Women and men with distressing low sexual desire exhibit sexually dimorphic brain processing.

Distressing low sexual desire, termed Hypoactive Sexual Desire Disorder (HSDD), affects approximately 10% of women and 8% of men. In women, the 'top-down' theory of HSDD describes hyperactivity in higher-level cognitive brain regions, suppressing lower-level emotional/sexual brain areas. However, it is unknown how this neurofunctional disturbance compares to HSDD in men. To investigate this, we employed task-based functional MRI in 32 women and 32 men with HSDD to measure sexual-brain processing during sexual versus non-sexual videos, as well as psychometric questionnaires to assess sexual desire/arousal. We demonstrate that women had greater activation in higher-level and lower-level brain regions, compared to men. Indeed, women who had greater hypothalamic activation in response to sexual videos, reported higher psychometric scores in the evaluative (r = 0.55, P = 0.001), motivational (r = 0.56, P = 0.003), and physiological (r = 0.57, P = 0.0006) domains of sexual desire and arousal after watching the sexual videos in the scanner. By contrast, no similar correlations were observed in men. Taken together, this is the first direct comparison of the neural correlates of distressing low sexual desire between women and men. The data supports the 'top-down' theory of HSDD in women, whereas in men HSDD appears to be associated with different neurofunctional processes.

Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival.

Objectives: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis. Design and methods: Single-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure. Results: Non-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 - 0.71) or both (HR 0.41, CI 0.25 - 0.64) but not in those who only developed non-endocrine irAEs. Conclusions: Women may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this.

Exploring the bi-directional relationship between periodontitis and dyslipidemia: a comprehensive systematic review and meta-analysis.

AIM: As periodontitis and dyslipidemia are diseases that occur with high incidence, the relationship between them has attracted much attention. Previous studies on these diseases have tended to focus on lipid parameters and periodontitis, we aimed to investigate the relationship between dyslipidemia and periodontitis. MATERIALS AND METHODS: A comprehensive search to identify the studies investigating the relationship between dyslipidemia and periodontitis was performed on PubMed, Web of Science and Cochrane Library before the date of August, 2023. Studies were considered eligible if they contained data on abnormal blood lipid parameters and periodontitis. Studies that reported mean differences and 95% confidence intervals or odds ratios were used. RESULTS: A total of 73 publications were included in the meta-analysis. Hyper total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and lower high-density lipoprotein (HDL) levels are risk factors for periodontitis. Periodontal disease is a risk factor for high TG and low HDL levels. Three months after periodontal treatment, the levels of TC, TG and HDL were significantly improved, and statin treatment only improved gingival index (GI) levels compared to that of the dietary control. CONCLUSIONS: The findings reported here suggest that the mutual promotion of periodontitis and dyslipidemia can be confirmed. Non-surgical periodontal therapy may improve lipid abnormalities. It can't be demonstrated whether systematic application of statins have a better effect on the improvement in periodontal status in patients with dyslipidemia compared to that of the control.

Pharmacotherapy for chronic obesity management: a look into the future.

Substantial leaps have been made in the drug discovery front in tackling the growing pandemic of obesity and its metabolic co-morbidities. Greater mechanistic insight and understanding of the gut-brain molecular pathways at play have enabled the pursuit of novel therapeutic agents that possess increasingly efficacious weight-lowering potential whilst remaining safe and tolerable for clinical use. In the wake of glucagon-like peptide 1 (GLP-1) based therapy, we look at recent advances in gut hormone biology that have fermented the development of next generation pharmacotherapy in diabesity that harness synergistic potential. In this paper, we review the latest data from the SURPASS and SURMOUNT clinical trials for the novel 'twincretin', known as Tirzepatide, which has demonstrated sizeable body weight reduction as well as glycaemic efficacy. We also provide an overview of amylin-based combination strategies and other emerging therapies in the pipeline that are similarly providing great promise for the future of chronic management of obesity.

Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.

