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Background COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia. Methods Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed. Results The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53–43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52–38.4]). Comorbidities were more frequent in the PE+ group (63.6% vs 31.5%, p = 0.03), as well as prematurity (81.8% vs 41.6%, p = 0.02), low birth weight (63.6% vs 24.7%, p = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% vs 27.0%, p = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34–4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant. Conclusions Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia.

Deepinder K Dhaliwal,1 Viktor Chirikov,2 Jordana Schmier,2 Sanika Rege,2 Schalon Newton3 1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 2OPEN Health Evidence & Access, Bethesda, MD, USA; 3Trefoil Therapeutics, Inc., San Diego, CA, USACorrespondence: Schalon Newton, Trefoil Therapeutics, Inc., 6330 Nancy Ridge Dr Suite 103, San Diego, CA, 92121, USA, Tel +1 949 678 9572, Email snewton@trefoiltherapeutics.comPurpose: To assess the incremental burden of corneal transplant surgery for US commercially insured patients with Fuchs endothelial corneal dystrophy (FECD) treated with endothelial keratoplasty (EK) compared to controls.Methods: The study design was retrospective cohort using IBM® MarketScan® claims (January 2014–September 2019) and included EK-treated (N=1562) and control patients (N=23,485) having ≥ 12 months’ enrollment before and after diagnosis, who were subsequently matched on select characteristics. The index date was the beginning of the pre-operative period (3 months before EK); synthetic EK index was assigned for controls. All-cause, eye-disease, and complication-related healthcare resource utilization (HCRU) and costs were compared up to 36 months post index. For a small subset of patients, patient data were linked to the Health and Productivity Management supplemental database, which integrates data on productivity loss and disability payments.Results: Matched cohorts included 804 EK-treated and 1453 controls with average age 65.7 years, 1383 (61%) female. Over 12 months of follow-up, all-cause ($41,199 vs $20,222, p< 0.001) and eye-disease related costs ($22,951 vs $1389, p< 0.001) were higher among EK-treated patients than controls. The cost differential increased additionally by $1000–$2000 per annum by 36 months of follow-up. While balanced at baseline, over follow-up EK-treated patients had higher prevalence of glaucoma, elevated intraocular pressure, cataract, cataract surgery, diagnosis of cornea transplant rejection, retinal edema. By 36 month of follow-up, EK-treated patients had 9 more short-term disability days, resulting in $2992 additional burden of disability payments.Conclusion: This study found a higher cost burden among FECD patients receiving EK treatment versus those who did not. With a shift in management of FECD, cost burden estimates generated in this study could serve as an important benchmark for future studies.Keywords: cornea transplantation, cost analysis, glaucoma, retrospective study

Os autores realizaram uma revisão da literatura com a finalidade de observar as prevalências dos principais agentes causadores das cervicites emnosso meio e em serviços estrangeiros. Para a clamídia foram encontradas prevalências entre 2,6% e 13,9 com média em torno de 5,6%, lembrandoque a taxa mais alta observada de 13,9% foi estudo avaliando população de jovens americanos com idade entre 18 e 26 anos. Para o gonococo, a pre-valência observada foi significativamente menor, variando de 0,43 a 19,0 com média de 5,43, embora este valor não seja “real”, pois o estudo querevelou taxa de 19% foi realizado na África entre clínicas que atendem pacientes com DST, o que fez com que a média se elevasse. No Brasil a prevalência de clamídia também foi extremamente variada o estudo mais significativo mostrou taxas oscilando entre 0,6 e 20,2%, avaliando-se 16 esta-dos brasileiros, sendo que para o Gonoco as taxas são escassas e difíceis de se extrair uma conclusão. Desta forma podemos concluir que estes microorganismos, principalmente a clamídia, são muito freqüentes e merecem avaliação mais detalhada, principalmente no sentido de se observar as taxas reais de sua prevalência em nosso meio.

