Plasma Melatonin and Progesterone Profiles of Suffolk and Romney Marsh Ewes Implanted with Melatonin during Anoestrus Season at Lower Latitudes in Southern Hemisphere

Background: The subcutaneous implants of melatonin are stimulatory and mimic the positive effects of short photoperiod on reproduction in small ruminants. This study investigated the daily plasma melatonin profiles in ewes treated with melatonin implants and kept under natural photoperiod in Southeastern Brazil. The plasma progesterone concentrations were also investigated before and after melatonin implantation.Materials, Methods & Results: Romney Marsh (n = 11) and Suffolk (n = 10) ewes, which had been isolated from rams for at least 2 months prior to the beginning of the trial, were randomly allocated in two groups based on melatonin implant treatment (with or without melatonin implant). For plasma melatonin concentration, 43 days after melatonin implantation and 3 days before the ram introduction blood samples were collected every 2 hours during 24 hours. For plasma progesterone concentrations, blood samples were collected every once to twice a week for 2 different periods: prior to melatonin implantation and 46 days after the melatonin implantation and at the same day of the introduction of rams. The hormonal concentrations were determined by the radioimmunoassay method (RIA). The data were analyzed according to MIXED procedure (SAS) as repeated measurements for random animal effects. The effect of melatonin treatment on plasma melatonin 24-h period varied according to the breed. At the dark-phase, there were no plasma melatonin differences (P > 0.05) between implanted and no-implanted (228.02 ± 58.39 vs. 169.59 ± 48.39) Romney Marsh ewes whereas for Suffolk ewes the plasma melatonin levels were higher in implanted (305.61 ± 68.39 pg/mL) than no-implanted (151.26 ± 38.35 pg/mL) ones. At the light-phase, melatonin treatment effects could be evidenced and these differences (P than 1 ng/mL in implanted and no-implanted Suffolk ewes. In implanted Romney Marsh ewes the elevation of progesterone mean values was weak whereas in no-implanted Romney Marsh ewes the progesterone levels were maintained ˂ 1 ng/mL during all the blood sample collection times.Discussion: The melatonin treatment also produced a similar model of daily melatonin levels as reported previously by others, which is characterized by high plasma melatonin concentrations during the light phase of the day. The effect of melatonin implants on plasma melatonin profiles interacted with breed confirming an individual response to melatonin implantation which is proportional to genetic individual variation pattern of melatonin secretion. Before the melatonin implantation all Romney Marsh and Suffolk ewes were judged to be in non-ovulatory period (anoestrus) with plasma progesterone mean values lower than 1 ng/mL. The melatonin treatment helped to induce the ovulatory activity in most of the ewes that were in anestrous at the time of melatonin implantation and the efficacy of this treatment depends on the individual variation in ovulatory response to ram introduction. In Southeastern Brazil., melatonin implant altered the daily plasma melatonin profiles of Suffolk and Romney Marsh ewes by increasing the melatonin levels during the light-phase of the day. Melatonin implant also induced an ovulatory response in Suffolk and Romney Marsh after the introduction of the rams. For no-implanted Suffolk ewes, the male effect is sufficient to provoke an ovulatory response

DIP during perioperative chemotherapy

Purpose : Drug-induced interstitial pneumonia (DIP) that occurs during chemotherapy for breast cancer is a rare but a serious adverse event. Treatments of DIP requires interruption of breast cancer treatment, which may affect the patient’s prognosis. However, there are few reports which discuss DIP during breast cancer treatments. Purpose of this report is to make clear how DIP occurred and influenced breast cancer treatment in our hospital. Patients and Methods : A total of 74 patients who started perioperative chemotherapy in Tokushima Municipal Hospital for breast cancer from January 2019 to December 2020 were evaluated for DIP. Patients’ and tumors’ characteristics, and regimens which caused DIP were investigated. The clinical courses of the DIP patients were also followed up. Results : Twelve of the 74 patients developed DIP. All 12 patients had histories of cyclophosphamide administration ; however, the causative drug could not be determined. Ten of the 12 patients were treated with steroids, and all the patients recovered ultimately from the interstitial pneumonia. While chemotherapy was administered in six patients after mild DIP, no relapse of pneumonia was observed. Conclusion : DIP during perioperative chemotherapy for breast cancer was resolved with appropriate treatment. Patients were able to resume breast cancer treatment with minimal interruption

