Cross-Talk Between Clinical and Host-Response Parameters of Periodontitis in Smokers

Background and Objective Periodontal diseases are a major public health concern leading to tooth loss and have also been shown to be associated with several chronic systemic diseases. Smoking is a major risk factor for the development of numerous systemic diseases, as well as periodontitis. While it is clear that smokers have a significantly enhanced risk for developing periodontitis leading to tooth loss, the population varies regarding susceptibility to disease associated with smoking. This investigation focused on identifying differences in four broad sets of variables, consisting of: (i) host‐response molecules; (ii) periodontal clinical parameters; (iii) antibody responses to periodontal pathogens and oral commensal bacteria; and (iv) other variables of interest, in a population of smokers with (n = 171) and without (n = 117) periodontitis. Material and Methods Bayesian network structured learning (BNSL) techniques were used to investigate potential associations and cross‐talk between the four broad sets of variables. Results BNSL revealed two broad communities with markedly different topology between the populations of smokers, with and without periodontitis. Confidence of the edges in the resulting network also showed marked variations within and between the periodontitis and nonperiodontitis groups. Conclusion The results presented validated known associations and discovered new ones with minimal precedence that may warrant further investigation and novel hypothesis generation. Cross‐talk between the clinical variables and antibody profiles of bacteria were especially pronounced in the case of periodontitis and were mediated by the antibody response profile to Porphyromonas gingivalis

A nutrigenetic approach to investigate the relationship between metabolic traits and vitamin D status in an Asian Indian population

Studies in Asian Indians have examined the association of metabolic traits with vitamin D status. However, findings have been quite inconsistent. Hence, we aimed to explore the relationship between metabolic traits and 25-hydroxyvitamin D [25(OH)D] concentrations. We investigate whether this relationship was modified by lifestyle factors using a nutrigenetic approach in 545 Asian Indians randomly selected from the Chennai Urban Rural Epidemiology Study (219 normal glucose tolerant individuals, 151 with pre-diabetes and 175 individuals with type 2 diabetes). A metabolic genetic risk score (GRS) was developed using five common metabolic disease-related genetic variants. There was a significant interaction between metabolic GRS and carbohydrate intake (energy%) on 25(OH)D (Pinteraction = 0.047). Individuals consuming a low carbohydrate diet (≤62%) and those having lesser number of metabolic risk alleles (GRS ≤ 1) had significantly higher levels of 25(OH)D (p = 0.033). Conversely, individuals consuming a high carbohydrate diet despite having lesser number of risk alleles did not show a significant increase in 25(OH)D (p = 0.662). In summary, our findings show that individuals carrying a smaller number of metabolic risk alleles are likely to have higher 25(OH)D levels if they consume a low carbohydrate diet. These data support the current dietary carbohydrate recommendations of 50%–60% energy suggesting that reduced metabolic genetic risk increases 25(OH)D

Antidepressant exposure causes a nonmonotonic reduction in anxiety-related behaviour in female mosquitofish

Worldwide, biologically active pharmaceuticals, such as psychoactive drugs, are routinely detected in aquatic ecosystems. In this regard, selective serotonin reuptake inhibitors (SSRIs), a class of antidepressant, are of major environmental concern. Through targeted action on evolutionarily conserved physiological pathways, SSRIs could alter ecologically important behaviours in exposed organisms. Here, using two field-realistic dosages (measured concentrations: 18 and 215 ng/L) of the SSRI fluoxetine (Prozac), we examined the effects of exposure on anxiety-related behaviours in wild-caught female mosquitofish, Gambusia holbrooki. Anxiety-related behaviour was assessed using a light/dark transition test, with the swimming activity of fish recorded under two alternating light conditions, complete darkness and bright light, with the shift in light condition used to induce an anxiety-like response. Fluoxetine exposure resulted in a nonmonotonic decrease in anxiety-related behaviour (i.e. nonlinear with dose), with fish in the low-fluoxetine treatment being less responsive to shifts in light condition compared to unexposed fish. There was no such difference between unexposed and high-exposed fish. Further, we detected a significant interaction between exposure treatment and fish weight on general swimming activity, suggesting the presence of a mass-specific effect of fluoxetine. More broadly, contaminant-induced disruption of animal behaviour—as documented here—could have wide-reaching effects on population-level fitness

Sex-specific effects of mitochondrial haplotype on metabolic rate in Drosophila melanogaster support predictions of the Mother's Curse hypothesis

