Severity and impact of accidental bowel leakage two decades after no, one, or two sphincter injuries.

BACKGROUND: Information about the long-term severity and subjective impact of anal incontinence in women after 1 or 2 consecutive obstetrical anal sphincter injuries is still scarce and contradictory. OBJECTIVE: This study aimed to describe the severity and impact of anal incontinence among women with 2 previous deliveries 2 decades after birth and to analyze the relative effect of 1 vs 2 obstetrical anal sphincter injuries in comparison with no obstetrical anal sphincter injuries and the possible influence of obstetrical anal sphincter injury on other pelvic floor disorders. STUDY DESIGN: We linked prospectively registered data in the Swedish Medical Birth Register with information from a postal and web-based questionnaire in 2015. Statistics Sweden identified women with 2 vaginal births from 1992 to 1998, and a simple random sample of 11,000 women was drawn from a source cohort of 64,687 women. To achieve equal-sized groups of women with 1 or 2 obstetrical anal sphincter injuries, the latter group was oversampled from 1987 to 2000. The final study cohorts consisted of 6760 women with no obstetrical anal sphincter injury, 357 women with 1 injury, and 324 women with 2 obstetrical anal sphincter injuries. Third- and fourth-degree perineal tears were grouped together for analysis. Anal incontinence was defined as either fecal or isolated gas incontinence, and fecal incontinence was defined as involuntary leakage of solid or liquid stool with or without concomitant gas. Frequencies of leakage of stool and gas were dichotomized into low frequency (less than once a month) and high frequency (several times a month or more often). Pairwise comparisons were analyzed using Fisher exact tests, Mantel-Haenszel statistics, and the Mann-Whitney U test. Trends were analyzed using Mantel-Haenszel statistics and the Spearman rank correlation test. Logistic regression models were used to obtain the age- and body-mass-index -adjusted odds ratios for outcomes. Statistical significance was set at P<.05. RESULTS: The response rate was 65.5% in the randomly selected cohort and 70.1% among women with 2 obstetrical anal sphincter injuries. Bothersome fecal incontinence occurred in 3.3% (212/6458) of women without obstetrical anal sphincter injury, in 10.4% (36/345) (adjusted odds ratio, 3.25; 95% confidence interval, 2.23-4.73) of those with 1 injury, and in 16.5% (52/315) (adjusted odds ratio, 5.16; 95% confidence interval, 3.69-7.22) of those with 2 obstetrical anal sphincter injuries (trend P<.0001). Fecal incontinence was perceived as bothersome in 28.2% (212/753) of women without an obstetrical anal sphincter injury compared with in 43.9% (36/82) and 46.0% (52/113) of those with 1 or 2 obstetrical anal sphincter injuries (trend P<.0001). Leakage of liquid stool occurred in 10.8% (724/6717) of those without injury, in 21.7% (77/355) of women with 1 injury, and 34.9% (113/324) of women with 2 obstetrical anal sphincter injuries (trend P<.0001). Incontinence affecting daily life was reported by 8.6% (577/6672) of women without injury and by 19.7% (69/351) and 29.6% (96/324) of women with 1 and 2 sphincter injuries, respectively (trend P<.0001). The mean Jorge-Wexner score was 2.44, 3.26, and 3.88 for women with no, 1, or 2 sphincter injuries (trend P<.0001). Among women with a Jorge-Wexner score of 6, >50% had bothersome anal incontinence. The adjusted odds ratio for the overall effect of 1 vs 2 obstetrical anal sphincter injuries on measures of anal incontinence was 2.19 (95% confidence interval, 1.68-2.85) and 3.91 (95% confidence interval, 3.06-5.00), respectively, when compared with no obstetrical anal sphincter injury (both P<.0001). Having 1 or 2 obstetrical anal sphincter injuries had no significant effect on other pelvic floor disorders or on lower urinary tract symptoms (P=.73 and P=.69). CONCLUSION: A consistent additive effect of 1 or 2 sphincter injuries on the severity and impact of anal incontinence was observed in women 2 decades after 2 vaginal births. This information is important for healthcare economics, clinical practice, and policy.

Exposures during pregnancy and at birth are associated with the risk of offspring eating disorders.