Importance: The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behavior. Objective: To determine the physiological, behavioral, neural, and hormonal effects of kisspeptin administration in men with HSDD. Design, Setting, and Participants: This double-blind, 2-way crossover, placebo-controlled randomized clinical trial was performed at a single academic research center in the UK. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioral, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli (short and long video tasks). The trial was conducted between January 11 and September 15, 2021, and data analysis was performed between October and November 2021. Interventions: Participants attended 2 study visits at least 7 days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate-matched placebo. Main Outcomes and Measures: Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level-dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioral measures of sexual desire and arousal. Results: Of the 37 men randomized, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass index of 24.9 (5.4). On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003). Furthermore, improvements in several secondary analyses were observed, including significant increases in penile tumescence in response to sexual stimuli (by up to 56% more than placebo; mean difference = 0.28 units [95% CI, 0.04-0.52 units]; P = .02) and behavioral measures of sexual desire-most notably, increased happiness about sex (mean difference = 0.63 points [95% CI, 0.10-1.15 points]; P = .02). Conclusions and Relevance: Collectively, this randomized clinical trial provides the first evidence to date showing that kisspeptin administration substantially modulates sexual brain processing in men with HSDD, with associated increases in penile tumescence and behavioral measures of sexual desire and arousal. These data suggest that kisspeptin has potential as the first pharmacological treatment for men with low sexual desire. Trial Registration: isrctn.org Identifier: ISRCTN17271094.

Advances in stress and depression research.

PURPOSE OF REVIEW: Stress plays a central role in the onset and course of depression. However, only a subset of people who encounter stressful life events go on to experience a depressive episode. The current review highlights recent advances in understanding when, why, and for whom the stress-depression link occurs, and we identify avenues for future research. RECENT FINDINGS: In the last 18 months, researchers have taken a more nuanced perspective on the biopsychosocial mechanisms critical to the stress-depression link. For example, examination of specific facets of emotion regulation, including emotion regulation flexibility and interpersonal emotion regulation, has been critical to understanding its role in depression. Similarly, refined investigations of social support allowed researchers to identify distinct - and occasionally opposite - outcomes depending on the context or manner in which the support was provided. Researchers also documented that the stress-depression link was enhanced by dysregulation of several stress-sensitive biological systems, such as the immune system, microbiome, endocrine system, and neuroanatomical substrates. SUMMARY: Recent studies highlight the importance of adopting a nuanced understanding of mechanisms and moderators that explain the stress-depression link. We also encourage continued engagement in collaborative, open science that uses multiple methods to study the full breadth of human diversity.

The interaction of CD300lf and ceramide reduces the development of periodontitis by inhibiting osteoclast differentiation.

AIM: The regulation of osteoclasts (OCs) by inhibitory immunoreceptors maintains bone homeostasis and is considered an important determinant of the extent of periodontal pathology. The aim of this study was to investigate the role of the inhibitory immunoreceptor CD300lf and its ligand ceramide in osteoclastogenesis in periodontitis. MATERIALS AND METHODS: The expression of CD300lf was measured in vitro and in a ligature-induced periodontitis model. The effect of CD300lf ablation on osteoclastogenesis was examined in ligature-retained and ligature removal periodontitis models. The effect of ceramide, the ligand of CD300lf, was examined in osteoclastogenesis in vitro and in vivo by smearing 20 µg of ceramide dissolved in carboxymethylcellulose on teeth and gingiva every other day in an experimental periodontitis model and ligature removal model. RESULTS: CD300lf expression was downregulated during osteoclastogenesis. Ablation of CD300lf in the ligature-induced periodontitis model increased the number of OCs and exacerbated bone damage. Bone resorption caused by CD300lf ablation was reversible following ligature removal. CD300lf-ceramide binding suppressed osteoclastogenesis in vitro and inhibited alveolar bone loss in a mouse periodontitis model. CONCLUSIONS: Our findings reveal that CD300lf-ceramide binding plays a critical negative role in alveolar bone loss in periodontitis by inhibiting OCs differentiation.

Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men.

