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Small extracellular vesicles (sEVs) play a central role in cell-to-cell communication in normal physiology and in disease, including gestational diabetes mellitus (GDM). The goal of the present study was to test the hypothesis that chronic administration of sEVs isolated from GDM causes glucose intolerance in healthy pregnant mice. Small EVs were isolated from plasma between 24 and 28 weeks gestation from healthy pregnant women (controls) and GDM, and infused intravenously for 4 days in late pregnant mice using a mini-osmotic pump. Subsequently in vivo glucose tolerance was assessed, and muscle and adipose tissue insulin sensitivity and islet glucose stimulated insulin secretion (GSIS) were determined in vitro. Mice infused with sEVs from GDM developed glucose intolerance. Administration of sEVs from controls, but not sEVs from GDM women, stimulated islet GSIS and increased fasting insulin levels in pregnant mice. Neither infusion of sEVs from controls nor from GDM women affected muscle insulin sensitivity, placental insulin or mTOR signaling, placental and fetal weight. Moreover, these results were not associated with immunomodulatory effects as human sEVs did not activate mouse T cells in vitro. We suggest that circulating sEVs regulate maternal glucose homeostasis in pregnancy and may contribute to the attenuated islet insulin secretion and more pronounced glucose intolerance in GDM as compared with healthy pregnancy.

Asthma and obesity are both inflammatory complications of pregnancy and when combined contribute to an increased risk of uncontrolled asthma during pregnancy and poor perinatal outcomes. Our previous work has identified the presence of maternal asthma is associated with a proinflammatory milieu in the placenta and reduced fetal growth. The current study was designed to determine the relationships between immunomodulatory metabolic pathways and inflammation and establish whether these pathways are associated with uncontrolled asthma in obese pregnant women. Fifty-three obese (BMI >30) pregnant women were recruited prospectively. Participants were classified as having no asthma, controlled asthma, and uncontrolled asthma based on a doctor diagnosis and assessment using the Asthma Control Questionnaire (ACQ). Circulating plasma concentrations of metabolic hormones leptin, adiponectin, insulin, glucose, and extracellular vesicle (EVs) associated cytokines were measured at 18- and 36-weeks gestation. Concentrations of metabolic and inflammatory markers among obese participants with or without asthma were not significantly different throughout gestation. However total adiponectin concentrations increased as gestation progressed in obese, non-asthmatic women but did not increase in women with asthma. Plasma adiponectin and leptin levels in women with uncontrolled asthma were positively correlated with EV inflammatory markers including GM-CSF, IL-6, TNFα and IFNγ protein. This study demonstrated that most metabolic markers remain unchanged with the presence and severity of asthma in obese pregnant women. However, differences in the associations between metabolic and inflammatory pathways were observed in women with asthma and may be one of the mechanisms contributing to uncontrolled asthma in obese pregnant women.

The World Professional Association for Transgender Health has recently updated its Standards of Care (SOC) clinical guidelines for the transgender and gender diverse (TGD) population. This article aims to outline the 2012 SOC for surgical management of TGD people and describe the changes to the surgical management guidelines in this year's update.The surgical management guidelines between the 7th and 8th SOC were compared and contrasted. The 8th SCO included language that broadened surgical interventions and emphasized the new responsibilities of surgeons. Major changes include reducing the number of letters of referral by a mental health provider to one for those choosing to undergo surgical treatment.The latest surgical management guidelines for the TGD population emphasizes a holistic approach utilizing a multidisciplinary team in both pre- and postoperative settings.

Gender dysphoria affects over 1 million American adults. Vaginoplasty is a critical step in gender affirmation, and many patients have insufficient genital skin for full-depth penile inversion vaginoplasty (PIV). We reviewed the literature for technical considerations addressing this and present our data supporting the use of peritoneal flaps (Davydov technique).A comprehensive review of modern literature was conducted. Second, we present a retrospective case review of our experience with PIV, including data from procedures utilizing peritoneal flaps.We identified 20 original articles, including retrospective and prospective case and cohort studies. Approaches included the application of local soft tissue grafts and flaps, peritoneal flaps, and intestinal segments. Between June 2018 and February 2021, 47 patients at our institution, underwent PIV for the treatment of gender dysphoria. Nineteen of those patients underwent robotic-assisted peritoneal flap procedure in addition to PIV. In this cohort, the mean follow-up was 200.6 ± 124.8 days. Mean neovaginal depth was 13.1 ± 3.0 cm intra-operatively and 11.0 cm at the last follow-up. Twenty-six percent of complications were Clavien Grade 1 or 2; others included wound dehiscence (30.4%), perianal and urethral fistula (13.0%), and neovaginal stenosis (8.7%). The majority of patients reported satisfactory results in terms of sexual function with intact tactile and erogenous sensation. Almost half were able to have penetrative vaginal intercourse at the last follow-up. We did not aim to perform statistical calculations to compare the outcomes of PIV with and without robotic-assisted peritoneal flap augmentation, as the groups were not constructed in that manner. However, it is evident that anatomical and functional results as well as the distribution of postoperative complications seem similar.Vaginoplasty is indicated in a growing population of patients with a wide range of medical histories and anatomic variations. Genitourinary reconstructive surgeons must have several methods to achieve full-depth vaginoplasty in cases of inadequate genital skin. Peritoneal flaps serve as a versatile, safe, and functionally advantageous solution.

