Interleukin-4 receptor alpha chain and STAT6 signaling inhibit gamma interferon but not Th2 cytokine expression within schistosome granulomas

Compared to wild-type (WT) mice, schistosome granulomas in Stat6 knockout (KO) mice lacked eosinophils and had Th1 features. Interleukin-4 (IL-4) acts through Stat6 in assisting Th2 cell development. The importance of Stat6 for Th2-cell development within schistosome granulomas had not been explored. Therefore we studied gamma interferon (IFN-gamma), IL-4, and IL-5 production in granulomas from Stat6 KO and WT mice. Dispersed granuloma cells from Stat6 KO and WT mice made similar amounts of IL-4 and IL-5. Only Stat6 KO granuloma cells released IFN-gamma. Granuloma T cells contained most of the IL-4, IL-5, and IFN-gamma mRNA and secreted these cytokines. In Stat6 KO mice, 16.6% of the granuloma cells were CD4(+). Of these, 10.7% stained for IFN-gamma and/or IL-4 by intracytoplasmic flow analysis. Few CD4(-) T cells stained positively. The IL-4-producing T cells did not stain for DX5 or with labeled alpha-GalCer CD1d tetramer, suggesting an absence of NK T cells. Thus, conventional Th cells in Stat6 KO granulomas produce IFN-gamma and Th2 cytokines. Stat6 limits IFN-gamma production but is unnecessary for Th2-cell development or localization within the granuloma.     

Genes encoded in the major histocompatibility complex affecting the generation of peptides for TAP transport

The B cell line 721.174 has lost the ability to present intracellular antigens to major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL). This phenotype results from a homozygous deletion in the MHC that includes the peptide transporter genes TAP1 and TAP2, and the proteasome subunits LMP2 and LMP7. Recent work has shown that such cells transfected with TAP genes load their class I molecules with endogenous peptides, and present several viral epitopes to class I-restricted CTL. These data implied that the LMP2 and LMP7 genes were not required for the presentation of most epitopes through class I molecules. By contrast, while confirming the previous reports, we have identified several epitopes that appear to require genes in the MHC in addition to the TAP for their presentation. Further analysis localizes the defect to proteolysis in the cytosol. In one case, presentation could be partially restored by re-expression of full-length LMP7. Control experiments with LMP7, from which the putative pro-region had been removed, failed to restore presentation, and this lack of effect correlated with failure of the shortened LMP7 to incorporate into the proteasome. These results suggest a role for LMP7 in the generation of a viral epitope, but leave open the possibility that additional genes within the .174 deletion are required for full restoration of antigen presentation.     

Lassa fever. Effective therapy with ribavirin

In a study of Lassa fever in Sierra Leone, West Africa, we identified two variables associated with a high risk of death, and we evaluated the efficacy of ribavirin and Lassa virus-convalescent plasma for the treatment of Lassa fever. A serum aspartate aminotransferase level greater than or equal to 150 IU per liter at the time of hospital admission was associated with a case-fatality rate of 55 percent (33 of 60). Patients with the same risk factor who were treated for 10 days with intravenous ribavirin, begun within the first 6 days after the onset of fever, had a case-fatality rate of 5 percent (1 of 20) (P = 0.0002 by Fisher's exact test). Patients whose treatment began seven or more days after the onset of fever had a case-fatality rate of 26 percent (11 of 43) (P = 0.01). Viremia with levels greater than or equal to 10(3.6) TCID50 per milliliter on admission was associated with a case-fatality rate of 76 percent (35 of 46). Patients with this risk factor who were treated with intravenous ribavirin within the first six days after onset of fever had a case-fatality rate of 9 percent (1 of 11) (P = 0.006), whereas those treated after seven days or more of illness had a fatality rate of 47 percent (9 of 19) (P = 0.035). Oral ribavirin was also effective in patients at high risk of death. Lassa-convalescent plasma did not significantly reduce mortality in any of the high-risk groups. We conclude that ribavirin is effective in the treatment of Lassa fever and that it should be used at any point in the illness, as well as for postexposure prophylaxis.     

Prognostic factors determining response to antidepressant drugs in psychiatric out-patients and general practice

The outcome of antidepressant drug treatment was measured in 200 patients, 145 seen in psychiatric out-patient clinics and 55 in general practice, after 4 weeks of therapy. The results of the 200 patients taken together suggested that prognosis was largely determined by factors dependent on the natural history of the disorder and that clinical symptoms were unimportant, but when the results for patients in each drug group were analysed separately symptoms were more important than natural history factors. We conclude that clinical symptoms are only important predictors of response to antidepressant drugs when the patients studied are homogeneous with regard to natural history factors, particularly duration of illness.     

Influence of iron on in vivo proliferation and lethality of L1210 cells

The ability of iron to stimulate the growth of L1210 cells both in DBA-2 mice and in cell culture is evaluated. Although in vitro stimulation is absent, in vivo studies clearly indicate higher numbers of tumor cells in the presence of supplemental iron. When mice were given iron i.p., at levels comparable to clinical doses for humans (24 mg/kg body weight), the tumor load recovered from their peritoneum was substantially greater than from controls without iron supplements. Furthermore, at higher levels of supplemental iron (250 mg Fe/kg body weight), the pretreated animals inoculated with L1210 cells died in 9.7 d whereas controls died in 12.2 d (i.e., 25% faster). As expected, the lower iron dose (24 mg/kg) also resulted in shorter life spans, although the effects were less striking. It is the belief of these authors that these data support the opinion that "anemia of chronic disease" associated with leukemia and possibly other malignancies may represent a host defense mechanism as has been postulated by others (1, 8).     

