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Several lines of evidence have demonstrated that the cannabinoid type 1 receptor (CBFluorescent neural tract tracers were deposited in either CPu or in SNpr. Wistar rats received injection of vehicle, anandamide (AEA), either at low (50 pmol) or high (100 pmol) concentrations in CPu followed by bicuculline microinjections in dlSC.Connections between CPu, the SNpr and dlSC were demonstrated. The GABAThese findings suggest that while pre-synaptic CB1-signalling subserves an indirect facilitatory effect of AEA on striato-nigral pathways causing panicolytic-like responses through midbrain tectum enhanced activity, post-synaptic TRPV

Context and objectives :The unexpected pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected several activities and exposed workers, students and the large mass of unemployed people to an economic and psychological pressure that could lead to various problems, such as anxiety, fear, depression and insomnia, consequently causing impairment of quality of life. Method: A cross-sectional study was conducted using the COVID-19 Peri-Traumatic Distress Index (CPDI) and the Fear of COVID-19 Scale (FCV-19S) to measure peri-traumatic stress and fear, such as psychological reactions during the 2019 coronavirus disease (COVID-19) pandemic. An online spreadsheet was used as a data collection tool to send the questionnaire and scales to a sample of 1,844 participants. Data were analyzed in groups of health professionals, students and teachers, and an analysis was performed between unemployed and employed people in order to evaluate the impact of employment on the population’s mental health. Results: All groups presented from moderate to high CPDI and FCV-19S scores, and students and unemployed people had higher levels of stress and fear. Conclusion: COVID-19 pandemic had a significant impact on the Brazilian population, with students and the unemployed showing the highest rates of stress and fear.

Background Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019–2020 influenza vaccine against influenza-associated hospitalization in the United States. Methods We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve-transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases vs test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. Results A total of 3116 participants were included, including 18% (n = 553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (n = 2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI], 27%–52%). VE against A(H1N1)pdm09 viruses was 40% (95% CI, 24%–53%) and 33% against B viruses (95% CI, 0–56%). Of the 2 major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A + 187A,189E) was 59% (95% CI, 34%–75%) whereas no VE was observed against the other group (5A + 156K) (–1% [95% CI, –61% to 37%]). Conclusions In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

Dor é uma experiência pessoal e subjetiva que pode apenas ser sentida pelo sofredor. A dor aguda tem a finalidade de avisar o indivíduo que algo está errado. Contudo, a dor crônica (DC) é um problema global de saúde, que afeta a qualidade de vida e torna o indivíduo parcial ou totalmente incapacitado. A pesquisa básica utiliza diversos modelos animais para o estudo da dor aguda ou crônica, bem como para o estudo das principais comorbidades oriundas de sua cronificação como a ansiedade e a depressão. Esta revisão aborda os modelos animais mais comumente utilizados neste contexto.

Background Coronavirus disease (COVID-19) can cause severe illness and death. Predictors of poor outcome collected on hospital admission may inform clinical and public health decisions. Methods We conducted a retrospective observational cohort investigation of 297 adults admitted to 8 academic and community hospitals in Georgia, United States, during March 2020. Using standardized medical record abstraction, we collected data on predictors including admission demographics, underlying medical conditions, outpatient antihypertensive medications, recorded symptoms, vital signs, radiographic findings, and laboratory values. We used random forest models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for predictors of invasive mechanical ventilation (IMV) and death. Results Compared with age Conclusions After adjustment for patient and clinical characteristics, older age was the strongest predictor of death, exceeding comorbidities, abnormal vital signs, and laboratory test abnormalities. That coronary artery disease, but not chronic lung disease, was associated with death among hospitalized patients warrants further investigation, as do associations between certain antihypertensive medications and death.

SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in the United States during January 2020 (1). Since then, >980,000 cases have been reported in the United States, including >55,000 associated deaths as of April 28, 2020 (2). Detailed data on demographic characteristics, underlying medical conditions, and clinical outcomes for persons hospitalized with COVID-19 are needed to inform prevention strategies and community-specific intervention messages. For this report, CDC, the Georgia Department of Public Health, and eight Georgia hospitals (seven in metropolitan Atlanta and one in southern Georgia) summarized medical record-abstracted data for hospitalized adult patients with laboratory-confirmed* COVID-19 who were admitted during March 2020. Among 305 hospitalized patients with COVID-19, 61.6% were aged

Dolutegravir-based regimens are now standard of care for human immunodeficiency virus treatment for millions of people around sub-Saharan Africa. To ensure its continued efficacy, monitoring of emerging drug resistance that inform a treatment strategy among those failing is crucial. In this report, we outline the US President’s Emergency Plan for AIDS Relief to leverage viral load infrastructure to implement effective drug resistance surveillance in the countries it supports.