Background: Delayed puberty in males is almost invariably associated with constitutional delay of growth and puberty (CDGP) or congenital hypogonadotrophic hypogonadism (CHH). Establishing the cause at presentation is challenging, with "red flag" features of CHH commonly overlooked. Thus, several markers have been evaluated in both the basal state or after stimulation e.g. with gonadotrophin releasing hormone agonist (GnRHa).Insulin-like peptide 3 (INSL3) is a constitutive secretory product of Leydig cells and thus a possible candidate marker, but there have been limited data examining its role in distinguishing CDGP from CHH. In this manuscript, we assess INSL3 and inhibin B (INB) in two cohorts: 1. Adolescent boys with delayed puberty due to CDGP or CHH and 2. Adult men, both eugonadal and having CHH. Materials and methods: Retrospective cohort studies of 60 boys with CDGP or CHH, as well as 44 adult men who were either eugonadal or had CHH, in whom INSL3, INB, testosterone and gonadotrophins were measured. Cohort 1: Boys with delayed puberty aged 13-17 years (51 with CDGP and 9 with CHH) who had GnRHa stimulation (subcutaneous triptorelin 100mcg), previously reported with respect to INB. Cohort 2: Adult cohort of 44 men (22 eugonadal men and 22 men with CHH), previously reported with respect to gonadotrophin responses to kisspeptin-54. Results: Median INSL3 was higher in boys with CDGP than CHH (0.35 vs 0.15 ng/ml; p=0.0002). Similarly, in adult men, median INSL3 was higher in eugonadal men than CHH (1.08 vs 0.05 ng/ml; p<0.0001). However, INSL3 more accurately differentiated CHH in adult men than in boys with delayed puberty (auROC with 95% CI in adult men: 100%, 100-100%; boys with delayed puberty: 86.7%, 77.7-95.7%).Median INB was higher in boys with CDGP than CHH (182 vs 59 pg/ml; p<0.0001). Likewise, in adult men, median INB was higher in eugonadal men than CHH (170 vs 36.5 pg/ml; p<0.0001). INB performed better than INSL3 in differentiating CHH in boys with delayed puberty (auROC 98.5%, 95.9-100%), than in adult men (auROC 93.9%, 87.2-100%). Conclusion: INSL3 better identifies CHH in adult men, whereas INB better identifies CHH in boys with delayed puberty.

Same-Day Home Recovery for Benign Foregut Surgery.

Importance: Same-day home recovery (SHR) is now the standard of care for many major surgical procedures and has the potential to become standard practice for benign foregut procedures (eg, hiatal hernia repair, fundoplication, and Heller myotomy). Objective: To determine whether SHR for patients undergoing benign foregut surgery is feasible, safe, and effective. Design, Setting, and Participants: This prospective cohort study took place across 19 medical centers within an integrated health care system in northern California from January 2019 through September 2021. Participants included consecutive patients undergoing elective benign foregut surgery. Exposures: Standardized SHR program. Main Outcomes and Measures: The primary end point was the rate of SHR. The secondary end points were 7-day and 30-day rates of postoperative emergency department visits, hospital readmissions, and reoperations. Results: Of 1248 patients who underwent benign foregut surgery from January 2017 through September 2021, 558 were patients before implementation of the SHR program and 690 were patients postimplementation. The mean age of patients was 60 years, and 759 (59%) were female. The preimplementation SHR rate was 64 of 558 patients (11.5%) in 2018 and increased to 82 of 113 patients (72.6%) by 2021 (94/350 [26.9%] in 2019 and 112/227 [49.3%] in 2020; P < .001). There were no statistical differences in the 7-day and 30-day rates of postoperative emergency visits, hospital readmissions, and reoperations or 30-day mortality in the SHR vs non-SHR groups in the postimplementation era. Conclusions and Relevance: In this study, implementation of a regional SHR program among patients undergoing elective benign foregut surgery was feasible, safe, and effective. The changes in perioperative care require comprehensive patient education and full multidisciplinary support. An SHR program for benign foregut procedures has the potential to improve patient care and cost-effectiveness in care delivery.

Regulation of autoimmune disease progression by Pik3ip1 through metabolic reprogramming in T cells and therapeutic implications.

