Administration of Bifidobacterium animalis subsp. lactis strain BB-12® in healthy children: characterization, functional composition, and metabolism of the gut microbiome.

Introduction: The consumption of probiotics may influence children's gut microbiome and metabolome, which may reflect shifts in gut microbial diversity composition and metabolism. These potential changes might have a beneficial impact on health. However, there is a lack of evidence investigating the effect of probiotics on the gut microbiome and metabolome of children. We aimed to examine the potential impact of a two (Streptococcus thermophilus and Lactobacillus delbrueckii; S2) vs. three (S2 + Bifidobacterium animalis subsp. lactis strain BB-12) strain-supplemented yogurt. Methods: Included in this study were 59 participants, aged one to five years old, recruited to phase I of a double-blinded, randomized controlled trial. Fecal samples were collected at baseline, after the intervention, and at twenty days post-intervention discontinuation, and untargeted metabolomics and shotgun metagenomics were performed. Results: Shotgun metagenomics and metabolomic analyses showed no global changes in either intervention group's gut microbiome alpha or beta diversity indices, except for a lower microbial diversity in the S2 + BB12 group at Day 30. The relative abundance of the two and three intervention bacteria increased in the S2 and S2 + BB12 groups, respectively, from Day 0 to Day 10. In the S2 + BB12 group, the abundance of several fecal metabolites increased at Day 10, including alanine, glycine, lysine, phenylalanine, serine, and valine. These fecal metabolite changes did not occur in the S2 group. Discussion: In conclusion, there were were no significant differences in the global metagenomic or metabolomic profiles between healthy children receiving two (S2) vs. three (S2 + BB12) probiotic strains for 10 days. Nevertheless, we observed a significant increase (Day 0 to Day 10) in the relative abundance of the two and three probiotics administered in the S2 and S2 + BB12 groups, respectively, indicating the intervention had a measurable impact on the bacteria of interest in the gut microbiome. Future research using longer probiotic intervention durations and in children at risk for gastrointestinal disorders may elucidate if functional metabolite changes confer a protective gastrointestinal effect.

Association of inflammation biomarkers with food cravings and appetite changes across the menstrual cycle.

IMPORTANCE: Premenstrual symptoms, including food cravings, are often a regular complaint among menstruating women. However, existing evidence regarding the biological mechanisms by which these food cravings occur remains unclear. Inflammation may play an essential role in the occurrence of these food cravings before menstruation. OBJECTIVE: The purpose of the present study was to examine the associations between inflammatory markers and the risk of moderate/severe food cravings while accounting for changes in hormone levels and stress across the menstrual cycle. DESIGN, SETTING, AND PARTICIPANTS: The BioCycle Study followed women (n = 259) aged 18-44 for two menstrual cycles. Food cravings (via questionnaire) were assessed up to four times per cycle. Each assessment corresponded to menses and mid-follicular, ovulation, and luteal phases of the menstrual cycle. A wide range of cytokine and chemokine levels (hsCRP, GCSF, GMCSF, IL-4, IL-6, RANTES, MIP1B, etc.) were assessed in blood samples collected at up to 8 visits per cycle, with visits timed using fertility monitors. MAIN OUTCOMES AND MEASURES: Cravings for chocolate, sweets, salty, and other foods, and changes in appetite were determined to estimate the odds of moderate or severe cravings. Associations between inflammatory markers and risk of reporting a moderate/severe craving symptom at each cycle visit was determined using weighted generalized linear models (e.g., marginal structural models). Models were adjusted for age, BMI, and race, as well as time-varying covariates such as estradiol, stress, leptin, and total energy intake, and accounted for repeated measures (i.e., multiple cycles per woman). Both inflammatory markers and reports of cravings were modeled to account for variation at each visit. RESULTS: An association between higher inflammatory biomarkers such as hsCRP, GCSF, GMCSF, IL-4, IL-6, RANTES, MIP, and increased risk of moderate/severe cravings were identified across the menstrual cycle all risk ratio>1, all CIs range 0.71-2.38. hsCRP retained statistical significance after false discovery rate correction with chocolate, sweet, and salty cravings, while GCSF, GMCSF, IL-6, and RANTES retained significance with chocolate and sweet cravings only. CONCLUSION: and Relevance: The results suggest a potential role of inflammation in food cravings and appetite changes across the menstrual cycle.

