Do genetic risk scores for childhood adiposity operate independent of BMI of their mothers?

OBJECTIVES: Genetic predisposition and maternal body mass index (BMI) are risk factors for childhood adiposity, defined by either BMI or overweight. We aimed to investigate whether childhood-specific genetic risk scores (GRSs) for adiposity-related traits are associated with childhood adiposity independent of maternal BMI, or whether the associations are modified by maternal BMI. METHODS: We constructed a weighted 26-SNP child BMI-GRS and a weighted 17-SNP child obesity-GRS in overall 1674 genotyped children within the Danish National Birth Cohort. We applied a case-cohort (N = 1261) and exposure-based cohort (N = 912) sampling design. Using logistic regression models we estimated associations of the GRSs and child overweight at age 7 years and examined if the GRSs influence child adiposity independent of maternal BMI (per standard deviation units). RESULTS: In the case-cohort design analysis, maternal BMI and the child GRSs were associated with increased odds for childhood overweight [OR for maternal BMI: 2.01 (95% CI: 1.86; 2.17), OR for child BMI-GRS: 1.56 (95% CI: 1.47; 1.66), and OR for child obesity-GRS 1.46 (95% CI: 1.37; 1.54)]. Adjustment for maternal BMI did not change the results, and there were no significant interactions between the GRSs and maternal BMI. However, in the exposure-based cohort design analysis, significant interactions between the child GRSs and maternal BMI on child overweight were observed, suggesting 0.85-0.87-fold attenuation on ORs of child overweight at higher values of maternal BMI and child GRS. CONCLUSION: GRSs for childhood adiposity are strongly associated with childhood adiposity even when adjusted for maternal BMI, suggesting that the child-specific GRSs and maternal BMI contribute to childhood overweight independent of each other. However, high maternal BMI may attenuate the effects of child GRSs in children.

Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities.

Obesity is a major risk factor for cardiometabolic diseases. Nevertheless, a substantial proportion of individuals with obesity do not suffer cardiometabolic comorbidities. The mechanisms that uncouple adiposity from its cardiometabolic complications are not fully understood. Here, we identify 62 loci of which the same allele is significantly associated with both higher adiposity and lower cardiometabolic risk. Functional analyses show that the 62 loci are enriched for genes expressed in adipose tissue, and for regulatory variants that influence nearby genes that affect adipocyte differentiation. Genes prioritized in each locus support a key role of fat distribution (FAM13A, IRS1 and PPARG) and adipocyte function (ALDH2, CCDC92, DNAH10, ESR1, FAM13A, MTOR, PIK3R1 and VEGFB). Several additional mechanisms are involved as well, such as insulin-glucose signalling (ADCY5, ARAP1, CREBBP, FAM13A, MTOR, PEPD, RAC1 and SH2B3), energy expenditure and fatty acid oxidation (IGF2BP2), browning of white adipose tissue (CSK, VEGFA, VEGFB and SLC22A3) and inflammation (SH2B3, DAGLB and ADCY9). Some of these genes may represent therapeutic targets to reduce cardiometabolic risk linked to excess adiposity.

Intermittent catheterization: Clinical practice guidelines from Association Française d'Urologie (AFU), Groupe de Neuro-urologie de Langue Française (GENULF), Société Française de Médecine Physique et de Réadaptation (SOFMER) and Société Interdisciplinaire Francophone d'UroDynamique et de Pelvi-Périnéologie (SIFUD-PP).

