Use of Fermented Red Clover Isoflavones in the Treatment of Overactive Bladder in Postmenopausal Women: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Postmenopausal women are at risk of developing an overactive bladder (OAB). Conventional vaginal estrogen has shown promise for symptom relief. Isoflavones have proven effective as an alternative to estrogen treatment against menopause-related symptoms. However, its effect on OAB symptoms has not been studied. This study investigates if fermented red clover isoflavones reduce OAB symptoms in postmenopausal women. In this randomized, double-blinded, placebo-controlled trial, women were administered red clover extract (RCE) or a placebo twice daily for three months. Women filled out the International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) and Urinary Incontinence Short Form (ICIQ-UI-SF), together with a fluid intake and voiding diary. A total of 33 women (16 in the RCE group and 17 in the placebo group) were included in the analysis. Baseline demographics and OAB characteristics were comparable across groups. Intake of RCE did not lead to significant relief in most urinary bladder symptom measures, although a significant reduction in the bother of urinary urgency (p = 0.033) and a tendency towards a decreased ICIQ-OAB score were observed (p = 0.056). In contrast, the placebo exhibited a significant decrease in the ICIQ-OAB score (p = 0.021) and in some diary outcomes. We found that an intake of isoflavones did not relieve OAB symptoms in postmenopausal women.

Children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorder share distinct microbiota compositions.

An association has been suggested between altered gut microbiota, and attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), respectively. Thus, we analyzed the gut microbiota composition in children and adolescents with or without these disorders and evaluated the systemic effects of these bacteria. We recruited study participants diagnosed with ADHD, ASD, and comorbid ADHD/ASD, while the control groups consisted both of siblings and non-related children. The gut microbiota was analyzed by 16S rRNA gene sequencing of the V4 region, while the concentration of lipopolysaccharide-binding protein (LBP), cytokines, and other signaling molecules were measured in plasma. Importantly the gut microbiota compositions of cases with ADHD and ASD were highly similar for both alpha- and beta-diversity while differing from that of non-related controls. Furthermore, a subset of ADHD and ASD cases had an increased LBP concentration compared to non-affected children, which was positively correlated with interleukin (IL)-8, 12, and 13. These observations indicate disruption of the intestinal barrier and immune dysregulation among the subset of children with ADHD or ASD.

Perception of Patients with Cancer Enquiring About Adjuvant Therapy with Cannabis Medicine for Palliation of Symptoms: An Interview Study among Danish Health Care Professionals.

Background: A medicinal cannabis pilot program was launched in Denmark in 2018 to support patients as countermeasure against self-medication by use of cannabis products from the illicit market. The aim was to facilitate patient access to adjuvate therapy using medicinal cannabis under the guidance of physicians. Objective: The aim of this interview study was to elucidate how health care professionals (HCPs) perceive cancer patients enquiring about cannabis medicine (CM), including medicinal cannabis and cannabis-based medicine, for adjuvant palliative therapy. Design: The program used semistructured qualitative research interviews with thematic analysis. Setting/Participants: Fifty HCPs took part in the study with 10 informants in each of the following 5 groups: oncologists, palliative care specialists, general practitioners, registered nurses in oncology, and in palliative care. Results: The informants reported that optional CM as adjuvant therapy was only discussed when initiated by the patient or relatives. Reluctance by HCPs to enter into a dialogue about CM with their patients was mainly explained by the lack of clinical evidence for the use of CM in palliative care of patients with cancer. None of the oncologists had ever prescribed CM, while three palliative care specialists and two general practitioners had issued prescriptions on rare occasions. Conclusion: HCPs involved in cancer treatment and palliative care are in general reluctant to discuss optional adjuvant CM therapy with their patients. The Danish health care authorities need to address this barrier to ensure that patients eligible for CM therapy are given this option as intended by the launch of the national pilot program.

Voided Urinary Microbiota Is Stable Over Time but Impacted by Post Void Storage.