BACKGROUND: Eating disorders (ED) are severe psychiatric disorders, commonly debuting early. Aberrances in the intrauterine environment and at birth have been associated with risk of ED. Here, we explore if, and at what effect size, a variety of such exposures associate with offspring ED, that is, anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS). METHODS: This population-based cohort study, conducted from September 2021 to August 2023, used Finnish national registries of all live births in 1996-2014 (N = 1,097,753). Cox proportional hazards modeling was used to compare ED risk in exposed versus unexposed offspring, adjusting for potential confounders and performing sex-stratified analyses. RESULTS: A total of 6614 offspring were diagnosed with an ED; 3668 AN, 666 BN, and 4248 EDNOS. Lower risk of offspring AN was seen with young mothers, continued smoking, and instrumental delivery, while higher risk was seen with older mothers, inflammatory disorders, prematurity, small for gestational age, and low Apgar. Offspring risk of BN was higher with continued smoking and prematurity, while lower with postmature birth. Offspring risk of EDNOS was lower with instrumental delivery, higher for older mothers, polycystic ovary syndrome, insulin-treated pregestational diabetes, antibacterial treatment, prematurity, and small for gestational age. Sex-specific associations were found. CONCLUSIONS: Several prenatal and at birth exposures are associated with offspring ED; however, we cannot exclude confounding by maternal BMI. Nevertheless, several exposures selectively associate with risk of either AN, BN, or EDNOS, and some are sex-specific, emphasizing the importance of subtype- and sex-stratified analyses of ED. PUBLIC SIGNIFICANCE: We define environmental factors involved in the development of different ED, of importance as preventive measure, but also in order to aid in defining the molecular pathways involved and thus in the longer perspective contribute to the development of pharmacological treatment of ED.

GRK3 deficiency elicits brain immune activation and psychosis.

The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3-/- mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1ß, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3-/- mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders.

Fecal incontinence in nonpregnant nulliparous women aged 25 to 64 years-a randomly selected national cohort prevalence study.

BACKGROUND: The extent to which fecal incontinence is associated with obstetrical history or pelvic floor injuries is still a controversial and unresolved issue. One crucial first step toward answering this question is the need to study fecal incontinence in nonpregnant, nulliparous women. OBJECTIVE: The aim of this study was to present detailed, descriptive measures of the accidental leakage of liquid or solid stool and gas in a randomly selected, large national cohort of nonpregnant, nulliparous women aged 25 to 64 years. STUDY DESIGN: The Swedish Total Population Register identified the source population. Four independent, age-stratified, simple random samples in a total of 20,000 nulliparous women aged 25 to 64 years were drawn from 625,810 eligible women. Information was collected in 2014 using postal and web-based questionnaires. The 40-item questionnaire included questions about the presence and frequency of the leakage of solid and liquid stool and gas, which provided the basis for the generic terms fecal and anal incontinence. Statistical analyses of the differences between the groups were performed using the Fisher's exact test for dichotomous variables and the Mann-Whitney U-test for continuous variables. The trend between >2 ordered categories of dichotomous variables was analyzed with Mantel-Haenszel statistics. When analyzing the trend between multiple ordered vs nonordered categorical variables, the Kruskal-Wallis test was used. The age-related probability and risk increase per 10 years for incontinence parameters was calculated from logistic regression models adjusted for body mass index. RESULTS: The study population was 9197 women, and the response rate was 52.2%, ranging from 44.7% in women aged 25 to 34 years to 62.4% among those from 55 to 64 years. All the types of incontinence, except severe isolated gas incontinence, increased with age up to 64 years. The estimated probability of fecal incontinence was 8.8% at age 25 years and 17.6% at age 64. The leakage of liquid stool was dominant, occurring in 93.1% (95% confidence interval, 91.4-94.5) of the women with fecal incontinence, whereas leakage of solid stool occurred in 33.9% (95% confidence interval, 31.1-36.7), of which approximately 80% also had concomitant leakage of liquid stool. The leakage of liquid stool increased markedly up to age 65, whereas the increase in the isolated leakage of solid stool was negligible across all ages (overall <0.4%). Liquid and solid stool, separate or in combination, co-occurred with gas in approximately 80%. The distribution pattern of the different types of leakage, single or combined, was similar in all the age groups. Both age and body mass index (kg/m2) were risk factors for fecal incontinence (P<.0001), with an interaction effect of P=.16. CONCLUSION: Abnormal stool consistency has been identified as the strongest risk factor for accidental bowel leakage. The same pattern characterized by a dominance of liquid stool and gas leakage, prevalent concomitant leakage of solid and liquid stool, and a negligible rate of isolated leakage of solid feces was observed across all ages. The low rates of isolated leakage of solid stool support the impression that dysfunction of the continence mechanism of the pelvic floor had a negligible role for bowel incontinence, which is essential information for comparison with women with birth-related injuries.

