (7.36-7.41), HCO3 43.1 mmol/L (23-27 mmol/L), LH 0.15 mIU/mL (1.9-12.5 mIU/mL), FSH 1.02 mIU/mL (2.5-10 mIU/mL), estradiol 84.1 pg/mL (< 32.2 pg/mL), ACTH 365.0 pg/mL and 98.6 pg/mL (< 46 pg/mL), cortisol > 75 ug/dL (5.27-22.5 ug/dL), urinary cortisol 3790 ug/24h (4-60 ug/24h), testosterone 333 ng/dL (12 - 59 ng/dL), free testosterone 10.12 ng/dL (0.08-1.1 ng/dL), dehydrotestosterone 1,620 pg/mL (< 596 pg/mL), androstenedione > 10 ng/mL (0.3-3.3 ng/mL). The dosages of ACTH and cortisol were performed after the dexamethasone suppression test and a pituitary MRI was normal. The MRI of the abdomen and pelvis showed multiple solid nodular lesions in liver with varying sizes compatible with metastatic disease, in addition, showed the increase in the bilateral volume of the adrenals. Liver biopsy was performed exhibiting carcinoma infiltration with IHC compatible with neuroendocrine tumor, positive for: CDX-2, SATB2, chromogranin A and synaptophysin (waiting for ACTH). Other primary sites were ruled out. The patient was initially treated with Etomidate in a continuous infusion, without tolerance and little control of hypercortisolism, after initiating Ketoconazole which was suspended due to hepatotoxicity, and then underwent bilateral adrenalectomy. Unfortunately, she died 4 days after surgery due to septic shock. Conclusion: This case report brings a very rare association of Cushing's syndrome by ectopic ACTH due to cervical cancer, with less than 10 cases reported, in which we highlight the diagnostic difficulty, the complexity of treatment and the high risk of morbidity and mortality. Presentation: 6/1/2024

The Impact of the COVID-19 Pandemic on Trading in the Stock Market: A Legal Perspective

The COVID-19 pandemic significantly impacted global stock markets, leading to unprecedented volatility and legal challenges. This study explores how the pandemic altered trading behavior and examines the associated legal ramifications. In March 2020, stock markets experienced a sharp decline, prompting the U.S. Federal Reserve and other regulatory bodies to intervene. While markets rebounded, volatility persisted, introducing heightened risks for investors. Non- professional investors became more active, complicating regulatory oversight. From a legal perspective, the pandemic raised concerns about stock price manipulation, insider trading, and market abuse. Regulators, like the U.S. Securities and Exchange Commission (SEC), responded by implementing temporary measures to maintain market integrity. These legal frameworks, designed for traditional crises, struggled to address the unique challenges posed by COVID-19. Furthermore, the pandemic revealed gaps in existing laws, prompting calls for updated regulations to manage market disruptions during non-financial crises. The study underscores the need for ongoing legal adaptation to safeguard markets and prevent exploitation during global emergencies. As the pandemic evolved, so did the legal landscape, with cases emerging that highlighted both opportunistic trading and regulatory inadequacies. This research contributes to understanding the intersection of market volatility and legal frameworks in times of crisis.

Growth performance, blood health, and antioxidant status of freshwater carp under brackish water rearing system: Sustainable aquaculture approach in arid and semi-arid conditions

Global warming, water salinization, and increased anthropogenic usage of freshwater sources have had severe effects on water sources and aquaculture practices, which is consequently putting pressure on aquatic fauna and fish production. Hence, brackish water can be used as an alternative and sustainable approach to meet the increasing food requirements. Four groups with triplicates were designed to evaluate the impact of brackish water on Cirrhinus mrigala (n = 100) for 180 days; T0: control group (freshwater), T1: (5.45 ppt salinity), T2: (8.45 ppt salinity) and T3 (12.45 ppt salinity). Little behavioural alterations and normal feeding were observed in all experimental groups as compared to control group, except group T3. Survival rate was 100 % in all groups excluding group T3, which had shown 88 % survival rate (P < 0.05), while mean weight gain and length gain were observed better with low FCR in T1 and T2 groups (P < 0.05) but best growth rate observed at 5 ppt salinity level. Significant reduction in haemoglobin (Hb), hematocrit (HCT), red blood cells (RBCs) and increase in white blood cells (WBCs) and platelets (PLTs) was observed in group T3 compared to other experimental groups (P < 0.05). ALT, AST, ALP, urea, creatinine, and triglycerides, exhibited significant changes in T3 group after 180 days (P < 0.05). Erythrocytes had shown morphological alterations as; micronuclei, notching, blebbing, pear-shaped nuclei and spherocytes in T3 group. Significant increase in DNA damage in various tissues had indicated potential genotoxic impact of highly saline brackish water. Oxidative stress markers were increased significantly and antioxidants reduced (P < 0.05) at high salinity level brackish water (T3) until 180 days. In conclusion, C. mrigala can potentially grow well in brackish water system at 5 ppt salinity whereas, rise in salinity level (12 ppt) is detrimental to freshwater fish health and growth.

