Sodium valproate treatment reverses endothelial dysfunction in aorta from rabbits with acute myocardial infarction.

Sodium valproate (VPA), a histone deacetylase (HDAC) inhibitor, could be a promising candidate to treat acute myocardial infarction (AMI). In this study, AMI was induced in New Zealand White rabbits by occluding the left circumflex coronary artery for 1 h, followed by reperfusion. The animals were distributed into three experimental groups: the sham-operated group (SHAM), the AMI group and the AMI + VPA group (AMI treated with VPA 500 mg/kg/day). After 5 weeks, abdominal aorta was removed and used for isometric recording of tension in organ baths or protein expression by Western blot, and plasma for the determination of nitrate/nitrite (NOx) levels by colorimetric assay. Our results indicated that AMI induced a reduction of the endothelium-dependent response to acetylcholine without modifying the endothelium-independent response to sodium nitroprusside, leading to endothelial dysfunction. VPA treatment reversed AMI-induced endothelial dysfunction and even increased NO sensitivity in vascular smooth muscle. This response was consistent with an antioxidant effect of VPA, as it was able to reverse the superoxide dismutase 1 (SOD 1) down-regulation induced by AMI. Our experiments also ruled out that the VPA mechanism was related to eNOS, iNOS, sGC and arginase expression or changes in NOx plasma levels. Therefore, we conclude that VPA improves vasodilation by increasing NO bioavailability, likely due to its antioxidant effect. Since endothelial dysfunction was closely related to AMI, VPA treatment could increase aortic blood flow, making it a potential agent in reperfusion therapy that can prevent the vascular damage.

Immunomodulation with AM3 and antioxidants creates an adequate framework for skin repair and decreases the monocyte proinflammatory stage in smoker women.

Smoking has been considering a crucial factor in promoting skin and systemic aging that is associated with the development of a low-level, systemic, chronic inflammation known as "inflammaging" in which monocytes play a pivotal role. Our aim was to investigate the effects of AM3 plus antioxidants vs placebo in the activation status, function of monocytes and cutaneous aging parameters in healthy smoker middle-aged women. A total of 32 women were 1:1 randomly assigned to AM3 plus antioxidants or placebo for three months. Peripheral mononuclear blood cells and cutaneous biopsy were obtained and flow cytometry and immunohistological studies, respectively, were performed before and after the treatment. AM3 plus antioxidants treatment compared with placebo significantly reduced the monocyte production of the proinflammatory interleukin 1 (IL-1), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) cytokines as well as increased the regulatory IL-10 in middle-aged smoker women. Furthermore, AM3 and antioxidants did not modify ROS production by monocytes and granulocytes but increased their phagocytic activity. The active combination also stimulated a significative increase in reticular dermis depth as well as an increase in the expression of CD117 and CD31. Thus, AM3 and antioxidants treatment reduces the systemic proinflammatory monocyte disturbance of heathy smoker middle-aged women and encourage skin repair mechanisms.

A Randomized Controlled Trial to Evaluate the Impact of an Exercise Therapy Program Based on Sports in People with Acquired Brain Injury: Discover Study Protocol.

INTRODUCTION: Acquired brain injury (ABI) constitutes a significant and growing global public health concern. People with ABI often face a range of physical and psychosocial challenges that span the domains of "body structure and function", "activity", and "participation", as defined by the International Classification of Functioning, Disability, and Health. Multidisciplinary approaches based on exercise therapy with social leisure activities are essential to improve physical recovery and health-related quality of life after injury. METHODS: Adults with ABI, aged > 18 years, in the subacute or chronic stage (within more than one month after the injury) will be recruited through a rehabilitation center. Adults will be randomized to receive either a racket sports-based exercise therapy program combined with usual care (sET) or usual care alone (UC) using a random number sequence with a 1:1 allocation ratio. sET intervention consists of an 8-week exercise therapy program focusing on different racket sports skills, 1 h in duration, 2 days/week. It will be delivered by a physiotherapist in tailored, face-to-face, group-based sessions. Primary outcomes will be the health-related quality of life (SF-36) and upper extremity motor function (Fugl-Meyer Assessment-Upper Extremity Scale). DISCUSSION: The study proposes an intervention that combines sports-based exercise therapy with usual care. It aims to determine whether this intervention improves the health-related quality of life and upper limb motor function in adults with ABI compared with usual care alone. The results of this study may have clinical implications for the rehabilitation of this population.

