A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia.

The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (ß-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.

The role of diet quality and dietary patterns in predicting muscle mass and function in men over a 15-year period.

A growing body of evidence suggests that diet quality may predict muscle health. This study found that a "Traditional" dietary pattern predicted greater muscle mass, and an anti-inflammatory diet predicted greater muscle mass and better muscle function over 15 years. These findings reinforce the importance of optimising dietary behaviours for healthy ageing. INTRODUCTION: Research investigating the roles of individual nutrients in muscle health fails to account for the synergistic relationships between foods and nutrients. This study aimed to investigate the predictive value of diet quality and dietary patterns for muscle mass and function in men over a 15-year period. METHODS: This longitudinal study was conducted in 522 men from the Geelong Osteoporosis Study with complete dietary and muscle mass or muscle function data at both baseline and 15-year follow-up assessments. Dietary exposures were extracted from food frequency questionnaires and included the Australian Recommended Food Score, the Dietary Inflammatory Index (DII®), and three a posteriori dietary patterns: Plant-focused, Western, and Traditional (Anglo-Australian). Outcome variables included dual-energy X-ray absorptiometry-derived skeletal muscle index (SMI) and muscle function measured with the timed up-and-go (TUG) test. RESULTS: An anti-inflammatory diet and higher scores on a Traditional dietary pattern both predicted greater SMI ((B: -0.04 (95%CI -0.08, -0.00) kg/m2) and (B: 0.12 (95%CI 0.04, 0.20) kg/m2), respectively), while a pro-inflammatory diet predicted slower TUG (B: 0.11 (95%CI 0.001, 0.21) sec) over the 15-year follow-up period. These associations remained significant following adjustment for confounding variables. There were no associations observed for other dietary exposures. CONCLUSION: A Traditional dietary pattern higher in vegetables, wholegrain cereals, and animal protein was associated with greater skeletal muscle mass, and an anti-inflammatory diet, also rich in vegetables, fruit, and wholegrain cereals, was associated with greater skeletal muscle mass and better muscle function over 15 years.

The association between higher maternal pre-pregnancy body mass index and increased birth weight, adiposity and inflammation in the newborn.

BACKGROUND: Excess adiposity and adiposity-related inflammation are known risk factors for cardiovascular disease in adults; however, little is known regarding the determinants of adiposity-related inflammation at birth. OBJECTIVES: The aim of this study was to investigate the association between maternal pre-pregnancy BMI and newborn adiposity and inflammation. METHODS: Paired maternal (28-week gestation) and infant (umbilical cord) blood samples were collected from a population-derived birth cohort (Barwon Infant Study, n = 1074). Data on maternal comorbidities and infant birth anthropomorphic measures were compiled, and infant aortic intima-media thickness was measured by trans-abdominal ultrasound. In a selected subgroup of term infants (n = 161), matched maternal and cord lipids, high-sensitivity C-reactive protein (hsCRP) and maternal soluble CD14 were measured. Analysis was completed by using pairwise correlation and linear regression. Because of their non-normal distribution, pathology blood measures were log transformed prior to analysis. RESULTS: Maternal pre-pregnancy BMI was positively associated with increased birth weight (mean difference 17.8 g per kg m-2 , 95% CI 6.6 to 28.9; p = 0.002), newborn mean skin-fold thickness (mean difference 0.1 mm per kg m-2 , 95% CI 0.0 to 0.1; p < 0.001) and cord blood hsCRP (mean difference of 4.2% increase in hsCRP per kg m-2 increase in pre-pregnancy BMI, 95% CI 0.6 to 7.7%, p = 0.02), but not cord blood soluble CD14. Inclusion of maternal hsCRP as a covariate attenuated the associations between pre-pregnancy BMI and both newborn skin-fold thickness and cord blood hsCRP. CONCLUSION: Higher maternal pre-pregnancy BMI is associated with increased newborn adiposity and inflammation. These associations may be partially mediated by maternal inflammation during pregnancy.

