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Abstract Background Carnitine facilitates the flux of long-chain fatty acids for hepatic mitochondrial beta-oxidation, which acts to ameliorate the negative energy balance commonly affecting high-yielding dairy cows. Inflammation triggered by lipopolysaccharide (LPS) load can however pose a challenge to the metabolic integrity via the expression of pro-inflammatory mediators, leading to immune system activation and respective metabolic alterations. The effect of enhanced carnitine availability on hepatic metabolome profiles during an inflammatory challenge has not yet been determined in dairy cows. Herein, Holstein cows were supplemented with 25 g/d rumen-protected carnitine from 42 d prepartum until 126 d postpartum (n = 16) or assigned to the control group with no supplementation during the same period (n = 14). We biopsied the liver of the cows before (100 d postpartum) and after (112 d postpartum) an intravenous injection of 0.5 µg/kg LPS. Liver samples were subjected to a targeted metabolomics analysis using the AbsoluteIDQ p180 Kit (Biocrates Life Sciences AG, Innsbruck, Austria). Results Multivariate statistical analyses revealed that hepatic metabolome profiles changed in relation to both the carnitine supplementation and the LPS challenge. Comparing the metabolite profiles on 100 d, carnitine increased the concentration of short- and long-chain acyl-carnitines, which may be explained by an enhanced mitochondrial fatty acid shuttle and hence greater energy availability. The LPS injection affected hepatic metabolite profiles only in the carnitine supplemented group, particularly altering the concentration of biogenic amines. Conclusions Our results point to interactions between an acute hepatic inflammatory response and biogenic amine metabolism, depending on energy availability.

In recent years, significant progress has been made in 5q Spinal Muscular Atrophy therapeutics, emphasizing the importance of early diagnosis and intervention for better clinical outcomes. Characterized by spinal cord motor neuron degeneration, 5q-SMA leads to muscle weakness, swallowing difficulties, respiratory insufficiency, and skeletal deformities. Recognizing the pre-symptomatic phases supported by screening and confirmatory genetic tests is crucial for early diagnosis. This work addresses key considerations in implementing 5q-SMA screening within the Brazilian National Newborn Screening Program and explores Brazil's unique challenges and opportunities, including genetic tests, time-to-patient referral to specialized centers, program follow-up, and treatment algorithms. We aim to guide healthcare professionals and policymakers, facilitating global discussions, including Latin American countries, and knowledge-sharing on this critical subject to improve the care for newborns identified with 5q SMA. [ABSTRACT FROM AUTHOR]

BackgroundSickle cell disease (SCD) may cause several impacts to patients and the whole society. About 4% of the population has the sickle cell trait in Brazil, and 60,000 to 100,000 have SCD. However, despite recognizing the significant burden of disease, little is known about SCD costs.ObjectiveTo estimate SCD societal costs based on disease burden modelling, under Brazilian societal perspective.MethodsA disease burden model was built considering the societal perspective and a one-year time horizon, including direct medical and indirect costs (morbidity and mortality). The sum of life lost and disability years was considered to estimate disability-adjusted life years (DALYs). Data from a public database (DATASUS) and the prevalence obtained from literature or medical experts were used to define complications prevalence and duration. Costs were defined using data from the Brazilian public healthcare system table of procedures and medications (SIGTAP) and the human capital method.ResultsAnnual SCD cost was 413,639,180 USD. Indirect cost accounted for the majority of burden (70.1% of the total; 290,158,365 USD vs 123,480,816 USD). Standard of care and chronic complications were the main source of direct costs among adults, while acute conditions were the main source among children. Vaso-occlusive crisis represented the complication with the highest total cost per year in both populations, 11,400,410 USD among adults and 11,510,960 USD among children.ConclusionsSCD management may impose an important economic burden on Brazilian society that may reach more than 400 million USD per year.

