Supplementation with green tea and oregano extracts on productive characteristics, blood metabolites, and antioxidant status of Jersey cows during the transition period

Plant extracts have been recognized as beneficial to human health and have been evaluated as feed additive for domestic and companion animals. This study evaluated oregano and green tea extracts fed to Jersey cows from approximately 21 d before calving to 21 d after calving on milk production, milk composition, and blood metabolites as well as investigated immunological and antioxidant attributes. Twenty-four Jersey cows with 441±27 kg of BW, 3.5±0.3 of body condition score (BCS), and 2.7±1.8 lactations were selected at approximately 28d before the expected parturition date and were randomly assigned to three treatments with eight cows each: without plant extracts in diet (control – CON), addition of 10g per day of oregano extract (OR), and addition of 5g per day of green tea extract (GT). Feed intake, BW, BCS, blood metabolites, hemogram as well as oxidative stress biomarkers were evaluated from approximately 3 weeks prepartum to 3 weeks postpartum (transition period) while milk production and composition were evaluated during the first 3 weeks of lactation. Plant extracts did not change BW, BCS, and DM intake (DMI) throughout the transition period, but OR increased in approximately 20% total digestive nutrients and metabolizable energy intake on days 15 and 16 postpartum compared with CON. In the prepartum, OR increased in 48% platelets count compared to the CON, while GT augmented in 142% eosinophils compared with CON. Oregano extract reduced the levels of reactive species in the erythrocytes in 40% during prepartum and postpartum compared with CON, while GT reduced its levels in 24 and 29% during prepartum and postpartum, respectively, when compared with CON. In the postpartum period, OR increased in 60% the carbonylated protein content compared with CON, while GT reduced in 45% the levels of reactive species in plasma compared with CON. During the postpartum, both extracts increased in 33% the concentration of reduced glutathione when compared with CON. Moreover, GT tended to decrease feed efficiency in 11% when compared with CON; OE reduced milk pH and somatic cell count when compared with CON. In conclusion, OE and GT did not expressively affect immunological attributes in blood but reduce some oxidative stress biomarkers without compromising productive traits of Jersey cows during the transition period

Emprego dos parâmetros farmacocinéticos/farmacodinâmicos (PK/PD) na terapia antimicrobiana de pacientes em terapia intensiva em um hospital público do interior de Rondônia : Use of pharmacokinetic/pharmacodynamic parameters (PK/PD) in the antimicrobial therapy of patients in intensive care in a public hospital in the countryside of Rondônia

Os parâmetros farmacocinéticos/farmacodinâmicos (PK/PD) de antimicrobianos consistem na relação entre a exposição aos antibióticos e o alcance dos efeitos terapêuticos desejáveis visando à prescrição de dosagens suficientes do fármaco para inibir o crescimento bacteriano. Atualmente três tipos de relações PK/PD foram estabelecidos para os antibióticos: fCmax>CIM; %fT>CIM e a relação entre a exposição ao antibiótico e a CIM (fAUC/CIM). Para otimização desses parâmetros é essencial a avaliação de variáveis como clearance de creatinina, volume de distribuição do fármaco, depuração renal, ligação do fármaco a proteínas plasmáticas, tempo de infusão do fármaco, intervalo das dosagens, características físico-químicas do medicamento entre outros. O trabalho proposto avaliou a aplicação de parâmetros PK/PD na prescrição de antibióticos de pacientes internados em unidades de terapia intensiva (UTI). Assim sendo, foi realizado um estudo observacional, transversal com coorte retrospectiva entre março de 2022 a abril de 2022. A amostra validada contou com a análise de prescrições e fichas de antimicrobianos de 31 pacientes, sendo ao todo 42 esquemas terapêuticos prescritos. A terapia variou entre 05 a 14 dias de tratamento, tendo como predominante o tempo de tratamento de 07 dias (47,6%) bem como o foco respiratório (54,7%). Já em relação à classe de antibióticos, obteve-se uma prevalência de prescrição de betalactâmicos (78,6%), sendo que entre esses a ceftriaxona e o meropenem obtiveram uma frequência maior de solicitações (23,8%). Em relação aos parâmetros PK/PD, houve predominância de antibióticos com perfil fT>CIM (78,6%). Por outro lado, somente para 04 esquemas terapêuticos detalhou-se o tempo de infusão.  Além do mais, predominaram-se antibióticos hidrofílicos e com baixa ligação a proteínas plasmáticas, com exceção da ceftriaxona. Nesse último caso, não houve ajuste do fármaco em relação à dosagem de albumina sérica. Por fim, 18 prescrições de antibióticos coincidiram com clearance de creatinina diminuído sendo realizado ajuste para 08 esquemas de tratamento. Entretanto, para pacientes com depuração renal aumentada, houve prescrição de dose máxima para somente 01 esquema terapêutico