The Role of Aryl Hydrocarbon Receptor in the Endothelium: A Systematic Review.

Activation of the aryl hydrocarbon receptor (AhR) has been shown to be important in physiological processes other than detoxification, including vascular homeostasis. Although AhR is highly expressed in the endothelium, its function has been poorly studied. This systematic review aims to summarise current knowledge on the AhR role in the endothelium and its cardiovascular implications. We focus on endogenous AhR agonists, such as some uremic toxins and other agonists unrelated to environmental pollutants, as well as studies using AhR knockout models. We conclude that AhR activation leads to vascular oxidative stress and endothelial dysfunction and that blocking AhR signalling could provide a new target for the treatment of vascular disorders such as cardiovascular complications in patients with chronic kidney disease or pulmonary arterial hypertension.

Prevalence and Clinical Characteristics of Children With Nonsevere Tuberculosis in Spain.

BACKGROUND: To assess the prevalence and characteristics of nonsevere TB among children in Spain. It has been recently demonstrated that these children can be treated with a 4-month regimen instead of the classical 6-month treatment regimen, with the same effectivity and outcomes, decreasing toxicity and improving adherence. METHODS: We conducted a retrospective cohort study in a cohort of children ≤16 years of age with TB. Nonsevere TB cases included smear-negative children with respiratory TB confined to 1 lobe, with no significant airway obstruction, no complex pleural effusion, no cavities and no signs of miliary disease, or with peripheral lymph-node disease. The remaining children were considered to have severe TB. We estimated the prevalence of nonsevere TB and compared the clinical characteristics and outcomes between children with nonsevere and severe TB. RESULTS: A total of 780 patients were included [46.9% males, median age 5.5 years (IQR: 2.6-11.1)], 477 (61.1%) of whom had nonsevere TB. Nonsevere TB was less frequent in children <1 year (33% vs 67%; P < 0.001), and >14 years of age (35% vs 65%; P = 0.002), mostly diagnosed in contact tracing studies (60.4% vs 29.2%; P < 0.001) and more frequently asymptomatic (38.3% vs 17.7%; P < 0.001). TB confirmation in nonsevere disease was less frequent by culture (27.0% vs 57.1%; P < 0.001) and by molecular tests (18.2% vs 48.8%; P < 0.001). Sequelae were less frequent in children with nonsevere disease (1.7 vs 5.4%; P < 0.001). No child with nonsevere disease died. CONCLUSIONS: Two-thirds of children had nonsevere TB, mostly with benign clinical presentation and negative microbiologic results. In low-burden countries, most children with TB might benefit from short-course regimens.

Features of Mpox infection: The analysis of the data submitted to the ID-IRI network.

Background: Mpox is a rare zoonotic disease caused by the Mpox virus. On May 21, 2022, WHO announced the emergence of confirmed Mpox cases in countries outside the endemic areas in Central and West Africa. Methods: This multicentre study was performed through the Infectious Diseases International Research Initiative network. Nineteen collaborating centres in 16 countries participated in the study. Consecutive cases with positive Mpoxv-DNA results by the polymerase chain reaction test were included in the study. Results: The mean age of 647 patients included in the study was 34.5.98.6% of cases were males, 95.3% were homosexual-bisexual, and 92.2% had a history of sexual contact. History of smallpox vaccination was present in 3.4% of cases. The median incubation period was 7.0 days. The most common symptoms and signs were rashes in 99.5%, lymphadenopathy in 65.1%, and fever in 54.9%. HIV infection was present in 93.8% of cases, and 17.8% were followed up in the hospital for further treatment. In the two weeks before the rash, prodromal symptoms occurred in 52.8% of cases. The incubation period was 3.5 days shorter in HIV-infected Mpox cases with CD4 count <200/µL, we disclosed the presence of lymphadenopathy, a characteristic finding for Mpox, accompanied the disease to a lesser extent in cases with smallpox vaccination. Conclusions: Mpox disseminates globally, not just in the endemic areas. Knowledge of clinical features, disease transmission kinetics, and rapid and effective implementation of public health measures are paramount, as reflected by our findings in this study.