No significant salt or sweet taste preference or sensitivity differences following ad libitum consumption of ultra-processed and unprocessed diets: a randomized controlled pilot study.

Ultra-processed food consumption has increased worldwide, yet little is known about the potential links with taste preference and sensitivity. This exploratory study aimed to (i) compare sweet and salty taste detection thresholds and preferences following consumption of ultra-processed and unprocessed diets, (ii) investigate whether sweet and salty taste sensitivity and preference were associated with taste substrates (i.e. sodium and sugar) and ad libitum nutrient intake, and (iii) examine associations of taste detection thresholds and preferences with blood pressure (BP) and anthropometric measures following consumption of ultra-processed and unprocessed diets. In a randomized crossover study, participants (N = 20) received ultra-processed or unprocessed foods for 2 weeks, followed by the alternate diet. Baseline food intake data were collected prior to admission. Taste detection thresholds and preferences were measured at the end of each diet arm. Taste-substrate/nutrient intake, body mass index (BMI), and body weight (BW) were measured daily. No significant differences were observed in participant salt and sweet detection thresholds or preferences after 2 weeks on ultra-processed or unprocessed diets. There was no significant association between salt and sweet taste detection thresholds, preferences, and nutrient intakes on either diet arm. A positive correlation was observed between salt taste preference and systolic BP (r = 0.59; P = 0.01), BW (r = 0.47, P = 0.04), and BMI (r = 0.50; P = 0.03) following consumption of the ultra-processed diet. Thus, a 2-week consumption of an ultra-processed diet does not appear to acutely impact sweet or salty taste sensitivity or preference. Trial Registration: ClinicalTrials.gov Identifier NCT03407053.

Association of Inflammation Biomarkers with Food Cravings and Appetite Changes Across the Menstrual Cycle.

Background: Premenstrual symptoms, including food cravings, are often a regular complaint among menstruating women. However, existing evidence regarding the biological mechanisms by which these food cravings occur remains unclear. Inflammation may play an essential role in the occurence of these food cravings before menstruation. Purpose: The purpose of the present study was to examine the associations between inflammatory markers and the risk of moderate/severe food cravings while accounting for changes in hormone levels and stress across the menstrual cycle. Methods: The BioCycle Study followed women (n=259) aged 18-44 for two menstrual cycles. Food cravings (via questionnaire) were assessed up to four times per cycle. Each assessment corresponded to menses and mid-follicular, ovulation, and luteal phases of the menstrual cycle. A wide range of cytokine and chemokine levels (hsCRP, GCSF, GMCSF, IL-4, IL-6, RANTES, MIP1B, etc.) were assessed in blood samples collected at up to 8 visits per cycle, with visits timed using fertility monitors. Cravings for chocolate, sweets, salty, and other foods, and changes in appetite were determined to estimate the odds of moderate or severe cravings. Associations between inflammatory markers and risk of reporting a moderate/severe craving symptom at each cycle visit was determined using weighted generalized linear models (e.g., marginal structural models). Models were adjusted for age, BMI, and race, as well as time-varying covariates such as estradiol, stress, leptin, and total energy intake, and accounted for repeated measures (i.e., multiple cycles per woman). Both inflammatory markers and reports of cravings were modeled to account for variation at each visit. Results: An association between higher inflammatory biomarkers such as hsCRP, GCSF, GMCSF, IL-4, IL-6, RANTES, MIP1B, and increased risk of moderate/severe cravings were identified across the menstrual cycle |all risk ratio>0.8, all CIs range>0.7-0.9|. hsCRP retained statistical significance after false discovery rate correction with chocolate, sweet, and salty cravings, while GCSF, GMCSF, IL-6, and RANTES retained significance with chocolate and sweet cravings only. Conclusion: The results suggest a potential role of inflammation in food cravings and appetite changes across the menstrual cycle.