Digitally accessible space: Discovery of the distinctive locational characteristics of restaurants with online reservation

The widespread adoption of ICT including mobile apps and their online services has significantly reshaped human activities in urban spaces. The complex interaction between ICT on urban space presents challenges in understanding their relationships. This study aims to discover the empirical evidence of the spatial variance of urban space linked to ICT. To pursue this objective, this study defines spaces that leverage ICT-based activities as Digitally Accessible Spaces (DAS), and choose restaurants that provide online reservation services through NAVER, which is the most dominant search engine in South Korea. Based on fundamental measurements in location theory, we stratified the entire area in Seoul into four groups in order of profitability. Using the location quotient (LQ), we quantified the locational characteristics of DAS compared to overall restaurants. Consequently, three measurements, which are density of marketplace, distance from public transit, and proper land use, indicate that the second-tier profitable areas commonly possess the largest portion of DAS. These characteristics provided empirical evidence supporting previous studies highlighting the liberation effect and altered travel behavior resulting from ICT-based activity through qualitative and theoretical approaches. We expect that this study can contribute to further research related to the interaction between digital space and physical space.

Evaluating intra- and inter-life stage density-dependent dynamics for management of perennial amphidromous fish.

Compensatory density-dependent (DD) processes play an integral role in fisheries management by underpinning fundamental population demographics. However, DD processes are often assessed only for specific life stages, likely resulting in misleading evaluations of population limitations. Here, we assessed the relative roles of intra- and inter-life stage DD interactions in shaping the population dynamics of perennial freshwater fish with demographically open populations. Specifically, we monitored populations of amphidromous banded kōkopu (Galaxias fasciatus), giant kōkopu (Galaxias argenteus), and shortjaw kōkopu (Galaxias postvectis) in five streams where migratory post-larvae are fished and in three no-take ("closed") streams located on New Zealand's South Island for two years. Using mark-recapture data, we investigated whether fishing altered densities of "small" (non-territorial recruits ≤1-year-old) and "large" (territorial fish >1-year-old) kōkopu size classes, and how subsequent density shifts affected the apparent survival and growth of each class while controlling for other confounding factors (e.g., habitat characteristics). We found that closed areas had substantially greater biomass of small kōkopu, particularly following the two-month fishing season. Despite this greater influx of recruits, there was no difference in the biomass of large kōkopu at the species level, or as a combined assemblage between stream types. This indicated that although fishing of post-larvae reduced recruit influxes into adult habitats, there was no subsequent evidence of recruitment-limitation within adult populations. Instead, kōkopu demographics were underpinned by intra- and inter-life stage DD competition and predation. Greater large fish densities played a key role in regulating the survival, growth, and/or presence of various kōkopu classes. In contrast, greater small fish densities had positive effects on the growth of opportunistic and insectivorous congeners, likely due to cannibalism and altered foraging behaviors, respectively. Our study details the prominent role of intra- and inter-life stage DD interactions in regulating the population dynamics of perennial migratory freshwater fishes, even in populations with inhibited recruit and juvenile availability. We emphasize the importance for fisheries management to implement recruitment dependencies and complex interactions between distinct life stages to avoid deleterious DD responses and ensure population persistence.