Características anuais da atividade estral em borregas lanadas e deslanadas mantidas sob condição subtropical

The increased emphasis placed on lamb production in Brazil points to the need for a better knowledge of the annual pattern of reproductive activity in ewe lambs. This study evaluates the annual estrous activity pattern of hair and wool ewe lambs raised in southeast Brazil. Estrous characteristics were recorded for 12 months in ten Santa Inês and 21 Romney Marsh and Suffolk ewe lambs. Santa Inês ewe lambs exhibited a greater length of the normal estrous cycle (14 to 19 days) than Romney Marsh and Suffolk ewe lambs (17.0 ± 0.1 days vs. 16.5 ± 0.2 and 15.9 ± 0.2 days). All the ewe lambs presented a greater number of periods of estrus per animal per month for single estrous cycles (up to 26 days) during autumn and winter. During spring and summer there was a reduction of this number but this decline varied according to the breed. For Santa Inês ewe lambs the reduction was only significant in the summer. For wool ewe lambs the reduction was significant in both seasons but was more accentuated for Romney Marsh. The Romney Marsh ewe lambs had a more restricted breeding season than Suffolk and both presented optimal estrus activity in autumn and winter. Santa Inês ewe lambs had a continuous distribution of estrous cycles along the year, although presenting a reduction in the number of estrous periods in the summer. The ewe lambs of three breeds presented characteristics of sexual immaturity, like irregular estrous cycles and silent ovulations.Em função do maior interesse pela ovinocultura de corte na região Sudeste do Brasil há necessidade de conhecer melhor o padrão anual da atividade reprodutiva das borregas. Esse estudo avaliou esse padrão anual em borregas deslanadas e lanadas criadas nessa região. A atividade cíclica reprodutiva foi avaliada durante 12 meses em dez borregas da raça Santa Inês e 21 borregas das raças Romney Marsh (11) e Suffolk (10). A duração dos ciclos estrais normais (14 a 19 dias) das fêmeas Santa Inês foi maior do que a duração observada nas fêmeas Romney Marsh e Suffolk (17,0 ± 0,1 dias vs. 16,5 ± 0,2 e 15,9 ± 0,2 dias). Todas as borregas apresentaram um elevado número de períodos de estros/animal/mês para ciclos estrais simples (até 26 dias) durante o outono e inverno. Houve redução desse número durante a primavera e o verão, mas esse declínio variou conforme a raça. Para as borregas Santa Inês essa redução só foi significativa no verão enquanto que para as fêmeas das raças lanadas, a redução foi significativa em ambas as estações e mais acentuada nas fêmeas Romney Marsh. As fêmeas dessa raça também apresentaram uma estação reprodutiva mais restrita do que as fêmeas Suffolk havendo uma concentração dos estros durante o outono e inverno para as fêmeas de ambas as raças. As fêmeas Santa Inês apresentaram uma distribuição equilibrada dos estros ao longo do ano embora tenha havido uma redução do número de período de estros durante o verão. As borregas das três raças apresentaram características de imaturidade sexual como ciclos estrais irregulares e ovulações silenciosas

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Effects of nutrition on reproductive cyclic activity and on plasmatic melatonin concentration for ewes in pasture and submitted to the male effect, during seasonal anoestrus.

