Mpox outbreak in Rio de Janeiro, Brazil: A translational approach.

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.

Four-week inhibition of the renin-angiotensin system in spontaneously hypertensive rats results in persistently lower blood pressure with reduced kidney renin and changes in expression of relevant gene networks.

AIMS: Prevention of human hypertension is an important challenge and has been achieved in experimental models. Brief treatment with renin-angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this fascinating phenomenon, but relevant changes in gene expression are unknown. METHODS: In SHR, we studied the effect of treatment between 10 and 14 weeks of age with the angiotensin receptor blocker, losartan, or the angiotensin-converting enzyme (ACE) inhibitor, perindopril (with controls for non-specific effects of lowering BP) on differential RNA expression, DNA methylation and renin immunolabelling in the kidney at 20 weeks of age. RESULTS: RNA sequencing revealed a 6-fold increase in renin gene (Ren) expression during losartan treatment (P < 0.0001). Six weeks after losartan, arterial pressure remained lower (P = 0.006), yet kidney Ren showed reduced expression by 23% after losartan (P = 0.03) and by 43% after perindopril (P = 1.4 x 10-6) associated with increased DNA methylation (P = 0.04). Immunolabelling confirmed reduced cortical renin after earlier RAS blockade (P = 0.002). RNA sequencing identified differential expression of mRNAs, miRNAs and lncRNAs with evidence of networking and co-regulation. These included 13 candidate genes (Grhl1, Ammecr1l, Hs6st1, Nfil3, Fam221a, Lmo4, Adamts1, Cish, Hif3a, Bcl6, Rad54l2, Adap1, Dok4), the miRNA miR-145-3p and the lncRNA AC115371. Gene ontogeny analyses revealed that these networks were enriched with genes relevant to BP, RAS and the kidneys. CONCLUSIONS: Early RAS inhibition in SHR resets genetic pathways and networks resulting in a legacy of reduced Ren expression and BP persisting for a minimum of 6 weeks.

An Evaluation of the Antibacterial, Antileishmanial, and Cytotoxic Potential of the Secondary Metabolites of Streptomyces sp. ARH (A3).

This study aimed to evaluate the antibacterial, leishmanicidal, and cytotoxic potential of metabolites produced by bacteria isolated from rhizosphere soil samples. The bacterium was identified by genome sequencing as Streptomyces kronopolitis. A preliminary screening was carried out for the antimicrobial activity of S. kronopolitis, demonstrating activity against Staphylococcus aureus ATCC 6538, Corynebacterium diphtheriae ATCC 27010, C. diphtheriae ATCC 27012, and Mycobacterium abscessus, with inhibition halos of sizes 25, 36, 29, and 33 mm, respectively. To obtain secondary metabolites, the bacteria were subjected to submerged fermentation, and the metabolites were extracted using the liquid-liquid method with ethyl acetate. There was a similar MIC for M. abscessus and the two strains of C. diphtherium, reaching a concentration of 12.5 µg/mL, while that of S. aureus was 0.048 µg/mL. Assays for leishmanicidal activity and cytotoxicity against HEp-2 cells and red blood cells were performed. The metabolite showed an IC50 of 9.0 ± 0.9 µg/mL and CC50 of 221.2 ± 7.0 µg/mL. This metabolite does not have hemolytic activity and is more selective for parasites than for mammalian cells, with a selectivity index of 24.6. Thus, the studied metabolite may be a strong candidate for the development of less toxic drugs to treat diseases caused by pathogens.

Validation of a sleep staging classification model for healthy adults based on two combinations of a single-channel EEG headband and wrist actigraphy.