Summary: Although mice mostly communicate in the ultrasonic range, they also emit audible calls. We demonstrate that mice selectively bred for high anxiety-related behavior (HAB) have a high disposition for emitting sonic calls when caught by the tail. The vocalization was unrelated to pain but sensitive to anxiolytics. As revealed by manganese-enhanced MRI, HAB mice displayed an increased tonic activity of the periaqueductal gray (PAG). Selective inhibition of the dorsolateral PAG not only reduced anxiety-like behavior but also completely abolished sonic vocalization. Calls were emitted at a fundamental frequency of 3.8 kHz, which falls into the hearing range of numerous predators. Indeed, playback of sonic vocalization attracted rats if associated with a stimulus mouse. If played back to HAB mice, sonic calls were repellent in the absence of a conspecific but attractive in their presence. Our data demonstrate that sonic vocalization attracts both predators and conspecifics depending on the context.

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape vigor from innate and conditioned threats. Cholecystokinin (cck)-expressing cells in the hypothalamic dorsal premammillary nucleus (PMd) are necessary for initiating escape from innate threats via a projection to the dorsolateral periaqueductal gray (dlPAG). We now show that in mice PMd-cck cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Intriguingly, PMd-cck and dlPAG activity in mice showed higher mutual information during exposure to innate and conditioned threats. In parallel, human functional magnetic resonance imaging data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd-dlPAG circuit as a central node, controlling escape vigor elicited by both innate and conditioned threats.

Animals must balance needs to approach threats for risk assessment and to avoid danger. The dorsal periaqueductal gray (dPAG) controls defensive behaviors, but it is unknown how it represents states associated with threat approach and avoidance. We identified a dPAG threatavoidance ensemble in mice that showed higher activity farther from threats such as the open arms of the elevated plus maze and a predator. These cells were also more active during threat avoidance behaviors such as escape and freezing, even though these behaviors have antagonistic motor output. Conversely, the threat approach ensemble was more active during risk assessment behaviors and near threats. Furthermore, unsupervised methods showed that avoidance/approach states were encoded with shared activity patterns across threats. Lastly, the relative number of cells in each ensemble predicted threat avoidance across mice. Thus, dPAG ensembles dynamically encode threat approach and avoidance states, providing a flexible mechanism to balance risk assessment and danger avoidance.

The origin of diamonds from Serra do Espinhaço in Diamantina region (State of Minas Gerais) and in Chapada Diamantina, Lençóis region (State of Bahia) remains uncertain, even taking into account the ample research carried out during the last decades. The lack of typical satellite minerals in both districts makes a kimberlitic source for these diamonds uncertain. In mid 18th century the occurrence of a metamorphosed igneous rock composed of martite, sericite and tourmaline was described in Diamantina region and named hematitic phyllite, considered by some researchers as a possible diamond source. Similar rocks were found in Lençóis and examined petrographically and their heavy mineral concentration was investigated by means of scanning electron microscopy (SEM). Petrographic analyses indicated an igneous origin for these rocks and SEM analyses showed the discovery of microdiamonds. Geochronological studies using the Ar/Ar technique in muscovites yielded minimum ages of 1515 ± 3 Ma, which may correlate with 1710 ± 12 Ma from U-Pb method in igneous zircons from the hematitic phyllites. Both rock types also have the same mineral and chemical composition which leads to the conclusion that the intrusive rocks were protolith of the hematitic phyllites. This first discovery of microdiamonds in intrusive rocks opens the possibility of new investigation models for diamond mineralization in Brazilian Proterozoic terrains.A origem dos diamantes da Serra do Espinhaço na região de Diamantina, Minas Gerais e na Chapada Diamantina, na região de Lençóis, Bahia, permanece incerta apesar das inúmeras pesquisas desenvolvidas, ao longo das últimas décadas. A ausência de minerais satélites típicos em ambos os distritos, torna incerta a possibilidade de fonte kimberlítica para os diamantes. Na região de Diamantina registra-se, desde meados do século XVIII, a ocorrência de uma rocha metamórfica, composta por martita, sericita e turmalina, denominada filito hematítico e considerada por alguns pesquisadores como uma provável fonte dos diamantes. Rochas similares foram encontradas na região de Lençóis e submetidas a estudos petrográficos tendo a concentração de minerais pesados sido investigada por microscopia eletrônica de varredura (MEV). As análises petrográficas permitiram determinar uma origem ígnea para as rochas e as análises de MEV mostraram a ocorrência de microdiamantes. Estudos geocronológicos com a técnica Ar/Ar em muscovitas revelaram idades de 1515 ±3 m.a. que são correlacionáveis às idades de 1710 ±12 m.a., obtidas pelo método U-Pb, em zircões dos filitos hematíticos. Ambos litotipos apresentam composições química e mineralógica idênticas o que permite concluir que os filitos hematíticos tiveram como protólito as rochas intrusivas. Essa descoberta inédita de microdiamantes nas rochas intrusivas descortina a possibilidade de adoção de novos modelos prospectivos para mineralizações de diamantes em terrenos do Proterozóico brasileiro.

