A narrative review of pelvic floor muscle training in the management of incontinence following prostate treatment

Background and ObjectiveUrinary incontinence following prostate treatment (IPT) is a common complication with corresponding negative impacts on quality of life. Pelvic floor muscle training (PFMT) is a non-invasive treatment strategy to treat combat this clinical issue, and has been recognized by medical associations globally and increasingly supported by large bodies of literature. Accordingly, many studies demonstrate a significant benefit of pelvic floor muscle training to continence status and quality of life in men with incontinence following prostate treatment. However, related research is limited by variety in treatment regimens, outcome measures, and study designs, with unclear impact on treatment success. We aim to provide a brief overview of pathology and incidence of incontinence following prostate surgery and an understanding how PFMT is currently used to treat and prevent this clinical consequence.MethodsA comprehensive literature search was conducted utilizing PubMed, Medline, and Google Scholar. Search criteria included systematic reviews and randomized control trials published in the year 2000 to present. References of resulting studies were further analyzed to identify further articles of relevance. Keywords searched included: “post-prostatectomy incontinence”, “pelvic muscle strengthening”, “Benign Prostatic Hyperplasia”, and “pelvic floor muscle training”. Peer-reviewed publications that demonstrated a novel addition to the existing body of literature on this subject were included.Key Content and FindingsUpon review of the current research landscape, PFMT is largely supported in treatment of IPT. Analysis of current literature on this subject demonstrates heterogeneity in protocols, measures of treatment success, and patient numbers. Nevertheless, benefits to continence and quality of life are noted across an expansive body of literature and as such, PFMT is therefore recommended as an important part of the treatment algorithm following radical prostatectomy.ConclusionsPFMT is an important and effective part of the treatment algorithm in the prevention and treatment of IPT. Additional research is needed to more extensively assess PFMT’s role in treating this clinical consequence, especially following other prostate surgeries.     

In Vitro Digestibility and Bioaccessibility of Nutrients and Non-Nutrients Composing Extruded Brewers’ Spent Grain

This study aimed to evaluate the effect of the extrusion process on the bioaccessibility of brewers’ spent grain (BSG) nutrients (carbohydrates and proteins) and non-nutrients (bioactive compounds). BSG and extruded BSG (EBSG) were digested in vitro simulating human oral-gastro-intestinal digestion and colonic fermentation. The duodenal bioaccessibility of glucose, amino acids and phenolic compounds was analyzed. The fermentability of the dietary fiber was assessed by analysis of short-chain fatty acids. Additionally, assessment of the bioaccessibility of phenolic compounds after colonic fermentation was undertaken. The antioxidant, anti-inflammatory and antidiabetic properties of the bioaccessible compounds were studied. Extrusion caused no change in the digestibility of gluten and glucose bioaccessibility (p > 0.05). Moreover, the bioaccessibility of amino acids and phenolic compounds significantly increased (p < 0.05) due to extrusion. However, higher short-chain fatty acid content was formed in colonic fermentation of BSG (p < 0.05) compared to EBSG. The latter inhibited intracellular ROS formation in IEC-6 cells and showed anti-inflammatory properties in RAW264.7 cells. With respect to antidiabetic properties, glucose absorption was lower, and the inhibition of carbohydrases higher (p < 0.05), in the presence of EBSG compared to BSG. The effects of EBSG and BSG digests on glucose transporters were not significantly different (p > 0.05). In conclusion, extrusion positively affected the nutritional value and health-promoting properties of BSG.     

Assessment of Objective and Subjective Cognitive Function in Patients With Treatment-Resistant Depression Undergoing Repeated Ketamine Infusions

BackgroundSubanesthetic ketamine infusions can elicit rapid and sustained antidepressant effects, yet the potential cognitive impact of ketamine has not been thoroughly examined. This study measured changes in objective and subjective cognitive function following repeated ketamine treatment.MethodsThirty-eight patients with treatment-resistant depression were administered cognitive assessments before and after undergoing 7 i.v. ketamine infusions (0.5 mg/kg over 40 minutes) within a clinical trial examining the efficacy of single and repeated administrations. Depression severity and perceived concentration were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms Self-Report.ResultsTwenty-three participants (60.5%) responded after repeated infusions (≥50% decrease in MADRS total scores). We measured significant improvements in several cognitive domains, including attention, working memory, verbal, and visuospatial memory (effect sizes ranging from Cohen d = 0.37–0.79). Cognitive changes were attributed to reduction in depressive symptoms except for improvement in verbal memory, which remained significant after adjustment for change in MADRS total score (P = .029, η _p²=0.13). Only responders reported improvement in subjective cognitive function with repeated ketamine administration (MADRS item 6, P < .001, d = 2.00; Quick Inventory of Depressive Symptoms Self-Report item 10, P < .001, d = 1.36).ConclusionA short course of repeated ketamine infusions did not impair neurocognitive function in patients with treatment-resistant depression. Further research is required to understand the potential mediating role of response and remission on improved cognitive function accompanying ketamine treatment as well as to examine longer-term safety outcomes. ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01945047","term_id":"NCT01945047"}}NCT01945047     

