Does inter-vertebral range of motion increase after spinal manipulation? A prospective cohort study.

Background: Spinal manipulation for nonspecific neck pain is thought to work in part by improving inter-vertebral range of motion (IV-RoM), but it is difficult to measure this or determine whether it is related to clinical outcomes. Objectives: This study undertook to determine whether cervical spine flexion and extension IV-RoM increases after a course of spinal manipulation, to explore relationships between any IV-RoM increases and clinical outcomes and to compare palpation with objective measurement in the detection of hypo-mobile segments. Method: Thirty patients with nonspecific neck pain and 30 healthy controls matched for age and gender received quantitative fluoroscopy (QF) screenings to measure flexion and extension IV-RoM (C1-C6) at baseline and 4-week follow-up between September 2012-13. Patients received up to 12 neck manipulations and completed NRS, NDI and Euroqol 5D-5L at baseline, plus PGIC and satisfaction questionnaires at follow-up. IV-RoM accuracy, repeatability and hypo-mobility cut-offs were determined. Minimal detectable changes (MDC) over 4 weeks were calculated from controls. Patients and control IV-RoMs were compared at baseline as well as changes in patients over 4 weeks. Correlations between outcomes and the number of manipulations received and the agreement (Kappa) between palpated and QF-detected of hypo-mobile segments were calculated. Results: QF had high accuracy (worst RMS error 0.5o) and repeatability (highest SEM 1.1o, lowest ICC 0.90) for IV-RoM measurement. Hypo-mobility cut offs ranged from 0.8o to 3.5o. No outcome was significantly correlated with increased IV-RoM above MDC and there was no significant difference between the number of hypo-mobile segments in patients and controls at baseline or significant increases in IV-RoMs in patients. However, there was a modest and significant correlation between the number of manipulations received and the number of levels and directions whose IV-RoM increased beyond MDC (Rho=0.39, p=0.043). There was also no agreement between palpation and QF in identifying hypo-mobile segments (Kappa 0.04-0.06). Conclusions: This study found no differences in cervical sagittal IV-RoM between patients with non-specific neck pain and matched controls. There was a modest dose-response relationship between the number of manipulations given and number of levels increasing IV-RoM - providing evidence that neck manipulation has a mechanical effect at segmental levels. However, patient-reported outcomes were not related to this

Perspectives on the chemical etiology of breast cancer.

Multiple factors, known and unknown, contribute to human breast cancer. Hereditary, hormonal, and reproductive factors are associated with risk of breast cancer. Environmental agents, including chemical carcinogens, are modifiable risk factors to which over 70% of breast cancers have been attributed. Polymorphisms of drug-metabolizing enzymes may influence risk of breast cancer from environmental chemicals, dietary agents, and endogenous steroids. The environmental factors discussed in this review include pollutants, occupational exposures, tobacco smoke, alcohol, and diet. Aromatic amines are discussed as potential mammary carcinogens, with a focus on heterocyclic amine food pyrolysis products. These compounds are excreted into the urine after consumption of meals containing cooked meats and have recently been detected in the breast milk of lactating women

Influence of genetic factors on toluene diisocyanate-related symptoms: evidence from a cross-sectional study