STUDY OBJECTIVES: The aim of this study was to develop a sleep staging classification model capable of accurately performing on different wearable devices. METHODS: Twenty-three healthy subjects underwent a full-night type I polysomnography and used two devices' combinations: (A) flexible single-channel electroencephalogram headband+actigraphy (N=12) and (B) rigid single-channel electroencephalogram headband+actigraphy (N=11). The signals were segmented into 30-second epochs according to polysomnographic stages (scored by a board-certified sleep technologist) (model ground truth) and 18 frequency and time features were extracted. The model consisted of an ensemble of bagged decision trees. Bagging refers to bootstrap aggregation to reduce overfitting and improve generalization. To evaluate the model, a training dataset under 5-fold cross-validation and an 80-20% dataset split was used. The headbands were also evaluated without the actigraphy feature. Subjects also completed a usability evaluation (comfort, pain while sleeping, and sleep disturbance). RESULTS: Combination A had an F1-score of 98.4% and the flexible headband alone of 97.7% (error rate for N1: combination A=9.8%; flexible headband alone=15.7%). Combination B had an F1-score of 96.9% and the rigid headband alone of 95.3% (error rate for N1: combination B=17.0%; rigid headband alone=27.7%); in both, N1 was more confounded with N2. CONCLUSIONS: We developed an accurate sleep classification model based on a single-channel EEG device, and actigraphy was not an important feature of the model. Both headbands were found to be useful, with the rigid one being more disruptive to sleep. Future research can improve our results by applying the developed model in a population with sleep disorders. CLINICAL TRIAL REGISTRATION: Actigraphy, Wearable EEG Band and Smartphone for Sleep Staging (ID NCT04943562).

Unraveling the diversity and dissemination dynamics of antimicrobial resistance genes in Enterobacteriaceae plasmids across diverse ecosystems.

AIM: The objective of this study was to investigate the antimicrobial resistance genes (ARGs) in plasmids of Enterobacteriaceae from soil, sewage, and feces of food-producing animals and humans. METHODS AND RESULTS: The plasmid sequences were obtained from the NCBI database. For the identification of ARG, comprehensive antibiotic resistance database (CARD), and ResFinder were used. Gene conservation and evolution were investigated using DnaSP v.6. The transfer potential of the plasmids was evaluated using oriTfinder and a MOB-based phylogenetic tree was reconstructed using Fastree. We identified a total of 1064 ARGs in all plasmids analyzed, conferring resistance to 15 groups of antibiotics, mostly aminoglycosides, beta-lactams, and sulfonamides. The greatest number of ARGs per plasmid was found in enterobacteria from chicken feces. Plasmids from Escherichia coli carrying multiple ARGs were found in all ecosystems. Some of the most abundant genes were shared among all ecosystems, including aph(6)-Id, aph(3'')-Ib, tet(A), and sul2. A high level of sequence conservation was found among these genes, and tet(A) and sul2 are under positive selective pressure. Approximately 62% of the plasmids carrying at least one ARG were potentially transferable. Phylogenetic analysis indicated a potential co-evolution of Enterobacteriaceae plasmids in nature. CONCLUSION: The high abundance of Enterobacteriaceae plasmids from diverse ecosystems carrying ARGs reveals their widespread distribution and importance.

Selective transduction and photoinhibition of pre-Bötzinger complex neurons that project to the facial nucleus in rats affects nasofacial activity.

The pre-Bötzinger complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetized and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviors. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviors have been associated with the development and progression of diseases.