Metabolic alterations could profoundly affect immune functions and influence the progression and outcome of autoimmune diseases. However, the detailed mechanisms and their therapeutic potential remain to be defined. Here, we show that phosphatidylinositide 3-kinase interacting protein 1 (Pik3ip1), a newly identified negative immune regulator, is notably down-regulated in several major autoimmune diseases through a previously unidentified mechanism mediated by interleukin-21/p38 mitogen-activated protein kinase/a disintegrin and metalloprotease-17 (ADAM17) pathway. Down-regulation of Pik3ip1 in T cells causes a major metabolic shift from oxidative phosphorylation toward aerobic glycolysis, leading to their overactivation and aggressive disease progression in experimental autoimmune encephalomyelitis (EAE) mouse model. Suppression of hypoxia-inducible factor 1α (Hif1α) or pharmacologic inhibition of glycolysis could reverse these phenotypes and largely mitigate EAE severity. Our study reveals a previously unrecognized role of Pik3ip1 in metabolic regulation that substantially affects the inflammatory loop in the autoimmune setting and identifies the Pik3ip1/Hif1α/glycolysis axis as a potential therapeutic target for treatment of autoimmune diseases.

Current Perspectives on Kisspeptins Role in Behaviour.

The neuropeptide kisspeptin is now well-established as the master regulator of the mammalian reproductive axis. Beyond the hypothalamus, kisspeptin and its cognate receptor are also extensively distributed in extra-hypothalamic brain regions. An expanding pool of animal and human data demonstrates that kisspeptin sits within an extensive neuroanatomical and functional framework through which it can integrate a range of internal and external cues with appropriate neuroendocrine and behavioural responses. In keeping with this, recent studies reveal wide-reaching effects of kisspeptin on key behaviours such as olfactory-mediated partner preference, sexual motivation, copulatory behaviour, bonding, mood, and emotions. In this review, we provide a comprehensive update on the current animal and human literature highlighting the far-reaching behaviour and mood-altering roles of kisspeptin. A comprehensive understanding of this important area in kisspeptin biology is key to the escalating development of kisspeptin-based therapies for common reproductive and related psychological and psychosexual disorders.

The niche-specialist and age-related oral microbial ecosystem: crosstalk with host immune cells in homeostasis.

Although characterization of the baseline oral microbiota has been discussed, the current literature seems insufficient to draw a definitive conclusion on the interactions between the microbes themselves or with the host. This study focuses on the spatial and temporal characteristics of the oral microbial ecosystem in a mouse model and its crosstalk with host immune cells in homeostasis. The V3V4 regions of the 16S rRNA gene of 20 samples from four niches (tongue, buccal mucosa, keratinized gingiva and hard palate) and 10 samples from two life stages (adult and old) were analysed. Flow cytometry (FCM) was used to investigate the resident immune cells. The niche-specialist and age-related communities, characterized based on the microbiota structure, interspecies communications, microbial functions and interactions with immune cells, were addressed. The phylum Firmicutes was the major component in the oral community. The microbial community profiles at the genus level showed that the relative abundances of the genera Bacteroides, Lactobacillus and Porphyromonas were enriched in the gingiva. The abundance of the genera Streptococcus, Faecalibaculum and Veillonella was increased in palatal samples, while the abundance of Neisseria and Bradyrhizobium was enriched in buccal samples. The genera Corynebacterium, Stenotrophomonas, Streptococcus and Fusobacterium were proportionally enriched in old samples, while Prevotella and Lacobacillus were enriched in adult samples. Network analysis showed that the genus Lactobacillus performed as a central node in the buccal module, while in the gingiva module, the central nodes were Nesterenkonia and Hydrogenophilus. FCM showed that the proportion of Th1 cells in the tongue samples (38.18 % [27.03-49.34 %]) (mean [range]) was the highest. The proportion of γδT cells in the buccal mucosa (25.82 % [22.1-29.54 %]) and gingiva (20.42 % [18.31-22.53 %]) samples was higher (P<0.01) than those in the palate (14.18 % [11.69-16.67 %]) and tongue (9.38 % [5.38-13.37 %] samples. The proportion of Th2 (31.3 % [16.16-46.44 %]), Th17 (27.06 % [15.76-38.36 %]) and Treg (29.74 % [15.71-43.77 %]) cells in the old samples was higher than that in the adult samples (P<0.01). Further analysis of the interplays between the microbiomes and immune cells indicated that Th1 cells in the adult group, nd Th2, Th17 and Treg cells in the old group were the main immune factors strongly associated with the oral microbiota. For example, Th2, Th17 and Treg cells showed a significantly positive correlation with age-related microorganisms such as Sphingomonas, Streptococcus and Acinetobacter, while Th1 cells showed a negative correlation. Another positive correlation occurred between Th1 cells and several commensal microbiomes such as Lactobacillus, Jeotgalicoccus and Sporosarcina. Th2, Th17 and Treg cells showed the opposite trend. Together, our findings identify the niche-specialist and age-related characteristics of the oral microbial ecosystem and the potential associations between the microbiomes and the mucosal immune cells, providing critical insights into mucosal microbiology.

