Changes in Metabolic Parameters of Hemoglobin A1c, Weight, and Blood Pressure During and After COVID-19 Stay-at-Home Orders.

BACKGROUND: Due to the COVID-19 pandemic, a "state of emergency" was declared in North Carolina on March 10, 2020. Subsequent "stay-at-home" (SAH) orders restricted activities including use of fitness facilities, and teleworking was encouraged. This study investigates metabolic effects of these changes in activity level. METHODS: This retrospective prepost study included adults diagnosed with type 2 diabetes mellitus and hypertension with hemoglobin A1c (HbA1c), weight, and blood pressure (BP) measurements for 3 time periods: 3/10/2019-9/9/2019 ("pre-SAH"), 3/10/2020-9/9/2020 ("during SAH"), and 3/10/2021-9/9/2021 ("post-SAH"). The primary outcome was change in HbA1c pre-SAH to during SAH and during SAH to post-SAH. Secondary outcomes were changes in weight, systolic BP (SBP), and diastolic BP (DBP) over the same periods. Exploratory outcomes included health care utilization. Paired t test compared outcomes between time periods using Bonferroni-adjusted α of 0.025 for significance. RESULTS: Analysis included 301 participants with an average age of 69.8 years. HbA1c, SBP, and DBP trended up from pre-SAH to during SAH and then decreased post-SAH with a significant change only for DBP from during SAH to post-SAH (74.2 mmHg to 73.6 mmHg, P < .001). Weight trended down across the 3 study periods. In-office visits significantly decreased from pre-SAH to during SAH, and telehealth visits significantly decreased from during SAH to post-SAH (both P < .001). CONCLUSIONS: With the exception of DBP, findings reveal consistency in HbA1c, weight, and BP across time periods before, during, and after COVID-19 SAH orders in North Carolina.

Essential agriculture, sacrificial labor, and the COVID-19 pandemic in the US South.

As farmworkers were reframed as "essential" workers during the COVID-19 pandemic, US growers demanded unfettered access to foreign farm labor. After initially announcing a freeze on all immigration processing, the Trump administration bowed to farmers' demands, granting a single exception for agricultural guestworkers under the H-2A visa program. Through a focus on H-2A farmworkers in Georgia, this paper highlights how the pandemic exacerbated farm labor conditions in the US South. The author interrogates these conditions through the lens of racial capitalism, exposing the legacies of plantation political economies and a longstanding agricultural labor system premised on devaluing racialized labor. These histories are obscured by the myth of agricultural exceptionalism-the idea that agriculture is too different and important to be subject to the same rules and regulations as other industries. Agricultural exceptionalism naturalizes the racial capitalist system and informs state responses that privilege agricultural production through the exploitation of farmworkers, remaking "essential" farmworkers as sacrificial labor.

Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis.

Variability in bacterial sterilization is a key feature of Mycobacterium tuberculosis (Mtb) disease. In a population of human macrophages, there are macrophages that restrict Mtb growth and those that do not. However, the sources of heterogeneity in macrophage state during Mtb infection are poorly understood. Here, we perform RNAseq on restrictive and permissive macrophages and reveal that the expression of genes involved in GM-CSF signaling discriminates between the two subpopulations. We demonstrate that blocking GM-CSF makes macrophages more permissive of Mtb growth while addition of GM-CSF increases bacterial control. In parallel, we find that the loss of bacterial control that occurs in HIV-Mtb coinfected macrophages correlates with reduced GM-CSF secretion. Treatment of coinfected cells with GM-CSF restores bacterial control. Thus, we leverage the natural variation in macrophage control of Mtb to identify a critical cytokine response for regulating Mtb survival and identify components of the antimicrobial response induced by GM-CSF.

Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network.

Upon recognition of a microbial pathogen, the innate and adaptive immune systems are linked to generate a cell-mediated immune response against the foreign invader. The culture filtrate of Mycobacterium tuberculosis contains ligands, such as M. tuberculosis tRNA, that activate the innate immune response and secreted Ags recognized by T cells to drive adaptive immune responses. In this study, bioinformatics analysis of gene-expression profiles derived from human PBMCs treated with distinct microbial ligands identified a mycobacterial tRNA-induced innate immune network resulting in the robust production of IL-12p70, a cytokine required to instruct an adaptive Th1 response for host defense against intracellular bacteria. As validated by functional studies, this pathway contained a feed-forward loop, whereby the early production of IL-18, type I IFNs, and IL-12p70 primed NK cells to respond to IL-18 and produce IFN-γ, enhancing further production of IL-12p70. Mechanistically, tRNA activates TLR3 and TLR8, and this synergistic induction of IL-12p70 was recapitulated by the addition of a specific TLR8 agonist with a TLR3 ligand to PBMCs. These data indicate that M. tuberculosis tRNA activates a gene network involving the integration of multiple innate signals, including types I and II IFNs, as well as distinct cell types to induce IL-12p70.