Symptoms of fecal incontinence two decades after no, one, or two obstetrical anal sphincter injuries.

BACKGROUND: The long-term effects of 1 or 2 consecutive obstetrical anal sphincter injuries on bowel continence are still inadequately investigated, and published results remain contradictory. OBJECTIVE: This study aimed to present detailed descriptive measures of the current bowel incontinence 20 years after the first birth in women who had 2 vaginal deliveries with and without sphincter injuries. STUDY DESIGN: Birth register data were used prospectively and linked to information from a questionnaire survey about current symptoms. Women with 2 singleton vaginal births, from 1992 to 1998, and no further births were retrieved and surveyed by the Swedish Medical Birth Register and Statistics Sweden in 2015. A simple random sample of 11,000 women was drawn from a source cohort of 64,687 women. The cumulative effect was studied in all women with a repeat sphincter injury from 1987 to 2000. Postal and web-based questionnaires were used. The study population consisted of 6760 women with no sphincter injury, 357 with 1 sphincter injury, and 324 women with 2 sphincter injuries. Women with 2 deliveries without sphincter injuries aged 40 to 60 years as reference, were compared with those of women that sustained 1 or 2 consecutive sphincter injuries. Here, third- and fourth-degree perineal tears were presented as 1 group. Fecal incontinence was defined as current involuntary leakage of solid or liquid stool, with and without concomitant leakage of gas. The Fisher exact test and the Mann-Whitney U test were used to compare the results of the 2 groups. The trend was analyzed using the Mantel-Haenszel statistics. Logistic regression models obtained the estimated age-related probability of fecal incontinence components. RESULTS: The risk of sphincter injury at first delivery was 3.9%, and the risk of a repeat sphincter injury was 10.0% (odds ratio, 2.70; 95% confidence interval, 1.80-4.07). The overall prevalence of fecal incontinence in women without sphincter injuries was 11.7%, which doubled to 23.8% (odds ratio, 2.27; 95% confidence interval, 1.75-2.94) in those with 1 sphincter injury and more than tripled to 36.1% (odds ratio, 3.97; 95% confidence interval, 3.11-5.07) after 2 sphincter injuries (trend P<.0001). The proportion of women with severe fecal incontinence increased 3-fold and 5-fold from 1.8% after no obstetrical anal sphincter injury to 5.4% (95% confidence interval, 3.3-8.2) and 9.0% (95% confidence interval, 6.1-12.6) after 1 or 2 obstetrical anal sphincter injuries, respectively (trend P<.0001). In women without sphincter injuries, the estimated probability of fecal incontinence increased from 7.0% at the age of 40 years to 19.8% at the age of 60 years. In contrast, in women with 1 or 2 sphincter injuries, the estimated probability of fecal incontinence increased from 26.1% and 33.3%, respectively, at the age of 40 years to 36.8% and 48.8% at the age of 60 years. The prevalence of fecal incontinence increased after 52 years of age in women with 1 or 2 sphincter injuries. The dominant types of leakage in women with fecal incontinence were the combination of liquid stool and gas, and the triple combination consisting of solid and liquid stools and gas. The triple combination increased from 18.9% in those without sphincter injury to 28.2% in women with 2 injuries (trend P=.0204). CONCLUSION: The risk of sustaining a repeat sphincter injury at the second delivery was almost tripled compared with the risk at the first delivery. Furthermore, 1 or 2 sphincter injuries brought severe long-term consequences for bowel continence. Accidental leakage of stool and gas increased with each sphincter injury, and the effect was proportionally cumulative. After the age of 52 years, the prevalence of fecal incontinence seemed to accelerate.