[Research Updates: The Role of Interaction between Oral Microbiota, Immune Cells, and Epithelial Barrier in Oral Mucosal Homeostasis and Pathogenesis].

In a healthy state, the interaction between the oral microorganisms, mucosal immune cells and epithelial barrier can maintain the oral microecological stability. However, the oral microecology is disrupted under a diseased state and various pathogenic bacteria and their virulence factors and metabolites irritate the immune system, which causes direct or indirect damage to the epithelial barrier, promotes the pathogenesis and progression of oral mucosal diseases, and triggers immune inflammatory response or the irreversible transformation from inflammation into cancer. We herein reviewed the interaction between oral microorganisms, immune cells and epithelial barrier from two perspectives, the maintenance of the oral homeostasis and the pathogenesis of oral mucosal diseases. We intended to gain further understanding of the oral mucosal homeostasis and the mechanism of action of the pathogenesis and progression of oral mucosal diseases, and to provide thereby ideas and scientific and theoretical basis for developing new strategies for the diagnosis and treatment of oral mucosal diseases through re-establishing mucosal homeostasis.

Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men.

CONTEXT: Osteoporosis results from disturbances in bone formation and resorption. Recent nonhuman data suggest that the reproductive hormone kisspeptin directly stimulates osteoblast differentiation in vitro and thus could have clinical therapeutic potential. However, the effects of kisspeptin on human bone metabolism are currently unknown. OBJECTIVE: To assess the effects of kisspeptin on human bone metabolism in vitro and in vivo. METHODS: In vitro study: of Mono- and cocultures of human osteoblasts and osteoclasts treated with kisspeptin. Clinical study: Randomized, placebo-controlled, double-blind, 2-way crossover clinical study in 26 men investigating the effects of acute kisspeptin administration (90 minutes) on human bone metabolism, with blood sampling every 30 minutes to +90 minutes. Cells for the in vitro study were from 12 male blood donors and 8 patients undergoing hip replacement surgery. Twenty-six healthy eugonadal men (age 26.8 ±â€…5.8 years) were included in the clinical study. The intervention was Kisspeptin (vs placebo) administration. The main outcome measures were changes in bone parameters and turnover markers. RESULTS: Incubation with kisspeptin in vitro increased alkaline phosphatase levels in human bone marrow mesenchymal stem cells by 41.1% (P = .0022), and robustly inhibited osteoclastic resorptive activity by up to 53.4% (P < .0001), in a dose-dependent manner. Kisspeptin administration to healthy men increased osteoblast activity, as evidenced by a 20.3% maximal increase in total osteocalcin (P = .021) and 24.3% maximal increase in carboxylated osteocalcin levels (P = .014). CONCLUSION: Collectively, these data provide the first human evidence that kisspeptin promotes osteogenic differentiation of osteoblast progenitors and inhibits bone resorption in vitro. Furthermore, kisspeptin acutely increases the bone formation marker osteocalcin but not resorption markers in healthy men, independent of downstream sex steroid levels. Kisspeptin could therefore have clinical therapeutic application in the treatment of osteoporosis.