Postbiotics and Kidney Disease

Chronic kidney disease (CKD) is projected to become the fifth global cause of death by 2040 as a result of key shortcomings in the current methods available to diagnose and treat kidney diseases. In this regard, the novel holobiont concept, used to describe an individual host and its microbial community, may pave the way towards a better understanding of kidney disease pathogenesis and progression. Microbiota-modulating or -derived interventions include probiotics, prebiotics, synbiotics and postbiotics. As of 2019, the concept of postbiotics was updated by the International Scientific Association of Probiotics and Prebiotics (ISAPP) to refer to preparations of inanimate microorganisms and/or their components that confer a health benefit to the host. By explicitly excluding purified metabolites without a cellular biomass, any literature making use of such term is potentially rendered obsolete. We now review the revised concept of postbiotics concerning their potential clinical applications and research in kidney disease, by discussing in detail several formulations that are undergoing preclinical development such as GABA-salt for diet-induced hypertension and kidney injury, sonicated Lactobacillus paracasei in high fat diet-induced kidney injury, GABA-salt, lacto-GABA-salt and postbiotic-GABA-salt in acute kidney injury, and O. formigenes lysates for hyperoxaluria. Furthermore, we provide a roadmap for postbiotics research in kidney disease to expedite clinical translation.     

Evaluation of the multimorbidity network and its relationship with clinical phenotypes in chronic obstructive pulmonary disease: The GALAXIA study

BackgroundChronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition, in which taking into consideration clinical phenotypes and multimorbidity is relevant to disease management. Network analysis, a procedure designed to study complex systems, allows to represent connections between the distinct features found in COPD.MethodsNetwork analysis was applied to a cohort of patients with COPD in order to explore the degree of connectivity between different diseases, taking into account the presence of two phenotypic traits commonly used to categorize patients in clinical practice: chronic bronchitis (CB⁺/CB⁻) and the history of previous severe exacerbations (Ex⁺/Ex⁻). The strength of association between diseases was quantified using the correlation coefficient Phi (ɸ).ResultsA total of 1726 patients were included, and 91 possible links between 14 diseases were established. Although the four phenotypically defined groups presented a similar underlying comorbidity pattern, with special relevance for cardiovascular diseases and/or risk factors, classifying patients according to the presence or absence of CB implied differences between groups in network density (mean ɸ: 0.098 in the CB⁻ group and 0.050 in the CB⁺ group). In contrast, between‐group differences in network density were small and of questionable significance when classifying patients according to prior exacerbation history (mean ɸ: 0.082 among Ex⁻ subjects and 0.072 in the Ex⁺ group). The degree of connectivity of any given disease with the rest of the network also varied depending on the selected phenotypic trait. The classification of patients according to the CB⁻/CB⁺ groups revealed significant differences between groups in the degree of conectivity between comorbidities. On the other side, grouping the patients according to the Ex⁻/Ex⁺ trait did not disclose differences in connectivity between network nodes (diseases).ConclusionsThe multimorbidity network of a patient with COPD differs according to the underlying clinical characteristics, suggesting that the connections linking comorbidities between them vary for different phenotypes and that the clinical heterogeneity of COPD could influence the expression of latent multimorbidity. Network analysis has the potential to delve into the interactions between COPD clinical traits and comorbidities and is a promising tool to investigate possible specific biological pathways that modulate multimorbidity patterns.     

Programmed cell death ligand 1 expression in aggressive pediatric non-Hodgkin lymphomas: frequency,genetic mechanisms,and clinical significance

Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are immunomodulatory molecules over-expressed in lymphomas and are promising immunotherapy targets for hematologic malignancies. However, studies of PD-1/PD-L1 overexpression and their clinical significance in aggressive pediatric non-Hodgkin lymphomas (NHL) are limited. We assessed PD-1/PD-L1 overexpression using immunohistochemistry in 68 aggressive pediatric NHL: ALK-positive anaplastic large cell lymphoma (ALK+ ALCL, n=8), Burkitt lymphoma (BL, n=27), and large B-cell lymphoma (LBCL) de novo LBCL, n=22 and diffuse LBCL arising as monomorphic post-transplant lymphoproliferative disorder [PTLD-DLBCL], n=11. In LBCL, correlations between PD-L1 overexpression and Epstein-Barr virus (EBV) status, cell of origin, stage, nodal status, overall survival (OS), and event-free survival (EFS) were examined. The genetic mechanisms of PD-L1 overexpression were investigated using targeted next-generation sequencing (NGS) and cytogenetic data. All ALK+ ALCL samples, 50.0% of de novo LBCL (11/22), 72.7% of PTLD-DLBCL (8/11), and no BL overexpressed PD-L1. Overexpressed PD-L1 correlated with EBV positivity (P=0.033) in LBCL and lower EFS in de novo LBCL (P=0.017). NGS of select LBCL revealed distinct somatic mutations and an ultra-hypermutated PTLD-DLBCL. Most cases with 9p24.1 copy gains overexpressed PD-L1 although some cases had no discernible genetic drivers of PD-L1 overexpression. Overexpressed PD-L1 is common in pediatric LBCL, associated with EBV positivity and 9p24.1 gains, and may have prognostic significance in de novo LBCL. Furthermore, diverse molecular mechanisms for PD-L1 overexpression in aggressive pediatric NHL can occur. Thus, additional studies exploring the therapeutic and prognostic significance and molecular mechanisms of PD-L1 overexpression in aggressive pediatric NHL are warranted.     

Reproductive toxicity evaluation of dietary butyl benzyl phthalate (BBP) in rats

Butyl benzyl phthalate (BBP) was administered in the diet at 0, 750, 3750, and 11,250 ppm ad libitum to 30 rats per sex per dose for two offspring generations, one litter/breeding pair/generation, through weaning of F2 litters. Adult F0 systemic toxicity and adult F1 systemic and reproductive toxicity were present at 11,250 ppm (750 mg/kg per day). At 11,250 ppm, there were reduced F1 and F2 male anogenital distance (AGD) and body weights/litter during lactation, delayed acquisition of puberty in F1 males and females, retention of nipples and areolae in F1 and F2 males, and male reproductive system malformations. At 3750 ppm (250 mg/kg per day), only reduced F1 and F2 offspring male AGD was present. There were no effects on parents or offspring at 750 ppm (50 mg/kg per day). The F1 parental systemic and reproductive toxicity no observable adverse effect level (NOAEL) was 3750 ppm. The offspring toxicity NOAEL was 3750 ppm. The offspring toxicity no observable effect level (NOEL) was 750 ppm, based on the presence of reduced AGD in F1 and F2 males at birth at 3750 ppm, but no effects on reproductive development, structures, or functions.     

Burkholderia thailandensis Isolated from the Environment,United States

Burkholderia thailandensis, an opportunistic pathogen found in the environment, is a bacterium closely related to B. pseudomallei, the cause of melioidosis. Human B. thailandensis infections are uncommon. We isolated B. thailandensis from water in Texas and Puerto Rico and soil in Mississippi in the United States, demonstrating a potential public health risk.     

Prevalence of Chikungunya,Dengue and Zika viruses in blood donors: a systematic literature review and meta-analysis

BackgroundBlood transfusion centres should understand the epidemiology of emerging diseases that are transmissible through the transfusion of blood components. The risk of transmission of arboviruses through this route has become apparent in recent years. The aim of our study is to summarise the reported prevalence (viraemic rate, seroprevalence and/or antigen detection) of Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) viruses in blood donors according to screening test used and world region.Materials and methodsWe conducted a systematic literature review and meta-analysis having searched for information in the main bibliographic databases (MEDLINE, Embase, and Scopus). The prevalence for each of the viruses was calculated according to the screening test used and geographic location.ResultsWe included 18 records on CHIKV, 71 on DENV, and 27 on ZIKV. The highest prevalences of RNA for CHIKV were 1.9% in Puerto Rico (2014), 1.0% in Thailand (2009), and 1.0% in French Polynesia (2014–15). The highest prevalences of RNA for DENV were 5.5% in Saudi Arabia (2015–16), 2.3% in Madeira, Portugal (2012–13), and 0.6% in Brazil (2012). The highest prevalences of RNA for ZIKV were 2.8% in French Polynesia (2013–14), 2.7% in Brazil (2015–16), and 1.8% in Martinique (2016). Overall seroprevalence, as assessed by IgG antibodies, was 21.6% for CHIKV, 24.0% for DENV, and 5.1% for ZIKV.DiscussionOur study shows a high proportion of donors who are viraemic and asymptomatic, especially during outbreaks, with prevalences surpassing 5% for DENV, 1% for CHIKV, and 2% for ZIKV. These data confirm a clear threat to blood transfusion safety. The elevated seroprevalence for these three arboviruses is also indicative of their wide circulation in populations, correlating with an increased risk of infected but asymptomatic donors. Health centres and institutions must address this threat, especially in tropical regions where the biggest outbreaks occur.