An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female anorectal dysfunction.

INTRODUCTION: The terminology for anorectal dysfunction in women has long been in need of a specific clinically-based Consensus Report. METHODS: This Report combines the input of members of the Standardization and Terminology Committees of two International Organizations, the International Urogynecological Association (IUGA) and the International Continence Society (ICS), assisted on Committee by experts in their fields to form a Joint IUGA/ICS Working Group on Female Anorectal Terminology. Appropriate core clinical categories and sub classifications were developed to give an alphanumeric coding to each definition. An extensive process of twenty rounds of internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). RESULTS: A Terminology Report for anorectal dysfunction, encompassing over 130 separate definitions, has been developed. It is clinically based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different specialty groups involved in female pelvic floor dysfunction. Female-specific anorectal investigations and imaging (ultrasound, radiology and MRI) has been included whilst appropriate figures have been included to supplement and help clarify the text. Interval review (5-10 years) is anticipated to keep the document updated and as widely acceptable as possible. CONCLUSION: A consensus-based Terminology Report for female anorectal dysfunction terminology has been produced aimed at being a significant aid to clinical practice and a stimulus for research. Neurourol. Urodynam. 36:10-34, 2017. © 2016 Wiley Periodicals, Inc., and The International Urogynecological Association

Anal Incontinence

This open access book describes the latest advances in the anal incontinence diagnostic and therapeutic processes. Anal incontinence is a devastating condition heavily impacting on the patients’ lives. Those suffering from this disorder are generally very embarrassed and reluctant to undergo an appropriate clinical evaluation, thus becoming more isolated and worsening the quality of their life. Luckily, nowadays a wide range of treatments is available to improve this oppressive condition; however, the recognition of the related pathophysiological alterations is mandatory to grant its successful management. This volume will help the surgeons community to keep abreast of developments in diagnostics and treatment of this impairing condition. and will provide all health professionals with the appropriate tools to face this impairing condition

Anal Incontinence

This open access book describes the latest advances in the anal incontinence diagnostic and therapeutic processes. Anal incontinence is a devastating condition heavily impacting on the patients’ lives. Those suffering from this disorder are generally very embarrassed and reluctant to undergo an appropriate clinical evaluation, thus becoming more isolated and worsening the quality of their life. Luckily, nowadays a wide range of treatments is available to improve this oppressive condition; however, the recognition of the related pathophysiological alterations is mandatory to grant its successful management. This volume will help the surgeons community to keep abreast of developments in diagnostics and treatment of this impairing condition. and will provide all health professionals with the appropriate tools to face this impairing condition

The effect of ageing on the innervation and total collagen content of human colon.

This thesis addressed the enteric innervations and total collagen content and its distribution within the functional sublayers, namely: mucosa, submucosa and muscularis externa (circular muscle (CM) and taenia coli (TC)) in ageing human colon.Macroscopically normal ascending (AC) and descending (DC) colon was obtained at surgery from cancer patients without diagnosis of diverticular disease or inflammatory bowel disease. Masson’s trichrome and Picrosirius red stains were employed to identify the total collagen content and distribution within the colonic wall. A hydroxyproline assay evaluated the total collagen concentration in the formalin-fixed, paraffin-embedded human colonic samples. Assessment of the subtypes of enteric glial cells (EGCs) and calretinin- immunoreactive (IR) enteric neurons were demonstrated by immunohistochemical method. Standardized procedures were utilised to ensure unbiased counting and densitometric evaluation for further quantitative analysis.The results of the present study demonstrated that greater a collagen content was present in the submucosa and muscularis externa, particularly the TC in the elderly (≥ 65 years) samples compared to adult (< 65 years). The density of S100-IR EGCs declined among the elderly in the CM and within the myenteric plexus (MP) per ganglionic area. There was little or no GFAP-IR EGCs in both adult and elderly colon. Among the elderly, the density of calretinin-IR neurons and fibres were decreased in the submucosal plexus of AC but not clearly in the DC. In the mucosal layer of both AC and DC, the decrease in density of calretinin-IR fibres was greater in the AC compared to DC. Sex related differences were not found when data combined in both the AC and DC samples. Collectively, these results indicate that there are region and sublayer dependent changes in the distribution of total collagen fibres, EGCs and calretinin-IR enteric neurons in ageing human colon. This age-related structural change may differentially impact upon specialised functions and affect colonic physiology

Major prospects for exploring canine vector borne diseases and novel intervention methods using 'omic technologies