Background and Aims: Patients and the general public are under insurmountable psychological pressure which may lead to various psychological problems, such as anxiety, fear, depression, and insomnia, causing, consequently, the impaired quality of life. Psychological crisis intervention plays a pivotal role in the overall deployment of health-related quality of life and disease control. A novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS- CoV-2), a pathogen of the new coronavirus disease (COVID-19), has affected several sector activities, including people’s health. To enhance infection control methods, appropriate interventions, and public health policies, the present study aims to assess the fear and peri-traumatic stress during the COVID-19 inBrazil. Method: A cross-sectional survey has been conducted from April 12th to 18th from 2020, using the Peri-Traumatic Distress Scale (CPDI) and the Fear Scale (FCV-19S) aiming to measure the peri-traumatic stress and fear as psychological reactions during the COVID-19 pandemic. For that purpose, an online spreadsheet was used to send the questionnaire and scales to a sample of 1844 participants as a collecting information tool. After the data analysis, the individuals were separated into 4 groups: Group 1 (1232) population without chronic health conditions; group 2 (298) patients with previous psychological suffering, group 3 (229) patients with cardiovascular diseases, group 4 (71) patients with diabetes. For analysis, G1 were considered control for comparison with groups 2, 3 and 4. Results: All the groups showed the CPDI and FCV-19S increased in comparison with the G1 group. Concerning CPDI, the G 3 was increased when compared to G1, G2 and G4. The G3 had the FCV-19S higher in comparison with G1, G2 and G4. The Wilcoxon-Mann-Whitney test showed a statistical difference between the control group in comparison with 2 and 3 groups (Mann-Whitney p Conclusion: The COVID-19 pandemic had a significant impact on the Brazilian population, with patients with heart disease and hypertension presenting the highest numbers of stress and fear, with numbers comparable and even higher than those who reported previous psychological distress.

Defensive responses are neurophysiological processes crucial for survival during threatening situations. Defensive immobility is a common adaptive response, in rodents, elaborated by ventrolateral periaqueductal gray matter (vlPAG) when threat is unavoidable. It is associated with somatosensory and autonomic reactions such as alteration in the sensation of pain and rate of respiration. In this study, defensive immobility was assessed by chemical stimulation of vlPAG with different doses of NMDA (0.1, 0.3, and 0.6 nmol). After elicitation of defensive immobility, antinociceptive and respiratory response tests were also performed. Results revealed that defensive immobility was followed by a decrease in the nociceptive perception. Furthermore, the lowest dose of NMDA induced antinociceptive response without eliciting defensive immobility. During defensive immobility, respiratory responses were also disturbed. Interestingly, respiratory rate was increased and interspersed with prolonged expiratory phase of breathing. These findings suggest that vlPAG integrates three different defensive behavioral responses, contributing to the most effective defensive strategies during threatening situations.

BackgroundIn early 2020, an outbreak of coronavirus disease 2019 occurred among passengers and crew of the Diamond Princess cruise ship. During February 16–17, some US citizens, residents, and their partners voluntarily repatriated to the US from Japan.MethodsWe conducted a retrospective, longitudinal evaluation of repatriated travelers where the outcome of interest was a positive test for SARS-CoV-2. Travelers who tested positive for SARS-CoV-2 were isolated in hospitals or at home under county isolation orders and underwent serial testing by real-time reverse transcription polymerase chain reaction (RT-PCR) approximately every other day, as contemporaneous US guidance required two consecutive negative tests collected ≥24 hours apart and symptom improvement before release from isolation.ResultsAmong quarantined repatriated travelers, 14% tested positive for SARS-CoV-2. One-fifth of infected travelers initially tested negative but were identified on subsequent testing. All infected travelers remained asymptomatic or developed mild symptoms during isolation. Many travelers remained in prolonged isolation because of persistent viral detection based on contemporaneous policies.ConclusionOur findings support testing within 3-5 days after possible SARS-CoV-2 exposure to comprehensively identify infections and mitigate transmission and lend support to symptom- and time-based isolation recommendations, rather than test-based criteria.

Nasopharyngeal swabs (NPS) collected by trained healthcare professionals are the preferred specimen for SARS-CoV-2 testing. Self-collected specimens might decrease patient discomfort, conserve healthcare resources, and be preferred by patients. During August – November 2020, 1,806 adults undergoing SARS-CoV-2 testing in Denver, Colorado and Atlanta, Georgia, provided self-collected anterior nares swabs (ANS) and saliva specimens before NPS collection. Compared to NPS, sensitivity for SARS-CoV-2 detection by rRT-PCR appeared higher for saliva than for ANS (85% versus 80% in Denver; 67% versus 58% in Atlanta) and higher among participants reporting current symptoms (94% and 87% in Denver; 72% and 62% in Atlanta, for saliva and ANS, respectively) than among those reporting no symptoms (29% and 50% in Denver; 50% and 44% in Atlanta, for saliva and ANS, respectively). Compared to ANS, saliva was more challenging to collect and process. Self-collected saliva and ANS are less sensitive than NPS for SARS-CoV-2 detection; however, they offer practical advantages and might be most useful for currently symptomatic patients.