Venom comparisons of endemic and micro-endemic speckled rattlesnakes Crotalus mitchellii, C. polisi and C. thalassoporus from Baja California Peninsula.

A high diversity of rattlesnake species can be found in the Baja California peninsula and the island of the Gulf of California, nevertheless, their venom has been poorly evaluated. The aim of this work was to present the first characterization of endemic Crotalus mitchellii, micro endemic C. polisi and C. thalassoporus venoms. All samples provoke human plasma coagulation showing doses in the rank of 2.3-41.0 µg and also produce rapid hydrolysis of the alpha chain of bovine fibrinogen while the beta chain is attacked at larger incubation periods by C. polisi and especially by C. thalassoporus. Phospholipase activity ranging from 23.2 to 173.8 U/mg. The venoms of C. thalassoporus and C. polisi show very high hemorrhagic activity (from 0.03 to 0.31 µg). A total of 130 toxin-related proteins were identified and classified into ten families. Crotalus mitchellii venom was characterized by high abundance of crotoxin-like and other phospholipase proteins (34.5%) and serine proteinases (29.8%). Crotalus polisi showed a similar proportion of metalloproteinases (34%) and serine proteinases (22.8%) components with important contribution of C-type lectins (14.3%) and CRiSP (14.0%) proteins. Venom of C. thalassoporus is dominated by metalloproteases that amount to more than 66% of total toxin proteins. These results provide a foundation for comprehending the biological, ecological and evolutionary significance of venom composition of speckled rattlesnake from the Baja California peninsula.

AAGGG repeat expansions trigger RFC1-independent synaptic dysregulation in human CANVAS Neurons.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late onset, recessively inherited neurodegenerative disorder caused by biallelic, non-reference pentameric AAGGG(CCCTT) repeat expansions within the second intron of replication factor complex subunit 1 (RFC1). To investigate how these repeats cause disease, we generated CANVAS patient induced pluripotent stem cell (iPSC) derived neurons (iNeurons) and utilized calcium imaging and transcriptomic analysis to define repeat-elicited gain-of-function and loss-of-function contributions to neuronal toxicity. AAGGG repeat expansions do not alter neuronal RFC1 splicing, expression, or DNA repair pathway functions. In reporter assays, AAGGG repeats are translated into pentapeptide repeat proteins that selectively accumulate in CANVAS patient brains. However, neither these proteins nor repeat RNA foci were detected in iNeurons, and overexpression of these repeats in isolation did not induce neuronal toxicity. CANVAS iNeurons exhibit defects in neuronal development and diminished synaptic connectivity that is rescued by CRISPR deletion of a single expanded allele. These phenotypic deficits were not replicated by knockdown of RFC1 in control neurons and were not rescued by ectopic expression of RFC1. These findings support a repeat-dependent but RFC1-independent cause of neuronal dysfunction in CANVAS, with important implications for therapeutic development in this currently untreatable condition.

Hydrogel-Based Biosensors.

There is an increasing interest in sensing applications for a variety of analytes in aqueous environments, as conventional methods do not work reliably under humid conditions or they require complex equipment with experienced operators. Hydrogel sensors are easy to fabricate, are incredibly sensitive, and have broad dynamic ranges. Experiments on their robustness, reliability, and reusability have indicated the possible long-term applications of these systems in a variety of fields, including disease diagnosis, detection of pharmaceuticals, and in environmental testing. It is possible to produce hydrogels, which, upon sensing a specific analyte, can adsorb it onto their 3D-structure and can therefore be used to remove them from a given environment. High specificity can be obtained by using molecularly imprinted polymers. Typical detection principles involve optical methods including fluorescence and chemiluminescence, and volume changes in colloidal photonic crystals, as well as electrochemical methods. Here, we explore the current research utilizing hydrogel-based sensors in three main areas: (1) biomedical applications, (2) for detecting and quantifying pharmaceuticals of interest, and (3) detecting and quantifying environmental contaminants in aqueous environments.