Temporal trends in obstetric anal sphincter injury from the first vaginal delivery in Austria, Canada, Norway, and Sweden.

INTRODUCTION: Obstetric anal sphincter injuries (OASI) are severe complications that can cause considerable short- and long-term morbidity. Austria, Canada, Norway, and Sweden have similar socio-economic characteristics, and all four countries have access to national birth registers. In this study, we hypothesized that the incidence of OASI should be very similar for different obstetric scenarios in these four countries. Therefore, the aim was to compare the incidence of OASI in these four countries in primiparous women, with spontaneous or instrumental delivery (vacuum or forceps), and in women with a first vaginal birth after cesarean section (VBAC). MATERIAL AND METHODS: Aggregated data on 1 933 930 vaginally delivered primiparous women and women with VBAC were retrieved from the birth registers gathered in Austria, Canada, Norway, and Sweden. The annual rate of OASI (ICD-10 codes O70.2-O70.3) was presented as the percentage of women with a spontaneous delivery, vacuum or forceps delivery, and a VBAC during the period 2004-2016. RESULTS: The incidence of OASI varied considerably between countries and over time. Canada and Sweden had the highest rates, and Austria and Norway the lowest. In Norway, the rate of OASI decreased consistently for all types of deliveries after introducing a perineal protection program in 2004 (p < 0.001). During vacuum delivery, the incidence of OASI varied between countries from 4.1% to 15.5% across the study period. In Canada and Norway, the rate of OASI after a forceps delivery was similar in 2004 at ~20% and with differing trajectories to 24.3% (ß 0.49) and 6.2% (ß -1.15) (trend, all p < 0.001) in 2016. CONCLUSIONS: This comparative register study suggests that there may be considerable potential for lowering the incidence of OASI. The perineal protection program implemented by Norway has been successful. Each country should critically, without prejudice, analyze their current clinical practices and rate of OASI and consider the best preventive strategy.

Aberrant inflammatory profile in acute but not recovered anorexia nervosa.

Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality and relapse rates. Even though changes in inflammatory markers and cytokines are known to accompany cachexia associated with somatic disorders such as cancer and chronic kidney disorder, studies on inflammatory markers in AN are rare and typically include few individuals. Here, we utilize an Olink Proteomics inflammatory panel to explore the concentrations of 92 preselected inflammation-related proteins in plasma samples from women with active AN (N = 113), recovered from AN (AN-REC, N = 113), and normal weight healthy controls (N = 114). After correction for multiple testing, twenty-five proteins differed significantly between the AN group and controls (lower levels: ADA, CCL19, CD40, CD5, CD8A, CSF1, CXCL1, CXCL5, HGF, IL10RB, IL12B, 1L18R1, LAP TGFß1, MCP3, OSM, TGFα, TNFRSF9, TNFS14 and TRANCE; higher levels: CCL11, CCL25, CST5, DNER, LIFR and OPG). Although more than half of these differences (N = 15) were present in the comparison between AN and AN-REC, no significant differences were seen between AN-REC and controls. Furthermore, twenty-five proteins correlated positively with BMI (ADA, AXIN1, CASP8, CD5, CD40, CSF1, CXCL1, CXCL5, EN-RAGE, HGF, IL6, IL10RB, IL12B, IL18, IL18R1, LAP TGFß1, OSM, SIRT2, STAMBP, TGFα, TNFRSF9, TNFS14, TRANCE, TRAIL and VEGFA) and four proteins correlated negatively with BMI (CCL11, CCL25, CCL28 and DNER). These results suggest that a dysregulated inflammatory status is associated with AN, but, importantly, seem to be confined to the acute illness state.

Hypothalamic Structural and Functional Imbalances in Anorexia Nervosa.

