Quasi-experimental.
To explore for associations between demographic, patient history, and physical examination variables and short-term improvement in self-reported disability following dry needling ...therapy performed on individuals with low back pain (LBP).
Dry needling is an intervention used with increasing frequency in patients with LBP; however, the characteristics of patients who are most likely to respond are not known.
Seventy-two volunteers with mechanical LBP participated in the study. Potential prognostic factors were collected from baseline questionnaires, patient history, and physical examination tests. Treatment consisted of dry needling to the lumbar multifidus muscles bilaterally, administered during a single treatment session. Improvement was based on percent change on the Oswestry Disability Index at 1 week. The univariate and multivariate associations between 33 potential prognostic factors and improved disability were assessed with correlation coefficients and multivariate linear regression.
Increased LBP with the multifidus lift test (rpb = 0.31, P = .01) or during passive hip flexion performed with the patient supine (rpb = 0.23, P = .06), as well as positive beliefs about acupuncture/dry needling (rho = 0.22, P = .07), demonstrated univariate associations with Oswestry Disability Index improvement. Aggravation of LBP with standing (rpb = -0.27, P = .03), presence of leg pain (rpb = -0.29, P = .02), and any perception of hypermobility in the lumbar spine (rpb = -0.21, P = .09) were associated with less improvement. The multivariate model identified 2 predictors of improved disability with dry needling: pain with the multifidus lift test and no aggravation with standing (R(2) = 0.16, P = .01).
Increased LBP with the multifidus lift test was the strongest predictor of improved disability after dry needling, suggesting that the finding of pain during muscle contraction should be studied in future dry needling studies.
Prognosis, level 1b.
Objective
Obesity in childhood is associated with an inflammatory state in adipose tissue and liver, which elevates risk for diabetes and liver disease. No prior study has examined associations ...between pathologies occurring in adipose tissue and liver to identify elements of tissue damage associated with type 2 diabetes risk. This study sought to determine whether inflammation and fibrosis in abdominal subcutaneous adipose tissue (SAT) in obese/overweight children (BMI‐z 2.3 ± 0.76) was related to the extent of observed liver disease or type 2 diabetes risk.
Methods
Biopsy samples of abdominal (SAT) and liver were simultaneously collected from 33 Italian children (mean BMI 28.1 ± 5.1 kg/m2 and mean age 11.6 ± 2.2 years) with confirmed NAFLD. Histology and immunohistochemistry were conducted on biopsies to assess inflammation and fibrosis in adipose tissue and fibrosis and inflammation in liver.
Results
Presence vs. absence of crown‐like structures (CLS) in SAT was significantly related to liver fibrosis scores (1.7 ± 0.7 vs. 1.2 ± 0.7, P = 0.04) independent of BMI. SAT fibrosis was significantly correlated with a lower disposition index (r = −0.48, P = 0.006). No other adipose measures were associated with liver disease parameters.
Conclusion
Markers of subcutaneous white adipose tissue inflammation are associated with greater extent of liver fibrosis independent of obesity and SAT fibrosis may contribute to diabetes risk through reduced insulin secretion.
The calcium sensing receptor (CaSR) in the distal nephron decreases the propensity for calcium stones. Here we investigate if the apical CaSR in the proximal tubule also prevents stone formation ...acting via regulation of apical dicarboxylate and citrate transport. Urinary citrate, partially reabsorbed as a dicarboxylate in the proximal tubule lumen, inhibits stone formation by complexing calcium. We previously demonstrated a novel apical calcium-sensitive dicarboxylate transport system in OK proximal tubule cells. This calcium-sensitive process has the potential to modulate the amount of citrate available to complex increased urinary calcium. Using isotope labeled succinate uptake in OK cells along with various pharmacologic tools we examined whether the CaSR alters apical dicarboxylate transport and through which signal transduction pathways this occurs. Our results indicate that in the proximal tubule CaSR adjusts apical dicarboxylate transport, and does so via a CaSR → G
q
→ PKC signaling pathway. Thus, the CaSR may decrease the propensity for stone formation via actions in both proximal and distal nephron segments.