Effects of Exercise Programs on Functional Capacity and Quality of Life in People With Acquired Brain Injury: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aims of this systematic review and meta-analyses were to evaluate the effects of exercise on the functional capacity and quality of life (QoL) of people with acquired brain injury (ABI) and to analyze the influence of training variables. METHODS: Five electronic databases (MEDLINE, Cochrane Library, CINAHL, SportDiscus, and Web of Science) were searched until October 2021 for clinical trials or experimental studies examining the effects of exercise on the functional capacity and QoL in adults with ABI and comparing exercise interventions with non-exercise (usual care). RESULTS: Thirty-eight studies were evaluated. A total sample of 2219 people with ABI (exercise, n = 1572; control, n = 647) were included in the quantitative analysis. A greater improvement was observed in walking endurance (z score = 2.84), gait speed (z score = 2.01), QoL physical subscale (z score = 3.42), and QoL mental subscale (z score = 3.00) was observed in the experimental group than in the control group. In addition, an improvement was also observed in the experimental group in the "Timed Up and Go" Test scores and balance without differences from the control group. Significant interactions were also observed between the rehabilitation phases, type, frequency and volume of training, and overall effects. CONCLUSION: The results suggest that exercise improves functional capacity and QoL regardless of model training, highlighting the effectiveness of long-term exercise that includes short sessions with components such as strength, balance, and aerobic exercise. IMPACT: The results shown in this systematic review with meta-analysis will allow physical therapists to better understand the effects of training on people with ABI.

Activating de novo monoallelic variants causing inborn errors of immunity in two unrelated children born of HIV-seroconcordant couples.

INTRODUCTION: Around 20% of all inborn errors of immunity (IEI) are autosomal dominant or monoallelic, either by haploinsufficiency, negative dominance, or gain of function (GOF). GOF phenotypes usually include autoinflammation, autoimmunity, lymphoproliferation, allergies, and some infections. CASE SERIES: We describe the cases of two unrelated patients born of HIV-seroconcordant parents. Both patients are HIV-negative but carry de novo GOF missense variants that resulted in inflammatory lymphoproliferative IEI diseases: signal transducer and activator of transcription 3 (STAT3)-GOF and phosphatidylinositol 3-kinase, catalytic delta (PIK3CD)-GOF. Both variants were found through whole-exome sequencing and confirmed by Sanger.An 11-year-old male with recurrent sinopulmonary infections, dysmorphism, growth delay, bronchiectasis, and mild mental retardation, as well as lymphopenia, thrombocytopenia, and high immunoglobulin M. Both his parents were known to be HIV-positive under anti-retroviral treatment. HIV infection was repeatedly ruled out in the patient, whom through whole-exome sequencing was found to have a heterozygous missense variant in exon 24 of PIK3CD, a hotspot transition, and the most reported variant in PIK3CD-GOF patients.A 6-year-old male with autoimmune hemolytic anemia, lymphoproliferation, short stature, and intractable diarrhea. Both his parents were found to be HIV-positive. HIV was repeatedly ruled out in the patient by ELISA and viral load. He was found to have a heterozygous missense/splice variant in exon 22 of STAT3, a hotspot transition, and the most reported variant in STAT3-GOF patients. DISCUSSION: The AID/APOBEC3 A-H family of proteins are cytidine deaminases that induce G>A hypermutation in both the invading viral DNA and the host genome, which results in stop codons inside the endogenized retroviral sequence. Both variants found in our patients are G to A transitions. Retroviral infection might thus have resulted in host genome instability, and our patients' rare congenital diseases are the unfortunate consequence of somatic hypermutation in one of their parents' gametes.

Cerium dioxide nanoparticles modulate antioxidant defences and change vascular response in the human saphenous vein.