The hypothalamus contains integrative systems that support life, including physiological processes such as food intake, energy expenditure, and reproduction. Here, we show that anorexia nervosa (AN) patients, contrary to normal weight and constitutionally lean individuals, respond with a paradoxical reduction in hypothalamic levels of glutamate/glutamine (Glx) upon feeding. This reversal of the Glx response is associated with decreased wiring in the arcuate nucleus and increased connectivity in the lateral hypothalamic area, which are involved in the regulation on a variety of physiological and behavioral functions including the control of food intake and energy balance. The identification of distinct hypothalamic neurochemical dysfunctions and associated structural variations in AN paves the way for the development of new diagnostic and treatment strategies in conditions associated with abnormal body mass index and a maladaptive response to negative energy balance.

Epigenetic regulation of the cannabinoid receptor CB1 in an activity-based rat model of anorexia nervosa.

OBJECTIVE: Both environmental and genetic factors are known to contribute to the development of anorexia nervosa (AN), but the exact etiology remains poorly understood. Herein, we studied the transcriptional regulation of the endocannabinoid system, an interesting target for body weight maintenance and the control of food intake and energy balance. METHOD: We used two well-characterized animal models of AN: (a) the activity-based anorexia (ABA) model in which rats, housed with running wheels and subjected to daily food restriction, show reductions in body weight and increase in physical activity; (b) the genetic anx/anx mouse displaying the core features of AN: low food intake and emaciation. RESULTS: Among the evaluated endocannabinoid system components, we observed a selective and significant down-regulation of the gene encoding for the type 1 cannabinoid receptor (Cnr1) in ABA rats' hypothalamus and nucleus accumbens and, in the latter area, a consistent, significant and correlated increase in DNA methylation at the gene promoter. No changes were evident in the anx/anx mice except for a down-regulation of Cnr1, in the prefrontal cortex. DISCUSSION: Our findings support a possible role for Cnr1 in the ABA animal model of AN. In particular, its regulation in the nucleus accumbens appears to be triggered by environmental cues due to the consistent epigenetic modulation of the promoter. These data warrant further studies on Cnr1 regulation as a possible target for treatment of AN.

The symptom of vaginal bulging in nulliparous women aged 25-64 years: a national cohort study.

INTRODUCTION AND HYPOTHESIS: Vaginal bulging is considered the key symptom for genital organ prolapse. The aim was to investigate the age-related prevalence and frequency of symptomatic pelvic organ prolapse (sPOP) and other pelvic floor symptoms in nonpregnant nullipara aged 25-64 years. METHODS: This national postal and web-based questionnaire survey was conducted in 2014 and included four independent random samples of women aged 25-34, 35-44, 45-54, and 55-64 years. The association of sPOP with demographics and with other pelvic floor conditions and with clustering to other pelvic floor conditions, was presented in women with and without sPOP. Logistic regression was used to identify and rank variables associated with symptomatic prolapse. RESULTS: The response rate was 52% (n = 10,187) and 726 nullipara confirmed sPOP. Women with sPOP were younger (p < 0.001), shorter (p < 0.001), and more often overweight and obese (p < 0.01) compared with asymptomatic women. Previous surgery for prolapse was reported by 15 women only (0.16%). Symptomatic POP decreased from 9.8% in the youngest age group (25-34 years) to 6.1% in the oldest (55-64 years) (p < 0.0001). Symptomatic POP was more often experienced as bothersome (p = 0.012), and aggravated by straining and heavy lifting (p = 0.003), in older women. Vaginal/vulval chafing/rubbing feeling was most prevalent among the youngest 14.2%, decreasing to 7.8% among the oldest (<0.0001). This symptom occurred three to five times more often in those with sPOP (p < 0.0001). Clustering of pelvic floor symptoms was four times more prevalent in women with sPOP (23.2% versus 6.1%) (p < 0.0001). CONCLUSIONS: The high prevalence of sPOP in this study was contradictory to most earlier reports, which have shown that genital prolapse is rare in nullipara. The explanation of our results may be the low probability of the clinical condition, the dominance of weak and infrequent symptoms, and not least clustering of alternative conditions mimicking sPOP.

The Science Behind the Academy for Eating Disorders' Nine Truths About Eating Disorders.