Background: New sensitive techniques have revealed a thriving bacterial community in the human urinary tract, challenging the perception that urine in healthy humans is sterile. While the functional role of this urinary microbiota is unknown, dysbiosis has been linked to urgency urinary incontinence and risk of urinary tract infections. When comparing studies, it is crucial to account for possible confounders introduced due to methodological differences. Here we investigated whether collection and storage conditions had any impact on the urinary microbial composition. Results: For comparison of different storage conditions, midstream urine was collected from five healthy adult female donors and analyzed by 16S rRNA gene sequencing. Samples stored at -80 and -20°C, but not 4°C, were found to be comparable to freshly handled voided urine. Using the same methods, the daily or day-to-day variation in urinary microbiota was investigated in 19 healthy donors, including four women, five men, five girls, and five boys. Apart from two male adult donors, none of the tested conditions gave rise to significant differences in alpha and beta diversities between individuals. Conclusion: The composition of voided urinary microbiota was found to be effectively maintained by freezing, but not storage at 4°C. In addition, we did not observe any intrapersonal daily or day-to-day variations in microbiota composition in women, girls or boys. Together our study supports present methodologies that can be used in future studies investigating the urinary microbiota.

Gut microbiota profiles of autism spectrum disorder and attention deficit/hyperactivity disorder: A systematic literature review.

Accumulating evidence has implicated an involvement of the gut-brain axis in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), however with highly diverse results. This systematic review aims to describe and evaluate studies investigating the gut microbiota composition in individuals with ASD or ADHD and to evaluate if variations in gut microbiota are associated with these disorders. Twenty-four articles were identified in a systematic literature search of PubMed and Embase up to July 22, 2019. They consisted of 20 studies investigating ASD and four studies investigating ADHD. For ASD, several studies agreed on an overall difference in ß-diversity, although no consistent bacterial variation between all studies was reported. For ADHD, the results were more diverse, with no clear differences observed. Several common characteristics in gut microbiota function were identified for ASD compared to controls. In contrast, highly heterogeneous results were reported for ADHD, and thus the association between gut microbiota composition and ADHD remains unclear. For both disorders, methodological differences hampered the comparison of studies.

Living with a Hope of Survival Is Challenged by a Lack of Clinical Evidence: An Interview Study among Cancer Patients Using Cannabis-Based Medicine.

Background: There is an increasing focus among cancer patients on the use of cannabis-based medicine (CBM) as a supplement to conventional palliative care. However, physicians are reluctant to engage in dialog with the patients as clinical evidence is lacking. As a result, the patients are often left alone to rely on their own judgment in purchasing CBM products on the illegal market. Objective: Our study aimed to collect information from CBM treatment-experienced cancer patients receiving palliative care regarding treatment decision rationale and outcome. Design: A qualitative interview study using thematic analysis was performed. Setting/Participants: A total of 20 informants took part in individual interviews. Results: To the question addressing the main rationale for starting CBM treatment, all 20 patients responded that they carried a hope that cannabis would have a curative effect on the cancer disease. Most patients reported relief of symptoms, such as insomnia, anxiety, nausea, and pain, after initiation of CBM treatment, but this outcome was perceived as less of a focus in comparison to hope of a cure. Conclusion: This study contributes with knowledge from the perspective of the cancer patient in palliative care regarding the decision behind the use of CBM. There seems to be striving for surviving cancer based on the rationale that cannabis may constitute curative properties. Relief of symptoms is perceived as a secondary reason for treatment. This knowledge is essential in the dialog between the health professional and the cancer patient about the use of CBM products for treatment.

A systematic review with epidemiological update of male genital schistosomiasis (MGS): A call for integrated case management across the health system in sub-Saharan Africa.

Male genital schistosomiasis (MGS) is a gender specific manifestation of urogenital schistosomiasis (UGS) first described in 1911 by Madden in Egypt. Today, while affecting millions of men and boys worldwide, MGS receives insufficient attention, especially in sub-Saharan Africa (SSA). To provide a systematic review with an epidemiological update of MGS, we inspected both online and hardcopy resources in our appraisal. A total of 147 articles were eventually identified, only 31 articles were exclusively focused on MGS with original or targeted research. From these, we discuss pertinent clinico-pathological features of MGS, highlight the possible connection and interplay with HIV, and assess current diagnostic techniques alongside consideration of their use and application in SSA. To appreciate the burden of MGS more fully, especially in endemic areas, there is a clear need for better surveillance and longitudinal population research to investigate the best point-of-care (POC) diagnostic and its performance through time. Furthermore, to optimise individual case management, exploration of alternative praziquantel dosing regimens is needed for MGS in men with or without HIV co-infection.