Irish and New Zealand Midwives' expertise at preserving the perineum intact (the MEPPI study): Perspectives on preparations for birth.

OBJECTIVES: perineal trauma during birth can result in short or long term morbidity for women. Internationally, rates of episiotomy and severe perineal tears vary considerably. In New Zealand, in 2011, and in a trial of midwife-led care in Ireland, episiotomy rates were found to be considerably lower than those in many other countries. A qualitative exploratory study was undertaken to ascertain how midwives achieve these low rates, in these countries and settings. DESIGN AND PARTICIPANTS: a qualitative exploratory study was conducted. Midwives expert in preserving the perineum intact (PPI) from two maternity units in the Republic of Ireland and from varied birth settings in New Zealand, were eligible to participate. Twenty-one consenting midwives took part, seven from Ireland and 14 from New Zealand. METHODS: university ethical approval was granted. Face-to-face, semi-structured interviews were used to collect the data. Interviews were recorded and transcribed verbatim. The data were analysed using Ethnograph software and were organised into prominent themes. FINDINGS: four themes were identified; 'Sources of knowledge for PPI', 'Associated factors', 'Decision-making on episiotomy', and 'Preparations for PPI'. Participants drew heavily on multiple sources of knowledge in building their own expertise for PPI. Physical characteristics of the perineum featured prominently as factors leading to PPI. Episiotomy was, in the main, only performed when there were signs of fetal distress. Antenatal perineal massage was supported. CONCLUSION: this study provides valuable insight into the views and skills of midwives, with expertise in PPI at birth, adding to the body of evidence on this topic.

Irish and New Zealand midwives' expertise in expectant management of the third stage of labour: the 'MEET' study.

OBJECTIVE: to explore the views of expert midwives in Ireland and New Zealand of the skills they employ in expectant management of the third stage of labour (EMTSL). DESIGN: university ethical approval was granted for a qualitative descriptive study in 2010. Recorded, semi-structured interviews were undertaken. Constant comparative analysis was used. SETTING: community birth settings in Ireland and New Zealand. PARTICIPANTS: 27 consenting midwives who used EMTSL in at least 30% of births, with PPH rates less than 4%. FINDINGS: the majority of respondents believed the third stage was a special time of parent-baby discovery and 'watchful waiting', with no intervention necessary. Great importance was placed on women's feelings, behaviour and a calm environment. Skin-to-skin contact, breast feeding, not clamping the cord, upright positions and maternal effort, sometimes assisted by gentle cord-traction were also used. KEY CONCLUSIONS: some components of EMTSL identified by these expert midwives are not recorded in text-books, but are based on experience and expertise. These elements of EMTSL add to midwifery knowledge and provide a basis for further discussion on how normal physiology can be supported during the third stage. IMPLICATIONS FOR PRACTICE: use of these elements is recommended for women who request EMTSL, and for those in countries without ready access to uterotonics.

T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism.

We investigated the mechanisms by which T-cell cytokines are able to influence the Toll-like receptor (TLR)-induced, vitamin D-dependent antimicrobial pathway in human monocytes. T-cell cytokines differentially influenced TLR2/1-induced expression of the antimicrobial peptides cathelicidin and DEFB4, being up-regulated by IFN-γ, down-regulated by IL-4, and unaffected by IL-17. The Th1 cytokine IFN-γ up-regulated TLR2/1 induction of 25-hydroxyvitamin D-1α-hydroxylase (i.e., CYP27B1), leading to enhanced bioconversion of 25-hydroxyvitamin D(3) (25D(3)) to its active metabolite 1,25D(3). In contrast, the Th2 cytokine IL-4, by itself and in combination with the TLR2/1 ligand, induced catabolism of 25D(3) to the inactive metabolite 24,25D(3), and was dependent on expression of vitamin D-24-hydroxylase (i.e., CYP24A1). Therefore, the ability of T-cell cytokines to differentially control monocyte vitamin D metabolism represents a mechanism by which cell-mediated immune responses can regulate innate immune mechanisms to defend against microbial pathogens.

Transcriptional profiles of Treponema denticola in response to environmental conditions.

The periodontal pathogen T. denticola resides in a stressful environment rife with challenges, the human oral cavity. Knowledge of the stress response capabilities of this invasive spirochete is currently very limited. Whole genome expression profiles in response to different suspected stresses including heat shock, osmotic downshift, oxygen and blood exposure were examined. Most of the genes predicted to encode conserved heat shock proteins (HSPs) were found to be induced under heat and oxygen stress. Several of these HSPs also seem to be important for survival in hypotonic solutions and blood. In addition to HSPs, differential regulation of many genes encoding metabolic proteins, hypothetical proteins, transcriptional regulators and transporters was observed in patterns that could betoken functional associations. In summary, stress responses in T. denticola exhibit many similarities to the corresponding stress responses in other organisms but also employ unique components including the induction of hypothetical proteins.