Associations of a multidimensional polygenic sleep health score and a sleep lifestyle index on health outcomes and their interaction in a clinical biobank.

Sleep is a complex behavior regulated by genetic and environmental factors, and is known to influence health outcomes. However, the effect of multidimensional sleep encompassing several sleep dimensions on diseases has yet to be fully elucidated. Using the Mass General Brigham Biobank, we aimed to examine the association of multidimensional sleep with health outcomes and investigate whether sleep behaviors modulate genetic predisposition to unfavorable sleep on mental health outcomes. First, we generated a Polygenic Sleep Health Score using previously identified single nucleotide polymorphisms for sleep health and constructed a Sleep Lifestyle Index using data from self-reported sleep questions and electronic health records; second, we performed phenome-wide association analyses between these indexes and clinical phenotypes; and third, we analyzed the interaction between the indexes on prevalent mental health outcomes. Fifteen thousand eight hundred and eighty-four participants were included in the analysis (mean age 54.4; 58.6% female). The Polygenic Sleep Health Score was associated with the Sleep Lifestyle Index (ß=0.050, 95%CI=0.032, 0.068) and with 114 disease outcomes spanning 12 disease groups, including obesity, sleep, and substance use disease outcomes (p<3.3×10-5). The Sleep Lifestyle Index was associated with 458 disease outcomes spanning 17 groups, including sleep, mood, and anxiety disease outcomes (p<5.1×10-5). No interactions were found between the indexes on prevalent mental health outcomes. These findings suggest that favorable sleep behaviors and genetic predisposition to healthy sleep may independently be protective of disease outcomes. This work provides novel insights into the role of multidimensional sleep on population health and highlights the need to develop prevention strategies focused on healthy sleep habits.

Assessment of the Roles of Magnesium and Zinc in Clinical Disorders.

The ability and facility of magnesium (Mg2+) and zinc (Zn2+) to interact with phosphate ions confer them the characteristics of essential trace elements. Trace elements are extremely necessary for the basic nucleic acid chemistry of cells of all known living organisms. More than 300 enzymes require zinc and magnesium ions for their catalytic actions, including all the enzymes involved in the synthesis of ATP. In addition, enzymes such as isomerases, oxidoreductases, lyases, transferases, ligases and hydrolases that use other nucleotides to synthesize DNA and RNA require magnesium and zinc. These nucleotides may trigger oxidative damage or important changes against free radicals. In the same way, nucleotides may play an important role in the pathophysiology of degenerative diseases, including in some clinical disorders, where vascular risk factors, oxidative stress and inflammation work to destabilize the patients` homeostatic equilibrium. Indeed, reduced levels of zinc and magnesium may lead to inadequate amount of antioxidant enzymes, and thus, acts as an important contributing factor for the induction of oxidative stress leading to cellular or tissue dysfunction. Hence, the development of zinc or magnesium enzyme inhibitors could be a novel opportunity for the treatment of some human disorders. Therefore, the objective of the present work was to assess the clinical benefits of zinc and magnesium in human health and their effects in some clinical disorders.

Anxiety, depression, stress, worry about COVID-19 and fear of loneliness during COVID-19 lockdown in Peru: A network analysis approach.

This study aims to examine the relationships between symptoms of anxiety, depression, stress, worry about COVID-19 and fear of loneliness during COVID-19 lockdown in Peru using network analysis. There were 854 participants aged 18 to 50 years (Mean = 36.54; SD = 9.23); 634 females (74.20%) and 220 males (25.80%), who completed the Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire (PHQ-9), Perceived Stress Scale (PSS-10), Preoccupation with COVID-19 Contagion (PRE-COVID-19), Brief Scale of Fear of Loneliness (BSFL). A partial unregularized network was estimated through the ggmModSelect function. Expected influence (EI) and bridging EI values were calculated to identify central symptoms and bridging symptoms respectively. The results reveal those two symptoms of depression-stress and anxiety-were the most central symptoms in the network. Depressive symptoms are at the same time the most comorbid and it is shown that there are no differences in the network when compared between those who left home and those who did not leave home during lockdown. Depressive symptoms are concluded to be central and bridging in the network and interconnected with some symptoms of stress and anxiety. These findings may be important to understand the experience of COVID-19 lockdown in Peru.