ABSTRACT Dairy cows respond individually to stressful situations, even under similar feeding and housing conditions. The phenotypic responsiveness might trace back to their microbiome and its interactions with the host. This long-term study investigated the effects of calving, lipopolysaccharide (LPS)-induced inflammation, and l-carnitine supplementation on fecal bacteria and metabolites, dairy cow milk production, health, energy metabolism, and blood metabolites. Fifty-four multiparous Holstein dairy cows were examined over a defined period of life (168 days). The obtained data allowed a holistic analysis combining microbiome data such as 16S rRNA amplicon sequencing and fecal targeted metabolome (188 metabolites) with host parameters. The conducted analyses allowed the definition of three enterotype-like microbiome clusters in dairy cows which could be linked to the community diversity and dynamics over time. The microbiome clusters were discovered to be treatment independent, governed by Bifidobacterium (C-Bifi), unclassified (uncl.) Clostridiales (C-Clos), and unclassified Spirochaetaceae (C-Spiro). Animals between the clusters varied significantly in terms of illnesses, body weight, microbiome composition, and milk and blood parameters. C-Bifi animals were healthier and leaner with a less diverse but dynamic microbiome. C-Spiro animals were heavier, but the diversity of the static microbiome was higher. This pioneering study uncovered microbiome clusters in dairy cows, each contributing differently to animal health and productive performance and with a crucial role of Bifidobacterium. IMPORTANCE The health of dairy cows has to be carefully considered for sustainable and efficient animal production. The microbiome of animals plays an important role in the host’s nutrient supply and regulation of immune functions. We show that a certain composition of the fecal microbiome, called microbiome clusters, can be linked to an animal’s health at challenging life events such as calving and inflammation. Cows with a specific set of bacteria have coped better under these stressors than have others. This novel information has great potential for implementing microbiome clusters as a trait for sustainable breeding strategies.

Abstract Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. Environmental factors can influence gene expression and cell function by modifying epigenetic marks, impacting the developing embryo as well as future generations of offspring. The impact of phthalates on placental gene methylation and expression is largely unknown. We studied the effect of maternal phthalate exposure on the human placental DNA methylome and transcriptome. We determined epigenome-wide DNA methylation marks (Illumina Infinium Human Methylation 850k BeadChip) and gene expression (Agilent whole human genome array) associated with phthalate exposure in first trimester placenta. Integrative genomic analysis of candidate genes was performed to define gene methylation-expression relationships. We identified 39 genes with significantly altered methylation and gene expression in the high phthalate exposure group. Most of these relationships were inversely correlated. This analysis identified epidermal growth factor receptor (EGFR) as a critical candidate gene mediating the effects of phthalates on early placental function. Although additional studies are needed to determine the functional consequences of these changes, our findings are consistent with the model that phthalates impact placental function by modulating the expression of critical placental genes through epigenetic regulation.

Abstract Background Large numbers of post-deployment U.S. veterans are diagnosed with post-traumatic stress disorder (PTSD) and/or traumatic brain injury (TBI), leading to an urgent need for effective interventions to reduce symptoms and increase veterans’ coping. PTSD includes anxiety, flashbacks, and emotional numbing. The symptoms increase health care costs for stress-related illnesses and can make veterans’ civilian life difficult. Methods We used a randomized wait-list controlled design with repeated measures of U.S. military veterans to address our specific aim to test the efficacy of a 6-week therapeutic horseback riding (THR) program for decreasing PTSD symptoms and increasing coping self-efficacy, emotion regulation, social and emotional loneliness. Fifty-seven participants were recruited and 29 enrolled in the randomized trial. They were randomly assigned to either the horse riding group (n = 15) or a wait-list control group (n = 14). The wait-list control group experienced a 6-week waiting period, while the horse riding group began THR. The wait-list control group began riding after 6 weeks of participating in the control group. Demographic and health history information was obtained from all the participants. PTSD symptoms were measured using the standardized PTSD Checklist-Military Version (PCL-M). The PCL-M as well as other instruments including, The Coping Self Efficacy Scale (CSES), The Difficulties in Emotion Regulation Scale (DERS) and The Social and Emotional Loneliness Scale for Adults-short version (SELSA) were used to access different aspects of individual well-being and the PTSD symptoms. Results Participants had a statistically significant decrease in PTSD scores after 3 weeks of THR (P ≤ 0.01) as well as a statistically and clinically significant decrease after 6 weeks of THR (P ≤ 0.01). Logistic regression showed that participants had a 66.7% likelihood of having lower PTSD scores at 3 weeks and 87.5% likelihood at 6 weeks. Under the generalized linear model(GLM), our ANOVA findings for the coping self-efficacy, emotion regulation, and social and emotional loneliness did not reach statistical significance. The results for coping self-efficacy and emotion regulation trended in the predicted direction. Results for emotional loneliness were opposite the predicted direction. Logistic regression provided validation that outcome effects were caused by riding longer. Conclusion The findings suggest that THR may be a clinically effective intervention for alleviating PTSD symptoms in military veterans.