INTRODUCTION: Our objective was to provide guidelines covering all aspects of intermittent catheterisation (intermittent self-catheterisation and third-party intermittent catheterisation). MATERIALS AND METHODS: A systematic review of the literature based on Pubmed, Embase, Google scholar was initiated in December 2014 and updated in April 2019. Given the lack of robust data and the numerous unresolved controversial issues, guidelines were established based on the formal consensus of experts from steering, scoring and review panels. RESULTS: This allowed the formulation of 78 guidelines, extending from guidelines on indications for intermittent catheterisation, modalities for training and implementation, choice of equipment, management of bacteriuria and urinary tract infections, to the implementation of intermittent catheterisation in paediatric, geriatric populations, benign prostatic hyperplasia patients and continent urinary diversion patients with a cutaneous reservoir as well as other complications. These guidelines are pertinent to both intermittent self-catheterisation and third-party intermittent catheterisation. CONCLUSION: These are the first comprehensive guidelines specifically aimed at intermittent catheterisation and extend to all aspects of intermittent catheterisation. They assist in the clinical decision-making process, specifically in relation to indications and modalities of intermittent catheterisation options. These guidelines are intended for urologists, gynaecologists, geriatricians, paediatricians, neurologists, physical and rehabilitation physicians, general practitioners and other health professionals including nurses, carers….

Evidence of genetic predisposition for metabolically healthy obesity and metabolically obese normal weight.

Obesity has evolved into a global pandemic that constitutes a major threat to public health. The majority of obesity-related health care costs are due to cardiometabolic complications, such as insulin resistance, dyslipidemia, and hypertension, which are risk factors for Type 2 diabetes and cardiovascular disease. However, many obese individuals, often called metabolically healthy obese (MHO), seem to be protected from these cardiometabolic complications. Conversely, there is a group of individuals who suffer from cardiometabolic complications despite being of normal weight; a condition termed metabolically obese normal weight (MONW). Recent large-scale genomic studies have provided evidence that a number of genetic variants show an association with increased adiposity but a favorable cardiometabolic profile, an indicator for the genetic basis of the MHO and MONW phenotypes. Many of these loci are located in or near genes that implicate pathways involved in adipogenesis, fat distribution, insulin signaling, and insulin resistance. It has been suggested that a threshold for subcutaneous adipose tissue expandability may be at play in the manifestation of MHO and MONW, where expiry of adipose tissue storage capacity could lead to ectopic lipid accumulation in non-adipose tissues such as liver, muscle, heart, and pancreatic beta cells. Understanding the genetic aspects of the mechanisms that underpin MHO and MONW is crucial to define appropriate public health action points and to develop effective intervention measures.

A multi-centre randomised clinical trial of oral hygiene interventions following stroke-A 6-month trial.

Maintaining good oral hygiene is important following stroke. This study aimed to evaluate the effectiveness of two oral health promotion (OHP) programmes to reduce dental plaque levels following stroke. A multi-centre randomised clinical control trial was conducted among patients hospitalised following stroke in Malaysia. Patients were randomly allocated to two OHP groups: (i) control group who received the conventional method for plaque control-daily manual tooth brushing with a standardised commercial toothpaste, (ii) test group-who received an intense method for plaque control-daily powered tooth brushing with 1% Chlorhexidine gel. Oral health assessments were performed at baseline, at 3 months and 6 months post-intervention. Within- and between-group changes in dental plaque were assessed over time. Regression analyses were conducted on dental plaque levels at 6 months controlling for OHP group, medical, dental and socio-demographic status. The retention rate was 62.7% (54 of 86 subjects). Significant within-group changes of dental plaque levels were evident among the test group (P < .001) and the control group (P < .001). No significant between-group changes of dental plaque levels were apparent (P > .05). Regression analyses identified that baseline plaque levels (adjusted ß = 0.79, P < .001) and baseline functional dependency level (adjusted ß = -0.34, P < .05) were associated with dental plaques levels at the end of the trial (6 months). Both, "Conventional" and "Intense" oral health promotion programmes may successfully reduce dental plaque during stroke rehabilitation and are of comparable effectiveness. Baseline dental plaque levels and functional dependency level were key factors associated with dental plaque levels at follow-up at 6 months.

Oro-facial impairment in stroke patients.