While breathing seems to come easy, it is a complex process in which many muscles coordinate to allow air to flow into the lungs. These muscles also control the flow of air we breathe out to allow us to talk, sing, eat, or drink. The brain circuits that control these muscles, can also influence other parts of the brain. The preBötzinger Complex, which is a key region of brainstem circuits that generate and control breathing, contains neurons that also project widely, connecting to other regions of the brain. This helps to modulate the sense of smell, emotional state, heart rate, and even blood pressure. Understanding how the preBötzinger Complex is organized can untangle how breathing can influence these other processes. Melo et al. wanted to learn whether they could manipulate the activity of a subgroup of preBötzinger Complex neurons that project into the facial nucleus ­ a region of the brain that controls the muscles of the face when we breathe ­ without affecting breathing. If this can be done, it might also be possible to affect blood pressure by manipulating selective preBötzinger neurons, and thus the development of hypertension, without having any impact on breathing. To test this hypothesis, Melo et al. used rats in which the activation of preBötzinger Complex neurons that project into the facial nucleus was blocked. This decreased the activity of the muscles around the nose with hardly any effect on breathing. Melo et al. also found that the state of consciousness of the rat (anesthetized or conscious) could affect how preBötzinger Complex neurons control these muscles. Melo et al. also observed that preBötzinger Complex neurons projecting into the facial nucleus had projections into many other regions in the brainstem. This might help to the coordinate respiratory, cardiovascular, orofacial, and potentially other physiological functions. The findings of Melo et al. set a technical foundation for exploring the influence of specific subgroups of preBötzinger Complex neurons on respiratory modulation of other physiological activities, including blood pressure and heart rate and in conditions, such as hypertension and heart failure. More broadly, most brain regions contain complex and heterogeneous groups of neurons and the strategy validated by Melo et. al. could be applied to unravel other brain-function relationships.

Longitudinal study of humoral immunity against SARS-CoV-2 of health professionals in Brazil: the impact of booster dose and reinfection on antibody dynamics.

Introduction: The pandemic caused by SARS-CoV-2 has had a major impact on health systems. Vaccines have been shown to be effective in improving the clinical outcome of COVID-19, but they are not able to fully prevent infection and reinfection, especially that caused by new variants. Methods: Here, we tracked for 450 days the humoral immune response and reinfection in 52 healthcare workers from Brazil. Infection and reinfection were confirmed by RT-qPCR, while IgM and IgG antibody levels were monitored by rapid test. Results: Of the 52 participants, 19 (36%) got reinfected during the follow-up period, all presenting mild symptoms. For all participants, IgM levels dropped sharply, with over 47% of them becoming seronegative by the 60th day. For IgG, 90% of the participants became seropositive within the first 30 days of follow-up. IgG antibodies also dropped after this period reaching the lowest level on day 270 (68.5 ± 72.3, p<0.0001). Booster dose and reinfection increased the levels of both antibodies, with the interaction between them resulting in an increase in IgG levels of 130.3 arbitrary units. Conclusions: Overall, our data indicate that acquired humoral immunity declines over time and suggests that IgM and IgG antibody levels are not associated with the prevention of reinfection.

Acute inhibition of nicotinamide adenine dinucleotide phosphate oxidase in the commissural nucleus of the solitary tract reduces arterial pressure and renal sympathetic nerve activity in renovascular hypertension.

BACKGROUND: A growing body of evidence suggests that oxidative stress plays a role in the pathophysiology of hypertension. However, the involvement of the reactive oxygen species (ROS) in the commissural nucleus of the solitary tract (commNTS) in development the of hypertension remains unclear. METHOD: We evaluated the hemodynamic and sympathetic responses to acute inhibition of NADPH oxidase in the commNTS in renovascular hypertensive rats. Under anesthesia, male Holtzman rats were implanted with a silver clip around the left renal artery to induce 2-kidney 1-clip (2K1C) hypertension. After six weeks, these rats were anesthetized and instrumented for recording mean arterial pressure (MAP), renal blood flow (RBF), renal vascular resistance (RVR), and renal sympathetic nerve activity (RSNA) during baseline and after injection of apocynin (nicotinamide adenine dinucleotide phosphate oxidase inhibitor), NSC 23766 (RAC inhibitor) or saline into the commNTS. RESULTS: Apocynin into the commNTS decreased MAP, RSNA, and RVR in 2K1C rats. NSC 23766 into the commNTS decreased MAP and RSNA, without changing RVR in 2K1C rats. CONCLUSION: These results demonstrate that the formation of ROS in the commNTS is important to maintain sympathoexcitation and hypertension in 2K1C rats and suggest that NADPH oxidase in the commNTS could be a potential target for therapeutics in renovascular hypertension.