Nanoparticles have a promising future in biomedical applications and knowing whether they affect ex vivo vascular reactivity is a necessary step before their use in patients. In this study, we have evaluated the vascular effect of cerium dioxide nanoparticles (CeO2NPs) on the human saphenous vein in response to relaxing and contractile agonists. In addition, we have measured the protein expression of key enzymes related to vascular homeostasis and oxidative stress. We found that CeO2NPs increased expression of both SOD isoforms, and the consequent reduction of superoxide anion would enhance the bioavailability of NO explaining the increased vascular sensitivity to sodium nitroprusside in the presence of CeO2NPs. The NOX4 reduction induced by CeO2NPs may lead to lower H2O2 synthesis associated with vasodilation through potassium channels explaining the lower vasodilation to bradykinin. In addition, we showed for the first time, that CeO2NPs increase the expression of ACE2 in human saphenous vein, and it may be the cause of the reduced contraction to angiotensin II. Moreover, we ruled out that CeO2NPs have effect on the protein expression of eNOS, sGC, BKca channels and angiotensin II receptors or modify the vascular response to noradrenaline, endothelin-1 and TXA2 analogue. In conclusion, CeO2NPs show antioxidant properties, and together with their vascular effect, they could be postulated as adjuvants for the treatment of cardiovascular diseases.

Ventral hippocampus-lateral septum circuitry promotes foraging-related memory.

Remembering the location of a food or water source is essential for survival. Here, we reveal that spatial memory for food location is reflected in ventral hippocampus (HPCv) neuron activity and is impaired by HPCv lesion. HPCv mediation of foraging-related memory involves communication to the lateral septum (LS), as either reversible or chronic disconnection of HPCv-to-LS signaling impairs spatial memory retention for food or water location. This neural pathway selectively encodes appetitive spatial memory, as HPCv-LS disconnection does not affect spatial memory for escape location in a negative reinforcement procedure, food intake, or social and olfactory-based appetitive learning. Neural pathway tracing and functional mapping analyses reveal that LS neurons recruited during the appetitive spatial memory procedure are primarily GABAergic neurons that project to the lateral hypothalamus. Collective results emphasize that the neural substrates controlling spatial memory are outcome specific based on reinforcer modality.

Benefits of physical exercise programs toward people with acquired brain injury: A protocol for systematic review and meta-analysis.

BACKGROUND: Exercise has proven to be a tool improving health related quality of life in people with acquired brain injury (ABI) as part of multidisciplinary team during the subacute and chronic phase. While intervention studies and revisions have been increased in recent years, there is no consensus about the type, frequency and variables of control in exercise interventions. Besides, this collective need programs that respond to different functional levels, given the heterogeneity of people with ABI, not only because of the etiology, but also because of the severity differences over their deficits. The aim of this systematic review and meta-analysis is to summarize the evidence regarding the relationship between exercise and health related quality of life in subacute and chronic phase. METHODS: A protocol of systematic review and meta-analysis will examine the benefits of physical exercise (PE) toward people with ABI will be conducted. A comprehensive search will be conducted in the following electronic databases: MEDLINE, The Cochrane Library, CINAHL, SportDiscus, and Web of Science from inception to July 2020. Independent review authors will evaluate the title and abstract for each trial and disagreements will be solved by discussion with a third author if necessary. Standard pairwise meta-analysis, including heterogeneity analysis, subgroup analysis, and sensitivity analysis, will be performed using the Stata software. The quality evaluation of this study will be completed using the Cochrane collaboration risk of bias tool and the risk of bias assessment will be conducted by the World Health Organization grading of recommendations, assessment, development, and evaluation. The review will be reported in accordance to the preferred reporting items for systematic reviews and meta-analyses statement. RESULTS AND CONCLUSSION: This systematic review and meta-analysis protocol will provide an overview regarding the benefits of PE on functioning, social participation and quality of life toward people with ABI. The variability of outcomes across PE from the selected studies will provide important information for future trial designs. Results of the proposed review will inform practice and the design of future clinical trials. This study will summarize all the selected trials aimed at estimating the effectiveness of applying physical activity programs to ABI users.Systematic review registration number: PROSPERO CRD42020191779.

Gender roles and intimate partner violence among female university students in Spain: A cross-sectional study.