Naive and memory human B cells have distinct requirements for STAT3 activation to differentiate into antibody-secreting plasma cells

Long-lived antibody memory is mediated by the combined effects of long-lived plasma cells (PCs) and memory B cells generated in response to T cell–dependent antigens (Ags). IL-10 and IL-21 can activate multiple signaling pathways, including STAT1, STAT3, and STAT5; ERK; PI3K/Akt, and potently promote human B cell differentiation. We previously showed that loss-of-function mutations in STAT3, but not STAT1, abrogate IL-10– and IL-21–mediated differentiation of human naive B cells into plasmablasts. We report here that, in contrast to naive B cells, STAT3-deficient memory B cells responded to these STAT3-activating cytokines, differentiating into plasmablasts and secreting high levels of IgM, IgG, and IgA, as well as Ag-specific IgG. This was associated with the induction of the molecular machinery necessary for PC formation. Mutations in IL21R, however, abolished IL-21–induced responses of both naive and memory human B cells and compromised memory B cell formation in vivo. These findings reveal a key role for IL-21R/STAT3 signaling in regulating human B cell function. Furthermore, our results indicate that the threshold of STAT3 activation required for differentiation is lower in memory compared with naive B cells, thereby identifying an intrinsic difference in the mechanism underlying differentiation of naive versus memory B cells.This work was funded by project and program grants from the National Health and Medical Research Council (NHMRC) of Australia (to E.K. Deenick, C.S. Ma, D.A. Fulcher, M.C. Cook, and S.G. Tangye) and the Rockefeller University Center for 541 Clinical and Translational science (5UL1RR024143 to J.L. Casanova). C.S. Ma is a recipient of a Career Development Fellowship, L.J. Berglund is a recipient of a Medical Postgraduate Scholarship, and S.G. Tangye is a recipient of a Principal Research Fellowship from the NHMRC of Australia. L. Moens is the recipient of a Postdoctoral Fellowship from the Research Foundation-Flanders (FWO), Belgium

B cell–intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans

Engagement of cytokine receptors by specific ligands activate Janus kinase–signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyte behavior remain incompletely defined. Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a potent regulator of B cell differentiation. We have studied patients with inactivating mutations in STAT1 or STAT3 to dissect their contribution to B cell function in vivo and in response to IL-21 in vitro. STAT3 mutations dramatically reduced the number of functional, antigen (Ag)-specific memory B cells and abolished the ability of IL-21 to induce naive B cells to differentiate into plasma cells (PCs). This resulted from impaired activation of the molecular machinery required for PC generation. In contrast, STAT1 deficiency had no effect on memory B cell formation in vivo or IL-21–induced immunoglobulin secretion in vitro. Thus, STAT3 plays a critical role in generating effector B cells from naive precursors in humans. STAT3-activating cytokines such as IL-21 thus underpin Ag-specific humoral immune responses and provide a mechanism for the functional antibody deficit in STAT3-deficient patients

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Public Health Impacts and Intra-Urban Forced Displacement due to Climate Gentrification in the Greater Miami Area—Community Lawyering for Environmental Justice and Equitable Development