Relationship between metabolic profile, diseases, productive and reproductive performance in highproducing Holstein cows in the postpartum period / Relação entre o perfil metabólico, doenças, desempenho produtivo e reprodutivo de vacas Holandesas recém-paridas de alta produção

The present study aimed to monitor Holstein cows in the postpartum period, and to evaluate the occurrence of clinical diseases and their relationship with metabolic profile, milk yield and composition, and reproductive performance. One hundred and five Holstein cows, 32 primiparous and 73 multiparous, from two dairy herds in Arapoti, Paraná State, were clinically monitored up to ten days after calving. The clinical occurrences diagnosed were: dystocia, metritis, retained placenta, clinical hypocalcemia, displaced abomasum, mastitis, pneumonia, and digital dermatitis. Blood samples were collected at one, two, five, and ten days postpartum for analysis of non-esterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), and total calcium. Individual milk yield was measured up to 100 days in milk (DIM), and the first test-day was evaluated for milk composition. Statistical analyses were conducted using the MIXED procedure of SAS, and the fixed effects of farm (A and B), parity (primiparous and multiparous), and occurrence of clinical diseases (sick and healthy cows) were included. Forty-eight cows (45.7%) had one or more clinical occurrences. In these sick cows, the BHB concentration at five DIM was higher (P = 0.06) than in healthy cows; 0.78 and 0.57 mmol L-1, respectively. Regarding milk yield, cows with one or more clinical occurrences had lower (P < 0.01) daily milk yield up to 30 DIM, and had a tendency of lower (P = 0.09) accumulated production up to 100 DIM than healthy cows. Sick cows had a tendency to show lower (P = 0.08) milk total solids content than healthy cows; 12.04 and 12.60%, respectively. There were no significant differences between sick and healthy animals in the remaining milk components, or the reproductive parameters assessed. The differences observed for days in the first artificial insemination (AI), AI number, and days open occurred due to the effect of the herd.(AU)

O objetivo deste estudo foi monitorar vacas Holandesas no pós-parto e avaliar a ocorrência de doenças clínicas e sua relação com o perfil metabólico, a produção de leite e sua composição e o desempenho reprodutivo. Foram monitoradas clinicamente durante 10 dias após o parto, 105 vacas da raça Holandesa, 32 primíparas e 73 multíparas, de dois rebanhos leiteiros em Arapoti, Paraná. As ocorrências clínicas diagnosticadas foram: distocia, metrite, retenção de placenta, hipocalcemia clínica, deslocamento de abomaso, mastite, pneumonia e dermatite digital. Amostras de sangue foram coletadas nos dias 1, 2, 5 e 10 após o parto para análises de ácidos graxos não-esterificados (AGNE), ß-hidroxibutirato (BHB) e cálcio total. A produção de leite individual foi mensurada até 100 dias em leite (DEL) e para a composição do leite foi avaliado o primeiro controle leiteiro oficial após o parto. As análises estatísticas foram conduzidas pelo procedimento MIXED do SAS e foram incluídos os efeitos fixos de fazenda (A e B), paridade (primíparas e multíparas) e ocorrência de doenças clínicas (vacas doentes e saudáveis). Quarenta e oito vacas (45,7%) apresentaram uma ou mais doenças clínicas. Nestas vacas doentes a concentração de BHB no 5o dia pós-parto foi superior (P = 0,06) a de vacas saudáveis; 0,78 e 0,57 mmol L-1, respectivamente. Em relação a produtividade, vacas com uma ou mais doenças clínicas apresentaram menores (P < 0,01) produções diárias até 30 DEL e tendência de menores (P = 0,09) produções acumuladas até 100 DEL em relação a vacas sadias. Vacas doentes apresentaram uma tendência de menor (P = 0,08) porcentagem de sólidos totais no leite do que vacas saudáveis; 12,04 e 12,60%, respectivamente. Não houve diferenças significativas entre animais doentes e saudáveis para os outros componentes do leite, bem como nos parâmetros reprodutivos avaliados. As diferenças observadas para dias até a primeira inseminação artificial (IA), número de IA e dias abertos ocorreram devido ao efeito de rebanho.(AU)

Goats reinfected with toxoplasma gondii: loss of viable prolificacy and gross revenue / Cabras reinfectadas com toxoplasma gondii: perdas de prolificidade viável e receita bruta