Vitamin D insufficiency in the first 6 months of infancy and challenge-proven IgE-mediated food allergy at 1 year of age: a case-cohort study.

BACKGROUND: Ecological evidence suggests vitamin D insufficiency (VDI) due to lower ambient ultraviolet radiation (UVR) exposure may be a risk factor for IgE-mediated food allergy. However, there are no studies relating directly measured VDI during early infancy to subsequent challenge-proven food allergy. OBJECTIVE: To prospectively investigate the association between VDI during infancy and challenge-proven food allergy at 1 year. METHODS: In a birth cohort (n = 1074), we used a case-cohort design to compare 25-hydroxyvitamin D3 (25(OH)D3 ) levels among infants with food allergy vs a random subcohort (n = 274). The primary exposures were VDI (25(OH)D3 <50 nM) at birth and 6 months of age. Ambient UVR and time in the sun were combined to estimate UVR exposure dose. IgE-mediated food allergy status at 1 year was determined by formal challenge. Binomial regression was used to examine associations between VDI, UVR exposure dose and food allergy and investigate potential confounding. RESULTS: Within the random subcohort, VDI was present in 45% (105/233) of newborns and 24% (55/227) of infants at 6 months. Food allergy prevalence at 1 year was 7.7% (61/786), and 6.5% (53/808) were egg-allergic. There was no evidence of an association between VDI at either birth (aRR 1.25, 95% CI 0.70-2.22) or 6 months (aRR 0.93, 95% CI 0.41-2.14) and food allergy at 1 year. CONCLUSIONS: There was no evidence that VDI during the first 6 months of infancy is a risk factor for food allergy at 1 year of age. These findings primarily relate to egg allergy, and larger studies are required.

[Psychology and sexology are essential, from diagnosis to comprehensive care of endometriosis]. / Psychologie et sexologie : une approche essentielle, du diagnostic à la prise en charge globale de l'endométriose.

Endometriosis, defined by the presence of endometrial tissue outside the uterine cavity, is a common but often under diagnosed pathology. The clinical manifestations are varied (chronic pelvic pain, urinary or gastrointestinal symptoms) and can sometimes be very frustrated, delaying the diagnosis. This delay in diagnosis can be a high source of stress responsible for an important psychological impact in these patients, having a sense of misunderstanding and neglect of the medical profession. This climate of stress and anxiety can cause alteration of behavior including sexual disorders. In addition, endometriosis can be revealed as part of an infertility evaluation, and the patient and the couple can already be affected by this situation. The clinical and psychological impact of endometriosis inevitably leads to an impairment of patient's quality of life and sexuality. The objective of this article is to show the psychological consequences of endometriosis and its impact on sexuality, in order to highlight this essential aspect for a comprehensive care of patients.

The effects of maternal anxiety during pregnancy on IGF2/H19 methylation in cord blood.

Compelling evidence suggests that maternal mental health in pregnancy can influence fetal development. The imprinted genes, insulin-like growth factor 2 (IGF2) and H19, are involved in fetal growth and each is regulated by DNA methylation. This study aimed to determine the association between maternal mental well-being during pregnancy and differentially methylated regions (DMRs) of IGF2 (DMR0) and the IGF2/H19 imprinting control region (ICR) in newborn offspring. Maternal depression, anxiety and perceived stress were assessed at 28 weeks of pregnancy in the Barwon Infant Study (n=576). DNA methylation was measured in purified cord blood mononuclear cells using the Sequenom MassArray Platform. Maternal anxiety was associated with a decrease in average ICR methylation (Δ=-2.23%; 95% CI=-3.68 to -0.77%), and across all six of the individual CpG units in anxious compared with non-anxious groups. Birth weight and sex modified the association between prenatal anxiety and infant methylation. When stratified into lower (⩽3530 g) and higher (>3530 g) birth weight groups using the median birth weight, there was a stronger association between anxiety and ICR methylation in the lower birth weight group (Δ=-3.89%; 95% CI=-6.06 to -1.72%), with no association in the higher birth weight group. When stratified by infant sex, there was a stronger association in female infants (Δ=-3.70%; 95% CI=-5.90 to -1.51%) and no association in males. All the linear regression models were adjusted for maternal age, smoking and folate intake. These findings show that maternal anxiety in pregnancy is associated with decreased IGF2/H19 ICR DNA methylation in progeny at birth, particularly in female, low birth weight neonates. ICR methylation may help link poor maternal mental health and adverse birth outcomes, but further investigation is needed.