Cannabinoid receptor type 1 (CB1R) is widely distributed in the substantia nigra pars reticulata (SNpr). However, the role of CB1R at the SNpr level in threatening situations is poorly understood. We investigated the role of CB1R in the SNpr on the expression of fear responses in mice confronted with urutu-cruzeiro pit vipers. First, a bidirectional neurotracer was injected into the SNpr; then, immunostaining of the vesicular GABA transporter was conducted at the levels of the striatum (CPu) and deep layers of the superior colliculus (dlSC). In addition, CB1R immunostaining and GABA labelling were performed in the SNpr. Using a prey-versus-snake paradigm, mice were pretreated with the CB1R antagonist AM251 (100 pmol) and treated with the endocannabinoid anandamide (AEA, 5 pmol) in the SNpr, followed by bicuculline (40 ng) in the dlSC, and were then confronted with a snake. Bidirectional neural tract tracers associated with immunofluorescence showed the GABAergic striatonigral disinhibitory and nigrotectal inhibitory pathways. Furthermore, we showed that CB1R labelling was restricted to axonal fibres surrounding SNpr GABAergic cells. We also demonstrated a decrease in the defensive behaviours of mice treated with AEA in the SNpr, but this effect was blocked by pre-treatment with AM251 in this structure. Taken together, our results show that the panicolytic consequences of the AEA enhancement in the SNpr are signalled by CB1R, suggesting that CB1R localised in axon terminals of CPu GABAergic neurons in the SNpr modulates the activity of the nigrotectal GABAergic pathway during the expression of defensive behaviours in threatening situations.

Patients and the general public are under insurmountable psychological pressure which may lead to various psychological problems, such as anxiety, fear, depression, and insomnia, causing, consequently, the impaired quality of life. Psychological crisis intervention plays a pivotal role in the overall deployment of health-related quality of life and disease control. A novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARSCoV-2), a pathogen of the new coronavirus disease (COVID-19), has affected several sector activities, including people's health. To enhance infection control methods, appropriate interventions, and public health policies, the present study aims to assess the fear and peri-traumatic stress during the Covid-19 in Brazil. Method: A cross-sectional survey has been conducted from April 12th to 18th using the Peri-Traumatic Distress Scale (CPDI) and the Fear Scale (FCV-19S) aiming to measure the peri-traumatic stress and fear as psychological reactions during the COVID-19 pandemic. For that purpose, an online spreadsheet was used to send the questionnaire and scales to a sample of 1844 participants as a collecting information tool. After the data analysis, the individuals were separated into 4 groups: Group 1 (1232) population without chronic health conditions; group 2 (298) patients with previous psychological suffering, group 3 (229) patients with cardiovascular diseases, group 4 (71) patients with diabetes. For analysis, G1 and were considered control for comparison with groups 2, 3 and 4 in accordance with One-Way Anova followed by Bonferroni test. Results: All the groups showed the CPDI and FCV-19S increased in comparison with the G1 group. Concerning CPDI, the G 3 was increased when compared to G1, G2 and G4. The G3 had the FCV-19S higher in comparison with G1, G2 and G4. The Wilcoxon-Mann-Whitney test showed a statistical difference between the control group in comparison with 2 and 3 groups (Mann-Whitney p< 0.05). Conclusion: The COVID-19 pandemic had a significant impact on the Brazilian population, with patients with heart disease and hypertension presenting the highest numbers of stress and fear, with numbers comparable and even higher than those who reported previous psychological distress.

COVID-19 pandemic continues to spread exponentially worldwide, especially in America. At the end of August 2020, Brazil is one of the most affected countries with more than three and a half million cases and up to 114,250 deaths. This study aims to assess the fear and peri-traumatic stress during the COVID-19 pandemics in Brazil, to enhance infection control methods, appropriate interventions, and public health policies. A cross-sectional survey has been conducted from April 12th to 18th using the Peri-Traumatic Distress Scale (CPDI) and the Fear Scale (FCV-19S) aiming to measure the peri-traumatic stress and fear as psychological reactions during the COVID-19 pandemic. For that purpose, an online spreadsheet was used to send the questionnaire and scales to a sample of 1844 participants as a collecting information tool. Significant positive relationship (r = 0.660, p < 0.001) and internal consistencies on CPDI and FCV-195 scales (Cronbach Alfa scores 0.90 and 0.88 respectively) were shown. Results highlight significant gender differences as in both scales women’s mean scores are higher showing that it is paramount that women’s voices were represented in policy spaces as socially constructed gender roles place them in a strategic position to enhance multi-level interventions (primary and secondary effects of COVID-19), equitable policies, and new approaches to control the pandemic.