O presente trabalho teve como objetivo avaliar os efeitos de diferentes condições nutricionais (suplementação e não suplementação) na atividade cíclica reprodutiva (ACR) em ovelhas das raças Santa Inês (SI), Romney Marsh (RM) e Suffolk (SU) mantidas sob pastejo, e submetidas ao efeito macho, durante época de anestro sazonal sob fotoperíodo natural no Estado de São Paulo. Avaliou-se também os efeitos destes tratamentos nas concentrações plasmáticas de melatonina (MEL) e na duração (horas) da secreção noturna deste hormônio. Todos animais foram mantidos sob pastejo, sendo que metade de cada raça recebeu suplementação e a outra não, caracterizando os tratamentos de suplementação e não suplementação, respectivamente. O tratamento de suplementação forneceu de 100 a 110% dos requerimentos protéicos (PB) e de 130 a 140% dos requerimentos energéticos (NDT), enquanto que o tratamento de não suplementação forneceu de 60 a 70% de PB e 100% de NDT. Os tratamentos nutricionais iniciaram 21 dias antes da introdução dos machos, e continuaram por todo o período de permanência dos mesmos (45 dias). Para o efeito macho, foram utilizados três machos (rufiões), impregnados com tinta na região prepucial para detecção do estro, os quais permaneceram isolados das fêmeas por um período de 60 dias. Colheitas de sangue foram realizadas antes (a cada 3 dias) e após (a cada 2 dias) a introdução dos machos, para dosagem de progesterona plasmática, a fim de monitorar a ACR das fêmeas. Foram também realizadas colheitas de sangue para dosagem de MEL plasmática: antes do início do experimento, antes da introdução dos machos e no final do experimento, em período de 24 horas, a cada 2 (noite) ou 4 (dia) horas. Os parâmetros avaliados foram: ganho de peso, ACR após introdução dos machos nos animais que se encontravam em anestro, dias para retorno da ACR, concentrações plasmáticas de MEL, duração da secreção de MEL. Estes parâmetros foram analisados utilizando o procedimento GLM no SAS, seguido pelo teste de ukey para estabelecer a comparação entre médias. O tratamento nutricional teve efeito no ganho de peso (P<0,001), no número de dias para retorno da ACR (P<0,1), nas concentrações de MEL (P<0,1) e na duração da secreção deste hormônio (P<0,1). Animais suplementados apresentaram em média, maior ganho de peso, maiores concentrações de MEL plasmática, e maior duração da secreção deste hormônio. Diferenças raciais foram encontradas para ganho de peso, retorno da ACR e concentrações plasmáticas de MEL. Fêmeas SI, perderam peso, enquanto que as RM mantiveram e as SU ganharam peso durante todo o período experimental, independente do tratamento nutricional. Todas as fêmeas SI retornaram à ACR em média 5 dias após a introdução dos machos, já as fêmeas SU suplementadas não retornaram à ACR, enquanto que as não suplementadas retornaram em 23 dias. Nenhuma ovelha RM retornou à ACR. Assim, conclui-se que para a raça SI só efeito macho é eficiente em ativar o retorno da ACR, e para a raça SU, deve-se aliar esta prática com um bom manejo nutricional, e para a RM, o efeito macho mesmo associado à nutrição não são capazes de amenizar a estacionalidade da ACR. E por fim, a nutrição afeta a duração da secreção de MEL.This study evaluated the effects of different nutritional conditions (suplementation and no suplementation) in reproductive cyclic activity (RCA) for Santa Inês (SI), Romney Marsh (RM) and Suffolk (SU) breeds, in pasture, submitted to the male effect, during seasonal anoestrus, under natural photoperiod in São Paulo State. It was also evaluated the effects of nutritional treatments for plasmatic melatonin (MEL) concentration and for the duration of MEL secretion. All ewes were mainted in pasture, receiving food supplementation or not, distinguishing the supplementation or not supplementation treatments. The supplementation treatment supplied 100-110% of protein requeriments (CP) and 130-140% of energy requeriments (TDN). The no supplementation treatment supplied 60-70% CP and 100% TDN requeriments. The nutritional treatments were started 21 days before the rams introduction and lasted throughout the permanence period (45 days). To the male effect, it used three vasectomized rams impregnated with ink at the prepucial area in order to facilitate the estrus verification, isolated from the females for 60 days. Blood samples were collected before (every 3 days) and after (every 2 days) the rams introduction to determine de plasmatic progesterone to follow up the ewes reproductive cyclic activity (RCA). Blood samples were also collected to determine the plasmatic MEL dosage: before the beginning of the experiment, before the rams introduction and in the end of the experiment, during 24 hours, every 2 dark hours or 4 light hours. There was evaluated the following parameters: weight gain, RCA after male introduction for the ewes in anoestrus, days to RCA return, MEL concentration and MEL secretion duration. The parameters were analyzed by analisis of variance using the GLM (General Linear Procedure) of the Statistical System (SAS) software. Tukey test was used to compare means. The nutritional treatment resulted efficient for weight gain (P<0,001), days to return RCA (P<0,1), MEL concentration (P<0,1) and the duration of its hormone secretion (P<0,1). Supplemented ewes showed higher weight gain, higher MEL plasmatic concentration and higher hormone secretion duration in average. There was verified breed differences for weight gain, RCA return and MEL plasmatic concentration. SI ewes lost weight in average, RM ewes maintained it and SU ewes gained weight during the whole experimental period not taking into account the nutritional treatment. SI ewes had, in average, their RCA returned 5 days after the rams introduction not taking into account the nutritional treatment. However, SU ewes presented different behaviours due treatments: the ones that received supplementation did not return the RCA while, the non supplemented ones returned the RCA within 23 days. RM ewes did not return RCA no matter which treatment had received. Therefore, one may conclude that for SI ewes the male effect is enough for the RCA return. For SU breed one should combine this practice to good nutritional management. And for RM neither the male effect nor the nutrition are capable to diminish the RCA seasonally. Finally, one may conclude that the nutrition affects the amount and duration of MEL secretion