Comparison of diagnostic performance of RT-qPCR, RT-LAMP and IgM/IgG rapid tests for detection of SARS-CoV-2 among healthcare workers in Brazil.

BACKGROUND: COVID-19 has become a major public health problem after the outbreak caused by SARS-CoV-2 virus. Great efforts to contain COVID-19 transmission have been applied worldwide. In this context, accurate and fast diagnosis is essential. METHODS: In this prospective study, we evaluated the clinical performance of three different RNA-based molecular tests - RT-qPCR (Charité protocol), RT-qPCR (CDC (USA) protocol) and RT-LAMP - and one rapid test for detecting anti-SARS-CoV-2 IgM and IgG antibodies. RESULTS: Our results demonstrate that RT-qPCR using the CDC (USA) protocol is the most accurate diagnostic test among those evaluated, while oro-nasopharyngeal swabs are the most appropriate biological sample. RT-LAMP was the RNA-based molecular test with lowest sensitivity while the serological test presented the lowest sensitivity among all evaluated tests, indicating that the latter test is not a good predictor of disease in the first days after symptoms onset. Additionally, we observed higher viral load in individuals who reported more than 3 symptoms at the baseline. Nevertheless, viral load had not impacted the probability of testing positive for SARS-CoV-2. CONCLUSION: Our data indicates that RT-qPCR using the CDC (USA) protocol in oro-nasopharyngeal swabs samples should be the method of choice to diagnosis COVID-19.

The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy.

Reactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Here, we investigated the impact of the BAF complex inhibitor pyrimethamine on the reservoir of people living with HIV-1 (PLWH). Twenty-eight PLWH on suppressive antiretroviral therapy were randomized (1:1:1:1 ratio) to receive pyrimethamine, valproic acid, both, or no intervention for 14 days. The primary end point was change in cell-associated unspliced (CA US) HIV-1 RNA at days 0 and 14. We observed a rapid, modest, and significant increase in (CA US) HIV-1 RNA in response to pyrimethamine exposure, which persisted throughout treatment and follow-up. Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine. Pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir. These data demonstrate that the licensed drug pyrimethamine can be repurposed as a BAF complex inhibitor to reverse HIV-1 latency in vivo in PLWH, substantiating its potential advancement in clinical studies.

Qualidade de vida de pessoas com úlceras do pé diabético em tratamento ambulatorial: estudo transversal / Calidad de vida de personas con úlceras diabéticas en tratamiento ambulatorio: estudio transversal / Quality of life of people with diabetic foot ulcers in outpatient treatment: cross-sectional study

Objetivo: analisar a qualidade de vida de pessoas com úlceras do pé diabético em tratamento ambulatorial. Método: estudo descritivo e transversal, realizado entre fevereiro e abril de 2019, com 50 pessoas com Diabetes Mellitus, acompanhados em ambulatório especializado. Foram aplicados o questionário sociodemográfico e clínico, o instrumento Freiburg Life Quality Assessment Wound Versão Feridas (FLQA-WK), estatística descritiva e os testes de Comparação t de Student e Anova. Resultados: observou-se menor escore no domínio sintomas físicos (1.84) e maior no domínio vida diária (3.52). O escore total de qualidade de vida foi de 2.61, numa escala que varia de um a cinco, com correlação significativa entre as variáveis clínicas, como tempo de diagnóstico de diabetes >10 anos (p-valor=0,005), internações hospitalares (p-valor=0,019) e nefropatia (p-valor=0,001). Conclusão: a qualidade de vida foi considerada regular, com alteração no domínio vida diária, sendo influenciada negativamente por variáveis clínicas.