Administration of Bifidobacterium animalis subsp. lactis Strain BB-12 ® in Healthy Children: Characterization, Functional Composition, and Metabolism of the Gut Microbiome.

The consumption of probiotics may influence children's gut microbiome and metabolome, which may reflect shifts in gut microbial diversity composition and metabolism. These potential changes might have a beneficial impact on health. However, there is a lack of evidence investigating the effect of probiotics on the gut microbiome and metabolome of children. We aimed to examine the potential impact of a two ( Streptococcus thermophilus and Lactobacillus delbrueckii ; S2) vs . three (S2 + Bifidobacterium animalis subsp. lactis strain BB-12) strain-supplemented yogurt. Included in this study were 59 participants, aged one to five years old, recruited to phase I of a double-blinded, randomized controlled trial. Fecal samples were collected at baseline, after the intervention, and at twenty days post-intervention discontinuation, and untargeted metabolomics and shotgun metagenomics were performed. Shotgun metagenomics and metabolomic analyses showed no global changes in either intervention group's gut microbiome alpha or beta diversity indices. The relative abundance of the two and three intervention bacteria increased in the S2 and S2 + BB12 groups, respectively, from Day 0 to Day 10 . In the S2+BB12 group, the abundance of several fecal metabolites was reduced at Day 10 , including alanine, glycine, lysine, phenylalanine, serine, and valine. These fecal metabolite changes did not occur in the S2 group. Future research using longer probiotic intervention durations and in children at risk for gastrointestinal disorders may elucidate if functional metabolite changes confer a protective gastrointestinal effect.

Ciclesonide activates glucocorticoid signaling in neonatal rat lung but does not trigger adverse effects in the cortex and cerebellum.

Synthetic glucocorticoids (sGCs) such as dexamethasone (DEX), while used to mitigate inflammation and disease progression in premature infants with severe bronchopulmonary dysplasia (BPD), are also associated with significant adverse neurologic effects such as reductions in myelination and abnormalities in neuroanatomical development. Ciclesonide (CIC) is a sGC prodrug approved for asthma treatment that exhibits limited systemic side effects. Carboxylesterases enriched in the lower airways convert CIC to the glucocorticoid receptor (GR) agonist des-CIC. We therefore examined whether CIC would likewise activate GR in neonatal lung but have limited adverse extra-pulmonary effects, particularly in the developing brain. Neonatal rats were administered subcutaneous injections of CIC, DEX or vehicle from postnatal days 1-5 (PND1-PND5). Systemic effects linked to DEX exposure, including reduced body and brain weight, were not observed in CIC treated neonates. Furthermore, CIC did not trigger the long-lasting reduction in myelin basic protein expression in the cerebral cortex nor cerebellar size caused by neonatal DEX exposure. Conversely, DEX and CIC were both effective at inducing the expression of select GR target genes in neonatal lung, including those implicated in lung-protective and anti-inflammatory effects. Thus, CIC is a promising, novel candidate drug to treat or prevent BPD in neonates given its activation of GR in neonatal lung and limited adverse neurodevelopmental effects. Furthermore, since sGCs such as DEX administered to pregnant women in pre-term labor can adversely affect fetal brain development, the neurological-sparing properties of CIC, make it an attractive alternative for DEX to treat pregnant women severely ill with respiratory illness, such as with asthma exacerbations or COVID-19 infections.

Associations of Taste Perception with Tobacco Smoking, Marijuana Use, and Weight Status in the National Health and Nutrition Examination Survey.