BACKGROUND: Traditional gender roles (GRs) have a considerable influence on relationships among couples. These can lead to negative health effects in women; however, their impact on intimate partner violence (IPV) has been less explored, especially among younger women. OBJECTIVE: To explore the association between traditional GRs and several indicators of IPV on a sample of Spanish female university students involved in heterosexual dating relationships. METHODS: A cross-sectional study involving female university students (n = 1,005) pursuing ten degrees (four Health Science degrees and six Social Sciences degrees). Data were collected using two validated scales: 1) the Questionnaire on the Gender Determinants of Contraception (COGANT), used to examine four traditional GRs (submissive, blind, and passive attitudes of female students, and male dominance), and 2) the Dating Violence Questionnaire-R (DVQ-R) scale, used to measure five types of IPV-behaviors (coercion, detachment, humiliation, sexual violence, and physical violence), perceived fear, entrapment, and abuse. Logistic and linear regressions were conducted to study the association between GR and a series of IPV indicators in dating relationships. RESULTS: Traditional GRs were highly prevalent (57.0% submissive, 52.0% blind attitude, 75.7% passive, and 31.7% identified their boyfriend as being dominant). Up to 66.3% experienced some type of violent behavior. All GRs were significantly associated with IPV indicators. A submissive attitude in female students was the GR that was most strongly associated to total IPV-behavior (adjusted odd ratio [OR] = 3.18; 95% confidence interval [CI]: 2.29-4.42), followed by male dominance (OR = 2.79: 95% CI:1.71: 4.54). Both GRs were also highly associated with perceived fear, entrapment, and abuse. CONCLUSIONS: A high presence of traditional GRs was found in the relationships held by female university students, which was significantly associated with IPV indicators. Universities must adopt policies for gender equality and raise awareness on dating violence.

Restless legs-like syndrome as an emergent adverse event of CGRP monoclonal antibodies: A report of two cases.

BACKGROUND: One of the advantages of CGRP monoclonal antibodies is their excellent safety and tolerability. However, postmarketing surveillance, is essential to detect potential rare emergent adverse events. OBJECTIVES: To report two patients who developed restless legs syndrome symptoms after treatment with CGRP antibodies. METHODS AND RESULTS: Two women with chronic refractory migraine, with no significant medical antecedents, developed typical restless legs syndrome symptoms 1.5 and 4 months after starting erenumab 140 mg, respectively. In case 1 symptoms resolved when erenumab was stopped for two months but reappeared on galcanezumab. In both patients migraine attacks had dramatically decreased and no iron deficiency was found. CONCLUSIONS: Even though caution is needed before establishing a causal relationship, these cases suggest that restless legs-like symptoms might be an emergent adverse event of CGRP antibodies, regardless of the mechanism of action. We propose that plastic changes in CGRP sensory fibers, which are very abundant in legs, induced by CGRP monoclonal antibodies could be the reason for restless legs syndrome development.

Gut microbial taxa elevated by dietary sugar disrupt memory function.

Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Excessive consumption of sugar and other unhealthy dietary factors during early life developmental periods yields changes in the gut microbiome as well as neurocognitive impairments. However, it is unclear whether these two outcomes are functionally connected. Here we explore whether excessive early life consumption of added sugars negatively impacts memory function via the gut microbiome. Rats were given free access to a sugar-sweetened beverage (SSB) during the adolescent stage of development. Memory function and anxiety-like behavior were assessed during adulthood and gut bacterial and brain transcriptome analyses were conducted. Taxa-specific microbial enrichment experiments examined the functional relationship between sugar-induced microbiome changes and neurocognitive and brain transcriptome outcomes. Chronic early life sugar consumption impaired adult hippocampal-dependent memory function without affecting body weight or anxiety-like behavior. Adolescent SSB consumption during adolescence also altered the gut microbiome, including elevated abundance of two species in the genus Parabacteroides (P. distasonis and P. johnsonii) that were negatively correlated with hippocampal function. Transferred enrichment of these specific bacterial taxa in adolescent rats impaired hippocampal-dependent memory during adulthood. Hippocampus transcriptome analyses revealed that early life sugar consumption altered gene expression in intracellular kinase and synaptic neurotransmitter signaling pathways, whereas Parabacteroides microbial enrichment altered gene expression in pathways associated with metabolic function, neurodegenerative disease, and dopaminergic signaling. Collectively these results identify a role for microbiota "dysbiosis" in mediating the detrimental effects of early life unhealthy dietary factors on hippocampal-dependent memory function.

The presence of chemosensory cues transmitted through the mother's milk increases the search and ingestion responses toward bitter and sour solutions.