Objetivo: analizar la calidad de vida de personas con úlceras diabéticas en tratamiento ambulatorio. Método: estudio descriptivo y transversal, realizado entre febrero y abril de 2019, con 50 personas con Diabetes Mellitus, acompañados en ambulatorio especializado. Fueron aplicados el cuestionario sociodemográfico y clínico, el instrumento Freiburg Life Quality Assessment Wound Versión Heridas (FLQA-WK), estadística descriptiva y los test de Comparación t de Student y Anova. Resultados: se observó menor escore en el dominio síntomas físicos (1.84) y mayor en el dominio vida diaria (3.52). El puntaje total de calidad de vida fue de 2.61, en una escala que varía de uno a cinco, con correlación significativa entre las variables clínicas, como tiempo de diagnóstico de diabetes >10 años (p-valor=0,005), internaciones hospitalarias (p-valor=0,019) y nefropatía (p-valor=0,001). Conclusión: la calidad de vida fue considerada regular, con alteración en el dominio vida diaria, siendo influenciada negativamente por variables clínicas.

Objective: to analyze the quality of life of people with diabetic foot ulcers in outpatient treatment. Method: descriptive and cross-sectional study, conducted between February and April 2019, with 50 people with Diabetes Mellitus, followed in a specialized outpatient clinic. The sociodemographic and clinical questionnaire, the Freiburg Life Quality Assessment Wound Version (FLQA-WK), descriptive statistics and the Student's t-comparison and Anova tests were applied. Results: a lower score was observed in the physical symptoms domain (1.84) and a higher score in the daily life domain (3.52). The total quality of life score was 2.61, on a scale ranging from one to five, with significant correlation between clinical variables, such as time of diagnosis of diabetes >10 years (p-value=0.005), hospital admissions (p-value=0.019) and nephropathy (p-value=0.001). Conclusion: quality of life was considered regular, with changes in the daily life domain, being negatively influenced by clinical variables.

Students Satisfaction with the Use of PlayDoh® as a Tool to Actively Learn 3D Veterinary Anatomy More Accurately.

Understanding veterinary anatomy is an essential skill for the study of veterinary medicine as well as for diagnostic imaging and therapy. Dissection facilities are increasingly limited in some schools and its alternatives have often focussed on using two-dimensional images. However, the study of veterinary anatomy is mainly concerned with identifying structures and spatial relationships between them within a 3D space, and the use of 2D teaching approaches does not provide accurate information. We tested whether PlayDoh® student-built models could be an inexpensive potential tool beneficial to veterinary students learning anatomy in three distinct scenarios: (1) during a lecture, introducing a new concept; (2) during a flipped classroom approach where a video-podcast lecture was to be watched by the students prior to the lecture and (3) as a revision session where students brought their own questions and created, under supervision, their own models to respond to them. PlayDoh® sessions benefitted 172 first-year Veterinary Medicine and Animal Science students. The most accurate visualisation of anatomical structures in 3D was the principal benefit mentioned by the learners (35%). In addition, the learners noted that the technique would help with 'retention' (18%). According to the students' preferences, it was possible to create four groups: A, B, C and D. Group A encompassed the methodologies most liked by students and consisted of lectures, dissection and demonstrations. Group B included demonstrations and 3D modelling using PlayDoh®. Group C consisted of 3D modelling using PlayDoh®, books and online and, finally, group D included the methodologies least preferred by students, i.e. online and PBL. Our findings suggest that using 3D PlayDoh® modelling has potential as a method to enhance the learning of veterinary anatomy and may be most valuable to those students learning more complex subject areas that require a 3D teaching approach in practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01892-y.