Introdução: A gordura epicárdica (GE) é biologicamente ativa e, por meio de seu efeito parácrino, interage com o miocárdio atrial e pode estar envolvida no remodelamento atrial observado em obesos. A duração da onda P (DOP) é um marcador não invasivo do tempo de condução atrial e reflete alterações relacionadas ao remodelamento atrial. Os efeitos da redução da GE induzida pela cirurgia bariátrica sobre a DOP ainda não foram definidos. Métodos: Recrutamos prospectivamente 22 obesos mórbidos sem outras comorbidades na Unidade de Cirurgia Bariátrica do Hospital das Clínicas da Universidade de São Paulo. Os pacientes foram submetidos a avaliações clínica e laboratorial, além de eletrocardiograma (ECG) de 12 derivações, ecocardiograma bidimensional e Holter de 24 h. A mesma avaliação foi realizada 12 meses após a cirurgia bariátrica. A fim de que as variáveis contínuas fossem comparadas, foram utilizados os testes T pareado e de Wilcoxon. Já para avaliar a associação entre variáveis independentes foi utilizado um modelo de regressão para medidas repetidas. Resultados: Ao todo, 20 pacientes completaram o protocolo (idade: 36,35 ± 10,26 anos, 18 mulheres). Houve uma redução significativa da DOP, do índice de massa corporal (IMC) e da GE após cirurgia bariátrica (p

l-carnitine plays an important role in energy metabolism through supporting the transport of activated fatty acids to the subcellular site of β-oxidation. An acute phase reaction (APR) is known as an energy consuming process. Lipopolysaccharides (LPS) are often used in animal models to study intervention measures during innate immune responses such as APR. Thus, the aim of the study was to investigate the effects of dietary l-carnitine supplementation during an LPS-induced APR in mid-lactating German Holstein cows. Animals were assigned to a control (CON, n = 26) or l-carnitine group (CAR, n = 27, 25 g rumen-protected l-carnitine/cow/d) and received an intravenous injection of LPS (0.5 μg/kg body weight) at day 111 post-partum. Blood samples were collected from day 1 pre-injection until day 14 post-injection (pi). From 0.5 h pi until 72 h pi blood samplings and clinical examinations were performed in short intervals. Clinical signs of the APR were not altered in group CAR except rumen motility which increased at a lower level compared to the CON group after a period of atonia. Group CAR maintained a higher insulin level compared to group CON even up to 72 h pi which might support glucose utilization following an APR.

P-wave dispersion (PWD, Pd or Pdis) is a noninvasive electrocardiographic (ECG) marker for atrial remodeling and predictor for atrial fibrillation (AF). PWD is defined as the difference between the widest and the narrowest P-wave duration recorded from the 12 ECG leads. Increased P-wave duration and PWD reflect prolongation of intraatrial and interatrial conduction time with lack of a well-coordinated conduction system within the atrial muscles, with inhomogeneous, asynchronic, pro-inflammatory and anti-inflammatory effect mediated by interleukin-6 (IL-6) in patients with the CG + GG genotype IL-6 -634C/G polymorphism [1] and discontinuous propagation of sinus impulses mainly between the left and right atria, interstitial/extracellular fibroblast activation and collagen deposition with fibrosis (via TGF-β) in atrial tissue, insufficient blood supply, significant not isotropic myoelectric activity, and thin wall thickness and consequent expansion tendency all well-known electrophysiological characteristics in patients with atrial arrhythmias and especially paroxysmal atrial fibrillation (PAF) [2].