Our sleep-wake cycle is determined by the interaction between our homeostatic sleep drive and circadian rhythm. Each of us has a personalised biological rhythm or chronotype that determines the optimal time to fall asleep and wake up. Chronic sleep deprivation has been linked to the development of several physical and mental health disorders, as well as accidents and occupational errors. Around the world, growing recognition of the importance of sleep has led to the adoption of practices that promote sleep health. Given that Singaporeans were consistently found to be one of the most sleep-deprived populations in the world, we believe that there is an urgent need to pursue the introduction of community-based sleep health interventions here. This includes sleep education and promotion of sleep hygiene, adopting practices to reduce social jetlag and improve sleep health, and enhancing screening and treatment of sleep disorders.

Spontaneous preterm birth is the leading cause of neonatal mortality and morbidity globally. Activation of the maternal immune system leads to a downstream cascade of proinflammatory events that culminate in the activation of spontaneous uterine contractions and the rupture of the foetal membranes. Anti-inflammatory agents may be a novel therapeutic approach to prevent inflammation-induced myometrial contractions and premature rupture of foetal membranes. The polyphenol gallic acid has been previously shown to exert potent anti-inflammatory effects. Thus, this study aimed to determine the effect of gallic acid on proinflammatory and pro-labour mediators in cytokine-stimulated gestational tissues in vitro. In primary human cells isolated from myometrium and foetal membranes (decidua, and amnion mesenchymal and epithelial cells), gallic acid treatment suppressed inflammation-induced expression of proinflammatory cytokines and chemokines and extracellular matrix-degrading and matrix-remodelling enzymes. Gallic acid also significantly inhibited inflammation-induced myometrial activation as evidenced by decreased expression of contraction-associated proteins, the uterotonic PGF2α and collagen cell contractility. Using a global proteomic approach, gallic acid may differentially regulate proteins associated with collagen synthesis, cell contractility and protein synthesis in primary myometrial and decidual cells. In summary, gallic acid inhibited inflammation-induced mediators involved in active labour in primary cells isolated from myometrium and foetal membranes. These in vitro studies suggest that the polyphenol gallic acid may be able to suppress the production of proinflammatory and pro-labour mediators involved in myometrial contractions and rupture of foetal membranes. Future preclinical studies may elucidate the efficacy of gallic acid in preventing inflammation-driven preterm birth.

Purpose: Transparently reported, high-quality randomized controlled trials (RCTs) play a critical role in guiding evidence based clinical practice and informing evidence-based guidelines in patient...

Small extracellular vesicles (sEVs) released from the extravillous trophoblast (EVT) are known to regulate uterine spiral artery remodeling during early pregnancy. The bioactivity and release of these sEVs differ under differing oxygen tensions and in aberrant pregnancy conditions. Whether the placental cell-derived sEVs released from the hypoxic placenta contribute to the pathophysiology of preeclampsia is not known. We hypothesize that, in response to low oxygen tension, the EVT packages a specific set of proteins in sEVs and that these released sEVs interact with endothelial cells to induce inflammation and increase maternal systemic blood pressure. Using a quantitative MS/MS approach, we identified 507 differentially abundant proteins within sEVs isolated from HTR-8/SVneo cells (a commonly used EVT model) cultured at 1% (hypoxia) compared with 8% (normoxia) oxygen. Among these differentially abundant proteins, 206 were up-regulated and 301 were down-regulated (P < 0.05), and they were mainly implicated in inflammation-related pathways. In vitro incubation of hypoxic sEVs with endothelial cells, significantly increased (P < 0.05) the release of GM-CSF, IL-6, IL-8, and VEGF, when compared with control (i.e. cells without sEVs) and normoxic sEVs. In vivo injection of hypoxic sEVs into pregnant rats significantly increased (P < 0.05) mean arterial pressure with increases in systolic and diastolic blood pressures. We propose that oxygen tension regulates the release and bioactivity of sEVs from EVT and that these sEVs regulate inflammation and maternal systemic blood pressure. This novel oxygen-responsive, sEVs signaling pathway, therefore, may contribute to the physiopathology of preeclampsia.