Stroke is considered one of the leading causes of death and acquired disability with a peak prevalence over the age of 80 years. Stroke may cause debilitating neurological deficiencies that frequently result in sensory deficits, motor impairment, muscular atrophy, cognitive deficits and psychosocial impairment. Oro-facial impairment may occur due to the frequent involvement of the cranial nerves' cortical representation areas, central nervous system pathways or motoneuron pools. The aim of this narrative, non-systematic review was to discuss the implications of stroke on oro-facial functions and oral health-related quality of life (OHRQoL). Stroke patients demonstrate an impaired masticatory performance, possibly due to reduced tongue forces and disturbed oral sensitivity. Furthermore, facial asymmetry is common, but mostly discrete and lip restraining forces are reduced. Bite force is not different between the ipsi- and contra-lesional side. In contrast, the contra-lesional handgrip strength and tongue-palate contact during swallowing are significantly impaired. OHRQoL is significantly reduced mainly because of the functional impairment. It can be concluded that impaired chewing efficiency, dysphagia, facial asymmetry, reduced lip force and OHRQoL are quantifiable symptoms of oro-facial impairment following a stroke. In the absence of functional rehabilitation, these symptoms seem not to improve. Furthermore, stroke affects the upper limb and the masseter muscle differently, both, at a functional and a morphological level. The rehabilitation of stroke survivors should, therefore, also seek to improve the strength and co-ordination of the oro-facial musculature. This would in turn help improve OHRQoL and the masticatory function, subsequently preventing weight loss and malnutrition.

Oral Health Care Guidelines, Training, and Resources among Stroke Care Providers.

During a stroke, the mouth tends to become an unhealthy place and may give rise to various life-threatening conditions. To this end, there have been repeated calls to incorporate oral hygiene guidelines and practices for hospitalized stroke patients to prevent aspiration pneumonia and improve patients' oral health. The objective of the study was to determine health care providers' practices of oral health care among patients hospitalized after an occurrence of stroke and to determine health care providers' background and work environment effect on these practices. A cross-sectional study was conducted among stroke care providers in 13 public hospitals in Malaysia. The questionnaires distributed were self-administered, where nursing staff provided details of their oral health care practices for stroke patients. Information on the background of health care providers and work environment was also collected. Overall, a total of 780 responses from the registered nurses were obtained. Almost half of the respondents (48.1%) reported that they recommended toothbrushing twice or more per day to stroke patients. Two-thirds (64.7%) reported that they performed daily mouthwashing on their patient, while less than half (38.8%) reported daily oral hygiene assistance. Result of the analysis revealed that oral hygiene practices were significantly associated with having working wards ( P < 0.05), level of qualification ( P < 0.05), having oral health care guidelines ( P < 0.001), specific resources ( P < 0.05), and attending previous training in oral care ( P < 0.001). Provision of oral hygiene practices for hospitalized stroke patients is important. A lack of oral health care guidelines, support from dental professionals, specific resources, training, and assistance in daily oral care for patients is evident and detrimental to oral hygiene practices. The current findings have significant implications for new initiatives to support health care providers, particularly the registered nurses performing oral health care for hospitalized stroke patients. Knowledge Transfer Statement: This study may provide a basis of information for improving the delivery of oral health care to stroke patients. Enhancement in the training and improvement in the existing guidelines and resources is pivotal for the provision of better oral health care for the potential benefits to these patients, including their improved quality of life and disease prevention.

Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion.

Transmission of the two parental alleles to offspring deviating from the Mendelian ratio is termed Transmission Ratio Distortion (TRD), occurs throughout gametic and embryonic development. TRD has been well-studied in animals, but remains largely unknown in humans. The Transmission Disequilibrium Test (TDT) was first proposed to test for association and linkage in case-trios (affected offspring and parents); adjusting for TRD using control-trios was recommended. However, the TDT does not provide risk parameter estimates for different genetic models. A loglinear model was later proposed to provide child and maternal relative risk (RR) estimates of disease, assuming Mendelian transmission. Results from our simulation study showed that case-trios RR estimates using this model are biased in the presence of TRD; power and Type 1 error are compromised. We propose an extended loglinear model adjusting for TRD. Under this extended model, RR estimates, power and Type 1 error are correctly restored. We applied this model to an intrauterine growth restriction dataset, and showed consistent results with a previous approach that adjusted for TRD using control-trios. Our findings suggested the need to adjust for TRD in avoiding spurious results. Documenting TRD in the population is therefore essential for the correct interpretation of genetic association studies.