Decrease in Seminal HIV-1 RNA Load After Praziquantel Treatment of Urogenital Schistosomiasis Coinfection in HIV-Positive Men-An Observational Study.

BACKGROUND: Urogenital schistosomiasis due to Schistosoma hematobium infection is hypothesized to cause increased HIV-1 RNA shedding in semen in HIV co-infected men as result of chronic egg-induced inflammation in the prostate and the seminal vesicles. The effect of treatment with the antihelminthic agent praziquantel on seminal HIV-1 RNA load was assessed in this study. METHODS: HIV-1 RNA load was determined in blood plasma and semen at baseline and at 10-week follow-up. Praziquantel was administered at baseline and two weeks later. RESULTS: Eighteen HIV-positive men with S. haematobium co-infection were enrolled into the study. Status of antiretroviral therapy (ART): 6 ART-naïve and 12 ART-experienced. All participants became egg-negative in urine at follow-up. Among the ART-naïve men, the mean HIV-1 RNA load decreased by 0.32 log10 copies per mL (4.41 vs 4.09) in blood plasma from baseline to follow-up, and in semen by 1.06 log10 copies per mL (4.06 vs 3.00). CONCLUSIONS: This study demonstrated a decline in seminal HIV-1 RNA load following praziquantel treatment of urogenital schistosomiasis infection in HIV-positive men. The finding needs further exploration in a larger randomized study targeting praziquantel as a supplementary preventive measure of sexual transmission of HIV-1 in S. haematobium endemic areas in sub-Saharan Africa.

Deep sequencing of hepatitis C virus reveals genetic compartmentalization in cerebrospinal fluid from cognitively impaired patients.

BACKGROUND & AIMS: Hepatitis C virus (HCV) causes neuropsychiatric impairment and fatigue with recent studies suggesting HCV invasion of the central nervous system (CNS). Our previous finding that endothelial cells from the blood-brain barrier support HCV infection warrants further investigation to elucidate whether the CNS can serve as a reservoir for independent HCV evolution. METHODS: Cerebrospinal fluid (CSF) and plasma from six HCV-infected patients without liver disease or co-morbidities together with plasma from six healthy subjects were profiled for markers of immune activation and viral quasispecies measured by deep sequencing. Unsupervised data analyses were used to identify any associations between cytokine activation markers and clinical outcomes. RESULTS: Four of six HCV-infected patients showed significant evidence of cognitive dysfunction and fatigue. Deep sequencing revealed independent viral evolution within the CNS of two cognitively impaired patients. Principal component analysis of peripheral cytokines demonstrated that individuals without cognitive impairment clustered together while a distinct cytokine pattern emerged with patients exhibiting cognitive dysfunction and fatigue. CONCLUSIONS: Deep sequencing demonstrated unique viral variants in the CSF of two cognitively impaired patients consistent with CNS replication or sequestration. Meanwhile, compartmentalization was absent in infected patients with no neurocognitive impairment. Examination of cytokine profiles in HCV-infected patients with cognitive dysfunction revealed elevated peripheral cytokine levels resulting in a distinct cytokine profile that may be related to cognitive impairment or viral penetration into the CNS. Further studies to determine the significance of unique HCV variants within the CNS are warranted.

Clinical findings in a multi-ethnic adult hepatitis B virus patient population in Denmark with emphasis on genotypic characteristics.

OBJECTIVE: Most knowledge about chronic hepatitis B virus (HBV) infection is based upon studies in high-endemic areas with one or two predominant genotype(s). The aim of the study was to describe clinical characteristics of a heterogeneous genotypic HBV patient population in a low-endemic European country. METHODS: Data from HBV patients currently followed in a Danish university hospital and affiliated regional clinics were reviewed in accordance to genotype status. RESULTS: Of 540 HBV patients, 462 (86%) were of non-Danish ethnicity originating from 43 different countries. HBV genotype was known in 37% of the patients: A (11%), B (25%), C (25%), D (37%) and E (2%). Logistic regression analysis of pre-treatment data among genotype A-D patients receiving nucleos(t)ide analogue (NA) therapy revealed a decreased HBeAg rate by age (OR = 0.93; CI: 0.89-0.97; p < 0.01) and an increased rate in genotype C patients (OR = 20.5; CI: 3.3-129; p < 0.01). Among untreated patients HBeAg rate was also significantly decreased by age (OR = 0.90 (0.85:0.95; p < 0.0001), whereas the rate was increased in both genotype B and C patients (OR = 7.5; CI: 1.8-30.5; p < 0.01 and OR = 12.2; CI: 3.2-46.6; p < 0.001, respectively). No significant variation was found in HBV DNA level in any of the two groups when adjusting for age, gender, genotype and HBeAg. Increased liver pathology prevalence was, irrespectively of treatment status, associated to age and male gender, but not to any genotype. CONCLUSION: In this study population, genotype B and C was found associated with higher HBeAg rate but not with increased liver pathology.