Habitual smoking of tobacco and marijuana can lead to weight changes and poor diet quality. These effects may be caused by taste changes related to smoking and marijuana use. This study examined the associations among taste perceptions of a bitterant (quinine) and salt, tobacco and marijuana use, and weight status. We conducted a cross-sectional analysis of adults who responded to the National Health and Nutrition Examination Survey in 2013-2014. Participants (n = 2808; female = 51.7%) were adults ≥40 years with an average body mass index (BMI) of 29.6 kg/m2. Participants completed whole mouth and tongue tip assessments of bitter (quinine) and salty (NaCl) tastes, and questionnaires on demographics, cigarette, tobacco, and drug use. Measured height and weight were used to calculate BMI. Compared with never smokers, current smokers reported increased bitter ratings. Smoking status was not associated with salty taste intensity ratings after adjustment for demographic variables. Current marijuana users reported lower tongue tip quine ratings than never users. Among current smokers, current marijuana users had lower whole mouth quinine ratings than never users. Taste perception for salt and quinine for current and former smokers as well as marijuana smokers varied in whole mouth and tongue tip assessment. Changes in taste perception among cigarette smokers and marijuana consumers may be clinically relevant to address to improve diet and weight status.

Untargeted Metabolomic Approach Shows No Differences in Subcutaneous Adipose Tissue of Diabetic and Non-Diabetic Subjects Undergoing Bariatric Surgery: An Exploratory Study.

BACKGROUND: Obesity plays a major role in the development of insulin resistance (IR) and diabetes (T2DM). Increased adipose tissue (AT) is particularly of interest because it activates a chronic inflammatory response in adipocytes and other tissues. AT plays key endocrine and metabolic functions, acting in the regulation of insulin sensitivity and energy homeostasis. Additionally, it can be easily collected during bariatric surgery. The purpose of this pilot study was to explore the potential differences in AT metabolism, through comparing the untargeted metabolomic profiles of diabetic and non-diabetic obese patients undergoing bariatric surgery. METHODS: For this exploratory study, samples were collected from 17 subjects. Subcutaneous AT (SAT) samples from obese-diabetic (n = 8) and Obese-non-Diabetic (n = 9) subjects were obtained from the Human Metabolic Tissue Bank. Untargeted metabolomic profiling was performed by Metabolon® Inc. Statistical analysis was performed using the MetaboAnalyst 4.0 platform. RESULTS: Among the 421 metabolites identified and analyzed there were no significant differences between the Obese-Diabetics and the Obese-non-Diabetics. Small changes were observed by fold change analysis mainly in lipid (n = 12; e.g. NEFAs) and amino acid (n = 8; e.g. BCAAs) metabolic pathways. Dysregulation of these metabolites has been associated with IR and other T2DM-related pathophysiological processes. CONCLUSION: Obesity may influence SAT metabolism masking T2DM-dependent dysregulation. Better understanding the metabolic differences within SAT in diabetic populations may help identify potential biomarkers for diagnosis and monitoring of T2DM in patients undergoing bariatric surgery.

Metabolic Profiling of Blood and Urine for Exploring the Functional Role of the Microbiota in Human Health.

The quantification of metabolites in blood and urine allows nurses to explore new hypotheses about the microbiome. This review summarizes findings from recent studies with a focus on how the state of the science can influence future nursing research initiatives. Metabolomics can advance nursing research by identifying physiologic/pathophysiologic processes underlying patients' symptoms and can be useful for testing the effects of nursing interventions. To date, metabolomics has been used to study cardiovascular, respiratory, endocrine, autoimmune, and infectious conditions, with research focused on understanding the microbial metabolism of substrates resulting in circulating/excreted biomarkers such as trimethylamine N-oxide. This review provides specific recommendations for the collection of specimens and goals for future studies.

Prenatal drug exposure and neurodevelopmental programming of glucocorticoid signalling.