Because Miami-Dade County is “ground zero” for such climate effects as sea-level rise and increasingly hazardous, climate-driven Atlantic hurricanes, the coral rock ridge that runs along the Eastern coast of South Florida is a prime target for redevelopment and “climate” gentrification. Through a community and movement lawyering for environmental justice approach, we partnered with local community organizations to contribute to the ongoing work of community-driven equitable development. In partnership, we developed an environmental public health study to understand and document the public health effects on disadvantaged communities in Miami-Dade County from forced intra-urban displacement due to redevelopment that is being influenced by elevation concerns. We disseminated an online survey to examine environmental hazards, housing conditions, threat of displacement, and current mental and physical health status. We collected seventy-four responses between August 2021 and August 2022. The Qualtrics survey consisted of twenty-five questions to determine the breadth and extent of mental and physical health impacts due to threats of forced displacement related to redevelopment along the coral rock ridge. We assessed movement into and out of areas of gentrification in Miami-Dade County and any correlations with health impacts and forced displacement due to environmental housing conditions and redevelopment in these areas. Migration patterns by zip code and elevation were analyzed using data obtained from the U.S. Census Bureau and served to supplement and cross-validate geographical data and existing literature that showed a pattern of migration and movement in line with climate gentrification. This work was used to develop and support policies with the potential to slow down the rapid gentrification along the rock ridge and mitigate the process of forced displacement occurring amongst the environmental justice communities living there

Immigration Defense Waivers in Federal Criminal Plea Agreements

Immigration policy is back on the American public\u27s radar screen. The fields of immigration--a civil-law subject-and criminal law-a public-law subject-are quite distinct in both litigation practice and law school curricula. With exceptions along the U.S.--Mexican border, only in a small minority of federal cases do criminal attorneys need to know more than some very basic premises of immigration law. Aside from some very general information necessary for defense attorneys to provide adequate advisements according to Padilla v. Kentucky to their clients before entering guilty pleas and Continued Legal Education (CLE) training regarding what offenses have severe immigration consequences, the body of criminal practitioners have very little knowledge of the labyrinthine immigration law and its even more impenetrable regulations. ... This Article focuses on DOJ\u27s inclusion of waivers of immigration relief in plea agreements for non-citizen federal defendants and proposes some challenges to these waivers. Federal district and appellate judges, immigration judges (IJs), and the Board of Immigration Appeals (BIA) members will find below legal grounds to decline to accept these waivers. Such tools are critical to combat this new federal immigration waiver propensity-which is especially disturbing in light of Attorney General Sessions\u27 April 11, 2017 Memorandum requiring federal prosecutors to substantially broaden immigration prosecutions, and limiting discretion on whom not to deport. The government seeks waivers of critical rights without giving non-citizen defendants access to the tools and knowledge to make fully informed decisions. In Part I, we review the language of immigration waivers, which widely varies by jurisdiction, and include an appended chart tracking waivers from each U.S. Attorney\u27s Office that presently requests waivers as part of their standard plea agreements. In Part II, we briefly describe how removal orders are imposed by immigration judges, Department of Homeland Security (DHS) officers, and by federal district court judges, and discuss the effect these waivers will have in those proceedings. The Authors also include a discussion of the potential grounds of relief from removal, such as asylum, withholding of removal, and protection under\u27 the Convention Against Torture in conjunction with challenging the grounds for the deportation. Finally, we spend some time on the renewed use of a 1994 judicial removal statute, 8 U.S.C. § 1228. In Part III, we identify five methods for challenging these waivers. We first urge immigrants to demand hearings and to challenge the factual statements contained in the plea waivers. Next, we question the constitutionality of the judicial removal statute. Moving on, we suggest that defense attorneys who advise clients to sign these waivers may be providing ineffective assistance of counsel. Additionally, we note that ethics rules regarding competency prohibit most criminal defense attorneys from advising their clients regarding what immigration rights they are ceding, and similarly, prohibit prosecutors from seeking such waivers. Finally, we argue that public policy and international law obligations may prohibit enforcement of these waivers

Preventive Intervention for Urban, Low-Income Preschoolers at Familial Risk for Conduct Problems: A Randomized Pilot Study

Conducted a pilot study to test the feasibility of a prevention program for promoting parenting in families of preschoolers at high risk for behavior problems. Risk status was based on a family history of antisocial behavior and residence in a low-income, urban community. Thirty preschoolers (ages 2 1/2 to 5) and their parents were randomly assigned to a 1-year, home- and clinic-based intervention or to a no-intervention control condition. Despite families\u27 multiple risk factors, high rates of attendance and satisfaction were achieved. Relative to controls, intervention parents were observed to be significantly more responsive and use more positive parenting practices. Results support the feasibility of engaging high-risk families in an intensive prevention program. The meaningful changes achieved in parenting suggest that a preventive approach is promising for families with multiple risk factors