The high rate of antigenic drift in seasonal influenza viruses necessitates frequent changes in vaccine composition. Recent seasonal H3 vaccines do not protect against swine-origin H3N2 variant ...(H3N2v) strains that recently have caused severe human infections. Here, we report a human V
1-69 gene-encoded monoclonal antibody (mAb) designated H3v-47 that exhibits potent cross-reactive neutralization activity against human and swine H3N2 viruses that circulated since 1989. The crystal structure and electron microscopy reconstruction of H3v-47 Fab with the H3N2v hemagglutinin (HA) identify a unique epitope spanning the vestigial esterase and receptor-binding subdomains that is distinct from that of any known neutralizing antibody for influenza A H3 viruses. MAb H3v-47 functions largely by blocking viral egress from infected cells. Interestingly, H3v-47 also engages Fcγ receptor and mediates antibody dependent cellular cytotoxicity (ADCC). This newly identified conserved epitope can be used in design of novel immunogens for development of broadly protective H3 vaccines.
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•PBB-153 is higher in the registry than US population 40 years after the incident.•Those born after have higher PBB-153 compared to the same-aged US population.•PBB-153 remains higher ...in the highly-exposed groups than other Michigan residents.•PCB & PBDE are higher in the registry than the US in some demographic groups.
Widespread polybrominated biphenyls (PBBs) contamination occurred in Michigan from 1973 to 1974, when PBBs were accidentally substituted for a nutritional supplement in livestock feed. People who lived in the state were exposed to PBBs via several routes including ingestion, inhalation and skin absorption. PBBs sequestered in lipid-rich matrices such as adipose tissue, are slowly eliminated after entering the human body, and can also be transferred from a mother to her offspring through the placenta and breastfeeding. Due to the long biological half-lives of PBBs, as well as concerns from the exposed community, biomonitoring measurements were conducted from 2012 to 2015. Because of their similar structures, serum PBBs, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were all measured 40 years after the PBB contamination incident (N = 862). The serum PBB-153 levels among the original highly-exposed groups (i.e., chemical workers, the family of chemical workers, and individuals who lived on or received food from the contaminated farms) remains significantly higher than other Michigan residents. Several predictors such as sampling age, sex, and smoking status were significantly associated with the serum levels of some persistent organic pollutants (POPs). Higher average values and also wider ranges of serum POP levels were found in this study compared to the National Health and Nutrition Examination Survey (NHANES), with the most substantial difference in serum PBB-153. This was true for all groups of Michigan residents including those who were not part of the above-described highly-exposed groups. Moreover, the people born after the contamination incident began also have higher serum PBB-153 levels when compared with more recent NHANES data (2010–2014), which suggests potential intergenerational exposure and/or continued environmental exposure following the contamination period.
Erector spinae plane blocks (ESPBs) are frequently utilized when treating patients with multiple rib fractures. While previous work has demonstrated the efficacy of ESPB as an adequate method of pain ...control, there has been no work comparing a continuous ESPB to “best practice” multimodal pain control. We hypothesize that a continuous ESPB catheter combined with a multimodal pain regimen may be associated with a decrease in opioid requirements when compared to a multimodal pain regimen alone.
This was a retrospective observational cohort study at a level 1 trauma center from September 2016 through September 2021. Inclusion criteria included patients 18 y or older with at least three unilateral rib fractures who were not mechanically ventilated during admission. The primary outcome was the total morphine equivalents utilized throughout the index admission.
A total of 142 patients were included in this study, 71 in each cohort. Patients included had a mean age of 52.5 y, and 18% were female. Demographic data including injury severity score, total number of rib fractures, and length of stay were similar. While there was a trend toward a decrease in morphine equivalents in the patient cohort undergoing ESPB catheter placement, this was not found to be statistically significant (284.3 ± 244.8 versus 412.6 ± 622.2, P = 0.5).
While ESPB catheters are frequently utilized for analgesia in the setting of multiple rib fractures, there was no decrease in total opioid usage when compared with patients who were managed with a multimodal pain regimen alone. Further assessment comparing ESPB catheters to best practice multimodal pain control regimens through a prospective, multicenter trial is required to further validate these findings.