OBJECTIVE: In 2015, the Academy for Eating Disorders collaborated with international patient, advocacy, and parent organizations to craft the 'Nine Truths About Eating Disorders'. This document has been translated into over 30 languages and has been distributed globally to replace outdated and erroneous stereotypes about eating disorders with factual information. In this paper, we review the state of the science supporting the 'Nine Truths'. METHODS: The literature supporting each of the 'Nine Truths' was reviewed, summarized and richly annotated. RESULTS: Most of the 'Nine Truths' arise from well-established foundations in the scientific literature. Additional evidence is required to further substantiate some of the assertions in the document. Future investigations are needed in all areas to deepen our understanding of eating disorders, their causes and their treatments. CONCLUSIONS: The 'Nine Truths About Eating Disorders' is a guiding document to accelerate global dissemination of accurate and evidence-informed information about eating disorders. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Long-term effects of vacuum extraction on pelvic floor function: a cohort study in primipara.

INTRODUCTION AND HYPOTHESIS: We describe the prevalence of symptomatic pelvic organ prolapse (sPOP), urinary incontinence (UI), fecal incontinence (FI) and obstetric anal sphincter injury (OASI) 20 years after one vacuum extraction (VE) delivery compared with one spontaneous vaginal delivery (SVD) or one acute caesarean section (ACS). METHOD: We performed a register-based national cohort study of primipara who delivered between 1985 and 1988 and had no further deliveries. Medical Birth Register data were linked to data from postal questionnaires distributed 20 years after the birth (response rate 65.2 %, n = 5 236). Main outcome measures were prevalence and risk factors for pelvic floor disorders (PFDs) and OASI and their impact after VE compared with SVD and ACS. Multivariate logistic regression models were used. RESULTS: The late prevalence of UI, sPOP, and FI was almost identical between VE and SVD. VE almost tripled the rate of OASI compared with SVD (6.3 vs. 2.4 %, p < 0.001). FI rate after an OASI was similar for both VE and SVD [30.2 vs. 27.8 %, adjusted odds ratio (aOR) 1.12; 95 % confidence interval (CI) 0.49-2.56]. Comparing VE without laceration with VE complicated by OASI increased the rate of FI (from 15.4 to 30.2 %, aOR 2.55; 95 % CI 1.26-5.15) and UI (from 39.0 to 61.4 %, aOR 2.28; 95 % CI 1.19-4.34), but the rate of sPOP was almost unaltered (from 15.0 to 15.9 %). CONCLUSIONS: VE did not result in additional long-term PFDs provided the rate of OASI was similar to that after SVD. OASI after VE substantially increased the prevalence of FI and UI but did not alter the rate of sPOP.

Glucose intolerance and pancreatic ß-cell dysfunction in the anorectic anx/anx mouse.

Inflammation and impaired mitochondrial oxidative phosphorylation are considered key players in the development of several metabolic disorders, including diabetes. We have previously shown inflammation and mitochondrial dysfunction in the hypothalamus of an animal model for anorexia, the anx/anx mouse. Moreover, increased incidence of eating disorders, e.g., anorexia nervosa, has been observed in diabetic individuals. In the present investigation we evaluated whether impaired mitochondrial phosphorylation and inflammation also occur in endocrine pancreas of anorectic mice, and if glucose homeostasis is disturbed. We show that anx/anx mice exhibit marked glucose intolerance associated with reduced insulin release following an intraperitoneal injection of glucose. In contrast, insulin release from isolated anx/anx islets is increased after stimulation with glucose or KCl. In isolated anx/anx islets there is a strong downregulation of the mitochondrial complex I (CI) assembly factor, NADH dehydrogenase (ubiquinone) 1α subcomplex, assembly factor 1 (Ndufaf1), and a reduced CI activity. In addition, we show elevated concentrations of free fatty acids (FFAs) in anx/anx serum and increased macrophage infiltration (indicative of inflammation) in anx/anx islets. However, isolated islets from anx/anx mice cultured in the absence of FFAs do not exhibit increased inflammation. We conclude that the phenotype of the endocrine pancreas of the anx/anx mouse is characterized by increased levels of circulating FFAs, as well as inflammation, which can inhibit insulin secretion in vivo. The anx/anx mouse may represent a useful tool for studying molecular mechanisms underlying the association between diabetes and eating disorders.

