What about adolescents' mental health after the pandemics? An analyses of a grade II hospital.

OBJECTIVES: Suicidal ideation and suicide are serious situations that affect children and adolescents. The restrictions imposed by the SARS-CoV-2 pandemic have had a significant negative impact, due to social isolation, prolonged screen exposure and reduced outdoor activities. This study aims to compare the access to the Pediatric Emergency Department due to suicidal ideation and suicide attempts before and during the pandemic. METHODS: This descriptive and retrospective study analyzed clinical records of children/adolescents who attended a Level II Pediatric Emergency Department of a hospital due to suicidal ideation and/or suicide attempts, between March 2018 and March 2020 (pre-pandemic period) and April 2020 to March 2022 (pandemic period). Demographic (age and sex) and clinical (psychopharmacological therapy, discharge destination and follow-up psychiatric/psychological consultations) variables were collected. Statistical analysis was performed using Microsoft Excel 2022® and SPSS v20.0®, considering statistical significance at p<0.05. RESULTS: A total of 71 children/adolescents were admitted for suicidal ideation, with a median age of 15 years (minimum: 10 years, maximum: 17 years), 27 in pre-pandemic period and 44 in pandemic period (p<0.001). The majority were girls, with a significant increase in pandemic period (pre-pandemic: 55.6 %, pandemic: 79.6 %; p<0.05). The age group with the highest increase in admissions was 15 years. There was a significant increase in suicidal attempts among girls (p<0.05) as well as self-harm behaviors (p<0.01). There was also a significant increase in the number of psychology/child psychiatry follow-up consultations in pandemic period (p<0.05). Most patients were referred to another hospital in both periods (pre-pandemic: 55.6 %, pandemic: 68.2 %) at discharge. CONCLUSIONS: During the pandemic period, there was an increase in the number of suicidal ideation cases, particularly among females, as well as in suicide attempts cases, which appears to be correlated with the pandemic restrictions. Larger-scale studies are needed to draw more accurate conclusions.

Unraveling the Influence of Litter Size, Maternal Care, Exercise, and Aging on Neurobehavioral Plasticity and Dentate Gyrus Microglia Dynamics in Male Rats.

This study explores the multifaceted influence of litter size, maternal care, exercise, and aging on rats' neurobehavioral plasticity and dentate gyrus microglia dynamics. Body weight evolution revealed a progressive increase until maturity, followed by a decline during aging, with larger litters exhibiting lower weights initially. Notably, exercised rats from smaller litters displayed higher body weights during the mature and aged stages. The dentate gyrus volumes showed no significant differences among groups, except for aged sedentary rats from smaller litters, which exhibited a reduction. Maternal care varied significantly based on litter size, with large litter dams showing lower frequencies of caregiving behaviors. Behavioral assays highlighted the detrimental impact of a sedentary lifestyle and reduced maternal care/large litters on spatial memory, mitigated by exercise in aged rats from smaller litters. The microglial dynamics in the layers of dentate gyrus revealed age-related changes modulated by litter size and exercise. Exercise interventions mitigated microgliosis associated with aging, particularly in aged rats. These findings underscore the complex interplay between early-life experiences, exercise, microglial dynamics, and neurobehavioral outcomes during aging.

Non-Invasive Vagal Nerve Stimulation Pre-Treatment Reduces Neurological Dysfunction After Closed Head Injury in Mice.

Non-invasive vagus nerve stimulation (nVNS) has recently been suggested as a potential therapy for traumatic brain injury (TBI). We previously demonstrated that nVNS inhibits cortical spreading depolarization, the electrophysiological event underlying migraine aura, and is relevant to TBI. Our past work also suggests a role for interleukin-1 beta (IL-1ß) in cognitive deficits after closed head injury (CHI) in mice. We show that nVNS pre-treatment suppresses CHI-associated spatial learning and memory impairment and prevents IL-1ß activation in injured neurons, but not endothelial cells. In contrast, nVNS administered 10 min after CHI was ineffective. These data suggest that nVNS prophylaxis might ameliorate neuronal dysfunction associated with CHI in populations at high risk for concussive TBI.

A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke.