Rice bran contains essential nutrients, antioxidants, and bioactives with anti-inflammatory and diarrheal protective properties important for infants. This 6-month randomized controlled trial ...investigated the effects of heat-stabilized rice bran supplementation during Malian infant weaning. Fifty healthy 6-month-old infants were randomized to a rice bran intervention (N = 25) or non-intervention control group (N = 25). Intervention infants received dose-escalating rice bran supplementation for 6 months (1-5 g/day). Monthly infant dried blood spot and anthropometric measurements were collected. Dried blood spot metabolite abundances were compared monthly according to diet for six months. Supplementation resulted in favorable weight-for-age and weight-for-length z-score changes. Non-targeted dried blood spot-based metabolomics identified 796 metabolites, of which 33% had significant fold differences between groups (7-12 months). Lipids and amino acids represented 70.6% of the metabolites identified. Rice bran supplementation during infant weaning significantly modulated the metabolites involved in antioxidant defenses and with neuroactive properties including reduced glutathione, glycine, glutamate, cysteinylglycine, tryptophan betaine, and choline. These findings support rice bran as a weaning ingredient to meet infant nutritional requirements and with the potential to reduce oxidative stress and improve cognitive outcomes. This study provides evidence for dried blood spots as a cost-effective tool to detect infant biomarkers of nutritional and metabolic status.
Anti-Yo paraneoplastic cerebellar degeneration (PCD) is a devastating autoimmune complication of gynecological cancers. We hypothesized that as for other autoimmune diseases, specific HLA haplotypes ...are associated. We conducted high resolution HLA typing of Class I/Class II in 40 cases versus ethnically matched controls. Three cases with anti-Yo antibodies and peripheral neuropathy were also included. We detected protective effects of DPA1*01:03~DPB1*04:01 (OR=0, p=0.0008), DRB1*04:01~DQA1*03:03(OR=0, p=0.0016) and DPA1*01:03~DPB1*04:01 (OR=0.35, p=0.0047) overall. Increased DRB1*13:01~DQA1*01:03~DQB1*06:03 was also found in PCD ovarian cases (OR=5.4, p=0.0016). These results suggest differential genetic susceptibility to anti-Yo per cancer and with a primary HLA Class II involvement.
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•In this study, we found clear evidence of HLA allele association with anti Yo-PCD.•The strongest association identified a protective and susceptibility haplotype.•Another association also suggests CD8+ T or Natural Killer cell involvement.
Purpose:
Examine the feasibility and preliminary effects of a lifestyle intervention of rice bran plus navy bean supplementation, and physical activity (PA) education on intake of fiber and whole ...grains, and PA levels.
Design:
Randomized-controlled, single-blinded.
Setting:
Academic institution and free-living.
Subjects:
Adults >18 years, with ≥1 adenomatous polyp removed within 3 years.
Intervention:
Participants received powder and pre-prepared meals and snacks that contained either rice bran (30 g/day) plus navy bean (30 g/day), or Fibersol-2® (10 g/day), for 12-weeks. All participants received a 1-hour (PA) education session.
Measures:
Feasibility was assessed by recruitment and retention rates, and compliance to the study foods and procedures. Three-day food logs were analyzed using Nutritionist Pro™ to estimate fiber intake, and the Automated Self-Administered 24-hour (ASA24®) Dietary Assessment Tool calculated Healthy Eating Index (HEI) whole grain and total scores. PA was measured using an ActivPAL™ accelerometer.
Analysis:
Continuous data were summarized as median, range, and percent change from baseline to post-intervention.
Results:
N = 20 (86.9%) completed the intervention. Compliance was 92% in the rice bran plus navy bean versus 89% in Fibersol-2®. Navy bean consumption increased from 2 g/day to 30 g/day, and rice bran from 0 g/day to 30 g/day. Fiber intake (g/day) increased by 73% versus 82%, HEI whole grain improved by 270% versus 37%, and HEI total improved by 10% versus 9.1% in rice bran plus navy bean and Fibersol-2®, respectively. Total PA (MET-hours/day) showed minimal change for intervention (+0.04%) and control (+4%).
Conclusion:
Findings merit a larger trial of rice bran plus navy bean and PA to evaluate efficacy for dietary and cancer prevention-related outcomes.
Dietary intake of whole grains and legumes and adequate physical activity (PA) have been associated with reduced colorectal cancer (CRC) risk. A single-blinded, two-arm, randomized, ...placebo-controlled pilot trial was implemented to evaluate the impact of a 12-week dietary intervention of rice bran + navy bean supplementation and PA education on metabolite profiles and the gut microbiome among individuals at high risk of CRC.