ABSTRACT Introduction: Cardiac involvement is frequent in inflammatory myopathies. Electrocardiogram (ECG) may show evidence of this involvement and its changes should be well-known and described. Objectives: Due to the lack of studies in the literature, we conducted an analysis of the ECG findings in patients with dermatomyositis (DM) and polymyositis (PM), comparing them with a control group. Methods: This cross-sectional study compared the ECG of 86 individuals with no rheumatic disorders (controls) with 112 patients (78 DM and 34 PM), during 2010 to 2013. The ECG findings between DM and PM were also compared. Results: Demographic characteristics, comorbidities and ECG abnormalities were similar between controls and patients (p > 0.05), except for a higher frequency of left ventricular hypertrophy (LVH) in patients (10.7% vs. 1.2%, p = 0.008). Demographic characteristics, comorbidities, clinical and laboratory manifestations, were also similar between the groups PM and DM, except for the presence of cutaneous lesions only in DM. One third of the patients had ECG abnormalities, which were more prevalent in PM than DM (50% vs. 24.4%, p = 0.008). LVH, left atrial enlargement, rhythm and conduction abnormalities were more frequent in PM than DM (p < 0.05 for all), especially the left anterior fascicular block. Conclusions: We showed distinct ECG changes between DM and PM and a higher frequency of LVH in patients compared to controls. Investigation of cardiac involvement should be considered even in asymptomatic patients, especially PM. Further studies are necessary in order to determine the correlation of ECG findings with other complementary tests, clinical manifestations, disease activity and progression to other cardiac diseases.

Dairy cows are metabolically challenged during the transition period. Furthermore, the process of parturition represents an energy-consuming process. The degree of negative energy balance and recovery from calving also depends on the efficiency of mitochondrial energy generation. At this point, L-carnitine plays an important role for the transfer of fatty acids to the site of their mitochondrial utilisation. A control (n = 30) and an L-carnitine group (n = 29, 25 g rumen-protected L-carnitine per cow and day) were created and blood samples were taken from day 42 ante partum (ap) until day 110 post-partum (pp) to clarify the impact of L-carnitine supplementation on dairy cows, especially during the transition period and early puerperium. Blood and clinical parameters were recorded in high resolution from 0.5 h to 72 h pp. L-carnitine-supplemented cows had higher amounts of milk fat in early lactation and higher triacylglyceride concentrations in plasma ap, indicating increased efficiency of fat oxidation. However, neither recovery from calving nor energy balance and lipomobilisation were influenced by L-carnitine.

BACKGROUND:Prenatal exposures have known adverse effects on maternal and neonatal outcomes. Professional societies recommend routine screening for environmental, occupational, and dietary exposures to reduce exposures and their associated sequelae. OBJECTIVE:Our objective was to determine the frequency of environmental exposure screening by obstetricians and gynecologists (OBGYNs) at initial patient visits. STUDY DESIGN:Practicing OBGYNs were approached at the University of Colorado and by social media. The survey instrument queried demographics, environmental literacy, and screening practices. Statistical analysis was performed using Chi-square and two-sample t-test. RESULTS:We received 312 online survey responses (response rate of 12%). Responding OBGYNs were predominantly female (96%), board-certified (78%), generalists (65%) with a mean age of 37.1 years. Fewer than half of physicians screened for the following factors: occupational exposures, environmental chemicals, air pollution, pesticide use, personal care products, household cleaners, water source, use of plastics for food storage, and lead and mercury exposure. Eighty five percent of respondents reported that they did not feel comfortable obtaining an environmental history and 58% respondents reported that they performed no regular screening of environmental exposures. A higher frequency of screening was associated with > 4 years of practice (p = 0.001), and having read the environmental committee opinion (p =