Continuum de desmontes da saúde pública na crise do covid-19: o neofascismo de Bolsonaro / Continuum of public health dismantling during the covid-19 crisis: Bolsonaro's neofascism

Resumo Neste artigo, aprofunda-se a discussão crítica às políticas adotadas pelo governo Bolsonaro em relação à saúde pública, particularmente no que tange ao financiamento em geral, ao enfrentamento da pandemia e ao primeiro ano de implantação do novo modelo de "financiamento" para a Atenção Primária à Saúde (APS). A análise evidencia o acirramento da legitimidade restrita do regime político, assumida por políticas ultraneoliberais e pelo neofascismo do governo Bolsonaro. Estas formas de dominação - política e econômica - engendram uma conjuntura interna que visa remodelar a acumulação de capital na saúde pública via APS por meio de mecanismos "operacionais" burocráticos sutis de desconstrução da universidade do "financiamento". Na primeira parte, discute-se a abrangência da crise tripla do capital - sanitária, econômica e ecológica - e sua relação orgânica com o Estado no capitalismo dependente brasileiro, abrindo espaço para o crescimento da restrição do regime político endossado pela ascensão do neofascismo. Na segunda parte, aborda-se a escalada do desfinanciamento do Sistema Único de Saúde (SUS) em plena crise de covid-19 e os efeitos da implementação do modelo de financiamento da APS, evidenciando a continuidade do processo de valorização de um "SUS operacional" em detrimento do seu princípio de universalidade como dimensão neofascista do governo Bolsonaro.

Abstract This article deepens the critical discussion about the policies of the Bolsonaro government regarding public health, particularly regarding the general financing, the confrontation of the pandemic, and the first year of implementation of the new financing model for Primary Health Care (PHC). The analysis evidences the aggravation of the restrict legitimacy of the political regime, assumed by ultra-neoliberal policies and by the neofascism of the Bolsonaro government. These forms of domination - political and economic - produce an internal conjuncture that seeks to remodel the capital accumulation in public health by PHC by subtle bureaucratic "operational" mechanisms of deconstruction of financing universality. In the first part, the coverage of the triple crisis of the capital - sanitary, economic and ecological - and its organic relationship to the State in the Brazilian dependent capitalism is discussed, opening space to the increase of the restriction of the political regime endorsed by the ascension of the neofascism. In the second part, the increase of the de-financing of the Unified Health System (SUS) right in the middle of the covid-19 crisis and the effects of the implementation of the financing model of the PHC, evidencing the continuity of the process of valuing an "operational SUS" in detriment of its universality principle as a neofascist dimension of Bolsonaro's government.

Cancer patients admitted in the emergency department: A single-centre observational study.

OBJECTIVE: This study aims to analyse patients' clinical profiles seen at an emergency unit of a public oncology reference hospital in Belo Horizonte, Brazil. METHODS: This is a cross-sectional, observational, retrospective study, with data collection through patients' medical records seen between 2016 and 2018. The identification of patients was carried out through research on hospital admission authorization guides. RESULTS: A total of 2932 medical records were evaluated, of which only 21.5% were cancer patients. A cancer diagnosis was made for 21.5% of patients during hospitalisation. In this group, pain and weight loss are frequent symptoms, and haematological diseases (15.2%) were the most frequent tumour type. Patients with a previous cancer diagnosis presented the most prevalent tumour breast (18.3%) and altered consciousness level as a leading symptom. Analgesics were the most prescribed drugs in both groups. CONCLUSION: This study showed two distinct groups of cancer patients: with or without a previous cancer diagnosis. However, these two groups are comparable in almost all the variables analysed. Therefore, we believe that the factors that could guide the care in an emergency are related to education on cancer symptoms for the population to contribute to an early diagnosis and cancer training for emergency department (ED) professionals' to better monitor advanced-stage patients for symptom management.

Analysis of the distribution of vagal afferent projections from different peripheral organs to the nucleus of the solitary tract in rats.