Seasonal pattern of plasma progesterone, prolactine and melatonine concentrations in ewes kept at lower latitudes

O presente trabalho teve como objetivo estudar a atividade ovulatória ao longo do ano, as concentrações plasmáticas de melatonina e prolactina no período de 24 horas nos solstícios e equinócios de ovelhas lanadas Romney Marsh (10) e deslanadas Santa Inês (10) mantidas sob fotoperíodo natural em baixas latitudes no hemisfério Sul. Para o monitoramento da atividade ovulatória foram colhidas semanalmente sangue da veia jugular das fêmeas durante o período de um ano para determinação das concentrações plasmáticas de progesterona. Para a determinação das concentrações plasmáticas de prolactina e melatonina, foram realizadas colheitas de sangue a cada duas horas durante 24 horas nos dois solstícios e dois equinócios. As ovelhas das raças Santa Inês e Romney Marsh, apresentaram comportamento da atividade ovariana distintos, ou seja, as fêmeas lanadas foram estacionais, enquanto que as fêmeas deslanadas apresentaram atividade ovulatória o ano todo. O ciclo circadiano das concentrações plasmáticas de melatonina de ovelhas Romney Marsh e deslanadas Santa Inês apresentou um padrão sazonal idêntico, mas não apresentou um ritmo circanual. A duração da secreção noturna de melatonina acompanhou a duração do escotoperíodo de cada estação do ano. O perfil plasmático de prolactina de ovelhas Romney Marsh foi mais elevado que ovelhas Santa Inês em todas as estações, mas o padrão sazonal foi idêntico. As concentrações plasmáticas foram mais elevadas na primavera e no verão que no outono e inverno.This study evaluated the ovulatory activity throughout the year, plasma melatonin and prolactin concentrations on 24 hours during solstices and equinoces on wool (Romney Marsh - 10) and hair (Santa Inês - 10) ewes kept under natural photoperiod and lower latitudes in the southern hemisphere. To monitor the ovulatory activity, blood samples were collected weekly from the jugular vein throughout the year to determine the plasma progesterone concentrations. To determine the plasma melatonin and prolactin concentrations blood samples were collected each two hours during 24 hours on the solstices and equinoces. Santa Inês and Romney Marsh females showed different ovulatory activity. Wool ewes showed a strong seasonality, and hair ewes were in ovulatory activity all the year. The circadian cycle of plasma melatonin concentrations from Romney Marsh and Santa Inês females showed the same seasonal pattern, and did not showed circannual pattern. The duration of nocturnal secretion plasma melatonin was the same of scotoperiod duration on each season of the year. The plasma prolactin profile from Romney Marsh ewes were higher than Santa Inês ewes in all seasons, but the seasonal pattern was identic. Plasma concentrations were higher in spring and summer than autumm and winter