Extracellular vesicles (EVs) carry a wide range of molecules, such as proteins, RNAs, and DNA. EVs are secreted from a wide range of cells, including placental cells. Interestingly, EVs secreted from placental cells have been identified in maternal circulation as early as 6 weeks of gestation, and their concentration increases with the gestational age. While there is growing interest in elucidating the role of exosomes during normal and complicated pregnancies, progress in the field has been delayed because of the inability to quantify placental EVs from the maternal circulation. Recent reports have demonstrated the presence of placental-type alkaline phosphatase (PLAP) EVs only in the blood of pregnant women, indicating that PLAP is a marker to identify EVs secreted from the placenta. Therefore, here we describe a workflow to quantify placental EVs from maternal circulation using a targeted proteomics approach based on selecting specific peptides identified in the PLAP protein.

Introduction: Proton pump inhibitors (PPIs) are often prescribed beyond their medically-approved duration of use. Long-term PPI use has been linked with numerous adverse effects and contributes to polypharmacy. This study sought to understand the effect of evidence-based education to resident and faculty physicians on deprescribing inappropriate PPIs. We hypothesized that this educational intervention would result in fewer inappropriate PPI prescriptions. Methods: We performed a chart review on all adult patients in a family medicine residency program practice, identifying those inappropriately taking PPIs. All physicians in the practice participated in an educational intervention regarding deprescribing inappropriate PPIs and were given frequent reminders to continue their deprescribing efforts. We reviewed charts at the end of the study to identify patients with successful deprescribing attempts. Results: Of the 187 patients prescribed inappropriate PPIs in the study, 100 remained on PPIs at the end of the study (46.6% success rate). There was a significant decrease in the number of patients inappropriately prescribed PPIs by each physician over the course of the study, from a mean of 17.0 (beginning) to 9.1 (end). Conclusion: Physician education with reminders is an effective means of reducing the number of inappropriate PPIs prescribed in a family medicine residency practice. Future studies could investigate the effectiveness of educational interventions with other medication classes that are often prescribed inappropriately.

Exosomes are small nanovesicles that carry bioactive molecules which can be delivered to neighbouring cells to modify their biological functions. Studies have showed that exosomes from ovarian cancer (OVCA) cells can alter the cell migration and proliferation of cells within the tumour microenvironment, an effect modulated by the invasiveness capacity of their originating cells. Using an OVCA cell line xenograph mouse model, we showed that exosomes derived from a high invasiveness capacity cell line (exo-SKOV-3) promoted metastasis in vivo compared with exosomes from a low invasiveness capacity cell line (exo-OVCAR-3). Analysis from anin vivo imaging system (IVIS) revealed that exo-SKOV-3 formed metastatic niches, whereas exo-OVCAR-3 formed colonies of clustered cells close to the site of injection. Interestingly, kinetic parameters showed that the half-maximal stimulatory time (ST50) of tumour growth with exo-OVCAR-3 (4.0 ± 0.31 weeks) was significantly lower compared with the ST50 in mice injected with exo-SKOV-3 (4.5 ± 0.32 weeks). However, the number of metastic nodes in mice injected with exo-SKOV-3 was higher compared with exo-OVCAR-3. Using a quantitative mass spectrometry approach (SWATH MS/MS) followed by bioinformatics analysis using the Ingenuity Pathway Analysis (IPA), we identified a total of 771 proteins. Furthermore, 40 of these proteins were differentially expressed in tumour tissues from mice injected with exo-SKOV-3 compared with exo-OVCAR-3, and associated with Wnt canonical pathway (β-catenin). Finally, we identified a set of proteins which had elevated expression in the circulating exosomes in association with tumour metastasis. These observations suggest that exosomal signalling plays an important role in OVCA metastasis.

The da Vinci single-port (SP) system (Intuitive Surgical, Sunnyvale, CA) is the newest robotic platform released and approved for use in the urologist's armimentarium. This article (and complementary video) aims to summarize the most common problems that have been encountered at the University of Illinois at Chicago when using the SP system. Moreover, solutions to these issues will be presented.