Prenatal neurodevelopment is dependent on precise functioning of multiple signalling pathways in the brain, including those mobilised by glucocorticoids (GC) and endocannabinoids (eCBs). Prenatal exposure to drugs of abuse, including opioids, alcohol, cocaine and cannabis, has been shown to not only impact GC signalling, but also alter functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Such exposures can have long-lasting neurobehavioural consequences, including alterations in the stress response in the offspring. Furthermore, cannabis contains cannabinoids that signal via the eCB pathway, which is linked to some components of GC signalling in the adult brain. Given that GCs are frequently used in pregnancy to prevent complications of prematurity, and also that rates of cannabis use in pregnancy are increasing, the likelihood of foetal co-exposure to these compounds is high and may have additional implications for long-term neurodevelopment. Here, we present a discussion of GC signalling and the HPA axis, as well as the effects of prenatal drug exposure on these pathways and the stress response, and we explore the interactions between GC and EC signalling in the developing brain and potential for neurodevelopmental consequences.

A Systematic Review of Taste Differences Among People With Eating Disorders.

BACKGROUND: Eating disorders are a significant cause of morbidity and mortality. The etiology and maintenance of eating-disorder symptoms are not well understood. Evidence suggests that there may be gustatory alterations in patients with eating disorders. OBJECTIVE: This article systematically reviews research assessing gustatory differences in patients with anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). METHOD: A systematic review was performed, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, examining taste and eating disorders. We reviewed electronic databases and identified 1,490 peer-reviewed English-language studies. Of these, 49 met inclusion criteria. RESULTS: Studies employed psychophysical measures (n = 27), self-reported questionnaires (n = 5), and neuroimaging techniques (i.e., electroencephalography, functional magnetic resonance imaging; n = 17). Psychophysical studies showed that individuals with BN, in general, had greater preference for sweetness than healthy controls, and those with AN had a greater aversion for fat than controls. In neuroimaging studies, findings suggested that predictable administration of sweet-taste stimuli was associated with reduced activation in taste-reward regions of the brain among individuals with AN (e.g., insula, ventral, and dorsal striatum) but increased activation in BN and BED. DISCUSSION: To our knowledge, this systematic review is the first to synthesize literature on taste differences in AN, BN, and BED. The inconsistency and variability in methods used across studies increased difficulties in comparing studies and disease processes. Further studies with well-defined population parameters are warranted to better understand how taste varies in patients with eating disorders.

Adolescent obesity in the past decade: A systematic review of genetics and determinants of food choice.

BACKGROUND AND PURPOSE: As the incidence of global obesity increases, concerns about adverse health outcomes in adolescents continues to rise. The complexity and expense of this problem require early recognition and specific preventive treatments. Knowledge of genetics and determinants of food choices contributing to adolescent obesity warrants further examination. The primary goal was to appraise the literature from the past decade (2007-2017) on the current state of food choice and genetic determinants of adolescent overweight/obesity in the United States. The secondary goal was to determine trends in the literature and areas for future research. METHODS: A systematic review of research studies in the United States from 2007 to 2017 was completed. Database searches were conducted using CINAHL, Embase, PsycINFO, PsycArticles, PubMed, Scopus, Academic Search Complete, Web of Science, BIOSIS, and the Cochrane Library. A total of 535 studies were selected. Of these, 283 studies focused on determinants of food choices and 165 studies focused on genetic factors. CONCLUSIONS: A total of 41 full-text articles included in this literature review contained studies limited exclusively to adolescents. Stress factors related to food choices demonstrated a new trend being explored. The need for precision health, the application of genetic information, could uncover ways food choices affect adolescent obesity. IMPLICATIONS FOR PRACTICE: The etiology of adolescent obesity requires that nurses gain knowledge of genetics and food choice determinants to inform personalized treatments for adolescents, which may establish effective interventions that promote healthy weight achievement.

Personalized pediatric ophthalmology: a case report.

The availability of genetic sequencing has given physicians a new tool for diagnosis and treatment of disease, and "personalized medicine" has become an increasingly common term in general but not in pediatric ophthalmology. We present a case of a toddler who developed ataxia, opsoclonus, myoclonus, and developmental regression following anesthesia for a common otolaryngology procedure. The child was found to have a variant in the MT-ND6 gene (m.14484T>C), most commonly associated with Leber hereditary optic neuropathy, despite a phenotype more closely resembling Leigh syndrome. The incongruence of phenotype and genotype prompted whole exome sequencing, which identified an unexpected intronic missense mutation in RB1 (1960+5G>A), with a 90% penetrance for retinoblastoma. Limited evaluation of the posterior pole in clinic did not identify any lesions, and the risks and benefits of examination under anesthesia were discussed among neurology, ophthalmology, and anesthesiology. We report the outcome of these discussions. The value and risks of personalized medicine are discussed.