Isolation of novel IncA/C and IncN fluoroquinolone resistance plasmids from an antibiotic-polluted lake.

OBJECTIVES: Antibiotic-polluted environments may function as reservoirs for novel resistance plasmids not yet encountered in pathogens. The aims of this study were to assess the potential of resistance transfer between bacteria from such environments and Escherichia coli, and to characterize the conjugative elements involved. METHODS: Sediment samples from Kazipally lake and Asanikunta tank, two Indian lakes with a history of severe pollution with fluoroquinolones, were investigated. Proportions of resistant bacteria were determined by selective cultivation, while horizontal gene transfer was studied using a GFP-tagged E. coli as recipient. Retrieved transconjugants were tested for susceptibility by Etest(®) and captured conjugative resistance elements were characterized by WGS. RESULTS: The polluted lakes harboured considerably higher proportions of ciprofloxacin-resistant and sulfamethoxazole-resistant bacteria than did other Indian and Swedish lakes included for comparison (52% versus 2% and 60% versus 7%, respectively). Resistance plasmids were captured from Kazipally lake, but not from any of the other lakes; in the case of Asanikunta tank because of high sediment toxicity. Eight unique IncA/C and IncN resistance plasmids were identified among 11 sequenced transconjugants. Five plasmids were fully assembled, and four of these carried the quinolone resistance gene qnrVC1, which has previously only been found on chromosomes. Acquired resistance genes, in the majority of cases associated with class 1 integrons, could be linked to decreased susceptibility to several different classes of antibiotics. CONCLUSIONS: Our study shows that environments heavily polluted with antibiotics contain novel multiresistance plasmids transferrable to E. coli.

Hypothalamic mitochondrial dysfunction associated with anorexia in the anx/anx mouse.

The anorectic anx/anx mouse exhibits disturbed feeding behavior and aberrances, including neurodegeneration, in peptidergic neurons in the appetite regulating hypothalamic arcuate nucleus. Poor feeding in infants, as well as neurodegeneration, are common phenotypes in human disorders caused by dysfunction of the mitochondrial oxidative phosphorylation system (OXPHOS). We therefore hypothesized that the anorexia and degenerative phenotypes in the anx/anx mouse could be related to defects in the OXPHOS. In this study, we found reduced efficiency of hypothalamic OXPHOS complex I assembly and activity in the anx/anx mouse. We also recorded signs of increased oxidative stress in anx/anx hypothalamus, possibly as an effect of the decreased hypothalamic levels of fully assembled complex I, that were demonstrated by native Western blots. Furthermore, the Ndufaf1 gene, encoding a complex I assembly factor, was genetically mapped to the anx interval and found to be down-regulated in anx/anx mice. These results suggest that the anorexia and hypothalamic neurodegeneration of the anx/anx mouse are associated with dysfunction of mitochondrial complex I.

Multispecies synbiotics alleviate dextran sulfate sodium (DSS)-induced colitis: Effects on clinical scores, intestinal pathology, and plasma biomarkers in male and female mice.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the gastrointestinal tract and has been linked to an imbalance in gut bacteria. Synbiotics, which combine probiotics and prebiotics, are emerging as potential IBD treatments. AIM: To examine the effects of four synbiotic formulations on intestinal inflammation and peripheral biomarkers in a rodent IBD model of both sexes. METHODS: Colitis was induced in male and female C57BL/6 mice using 1% dextran sulfate sodium (DSS). Concurrently, a non-exposed control group was maintained. Starting on day 4 post-induction, DSS-exposed mice received one of four synbiotic preparations (Synbio1-4 composed of lactic acid bacteria, Bifidobacterium and dietary fibres), an anti-inflammatory drug used to treat IBD (mesalazine), or placebo (water) until day 14. Clinical symptoms and body weight were monitored daily. Blood samples (taken on days -3, 4, and 14, relative to DSS introduction), were used to analyze plasma biomarkers. At the end of the study, intestinal tissues underwent histological and morphological evaluation. RESULTS: Compared to placebo, the Synbio1-, 2- and 3-treated groups had improved clinical scores by day 14. Synbio1 was the only preparation that led to clinical improvements to scores comparable to those of controls. The Synbio1-and 3-treated groups also demonstrated histological improvements in the colon. Plasma biomarker analyses revealed significant Synbio1-induced changes in plasma IL17A, VEGFD, and TNFRSF11B levels that correlated with improved clinical or histological scores. Sex-stratified analyses revealed that most therapeutic-like effects were more pronounced in females. CONCLUSION: Our findings underscore the potential therapeutic benefits of specific synbiotics for IBD management. However, further research is needed to validate these outcomes in human subjects.