Oxytocin administration selectively improves olfactory detection thresholds for lyral in patients with schizophrenia.

BACKGROUND: Olfaction plays an important role in mammalian social behavior. Olfactory deficits are common in schizophrenia and correlate with negative symptoms and low social drive. Despite their prominence and possible clinical relevance, little is understood about the pathological mechanisms underlying olfactory deficits in schizophrenia and there are currently no effective treatments for these deficits. The prosocial neuropeptide oxytocin may affect the olfactory system when administered intranasally to humans and there is growing interest in its therapeutic potential in schizophrenia. METHODS: To examine this model, we administered 40IU of oxytocin and placebo intranasally to 31 patients with a schizophrenia spectrum illness and 34 age-matched healthy control participants in a randomized, double-blind, placebo-controlled, cross-over study. On each test day, participants completed an olfactory detection threshold test for two different odors: (1) lyral, a synthetic fragrance compound for which patients with schizophrenia have specific olfactory detection threshold deficits, possibly related to decreased cyclic adenosine 3',5'-monophosphate (cAMP) signaling; and (2) anise, a compound for which olfactory detection thresholds change with menstrual cycle phase in women. RESULTS: On the placebo test day, patients with schizophrenia did not significantly differ from healthy controls in detection of either odor. We found that oxytocin administration significantly and selectively improved olfactory detection thresholds for lyral but not for anise in patients with schizophrenia. In contrast, oxytocin had no effect on detection of either odor in healthy controls. DISCUSSION: Our data indicate that oxytocin administration may ameliorate olfactory deficits in schizophrenia and suggest the effects of intranasal oxytocin may extend to influencing the olfactory system. Given that oxytocin has been found to increase cAMP signaling in vitro a possible mechanism for these effects is discussed.

Orofacial functional impairments among patients following stroke: a systematic review.

OBJECTIVES: The objective of this study was to review orofacial functional impairments among patients following stroke, including objective and subjective assessment. METHODS: A structured search strategy was applied to three electronic databases (Pubmed, Embase, and Web of Science) to identify effective papers. Relevant data regarding subjects, method, outcomes, and key findings were extracted from the effective papers and the results were summarized. RESULTS: The initial search yielded 5227 papers, and 18 effective papers (Kappa: 0.971) were in accordance with the inclusion criteria. The patients with stroke consistently showed a decreased lip force, salivary flow rate, and chewing performance compared with the healthy controls. Due to equivocal results gained from the effective papers, the qualitative assessments regarding whether there was any change in masticatory force on the affected side and oral health-related quality of life were inconclusive. CONCLUSIONS: Existing evidence highlights a number of compromised orofacial functions experienced by patients following stroke. These impairments appear to be sustained, with spontaneous recovery unlikely to occur. While rehabilitative approaches may have the potential to improve orofacial function and quality of life following stroke, there is currently a lack of evidence-based interventions available to inform the development of comprehensive rehabilitation protocols.

Oxytocin administration enhances controlled social cognition in patients with schizophrenia.

BACKGROUND: Individuals with schizophrenia have functionally significant deficits in automatic and controlled social cognition, but no currently available pharmacologic treatments reduce these deficits. The neuropeptide oxytocin has multiple prosocial effects when administered intranasally in humans and there is growing interest in its therapeutic potential in schizophrenia. METHODS: We administered 40 IU of oxytocin and saline placebo intranasally to 29 male subjects with schizophrenia and 31 age-matched, healthy controls in a randomized, double-blind, placebo-controlled, cross-over study. Social cognition was assessed with The Awareness of Social Inference Test (TASIT) and the Reading the Mind in the Eyes Test (RMET). We examined the effects of oxytocin administration on automatic social cognition (the ability to rapidly interpret and understand emotional cues from the voice, face, and body); controlled social cognition (the ability to comprehend indirectly expressed emotions, thoughts, and intentions through complex deliberations over longer time periods); and a control task (the ability to comprehend truthful dialog and perform general task procedures) in individuals with and without schizophrenia using mixed factorial analysis of variance models. RESULTS: Patients with schizophrenia showed significant impairments in automatic and controlled social cognition compared to healthy controls, and administration of oxytocin significantly improved their controlled, but not automatic, social cognition, F(1, 58)=8.75; p=0.004. Conversely, oxytocin administration had limited effects on social cognition in healthy participants. Patients and controls performed equally well and there were no effects of oxytocin administration on the control task. DISCUSSION: Intact social cognitive abilities are associated with better functional outcomes in individuals with schizophrenia. Our data highlight the potentially complex effects of oxytocin on some but not all aspects of social cognition, and support the exploration of intranasal oxytocin as a potential adjunct treatment to improve controlled social cognition in schizophrenia.