Abstract
Children who are hard of hearing are at risk for developmental language and academic delays compared with children with normal hearing. Some work suggests that high-order cognitive function, ...including fluid intelligence, may relate to language and academic outcomes in children with hearing loss, but findings in these studies have been mixed and to date, there have been no studies of the whole-brain neural dynamics serving fluid intelligence in the context of hearing loss. To this end, this study sought to identify the impact of hearing loss and subsequent hearing aid use on the neural dynamics serving abstract reasoning in children who are hard of hearing relative to children with normal hearing using magnetoencephalography. We found significant elevations in occipital and parietal theta activity during early stimulus evaluation in children who are hard of hearing relative to normal-hearing peers. In addition, we found that greater hearing aid use was significantly related to reduced activity throughout the fronto-parietal network. Notably, there were no differences in alpha dynamics between groups during later-stage processing nor did alpha activity correlate with hearing aid use. These cross-sectional data suggest that differences in auditory experience lead to widespread alterations in the neural dynamics serving initial stimulus processing in fluid intelligence in children.
Heinrichs-Graham et al. report elevations in parieto-occipital theta activity during abstract reasoning in children with hearing loss relative to children with normal hearing. Theta activity throughout the fronto-parietal network was also related to the amount of hearing aid use, underscoring the importance of consistent hearing aid use on cognitive and brain development.
Graphical Abstract
Graphical abstract
Objective
Genetic variation in six genes has been associated with elevated liver fat and nonalcoholic fatty liver disease in adults. The influence of these genes on liver fat and whether a genetic ...risk score (GRS) would improve upon the ability of common clinical risk factors to predict elevated liver fat content (ELF) in Hispanic children was determined.
Design and Methods
223 obese Hispanic children were genotyped for six SNPs. MRI was used to measure liver fat. A GRS was tested for association with ELF using multivariate linear regression. Predictors were assessed via ROC curves and pair‐wise analysis was used to determine significance alone and combined with clinical markers.
Results
Only variants in PNPLA3 and APOC3 genes were associated with liver fat (P < 0.001, P = 0.01, respectively). Subjects with a GRS = 4 had ∼3‐fold higher liver fat content than subjects with GRS of 0 (15.1 ± 12.7 vs. 5.1 ± 3.7%, P = 0.03). While the addition of the GRS to a model containing BMI and liver enzymes increased ROC AUC from 0.83 to 0.85 95% CI, 0.79‐0.89, (P = 0.01), it does not improve detection of ELF from a clinical perspective.
Conclusions
Only PNPLA3 and APOC3 were related to ELF and a GRS comprised of these susceptibility alleles did not add to the discriminatory power of traditional biomarkers for clinical assessment of liver fat.
Summary
The colonization of the gut with microbes in early life is critical to the developing newborn immune system, metabolic function and potentially future health. Maternal microbes are ...transmitted to offspring during childbirth, representing a key step in the colonization of the infant gut. Studies of infant meconium suggest that bacteria are present in the foetal gut prior to birth, meaning that colonization could occur prenatally. Animal studies have shown that prenatal transmission of microbes to the foetus is possible, and physiological changes observed in pregnant mothers indicate that in utero transfer is likely in humans as well. However, direct evidence of in utero transfer of bacteria in humans is lacking. Understanding the timing and mechanisms involved in the first colonization of the human gut is critical to a comprehensive understanding of the early life gut microbiome. This review will discuss the evidence supporting in utero transmission of microbes from mother to infants. We also review sources of transferred bacteria, physiological mechanisms of transfer and modifiers of maternal microbiomes and their potential role in early life infant health. Well‐designed longitudinal birth studies that account for established modifiers of the gut microbiome are challenging, but will be necessary to confirm in utero transfer and further our knowledge of the prenatal microbiome.
Key Messages
Air pollution is a leading risk factor for death and disease globally.
Land use regression (LUR) modelling is a commonly used exposure assessment tool, but spatially resolved data are ...required to generate predictor variables in LUR models.
LUR model predictors can be derived at little or no cost from satellite data and high‐resolution imagery.
Air pollution is a major risk factor for death and disease, particularly in low‐ and middle‐income countries (LMIC) where concentrations are relatively high and large populations are exposed. High‐quality exposure assessment is integral to both air pollution epidemiologic studies and impact assessments. Land use regression (LUR) modelling is a powerful exposure assessment technique that uses the relationships between air pollution concentrations at discrete monitoring locations and the surrounding characteristics of those locations to model small‐scale spatial concentration gradients within cities. Regardless of whether they are calibrated based on local measurements or transferred from another location, LUR models require spatially resolved data on predictor variables that may be unavailable or of insufficient quality in many settings. We describe methods for deriving LUR model predictors, including land cover, road locations, and ger (Mongolian yurt) locations, from satellite data and high‐resolution imagery in Ulaanbaatar, Mongolia. These methods may allow LUR models to be developed for more locations in LMIC, potentially improving the quality of air pollution exposure assessments in those settings.