A comprehensive profile of TCF1+ progenitor and TCF1- terminally exhausted PD-1+CD8+ T cells in head and neck squamous cell carcinoma: implications for prognosis and immunotherapy.

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8+PD1+TCF1+ progenitor exhausted T cells (TCF1+Texprog) and CD8+PD1+TCF1- terminally exhausted T cells (TCF1-Texterm). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1-Texterm represented a greater proportion of CD8+PD1+Tex than TCF1+Texprog in most patients. TCF1+Texprog produced abundant TNFα, while TCF1-Texterm expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1-Texterm exhibited a polyfunctional TNFα+GZMB+IFNγ+ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1-Texterm were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1-Texterm was the major CD8+PD1+Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1-Texterm was associated with greater Treg abundance.

Changes in Circulating Kisspeptin Levels During Each Trimester in Women With Antenatal Complications.

CONTEXT: Antenatal complications such as hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR), gestational diabetes (GDM), and preterm birth (PTB) are associated with placental dysfunction. Kisspeptin has emerged as a putative marker of placental function, but limited data exist describing circulating kisspeptin levels across all 3 trimesters in women with antenatal complications. OBJECTIVE: We aimed to assess whether kisspeptin levels are altered in women with antenatal complications. METHODS: Women with antenatal complications (n = 105) and those with uncomplicated pregnancies (n = 265) underwent serial ultrasound scans and blood sampling at the Early Pregnancy Assessment Unit at Hammersmith Hospital, UK, at least once during each trimester (March 2014 to March 2017). The women with antenatal complications (HDP [n = 32], FGR [n = 17], GDM [n = 35], PTB [n = 11], and multiple complications [n=10]) provided 373 blood samples and the controls provided 930 samples. Differences in circulating kisspeptin levels were assessed. RESULTS: Third-trimester kisspeptin levels were higher than controls in HDP but lower in FGR. The odds of HDP adjusted for gestational age, maternal age, ethnicity, BMI, smoking, and parity were increased by 30% (95% CI, 16%-47%; P < 0.0001), and of FGR were reduced by 28% (95% CI, 4-46%; P = 0.025), for every 1 nmol/L increase in plasma kisspeptin. Multiple of gestation-specific median values of kisspeptin were higher in pregnancies affected by PTB (P = 0.014) and lower in those with GDM (P = 0.020), but not significantly on multivariable analysis. CONCLUSION: We delineate changes in circulating kisspeptin levels at different trimesters and evaluate the potential of kisspeptin as a biomarker for antenatal complications.

Risk characterisation of milk protein contamination in milk-alternative ice cream products sold as frozen desserts in the United States.

Milk protein is recognised as one of the eight most common food allergens in the United States, and one of the most common causes of fatal or near-fatal food-induced anaphylactic reactions globally. Undeclared allergens in food products are the leading cause of the U.S. Food and Drug Administration (FDA) requests for food recalls, with undeclared milk protein as the most frequently cited allergen. The purpose of this study was to evaluate the prevalence of milk protein contamination in milk-alternative ice cream products sold as frozen dessert in the U.S. and labelled as 'non-dairy', 'dairy-free', and/or 'vegan', and to characterise the potential risk for allergic individuals consuming these products. Thirty-two unique milk-alternative frozen dessert products, including flavours with and without inclusions, from 16 different brands, were tested for the presence of milk proteins using enzyme-linked immunosorbent assay. Milk protein was detected in three of the tested products: two contained solid inclusions, and one did not have inclusions. One of the three products with detectable milk protein had an advisory statement indicating the product was made in a facility that processed milk. Although no consensus exists as to the minimal dose of milk protein necessary to elicit an adverse effect in a milk-sensitised individual, the milk protein quantities in one serving of each of the three products exceeded some of the published thresholds. These results suggest that one serving of certain milk-alternative frozen dessert products could potentially elicit an allergic response in highly sensitive individuals.