Identification of State Markers in Anorexia Nervosa: Replication and Extension of Inflammation-Associated Biomarkers Using Multiplex Profiling.

Background: Proteomics offers potential for detecting and monitoring anorexia nervosa (AN) and its variant, atypical AN (atyp-AN). However, research has been limited by small protein panels, a focus on adult AN, and lack of replication. Methods: In this study, we performed Olink multiplex profiling of 92 inflammation-related proteins in females with AN/atyp-AN (n = 64), all of whom were ≤90% of expected body weight, and age-matched healthy control individuals (n = 44). Results: Five proteins differed significantly between the primary AN/atyp-AN group and the healthy control group (lower levels: HGF, IL-18R1, TRANCE; higher levels: CCL23, LIF-R). The expression levels of 3 proteins (lower IL-18R1, TRANCE; higher LIF-R) were uniquely disrupted in participants with AN in our primary model. No unique expression levels emerged for atyp-AN. In the total sample, 12 proteins (ADA, CD5, CD6, CXCL1, FGF-21, HGF, IL-12B, IL18, IL-18R1, SIRT2, TNFSF14, TRANCE) were positively correlated with body mass index and 5 proteins (CCL11, FGF-19, IL8, LIF-R, OPG) were negatively correlated with body mass index in our primary models. Conclusions: Our results replicate the results of a previous study that demonstrated a dysregulated inflammatory status in AN and extend those results to atyp-AN. Of the 17 proteins correlated with body mass index, 11 were replicated from a previous study that used similar methods, highlighting the promise of inflammatory protein expression levels as biomarkers of AN disease monitoring. Our findings underscore the complexity of AN and atyp-AN by highlighting the inability of the identified proteins to differentiate between these 2 subtypes, thereby emphasizing the heterogeneous nature of these disorders.

We examined 73 inflammation proteins in adolescent girls with anorexia nervosa (AN) and atypical AN and compared them with age-matched healthy control girls. Significant differences were found, driven by 5 key proteins (lower: HGF, IL-18R1, TRANCE; higher: CCL23, LIF-R). Three proteins (TRANCE, LIF-R, IL-18R1) uniquely distinguished low-weight participants with AN from control participants. Our study reveals distinct inflammation patterns in AN and atypical AN and sheds light on potential state-specific factors that underlie these disorders.

Occupational balance in parents of pre-school children: Potential differences between mothers and fathers.

BACKGROUND: Parents of young children are a vulnerable group with an increased risk of stress-related health problems compared to adults without children. Low occupational balance has been identified as a risk factor for stress-related disorders. AIM: The study aimed to describe occupational balance in parents of pre-school children and to explore potential differences between mothers and fathers. METHOD: Data were collected by a web-based survey based on the Occupational Balance Questionnaire (OBQ11). A total of 302 working parents (200 mothers and 102 fathers) with at least one child under seven years of age were included in the study. FINDINGS: Mothers reported lower occupational balance than fathers with a median value of 10 for mothers and 12 for fathers (p = 0.029). Mothers rated significantly lower than fathers in three items; 'Balance between work, home, family, leisure, rest and sleep', 'Having sufficient time for doing obligatory occupations' and 'Balance between doing things for others and for oneself'. CONCLUSION: The results indicate that caring for pre-school children may negatively impact both parents, impacting mothers' occupational balance to a greater degree. SIGNIFICANCE: Occupational therapists' knowledge could be utilised to increase awareness of the importance of occupational balance within health services and improve mothers' occupational balance.

Effects of a Synbiotic on Plasma Immune Activity Markers and Short-Chain Fatty Acids in Children and Adults with ADHD-A Randomized Controlled Trial.

Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota-gut-brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1ß-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels.