The cellular structure and lipid/protein composition of adipose tissue surrounding chronically stimulated lymph nodes in rats

To test the hypothesis that chronic immune stimulation of a peripheral lymph node induces the formation of additional mature adipocytes in adjacent adipose tissue, one popliteal lymph node of large male rats was stimulated by local injection of 10 microg or 20 microg lipopolysaccharide three times a week for 6 weeks. Adipocyte volumes in sites defined by their anatomical relations to the stimulated and homologous unstimulated popliteal lymph nodes were measured, plus adipocyte complement of the popliteal depot, and the lipid and protein content of adipocytes and adipose stroma. The higher dose of lipopolysaccharide doubled the mass of the locally stimulated lymph node and the surrounding adipose tissue enlarged by the appearance of additional mature adipocytes. Similar but smaller changes were observed in the popliteal adipose depot of the unstimulated leg and in a nodeless depot. The lipid content of the adipocytes decreased and that of the stroma increased dose-dependently in all samples measured but the changes were consistently greater in the depot surrounding the stimulated lymph node. The protein content of both adipocytes and stroma increased in samples surrounding the stimulated node. We conclude that chronic immune stimulation of lymphoid tissues induces the formation of more adipocytes in the adjacent adipose tissue. These findings suggest a mechanism for the selective hypertrophy of lymphoid-containing adipose depots in the HIV-associated adipose redistribution syndrome.     

Energy Balance,Eating Disorder Risk,and Pathogenic Behaviors Among Athletic Trainers

ContextResearch exists on energy balances (EBs) and eating disorder (ED) risks in physically active populations and occupations by settings, but the EB and ED risk in athletic trainers (ATs) have not been investigated.ObjectiveTo assess ATs'' energy needs, including the macronutrient profile, and examine ED risk and pathogenic behavioral differences between sexes (men, women) and job statuses (part time or full time) and among settings (college or university, high school, nontraditional).DesignCross-sectional study.SettingFree living in job settings.Patients or Other ParticipantsAthletic trainers (n = 46; male part-time graduate assistant ATs = 12, male full-time ATs = 11, female part-time graduate assistant ATs = 11, female full-time ATs = 12) in the southeastern United States.Main Outcome Measure(s)Anthropometric measures (sex, age, height, weight, body composition), demographic characteristics (job status [full- or part-time AT], job setting [college/university, high school, nontraditional], years of AT experience, exercise background, alcohol use), resting metabolic rate, energy intake (EI), total daily energy expenditure (TDEE), EB, exercise energy expenditure, macronutrients (carbohydrates, protein, fats), the Eating Disorder Inventory-3, and the Eating Disorder Inventory-3 Symptom Checklist.ResultsThe majority of participants (84.8%, n = 39) had an ED risk, with 26.1% (n = 12) engaging in at least 1 pathogenic behavior, 50% (n = 23) in 2 pathogenic behaviors, and 10.8% (n = 5) in >2 pathogenic behaviors. Also, 82.6% of ATs (n = 38) presented in negative EB (EI < TDEE). Differences were found in resting metabolic rate for sex and job status (F_1,45 = 16.48, P = .001), EI (F_1,45 = 12.01, P = .001), TDEE (F_1,45 = 40.36, P < .001), and exercise energy expenditure (F_1,38 = 5.353, P = .026). No differences were present in EB for sex and job status (F_1,45 = 1.751, P = .193); χ² analysis revealed no significant relationship between ATs'' sex and EB (= 0.0, P = 1.00) and job status and EB ( = 2.42, P = .120). No significant relationship existed between Daily Reference Intakes recommendations for all macronutrients and sex or job status.ConclusionsThese athletic trainers experienced negative EB, similar to other professionals in high-demand occupations. Regardless of sex or job status, ATs had a high ED risk and participated in unhealthy pathogenic behaviors. The physical and mental concerns associated with these findings indicate a need for interventions targeted at ATs'' health behaviors.     

The clinical pharmacokinetics of the novel antifolate N10-propargyl-5,8-dideazafolic acid (CB 3717)