Background: Gamma-aminobutyric acid (GABA)ergic and opioid systems play a crucial role in the neural modulation of innate fear organised by the inferior colliculus (IC). In addition, the IC is rich in GABAergic fibres and opioid neurons, which are also connected to other mesencephalic structures, such as the superior colliculus and the substantia nigra. However, the contribution of distinct opioid receptors (ORs) in the IC during the elaboration and expression of innate fear and panic-like responses is unclear. The purpose of the present work was to investigate a possible integrated action exerted by ORs and the GABAA receptor-mediated system in the IC on panic-like responses. Methods: The effect of the blockade of either µ1- or κ-ORs in the IC was evaluated in the unconditioned fear-induced responses elicited by GABAA antagonism with bicuculline. Microinjections of naloxonazine, a µ1-OR antagonist, or nor-binaltorphimine (nor-BNI), a κ-OR antagonist, were made into the IC, followed by intramesencephalic administration of the GABAA-receptor antagonist bicuculline. The defensive behaviours elicited by the treatments in the IC were quantitatively analysed, recording the number of escapes expressed as running (crossing), jumps, and rotations, over a 30-min period in a circular arena. The exploratory behaviour of rearing was also recorded. Results: GABAA-receptor blockade with bicuculline in the IC increased defensive behaviours. However, pretreatment of the IC with higher doses (5 µg) of naloxonazine or nor-BNI followed by bicuculline resulted in a significant decrease in unconditioned fear-induced responses. Conclusions: These findings suggest a role played by µ1- and κ-OR-containing connexions and GABAA receptor-mediated neurotransmission on the organisation of panic attack-related responses elaborated by the IC neurons.

BACKGROUND: The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens.METHODS: We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted.FINDINGS: Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2·9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain.INTERPRETATION: In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators.FUNDING: Bill & Melinda Gates Foundation.

Background: There is a controversy regarding the key role played by opioid peptide neurotransmission in the modulation of panic-attack-related responses. Aims: Using a prey versus rattlesnakes paradigm, the present work investigated the involvement of the endogenous opioid peptide-mediated system of the inferior colliculus in the modulation of panic attack-related responses. Methods: Wistar rats were pretreated with intracollicular administration of either physiological saline or naloxone at different concentrations and confronted with rattlesnakes ( Crotalus durissus terrificus). The prey versus rattlesnake confrontations were performed in a polygonal arena for snakes. The defensive behaviors displayed by prey (defensive attention, defensive immobility, escape response, flat back approach and startle) were recorded twice: firstly, over a period of 15 min the presence of the predator and a re-exposure was performed 24 h after the confrontation, when animals were exposed to the experimental enclosure without the rattlesnake. Results: The intramesencephalic non-specific blockade of opioid receptors with microinjections of naloxone at higher doses decreased both anxiety- (defensive attention and flat back approach) and panic attack-like (defensive immobility and escape) behaviors, evoked in the presence of rattlesnakes and increased non-defensive responses. During the exposure to the experimental context, there was a decrease in duration of defensive attention. Conclusions: These findings suggest a panicolytic-like effect of endogenous opioid receptors antagonism in the inferior colliculus on innate (panic attack) and conditioned (anticipatory anxiety) fear in rats threatened by rattlesnakes.

The COVID-19 started in China and took over the world becoming a pandemic, arriving in Latin America in mid-February 2020. The South American continent is going through a delicate political, economic, and social moment that reflects the fragility of our health systems and science, contagion rates reduction strategies, and health services overload. Nevertheless, several studies are being carried out in Brazil and worldwide aiming to understand the characteristics of the disease and the cure of people infected by the coronavirus. Therefore, we must consider science-based strategies to combat the pandemic and promote a health system that takes care of the population.

Gamma-aminobutyric acid (GABA)ergic and opioid systems play a crucial role in the neural modulation of innate fear organised by the inferior colliculus (IC). In addition, the IC is rich in GABAergic fibres and opioid neurons, which are also connected to other mesencephalic structures, such as the superior colliculus and the substantia nigra. However, the contribution of distinct opioid receptors (ORs) in the IC during the elaboration and expression of innate fear and panic-like responses is unclear. The purpose of the present work was to investigate a possible integrated action exerted by ORs and the GABAA receptor-mediated system in the IC on panic-like responses.The effect of the blockade of either µ1- or κ-ORs in the IC was evaluated in the unconditioned fear-induced responses elicited by GABAA antagonism with bicuculline. Microinjections of naloxonazine, a µ1-OR antagonist, or nor-binaltorphimine (nor-BNI), a κ-OR antagonist, were made into the IC, followed by intramesencephalic administration of the GABAA-receptor antagonist bicuculline. The defensive behaviours elicited by the treatments in the IC were quantitatively analysed, recording the number of escapes expressed as running (crossing), jumps, and rotations, over a 30-min period in a circular arena. The exploratory behaviour of rearing was also recorded.GABAA-receptor blockade with bicuculline in the IC increased defensive behaviours. However, pretreatment of the IC with higher doses (5 µg) of naloxonazine or nor-BNI followed by bicuculline resulted in a significant decrease in unconditioned fear-induced responses.These findings suggest a role played by µ1- and κ-OR-containing connexions and GABAA receptor-mediated neurotransmission on the organisation of panic attack-related responses elaborated by the IC neurons.