Olfaction is of major importance during early stages of life in altricial species. This sense allows newborns to develop different behaviors that will allow them to survive. Odors tend to be associated to contextual stimuli (such as warmth); this, in turn, enables the pups to recognize when to withdraw or approach. At the same time, olfaction modulates the acceptance of aversive flavors. The increase of approach responses toward a bitter substance during early life is enhanced by stimulation with familiar, pre-exposed odors. Newborn rats exhibit heightened grasp responses toward an artificial nipple dispensing quinine, and drink more of this bitter solution, in the presence of a pre-exposed odor (lemon or the mother's odor). The present research assessed the replicability of previous results by pre-exposing the subjects to the scent through maternal milk and using solutions with different aversive tastes. Half of the subjects (3 day-old Wistar rats) were pre-exposed to lemon odor through the maternal milk (the mother had previously ingested the lemon essence via an intragastric injection); 4 h later, all the rats were evaluated in the presence of the lemon odor with an artificial nipple containing quinine, citric acid, saline solution, or water. The results showed enhanced seeking and intake of the bitter (quinine) and sour solution (citric acid). However, this did not occur when the nipple contained water or saline solution. The evidence suggests that: During the early stages of development, familiar odors regulate the acceptance of non-palatable, otherwise rejected, flavors; and that the route of transmission of the pre-exposed odor can be through air, or through food (amniotic fluid in previous studies and, in this case, breast milk), that is, via the retronasal and orthonasal routes.

Major Surgery Affects Memory in Individuals with Cerebral Amyloid-ß Pathology.

BACKGROUND: Major surgery has been associated with perioperative neurocognitive disorders (PND), but the contributing factors and long-term prognosis are uncertain. We hypothesize that preclinical Alzheimer's disease (AD) might predispose to cognitive deterioration after surgery. OBJECTIVE: To analyze the effect of amyloid-ß on the cognitive trajectory after orthopedic surgery in a sample of non-demented subjects. METHODS: Non-demented individuals older than 65 years that were on the waiting list for orthopedic surgery with spinal anesthesia underwent a neuropsychological assessment before and after surgery. During surgery, cerebrospinal fluid samples were obtained to determine AD biomarkers. RESULTS: Cumulative incidence of PND was 55.2%during a mean follow-up of nine months. The most affected cognitive domains were executive function and constructional praxis. The presence of abnormal levels of amyloid-ß was associated to a postoperative impairment in verbal and visual memory tests. According to their AD biomarker profile, participants were categorized as either Amyloid Positive (A+) or Amyloid Negative (A-). The incidence of PND did not differ between both groups. The A- group showed a tendency similar to the global sample, worsening in executive function tests and improving on memory scales due to practice effects. In contrast, the A + group showed a notable worsening on memory performance. CONCLUSION: Our findings support the hypothesis that surgery may promote or accelerate memory decline in cognitively asymptomatic subjects with brain amyloid-ß deposits.

Transient serotonin depletion at adolescence, but not at early infancy, reduced subsequent anxiety-like behavior and alcohol intake in female mice.

RATIONALE: Serotonin (5-HT) plays an important role in the organization of the central nervous system and in the development of social interaction deficits and psychiatric disorders, including anxiety, depression, and addiction disorders. Notably, disruption of the 5-HT system during sensitive periods of development exerts long-term consequences, including altered anxiety response and problematic use of alcohol. OBJECTIVE: we analyzed, in mice, the effects of transient 5-HT depletion at infancy or adolescence on subsequent anxiety-like behavior and alcohol intake during adolescence. METHODS: C57/BL6 male and female mice were administered a 5-HT synthesis inhibitor (PCPA; 4-chloro-DL-phenylalanine methyl ester hydrochloride) at infancy (postnatal days 14-16 [PD14-16]) or adolescence (PD40-42). Eleven (± 1) days after treatment, mice were assessed for ethanol intake in daily two-bottle choice tests and for anxiety response via the elevated plus maze. RESULTS: Female, but not male, mice transiently depleted of 5-HT at adolescence (but not those depleted at the perinatal stage) exhibited a significant reduction in anxiety response, which was accompanied by a significant reduction on alcohol intake. CONCLUSION: Transient 5-HT inhibition at adolescence may act, in females, as a protective factor for the emergence of anxiety disorders and problematic use of alcohol during adolescence.