Tourists’ Experiences During the Covid-19 Pandemic in Plateau State, Nigeria: An Empirical Evaluation Using Chaos Theory

The safety of tourists’ health when visiting any tourism business is critical in tourism management and development. By using chaos theory, this study aimed to understand how 408 tourists in Plateau State, Nigeria, behaved toward tourism-related businesses during the COVID-19 pandemic. Completed and retrieved responses were analyzed descriptively using an inductive method, following a pragmatic approach. The findings of this investigation are consistent with chaos theory. Results from our survey indicate that 93% of tourists took precautions. This suggests that in an otherwise random and chaotic period of the tourism crisis, self-organization brought order and new stability. With a mean score of 40%, safety and hygiene were ranked as the two main influencing factors that changed tourists’ actual behaviour during the pandemic. The alteration in behaviour might be attributed to tourists’ awareness of their risk of catching the COVID-19 virus when visiting tourist attractions. Empirical evidence shows that non-interactive restriction techniques had a significant impact on tourist behaviour. Thus, the impact of the pandemic on tourists’ protective behaviour continues to play a part in tourists’ behaviour during and after the pandemic, implying that the chaos theory approach might be used as a crisis management tool in the tourism industry.

Temporal differential effects of post-injury alcohol consumption in a mouse model of blast-induced traumatic brain injury

Traumatic brain injury is a prevalent condition that affects millions worldwide with no clear understanding or effective therapeutic management available. Military soldiers have a high risk of exposure to blast-induced traumatic brain injury (bTBI). Furthermore, alcohol drinking is common in this population, and studies have shown that post-TBI alcohol exposure can result in memory loss. Hence, it is possible that alcohol could contribute to the overall pathological outcome of brain trauma. However, such a possibility has not been explored in detail. Here, we combined a mild bTBI (mbTBI) model with the drinking-in-the-dark (DID) paradigm to investigate the pathological synergy between mbTBI and alcohol consumption by examining brain oxidative stress levels and behavioral alterations in mice. The results revealed the anxiolytic and short-term memory improvement effects of post-trauma alcohol drinking examined at an early timepoint post mbTBI. However, extended alcohol drinking for up to three weeks post mbTBI impaired long-term memory and was accompanied by intensified oxidative stress in brain regions associated with memory and anxiety. These findings, as well as those from previous in vitro TBI/alcohol studies, suggest a pathological synergy of physical force and post-impact alcohol exposure. This knowledge could potentially aid in establishing guidelines for TBI victims to avoid further injury to their brains as well as to help maximize their recovery following TBI.

Cerebral venous thrombosis in children an 18-year review of a Portuguese hospital

IntroductionCerebral venous thrombosis (CVT) is an uncommon and clinically heterogeneous cerebrovascular particularly in children, only a few published case series focused in the pediatric population. Patients and methodsRetrospective single-center observational and analytical study of consecutive pediatric patients admitted in a level II Portuguese hospital with a confirmed diagnosis of CVT, from 2003 to 2021. Clinical presentation, neuroimaging findings, prothrombotic factors, treatment strategies, outcome and recanalization were documented. ResultsTwelve children were included (58% female). Mean age was 7.3 years. The most frequent symptoms were vomiting, headache and behavioral alterations. Infection was the triggering factor in 50% of the cases. The diagnosis of CVT was made based on imaging evidence of thrombosis through magnetic imaging resonance (MRI) with venography and/or computed tomography (CT) with venography. In 67% of cases there were multiples sinuses involved; the transverse sinus was the most affected, followed by the sigmoid sinus. In 83% of cases anticoagulant therapy was initiated with low molecular weight heparin (LMWH) and associated prothrombotic factors were investigated, with no major prothrombotic factors identified. No deaths occurred, but 30% had long-term neurological sequelae. One patient recurred 18 years later. ConclusionThe results of this study are consistent with data from other published studies. MRI is the preferred imaging method for diagnosis in children by avoiding ionizing radiation and allowing identification of subjacent causes. Anticoagulation with LMWH is recommended and important to reduce mortality and sequelae. Infectious diseases are the most common trigger for CVT and can also be the cause for high morbidity and poor outcomes.

Biomonitoring emerging hazards of pharmaceuticals in river water using gut microbiome and behavioural Daphnia magna responses