Purpose: The adaptation of BPI-B into North/Northeast of Brazil. The purpose of this study was the translation and adaptation of the BPI to Portuguese language, as spoken in Brazil, aiming at its posterior usage to measure both intensity and interference of pain in cancer patients’ life. Methods: The BPI-B was developed from the original BPI, using back-translation and committee review. The Back Translation was compared to the original BPI, as a result, the North/Northeast Brazilian version proved to have the same goals, and is similar to other current versions, observing its psychometrics properties. The inventory presented a final sample of 475 patients, whose average age was 54.37 years old (DP = 14.56), most female (58.9%). One hundred ninety-six patients in elementary school took part. It had its objective to group multiple indicators that responded to validation, precision and parsimony criteria. The patients answered the BPI at the very moment they were diagnosed as cancer cases. All of them were above 18 years old and they were also undergoing treatment at Cancer Ambulatory in a Hospital in Ceara, Brazil. The retest was carried, after about a month of the first application. In order to verify the reliability of inventory adaptation, the exploratory factorial analysis was used as the oblique rotation axis. Results: Exploratory factor analysis confirmed two underlying dimensions, pain severity, and pain interference, with Cronbach’s α 0.833 and 0.733, respectively. Conclusion: A proposition of a north/northeast Brazilian version of BPI turned out to be adequate, gathering evidences of adaptation and internal consistency similar to already validated versions.

It has been proposed that the post-ictal state is associated with the expression of hypoalgesia. It is clear that the projections among the periaqueductal gray matter (PAG), dorsal raphe nucleus (DRN) and locus coeruleus (LC) play a role in pain management. These mesencephalic structures have direct reciprocal opioid and monoaminergic projections to the LC that can possibly modulate post-ictal hypoalgesia. The goal of this study was to examine if LC-opioid and serotonergic/noradrenergic mechanisms signal the post-ictal hypoalgesic responses to tonic–clonic seizures produced by intraperitoneal administration of pentylenetetrazole (PTZ at 64 mg/kg), causing an ionophore γ-aminobutyric acid (GABA)-mediated Cl− influx antagonism. The rodents’ nociceptive threshold was measured by the tail-flick test. Intra-LC cobalt chloride (1.0 nM/0.2 μL) microinjections produced intermittent local synaptic inhibition and were able to reduce post-ictal hypoalgesia. Central administration of naltrexone (a non-selective antagonist for opioid receptors), naloxonazine (a selective antagonist for μ1-opioid-receptors), methysergide (a non-selective antagonist for serotonergic receptors) or ketanserin (an antagonist for both α1-noradrenergic and 5-Hydroxytryptamine(HT)2A/2C receptors) at 5.0 μg/0.2 μL, R-96544 (a 5-HT2A receptor selective antagonist) at 10 nM/0.2 μL, or RS-102221 (a 5-HT2C receptor selective antagonist) at 0.15 μg/0.2 μL into the LC also decreased post-ictal hypoalgesia. The data presented here suggest that the post-ictal antinociception mechanism involves the μ1-opiod, 5-HT2A- and 5-HT2C-serotonergic, and α1-noradrenergic receptors in the LC.

The dorsal raphe nucleus (DRN) is an important brainstem source of 5-hydroxytryptamine (5-HT), and 5-HT plays a key role in the regulation of panic attacks. The aim of the present study was to determine whether 5-HT1A receptor-containing neurons in the medial hypothalamus (MH) receive neural projections from DRN and to then determine the role of this neural substrate in defensive responses. The neurotracer biotinylated dextran amine (BDA) was iontophoretically microinjected into the DRN, and immunohistochemical approaches were then used to identify 5HT1A receptor-labelled neurons in the MH. Moreover, the effects of pre-treatment of the dorsomedial hypothalamus (DMH) with 8-OH-DPAT and WAY-100635, a 5-HT1A receptor agonist and antagonist, respectively, followed by local microinjections of bicuculline, a GABAA receptor antagonist, were investigated. We found that there are many projections from the DRN to the perifornical lateral hypothalamus (PeFLH) but also to DMH and ventromedial (VMH) nuclei, reaching 5HT1A receptor-labelled perikarya. DMH GABAA receptor blockade elicited defensive responses that were followed by antinociception. DMH treatment with 8-OH-DPAT decreased escape responses, which strongly suggests that the 5-HT1A receptor modulates the defensive responses. However, DMH treatment with WAY-100635 failed to alter bicuculline-induced defensive responses, suggesting that 5-HT exerts a phasic influence on 5-HT1A DMH neurons. The activation of the inhibitory 5-HT1A receptor had no effect on antinociception. However, blockade of the 5-HT1A receptor decreased fear-induced antinociception. The present data suggest that the ascending pathways from the DRN to the DMH modulate panic-like defensive behaviours and mediate antinociceptive phenomenon by recruiting 5-HT1A receptor in the MH.