Summary The pharmacokinetics of the new antifolate CB 3717 were studied in 20 patients during its phase-I clinical evaluation. The drug was administered at doses of 100–550 mg/m² in 1-h and 12-h infusions, resulting in peak plasma concentrations of CB 3717 of 40–200 M. There was a linear relationship between the dose and both CB 3717 AUC and peak plasma levels. Following a 1-h infusion, drug levels in the plasma decayed biphasically (t_1/2=49±9 min, t_1/2=739±209 min). 27%±2% of the dose was excreted in urine in the 24-h period after treatment, suggesting that the major route of elimination was via the bile. Furthermore, the parent compound CB 3717 and its desglutamyl metabolite, CB 3751, were found in a faecal collection although the metabolite was not detected in plasma or urine samples. Plasma protein binding of CB 3717 was extensive (97.6%±0.1%). Significant quantities of CB 3717 penetrated into ascitic fluid but not into cerebrospinal fluid.Residual drug was detected in postmortem kidney tissue from a patient who died of progressive disease 8 days after treatment with 330 mg/m² CB 3717. Thus, dose-limiting renal toxicity (maximum tolerated dose 600 mg/m²) may be due to drug precipitation in the renal tubules. Elevation of liver enzymes, in particular transaminases, occurred frequently as a toxic manifestation of CB 3717 therapy. In 11 patients studied after their first treatment there was a positive correlation between the rise in serum alanine transaminase and peak drug levels (r=0.69, P=0.02)These pharmacokinetic studies have shown that, by analogy with experimental systems, cytotoxic plasma levels of CB 3717 are archieved in man. In addition, they have been valuable in interpreting toxicities observed during phase-I clinical studies.This work was supported by grants from the Medical Research Council and Cancer Research Campaign, U. K.     

Racial Identity Clusters and Their Relation to Postpartum Maternal Functioning in Black Women

Maternal and Child Health Journal - Racial identity, which is the degree that individuals define themselves regarding their racial group membership, may influence the mental well-being of Black...     

Severe Acute Respiratory Syndrome Coronavirus 2 Seropositivity among Healthcare Personnel in Hospitals and Nursing Homes,Rhode Island,USA, July–August 2020

Healthcare personnel are recognized to be at higher risk for infection with severe acute respiratory syndrome coronavirus 2. We conducted a serologic survey in 15 hospitals and 56 nursing homes across Rhode Island, USA, during July 17–August 28, 2020. Overall seropositivity among 9,863 healthcare personnel was 4.6% (95% CI 4.2%–5.0%) but varied 4-fold between hospital personnel (3.1%, 95% CI 2.7%–3.5%) and nursing home personnel (13.1%, 95% CI 11.5%–14.9%). Within nursing homes, prevalence was highest among personnel working in coronavirus disease units (24.1%; 95% CI 20.6%–27.8%). Adjusted analysis showed that in hospitals, nurses and receptionists/medical assistants had a higher likelihood of seropositivity than physicians. In nursing homes, nursing assistants and social workers/case managers had higher likelihoods of seropositivity than occupational/physical/speech therapists. Nursing home personnel in all occupations had elevated seropositivity compared with hospital counterparts. Additional mitigation strategies are needed to protect nursing home personnel from infection, regardless of occupation.     

How Do Medical Students Perceive Diversity in Orthopaedic Surgery,and How Do Their Perceptions Change After an Orthopaedic Clinical Rotation?