Objetivos: analisar as características sociodemográficas das mulheres vítimas de violência sexual, avaliar a experiência sexual prévia, pesquisar a utilização de métodos anticoncepcionais por ocasião da violência e observar o período de tempo desde a agressão até o atendimento hospitalar. Métodos: foram analisados os dados de 117 fichas pré-codificadas, de um total de 134 atendimentos. As fichas foram utilizadas no atendimento de mulheres vítimas de violência sexual na Maternidade do Hospital de Clínicas de Curitiba no período de agosto de 1998 até junho de 2000. Resultados: a idade das mulheres variou de 5 a 49 anos, sendo que a metade era de jovens, com até 19 anos. A maioria tinha segundo grau completo ou incompleto, 41 (41,0%) eram estudantes e 82 (82,0%) eram solteiras. Na análise da experiência sexual prévia, constatou-se que cerca de um terço (32,4%) era virgem. Das mulheres que referiam ter vida sexual prévia, 35 (47,9%) usavam algum método anticoncepcional quando da agressão. Houve variação de 2 horas a 2 meses em relação ao tempo decorrido desde a violência sexual até a procura por atendimento. Conclusões: o número de mulheres vítimas de violência sexual evidencia a importância de um atendimento especializado a estas pacientes. Há também necessidade de este atendimento ser multidisciplinar, já que dentre as vítimas existem grupos que necessitam de atenção diferenciada, como por exemplo as crianças. O intervalo entre a violência sexual e a procura do serviço pode ser considerado como indício de que a população deve ter acesso a mais informações em relação à prevenção de gravidez e doenças sexualmente transmissíveis, inclusive a infecção pelo HIV.

BackgroundThe control arm of PATRICIA (PApilloma TRIal against Cancer In young Adults, NCT00122681) was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN) or clearance of infection, and associated determinants.Methods and findingsWomen aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI) was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ≥2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+) associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 women with 6902 6MPIs). Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65), 9.65 (5.97-15.60), 5.68 (3.50-9.21), 5.38 (2.87-10.06) and 3.87 (2.38-6.30) for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear.ConclusionsCervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance.

Translocator protein (TSPO) present in the outer mitochondrial membrane has been suggested to be critical for cholesterol import, a rate-limiting step for steroid hormone biosynthesis. Despite the importance of steroidogenesis in regulating reproductive functions, the developmental profile of TSPO expression in the gonads and accessory sex organs has not been completely characterized. As a first step towards understanding the function of TSPO, we studied its expression in male and female murine reproductive organs. We examined testes and ovaries at embryonic days 14.5 and 18.5, and postnatal days 0, 7, 14, 21 and 56 of development. In the adult testis, TSPO was expressed in both Leydig cells and Sertoli cells. In the developing testes TSPO expression was seen in immature Sertoli cells, fetal Leydig cells and gonocytes. In the ovary, TSPO was expressed in the ovarian surface epithelium, interstitial cells granulosa cells and luteal cells. Corpora lutea of ovaries from pregnant mice showed strong expression of TSPO. In the developing ovary, TSPO expression was seen in the squamous pregranulosa cells associated with germ line cysts, together with progressively increasing expression in interstitial cells and the ovarian surface epithelium. In adult mice, the epithelia of other reproductive tissues like the epididymis, prostate, seminal vesicle, oviduct and uterus also showed distinct patterns of TSPO expression. In summary, TSPO expression in both male and female reproductive tissues was not only restricted to steroidogenic cells. Expression in Sertoli cells, ovarian surface epithelium, efferent ductal epithelium, prostatic epithelium, seminal vesiclular epithelium, uterine epithelium and oviductal epithelium suggest either previously unknown sites for de novo steroidogenesis or functions for TSPO distinct from its well-studied role in steroid hormone production.