Adults (n=20) were randomized 1:1 to dietary intervention or control. All participants received PA education at baseline. Sixteen study foods were prepared with either heat-stabilized rice bran + navy bean powder or Fibersol
-2 as a placebo. Intervention participants consumed 30 g rice bran + 30 g navy bean powder daily; those in the control group consumed 10 g placebo daily. Non-targeted metabolite profiling was performed by UPLC-MS/MS to evaluate plasma, urine, and stool at 0, 6, and 12 weeks. Stool was also analyzed for primary and secondary bile acids (BAs) and short chain fatty acids (SCFAs) by UPLC-MS/MS and microbial community structure
16S amplicon sequencing. Two-way ANOVA was used to compare differences between groups for metabolites, and mixed models were used to compare differences between groups for BAs, SCFAs, and alpha and beta diversity measures of microbial community structure.
Across biological matrices, the intervention resulted in changes to several amino acid and lipid metabolites, compared to control. There was a 2.33-fold difference in plasma (p<0.001) and a 3.33-fold difference in urine (p=0.008) for the amino acid S-methylcysteine at 12 weeks. Fold-differences to 4-methoxyphenol sulfate in plasma and urine after 6 and 12 weeks (p<0.001) was a novel result from this combined rice bran and navy bean intervention in people. A 2.98-fold difference in plasma (p=0.002) and a 17.74-fold difference in stool (p=0.026) was observed for the lipid octadecenedioylcarnitine at 12 weeks. For stool BAs, 3-oxocholic acid was increased at 12 weeks compared to control within a subset of individuals (mean difference 16.2 ug/uL, p=0.022). No significant differences were observed between groups for stool SCFAs or microbial community structure.
Dietary intake of rice bran + navy beans demonstrates beneficial modulation of host and gut microbial metabolism and represents a practical and affordable means of increasing adherence to national guidelines for CRC control and prevention in a high-risk population.
Adenomatous polyps are associated with an increased risk of developing colorectal cancer. Physical activity (PA) and spending less time sedentary may reduce risk of polyp recurrence and cancer ...incidence. This study examined associations between PA, sedentary time, and stool metabolites in adults at high risk for developing colorectal cancer.
Participants were ≥18 years old with ≥1 adenomatous polyps removed in the previous 3 years. PA and sedentary time were assessed using an activPAL™ accelerometer. Stool samples were analyzed for short-chain fatty acids, and primary/secondary bile acid metabolites by mass spectrometry. Linear regression models examined associations between PA, sedentary time, and stool parameters, with dietary fiber as a covariate.
Participants (N = 21) were 59 (9) years old and had a body mass index of 28.1 (3.35 kg/m2). Light-intensity PA was associated with butyrate (β = 1.88; 95% confidence interval CI, 0.477 to 3.291) and propionate (β = 1.79; 95% CI, 0.862 to 2.724). Moderate to vigorous PA was associated with deoxycholic acid (β = -6.13; 95% CI, -12.14 to -0.11) and ursodeoxycholic acid (β = -0.45; 95% CI, -0.80 to -0.12) abundance.
Both light and moderate to vigorous PA were associated with gut microbial metabolite production. These findings suggest the importance of examining PA intensity alongside stool metabolites for colorectal cancer prevention.
To understand the health impact of long-duration spaceflight, one identical twin astronaut was monitored before, during, and after a 1-year mission onboard the International Space Station; his twin ...served as a genetically matched ground control. Longitudinal assessments identified spaceflight-specific changes, including decreased body mass, telomere elongation, genome instability, carotid artery distension and increased intima-media thickness, altered ocular structure, transcriptional and metabolic changes, DNA methylation changes in immune and oxidative stress-related pathways, gastrointestinal microbiota alterations, and some cognitive decline postflight. Although average telomere length, global gene expression, and microbiome changes returned to near preflight levels within 6 months after return to Earth, increased numbers of short telomeres were observed and expression of some genes was still disrupted. These multiomic, molecular, physiological, and behavioral datasets provide a valuable roadmap of the putative health risks for future human spaceflight.
The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to ...confounding and reverse causation.
To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.
Genomewide association studies (GWAS) published up to January 15, 2015.
GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.
Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.
Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.
Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs 95% CIs per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 95% CI, 0.67-0.90), abdominal aortic aneurysm (OR, 0.63 95% CI, 0.49-0.81), celiac disease (OR, 0.42 95% CI, 0.28-0.61) and interstitial lung disease (OR, 0.09 95% CI, 0.05-0.15).
It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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