Considerations When Designing a Microbiome Study: Implications for Nursing Science.

Nurse scientists play an important role in studying complex relationships among human genetics, environmental factors, and the microbiome, all of which can contribute to human health and disease. Therefore, it is essential that they have the tools necessary to execute a successful microbiome research study. The purpose of this article is to highlight important methodological factors for nurse scientists to consider when designing a microbiome study. In addition to considering factors that influence host-associated microbiomes (i.e., microorganisms associated with organisms such as humans, mice, and rats), this manuscript highlights study designs and methods for microbiome analysis. Exemplars are presented from nurse scientists who have incorporated microbiome methods into their program of research. This review is intended to be a resource to guide nursing-focused microbiome research and highlights how study of the microbiome can be incorporated to answer research questions.

Eating Behavior, Stress, and Adiposity: Discordance Between Perception and Physiology.

The purpose of the study was to examine the interrelationships among stress, eating behavior, and adiposity in a cohort of normal- and overweight individuals. Clinical markers of physiological stress (fasting serum cortisol) and adiposity (body mass index [BMI] and percent body fat) were obtained from participants selected for a natural history protocol ( n = 107). Self-reported data on eating behavior (using the Three-Factor Eating Questionnaire subscales such as Cognitive Restraint, Disinhibition, and Hunger) and psychological stress (via the Perceived Stress Scale) were evaluated. Demographic information was incorporated using principal component analysis, which revealed sex- and weight-based differences in stress, adiposity, and eating behavior measures. Following a cross-sectional and descriptive analysis, significant correlations were found between the Disinhibition and Hunger eating behavior subscales and measures of adiposity including BMI ( r = .30, p = .002 and r = .20, p = .036, respectively) and percent body fat ( r = .43, p = .000 and r = .22, p = .022, respectively). Relationships between stress measures and eating behavior were also evident in the analysis. Disinhibition and Hunger correlated positively with perceived stress ( r = .32, p .001 and r = .26, p = .008, respectively). However, Disinhibition varied inversely with serum cortisol levels ( r = -.25, p = .009). Future studies are warranted to better understand this paradox underlying the effects of perceived and physiological stress on eating behavior.

Statins impact primary embryonic mouse neural stem cell survival, cell death, and fate through distinct mechanisms.

Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthesis pathway (CBP), and are used for the prevention of cardiovascular disease. The anti-inflammatory effects of statins may also provide therapeutic benefits and have led to their use in clinical trials for preeclampsia, a pregnancy-associated inflammatory condition, despite their current classification as category X (i.e. contraindicated during pregnancy). In the developing neocortex, products of the CBP play essential roles in proliferation and differentiation of neural stem-progenitor cells (NSPCs). To understand how statins could impact the developing brain, we studied effects of pravastatin and simvastatin on primary embryonic NSPC survival, proliferation, global transcription, and cell fate in vitro. We found that statins dose dependently decrease NSPC expansion by promoting cell death and autophagy of NSPCs progressing through the G1 phase of the cell cycle. Genome-wide transcriptome analysis demonstrates an increase in expression of CBP genes following pravastatin treatment, through activation of the SREBP2 transcription factor. Co-treatment with farnesyl pyrophosphate (FPP), a CBP metabolite downstream of HMG-CoA reductase, reduces SREBP2 activation and pravastatin-induced PARP cleavage. Finally, pravastatin and simvastatin differentially alter NSPC cell fate and mRNA expression during differentiation, through a non-CBP dependent pathway.

A recurrent de novo missense mutation in UBTF causes developmental neuroregression.