A review of female genital schistosomiasis.

In a review of the studies on genital schistosomiasis, the cervix, the Fallopian tubes, and the vagina are the most common gynaecological sites to harbour Schistosoma haematobium. Lesions are caused by host responses to dead or viable schistosomiasis eggs and may render women with genital schistosomiasis susceptible to HIV. The typical genital changes, such as sandy patches and pathological blood vessels may make women susceptible to super-infection, cause contact bleeding, decreased fertility, abortions, discharge and bleeding. Further research is needed to find simple, low-tech diagnostic methods, treatment for chronic lesions, and to explore the preventive effects of mass drug administration on symptoms, sandy patches, HPV and the HIV epidemic.

Semen quality in Schistosoma haematobium infected men in Madagascar.

The seminal vesicles and the prostate are frequently affected by egg-induced inflammation in Schistosoma haematobium infected men. The objective of this study was to assess the semen quality in men with male genital schistosomiasis (MGS). The examination of the semen samples was performed in men aged 15 to 49 years living an S. haematobium endemic area in Madagascar prior to anti-schistosoma treatment with praziquantel and five months later. Men from the high endemic Sirama sugarcane plantation with positive egg excretion in the urine and circulating anodic antigen (CAA) present in serum (n=85) were compared to men (without egg excretion and no CAA) from the neighbouring low-endemic Mataipako village (n=57). The proportion of men with egg excretion in semen was significantly higher in Sirama than in Mataipako (53% versus 4%), whereas the median ejaculate volume was significantly lower in Sirama (1.8 ml versus 2.4 ml). There was no statistical difference in median spermatocyte counts and in the proportions of men detected with azoospermia. The mean apoptotic rate was 7.8% in a subgroup of 30 men from Sirama. A positive correlation was found between apoptotic rate and seminal eosinophil cationic protein (ECP) level (rho=0.560; P<0.001). At follow up, egg excretion and ECP level in semen declined significantly and were paralleled by a significant reduction in the apoptotic rate. The study suggests that S. haematobium infection is associated with sperm apoptosis and a reduced production of seminal fluid. Egg induced inflammation in the seminal vesicles and the prostate could be underlying mechanism for both observations.

Eosinophil cationic protein, soluble egg antigen, circulating anodic antigen, and egg excretion in male urogenital schistosomiasis.

Markers of male genital schistosomiasis (MGS) are needed to elucidate the consequences for reproductive health. Eosinophil cationic protein (ECP) and soluble egg antigen (SEA) in urine and semen, and circulating anodic antigen (CAA) in serum were assessed as MGS markers. Egg counts, ECP, and SEA in urine and CAA in serum, correlated positively. Seminal egg excretion exhibited marked day-to-day variations, but counts correlated positively with urinary egg counts and SEA in semen and with CAA. Positive predictive values with reference to seminal egg excretion were as follows: seminal ECP (52%), seminal SEA (83%), CAA (97%), and urinary egg excretion (82%). SEA in semen and CAA in serum constitute potential markers of MGS. However, urine egg counts as an indirect marker of MGS remains the preferred diagnostic method from a public health perspective.

Increased prevalence of leukocytes and elevated cytokine levels in semen from Schistosoma haematobium-infected individuals.