Citalopram and sertraline exposure compromises embryonic bone development.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression and, as a class of drugs, are among the most used medications in the world. Concern regarding possible effects of SSRI treatment on fetal development has arisen recently as studies have suggested a link between maternal SSRI use and an increase in birth defects such as persistent pulmonary hypertension, seizures and craniosynostosis. Furthermore, SSRI exposure in adults is associated with decreased bone mineral density and increased fracture risk, and serotonin receptors are expressed in human osteoblasts and osteoclasts. To determine possible effects of SSRI exposure on developing bone, we treated both zebrafish, during embryonic development, and human mesenchymal stem cells (MSCs), during differentiation into osteoblasts, with the two most prescribed SSRIs, citalopram and sertraline. SSRI treatment in zebrafish decreased bone mineralization, visualized by alizarin red staining and decreased the expression of mature osteoblast-specific markers during embryogenesis. Furthermore, we showed that this inhibition was not associated with increased apoptosis. In differentiating human MSCs, we observed a decrease in osteoblast activity that was associated with a decrease in expression of the osteoblast-specific genes Runx2, Sparc and Spp1, measured with quantitative real-time PCR (qRT-PCR). Similar to the developing zebrafish, no increase in expression of the apoptotic marker Caspase 3 was observed. Therefore, we propose that SSRIs inhibit bone development by affecting osteoblast maturation during embryonic development and MSC differentiation. These results highlight the need to further investigate the risks of SSRI use during pregnancy in exposing unborn babies to potential skeletal abnormalities.

[How to manage a woman with a sexual complaint in clinical practice?]. / En pratique, comment faire devant une femme exprimant une plainte sexuelle?

OBJECTIVE: To describe the main female sexual dysfunctions, their mechanisms, and the broad outlines of their therapeutic management. MATERIAL AND METHODS: Review of consensus conferences and published guidelines on this subject and a reflexion from our own clinical experience, in urogynaecological practice. RESULTS: Female sexual dysfunction is frequent and can present in different ways; pain, problems concerning desire and satisfaction. These symptoms can be associated with concomitant male sexual dysfunction. These symptoms can be managed by a gynaecologist if he/she is trained accordingly. Knowledge of this is essential for a gynaecologist in daily practice but also for an urologist treating both female urinary incontinence or pelvic prolapse and male sexual dysfunction. CONCLUSION: Women's sexual disorders can considerably affect the quality of life of the partner and the couple. As the patients hesitate to speak of such matters the clinician should begin the dialogue with simple open questions.

[Focus on intrauterine contraception in 15 questions and answers]. / Mise au point sur la contraception intra-utérine en 15 questions-réponses.

In recent years, intrauterine contraception has experienced a revival, explainable as much by the broadening of its indications as by the ever increasing demand, expressed by women, for a contraceptive method that is both reliable and not binding. In this review, we establish an up-to-date and comprehensive state of intrauterine contraception in 2010, by responding to key-questions, which arise from everyday practice in gynaecology.

Anorexia nervosa, osteoporosis and circulating leptin: the missing link.