Anatomical tracing studies examining the vagal system can conflate details of sensory afferent and motor efferent neurons. Here, we used a serotype of adeno-associated virus that transports retrogradely and exhibits selective tropism for vagal afferents, to map their soma location and central termination sites within the nucleus of the solitary tract (NTS). We examined the vagal sensory afferents innervating the trachea, duodenum, stomach, or heart, and in some animals, from two organs concurrently. We observed no obvious somatotopy in the somata distribution within the nodose ganglion. The central termination patterns of afferents from different organs within the NTS overlap substantially. Convergence of vagal afferent inputs from different organs onto single NTS neurons is observed. Abdominal and thoracic afferents terminate throughout the NTS, including in the rostral NTS, where the 7th cranial nerve inputs are known to synapse. To address whether the axonal labeling produced by viral transduction is so widespread because it fills axons traveling to their targets, and not just terminal fields, we labeled pre and postsynaptic elements of vagal afferents in the NTS . Vagal afferents form multiple putative synapses as they course through the NTS, with each vagal afferent neuron distributing sensory signals to multiple second-order NTS neurons. We observe little selectivity between vagal afferents from different visceral targets and NTS neurons with common neurochemical phenotypes, with afferents from different organs making close appositions with the same NTS neuron. We conclude that specific viscerosensory information is distributed widely within the NTS and that the coding of this input is probably determined by the intrinsic properties and projections of the second-order neuron.

Chemogenetic inhibition of Phox2-expressing neurons in the commissural NTS decreases blood pressure in anesthetized spontaneously hypertensive rats.

Interruption of the activity of neurons in the commissural portion of the nucleus of the solitary tract (cNTS) decreases blood pressure (BP) in experimental models of hypertension, such as the spontaneously hypertensive (SH) rat. To examine whether PHOX2B expressing cNTS neurons are involved in maintaining the elevated BP, we used replication-deficient viruses with a modified Phox2 binding site promoter to express the inhibitory chemogenetic allatostatin receptor or green fluorescent protein in the cNTS. Following administration of allatostatin, we observed a depressor and bradycardic response in anesthetized SH rats that expressed the allatostatin receptor. Injection of allatostatin did not affect BP or heart rate (HR) in control SH rats expressing green fluorescent protein in the cNTS. Immunohistochemistry showed that the majority of transduced cNTS neurons were PHOX2B-immunoreactive and some also expressed tyrosine hydroxylase. We conclude that in anesthetized SH rat, the Phox2B expressing cNTS neurons maintain elevated BP.

Development of eight wireless automated cages system with two lick-o-meters each for rodents.

Drinking behavior has been used in basic research to study metabolism, motivation, decision-making and different aspects of health problems, such as anhedonia and alcohol use disorders. In the majority of studies, liquid intake is measured by weighing the bottles before and after the experiment. This method does not tell much about the drinking microstructure, e.g., licking bouts and periods of preference for each liquid, which could be valuable to understand drinking behavior. To improve the data acquisition of drinking microstructure, companies have developed lick-o-meters devices that acquire timestamps when animals approach or drink from a specific sipper. Nevertheless, commercially available devices have elevated costs. Here, we present a low-cost alternative for a lick-o-meter system that allows wireless data acquisition of licking from eight cages with two sippers each. We run a three-phase validation protocol to ensure 1) proper choice of the sensor to detect licks; 2) adaptation of the device to a wireless transmission and realistic in silico tests; and 3) in vivo tests to correlate the amount of licks measured by the prototype and the bottle weight. The capacitive sensor presented appropriate recall and precision for our device. After adaptation to wireless transmission, the in silico validation demonstrated low reading and transmission errors for the device even when tested in extreme simultaneous licking conditions. Finally, a positive correlation between volume consumption and lick's count in the in vivo test was observed, showing that the prototype can be used for in vivo studies interested in rodent drinking microstructure.Significant StatementThis study presents an innovative and low-cost solution for drinking behavioral studies: a lick-o-meter system based on an open-source hardware platform with a user-friendly interface software, capable of simultaneously receiving data from eight automated cages with two drinking bottles each. The lick-o-meter brings an accessible device to acquire high-quality and detailed data. This device also has the possibility to be adaptable to new types of sensors or other neuroscience tools capable of measuring brain activity simultaneously to the behavior.