In this study, we investigated the seminal inflammatory response to egg infestation of the urogenital organs in 240 semen-donating men aged 15-49 years living in a Schistosoma haematobium-endemic area of Madagascar. In 29 subjects (12%) with excretion of > or =5 ova/ejaculate, leukocytospermia (>10(6) leukocytes/mL) and the presence of seminal lymphocytes and eosinophil leukocytes were each significantly more prevalent than in 74 subjects (31%) who were S. haematobium negative (P<.01). In addition, seminal levels of interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor- alpha were significantly higher among seminal egg-excreting subjects than among infection-negative subjects (P<.001). Sexually transmitted infection (STI) with Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and/or Trichomonas vaginalis did not act as a confounding factor for the observed associations. At follow-up, 6 months after systematic antischistosomiasis and STI syndrome treatment at baseline, the prevalence of seminal leukocytes decreased significantly among the previously seminal egg-positive subjects. The same tendency was observed for the posttreatment levels of cytokines. Numerous studies have already shown an association between STI-associated genital inflammation and human immunodeficiency virus (HIV) propagation. Therefore, the results of the present study suggest that male urogenital schistosomiasis may constitute a risk factor for HIV transmission, as a result of egg-induced inflammation in the semen-producing pelvic organs.

Health-related challenges in United States Peace Corps Volunteers serving for two years in Madagascar.

BACKGROUND: The United States Peace Corps has nearly 8000 Volunteers (PCVs) working in more than 70 countries, predominantly in the developing part of the world. The volunteers are challenged by many new and unfamiliar health problems, as a result of change in living conditions during their service. The goal of this study was to assess the health problems of PCVs in Madagascar, and to use this information to evaluate the effectiveness of the current PCV health support program. METHODS: PCVs, finalizing their 2 years of service, were enrolled in the study. Data were retrieved from individual Peace Corps service medical records, the close of service (COS) physical evaluation, and a PCV questionnaire, which elicited additional self-reported health problems and concerns. RESULTS: Sixty-nine PCVs took part in the study. Median age at COS was 24 years (95% CI 23-26 years), and the male/female ratio was 1 : 3.6 (15 males and 54 females). Skin, gastrointestinal and respiratory infections constituted the three most common reported health problems. Among the registered parasitic infections were ova and parasites in the stool (42.0%), confirmed and presumptive malaria (15.9%) and schistosomiasis (11.6%). Female PCVs more frequently reported dermatologic manifestations than male PCVs: postadolescent acne (48.2% vs. 13.3%) and telogen hair loss (33.3% vs. 6.7%). Amenorrhea, as the most commonly reported menstrual alteration during service, was reported by 15 (27.7%) female PCVs. CONCLUSIONS: The PCVs in Madagascar encounter a broad range of health-related problems, most of which are preventable infectious diseases. Reinforcement of the preservice personal health-training curriculum later during service is needed. Reported dermatologic and menstrual disturbances in female subjects may be associated with stress-related estrogen imbalance. More studies are warranted to assess the stress impact of long-term travel on the female physiology.

Sexual behavior and sexually transmitted infections in men living in rural Madagascar: implications for HIV transmission.

BACKGROUND: Madagascar is in the midst of a large HIV epidemic. Therefore, it is important to obtain relevant epidemiologic data that can be used to develop a preventive strategy. GOAL: The goal of the study was to assess sexual behavior and sexually transmitted infections (STIs) among men living in two coastal villages and one highland village with different levels of endemicity of urogenital schistosomiasis. STUDY DESIGN: Data were obtained from cross-sectional studies on male reproductive health. All men aged 15 to 49 years were offered enrollment. RESULTS: Of 401 men evaluated, 6.5% had used a condom and 45.6% reported having multiple partners in the previous 3 months. Symptoms of urethritis during the previous 7 days were reported by 128 men (31.9%). Urethritis was associated with the youngest age group (15-19 years) and the coastal villages, in which HIV antibodies were found in 0.9% and 2.5%, respectively. The prevalence of Schistosoma hematobium was 31.0% and 55.0% in these two villages, whereas none of the men in the highland village were infected. In bivariate analyses, urogenital schistosomiasis was associated with reported symptoms of urethritis, but it acted as a confounder in multivariate analyses. CONCLUSION: Several risk factors for HIV propagation exist in these rural areas in Madagascar. Young men in particular should be targeted for HIV/STI prevention. Treatment of urogenital schistosomiasis could be considered part of the syndromic STI treatment in areas where S hematobium is endemic, for patients seeking primary care for urethritis.