Microbial chemical signaling: a current perspective.

Communication among microorganisms is mediated through quorum sensing. The latter is defined as cell-density linked, coordinated gene expression in microbial populations as a response to threshold signal concentrations followed by induction of a synchronized population response. This phenomenon is used by a variety of microbes to optimize their survival in a constantly challenging, dynamic milieu, by correlating individual cellular functions to community-based requirements. The synthesis, secretion, and perception of quorum-sensing molecules and their target response play a pivotal role in quorum sensing and are tightly controlled by complex, multilayered and interconnected signal transduction pathways that regulate diverse cellular functions. Quorum sensing exemplifies interactive social behavior innate to the microbial world that controls features such as, virulence, biofilm maturation, antibiotic resistance, swarming motility, and conjugal plasmid transfer. Over the past two decades, studies have been performed to rationalize bacterial cell-to-cell communication mediated by structurally and functionally diverse small molecules. This review describes the theoretical aspects of cellular and quorum-sensing mechanisms that affect microbial physiology and pathobiology.

Oral health promotion interventions on oral reservoirs of staphylococcus aureus: a systematic review.

The oral cavity serves as a reservoir of Staphylococcus aureus for infection of the lower respiratory tract and cross-infection to other patients. This systematic review was designed to examine the effectiveness of oral health promotion interventions on this pathogen. The PubMed, ISI Web of Science, and Cochrane Library databases were searched for clinical trials assessing the effect of oral health promotion interventions on oral and oropharyngeal carriage of S. aureus. Oral health promotion interventions on oral reservoirs of S. aureus in both systemically healthy and medically compromised groups consisted of oral hygiene interventions only. There was a lack of evidence pertaining to the effectiveness of mechanical oral hygiene interventions against this pathogen. Chlorhexidine delivered in oral hygiene products such as mouthrinses, gels, and sprays appeared to have some utility against S. aureus, although some studies found equivocal effects. There was a dearth of studies investigating the efficacy of other chemical agents. Although many chemical agents contained in oral hygiene products have proven in vitro activity against S. aureus, their clinical effectiveness and potential role as adjuncts or alternative therapies to conventional treatment remain to be confirmed by further high-quality randomized controlled trials.

Clostridium difficile isolates with increased sporulation: emergence of PCR ribotype 002 in Hong Kong.

We identified a predominant clone of Clostridium difficile PCR ribotype 002, which was associated with an increased sporulation frequency. In 2009, 3,528 stool samples from 2,440 patients were tested for toxigenic C. difficile in a healthcare region in Hong Kong. A total of 345 toxigenic strains from 307 (13.3%) patients were found. Ribotype 002 was the predominant ribotype, which constituted 35 samples from 29 (9.4%) patients. The mean sporulation frequency of ribotype 002 was 20.2%, which was significantly higher than that of the 56 randomly selected ribotypes other than 002 as concurrent controls (3.7%, p < 0.001). Patients carrying toxigenic ribotype 002 were more frequently admitted from an elderly home (p = 0.01) and received more ß-lactam antibiotics in the preceding 3 months compared with the controls (p = 0.04) . The identification of toxigenic ribotype 002 in 2009 was temporally related to a significant increase in both the incidence of toxigenic C. difficile from 0.53 to 0.95 per 1,000 admissions (p < 0.001) and the rate of positive detection from 4.17% to 6.28% (p < 0.001) between period 1 (2004-2008) and period 2 (2009). This finding should alert both the physician and the infection control team to the establishment of and possible outbreaks by ribotype 002 in our hospitals, as in the case of ribotype 027.