BackgroundA diverse physician workforce improves the quality of care for all patients, and there is a need for greater diversity in orthopaedic surgery. It is important that medical students of diverse backgrounds be encouraged to pursue the specialty, but to do so, we must understand students’ perceptions of diversity and inclusion in orthopaedics. We also currently lack knowledge about how participation in an orthopaedic clinical rotation might influence these perceptions.Questions/purposes(1) How do the perceptions of diversity and inclusion in orthopaedic surgery compare among medical students of different gender identities, races or ethnicities, and sexual orientations? (2) How do perceptions change after an orthopaedic clinical rotation among members of demographic groups who are not the majority in orthopaedics (that is, cis-gender women, underrepresented racial minorities, other racial minorities, and nonheterosexual people)?MethodsWe surveyed students from 27 US medical schools who had completed orthopaedic rotations. We asked about their demographic characteristics, rotation experience, perceptions of diversity and inclusion in orthopaedics, and personal views on specialty choice. Questions were derived from diversity, equity, and inclusion climate surveys used at major academic institutions. Cis-gender men and cis-gender women were defined as those who self-identified their gender as men or women, respectively, and were not transgender. Forty-five percent (59 of 131) of respondents were cis-men and 53% (70 of 131) were cis-women; 49% (64 of 131) were white, 20% (26 of 131) were of underrepresented racial minorities, and 31% (41 of 131) were of other races. Eighty-five percent (112 of 131) of respondents were heterosexual and 15% (19 of 131) reported having another sexual orientation. We compared prerotation and postrotation perceptions of diversity and inclusion between majority and nonmajority demographic groups for each demographic domain (for example, cis-men versus cis-women). We also compared prerotation to postrotation perceptions within each nonmajority demographic group. To identify potential confounding variables, we performed univariate analysis to compare student and rotation characteristics across the demographic groups, assessed using an alpha of 0.05. No potential confounders were identified. Statistical significance was assessed at a Bonferroni-adjusted alpha of 0.0125. Our estimated response percentage was 26%. To determine limitations of nonresponse bias, we compared all early versus late responders and found that for three survey questions, late responders had a more favorable perception of diversity in orthopaedic surgery, whereas for most questions, there was no difference.ResultsBefore rotation, cis-women had lower agreement that diversity and inclusion are part of orthopaedic culture (mean score 0.96 ± 0.75) compared with cis-men (1.4 ± 1.1) (mean difference 0.48 [95% confidence interval 0.16 to 0.81]; p = 0.004), viewed orthopaedic surgery as less diverse (cis-women 0.71 ± 0.73 versus cis-men 1.2 ± 0.92; mean difference 0.49 [95% CI 0.20 to 0.78]; p = 0.001) and more sexist (cis-women 1.3 ± 0.92 versus cis-men 1.9 ± 1.2; mean difference 0.61 [95% CI 0.23 to 0.99]; p = 0.002), believed they would have to work harder than others to be valued equally (cis-women 2.8 ± 1.0 versus cis-men 1.9 ± 1.3; mean difference 0.87 [95% CI 0.45 to 1.3]; p < 0.001), and were less likely to pursue orthopaedic surgery (cis-women 1.4 ± 1.4 versus cis-men 2.6 ± 1.1; mean difference 1.2 [95% CI 0.76 to 1.6]; p < 0.001). Before rotation, underrepresented minorities had less agreement that diversity and inclusion are part of orthopaedic surgery culture (0.73 ± 0.72) compared with white students (1.5 ± 0.97) (mean difference 0.72 [95% CI 0.35 to 1.1]; p < 0.001). Many of these differences between nonmajority and majority demographic groups ceased to exist after rotation. Compared with their own prerotation beliefs, after rotation, cis-women believed more that diversity and inclusion are part of orthopaedic surgery culture (prerotation mean score 0.96 ± 0.75 versus postrotation mean score 1.2 ± 0.96; mean difference 0.60 [95% CI 0.22 to 0.98]; p = 0.002) and that orthopaedic surgery is friendlier (prerotation 2.3 ± 1.2 versus postrotation 2.6 ± 1.1; mean difference 0.41 [95% CI 0.14 to 0.69]; p = 0.004), more diverse (prerotation 0.71 ± 0.73 versus postrotation 1.0 ± 0.89; mean difference 0.28 [95% CI 0.08 to 0.49]; p = 0.007), less sexist (prerotation 1.3 ± 0.92 versus postrotation 1.9 ± 1.0; mean difference 0.63 [95% CI 0.40 to 0.85]; p < 0.001), less homophobic (prerotation 2.1 ± 1.0 versus postrotation 2.4 ± 0.97; mean difference 0.27 [95% CI 0.062 to 0.47]; p = 0.011), and less racist (prerotation 2.3 ± 1.1 versus postrotation 2.5 ± 1.1; mean difference 0.28 [95% CI 0.099 to 0.47]; p = 0.003). Compared with before rotation, after rotation cis-women believed less that they would have to work harder than others to be valued equally on the rotation (prerotation 2.8 ± 1.0 versus postrotation 2.5 ± 1.0; mean difference 0.31 [95% CI 0.12 to 0.50]; p = 0.002), as did nonheterosexual students (prerotation 2.4 ± 1.4 versus postrotation 1.8 ± 1.3; mean difference 0.56 [95% 0.21 to 0.91]; p = 0.004). Underrepresented minority students saw orthopaedic surgery as less sexist after rotation compared with before rotation (prerotation 1.5 ± 1.1 versus postrotation 2.0 ± 1.1; mean difference 0.52 [95% CI 0.16 to 0.89]; p = 0.007).ConclusionEven with an estimated 26% response percentage, we found that medical students of demographic backgrounds who are not the majority in orthopaedics generally perceived that orthopaedic surgery is less diverse and inclusive than do their counterparts in majority groups, but these views often change after a clinical orthopaedic rotation.Clinical RelevanceThese perceptions may be a barrier to diversification of the pool of medical student applicants to orthopaedics. However, participation in an orthopaedic surgery rotation is associated with mitigation of many of these negative perceptions among diverse students. Medical schools have a responsibility to develop a diverse workforce, and given our findings, schools should promote participation in a clinical orthopaedic rotation. Residency programs and orthopaedic organizations can also increase exposure to the field through the rotation and other means. Doing so may ultimately diversify the orthopaedic surgeon workforce and improve care for all orthopaedic patients.