Background: Toluene diisocyanate (TDI) is a highly reactive compound used in the production of, e. g., polyurethane foams and paints. TDI is known to cause respiratory symptoms and diseases. Because TDI causes symptoms in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Methods: Workers (N = 132) exposed to TDI and a non-exposed group ( N = 114) were analyzed for genotype (metabolising genes: CYP1A1*2A, CYP1A1*2B, GSTM1*O, GSTM3*B, GSTP1 1105V, GSTP1 A114V, GSTT1*O, MPO -463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, SULT1A1 R213H; immune-related genes: CCL5 -403, HLA-DQB1* 05, TNF-308, TNF-863) and symptoms of the eyes, upper and lower airways ( based on structured interviews). Results: For three polymorphisms: CYP1A1*2A, CYP1A1*2B, and TNF -308 there was a pattern consistent with interaction between genotype and TDI exposure status for the majority of symptoms investigated, although it did reach statistical significance only for some symptoms: among TDI-exposed workers, the CYP1A1 variant carriers had increased risk (CYP1A1*2A and eye symptoms: variant carriers OR 2.0 95% CI 0.68-6.1, p-value for interaction 0.048; CYP1A1*2B and wheeze: IV carriers OR = 12, 1.4-110, p-value for interaction 0.057). TDI-exposed individuals with TNF-308 A were protected against the majority of symptoms, but it did not reach statistical significance. In the non-exposed group, however, TNF -308 A carriers showed higher risk of the majority of symptoms ( eye symptoms: variant carriers OR = 2.8, 1.1-7.1, p-value for interaction 0.12; dry cough OR = 2.2, 0.69-7.2, p-value for interaction 0.036). Individuals with SULT1A1 213H had reduced risk both in the exposed and non-exposed groups. Other polymorphisms, showed associations to certain symptoms: among TDI-exposed, NAT1*10 carriers had a higher risk of eye symptoms and CCL5 -403 AG+AA as well as HLA-DQB1 *05 carriers displayed increased risk of symptoms of the lower airways. GSTM1, GSTM3 and GSTP1 only displayed effects on symptoms of the lower airways in the non-exposed group. Conclusion: Specific gene-TDI interactions for symptoms of the eyes and lower airways appear to exist. The results suggest different mechanisms for TDI- and non- TDI-related symptoms of the eyes and lower airways

COPI Is Required for Enterovirus 71 Replication

Enterovirus 71 (EV71), a member of the Picornaviridae family, is found in Asian countries where it causes a wide range of human diseases. No effective therapy is available for the treatment of these infections. Picornaviruses undergo RNA replication in association with membranes of infected cells. COPI and COPII have been shown to be involved in the formation of picornavirus-induced vesicles. Replication of several picornaviruses, including poliovirus and Echovirus 11 (EV11), is dependent on COPI or COPII. Here, we report that COPI, but not COPII, is required for EV71 replication. Replication of EV71 was inhibited by brefeldin A and golgicide A, inhibitors of COPI activity. Furthermore, we found EV71 2C protein interacted with COPI subunits by co-immunoprecipitation and GST pull-down assay, indicating that COPI coatomer might be directed to the viral replication complex through viral 2C protein. Additionally, because the pathway is conserved among different species of enteroviruses, it may represent a novel target for antiviral therapies

Multiple Advantageous Amino Acid Variants in the NAT2 Gene in Human Populations

Background: Genetic variation at NAT2 has been long recognized as the cause of differential ability to metabolize a wide variety of drugs of therapeutic use. Here, we explore the pattern of genetic variation in 12 human populations that significantly extend the geographic range and resolution of previous surveys, to test the hypothesis that different dietary regimens and lifestyles may explain inter-population differences in NAT2 variation. Methodology/Principal Findings: The entire coding region was resequenced in 98 subjects and six polymorphic positions were genotyped in 150 additional subjects. A single previously undescribed variant was found (34T>C; 12Y>H). Several aspects of the data do not fit the expectations of a neutral model, as assessed by coalescent simulations. Tajima's D is positive in all populations, indicating an excess of intermediate alleles. The level of between-population differentiation is low, and is mainly accounted for by the proportion of fast vs. slow acetylators. However, haplotype frequencies significantly differ across groups of populations with different subsistence. Conclusions/Significance: Data on the structure of haplotypes and their frequencies are compatible with a model in which slow-causing variants were present in widely dispersed populations before major shifts to pastoralism and/or agriculture. In this model, slow-causing mutations gained a selective advantage in populations shifting from hunting-gathering to pastoralism/agriculture. We suggest the diminished dietary availability of folates resulting from the nutritional shift, as the possible cause of the fitness increase associated to haplotypes carrying mutations that reduce enzymatic activity. © 2008 Luca et al