Survol des méthodes pour dégager des variables explicatives de la pollution atmosphérique dans un modèle de régression de l'utilisation du sol à partir de données de télédétection à Oulan‐Bator, Mongolie
La pollution atmosphérique est un facteur de risque important de mortalité et de morbidité, en particulier dans les pays à revenu faible et intermédiaire (PFR‐PRI) marqués par des concentrations relativement élevées auxquelles de nombreuses populations sont exposées. Une évaluation de haute qualité de l'exposition est indispensable pour les études épidémiologiques de la pollution atmosphérique et les études d'impact. La modélisation de l'utilisation du sol par régression constitue un procédé d'évaluation de l'exposition performant fondé sur les liens entre les concentrations de pollution atmosphérique à des stations de surveillance et les attributs particuliers de ces emplacements afin de modéliser les gradients locaux de concentration dans les villes. Peu importe que le calibrage des modèles de régression de l'utilisation du sol soit effectué avec des mesures locales ou soit transposé d'un autre site, ils requièrent des données spatiales fiables des variables explicatives qui peuvent néanmoins être manquantes ou de faible qualité dans plusieurs contextes. Nous présentons un survol des méthodes permettant de dégager des indicateurs d'un modèle de régression de l'utilisation du sol, y compris la couverture du sol, l'emplacement des voies, et les localisations des ger (yourte mongole), à partir de données satellitaires et d'images de haute résolution à Oulan‐Bator, Mongolie. Ces méthodes permettent d'élaborer des modèles de régression de l'utilisation du sol pour d'autres localités dans les PFR‐PRI afin d'améliorer la qualité des évaluations de l'exposition à la pollution atmosphérique dans ces contextes.
ObjectivesTo determine whether a weight-maintaining, moderate (50%) high-fat diet is deleterious to insulin sensitivity in healthy premenopausal women.Design/setting/participants23 African-American ...and non-Hispanic white, healthy, overweight, and obese premenopausal women recruited in New York City, USA, fed either a eucaloric, 1-week long high-fat (50% of total Kcal from fat) diet or a eucaloric, 1-week long low-fat (30% of total Kcal from fat) diet, assigned in a randomized crossover design.Main outcome measuresPeripheral insulin sensitivity and metabolic flexibility during a euglycemic hyperinsulinemic (80 mU/m2/min) clamp measured during the follicular phase of the menstrual cycle, at the end of each diet period.ResultsPeripheral insulin sensitivity (mg kg/fat-free mass/min (µU/mL)×10−1) was not decreased after the high-fat diet vs the low-fat diet (0.09±0.01 vs 0.08±0.01, p=0.09, respectively) in the combined group of African-American and white women, with no significant diet by race interaction (p=0.6). Metabolic flexibility (change in substrate utilization, ΔNPRQ, in response to insulin during the clamp) was similarly unaltered by the diet (0.12±0.01 vs 0.11, p=0.48, for the high-fat diet vs the low-fat diet, respectively) in the combined group of women, with no significant diet by race interaction (p=0.9). African–American women had a lower insulin clearance compared with the white women, regardless of the diet (p<0.05).ConclusionsWe conclude that a short term (1 week), moderate (50%), eucaloric high-fat diet does not lower peripheral insulin sensitivity in healthy, overweight and obese premenopausal women.
Insecticide resistance across sub-Saharan Africa may impact the continued effectiveness of malaria vector control. We investigated the association between carbamate and pyrethroid resistance with ...Anopheles gambiae s.l. parity, Plasmodium falciparum infection, and molecular insecticide resistance mechanisms in Guinea. Pyrethroid resistance was intense, with field populations surviving ten times the insecticidal concentration required to kill susceptible individuals. The L1014F kdr-N1575Y haplotype and I1527T mutation were significantly associated with mosquito survival following permethrin exposure (Prevalence Ratio; PR = 1.92, CI = 1.09-3.37 and PR = 2.80, CI = 1.03-7.64, respectively). Partial restoration of pyrethroid susceptibility following synergist pre-exposure suggests a role for mixed-function oxidases. Carbamate resistance was lower and significantly associated with the G119S Ace-1 mutation. Oocyst rates were 6.8% and 4.2% among resistant and susceptible mosquitoes, respectively; survivors of bendiocarb exposure were significantly more likely to be infected. Pyrethroid resistant mosquitoes had significantly lower parity rates than their susceptible counterparts (PR = 1.15, CI = 1.10-1.21). Our findings emphasize the need for additional studies directly assessing the influence of insecticide resistance on mosquito fitness.
Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery ...efforts are based on data from populations of European ancestry
. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific
. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations
. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States-where minority populations have a disproportionately higher burden of chronic conditions
-the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities.
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