We determined the reproductive parameters and clinical disorders in pregnant goats infected and reinfected with Toxoplasma gondii, and posteriorly the loss of gross revenue due to congenital toxoplasmosis was estimated. Of the 25 non-pregnant females negative for T. gondii, 20 were orally inoculated (ME 49 strain) and of these, 15 pregnant females chronically infected were orally reinoculated (VEG strain) with T. gondii oocysts. Five groups were formed (n=5): GI, GII and GIII (reinoculations at 40, 80 and 120 days of gestation, respectively), GIV (inoculation) and GV (no inoculation). Clinical and serological exams were performed on days 0 (prior to inoculation), 3, 6 9, 15 and 21 and every 7 days post-inoculation. Exams were also performed on day 3 and every 7 days post-reinoculation. Reproductive management was performed on all females and initiated when the females infected displayed IgG titers IFAT<1,024. From the average prolificacy indexes of each experimental group were estimated: total production of kilograms of live weight (total kg LW) of goats for slaughter, gross revenue and loss of gross revenue in U.S. dollars (US$), designed for a herd of 1,000 matrices. The unviable prolificacy indexes were 0.8 (GI), 1.2 (GII) and 0.2 (GIII). Clinical disorders affected 57.1% (GI), 75.0% (GII) and 16.7% (GIII) of the offspring of goats reinfected with T. gondii. Congenital toxoplasmosis in goats reinfected resulted in the loss of 26.5% of gross revenues, being GI (US$ 10,577.60 or 57.1%) and GII (US$ 12,693.12 or 60%) holders of the highest values and percentages of economic losses. It was found that congenital toxoplasmosis reinfection cause clinical disorders in goats chronically infected with T. gondii and their offspring with birth of unviable animals and loss of gross revenue, at different stages of pregnancy (40, 80 and 120 days of gestation)...

Nós determinamos os parâmetros reprodutivos e distúrbios clínicos em cabras gestantes infectadas e reinfectados com Toxoplasma gondii, e posteriormente, foi estimada a perda de receita bruta devido à toxoplasmose congênita. Das 25 fêmeas não prenhes negativas para T. gondii, 20 foram inoculadas oralmente (cepa ME 49) e, destas, 15 fêmeas gestantes infectadas cronicamente foram reinoculadas (cepa VEG), via oral, com oocistos de T. gondii. Cinco grupos foram formados (n = 5): GI, GII e GIII (reinoculações aos 40, 80 e 120 dias de gestação, respectivamente), GIV (inoculação) e GV (não inoculação). Exames clínicos e sorológicos foram realizados nos dias 0 (antes da inoculação), 3, 6 9, 15 e 21 e a cada sete dias após a inoculação. Os exames também foram realizados nos dias 3 e a cada sete dias de pós-reinoculação. Manejo reprodutivo foi realizado em todas as fêmeas e iniciou-se quando as fêmeas infectadas exibiram títulos de anticorpos IgG<1.024. A partir dos índices médios de prolificidade de cada grupo experimental foram estimados: a produção total de kg de peso vivo (total kg PV) de cabritos para o abate, receita bruta e perda de receita bruta em dólares norte-americanos (US$), projetadas para um rebanho de 1000 matrizes. Os índices de prolificidade inviáveis foram de 0,8 (GI), 1.2 (GII) e 0,2 (GIII). Distúrbios clínicos afetaram 57,1% (GI), 75,0% (GII) e 16,7% (GIII) das crias de cabras reinfectados com T. gondii. A toxoplasmose congênita em crias das cabras reinfectadas com T. gondii resultou na perda de 26,5% da receita bruta, sendo GI (US $ 10,577.60 e 57,1%) e GII (US $ 12,693.12 e 60.0%) os detentores dos mais altos valores e porcentagens de perdas econômicas. Verificou-se que a reinfecção toxoplásmica congênita causa distúrbios clínicos em cabras cronicamente infectadas com T. gondii e sua prole com o nascimento de animais inviáveis e perda de receita bruta, em diferentes fases da gestação (40, 80 e 120 dias de gestação)...