Evolutionary theory proposes that maternal inheritance of mitochondria will facilitate the accumulation of mitochondrial DNA (mtDNA) mutations that are harmful to males but benign or beneficial to females. Furthermore, mtDNA haplotypes sampled from across a given species distribution are expected to differ in the number and identity of these ‘male-harming’ mutations they accumulate. Consequently, it is predicted that the genetic variation which delineates distinct mtDNA haplotypes of a given species should confer larger phenotypic effects on males than females (reflecting mtDNA mutations that are male-harming, but female-benign), or sexually antagonistic effects (reflecting mutations that are male-harming, but female-benefitting). These predictions have received support from recent work examining mitochondrial haplotypic effects on adult life-history traits in Drosophila melanogaster. Here, we explore whether similar signatures of male-bias or sexual antagonism extend to a key physiological trait—metabolic rate. We measured the effects of mitochondrial haplotypes on the amount of carbon dioxide produced by individual flies, controlling for mass and activity, across 13 strains of D. melanogaster that differed only in their mtDNA haplotype. The effects of mtDNA haplotype on metabolic rate were larger in males than females. Furthermore, we observed a negative intersexual correlation across the haplotypes for metabolic rate. Finally, we uncovered a male-specific negative correlation, across haplotypes, between metabolic rate and longevity. These results are consistent with the hypothesis that maternal mitochondrial inheritance has led to the accumulation of a sex-specific genetic load within the mitochondrial genome, which affects metabolic rate and that may have consequences for the evolution of sex differences in life history

Multisite Evaluation of Prediction Models for Emergency Department Crowding Before and During the COVID-19 Pandemic

OBJECTIVE: To develop a machine learning framework to forecast emergency department (ED) crowding and to evaluate model performance under spatial and temporal data drift. MATERIALS AND METHODS: We obtained 4 datasets, identified by the location: 1-large academic hospital and 2-rural hospital, and time period: pre-coronavirus disease (COVID) (January 1, 2019-February 1, 2020) and COVID-era (May 15, 2020-February 1, 2021). Our primary target was a binary outcome that is equal to 1 if the number of patients with acute respiratory illness that were ED boarding for more than 4 h was above a prescribed historical percentile. We trained a random forest and used the area under the curve (AUC) to evaluate out-of-sample performance for 2 experiments: (1) we evaluated the impact of sudden temporal drift by training models using pre-COVID data and testing them during the COVID-era, (2) we evaluated the impact of spatial drift by testing models trained at location 1 on data from location 2, and vice versa. RESULTS: The baseline AUC values for ED boarding ranged from 0.54 (pre-COVID at location 2) to 0.81 (COVID-era at location 1). Models trained with pre-COVID data performed similarly to COVID-era models (0.82 vs 0.78 at location 1). Models that were transferred from location 2 to location 1 performed worse than models trained at location 1 (0.51 vs 0.78). DISCUSSION AND CONCLUSION: Our results demonstrate that ED boarding is a predictable metric for ED crowding, models were not significantly impacted by temporal data drift, and any attempts at implementation must consider spatial data drift

Evidence for the association between FTO gene variants and vitamin B12 concentrations in an Asian Indian population

Background Low vitamin B12 concentrations have been associated with major clinical outcomes, including adiposity, in Indian populations. The Fat mass and obesity-associated gene (FTO) is an established obesity-susceptibility locus; however, it remains unknown whether it influences vitamin B12 status. Hence, we investigated the association of two previously studied FTO polymorphisms with vitamin B12 concentrations and metabolic disease-related outcomes and examined whether these associations were modified by dietary factors and physical activity. Methods A total of 176 individuals with type 2 diabetes, 152 with pre-diabetes, and 220 normal glucose-tolerant individuals were randomly selected from the Chennai Urban Rural Epidemiology Study. Anthropometric, clinical, and biochemical investigations, which included body mass index (BMI), waist circumference, vitamin B12, homocysteine, and folic acid were measured. A validated food frequency questionnaire was used for dietary assessment and self-reported physical activity measures were collected. An unweighted genetic risk score (GRS) was calculated for two FTO single-nucleotide polymorphisms (rs8050136 and rs2388405) by summation of the number of risk alleles for obesity. Interaction analyses were performed by including the interaction terms in the regression model. Results The GRS was significantly associated with increased BMI (P = 0.009) and risk of obesity (P = 0.023). Individuals carrying more than one risk allele for the GRS had 13.13% lower vitamin B12 concentrations, compared to individuals carrying zero risk alleles (P = 0.018). No associations between the GRS and folic acid and homocysteine concentrations were observed. Furthermore, no statistically significant GRS-diet or GRS-physical activity interactions with vitamin B12, folic acid, homocysteine or metabolic-disease outcomes were observed. Conclusion The study shows for the first time that a genetic risk score using two FTO SNPs is associated with lower vitamin B12 concentrations; however, we did not identify any evidence for the influence of lifestyle factors on this association. Further replication studies in larger cohorts are warranted to investigate the association between the GRS and vitamin B12 concentrations

Unexpected role for IL-17 in protective immunity against hypervirulent Mycobacterium tuberculosis HN878 infection