The endogenous opioid peptide system has been implicated in the neural modulation of fear and anxiety organised by the dorsal midbrain. Furthermore, previous results indicate a fundamental role played by inferior colliculus (IC) opioid mechanisms during the expression of defensive behaviours, but the involvement of the IC µSpecific pathogen-free Wistar rats were treated with microinjection of the selective µThe blockade of µTaken together, these results suggest that a decrease in µ

Background: The endogenous opioid peptide system has been implicated in the neural modulation of fear and anxiety organised by the dorsal midbrain. Furthermore, previous results indicate a fundamental role played by inferior colliculus (IC) opioid mechanisms during the expression of defensive behaviours, but the involvement of the IC µ1-opioid receptor in the modulation of anxiety- and panic attack-related behaviours remains unclear. Using a prey-versus-snake confrontation paradigm, we sought to investigate the effects of µ1-opioid receptor blockade in the IC on the defensive behaviour displayed by rats in a dangerous situation. Methods: Specific pathogen-free Wistar rats were treated with microinjection of the selective µ1-opioid receptor antagonist naloxonazine into the IC at different concentrations (1.0, 3.0 and 5.0 µg/0.2 µL) and then confronted with rattlesnakes ( Crotalus durissus terrificus). The defensive behavioural repertoire, such as defensive attention, flat back approach (FBA), startle, defensive immobility, escape or active avoidance, displayed by rats either during the confrontations with wild snakes or during re-exposure to the experimental context without the predator was analysed. Results: The blockade of µ1-opioid receptors in the IC decreased the expression of both anxiety-related behaviours (defensive attention, FBA) and panic attack-related responses (startle, defensive immobility and escape) during the confrontation with rattlesnakes. A significant decrease in defensive attention was also recorded during re-exposure of the prey to the experimental apparatus context without the predator. Conclusion: Taken together, these results suggest that a decrease in µ1-opioid receptor signalling activity within the IC modulates anxiety- and panic attack-related behaviours in dangerous environments.

Many studies suggest that the substantia nigra, pars reticulata (SNpr), a tegmental mesencephalic structure rich in γ-aminobutyric acid (GABA)- and cannabinoid receptor-containing neurons, is involved in the complex control of defensive responses through the neostriatum-nigral disinhibitory and nigro-tectal inhibitory GABAergic pathways during imminently dangerous situations. The aim of the present work was to investigate the role played by CB1-cannabinoid receptor of GABAergic pathways terminal boutons in the SNpr or of SNpr-endocannabinoid receptor-containing interneurons on the effect of intra-nigral microinjections of cannabidiol in the activity of nigro-tectal inhibitory pathways. GABAA receptor blockade in the deep layers of the superior colliculus (dlSC) elicited vigorous defensive behaviour. This explosive escape behaviour was followed by significant antinociception. Cannabidiol microinjection into the SNpr had a clear anti-aversive effect, decreasing the duration of defensive alertness, the frequency and duration of defensive immobility, and the frequency and duration of explosive escape behaviour, expressed by running and jumps, elicited by transitory GABAergic dysfunction in dlSC. However, the innate fear induced-antinociception was not significantly changed. The blockade of CB1 endocannabinoid receptor in the SNpr decreased the anti-aversive effect of canabidiol based on the frequency and duration of defensive immobility, the frequency of escape expressed by running, and both the frequency and duration of escape expressed by jumps. These findings suggest a CB1 mediated endocannabinoid signalling in cannabidiol modulation of panic-like defensive behaviour, but not of innate fear-induced antinociception evoked by GABAA receptor blockade with bicuculline microinjection into the superior colliculus, with a putative activity in nigro-collicular GABAergic pathways.