UNLABELLED: Methods: Leptin levels were measured in 103 consecutive women with anorexia nervosa. Results: Spine BMD and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD. INTRODUCTION: The purpose of this study was to assess leptin levels and other biological variables in a population of anorexia nervosa patients. METHODS: Leptin levels were measured consecutively in 103 women with anorexia nervosa (AN) with a mean age of 24.9 +/- 7.4 years. Osteodensitometry was also performed by dual energy X-ray absorptiometry (DXA). RESULTS: Spine bone mineral density (BMD) and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD. The mean leptin level was 3.9 +/- 4.6 ng/mL (normal values, 3.5-11 ng/mL). The distribution of leptin values was not a Gaussian distribution, and a log-transformed was therefore performed. A significant correlation was found between leptin level and spinal BMD (r = 0.3; p = 0.002); significant correlations were observed for both femoral neck and total hip BMDs. When leptin level values were divided into tertiles, spine BMD and Z-score values were found to be significantly lower in the lower tertile (p = 0.04 and p = 0.02) compared with the highest tertile. For femoral neck BMDs, the T-score was slightly lower between low and high tertile, but the difference was not statistically significant (p = 0.07). When multivariate analyses were performed, two independent factors which could possibly account for the variance in spinal BMDs were found. Duration of amenorrhea and leptin level accounted for 27% of the variance (p < 0.0001). CONCLUSION: The mechanisms underlying bone loss in AN patients remain unclear and complex, involving hypoestrogenia as well as nutritional factors such as insulin-like growth factor and leptin.

[Vulvar intraepithelial neoplasias (VINs): patients' experience]. / Néoplasies vulvaires intraépithéliales (VIN): vécu des patientes.

Up to now, there are only a few studies to have dealt with the psychosexual consequences of vulvar intraepithelial neoplasias (VINs) and their surgical treatment. Yet, these consequences cannot be ignored. The patients' daily experience is always complicated, especially because the disease--rightly or not--is assimilated to cancer, is a sexually transmissible infection, affects a part of the body with particular symbols, but also because today there are no certainties whatever on this subject. From the observation of patients followed by a team of specialists, this article aims to describe most frequent reactions, try to explain them, and consider what medical accompaniment and counsel might be proposed in these circumstances.

[Diagnosis of vulvar intraepithelial neoplasias (VIN)]. / Diagnostic d'une néoplasie intraépithéliale vulvaire (VIN).

Vulvar pathology is located at the border between dermatology and gynaecology. The gynaecologist is concerned by VIN (vulvar intraepithelial neoplasia) lesions as patients meet them for that problem. He makes distinction with dermatologic lesions so as to refer proper patients to dermatologists. A recent classification of VIN has a major interest. One individualizes two kinds of precancerous lesions. The first one is lichen sclerosis with dermatologic treatment by dermocorticoids and the other aetiology is HPV infection with frequent association with cervical localisation. Gynaecologists are more familiar with this second aetiology. Thus, they have to (i) check for VIN, (ii) know their appearance and how the diagnosis can be made by biopsy, (iii) precise the aetiology, (iv) appreciate the severity of the disease, (v) discuss which treatment is indicated: destruction or surgery.

[New perspectives for pediatric surgery in the University of Brussels and the Brussels public health institutions, after 20 years of HUDERF (The University Hospital of Children Queen Fabiola)]. / Des perspectives nouvelles pour la chirurgie pédiatrique U.L.B./IRIS, après 20 ans d'HUDERF et autres aventures.

A Convention signed by the academic and political Authorities of the University of Brussels and IRIS (Brussels public health institutions) allows the creation of an Interhospital Department of Pediatric Surgery. The pediatric surgeons of the different hospitals have now the opportunity to organise a large cooperation on a clinical, research and teaching basis.

[The medico-surgical department of uro-nephrology, dialysis and renal transplantation in the Children's Hospital of Brussels]. / Le département médico-chirurgical d'uro-néphrologie, dialyse et transplantation rénale à l'HUDERF.

The department of pediatric uro-nephrology was created in 1977 in Brugmann hospital. Since then, various sectors have been developed including: hemodialysis and peritoneal dialysis, kidney transplantation, urological and genital surgery, antenatal screening and rapid management of uronephropathies, treatment of voiding dysfunction and neurogenic bladder, management of tubular and glomerular diseases. The progress in genetics, medical imaging, obstetrics, neonatology and surgery has allowed us to take care of our young patients within a multidisciplinary framework. The most original contributions of the department are related to the performance of combined liver-kidney transplantation in primary hyperoxaluria, to the determination of the natural history of several congenital anomalies of the kidney and urinary tract, to the assessment of the role of genetical mutations on tubular and glomerular diseases, to the usefulness of radioisotopic tracers in the measurement of renal function in infants, and to the study of experimental tolerization of

How to interpret a deterioration of split function?

