Objective
Post-migration stress and trauma impact the way Latino/a immigrants in the USA experience everyday life. Mindfulness-based interventions (MBIs) reduce stress and strengthen mental health by ...improving the response to stressors and promoting physical and psychological well-being; however, they have not been tested extensively with Latino/a immigrants in the USA, particularly MBIs implemented online. Thus, more information is needed about the feasibility of online MBIs adapted for Latino/a immigrants.
Method
This study focuses on the feasibility of an online MBI for Latina mothers and community staff members working with them (
n
= 41). Qualitative (three focus groups) data were collected to assess feasibility, appropriateness, acceptability, and quantitative (questionnaires) data asking about self-reported changes on stress, mindfulness, mind–body connection, subjective well-being, and perceived physical and mental health after the program.
Results
Participants in the three groups indicated the program was appropriate, feasible, and acceptable for Latina immigrant mothers and the staff serving them. Mothers’ and
Promotoras
’ (community health workers) mean scores for subjective well-being and perceived physical and mental health increased significantly from baseline to post-test. No significant changes were observed in surveys completed by the staff, even though focus group participants reported meaningful improvement.
Conclusion
Overall, the feasibility study was well received and relevant for the organization and the population they serve. The study’s findings provide guidance to others who are implementing online mindfulness practices with Latina immigrants and the staff that work with them.
Preregistration
This study is not preregistered.
The burden of non-alcoholic steatohepatitis (NASH) is growing and current pharmacologic treatments are limited by side effects and inconsistent efficacy. Pilot studies suggest that pentoxifylline ...(PTX) can reduce liver injury in patients with NASH.
We sought to determine the tolerability of PTX and its effect on aminotransferases and liver histology in patients with NASH.
Thirty patients with biopsy proven NASH were randomized in a 2:1 fashion to receive 1,200 mg PTX or placebo for 12 months. Metabolic parameters, aminotransferases, liver histology and hepatic gene expression changes were compared.
At baseline the groups were similar. Adverse events were mild, most frequently headache and abdominal cramps, and did not differ between groups (p = NS). After 12 months, ALT and AST decreased from 92 ± 12 IU/L to 67 ± 13 IU/L and 67 ± 6 IU/L to 47 ± 6 IU/L (p < 0.05), respectively in patients treated with PTX. No significant effect was seen with placebo. Steatosis and cellular ballooning improved in the PTX group (p < 0.05), whereas no histological feature of steatohepatitis improved with placebo. However, between groups comparison of both biochemical and histological features were nonsignificant.
Pentoxifylline is safe, well tolerated and improves transaminases and histology in patients with NASH when compared to baseline and may be a reasonable therapeutic modality for the treatment of NASH. However PTX failed to reduce transaminases compared to placebo and did not positively affect any of the metabolic markers postulated to contribute to NASH. Although animal data and small pilot studies in humans have suggested that PTX may be effective as a treatment for NASH, translating this therapy to clinical practice may prove challenging.
Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by ...choroidal neovascularisation (CNV). Here we show that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and that despite the expression of its ligands eotaxin-1, -2 and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor A (VEGF-A) neutralization, which is in clinical use at present, and, unlike VEGF-A blockade, is not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.
Summary
Systematic review and meta-analysis of the effect of moderate- to high-dose vitamin D supplementation in pregnancy on offspring bone mineralisation found a positive effect of vitamin D ...supplementation on offspring bone mineral density (BMD) at age 4–6 years, with a smaller effect on bone mineral content.
Purpose
A systematic review and meta-analysis was performed to assess the effect of pregnancy vitamin D supplementation on offspring bone mineral density (BMD) in childhood.
Methods
A literature search was conducted for published RCTs of antenatal vitamin D supplementation with assessment of offspring BMD or bone mineral content (BMC) by dual-energy X-ray absorptiometry (DXA) using MEDLINE and EMBASE up to 13th July 2022. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Study findings were grouped in two age groups of offspring assessment: neonatal period and early childhood (3–6 years). Random-effects meta-analysis of the effect on BMC/BMD at 3–6 years was performed using RevMan 5.4.1, yielding standardised mean difference (SMD) (95% CI).
Results
Five RCTs were identified with offspring assessment of BMD or BMC; 3250 women were randomised within these studies. Risk of bias was low in 2 studies and “of concern” in 3. Supplementation regimes and the control used (3 studies used placebo and 2 used 400 IU/day cholecalciferol) varied, but in all studies the intervention increased maternal 25-hydroxvitamin D status compared to the control group. Two trials assessing BMD in the neonatal period (total
n
= 690) found no difference between groups, but meta-analysis was not performed as one trial represented 96.4% of those studied at this age. Three trials assessed offspring whole-body-less-head BMD at age 4–6 years. BMD was higher in children born to mothers supplemented with vitamin D 0.16 SD (95% confidence interval 0.05, 0.27),
n
= 1358 with a smaller effect on BMC 0.07 SD (95% CI − 0.04, 0.19),
n
= 1351.
Conclusions
There are few RCTs published to address this question, and these are inconsistent in methodology and findings. However, meta-analysis of three trials suggests moderate- to high-dose vitamin D supplementation in pregnancy might increase offspring BMD in early childhood, but further trials are required to confirm this finding. (Prospero CRD42021288682; no funding received).
KIC 12557548 b is the first of a growing class of intriguing disintegrating planet candidates, which lose mass in the form of a metal-rich vapor that condenses into dust particles. Here, we follow up ...on two perplexing observations of the system: (1) the transits appeared shallower than average in 2013 and 2014, and (2) the parameters derived from a high-resolution spectrum of the star differed from other results using photometry and low-resolution spectroscopy. We observe five transits of the system with the 61-inch Kuiper telescope in 2016 and show that they are consistent with photometry from the Kepler spacecraft in 2009-2013, suggesting that the dusty tail has returned to normal length and mass. We also evaluate high-resolution archival spectra from the Subaru HDS spectrograph and find them to be consistent with a main-sequence Teff = 4440 70 K star in agreement with the photometry and low-resolution spectroscopy. This disfavors the hypothesis that planet disintegration affected the analysis of prior high-resolution spectra of this star. We apply Principal Component Analysis to the Kepler long-cadence data to understand the modes of disintegration. There is a tentative 491-day periodicity of the second principal component, which corresponds to possible long-term evolution of the dust grain sizes, though the mechanism on such long timescales remains unclear.
•Co-use of alcohol and cigarettes is common and is challenging to treat.•Varenicline and naltrexone are used to treat nicotine and alcohol use disorder.•The combination of varenicline and naltrexone ...may offer a better treatment outcome.•The combination therapy attenuated neural alcohol cue reactivity.•Naltrexone may be driving the reductions in cue-elicited brain response.
There is a strong bidirectional relationship between the use of alcohol and cigarettes which results in various challenges for treating those who co-use both substances. While varenicline and naltrexone each have FDA-approval for nicotine and alcohol use disorder, respectively, there is evidence that their clinical benefit may extend across the two disorders. Critically, the effect of combined varenicline and naltrexone on neural reactivity to alcohol cues among heavy drinking smokers has not yet been studied. Probing the effect of the combination therapy on alcohol cue-reactivity may give insight to the mechanisms underlying its efficacy.
Forty-seven heavy drinking smokers enrolled in two medication studies were randomized to receive varenicline alone (n = 11), varenicline plus naltrexone (n = 11), or placebo (n = 25). Participants completed an fMRI alcohol cue-reactivity task and rated their in-scanner alcohol craving. Whole-brain analyses examined the effect of medication on alcohol cue-elicited neural response.
Varenicline plus naltrexone attenuated alcohol cue-elicited activation in mesolimbic regions relative to varenicline alone and to placebo (Z > 2.3, p < 0.05). The combination varenicline and naltrexone group also endorsed lower in-scanner alcohol craving relative to varenicline alone group (p = 0.04).
These findings provide evidence for the benefit of combined therapy of varenicline and naltrexone over varenicline alone for the attenuation of alcohol cue-elicited neural activation. This study provides a preliminary proof-of-mechanism for this combination pharmacotherapy and suggests that naltrexone may be driving the reductions in cue-elicited alcohol craving in the brain. Further clinical studies using the combined therapy to treat heavy drinking smokers are warranted.
Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a ...subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. However, little is known about the immune response against HBZ in HTLV-1-infected individuals. In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC), ATL, and HAM/TSP patients using the luciferase immunoprecipitation system.
Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP. However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype. Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum. Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4+ T cell activation in HAM/TSP patients. Moreover, HBZ-specific antibody inhibited lymphoproliferation in the PBMC of HAM/TSP patients.
This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection. Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.
Despite experiencing problems related to using cannabis, very few undergraduate cannabis users are interested in treatment for cannabis-related problems or benefit from cannabis-focused online ...personalized feedback interventions (PFIs). Thus, it may be important to determine whether individuals perceive their problems as distressing, as only those who are distressed by their problems may be motivated to change their cannabis use or benefit from cannabis-related interventions. The current study examined cannabis-related problem distress, its relation to motivation to change cannabis use, and whether problem distress impacted outcomes of a problem-focused online PFI. Past-month cannabis-using undergraduates who endorsed experiencing at least one cannabis-related problem in the past 3 months were randomized to a PFI (n = 102) or a personalized normative feedback (PNF)-only condition (n = 102). Problem distress was robustly related to readiness, importance, and confidence to change cannabis use at baseline. Among those with high levels of problem distress at baseline, those in the PFI condition reported a greater decrease in problems than those in the PNF-only condition. This was not the case among those with lower levels of problem distress. Further, the number of cannabis-related problems did not moderate intervention outcomes. Cannabis users who perceive their problems as more distressing may be more motivated to change their cannabis use and more likely to benefit from a problem-focused PFI relative to a PNF-only intervention. Results have implications for the personalization of cannabis-focused interventions to maximize the impacts of interventions and decrease cannabis-related problems.
Public Health Significance
The current study suggests that college cannabis users who perceive their cannabis-related problems as distressing appear to benefit from a problem-focused personalized feedback intervention. Interventions that identify experiences that are seen as most problematic for each individual may be more effective because they are congruent with individuals' existing motivation to change.
BACKGROUNDLittle is known about pathogen-specific humoral immunity after chimeric antigen receptor-modified T (CAR-T) cell therapy for B cell malignancies.METHODSWe conducted a prospective ...cross-sectional study of CD19-targeted or B cell maturation antigen-targeted (BCMA-targeted) CAR-T cell therapy recipients at least 6 months posttreatment and in remission. We measured pathogen-specific IgG against 12 vaccine-preventable infections and the number of viral and bacterial epitopes to which IgG was detected ("epitope hits") using a serological profiling assay. The primary outcome was the proportion of participants with IgG levels above a threshold correlated with seroprotection for vaccine-preventable infections.RESULTSWe enrolled 65 children and adults a median of 20 months after CD19- (n = 54) or BCMA- (n = 11) CAR-T cell therapy. Among 30 adults without IgG replacement therapy (IGRT) in the prior 16 weeks, 27 (90%) had hypogammaglobulinemia. These individuals had seroprotection to a median of 67% (IQR, 59%-73%) of tested infections. Proportions of participants with seroprotection per pathogen were comparable to population-based studies, but most individuals lacked seroprotection to specific pathogens. Compared with CD19-CAR-T cell recipients, BCMA-CAR-T cell recipients were half as likely to have seroprotection (prevalence ratio, 0.47; 95% CI, 0.18-1.25) and had fewer pathogen-specific epitope hits (mean difference, -90 epitope hits; 95% CI, -157 to -22).CONCLUSIONSeroprotection for vaccine-preventable infections in adult CD19-CAR-T cell recipients was comparable to the general population. BCMA-CAR-T cell recipients had fewer pathogen-specific antibodies. Deficits in both groups support the need for vaccine and immunoglobulin replacement therapy studies.FUNDINGSwiss National Science Foundation (Early Postdoc Mobility grant P2BSP3_188162), NIH/National Cancer Institute (NIH/NCI) (U01CA247548 and P01CA018029), NIH/NCI Cancer Center Support Grants (P30CA0087-48 and P30CA015704-44), American Society for Transplantation and Cellular Therapy, and Juno Therapeutics/BMS.
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