A cisticercose é grave problema de saúde pública em várias regiões da Ásia, África e América Latina. Os estudos epidemiológicos baseados na freqüência de casos nos serviços especializados de neurologia, neurocirurgia, tomografia computadorizada, nas necrópsias e nos estudos soroepidemiológicos não permitem a avaliação da real prevalência populacional. O presente estudo teve como objetivo a análise da prevalência da cisticercose no município de Ribeirão Preto, através da notificação compulsória implantada em caráter pioneiro no Brasil. O coeficiente de prevalência foi de 54 casos/100000 habitantes, no período de 20-outubro-1992 a 31-de-dezembro de 199S. Os resultados indicaram, adicionalmente, que a cisticercose não está sob controle no nosso meio pois 21% dos casos notificados apresentavam a forma ativa. A notificação compulsória revelou ser recurso valioso para o estudo epidemiológico da cisticercose, permitindo, adicionalmente, o mapeamento das áreas mais afetadas para melhor direcionamento das estratégias de prevenção.Cysticercosis is a severe public health problem in several regions of Asia, Africa and Latin America. Epidemiologic studies based on the frequency of cases observed in specialized neurology, neurosurgery and computed tomography services, at autopsy and in seroepidemiologic studies do not permit the determination of the true prevalence of the disease in the population. The objective of the present study was to investigate the prevalence of cysticercosis by compulsory notification. The coefficient of prevalence was 54 cases/100000 inhabitants in the municipality of Ribeirão Preto. The results also indicated that cysticercosis is not under control in our region since 21% of cases presented the active form of the disease. Compulsory notification proved to be a valuable resource for the epidemiologic study of cysticercosis, also permitting the mapping of more affected areas for a better direction of prevention strategies.

The dorsolateral column of the periaqueductal gray (dlPAG) integrates aversive emotional experiences and represents an important site responding to life threatening situations, such as hypoxia, cardiac pain and predator threats. Previous studies have shown that the dorsal PAG also supports fear learning; and we have currently explored how the dlPAG influences associative learning. We have first shown that N-methyl-D-aspartate (NMDA) 100 pmol injection in the dlPAG works as a valuable unconditioned stimulus (US) for the acquisition of olfactory fear conditioning (OFC) using amyl acetate odor as conditioned stimulus (CS). Next, we revisited the ascending projections of the dlPAG to the thalamus and hypothalamus to reveal potential paths that could mediate associative learning during OFC. Accordingly, the most important ascending target of the dlPAG is the hypothalamic defensive circuit, and we were able to show that pharmacological inactivation using β-adrenoceptor blockade of the dorsal premammillary nucleus, the main exit way for the hypothalamic defensive circuit to thalamo-cortical circuits involved in fear learning, impaired the acquisition of the OFC promoted by NMDA stimulation of the dlPAG. Moreover, our tracing study revealed multiple parallel paths from the dlPAG to several thalamic targets linked to cortical-hippocampal-amygdalar circuits involved in fear learning. Overall, the results point to a major role of the dlPAG in the mediation of aversive associative learning via ascending projections to the medial hypothalamic defensive circuit, and perhaps, to other thalamic targets, as well. These results provide interesting perspectives to understand how life threatening events impact on fear learning, and should be useful to understand pathological fear memory encoding in anxiety disorders.