UBTF (upstream binding transcription factor) exists as two isoforms; UBTF1 regulates rRNA transcription by RNA polymerase 1, whereas UBTF2 regulates mRNA transcription by RNA polymerase 2. Herein, we describe 4 patients with very similar patterns of neuroregression due to recurrent de novo mutations in UBTF (GRCh37/hg19, NC_000017.10: g.42290219C > T, NM_014233.3: c.628G > A) resulting in the same amino acid change in both UBTF1 and UBTF2 (p.Glu210Lys [p.E210K]). Disease onset in our cohort was at 2.5 to 3 years and characterized by slow progression of global motor, cognitive and behavioral dysfunction. Notable early features included hypotonia with a floppy gait, high-pitched dysarthria and hyperactivity. Later features included aphasia, dystonia, and spasticity. Speech and ambulatory ability were lost by the early teens. Magnetic resonance imaging showed progressive generalized cerebral atrophy (supratentorial > infratentorial) with involvement of both gray and white matter. Patient fibroblasts showed normal levels of UBTF transcripts, increased expression of pre-rRNA and 18S rRNA, nucleolar abnormalities, markedly increased numbers of DNA breaks, defective cell-cycle progression, and apoptosis. Expression of mutant human UBTF1 in Drosophila neurons was lethal. Although no loss-of-function variants are reported in the Exome Aggregation Consortium (ExAC) database and Ubtf-/- is early embryonic lethal in mice, Ubtf+/- mice displayed only mild motor and behavioral dysfunction in adulthood. Our data underscore the importance of including UBTF E210K in the differential diagnosis of neuroregression and suggest that mainly gain-of-function mechanisms contribute to the pathogenesis of the UBTF E210K neuroregression syndrome.

Multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases and cancer.

BACKGROUND: Many recent studies suggest the immune system plays a significant role in the pathogenesis of autoimmune diseases, chronic inflammatory diseases, and cancer. MATERIALS AND METHODS: Literature published between 2001 and 2011 was reviewed for risk of cancer development in patients with autoimmune and chronic inflammatory diseases. Mode of risk assessment employed did not limit inclusion of studies. Autoimmune conditions developing after diagnosis of a pre-existing cancer were also considered. RESULTS: We report a pervasive, largely positive association between 23 autoimmune and inflammatory diseases and subsequent cancer development. We discuss associations for celiac disease, inflammatory bowel disease rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis in detail. We also address the less frequently reported development of some autoimmune conditions within the course of some malignancies, such as vitiligo developing in the course of melanoma. CONCLUSION: Evidence demonstrates that chronic inflammation and autoimmunity are associated with the development of malignancy. Additionally, patients with a primary malignancy may develop autoimmune like disease. These relationships imply a need for surveillance of patients on immunomodulatory therapies for potential secondary disease processes.

Multiple genes in the 15q13-q14 chromosomal region are associated with schizophrenia.

OBJECTIVE: The chromosomal region, 15q13-q14, including the α7 nicotinic acetylcholine receptor gene, CHRNA7, is a replicated region for schizophrenia. This study fine-mapped genes at 15q13-q14 to determine whether the association is unique to CHRNA7. METHODS: Family-based and case-control association studies were performed on Caucasian-non-Hispanic and African-American individuals from 120 families as well as 468 individual patients with schizophrenia and 144 well-characterized controls. Single-nucleotide polymorphism (SNP) markers were genotyped, and association analyses carried out for the outcomes of schizophrenia, smoking, and smoking in schizophrenia. RESULTS: Three genes were associated with schizophrenia in both ethnic populations: TRPM1, KLF13, and RYR3. Two SNPs in CHRNA7 were associated with schizophrenia in African-Americans, and a second SNP in CHRNA7 was significant for an association with smoking and smoking in schizophrenia in Caucasians. CONCLUSION: Results of these studies support association of the 15q13-q14 region with schizophrenia. The broad positive association suggests that more than one 15q gene may be contributing to the disorder, either in combination or through a regulatory mechanism.