Human diseases may be modeled in animals to allow preclinical assessment of putative new clinical interventions. Recent, highly publicized failures of large clinical trials called into question the rigor, design, and value of preclinical assessment. We established the Stroke Preclinical Assessment Network (SPAN) to design and implement a randomized, controlled, blinded, multi-laboratory trial for the rigorous assessment of candidate stroke treatments combined with intravascular thrombectomy. Efficacy and futility boundaries in a multi-arm multi-stage statistical design aimed to exclude from further study highly effective or futile interventions after each of four sequential stages. Six independent research laboratories performed a standard focal cerebral ischemic insult in five animal models that included equal numbers of males and females: young mice, young rats, aging mice, mice with diet-induced obesity, and spontaneously hypertensive rats. The laboratories adhered to a common protocol and efficiently enrolled 2615 animals with full data completion and comprehensive animal tracking. SPAN successfully implemented treatment masking, randomization, prerandomization inclusion and exclusion criteria, and blinded assessment of outcomes. The SPAN design and infrastructure provide an effective approach that could be used in similar preclinical, multi-laboratory studies in other disease areas and should help improve reproducibility in translational science.

Spreading Depolarizations Suppress Hematoma Growth in Hyperacute Intracerebral Hemorrhage in Mice.

BACKGROUND: Spreading depolarizations (SDs) occur in all types of brain injury and may be associated with detrimental effects in ischemic stroke and subarachnoid hemorrhage. While rapid hematoma growth during intracerebral hemorrhage triggers SDs, their role in intracerebral hemorrhage is unknown. METHODS: We used intrinsic optical signal and laser speckle imaging, combined with electrocorticography, to investigate the effects of SD on hematoma growth during the hyperacute phase (0-4 hours) after intracortical collagenase injection in mice. Hematoma expansion, SDs, and cerebral blood flow were simultaneously monitored under normotensive and hypertensive conditions. RESULTS: Spontaneous SDs erupted from the vicinity of the hematoma during rapid hematoma growth. We found that hematoma growth slowed down by >60% immediately after an SD. This effect was even stronger in hypertensive animals with faster hematoma growth. To establish causation, we exogenously induced SDs (every 30 minutes) at a remote site by topical potassium chloride application and found reduced hematoma growth rate and final hemorrhage volume (18.2±5.8 versus 10.7±4.1 mm3). Analysis of cerebral blood flow using laser speckle flowmetry revealed that suppression of hematoma growth by spontaneous or induced SDs coincided and correlated with the characteristic oligemia in the wake of SD, implicating the vasoconstrictive effect of SD as one potential mechanism of action. CONCLUSIONS: Our findings reveal that SDs limit hematoma growth during the early hours of intracerebral hemorrhage and decrease final hematoma volume.

The effect of sex and estrus cycle stage on optogenetic spreading depression induced migraine-like pain phenotypes.

BACKGROUND: Migraine is more prevalent in females, raising the possibility that sex and gonadal hormones modulate migraine. We recently demonstrated that minimally invasive optogenetic spreading depolarization (opto-SD) elicits robust periorbital allodynia. The objective of this study was to test the hypothesis that opto-SD induced migraine-like pain behavior is worse in females and varies during the estrus cycle. METHODS: Single or repeated opto-SDs were induced in male and female adult Thy1-ChR2-YFP transgenic mice. Von Frey monofilaments were used to test periorbital mechanical allodynia. Mouse grimace was also examined under increasing light intensity to quantify spontaneous discomfort and light-aversive behavior. Vaginal smears were obtained for estrus cycle staging at the end of behavioral testing. RESULTS: A multi-variable regression analysis was performed using a male and female cohort to test the effect of independent variables on periorbital allodynia. Opto-SD predicted lower periorbital thresholds as compared with sham stimulation (p < 0.0001). Additionally, female sex predicted lower periorbital thresholds compared with males (p = 0.011). There were significant interactions between opto-SD and time (interaction p = 0.030) as animals tended to recover from opto-SD allodynia over time, and between sex and time (p = 0.020) as females tended to take longer to recover. Proestrus, estrus (PE) and metestrus, diestrus (MD) stages were combined to represent high versus low circulating estradiol relative to progesterone, respectively. Multi-variable regression revealed an effect of estrus cycle (p = 0.015) on periorbital thresholds. In the sham group, PE had lower thresholds than MD. However, there was no interaction between opto-SD and the estrus cycle (p = 0.364). Grimace scores were also examined at incremental light intensities. There was an effect of opto-SD (p < 0.0001), light intensity (p = 0.001) and estrus cycle (p = 0.024) on grimace without interaction among them (three-way ANOVA). CONCLUSIONS: Female sex and estrus stages with high circulating estradiol relative to progesterone lower trigeminal pain thresholds and augment photosensitivity. In females, opto-SD increased pain behavior and photosensitivity irrespective of the estrus stage.

Inhibition of persistent sodium current reduces spreading depression-evoked allodynia in a mouse model of migraine with aura.

ABSTRACT: We investigated the efficacy of inhibiting persistent Na + currents (I NaP ) in acute rodent models of migraine with aura. Cortical spreading depression (SD) is a slow wave of neuronal and glial depolarization that underlies the migraine aura. Minimally invasive optogenetic SD (opto-SD) causes periorbital mechanical allodynia in mice, suggesting SD activates trigeminal nociceptors. Persistent Na + currents contribute to neuronal intrinsic excitability and have been implicated in peripheral and cortical excitation. We examined a preferential inhibitor of I NaP, GS-458967, on SD-induced periorbital allodynia, SD susceptibility, and formalin-induced peripheral pain. Periorbital mechanical allodynia was tested in male and female Thy1-ChR2-YFP mice after a single opto-SD event using manual von Frey monofilaments. GS-458967 (1 mg/kg, s.c.) or vehicle was dosed immediately after opto-SD induction, and allodynia was tested 1 hour later. The electrical SD threshold and KCl-induced SD frequency were examined in the cortex in male Sprague-Dawley rats after 1 hour pretreatment with GS-458967 (3 mg/kg, s.c.) or vehicle. Effects of GS-458967 (0.5-5 mg/kg, p.o.) on spontaneous formalin hind paw behavior and locomotion were also examined in male CD-1 mice. GS-458967 suppressed opto-SD-induced periorbital allodynia and decreased susceptibility to SD. GS-458967 also diminished early and late phase formalin-induced paw-licking behavior with early phase paw licking responding to lower doses. GS-458967 up to 3 mg/kg had no impact on locomotor activity. These data provide evidence that I NaP inhibition can reduce opto-SD-induced trigeminal pain behavior and support I NaP inhibition as an antinociceptive strategy for both abortive and preventive treatment of migraine.

Embracing Heterogeneity in The Multicenter Stroke Preclinical Assessment Network (SPAN) Trial.

The Stroke Preclinical Assessment Network (SPAN) is a multicenter preclinical trial platform using rodent models of transient focal cerebral ischemia to address translational failure in experimental stroke. In addition to centralized randomization and blinding and large samples, SPAN aimed to introduce heterogeneity to simulate the heterogeneity embodied in clinical trials for robust conclusions. Here, we report the heterogeneity introduced by allowing the 6 SPAN laboratories to vary most of the biological and experimental model variables and the impact of this heterogeneity on middle cerebral artery occlusion (MCAo) performance. We included the modified intention-to-treat population of the control mouse cohort of the first SPAN trial (n=421) and examined the biological and procedural independent variables and their covariance. We then determined their impact on the dependent variables cerebral blood flow drop during MCAo, time to achieve MCAo, and total anesthesia duration using multivariable analyses. We found heterogeneity in biological and procedural independent variables introduced mainly by the site. Consequently, all dependent variables also showed heterogeneity among the sites. Multivariable analyses with the site as a random effect variable revealed filament choice as an independent predictor of cerebral blood flow drop after MCAo. Comorbidity, sex, use of laser Doppler flow to monitor cerebral blood flow, days after trial onset, and maintaining anesthesia throughout the MCAo emerged as independent predictors of time to MCAo. Total anesthesia duration was predicted by most independent variables. We present with high granularity the heterogeneity introduced by the biological and model selections by the testing sites in the first trial of cerebroprotection in rodent transient filament MCAo by SPAN. Rather than trying to homogenize all variables across all sites, we embraced the heterogeneity to better approximate clinical trials. Awareness of the heterogeneity, its sources, and how it impacts the study performance may further improve the study design and statistical modeling for future multicenter preclinical trials.

Biographical ruptures by the COVID-19 pandemic on adolescent and young trans men and transmasculine people: demands for nursing.

OBJECTIVE: to understand the biographical ruptures caused by the COVID-19 pandemic on adolescent and young trans men and transmasculine people in the Brazilian context. METHOD: qualitative study - multicenter, online survey. A total of 97 self-identified trans men and 22 transmasculine people participated and completed a semi-structured form in two stages. The data was subjected to Reflective Thematic Content Analysis. The interpretation was made on a sociological basis, based on the concept of biographical rupture. RESULTS: five categories were derived: interruption of hormonization, surgeries and specialized follow-up; discomforts caused by the rupture of masculine characteristics, self-image, self-perception, and identity; vulnerability from the losses of family members and significant people, employment, and weakening of support networks; emergence of psycho-emotional problems, such as loss of meaning in life; demands for nursing care and valuing the life of transmasculine adolescents and young men in post-pandemic times. CONCLUSION: the biographical ruptures caused by the pandemic threatened the identities of trans and transmasculine people of adolescents and youth, degraded and interrupted biographies, leading them to the loss of meaning in life. Nursing professionals can be strategic and essential in overcoming threats by intervening early. KEYPOINTS: (1) Shows biographical ruptures in transmasculinities during the pandemic. (2) Elucidates threats to achieving the desired trans identity. (3) Reveals barriers in services that hinder hormone transition. (4) Presents the discourse of suicide and new stressors in mental health. (5) Raises calls for nursing practice/care in adolescent health.

Saúde mental de mulheres transgêneras: uma revisão integrativa de literatura / Salud mental de las mujeres transgénero: una revisión integradora de la literatura / Mental health of transgender women: an integrative literature review

Objetivo: conhecer a produção científica nacional e internacional acerca da saúde mental das mulheres transgêneras de 2007 a 2017. Método: revisão integrativa realizada na Biblioteca Virtual em Saúde, em abril de 2018. Analisaram-se os estudos em seis fases, agrupando-os em categorias temáticas. Resultados: dos 30 estudos selecionados emergiram sete categorias temáticas, a saber: "necessidades de saúde mental", "vulnerabilidade psicossocial", "processo transexualizador", "mulheres transgêneras jovens e na terceira idade", "relações sociais", "direitos civis e cidadania" e "relações entre as mulheres transgêneras e os serviços de saúde". Conclusões: mulheres transgêneras estão expostas a maiores riscos de desenvolverem transtornos mentais, em relação às pessoas cisgêneras parecendo ter relação com o preconceito, estigma, discriminação, e negação de direitos civis. São transtornos mais prevalentes nesta população: depressão, ansiedade, ideação/ tentativa de suicídio, abuso de álcool e outras drogas, os quais estão diretamente relacionados com o não acesso aos serviços de saúde.(AU)

Objetivo: conocer la producción científica nacional e internacional sobre la salud mental de mujeres transgénero de 2007 a 2017. Método: revisión realizada en la Biblioteca Virtual en Salud utilizando los filtros listados en las bases de datos de Literatura Latinoamericana y Brasileña, en abril de 2018. Se analizaron en seis fases, agrupándolos en categorías temáticas. Resultados: de los 30 estudios seleccionados surgieron siete categorías: "necesidades de salud mental", "vulnerabilidad psicosocial", "proceso transexual", "mujeres trans jóvenes y ancianas", "relaciones sociales", "derechos civiles y ciudadanía" y "relaciones entre mujeres transgénero y servicios de salud". Conclusiones: mujeres transgénero están expuestas a mayores riesgos de desarrollar trastornos mentales, en relación con las personas cisgénero que parecen estar relacionadas con prejuicios, estigma, discriminación y negación de los derechos civiles. Los trastornos más prevalentes: depresión, ansiedad, ideación/ intento suicida, abuso de drogas, estando relacionados con la falta de acceso a servicios de salud.(AU)

Objective: to know the national and international scientific production about the mental health of transgender women from 2007 to 2017. Method: this is an integrative review conducted at the Virtual Health Library, April 2018. The studies were analyzed in six phases, grouping them into thematic categories. Results: from the 30 selected studies, seven thematic categories emerged: "mental health needs", "psychosocial vulnerability", "transsexualising process", "young and old transgender women", "social relations", "civil rights and citizenship" and "relationships between transgender women and health services". Conclusions: transgender women are at greater risk of developing mental disorders than cisgender people appearing to be related to prejudice, stigma, discrimination, and denial of civil rights. The most prevalent disorders in this population are depression, anxiety, suicidal ideation / attempt, alcohol, and other drug abuse, which are directly related to non-access to health services.(AU)

All-Solution Processed Single-Layer WOLEDs Using [Pt(salicylidenes)] as Guests in a PFO Matrix.

Herein, we report the synthesis and characterization of two Pt(II) coordination compounds, the new platinum(II)[N,N'-bis(salicylidene)-3,4-diaminobenzophenone)] ([Pt(sal-3,4-ben)]) and the already well-known platinum(II)[N,N'-bis(salicylidene)-o-phenylenediamine] ([Pt(salophen)]), along with their application as guests in a poly [9,9-dioctylfluorenyl-2,7-diyl] (PFO) conjugated polymer in all-solution processed single-layer white organic light-emitting diodes. Completely different performances were achieved: 2.2% and 15.3% of external quantum efficiencies; 2.8 cd A-1 and 12.1 cd A-1 of current efficiencies; and 3103 cd m-2 and 6224 cd m-2 of luminance for the [Pt(salophen)] and [Pt(sal-3,4-ben)] complexes, respectively. The Commission Internationale de l'Eclairage (CIE 1931) chromaticity color coordinates are (0.33, 0.33) for both 0.1% mol/mol Pt(II):PFO composites at between approximately 3.2 and 8 V. The optoelectronic properties of doped and neat PFO films have been investigated, using steady-state and time-resolved photoluminescence. Theoretical calculations at the level of relativistic density functional theory explained these results, based on the presence of the Pt(II) central ion's phosphorescence emission, considering spin-orbit coupling relationships. The overall results are explained, taking into account the active layer morphological properties, along with the device's electric balance and the emitter's efficiencies, according to deep-trap space-charge models. Considering the very simple structure of the device and the ease of synthesis of such compounds, the developed framework can offer a good trade-off for solution-deposited white organic light-emitting diodes (WOLEDs), with further applications in the field of lighting and signage.

Rho-Kinase Inhibition Improves the Outcome of Focal Subcortical White Matter Lesions.

BACKGROUND: Subcortical white matter lesions are exceedingly common in cerebral small vessel disease and lead to significant cumulative disability without an available treatment. Here, we tested a rho-kinase inhibitor on functional recovery after focal white matter injury. METHODS: A focal corpus callosum lesion was induced by stereotactic injection of N5-(1-iminoethyl)-L-ornithine in mice. Fasudil (10 mg/kg) or vehicle was administered daily for 2 weeks, starting one day after lesion induction. Resting-state functional connectivity and grid walk performance were studied longitudinally, and lesion volumes were determined at one month. RESULTS: Resting-state interhemispheric functional connectivity significantly recovered between days 1 and 14 in the fasudil group (P<0.001), despite worse initial connectivity loss than vehicle before treatment onset. Grid walk test revealed an increased number of foot faults in the vehicle group compared with baseline, which persisted for at least 4 weeks. In contrast, the fasudil arm did not show an increase in foot faults and had smaller lesions at 4 weeks. Immunohistochemical examination of reactive astrocytosis, synaptic density, and mature oligodendrocytes did not reveal a significant difference between treatment arms. CONCLUSIONS: These data show that delayed fasudil posttreatment improves functional outcomes after a focal subcortical white matter lesion in mice. Future work will aim to elucidate the mechanisms.

The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results.

Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these cellular events provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment. Among other issues-such as incomplete mechanistic knowledge and faulty clinical trial design-a key contributor to prior translational failures may be insufficient scientific rigor during preclinical assessment: nonblinded outcome assessment; missing randomization; inappropriate sample sizes; and preclinical assessments in young male animals that ignore relevant biological variables, such as age, sex, and relevant comorbid diseases. Promising results are rarely replicated in multiple laboratories. We sought to address some of these issues with rigorous assessment of candidate treatments across 6 independent research laboratories. The Stroke Preclinical Assessment Network (SPAN) implements state-of-the-art experimental design to test the hypothesis that rigorous preclinical assessment can successfully reduce or eliminate common sources of bias in choosing treatments for evaluation in clinical studies. SPAN is a randomized, placebo-controlled, blinded, multilaboratory trial using a multi-arm multi-stage protocol to select one or more putative stroke treatments with an implied high likelihood of success in human clinical stroke trials. The first stage of SPAN implemented procedural standardization and experimental rigor. All participating research laboratories performed middle cerebral artery occlusion surgery adhering to a common protocol and rapidly enrolled 913 mice in the first of 4 planned stages with excellent protocol adherence, remarkable data completion and low rates of subject loss. SPAN stage 1 successfully implemented treatment masking, randomization, prerandomization inclusion/exclusion criteria, and blinded assessment to exclude bias. Our data suggest that a large, multilaboratory, preclinical assessment effort to reduce known sources of bias is feasible and practical. Subsequent SPAN stages will evaluate candidate treatments for potential success in future stroke clinical trials using aged animals and animals with comorbid conditions.

Migraine susceptibility is modulated by food triggers and analgesic overuse via sulfotransferase inhibition.

BACKGROUND/AIM: Certain constituents in migraine food triggers and non-steroidal anti-inflammatory drugs (NSAIDs) inhibit sulfotransferases (SULTs) that detoxify drugs/chemicals and play role in the metabolism of neurotransmitters. We aimed to dissect SULT1A1 modulation of CSD susceptibility and behavior in an in vivo experimental model using hesperidin, a SULT1A1 inhibitor found in citrus fruits (known migraine triggers) and mefenamic acid (SULT1A1 inhibitor), an NSAID to simulate medication overuse. METHODS: Hesperidin was used as SULT1A1 inhibitor found in citrus fruits, known migraine triggers and mefenamic acid (NSAID), another SULT1A1 inhibitor, was used to induce MO in rats. The groups were; 1) Hesperidin (ip) or its vehicle-DMSO (ip) 2) Chronic (4 weeks) mefenamic acid (ip) or its vehicle (ip) 3) Chronic mefenamic acid+hesperidin (ip) or DMSO (ip). CSD susceptibility was evaluated and behavioral testing was performed. SULT1A1 enzyme activity was measured in brain samples. RESULTS: Single-dose of hesperidin neither changed CSD susceptibility nor resulted in any behavioral change. Chronic mefenamic acid exposure resulted in increased CSD susceptibility, mechanical-thermal hypersensitivity, increased head shake, grooming and freezing and decreased locomotion. Single dose hesperidin administration after chronic mefenamic acid exposure resulted in increased CSD susceptibility and mechanical-thermal hypersensitivity, increased freezing and decreased locomotion. SULT1A1 enzyme activity was lower in mefenamic acid and mefenamic acid+hesperidin groups compared to their vehicles. CONCLUSION: Mefenamic acid and hesperidin have synergistic effect in modulating CSD susceptibility and pain behavior. Sulfotransferase inhibition may be the common mechanism by which food triggers and NSAIDs modulate migraine susceptibility. Further investigations regarding human provocation studies using hesperidin in migraine patients with medication overuse are needed.

Efficacy profile of noninvasive vagus nerve stimulation on cortical spreading depression susceptibility and the tissue response in a rat model.

BACKGROUND: Noninvasive vagus nerve stimulation (nVNS) has recently emerged as a promising therapy for migraine. We previously demonstrated that vagus nerve stimulation inhibits cortical spreading depression (CSD), the electrophysiological event underlying migraine aura and triggering headache; however, the optimal nVNS paradigm has not been defined. METHODS: Various intensities and doses of nVNS were tested to improve efficacy on KCl-evoked CSD frequency and electrical threshold of CSD in a validated rat model. Chronic efficacy was evaluated by daily nVNS delivery for four weeks. We also examined the effects of nVNS on neuroinflammation and trigeminovascular activation by western blot and immunohistochemistry. RESULTS: nVNS suppressed susceptibility to CSD in an intensity-dependent manner. Two 2-minute nVNS 5 min apart afforded the highest efficacy on electrical CSD threshold and frequency of KCl-evoked CSD. Daily nVNS for four weeks did not further enhance efficacy over a single nVNS 20 min prior to CSD. The optimal nVNS also attenuated CSD-induced upregulation of cortical cyclooxygenase-2, calcitonin gene-related peptide in trigeminal ganglia, and c-Fos expression in trigeminal nucleus caudalis. CONCLUSIONS: Our study provides insight on optimal nVNS parameters to suppress CSD and suggests its benefit on CSD-induced neuroinflammation and trigeminovascular activation in migraine treatment.

Biographical ruptures by the COVID-19 pandemic on adolescent and young trans men and transmasculine people: demands for nursing / Rupturas biográficas pela pandemia da COVID-19 sobre adolescentes e jovens homens trans e transmasculinos: demandas para a enfermagem / Rupturas biográficas por la pandemia del COVID-19 en adolescentes y jóvenes hombres trans y transmasculinos: demandas para la enfermería

Abstract Objective: to understand the biographical ruptures caused by the COVID-19 pandemic on adolescent and young trans men and transmasculine people in the Brazilian context. Method: qualitative study - multicenter, online survey. A total of 97 self-identified trans men and 22 transmasculine people participated and completed a semi-structured form in two stages. The data was subjected to Reflective Thematic Content Analysis. The interpretation was made on a sociological basis, based on the concept of biographical rupture. Results: five categories were derived: interruption of hormonization, surgeries and specialized follow-up; discomforts caused by the rupture of masculine characteristics, self-image, self-perception, and identity; vulnerability from the losses of family members and significant people, employment, and weakening of support networks; emergence of psycho-emotional problems, such as loss of meaning in life; demands for nursing care and valuing the life of transmasculine adolescents and young men in post-pandemic times. Conclusion: the biographical ruptures caused by the pandemic threatened the identities of trans and transmasculine people of adolescents and youth, degraded and interrupted biographies, leading them to the loss of meaning in life. Nursing professionals can be strategic and essential in overcoming threats by intervening early.

Resumo Objetivo: compreender as rupturas biográficas causadas pela pandemia da COVID-19 sobre adolescentes e jovens homens trans e pessoas transmasculinas no contexto do Brasil. Método: estudo qualitativo - survey on-line, multicêntrico. Participaram 97 homens trans e 22 pessoas transmasculinas, autoidentificados, que responderam formulário semiestruturado em duas etapas. Os dados foram submetidos à Análise de Conteúdo Temática Reflexiva. Realizou-se a interpretação com base sociológica, a partir do conceito de ruptura biográfica. Resultados: derivadas cinco categorias: interrupção da hormonização, cirurgias e acompanhamento especializado; desconfortos precipitados pela ruptura das características masculinas, autoimagem, autopercepção e identidade; vulnerabilidade a partir das perdas de familiares e pessoas significativas, emprego e fragilização das redes de apoio; emergência de problemas psicoemocionais, como perda do sentido da vida; demandas para o cuidado de enfermagem e valorização da vida de adolescentes e jovens transmasculinos no pós-pandemia. Conclusão: as rupturas biográficas provocadas pela pandemia ameaçaram as identidades de homens trans e pessoas transmasculinas de adolescentes e jovens, produziram degradação e descontinuidade das biografias, conduzindo-os à perda de sentido da vida. Profissionais de enfermagem podem ser estratégicos e essenciais na superação das ameaças, intervindo antecipadamente.

Resumen Objetivo: comprender las rupturas biográficas provocadas por la pandemia del COVID-19 en adolescentes y jóvenes hombres trans y personas transmasculinas en el contexto de Brasil. Método: estudio cualitativo - encuesta en línea - multicéntrico. Participaron 97 hombres trans y 22 personas transmasculinas autoidentificadas, que respondieron un formulario semiestructurado en dos etapas. Los datos se sometieron al Análisis de Contenido Temático Reflexivo. La interpretación se realizó sobre una base sociológica a partir del concepto de ruptura biográfica. Resultados: surgieron cinco categorías: interrupción de la terapia hormonal, cirugías y seguimiento especializado; malestares precipitados por la interrupción de las características masculinas, autoimagen, autopercepción e identidad; vulnerabilidad por la pérdida de familiares y seres queridos, empleo y debilitamiento de las redes de apoyo; aparición de problemas psicoemocionales, como la pérdida del sentido de la vida; demandas de atención de enfermería y valoración de la vida de adolescentes y jóvenes transexuales en el pospandemia. Conclusión: las rupturas biográficas provocadas por la pandemia amenazaron las identidades de los hombres trans y personas transmasculinas adolescentes y jóvenes, produjeron degradación y discontinuidad de las biografías, llevándolas a perder el sentido de la vida. Los profesionales de enfermería pueden ser estratégicos e imprescindibles en la superación de estas amenazas al promover una intervención anticipada.

Spreading depression as an innate antiseizure mechanism.

Spreading depression (SD) is an intense and prolonged depolarization in the central nervous systems from insect to man. It is implicated in neurological disorders such as migraine and brain injury. Here, using an in vivo mouse model of focal neocortical seizures, we show that SD may be a fundamental defense against seizures. Seizures induced by topical 4-aminopyridine, penicillin or bicuculline, or systemic kainic acid, culminated in SDs at a variable rate. Greater seizure power and area of recruitment predicted SD. Once triggered, SD immediately suppressed the seizure. Optogenetic or KCl-induced SDs had similar antiseizure effect sustained for more than 30 min. Conversely, pharmacologically inhibiting SD occurrence during a focal seizure facilitated seizure generalization. Altogether, our data indicate that seizures trigger SD, which then terminates the seizure and prevents its generalization.

Rapid hematoma growth triggers spreading depolarizations in experimental intracortical hemorrhage.

Recurrent waves of spreading depolarization (SD) occur in brain injury and are thought to affect outcomes. What triggers SD in intracerebral hemorrhage is poorly understood. We employed intrinsic optical signaling, laser speckle flowmetry, and electrocorticography to elucidate the mechanisms triggering SD in a collagenase model of intracortical hemorrhage in mice. Hematoma growth, SD occurrence, and cortical blood flow changes were tracked. During early hemorrhage (0-4 h), 17 out of 38 mice developed SDs, which always originated from the hematoma. No SD was detected at late time points (8-52 h). Neither hematoma size, nor peri-hematoma perfusion were associated with SD occurrence. Further, arguing against ischemia as a trigger factor, normobaric hyperoxia did not inhibit SD occurrence. Instead, SDs always occurred during periods of rapid hematoma growth, which was two-fold faster immediately preceding an SD compared with the peak growth rates in animals that did not develop any SDs. Induced hypertension accelerated hematoma growth and resulted in a four-fold increase in SD occurrence compared with normotensive animals. Altogether, our data suggest that spontaneous SDs in this intracortical hemorrhage model are triggered by the mechanical distortion of tissue by rapidly growing hematomas.

Challenges and prospects about the graphene role in the design of photoelectrodes for sunlight-driven water splitting.

Graphene and its derivatives have emerged as potential materials for several technological applications including sunlight-driven water splitting reactions. This review critically addresses the latest achievements concerning the use of graphene as a player in the design of hybrid-photoelectrodes for photoelectrochemical cells. Insights about the charge carrier dynamics of graphene-based photocatalysts which include metal oxides and non-metal oxide semiconductors are also discussed. The concepts underpinning the continued progress in the field of graphene/photoelectrodes, including different graphene structures, architecture as well as the possible mechanisms for hydrogen and oxygen reactions are also presented. Despite several reports having demonstrated the potential of graphene-based photocatalysts, the achieved performance remains far from the targeted benchmark efficiency for commercial application. This review also highlights the challenges and opportunities related to graphene application in photoelectrochemical cells for future directions in the field.

Optogenetic Spreading Depression Elicits Trigeminal Pain and Anxiety Behavior.

OBJECTIVE: Cortical spreading depression (SD) is an intense depolarization underlying migraine aura. Despite the weight of evidence linking SD to the pain phase of migraine, controversy remains over a causal role of SD in cephalgia because of the invasive nature of previous SD induction methods. To overcome this problem, we used a novel minimally invasive optogenetic SD induction method and examined the effect of SD on behavior. METHODS: Optogenetic SD was induced as a single event or repeatedly every other day for 2 weeks. End points, including periorbital and hindpaw mechanical allodynia, mouse grimace, anxiety, and working memory, were examined in male and female mice. RESULTS: A single SD produced bilateral periorbital mechanical allodynia that developed within 1 hour and resolved within 2 days. Sumatriptan prevented periorbital allodynia when administered immediately after SD. Repeated SDs also produced bilateral periorbital allodynia that lasted 4 days and resolved within 2 weeks after the last SD. In contrast, the hindpaw withdrawal thresholds did not change after repeated SDs suggesting that SD-induced allodynia was limited to the trigeminal region. Moreover, repeated SDs increased mouse grimace scores 2 days after the last SD, whereas a single SD did not. Repeated SDs also increased thigmotaxis scores as a measure of anxiety. In contrast, neither single nor repeated SDs affected visuospatial working memory. We did not detect sexual dimorphism in any end point. INTERPRETATION: Altogether, these data show a clinically congruent causal relationship among SD, trigeminal pain, and anxiety behavior, possibly reflecting SD modulation of hypothalamic, thalamic, and limbic mechanisms. ANN NEUROL 2021;89:99-110.