Transformation is a profound change process culminating in a fundamental shift in one's sense of self and way of being-in-the-world. Research on transformation is limited, particularly transformation as a holistic, bodily felt process. A process called Focusing was identified by Gendlin (1981), who formulated how the body participates in personal change and meaning creation. The aim of our study was to explore the characteristics and qualities of transformation by examining 19 published memoirs of people who had gone through a transformational experience via Focusing. Two questions guided the inquiry: What kind of inner environment is necessary for transformation? What are the characteristics and qualities of transformative experiences that unfold through a Focusing-oriented process to weave together a "new kind of person?" Researchers conducted a thematic analysis of the memoirs through a new qualitative method called Felt Sense Inquiry. Results revealed five themes: expanded bodily self, attuned attention, novelty, interactive exchange, and elastic time. Results suggest a way of experiencing that does not divide, but rather connects the person to a unified felt process that unfolds on its own. Future research comparing Focusing with other practices that seem to promote transformation may reveal "common factors" of transformation. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals (EDCs) adversely affect human health. Our objective was to determine the association of EDC exposure with earlier age of menopause.Cross-sectional survey using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2008 (n = 31,575 females). Eligible participants included: menopausal women >30 years of age; not currently pregnant, breastfeeding, using hormonal contraception; no history of bilateral oophorectomy or hysterectomy. Exposures, defined by serum lipid and urine creatinine-adjusted measures of EDCs, data were analyzed: > 90th percentile of the EDC distribution among all women, log-transformed EDC level, and decile of EDC level. Multi linear regression models considered complex survey design characteristics and adjusted for age, race/ethnicity, smoking, body mass index. EDCs were stratified into long (>1 year), short, and unknown half-lives; principle analyses were performed on those with long half-lives as well as phthalates, known reproductive toxicants. Secondary analysis determined whether the odds of being menopausal increased with EDC exposure among women aged 45-55 years.This analysis examined 111 EDCs and focused on known reproductive toxicants or chemicals with half-lives >1 year. Women with high levels of β-hexachlorocyclohexane, mirex, p,p'-DDE, 1,2,3,4,6,7,8-heptachlorodibenzofuran, mono-(2-ethyl-5-hydroxyhexyl) and mono-(2-ethyl-5-oxohexyl) phthalate, polychlorinated biphenyl congeners -70, -99, -105, -118, -138, -153, -156, -170, and -183 had mean ages of menopause 1.9 to 3.8 years earlier than women with lower levels of these chemicals. EDC-exposed women were up to 6 times more likely to be menopausal than non-exposed women.This study of a representative sample of US women documents an association between EDCs and earlier age at menopause. We identified 15 EDCs that warrant closer evaluation because of their persistence and potential detrimental effects on ovarian function. Earlier menopause can alter the quantity and quality of a woman's life and has profound implications for fertility, human reproduction, and our global society.

Fertility is important to women and men with cancer. While options for fertility preservation (FP) are available, knowledge regarding the medical application of FP is lacking. Therefore we examined FP practices for cancer patients among reproductive endocrinologists (REs). A 36 item survey was sent to board-certified REs. 98% of respondents reported counseling women with cancer about FP options. Oocyte and embryo cryopreservation were universally offered by these providers, but variability was noted in reported management of these cases-particularly for women with breast cancer. 86% of the respondents reported using letrozole during controlled ovarian stimulation (COS) in patients with estrogen receptor positive (ER+) breast cancer to minimize patient exposure to estrogen. 49% of respondents who reported using letrozole in COS for patients with ER+ breast cancer reported that they would also use letrozole in COS for women with ER negative breast cancer. Variability was also noted in the management of FP for men with cancer. 83% of participants reported counseling men about sperm banking with 22% recommending against banking for men previously exposed to chemotherapy. Overall, 79% of respondents reported knowledge of American Society for Clinical Oncology FP guidelines-knowledge that was associated with providers offering gonadal tissue cryopreservation (RR 1.82, 95% CI 1.14-2.90). These findings demonstrate that RE management of FP in cancer patients varies. Although some variability may be dictated by local resources, standardization of FP practices and communication with treating oncologists may help ensure consistent recommendations and outcomes for patients seeking FP.