The dorsal periaqueductal grey matter (dPAG) and the deep layers of the superior colliculus (dlSC) have been implicated in the organisation of innate fear-related defensive behaviours. Furthermore, GABAergic neurons from the substantia nigra pars reticulata (SNpr) connected to the dlSC and dPAG receive convergent disinhibitory inputs from the caudate-putamen (CPu), comprising the neostriatum, and modulate defence responses elicited by midbrain tectum stimulation. The purpose of this work was to study the effect of either excitatory cortico-neostriatal input blockade or neostriato-nigral GABAergic disinhibitory output activation on the responsivity of GABAergic nigro-collicular tonic inhibitory pathways during the elicitation of panic attack-like defensive responses produced by bicuculline administration into the dlSC. Thus, we investigated the effects of microinjection of either the synaptic activity blocker cobalt chloride (CoCl2) or the NMDA receptor agonist N-methyl-D-aspartic acid in the CPu on the elaboration of the defensive behaviour elicited by the selective blockade of GABAA receptors in the dlSC. Our findings showed that pretreatment of the neostriatum with CoCl2 caused clear anxiolytic and panicolytic-like effects, reducing the incidence and duration of alertness and diminishing defensive immobility and explosive escape responses. On the other hand, pretreatment of the neostriatum with NMDA (40 nmol) caused a pro-aversive effect, enhancing running and jumping responses elicited by GABAergic disinhibition in the dlSC. We conclude from the data that the neostriato-nigral disinhibitory and nigro-collicular inhibitory GABAergic pathways modulate innate fear and panic attack-like responses organised by dlSC neurons.

An increase in typhus group rickettsiosis and an expanding geographic range occurred in Texas, USA, over a decade. Because this illness commonly affects children, we retrospectively examined medical records from 2008–2016 at a large Houston-area pediatric hospital and identified 36 cases. The earliest known cases were diagnosed in 2011.

Decrease of γ-aminobutyric acid (GABA)-mediated neurotransmission in the dorsomedial hypothalamus (DMH) evokes instinctive fear-like responses. The aim of the present study was to investigate the involvement of the serotonin (5-HT)- and norepinephrine-mediated pathways of the endogenous pain inhibitory system, including the dorsal raphe nucleus (DRN) and the locus coeruleus (LC), in the defensive responses and antinociceptive processes triggered by the blockade of GABAergic receptors in the DMH. The intra-hypothalamic microinjection of the GABA A receptor antagonist bicuculline (40 ng/200 nL) elicited elaborate defensive behaviours interspersed with exploratory responses. This escape behaviour was followed by significantly increased pain thresholds, a phenomenon known as fear-induced antinociception. Furthermore, at 5 and 14 days after DRN serotonin-containing neurons were damaged using the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), the frequency and duration of alertness and escape behaviour evoked by the GABA A receptor blockade in the DMH decreased, as well as fear-induced antinociception. Pre-treatment with the non-selective 5-HT receptor antagonist methysergide, the 5-HT 2A/2C receptor antagonist ketanserin and the 5-HT 2A receptor selective antagonist R-96544 in the LC also decreased fear-induced antinociception, without significant changes in the expression of defensive behaviours. These data suggest that the serotonergic neurons of the DRN are directly involved in the organisation of defensive responses as well as in the elaboration of the innate fear-induced antinociception. However, serotonin-mediated inputs from the NDR to the LC modulate only fear-induced antinociception and not the defensive behaviours evoked by GABA A receptor blockade in the DMH.

Gamma-aminobutyric acid (GABA)ergic neurons of the substantia nigra pars reticulata (SNpr) are connected to the deep layers of the superior colliculus (dlSC). The dlSC, in turn, connect with the SNpr through opioid projections. Nociceptin/orphanin FQ peptide (N/OFQ) is a natural ligand of a Gi protein-coupled nociceptin receptor (ORL1; NOP) that is also found in the SNpr. Our hypothesis is that tectonigral opioid pathways and intranigral orphanin-mediated mechanisms modulate GABAergic nigrotectal connections. Therefore, the aim of this work was to study the role of opioid and NOP receptors in the SNpr during the modulation of defence reactions organised by the dlSC. The SNpr was pretreated with either opioid or NOP receptor agonists and antagonists, followed by dlSC treatment with bicuculline. Blockade of GABAA receptors in the dlSC elicited fear-related defensive behaviour. Pretreatment of the SNpr with naloxone benzoylhydrazone (NalBzoH), a μ-, δ-, and κ1-opioid receptor antagonist as well as a NOP receptor antagonist, decreased the aversive effect of bicuculline treatment on the dlSC. Either μ-opioid receptor activation or blockade by SNpr microinjection of endomorphin-1 (EM-1) and CTOP promoted pro-aversive and anti-aversive actions, respectively, that modulated the defensive responses elicited by bicuculline injection into the dlSC. Pretreatment of the SNpr with the selective NOP receptor antagonist JTC801 decreased the aversive effect of bicuculline, and microinjections of the selective NOP receptor agonist NNC 63-0532 promoted the opposite effect. These results demonstrate that opioid pathways and orphanin-mediated mechanisms have a critical role in modulating the activity of nigrotectal GABAergic pathways during the organisation of defensive behaviours.