Este estudo faz uma revisão atualizada da prevalência do Trichomonas vaginalis na população geral, bem como sua complexa interação com o hospedeiro e as consequências da infecção não diagnosticada. O Trichomonas vaginalis é um parasita extracelular das mucosas, especialmente a vaginal, que causa descarga vaginal, irritação e inflamação, podendo ser assintomático em quase 1/3 dos casos. Atualmente tem sido pouco encontrado em alguns centros, mas continua como causa importante de vulvovaginites no mundo, mantendo-se com taxas de 10% dos corrimentos vaginais em vários estudos epidemiológicos. É abordada a complexa relação parasita-hospedeiro, em que a resposta imunológica predispõe vaginose bacteriana e infecção pelo HIV, por mobilização das células de defesa (leucócitos, linfócitos T CD4 e macrófagos). As formas de diagnóstico são apontadas para facilitar a compreensão do diagnóstico. Foram apontadas ainda as formas de tratamento e em especial as dificuldades com casos de resistência medicamentosa.

Levando em conta o número restrito de casos em âmbito internacional e a ausência de publicações na literatura nacional, os autores apresentam três casos de crises motoras focais induzidas por movimentos em pacientes diabéticos com mais de 50 anos de idade. As crises eram numerosas, sendo também desencadeadas ao serem assumidas determinadas posturas. Em dois casos havia hiperglicemia não cetótica. Todos os pacientes apresentavam hemiparesia e, em dois, tal déficit desapareceu após o cotnrole das crises. No outro paciente a hemiparesia era decorrente de acidente vascular cerebral isquêmico instalado 6 meses antes. Síndrome parietal transitória foi observada nos três pacientes. O EEG crítico mostrou, em dois pacientes, descargas na região parieto-occipital e, em um, na região temporal média contralateral. As crises foram resistentes aos anticonvulsivantes, só havendo controle com o tratamento dos distúrbios metabólicos. São discutidos aspectos clínico-eletren-cefalográficos e etiopatogênicos. A pesquisa do caráter reflexo das crises e a dosagem da glicemia devem ser feitas em todos os pacientes idosos com crises motoras focais, face às implicações de ordem terapêutica e prognóstica.

Introdução: os meios de comunicação têm tido uma participação cada vez mais frequente e intensa nas pessoas, principalmente nos jovens, mas nãose tem conhecimento de que tipo de informação sobre erotização e prevenção de DST/Aids está sendo passada aos nossos adolescentes. Objetivos: avaliar a carga de informações a respeito de erotização e de prevenção de DST/Aids. Métodos: em estudo epidemiológico, foram selecionados colégios públicos e particulares da cidade de Curitiba. Foram distribuídos questionários a 600 alunos, de 5ª a 8ª série do ensino fundamental e do 1º ao 3ºano do ensino médio para verificar quais revistas e TV são mais lidos e vistos. Em uma segunda etapa, os principais meios referidos foram avaliadoscom relação ao conteúdo erótico e de prevenção de DST/Aids, conforme a classificação estipulada. Os dados finais foram computados e comparados. Resultados: a rede Globo foi a mais assistida. O horário mais assistido foi o das 20 horas às 22 horas. A revista mais lida foi à revista Veja. Nasegunda etapa, observamos que o canal de televisão com mais erotismo foi a MTV, que também foi o canal com mais mensagens sobre prevenção de DST/Aids. A revista que apresentou maior média de mensagens eróticas foi à revista Vejae a que apresentou maior conteúdo de informações sobre DST/Aids foi à revista Capricho. Conclusão: dentre as várias, destacamos: TV Globo, MTV, Veja, Caprichoe Super Interessante foram as maisconsumidas; a quantidade de mensagens de DST/Aids e anticoncepção é insignificante.

A relação entre doença inflamatória pélvica (DIP) e esterilidade tem sido motivo de inúmeras publicações e discussões na literatura. Na etiopatogenia observamos que dentre os vários agentes causadores de DIP a Chlamydia trachomatis é responsável pela maioria dos casos em nosso meio. Vários autores descrevem as alterações tubáreas e peritubáreas que podem ser desenvolvidas a partir-da doença inflamatória pélvica resultando, em muitos casos, em infertilidade. Na maioria das pacientes os sintomas são variados, tomando por vezes dificil o diagnóstico e a diferenciação de outras patologias genitais. A prevenção da doença inflamatória pélvica e de suas compli-cações depende principalmente do controle efetivo da transmissão da infecção.