A cost-effective Daphnia magna testing framework was applied to identify emerging hazards such as neurological and cardiovascular defects as well as antibiotic resistant genes (ARGs), related to pharmaceuticals present in waste water treated (WWTP) effluent discharged into rivers. D. magna juveniles were exposed during 48 h to water samples from three rivers in the vicinity of Barcelona (NE Spain), Besós, Llobregat and Onyar, upstream and downstream of WWTP discharging points. The analyses included measuring levels of 80 pharmaceutical residues in water samples by HPLC-MS, determination of the loads of different clinically relevant antibiotic resistant genes (ARGs) in both water samples and exposed animals, and assessment of toxic effects in feeding, heartbeat responses, and behavioural indicators. ARG prevalence in water, but not in gut microbiomes, was associated with the presence of bactericides in water. These results suggest that their levels were high enough to put a selective pressure over river microbial populations, but that Daphnia guts were not easily populated by environmental bacteria. Toxic effects were found in 20 to 43% of water samples, depending on the river, and related to water quality parameters and to pollutant levels. For example, heartbeats were correlated with salinity, whereas feeding impairment did so with high loads of suspended solids. In contrast, behavioural alterations were associated to the concentration of neuroactive chemicals. Accordingly, we hypothesize that measured neuroactive chemicals have caused the observed effects. If this also applies to local invertebrate populations, the environmental consequences may be severe and unpredictable.

The role of NMDA receptors in fish stress response: Assessments based on physiology of the caudal neurosecretory system and defensive behavior.

Stress strongly influences the physiology and behavior of animals, and leads into a pathological condition and disease. NMDA receptors (NMDARs) play a crucial role in the modulation of neural activity. To understand the role of NMDARs in fish stress response, we used NMDARs agonist aspartate to test the functional role of its input on the Dahlgren cell population in the caudal neurosecretory system (CNSS) of the olive flounder. In addition, the effect of the NMDARs antagonist D-AP5 on the expression of genes of the main secretory products of the CNSS after stress was investigated by using qPCR technology and the effect of the NMDARs antagonist D-AP5 on post-stress behavior was explored by behavioral methods. Ex vivo electrophysiological experiments showed that the NMDARs agonist aspartate enhanced the firing frequency of Dahlgren cells. Additionally, aspartate treatment increased the incidence of cells exhibiting bursting firing pattern, this result is corroborated by the observed upregulation in the expression of ion channels and major hormone genes in the CNSS. Furthermore, the excitatory influence of aspartate was effectively counteracted by NMDARs antagonist D-AP5. Interestingly, NMDARs antagonist D-AP5 treatment also significantly decreased the plasma cortisol levels and the expression of CRH, UI, and UII in CNSS after acute stress. Treatment with D-AP5 effectively attenuated the stress response, as evidenced by alterations in respiratory metabolism, sand-burying behavior, swimming distance, simulated capture, and escape response. In conclusion, modulation of Dahlgren cell excitability in the CNSS by NMDARs contributes to the regulation of the stress response, NMDARs antagonist D-AP5 can effectively suppress stress response in flounder by regulating the stress hormone expression and secretion. CLINICAL TRIAL REGISTRATION: Project code SHOU-DW-2022-032.

Isoacid supplementation influences feed sorting, chewing behaviors, and enteric methane emissions differentially in mid-lactation dairy cows depending on dietary forage level

Past studies have shown that isoacids (ISO) improve dairy cow performance, with effects varying based on dietary forage levels, leading us to speculate that ISO supplementation may also differentially affect enteric methane (CH4) emissions depending on dietary forage levels. Therefore, our primary objective was to examine the effects of ISO supplementation on enteric CH4 emissions in lactating dairy cows fed 2 forage NDF levels (FL), along with monitoring feed particle sorting and chewing behaviors to assess any potential interactions. Sixty-four (64) mid-lactation Holstein cows were utilized in a 10-wk long randomized complete block design trial. Parity, DIM, and prior milk yield (MY) for multiparous cows or genetic merit for primiparous cows were used as blocking factors. Cows were randomly assigned to 1 of 4 diets (n = 16 per diet) with a 2 × 2 factorial arrangement of treatment combinations, including 2 FL, 17 (LF) and 21% forage NDF (HF), without or with ISO supplementation (7.85 mmol/kg DM for isobutyrate and 3.44 mmol/kg DM for 2-methylbutyrate, respectively). Enteric CH4 and chewing activity (rumination and eating time) were measured using the GreenFeed system and sensor-based ear tag system, respectively. The particle size of each diet and ort from individual cows was measured using the Penn State Particle Separator, and a sorting index was calculated. A sorting index of 100 indicates no sorting, while values above or below 100 indicate sorting for or against, respectively. Data were analyzed using a mixed model including FL, ISO, and FL × ISO as fixed effects and block as a random effect (lme4 in R). Our result shows that ISO increased sorting index for long particle in LF (96.1 vs. 109; P < 0.01) but decreased it in HF (100.8 vs. 92.5; P = 0.04). In contrast, ISO did not affect the physically effective particle sorting index (P = 0.51) or intake (P = 0.27) regardless of FL. In alignment with the long particle sorting index, ISO decreased eating and chewing time in the HF but increased them in the LF diet (P < 0.01). In contrast, rumination time was comparable between FL (P = 0.70) and ISO levels (P = 0.19). In the LF diet, ISO supplementation reduced daily CH4 production (g/d) by 9% and intensity (g/kg of MY) by 18% (P < 0.01). In the HF diet, ISO supplementation led to a 10% increase in daily CH4 (P < 0.01) but did not change CH4 intensity (P = 0.17; g/kg of MY) due to improved milk production. Overall, ISO altered feed sorting, feeding behaviors and enteric CH4 emissions depending on FL.