A comparative evaluation of dietary exposure to glyphosate resulting from recommended U.S. diets.

Since its commercial introduction in 1974, national and international regulatory agencies have consistently reported no human health concerns associated with the herbicide glyphosate when used according to label directions. However, in 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as a probable human carcinogen. Despite IARC being the sole outlier in its conclusion, dietary exposure to glyphosate remains a health concern to some members of the public. While glyphosate residues have been detected in foods, it is unclear whether a specific eating pattern substantially contributes to glyphosate exposure. Therefore, dietary glyphosate intake was determined for three eating patterns recommended in the U.S. The 95th percentile of glyphosate ingestion at 2,000 calories/day for adults for the U.S.-Style, Mediterranean-Style, and Vegetarian eating patterns ranged from 38 to 960, 39 to 1100, and 39 to 880 µg/day, respectively. No significant differences were observed in glyphosate intake between the dietary styles, and the 95th percentile glyphosate intakes were well below the current U.S. EPA chronic oral reference dose (RfD) of 0.1 mg/kg/day. Our data demonstrate that ingestion of certain high residue foods, particularly grains and legumes, is a driver of total dietary glyphosate body burden regardless of dietary style.

Performance of plasma kisspeptin as a biomarker for miscarriage improves with gestational age during the first trimester.

OBJECTIVE: To compare the performance of kisspeptin and beta human chorionic gonadotropin (ßhCG), both alone and in combination, as biomarkers for miscarriage throughout the first trimester. DESIGN: Prospective, nested case-control study. SETTING: Tertiary Centre, Queen Charlotte Hospital, London, United Kingdom. PATIENT(S): Adult women who had miscarriages (n = 95, 173 samples) and women with healthy pregnancies (n = 265, 557 samples). INTERVENTION(S): The participants underwent serial ultrasound scans and blood sampling for measurement of plasma kisspeptin and ßhCG levels during the first trimester. MAIN OUTCOME MEASURE(S): The ability of plasma kisspeptin and ßhCG levels to distinguish pregnancies complicated by miscarriage from healthy pregnancies unaffected by miscarriage. RESULT(S): Gestation-adjusted levels of circulating kisspeptin and ßhCG were lower in samples from women with miscarriages than in women with healthy pregnancies by 79% and 70%, respectively. The area under the receiver-operating characteristic curve for identifying miscarriage during the first trimester was 0.874 (95% confidence interval [CI] 0.844-0.904) for kisspeptin, 0.859 (95% CI 0.820-0.899) for ßhCG, and 0.916 (95% CI 0.886-0.946) for the sum of the two markers. The performance of kisspeptin in identifying miscarriage improved with increasing length of gestation, whereas that of ßhCG worsened. A decision matrix incorporating kisspeptin, ßhCG, and gestational age had 83% to 87% accuracy for the prediction of miscarriage. CONCLUSION(S): Plasma kisspeptin is a promising biomarker for miscarriage and provides additional value to ßhCG alone, especially during later gestational weeks of the first trimester.

Crosstalk between the oral microbiota, mucosal immunity, and the epithelial barrier regulates oral mucosal disease pathogenesis.

Oral mucosal disease (OMD), which is also called soft tissue oral disease, is described as a series of disorders or conditions affecting the mucosa and soft tissue in the oral cavity. Its etiology is unclear, but emerging evidence has implicated the influence of the composition of the oral mucosa and saliva-resident microbiota. In turn, this dysbiosis effects the immune response balance and epithelial barrier function, followed by the occurrence and progression of OMD. In addition, oral microbial dysbiosis is diverse in different types of diseases and different disease progressions, suggesting that key causal pathogens may exist in various oral pathologies. This narrative literature review primarily discusses the most recent findings focusing on how microbial dysbiosis communicates with mucosal adaptive immune cells and the epithelial barrier in the context of five representative OMDs, including oral candidiasis (OC), oral lichen planus (OLP), recurrent aphthous ulcer (RAU), oral leukoplakia (OLK), and oral squamous cell carcinoma (OSCC), to provide new insight into the pathogenetic mechanisms of OMDs.