OBJECTIVE: A drop of split renal function often constitutes a criterion for pyeloplasty in hydronephrosis since it is considered as representing deterioration of the affected kidney. The aim of this work was to determine, in a selected population of patients with a drop of split function of at least 5%, if the evolution of single kidney glomerular filtration rate (SKGFR) was parallel to the one of split renal function. METHODS: From a large data basis, we found retrospectively only 29 children (10 below and 19 above two years of age at first examination) having had at least two Tc-99m mertiatide (Tc-99m MAG3) renographic explorations for various urological diseases, with a decrease of split function of at least 5% between the two examinations. Evolution of split function was compared to evolution of SKGFR obtained by means of the combination of Tc-99m MAG3 split function and overall glomerular filtration rate as given by the chromium Cr 51 ethylenediamine tetraacetic acid (EDTA) clearance. RESULTS: For the group above two years of age, SKGFR increased or remained stable in 63% of the cases, while in the children less than 2 years of age, a decrease of SKGFR was never observed, according to the maturation of overall GFR in this age group. Thus, the decrease of split function was not necessarily associated with a similar decrease of SKGFR. CONCLUSION: In patients with unilateral or bilateral urological disorders, deterioration of split renal function does not necessary correspond to a loss of function of the affected kidney. SKGFR often modifies the interpretation of split function.

Identification and characterization of a lymphocytic Rho-GTPase effector: rhotekin-2.

Rhotekin belongs to the group of proteins containing a Rho-binding domain that are target peptides (effectors) for the Rho-GTPases. We previously identified a novel cDNA with homology to human rhotekin and in this study we cloned and characterized the coding region of this novel 12-exon gene. The ORF encodes a 609 amino-acid protein comprising a Class I Rho-binding domain and pleckstrin homology (PH) domain. Cellular cDNA expression of this new protein, designated Rhotekin-2 (RTKN2), was shown in the cytosol and nucleus of CHO cells. Using bioinformatics and RTPCR we identified three major splice variants, which vary in both the Rho-binding and PH domains. Real-time PCR studies showed exclusive RTKN2 expression in pooled lymphocytes and further purification indicated sole expression in CD4(pos) T-cells and bone marrow-derived B-cells. Gene expression was increased in quiescent T-cells but negligible in activated proliferating cells. In malignant samples expression was absent in myeloid leukaemias, low in most B-cell malignancies and CD8(pos) T-cell malignancies, but very high in CD4(pos)/CD8(pos) T-lymphoblastic lymphoma. As the Rho family is critical in lymphocyte development and function, RTKN2 may play an important role in lymphopoiesis.

ORP3 splice variants and their expression in human tissues and hematopoietic cells.

ORP3 is a member of the newly described family of oxysterol-binding protein (OSBP)-related proteins (ORPs). We previously demonstrated that this gene is highly expressed in CD34(+) hematopoietic progenitor cells, and deduced that the "full-length" ORP3 gene comprises 23 exons and encodes a predicted protein of 887 amino acids with a C-terminal OSBP domain and an N-terminal pleckstrin homology domain. To further characterize the gene, we cloned ORP3 cDNA from PCR products and identified multiple splice variants. A total of eight isoforms were demonstrated with alternative splicing of exons 9, 12, and 15. Isoforms with an extension to exon 15 truncate the OSBP domain of the predicted protein sequence. In human tissues there was specific isoform distribution, with most tissues expressing varied levels of isoforms with the complete OSBP domain; while only whole brain, kidney, spleen, thymus, and thyroid expressed high levels of the isoforms associated with the truncated OSBP domain. Interestingly, the expression in cerebellum, heart, and liver of most isoforms was negligible. These data suggest that differential mRNA splicing may have resulted in functionally distinct forms of the ORP3 gene.