The present study examined the development of calcium binding protein-containing neurons in a timed series of fetal neocortical transplants. The immunoexpression of parvalbumin and calbindin, which are subpopulations of GABAergic neurons, have been widely studied in normal development and in disease and injury states. Because of their purported resistance to oxidative injury by their ability to buffer Ca ++ influx, these neurons have been particularly studied following ischemia. Because it is likely that oxidative stress is associated with the grafting procedure, we sought to determine if these neurons displayed enhanced survival characteristics. Normally, parvalbumin and calbindin represent about 5-10% of cortical neurons. Within 2-4 wk after grafting the expression of both proteins increased markedly in that a relatively larger number of neurons (27% for parvalbumin) were immunopositive. This increase was transitory, however, and by 4 mo and beyond, confocal microscopic data showed a reduction of over 50% of parvalbumin (+) neurons and processes. Calbindin (+) processes showed a qualitative change in that they were smaller with less terminal branching. Electron microscopy confirmed a substantial reduction in parvalbumin synaptic contacts. Interestingly, in older grafts, remaining parvalbumin neurons were those that were strongly NSE (+) suggesting a link between normal metabolism and Ca ++ buffering in grafted neurons. It is possible that in early grafts certain neuronal populations transiently upregulated calcium binding proteins as a defensive mechanism against Ca ++ influx associated with oxidative stress. Over time, however, following physiological normalization within grafts, the calcium binding protein (+) neurons are diminished, possibly due to lack of appropriate afferent input to the interneuronal pool.

The brainstem dorsal periaqueductal gray (dPAG) has been widely recognized as being a vital node orchestrating the responses to innate threats. Intriguingly, recent evidence also shows that the dPAG mediates defensive responses to fear conditioned contexts. However, it is unknown whether the dPAG displays independent or shared patterns of activation during exposure to innate and conditioned threats. It is also unclear how dPAG ensembles encode and predict diverse defensive behaviors. To address this question, we used miniaturized microscopes to obtain recordings of the same dPAG ensembles during exposure to a live predator and a fear conditioned context in male mice. dPAG ensembles encoded not only distance to threat, but also relevant features, such as predator speed and angular offset between mouse and threat. Furthermore, dPAG cells accurately encoded numerous defensive behaviors, including freezing, stretch-attend postures, and escape. Encoding of behaviors and of distance to threat occurred independently in dPAG cells. dPAG cells also displayed a shared representation to encode these behaviors and distance to threat across innate and conditioned threats. Last, we also show that escape could be predicted by dPAG activity several seconds in advance. Thus, dPAG activity dynamically tracks key kinematic and behavioral variables during exposure to threats, and exhibits similar patterns of activation during defensive behaviors elicited by innate or conditioned threats. These data indicate that a common pathway may be recruited by the dPAG during exposure to a wide variety of threat modalities.SIGNIFICANCE STATEMENT The dorsal periaqueductal gray (dPAG) is critical to generate defensive behaviors during encounters with threats of multiple modalities. Here we use longitudinal calcium transient recordings of dPAG ensembles in freely moving mice to show that this region uses shared patterns of activity to represent distance to an innate threat (a live predator) and a conditioned threat (a shock grid). We also show that dPAG neural activity can predict diverse defensive behaviors. These data indicate the dPAG uses conserved population-level activity patterns to encode and coordinate defensive behaviors during exposure to both innate and conditioned threats.

Naturalistic escape requires versatile context-specific flight with rapid evaluation of local geometry to identify and use efficient escape routes. It is unknown how spatial navigation and escape circuits are recruited to produce context-specific flight. Using mice, we show that activity in cholecystokinin-expressing hypothalamic dorsal premammillary nucleus (PMd-cck) cells is sufficient and necessary for context-specific escape that adapts to each environment's layout. In contrast, numerous other nuclei implicated in flight only induced stereotyped panic-related escape. We reasoned the dorsal premammillary nucleus (PMd) can induce context-specific escape because it projects to escape and spatial navigation nuclei. Indeed, activity in PMd-cck projections to thalamic spatial navigation circuits is necessary for context-specific escape induced by moderate threats but not panic-related stereotyped escape caused by perceived asphyxiation. Conversely, the PMd projection to the escape-inducing dorsal periaqueductal gray projection is necessary for all tested escapes. Thus, PMd-cck cells control versatile flight, engaging spatial navigation and escape circuits.