Altered Patterns of Maternal Behavior Transitions in Rats Exposed to Limited Bedding and Nesting Material Paradigm.

Maternal care plays a fundamental role in early life, and the alteration of its patterns can negatively affect the developmental course of the offspring in a myriad of domains in both rats and humans. The limited bedding and nesting (LBN) protocol is an extensively used paradigm in rodents to address the impact of altered maternal behavior patterns on infants' neurodevelopment. Here, we explore the altered patterns of maternal care in rats in LBN conditions by describing sequences of transition between maternal behavior components using network analysis. Using this technique, we capture how often maternal behavior transitions take place during the LBN period and which behaviors play central roles in those transitions over time. Female rats and their pups were placed in standard and LBN housing conditions from Postpartum Days 2 to 9, during which maternal behavior was observed during the light and dark phases. We used inferential statistical analysis to compare the maternal behavior profiles of control and LBN dams, and network analysis was used to capture the altered sequence of maternal behavior transitions during the period of LBN. Compared to control dams, LBN dams significantly increased their high crouch nursing posture during light/dark phases (p=0.018), and the number of behavioral transitions increased only during the dark phase (p=0.0004). Network analysis revealed specific altered patterns of behavioral transitions in LBN dams, characterized by the predominance of switches between active nursing postures during the first five days of the LBN protocol. Nursing behavior was the most disrupted component of maternal behavior under the LBN protocol, mainly during the dark phase. Network analysis can complement and extend traditional methods to gain a more thorough understanding of maternal care strategies and behavioral patterns in LBN conditions and potential consequences for the offspring.

Extreme weather events and disruptions to HIV services: a systematic review.

Extreme weather events pose a risk to health and disproportionately affect vulnerable groups, such as people living with HIV. We aimed to investigate the effects of extreme weather events on HIV testing uptake, HIV treatment and care, and HIV transmission. For this systematic review, we searched PubMed, Web of Science, and PsycINFO for peer-reviewed studies published between database inception and Aug 31, 2023. Eligible studies were English-language qualitative, quantitative observational (retrospective, prospective, cross-sectional, longitudinal, case-control, and cohort), and mixed-method studies, and randomised controlled trials related to HIV and extreme weather events. We excluded reviews, mathematical models, and case reports. After exporting the search results, two authors independently screened the titles and abstracts of identified articles, reviewing the full text of those that met the inclusion criteria. We used systems thinking to develop a framework linking extreme weather events and HIV and summarised the results using thematic narrative synthesis. Of the 6126 studies identified by the search, 27 met the inclusion criteria and were eligible for analysis, of which 19 were quantitative, six were qualitative, and two were mixed-method studies. We identified five main themes linking extreme weather events to HIV: economic and livelihood conditions (12 studies), psychosocial factors (19 studies), infrastructure damage and operational challenges (17 studies), migration and displacement (ten studies), and associated medical conditions and health-care needs (12 studies). We showed how these themes interact in complex ways, resulting in a reduction in uptake of HIV testing, interruption of HIV care and subsequent disease progression, altered risk behaviours, and an increased prevalence of HIV. Extreme weather events are associated with disruptions to HIV services. Owing to the design of the included studies, we could not establish a causal relationship between extreme weather events and HIV incidence, highlighting a research gap. Appropriate adaptations and mitigation policies that protect the health and wellbeing of people living with HIV during and after extreme weather events are warranted. Such actions will be crucial to achieving the UNAIDS goal of ending HIV as a public health threat by 2030. None.