Canine vector-borne diseases (CVBDs) are of major socioeconomic importance worldwide. Although many studies have provided insights into CVBDs, there has been limited exploration of fundamental molecular aspects of most pathogens, their vectors, pathogen-host relationships and disease and drug resistance using advanced, 'omic technologies. The aim of the present article is to take a prospective view of the impact that next-generation, 'omics technologies could have, with an emphasis on describing the principles of transcriptomic/genomic sequencing as well as bioinformatic technologies and their implications in both fundamental and applied areas of CVBD research. Tackling key biological questions employing these technologies will provide a 'systems biology' context and could lead to radically new intervention and management strategies against CVBDs

RECENT ADVANCES IN MOLECULAR MEDICINE AND TRANSLATIONAL RESEARCH

ABSTRACT BOO

Practical Clinical Andrology

This open access book offers a valuable resource for understanding the correct pathways in the context of sexual disorders, couple reproduction, gender identity dysphoria, conditions for which patients commonly ask for consultation and treatment. Based on clinical evidence, international guidelines and experts experience, practical clinical management strategies are presented for each condition. Each clinical care pathway is based on updated algorithm, level of evidence, photos and video-clips that describes the clinical presentations and the best practice management through diagnostic tools and medical or surgical treatment. Leading experts from the most important center of excellence in the field of sexual medicine joined to cover the field of andrology in its entirety, each of them dealing with a single topic from the top of their recognized experience and providing a complete and update textbook that will help urologists and other physicians in their daily clinical practice. This book is thought to be a practical and valuable reference for urologists, gynecologists, endocrinologists, psychiatrics and psychologists, and residents who are not specialty trained in andrology. It is designed for both young fellows training in different specialties and coming into contact with andrological issues for the first time and also more experienced clinicians and surgeons requiring updated guidelines and clear advice on the most controversial issues. This book will represent an invaluable quick consulting tool, updated in its scientific contents and rich in tables, images and video-clips

Effects of Chronic High Sucrose With Dietary or Drinking Inclusion on the Electrogenic Glucose Absorption in the Intestinal Tract of Mice (Mus musculus)

The long-term impact of high sugar diets, a factor in the development of obesity and type-2 diabetes, on the intestinal electrogenic sodium dependent glucose transport, the first portal of entry for glucose, is unknown. Here female C57bl/6 mice fed a normal standard chow diet, and 20% sucrose in the drinking water for 8 months, or 35% sucrose inclusion in the diet for 12 months were assessed. The drinking water sucrose treated mice developed obesity, whereas the solid dietary sucrose treated mice did not. Jejunal, ileal and colonic segment differences for electrogenic sodium dependent glucose transport kinetics, mRNA expression of sodium dependent glucose transporters, inflammatory mediators, and insulin signaling genes were assessed in all groups, as novel differences between segments were found in normal mice. Ex vivo intestinal Ussing chamber studies in normal mice characterizing the electrogenic sodium dependent glucose transport followed Hill Equation sigmoidal kinetics demonstrating low affinity, high capacity transport (Vmax of 100.8 ± 24.2 uA/cm2, K0.5 17.6 ± 0.9 mM) in the jejunum, high affinity, high capacity transport in the ileum (Vmax of 111.4 ± 17.5 uA /cm2, K0.5 7.4 ± 1.0 mM) and the absence of transport in the colon. The preferential fit of the kinetics to the Hill Equation sigmoidal kinetics in each of the tissues, suggest mouse SGLT are working allosterically, or that there are multiple transporters working together to create the currents observed, more than in other mammals previously reported. Although segmental differences in inhibition by dapagliflozin, an SGLT2 inhibitor or phloridzin dihydrate, an SGLT1 inhibitor were evident, gene expression analysis of the SGLT 1- 6 could not fully explain these regional differences in kinetics. Non-the-less, the kinetics were highly modified by sucrose treatments, with a significant shift in the segmental transport, with a decrease in transport in the proximal segments of the intestine and increase distally in both groups. Most notable was, a significant increase in the Vmax and K0.5 in the ileum of drinking water sucrose treated mice and the appearance of colonic glucose induced Hill equation kinetic transport in the solid dietary sucrose treated mice. Interestingly, the novel currents induced in mice treated with both drinking water sucrose and solid dietary sucrose diet were insensitive to inhibition by dapagliflozin or phloridzin dihydrate. This indicates that neither SGLT1 or SGLT2 were responsible for the changes in transport induced by the treatments. Paradoxically, the mRNA expression of SGLT1 was significantly increased in the jejunum, ileum and colon of the drinking water sucrose treated mice and, SGLT2 was significantly increased in the jejunum and colon of the solid dietary sucrose treated mice. Additionally, none of the other SGLT family members known for glucose transport assessed by qRT-PCR could account for the observed kinetic changes. This is suggestive of an orphan sodium dependent glucose transporter or posttranslational modification of the identified transporters. Finally, these kinetic changes do not seem to be caused by inflammation or dysfunctions in the insulin signaling pathway, as the genes for both inflammatory mediators and insulin signaling were generally unchanged from control mice in both groups. The exceptions, not consistent in all segments, was a significant increase in TGF-b1 in the drinking water sucrose treated mouse jejunum and ileum, and IRS-2 in the drinking water sucrose treated mouse jejunum. Identifying these novel segmental kinetic differences in electrogenic glucose absorption in the mouse intestine and the changes induced by chronical sucrose provided in the drinking water, including the appearance of a putative orphan transporter, not only adds to the understanding of the pathophysiology of the obesity, type-2 diabetes but could direct future therapy