The chemical neuroanatomy and the effects of central administration of opioid antagonists on the innate fear-induced responses elicited by electrical (at escape behaviour threshold) stimulation of the midbrain tectum were determined. The aim of the present work was to investigate the interaction between the tecto-nigral endogenous opioid peptide-mediated disinhibitory pathways and nigro-tectal inhibitory links in the control of panic-like behaviour and their organisation in the continuum comprised by the deep layers of the superior colliculus (dlSC) and the dorsolateral columns of the periaqueductal grey matter (dlPAG). Beta-endorphin-labelled neurons and fibres were found in the dorsal midbrain and also in the substantia nigra. Opioid varicose fibres and terminal buttons were widely distributed in PAG columns and in all substantia nigra subdivisions. Microinjections of naltrexone (a non-selective opioid receptor antagonist; 5.0μg/0.2μl) or nor-binaltorphimine (a selective κ-opioid receptor antagonist; 5.0μg/0.2μl) in the dlSC/dlPAG continuum, in independent groups of animals, induced significant increases in the escape thresholds for midbrain tectum electrical stimulation. The microinjection of naltrexone or nor-binaltorphimine into the SNpr also increased the escape behaviour threshold for electrical stimulation of dlSC/dlPAG. These morphological and neuropharmacological findings support previous evidence from our team for the role played by the interaction between opioidergic and GABAergic mechanisms in the modulation of innate fear-induced responses. The present data offer a neuroanatomical basis for both intratectal axo-axonic/pre-synaptic and tecto-nigral axo-somatic opioid inhibition of GABAergic nigro-tectal neurons that modulate the dorsal midbrain neurons related to the organisation of fear-related emotional responses.

It has been proposed that the post-ictal state is associated with the expression of hypoalgesia. It is clear that the projections among the periaqueductal gray matter (PAG), dorsal raphe nucleus (DRN) and locus coeruleus (LC) play a role in pain management. These mesencephalic structures have direct reciprocal opioid and monoaminergic projections to the LC that can possibly modulate post-ictal hypoalgesia. The goal of this study was to examine if LC-opioid and serotonergic/noradrenergic mechanisms signal the post-ictal hypoalgesic responses to tonic-clonic seizures produced by intraperitoneal administration of pentylenetetrazole (PTZ at 64mg/kg), causing an ionophore γ-aminobutyric acid (GABA)-mediated Cl

The hypothalamus is a forebrain structure critically involved in the organization of defensive responses to aversive stimuli. Gamma-aminobutyric acid (GABA)ergic dysfunction in dorsomedial and posterior hypothalamic nuclei is implicated in the origin of panic-like defensive behavior, as well as in pain modulation. The present study was conducted to test the difference between these two hypothalamic nuclei regarding defensive and antinociceptive mechanisms. Thus, the GABA(A) antagonist bicuculline (40 ng/0.2 µL) or saline (0.9% NaCl) was microinjected into the dorsomedial or posterior hypothalamus in independent groups. Innate fear-induced responses characterized by defensive attention, defensive immobility and elaborate escape behavior were evoked by hypothalamic blockade of GABA(A) receptors. Fear-induced defensive behavior organized by the posterior hypothalamus was more intense than that organized by dorsomedial hypothalamic nuclei. Escape behavior elicited by GABA(A) receptor blockade in both the dorsomedial and posterior hypothalamus was followed by an increase in nociceptive threshold. Interestingly, there was no difference in the intensity or in the duration of fear-induced antinociception shown by each hypothalamic division presently investigated. The present study showed that GABAergic dysfunction in nuclei of both the dorsomedial and posterior hypothalamus elicit panic attack-like defensive responses followed by fear-induced antinociception, although the innate fear-induced behavior originates differently in the posterior hypothalamus in comparison to the activity of medial hypothalamic subdivisions.

Intestinal parasites present close relationship with sanitary conditions water supply and hygiene habits which pose an important problem of public health with high prevalence among individuals with low socioeconomic status, especially in the younger population. In the present paper the authors performed the diagnostic of intestinal parasites in stool examination of children aged up to six years of age assisted by three public education facilities between September 2011 and July 2012 by using the new method of Mariano & Carvalho. Positivity observed for intestinal parasites reached 77.2 %, with rates ranging from 78.0 %, 72.3 and 84.2 % for the institution A, B and C respectively. Among the positive samples, there was higher frequency of contamination by protozoa (51.2 %), especially for Giardia lamblia (31.2 %). Among the helminthes, the most common were Ascaris lumbricoides (28.8 %) and Trichuris trichiura (17.6 %). The high prevalence of intestinal parasites, both protozoa and helminthes, was significantly associated with eating raw foods without proper hygiene. These results demonstrate the need for improved hygiene habits in parasitism prevention and adequate learning resources to teach preschoolers better habits of hygiene before the consumption of raw foods.