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one third of the world's population. Among these infections, clinical isolates belonging to the W-Beijing appear to be emerging, representing about 50% of Mtb isolates in East Asia, and about 13% of all Mtb isolates worldwide. In animal models, infection with W-Beijing strain, Mtb HN878, is considered "hypervirulent" as it results in increased mortality and causes exacerbated immunopathology in infected animals. We had previously shown the Interleukin (IL) -17 pathway is dispensable for primary immunity against infection with the lab adapted Mtb H37Rv strain. However, it is not known whether IL-17 has any role to play in protective immunity against infection with clinical Mtb isolates. We report here that lab adapted Mtb strains, such as H37Rv, or less virulent Mtb clinical isolates, such as Mtb CDC1551, do not require IL-17 for protective immunity against infection while infection with Mtb HN878 requires IL-17 for early protective immunity. Unexpectedly, Mtb HN878 induces robust production of IL-1β through a TLR-2-dependent mechanism, which supports potent IL-17 responses. We also show that the role for IL-17 in mediating protective immunity against Mtb HN878 is through IL-17 Receptor signaling in non-hematopoietic cells, mediating the induction of the chemokine, CXCL-13, which is required for localization of T cells within lung lymphoid follicles. Correct T cell localization within lymphoid follicles in the lung is required for maximal macrophage activation and Mtb control. Since IL-17 has a critical role in vaccine-induced immunity against TB, our results have far reaching implications for the design of vaccines and therapies to prevent and treat emerging Mtb strains. In addition, our data changes the existing paradigm that IL-17 is dispensable for primary immunity against Mtb infection, and instead suggests a differential role for IL-17 in early protective immunity against emerging Mtb strains. © 2014 Gopal et al

Circulating adiponectin mediates the association between omentin gene polymorphism and cardiometabolic health in Asian Indians

Background: Plasma omentin levels have been shown to be associated with circulating adiponectin concentrations and cardiometabolic disease-related outcomes. In this study, we aim to examine the association of omentin gene polymorphism with serum adiponectin levels and cardiometabolic health status using a genetic approach and investigate whether these associations are modified by lifestyle factors. Methods: The study included 945 normal glucose tolerant and 941 unrelated individuals with type 2 diabetes randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Study participants were classified into cardiometabolically healthy and unhealthy, where cardiometabolically healthy were those without hypertension, diabetes, and dyslipidemia. Fasting serum adiponectin levels were measured by radioimmunoassay. The omentin A326T (rs2274907) single nucleotide polymorphism (SNP) was screened by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Results: The ‘A’ allele of the omentin SNP was significantly associated with lower adiponectin concentrations after adjusting for age, sex, body mass index (BMI), waist circumference (WC) and cardiometabolic health status (p=1.90 x 10-47). There was also a significant association between circulating adiponectin concentrations and cardiometabolic health status after adjusting for age, sex, BMI, WC and Omentin SNP (p=7.47x10-10). However, after adjusting for age, sex, BMI, WC and adiponectin levels, the association of ‘A’ allele with cardiometabolic health status disappeared (p=0.79) suggesting that adiponectin serves as a mediator of the association between omentin SNP and cardiometabolic health status. There were no significant interactions between the SNP and dietary factors on adiponectin levels and cardiometabolic health status (p>0.25, for all comparisons). Conclusions: Our findings show that adiponectin might function as a mechanistic link between omentin SNP and increased risk of cardiometabolic diseases independent of common and central obesity in Asian Indians. Further studies are required to confirm the molecular mechanisms involved in this triangular relationship between omentin gene, adiponectin and cardiometabolic diseases

Diet and mitonuclear haplotype interactions affect growth rate in a slime mould

Abstract Trait expression in metazoans is strongly influenced by the balance of macronutrients (i.e. protein, carbohydrate and fat) in the diet. At the same time, an individual's genetic background seems to regulate the magnitude of phenotypic response to a particular diet. It needs to be better understood whether interactions between diet, genetic background and trait expression are found in unicellular eukaryotes. A protist—the slime mould, Physarum polycephalum can choose diets based on protein‐to‐carbohydrate (P:C) content to support optimal growth rate. Yet, the role of genetic background (variation in the mitochondrial and nuclear DNAs) in mediating growth rate response to dietary P:C ratios in the slime mould is unknown. Here, we studied the effects of interactions between mitochondrial and nuclear DNA haplotypes and diet (i.e. G × G × E interactions) on the growth rate of P. polycephalum. A genetic panel of six distinct strains of P. polycephalum that differ in their mitochondrial and nuclear DNA haplotypes was used to measure growth rate across five diets that varied in their P:C ratio and total calories. We first determined the strains' growth rate (total biomass and surface area) when grown on a set menu with access to a particular diet. We then assessed whether the growth rate of strains increased on a buffet menu with access to all diets. Our findings show that the growth rate of P. polycephalum is generally higher on diets containing more carbohydrates than protein and that total calories negatively affect the growth rate. Three‐way interactions between mitochondrial, nuclear haplotypes and dietary P:C ratios affected the strains' surface area of growth but not biomass. Intriguingly, strains did not increase their surface area and biomass when they had access to all diets on the buffet menu. Our findings have broad implications for our understanding of the effect of mitonuclear interactions on trait expression across diverse eukaryotic lineages