Bacterial lipopolysaccharides variably modulate in vitro biofilm formation of Candida species.

The objective of this study was to evaluate the effect of the bacterial endotoxin LPS on Candida biofilm formation in vitro. The effect of the LPS of Pseudomonas aeruginosa, Klebsiella pneumoniae, Serratia marcescens and Salmonella typhimurium on six different species of Candida, comprising Candida albicans ATCC 90028, Candida glabrata ATCC 90030, Candida krusei ATCC 6258, Candida tropicalis ATCC 13803, Candida parapsilosis ATCC 22019 and Candida dubliniensis MYA 646, was studied using a standard biofilm assay. The metabolic activity of in vitro Candida biofilms treated with LPS at 90 min, 24 h and 48 h was quantified by XTT reduction assay. Viable biofilm-forming cells were qualitatively analysed using confocal laser scanning microscopy (CLSM), while scanning electron microscopy (SEM) was employed to visualize the biofilm structure. Initially, adhesion of C. albicans was significantly stimulated by Pseudomonas and Klebsiella LPS. A significant inhibition of Candida adhesion was noted for the following combinations: C. glabrata with Pseudomonas LPS, C. tropicalis with Serratia LPS, and C. glabrata, C. parapsilosis or C. dubliniensis with Salmonella LPS (P<0.05). After 24 h of incubation, a significant stimulation of initial colonization was noted for the following combinations: C. albicans/C. glabrata with Klebsiella LPS, C. glabrata/C. tropicalis/C. krusei with Salmonella LPS. In contrast, a significant inhibition of biofilm formation was observed in C. glabrata/C. dubliniensis/C. krusei with Pseudomonas LPS, C. krusei with Serratia LPS, C. dubliniensis with Klebsiella LPS and C. parapsilosis/C. dubliniensis /C. krusei with Salmonella LPS (P<0.05). On further incubation for 48 h, a significant enhancement of biofilm maturation was noted for the following combinations: C. glabrata/C. tropicalis with Serratia LPS, C. dubliniensis with Klebsiella LPS and C. glabrata with Salmonella LPS, and a significant retardation was noted for C. parapsilosis/C. dubliniensis/C. krusei with Pseudomonas LPS, C. tropicalis with Serratia LPS, C. glabrata/C. parapsilosis/C. dubliniensis with Klebsiella LPS and C. dubliniensis with Salmonella LPS (P<0.05). These findings were confirmed by SEM and CLSM analyses. In general, the inhibition of the biofilm development of LPS-treated Candida spp. was accompanied by a scanty architecture with a reduced numbers of cells compared with the profuse and densely colonized control biofilms. These data are indicative that bacterial LPSs modulate in vitro Candida biofilm formation in a species-specific and time-dependent manner. The clinical and the biological relevance of these findings have yet to be explored.

Molecular adsorption onto metallic quantum wires.

We have studied the adsorption of mercaptopropionic acid, 2,2'-bipyridine, and dopamine onto electrochemically fabricated Cu nanowires. The nanowires are atomically thin with conductance quantized near integer multiples of 2e(2)/h. Upon molecular adsorption, the quantized conductance decreases to a fractional value, due to the scattering of the conduction electrons by the adsorbates. The decrease is as high as 50% for the thinnest nanowires whose conductance is at the lowest quantum step, and smaller for thicker nanowires with conductance at higher quantum steps. The adsorbate-induced conductance changes depend on the binding strengths of the molecules to the nanowires, which are in the order of mercaptopropionic acid, 2,2'-bipyridine, and dopamine, from strongest to weakest. The sensitive dependence of the quantized conductance on molecular adsorption may be used for molecular detection.