Interaction between Red Meat Intake and NAT2 Genotype in Increasing the Risk of Colorectal Cancer in Japanese and African Americans

Heterocyclic aromatic amines formed in cooked meat may be an underlying mechanism for the red meat-colorectal cancer (CRC) association. These compounds require bioactivaction by N-acetyltransferase 2 (NAT2). An interaction effect between red meat consumption and NAT2 in increasing CRC risk has been inconsistently reported in whites. We investigated this interaction in two populations in which the high-activity rapid NAT2 phenotype is 10- and 2-fold more common than in whites. We meta-analyzed four studies of Japanese (2,217 cases, 3,788 controls) and three studies of African Americans (527 cases, 4,527 controls). NAT2 phenotype was inferred from an optimized seven-SNP genotyping panel. Processed and total red meat intakes were associated with an increased CRC risk in Japanese and in both ethnic groups combined (P’s ≤ 0.002). We observed an interaction between processed meat intake and NAT2 in Japanese (P = 0.04), African Americans (P = 0.02), and in both groups combined (P = 0.006). The association of processed meat with CRC was strongest among individuals with the rapid NAT2 phenotype (combined analysis, OR for highest vs. lowest quartile: 1.62, 95% CI: 1.28–2.05; Ptrend = 8.0×10−5), intermediate among those with the intermediate NAT2 phenotype (1.29, 95% CI: 1.05–1.59; Ptrend = 0.05) and null among those with the slow phenotype (Ptrend = 0.45). A similar interaction was found for NAT2 and total red meat (Pinteraction = 0.03). Our findings support a role for NAT2 in modifying the association between red meat consumption and CRC in Japanese and African Americans

Assessments Related to the Physical, Affective and Cognitive Domains of Physical Literacy Amongst Children Aged 7–11.9 Years: A Systematic Review

Background Over the past decade, there has been increased interest amongst researchers, practitioners and policymakers in physical literacy for children and young people and the assessment of the concept within physical education (PE). This systematic review aimed to identify tools to assess physical literacy and its physical, cognitive and affective domains within children aged 7–11.9 years, and to examine the measurement properties, feasibility and elements of physical literacy assessed within each tool. Methods Six databases (EBSCO host platform, MEDLINE, PsycINFO, Scopus, Education Research Complete, SPORTDiscus) were searched up to 10th September 2020. Studies were included if they sampled children aged between 7 and 11.9 years, employed field-based assessments of physical literacy and/or related affective, physical or cognitive domains, reported measurement properties (quantitative) or theoretical development (qualitative), and were published in English in peer-reviewed journals. The methodological quality and measurement properties of studies and assessment tools were appraised using the COnsensus-based Standards for the selection of health Measurement INstruments risk of bias checklist. The feasibility of each assessment was considered using a utility matrix and elements of physical literacy element were recorded using a descriptive checklist. Results The search strategy resulted in a total of 11467 initial results. After full text screening, 11 studies (3 assessments) related to explicit physical literacy assessments. Forty-four studies (32 assessments) were relevant to the affective domain, 31 studies (15 assessments) were relevant to the physical domain and 2 studies (2 assessments) were included within the cognitive domain. Methodological quality and reporting of measurement properties within the included studies were mixed. The Canadian Assessment of Physical Literacy-2 and the Passport For Life had evidence of acceptable measurement properties from studies of very good methodological quality and assessed a wide range of physical literacy elements. Feasibility results indicated that many tools would be suitable for a primary PE setting, though some require a level of expertise to administer and score that would require training. Conclusions This review has identified a number of existing assessments that could be useful in a physical literacy assessment approach within PE and provides further information to empower researchers and practitioners to make informed decisions when selecting the most appropriate assessment for their needs, purpose and context. The review indicates that researchers and tool developers should aim to improve the methodological quality and reporting of measurement properties of assessments to better inform the field. Trial registration PROSPERO: CRD4201706221