The human urinary microbiome and how it relates to urogynecology

Introduction and hypothesis

Recent studies applying molecular techniques have demonstrated the presence of a urinary microbiota not detected by standard microbiological techniques. These have been found in the urine of healthy individuals and in those suffering from clinical symptoms. The present article reviews the findings of these studies to date, describing the molecular techniques, and specifically outlining any differences in microbiomes in relation to urogynecological disease. Further, the role of commensal bacteria in the lower urinary tract is considered.

Methods

An extensive literature search was conducted to identify articles on the microbiome of the female urinary tract in health and disease. We searched the electronic meta-databases Ovid MEDLINE® 1946–2015 and Embase 1974–2015. The keywords “microbiome, microbiota, bacterial colonization, microbiology, commensal bacteria, and bacteriuria” were searched in combination with “lower urinary tract symptoms, urogenital symptoms, urinary tract infection, overactive bladder and urinary incontinence.” A total of 426 papers were retrieved; 33 were included in this paper.

Results

The microbiome of the female lower urinary tract shows variance between individuals and between age groups. There are significant differences between the microbiota in the lower urinary tract of individuals with urological symptoms and those without, relating to type and proportion of commensal Lactobacillus spp. There is only weak evidence to suggest that Lactobacillus might be applied as a therapeutic measure.

Conclusions

It is still unclear what role microbiota plays in female urinary tract health. The discovery of bacteria in the urine of healthy individuals may have implications for future therapies for lower urinary tract symptoms.

     

Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions

Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome—even when completely “knocked out,” do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations “as a whole” can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient.     

Sedation and analgesia in the pediatric patient

The administration of sedation and analgesia for pediatric gastrointestinal procedures has become routine but is not standardized. For the most part, pediatric endoscopists are encouraged to use their clinical judgment to select between using intravenous (IV) sedation or general anesthesia on an individual patient basis. Commonly administered IV sedation regimens in children combine benzodiazepines with narcotics, but anesthesiologist administered propofol sedation is gaining acceptance among pediatric gastroenterologists. Guidelines for patient monitoring and new technologic advances may help to ensure patient safety for children undergoing endoscopic procedures, no matter what sedation regimen is used.     

Metacognitive mastery moderates the relationship of alexithymia with cluster C personality disorder traits in adults with substance use disorders

Cluster C personality disorder traits have been observed in substance use disorders and linked with poorer outcome. One potential factor which may cause these disturbances in personality function is alexithymia, or the inability to name and express emotion. There may be other proximate factors which moderate the impact of alexithymia on the expression of cluster C traits, such as metacognitive mastery, which is the ability to use knowledge about mental states of self and others to cope with distress and solve social problems. To examine the possibility that mastery mediated the effects of alexithymia on cluster C traits, we assessed each of these constructs using the Metacognitive Assessment Scale Abbreviated, Toronto Alexithymia Scale and SCID II among 58 adults in an early phase of recovery from substance misuse disorders in a residential setting. Results of a multiple regression revealed that, after controlling for symptom severity and severity of substance misuse history, metacognitive mastery moderated the effect of alexithymia on number of cluster C traits. A median split and subsequent ANCOVA revealed that participants with higher levels of alexithymia and poorer metacognitive mastery had more cluster C traits than the other groups. These findings may have clinical implications, suggesting that patients with substance use disorders may benefit from treatment which addresses metacognitive mastery.     

Determinants and Outcomes of Hospice Utilization Among Patients with Advance-Staged Hepatocellular Carcinoma in a Veteran Affairs Population

Background

Hospice provides integrative palliative care for advance-staged hepatocellular carcinoma (HCC) patients, but hospice utilization in HCC patients in the USA is not clearly understood.

Aims

We examined hospice use and subsequent clinical course in advance-staged HCC patients.

Methods

We conducted a retrospective study on a national, Veterans Affairs cohort with stage C or D HCC. We evaluated demographics, clinical factors, treatment, and clinical course in relation to hospice use.