Food Photography as a Tool to Assess Type,Quantity, and Quality of Foods in Parent-Packed Lunches for Preschoolers

ObjectiveExplore using food photography to assess packed lunches in a university-based Early Childhood Center and contextualize these photographs through parent interviews.MethodsAn explanatory sequential design was used. Packed lunches were photographed to assess the type and quantity of foods offered and consumed by Child and Adult Food Care Program components (fruit, vegetable, grain, and protein) and quality of foods offered using the Healthy Meal Index. Parent interviews aimed to understand motivations and behaviors related to packing lunch.ResultsData were collected on 401 lunches. Only 16.2% of lunches met all Child and Adult Food Care Program requirements. Most lunches included fruit (84%) and grains (82%), whereas fewer included vegetables (44%). Portion sizes were large, especially for grains (2.7 ± 1.5 servings). In interviews (n = 24), parents expressed tension between offering healthful items and foods they knew their child would eat, as well as concern about children going hungry.Conclusions and ImplicationsFood photography is a feasible methodology to capture parent-packed lunches for preschoolers and may have utility in nutrition education, particularly related to age-appropriate portion sizes.     

Decomposing Racial and Ethnic Disparities in Nursing Home Influenza Vaccination

ObjectivesQuantify how observable characteristics contribute to influenza vaccination disparities among White, Black, and Hispanic nursing home (NH) residents.DesignRetrospective cohort.Setting and ParticipantsShort- and long-stay U.S. NH residents aged ≥65 years.MethodsWe linked Minimum Data Set (MDS) and Medicare data to LTCFocUS and other facility data. We included residents with 6-month continuous enrollment in Medicare and an MDS assessment between October 1, 2013, and March 31, 2014. Residents were classified as short-stay (<100 days in NH) or long-stay (≥100 days in NH). We fit multivariable logistic regression models to assess the relationships between 27 resident and NH-level characteristics and receipt of influenza vaccination. Using nonlinear Oaxaca-Blinder decomposition, we decomposed the disparity in influenza vaccination between White versus Black and White versus Hispanic NH residents. Analyses were repeated separately for short- and long-stay residents.ResultsOur study included 630,373 short-stay and 1,029,593 long-stay residents. Proportions vaccinated against influenza included 67.2% of White, 55.1% of Black, and 54.5% of Hispanic individuals among short-stay residents and 84.2%, 76.7%, and 80.8%, respectively among long-stay residents. Across 4 comparisons, the crude disparity in influenza vaccination ranged from 3.4 to 12.7 percentage points. By equalizing 27 prespecified characteristics, these disparities could be reduced 37.7% to 59.2%. Living in a predominantly White facility and proxies for NH quality were important contributors across all analyses. Characteristics unmeasured in our data (eg, NH staff attitudes and beliefs) may have also contributed significantly to the disparity.Conclusions and ImplicationsThe racial/ethnic disparity in influenza vaccination was most dramatic among short-stay residents. Intervening on factors associated with NH quality would likely reduce these disparities; however, future qualitative research is essential to explore potential contributors that were unmeasured in our data and to understand the degree to which these factors contribute to the overall disparity in influenza vaccination.     

Soft Drink Consumption and Mental Health in Adolescents: A Longitudinal Examination

PurposePrevious studies showed associations between soft drink consumption and mental health problems in adolescents, but the direction of these effects is unknown. This study examines the hypotheses that soft drink consumption predicts aggression and depressive symptoms over time and that these mental health problems predict soft drink consumption.MethodsInterviews were conducted with 5,147 children and their caregivers from three sites at child ages 11, 13, and 16. At each time point, youth reported on their frequency of consuming soft drinks, aggressive behavior, and depressive symptoms. An autoregressive cross-lagged path model tested reciprocal relationships between soft drink consumption, aggressive behavior, and depressive symptoms over time.ResultsMore frequent consumption of soft drinks was associated with more aggressive behavior at each time point and depressive symptoms at ages 11 and 13 (r = .04 to .18, p ≤ .002). After adjusting for covariates and stability of each behavior over time, soft drink consumption at ages 11 and 13 predicted more aggressive behavior at the next time point (β = .08 and .06, p < .001). Aggressive behavior at age 13 also predicted more soft drink consumption at age 16 (β = .06, p = .002). Soft drink consumption at age 13 predicted fewer depressive symptoms (β = ?.04, p = .007), but depressive symptoms did not predict soft drink consumption.ConclusionsMore frequent consumption of soft drinks may contribute to aggressive behavior in adolescents over time; there is some support for reciprocal relationships. There is no evidence for soft drink consumption contributing to adolescents' depression. Future research should examine longitudinal effects over shorter intervals.     

A systematic review of reporting quality for anaesthetic interventions in randomised controlled trials

Interventions from randomised controlled trials can only be replicated if they are reported in sufficient detail. The results of trials can only be confidently interpreted if the delivery of the intervention was systematic and the protocol adhered to. We systematically reviewed trials of anaesthetic interventions published in 12 journals from January 2016 to September 2019. We assessed the detail with which interventions were reported, using the Consolidated Standards of Reporting Trials statement for non-pharmacological treatments. We analysed 162 interventions reported by 78 trials in 18,675 participants. Detail sufficiently precise to replicate the intervention was reported for 111 (69%) interventions. Intervention standardisation was reported for 135 (83%) out of the 162 interventions, and protocol adherence was reported for 20 (12%) interventions. Sixty (77%) out of the 78 trials reported the administrative context in which interventions were delivered and 36 (46%) trials detailed the expertise of the practitioners. We conclude that bespoke reporting tools should be developed for anaesthetic interventions and interventions in other areas such as critical care.