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape vigor from innate and conditioned threats. Cholecystokinin (cck)-expressing cells in the hypothalamic dorsal premammillary nucleus (PMd) are necessary for initiating escape from innate threats via a projection to the dorsolateral periaqueductal gray (dlPAG). We now show that in mice PMd-cck cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Intriguingly, PMd-cck and dlPAG activity in mice showed higher mutual information during exposure to innate and conditioned threats. In parallel, human functional magnetic resonance imaging data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd-dlPAG circuit as a central node, controlling escape vigor elicited by both innate and conditioned threats.

Animals must balance needs to approach threats for risk assessment and to avoid danger. The dorsal periaqueductal gray (dPAG) controls defensive behaviors, but it is unknown how it represents states associated with threat approach and avoidance. We identified a dPAG threatavoidance ensemble in mice that showed higher activity farther from threats such as the open arms of the elevated plus maze and a predator. These cells were also more active during threat avoidance behaviors such as escape and freezing, even though these behaviors have antagonistic motor output. Conversely, the threat approach ensemble was more active during risk assessment behaviors and near threats. Furthermore, unsupervised methods showed that avoidance/approach states were encoded with shared activity patterns across threats. Lastly, the relative number of cells in each ensemble predicted threat avoidance across mice. Thus, dPAG ensembles dynamically encode threat approach and avoidance states, providing a flexible mechanism to balance risk assessment and danger avoidance.

Background & Objectives: In today’s world, many adolescents face many problems due to social media distractions, one of the most important problem is mental health and its related problems. India has adolescents, a quarter of the total population and only a few studies were done on mental well-being among adolescents studying in government and private schools. The objectives of the study were to assess mental well-being among adolescents and to find out the association between mental well-being with selected sociodemographic variables. Methodology: This was a cross-sectional self-administered questionnaire based study. A convenient sampling method was used. Totally 184 male and female adolescents studying 9th to 12th standards from rural areas of government and private school students had voluntarily participated. To assess the mental well-being among adolescents Warwick Mental Well-being scale was used. All the collected data were cleaned, coded, and entered in MS Excel version 2007. Frequencies, Chi-square test, and Fisher’s exact test were analyzed by using SPSS software version 22.0. Results and Conclusion: The results were found that 59 % of adolescents were studying in a government school and 41% were studying in a private school. There was an association between mental well-being and the mother’s education, siblings, staying, domicile and extracurricular activities (p<0.05). This research study showed that the majority of the adolescents were having average level of mental well-being in the Vellore district of Tamil Nadu. [ABSTRACT FROM AUTHOR]

Microinstabilities drive turbulent fluctuations in inhomogeneous, magnetised plasmas. In the context of magnetic confinement fusion devices, this leads to an enhanced transport of particles, momentum and energy, thereby degrading confinement. In this work, we describe an application of the adjoint method to efficiently determine variations of gyrokinetic linear growth rates on a general set of external parameters in the local $\delta f$ -gyrokinetic model. We then offer numerical verification of this approach. When coupled with gradient-based techniques, this methodology can facilitate the optimisation process for the microstability of the confined plasmas across a high-dimensional parameter space. We present a numerical demonstration wherein the ion-temperature-gradient instability growth rate in a tokamak plasma is minimised with respect to flux surface shaping parameters. The adjoint method approach demonstrates a significant computational speed-up compared with a finite-difference gradient calculation. [ABSTRACT FROM AUTHOR]

The dorsal periaqueductal gray (dPAG) contains a tonically GABAergic network controlling defensive responses. Determining how this intrinsic dPAG inhibitory circuit functions might provide critical insights into how anti-predatory responses are organized. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia. Methods: Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed. Results: The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53–43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52–38.4]). Comorbidities were more frequent in the PE+ group (63.6% vs 31.5%, p = 0.03), as well as prematurity (81.8% vs 41.6%, p = 0.02), low birth weight (63.6% vs 24.7%, p = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% vs 27.0%, p = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34–4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant. Conclusions: Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia. [ABSTRACT FROM AUTHOR]