Goats reinfected with Toxoplasma gondii: loss of viable prolificacy and gross revenue / Cabras reinfectadas com Toxoplasma gondii: perdas de prolificidade viável e receita bruta

We determined the reproductive parameters and clinical disorders in pregnant goats infected and reinfected with Toxoplasma gondii, and posteriorly the loss of gross revenue due to congenital toxoplasmosis was estimated. Of the 25 non-pregnant females negative for T. gondii, 20 were orally inoculated (ME 49 strain) and of these, 15 pregnant females chronically infected were orally reinoculated (VEG strain) with T. gondii oocysts. Five groups were formed (n=5): GI, GII and GIII (reinoculations at 40, 80 and 120 days of gestation, respectively), GIV (inoculation) and GV (no inoculation). Clinical and serological exams were performed on days 0 (prior to inoculation), 3, 6 9, 15 and 21 and every 7 days post-inoculation. Exams were also performed on day 3 and every 7 days post-reinoculation. Reproductive management was performed on all females and initiated when the females infected displayed IgG titers IFAT<1,024. From the average prolificacy indexes of each experimental group were estimated: total production of kilograms of live weight (total kg LW) of goats for slaughter, gross revenue and loss of gross revenue in U.S. dollars (US$), designed for a herd of 1,000 matrices. The unviable prolificacy indexes were 0.8 (GI), 1.2 (GII) and 0.2 (GIII). Clinical disorders affected 57.1% (GI), 75.0% (GII) and 16.7% (GIII) of the offspring of goats reinfected with T. gondii. Congenital toxoplasmosis in goats reinfected resulted in the loss of 26.5% of gross revenues, being GI (US$ 10,577.60 or 57.1%) and GII (US$ 12,693.12 or 60%) holders of the highest values and percentages of economic losses. It was found that congenital toxoplasmosis reinfection cause clinical disorders in goats chronically infected with T. gondii and their offspring with birth of unviable animals and loss of gross revenue, at different stages of pregnancy (40, 80 and 120 days of gestation), being in the initial and intermediate stages of pregnancy the largest estimates of these losses.(AU)

Nós determinamos os parâmetros reprodutivos e distúrbios clínicos em cabras gestantes infectadas e reinfectados com Toxoplasma gondii, e posteriormente, foi estimada a perda de receita bruta devido à toxoplasmose congênita. Das 25 fêmeas não prenhes negativas para T. gondii, 20 foram inoculadas oralmente (cepa ME 49) e, destas, 15 fêmeas gestantes infectadas cronicamente foram reinoculadas (cepa VEG), via oral, com oocistos de T. gondii. Cinco grupos foram formados (n = 5): GI, GII e GIII (reinoculações aos 40, 80 e 120 dias de gestação, respectivamente), GIV (inoculação) e GV (não inoculação). Exames clínicos e sorológicos foram realizados nos dias 0 (antes da inoculação), 3, 6 9, 15 e 21 e a cada sete dias após a inoculação. Os exames também foram realizados nos dias 3 e a cada sete dias de pós-reinoculação. Manejo reprodutivo foi realizado em todas as fêmeas e iniciou-se quando as fêmeas infectadas exibiram títulos de anticorpos IgG<1.024. A partir dos índices médios de prolificidade de cada grupo experimental foram estimados: a produção total de kg de peso vivo (total kg PV) de cabritos para o abate, receita bruta e perda de receita bruta em dólares norte-americanos (US$), projetadas para um rebanho de 1000 matrizes. Os índices de prolificidade inviáveis foram de 0,8 (GI), 1.2 (GII) e 0,2 (GIII). Distúrbios clínicos afetaram 57,1% (GI), 75,0% (GII) e 16,7% (GIII) das crias de cabras reinfectados com T. gondii. A toxoplasmose congênita em crias das cabras reinfectadas com T. gondii resultou na perda de 26,5% da receita bruta, sendo GI (US $ 10,577.60 e 57,1%) e GII (US $ 12,693.12 e 60.0%) os detentores dos mais altos valores e porcentagens de perdas econômicas. Verificou-se que a reinfecção toxoplásmica congênita causa distúrbios clínicos em cabras cronicamente infectadas com T. gondii e sua prole com o nascimento de animais inviáveis e perda de receita bruta, em diferentes fases da gestação (40, 80 e 120 dias de gestação), sendo nas fases inicial e intermediária da gestação verificadas as maiores estimativas destes prejuízos.(AU)