Emergent patterns of cellular phenotypes in health and disease

The cellular framework that constitutes the building blocks of every living organism undergoes significant changes and transformations throughout its live time. In humans, many processes that involve these cellular changes can greatly influence the healthspan and survival of individuals, two of such processes include: aging and cancer. The two related, yet independent processes both arise due to the deterioration of ‘naïve’ cellular function, and the deficiency—later inability, of cells to properly regulate its physiology. Published studies have demonstrated a bi-phasic relationship between cancer and aging. With the incidences of cancer increasing with increasing age, followed by a plateau point and subsequent decrease; with cancer-type dependent shifts in this plateau point with age. There are a multitude of factors that affect the initiation and rate of progression of these cellular changes, and they stem from both intrinsic factors—such as the individuals’ underlying molecular and phenotypic profiles (i.e. genetics and protein expressions)—and extrinsic factors, such as lifestyle and environmental influences. To gain better understanding of these two naturally occurring processes, I took a piece-wise approach and asked two overarching questions. In regards to aging I asked how does the biochemical and biophysical features of cells construct the phenotypic portrait of human aging, and cane it be used to determine the biological age of individuals? Likewise, in regards to cancer: how does the cells’ physical properties associate with cancer progression and metastasis, and can it predict metastatic state based on the features of individual cells? In the first part of this study, I focus on human aging. Many studies have shown that there are marked changes in the cells’ molecular profiles and phenotypic behaviors with increasing age. To better understand this I procured a cohort of primary dermal fibroblasts and measured various aspects of the cellular biochemical framework (cell secretions, DNA damage response and DNA organization, cytoskeletal content and organization, and ATP content), as well as cellular biophysical features (morphology, motility, wound closure, traction strength, and cytoplasmic rheological properties). With this comprehensive approach, I was able to quantify age-dependent changes in various cellular features, and use these features to further predict biological age with a high degree of certainty. Knowing the biological age of an individual is important, since it is now apparent from the literature that the biological age is a better predictor of human healthspan and longevity than their corresponding chronological age. Secondly, according to the American Cancer Society, two out of every five persons in the US will develop cancer during his/her lifetime, with ninety percent of cancer-related deaths resulting from metastases, i.e. the migration of cancer cells from the primary tumor to distal sites in other organs. Since the completion of the Human Genome Project, researchers have focused on trying to understand the genetic basis of metastasis in an effort to better predict disease progression and uncover new therapeutic targets. However, possibly due to the inherent heterogeneity of cancer, no genetic signatures that clearly delineate cells from the primary tumors versus cells from metastatic sites have been found. Recent estimates suggest that millions of cells are shed from a primary tumor site each day, yet, progression to metastatic disease often take years, suggesting that metastasis is a highly inefficient process. From a biophysical perspective, I reasoned that in order to successfully overcome the difficult multi-step metastatic cascade—invasion and migration through the dense, tortuous stromal matrix, intravasation, survival of shear forces of blood flow, successful re-attachment to blood vessel walls, colonization at distal sites, and reactivation following dormancy—metastatic cells may share precise sets of physical properties. And these key physical properties (which can be thought of as the ensemble effects of it’s genetic, epigenetic and proteomic profiles, etc.) may contribute to the progression and diminished response to therapeutics exhibited by metastatic cells. Using a cohort of 13 clinically annotated PDAC (Pancreatic ductal adenocarcinoma) patient samples, cells were subjected to a phenotyping platform that I have co-developed—htCP (high-throughput cell phenotyping). This study revealed that using biophysical features described by the variations in the cellular morphological features, I was able to discover a phenotypic signature for metastasis, demonstrated in pancreatic and breast cancers, for both 2D and 3D environments