Results

We identified 814 patients with advanced HCC, of whom 597 (73.3%) used hospice. Oncologist management consistently predicted hospice use, irrespective of HCC treatment [no treatment: OR 2.25 (1.18–4.3), treatment: OR 1.80 (1.10–2.95)]. Among patients who received HCC treatment, hospice users were less likely to have insurance beyond VA benefits (47.2 vs. 60.0%, p = 0.01). Among patients without HCC treatment, hospice users were older (62.2 [17.2] vs. 60.2 [14.0] years, p = 0.05), white (62.1 vs. 52.9%, p = 0.01), resided in the Southern USA (39.5 vs. 31.8%, p = 0.05), and had a performance score ≥ 3 (41.9 vs. 31.8%, p = 0.01). The median time from hospice entry to death or end of study was 1.05 [2.96] months for stage C and 0.53 [1.18] months for stage D patients.

Conclusions

26.7% advance-staged HCC patients never entered hospice, representing potential missed opportunities for improving end-of-life care. Age, race, location, performance, insurance, and managing specialty can predict hospice use. Differences in managing specialty and short-term hospice use suggest that interventions to optimize early palliative care are necessary.

     

Venlafaxine alters microvascular perfusion, [I]-beta-CIT binding and BDI scores in flushing postmenopausal women

Background

Although 70% of postmenopausal women suffer from hot flashes the pathophysiology is poorly understood. The serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine provides relief of flushing although the mechanism is unknown and could involve a central effect and/or a peripheral effect. Using single photon emission computed tomography (SPECT) we studied the central serotonin transporter (SERT) in vivo using [¹²³I]-beta-carbomethoxy-3-β-(4-iodophenyl)tropane (beta-CIT) and, as previous studies have shown that reactivity of the skin blood vessels is enhanced in those who flush, we examined cutaneous microvascular perfusion.

Methods

Cutaneous microvascular perfusion was assessed in 31 postmenopausal women, with flushing, using laser Doppler imaging with iontophoresis (LDI + ION), before and after 8 weeks of treatment with venlafaxine. A sub-group of 14 of these women also had SPECT imaging at both time points to evaluate the availability of SERT in the brain. Flush frequency and score was recorded, and Beck Depression Inventory (BDI) II scores were assessed before and after treatment.

Results

Following treatment with venlafaxine, there was a significant reduction in the [¹²³I]-beta-CIT binding ratio, BDI scores, flushing and endothelial dependent perfusion response. [¹²³I]-Beta-CIT reduction was associated with BDI reduction (r² = 0.54; F = 8.8; p = 0.004), but not flushing reduction or perfusion reduction.

Conclusions

Venlafaxine resulted in a decrease in BDI II scores with an associated reduction in [¹²³I]-beta-CIT binding in a group of non-depressed women. It also improved flush frequency and severity which may be as a result of decreases seen in enhanced cutaneous microvascular perfusion.     

Designing a novel visible-light-driven heterostructure Ni–ZnO/S-g-C3N4 photocatalyst for coloured pollutant degradation

In this study, photocorrosion of ZnO is inhibited by doping Ni in the ZnO nanostructure and electron–hole recombination was solved by forming a heterostructure with S-g-C₃N₄. Ni is doped into ZnO NPs from 0 to 10% (w/w). Among the Ni-decorated ZnO NPs, 4% Ni-doped ZnO NPs (4NZO) showed the best performance. So, 4% Ni–ZnO was used to form heterostructure NCs with S-g-C₃N₄. NZO NPs were formed by the wet co-precipitation route by varying the weight percentage of Ni (0–10% w/w). Methylene blue (MB) was used as a model dye for photocatalytic studies. For the preparation of the 4NZO-x-SCN nanocomposite, 4NZO NPs were formed in situ in the presence of various concentrations of S-g-C₃N₄ (10–50% (w/w)) by using the coprecipitation route. The electron spin resonance (ESR) and radical scavenger studies showed that O₂⁻ and OH free radicals were the main reactive species that were responsible for MB photodegradation.

Ni-doped ZnO/S-g-C₃N₄ nanocomposites were formed as a novel heterostructure photocatalyst.