Fatores que influenciam a adesão de gestantes adolescentes às práticas recomendadas na assistência pré-natal / Factors influencing pregnant adolescents' adherence to best practices in prenatal care

Resumo Introdução a gravidez na adolescência apresenta vulnerabilidades biológica, econômica, epidemiológica e social, tornando a adesão às práticas de autocuidado fundamental para o bem-estar do binômio mãe e filho. Objetivo analisar a influência de variáveis sociodemográficas, clínicas e das orientações recebidas na adesão às práticas recomendadas na assistência pré-natal. Método estudo descritivo e quantitativo, realizado com 30 gestantes adolescentes que fizeram acompanhamento pré-natal em ambulatório. Resultados a média de idade foi de 15,7 anos, na sexarca, ou início da sexualidade, de 13,7 e de escolaridade 7,5. A maioria não possuía ocupação remunerada, tinha companheiro fixo e, apesar de não ter planejado a gravidez, ela era desejada. O pior escore de adesão foi no domínio controle de peso e alimentação e o melhor no domínio comportamento de risco. Conclusão apesar de não haver correlação estatisticamente significante entre as variáveis sociodemográficas e clínicas, os escores de adesão são superiores quando as gestantes adolescentes referem possuir companheiro fixo, ter planejado a gravidez e ter recebido orientações.

Abstract Background Pregnancy in adolescence presents biological, economic, epidemiological and social vulnerabilities, making adherence to self-care practices fundamental to the well-being of the mother-child binomial. Objective Analyze the influence of sociodemographic and clinical variables and the guidance received on adherence to best practices in prenatal care. Method This is a descriptive quantitative study conducted with 30 pregnant adolescents who underwent prenatal follow-up in an outpatient clinic. Results Mean age of participants was 15.7 years; they had their first sexual intercourse at age 13.7 and 7.5 years of formal education. Most participants had no paid occupation. They had a steady partner and, despite not having planned their pregnancies, they were desired. The worst self-care adherence score was observed in the weight control and nutrition domain, and the best in the risk behavior domain. Conclusion Although there was no statistically significant correlation between the sociodemographic and clinical variables, adherence scores are higher when pregnant adolescents report having a steady partner, having planned their pregnancies, and having received guidance.

Weak central coherence in adults with ASD: Evidence from eye-tracking and thematic content analysis of social scenes.

Central Coherence Weakness has been defined as a tendency for local rather than global processing that may underlie core deficits in Autism Spectrum Disorder (ASD). In social contexts it may be expressed in difficulties to integrate social cues arising from the recognition of emotions in faces or from the environment in order to understand people's interactions. A sample of 28 adults diagnosed with ASD Level 1 and 25 controls was submitted to a cartoon-like task with the instruction to describe social scenes and to Navon letter stimuli. Both quantitative measures and qualitative (thematic content analysis) procedures were used to assess performance. Heatmap and fixation preferences according to the stimuli quadrants were used to investigate eye-tracking patterns. A tendency to local processing, independently of the stimuli type, in the ASD participants was observed. Data from visual tracking by quadrants and from verbal reports suggest loss of social cues important for understanding context. Their reaction time and response duration were increased in relation to controls. The findings corroborate the idea that weak central coherence may be part of the cognitive phenotype in ASD.

Autistic adults often report difficulties in interpreting social situations. These difficulties are commonly associated with a tendency to visually focus on specific parts of the situation (known as local processing) to the detriment of the whole situation. This way of looking at things has been given the name "weak central coherence," and may result in difficulties in understanding a situation or other people's behaviors. A group of ASD and controls were asked to describe two different types of image, one showing a common social situation, the other Navon figure. Eye-tracking technology was used to analyze how the participants looked at the images (which part of the image and for how long) and asked about what they had seen. The results showed that in the group of autistic participants there was a tendency to focus on the details in both types of images. The analysis of the verbal reports revealed that the interpretation of the social contexts by those with ASD was not what was expected, associated with a specific focus on details. These findings may be useful for a better understanding of some difficulties experienced by ASD in social contexts and contribute to therapeutic treatments.