Proactive steps have been taken by the public healthcare sector in Singapore to bring about awareness of mental health in terms of mental health promotion, early recognition and seeking help, with an increasing focus on making mental healthcare accessible and delivering it within the community setting where possible. Examples are the Mental Health General Practitioner Partnership Programme, National Mental Health Blueprint and Community Mental Health Masterplan. The current challenge is to train and involve more primary care doctors in the care of persons with mental health conditions. This paper describes the goals of psychiatric training in primary care and the avenues for training that are available to family medicine residents and family physicians.

Background Caveolae proteins play diverse roles in cancer development and progression. In prostate cancer, non‐caveolar caveolin‐1 (CAV1) promotes metastasis, while CAVIN1 attenuates CAV1‐induced metastasis. Here, we unveil a novel mechanism linking CAV1 to selective loading of exosomes with metastasis‐promoting microRNAs. Results We identify hnRNPK as a CAV1‐regulated microRNA binding protein. In the absence of CAVIN1, non‐caveolar CAV1 drives localisation of hnRPNK to multi‐vesicular bodies (MVBs), recruiting AsUGnA motif‐containing miRNAs and causing their release within exosomes. This process is dependent on the lipid environment of membranes as shown by cholesterol depletion using methyl‐β‐cyclodextrin or by treatment with n‐3 polyunsaturated fatty acids. Consistent with a role in bone metastasis, knockdown of hnRNPK in prostate cancer PC3 cells abolished the ability of PC3 extracellular vesicles (EV) to induce osteoclastogenesis, and biofluid EV hnRNPK is elevated in metastatic prostate and colorectal cancer. Conclusions Taken together, these results support a novel pan‐cancer mechanism for CAV1‐driven exosomal release of hnRNPK and associated miRNA in metastasis, which is modulated by the membrane lipid environment., Highlights 1. Non‐caveolar caveolin‐1 drives non‐canonical localization of hnRNPK to multivesicular bodies (MVB) via membrane raft‐dependent mechanism. 2. MVB localized hnRNPK mediates EV loading of AsUGnA motif‐containing miRNA, which is required for EV‐induced in vitro osteoclastogenesiss. 3. Elevated EV hnRNPK in biofluids from metastatic cancer patients suggest a role as a biomarker.

Preeclampsia (PE) is associated with long-term morbidity in mothers and lifelong morbidities for their children, ranging from cerebral palsy and cognitive delay in preterm infants, to hypertension, diabetes and obesity in adolescents and young adults. There are several processes that are critical for development of materno-fetal exchange, including establishing adequate perfusion of the placenta by maternal blood, and the formation of the placental villous vascular tree. Recent studies provide persuasive evidence that placenta-derived extracellular vesicles (EVs) represent a significant intercellular communication pathway, and that they may play an important role in placental and endothelial cell (both fetal and maternal) function. These functions are known to be altered in PE. EVs can carry and transport a wide range of bioactive molescules that have potential to be used as biomarkers and therapeutic delivery tools for PE. EV content is often parent cell specific, thus providing an insight or "thumbprint" of the intracellular environment of the originating cell (e.g., human placenta). EV have been identified in plasma under both normal and pathological conditions, including PE. The concentration of EVs and their content in plasma has been reported to increase in association with disease severity and/or progression. Placenta-derived EVs have been identified in maternal plasma during normal pregnancy and PE pregnancies. They contain placenta-specific proteins and miRNAs and, as such, may be differentiated from maternally-derived EVs. The aim of this review, thus, is to describe the potential roles of EVs in preecmpatic pregnancies, focussing on EVs secreted from placental cells. The biogenesis, specificity of placental EVs, and methods used to characterise EVs in the context of PE pregnancies will be also discussed.

Background Gestational diabetes mellitus (GDM) is a serious public health issue affecting 9–15% of all pregnancies worldwide. Recently, it has been suggested that extracellular vesicles (EVs) play a role throughout gestation, including mediating a placental response to hyperglycaemia. Here, we investigated the EV-associated miRNA profile across gestation in GDM, assessed their utility in developing accurate, multivariate classification models, and determined the signaling pathways in skeletal muscle proteome associated with the changes in the EV miRNA profile. Methods Discovery: A retrospective, case–control study design was used to identify EV-associated miRNAs that vary across pregnancy and clinical status (i.e. GDM or Normal Glucose Tolerance, NGT). EVs were isolated from maternal plasma obtained at early, mid and late gestation (n = 29) and small RNA sequencing was performed. Validation: A longitudinal study design was used to quantify expression of selected miRNAs. EV miRNAs were quantified by real-time PCR (cases = 8, control = 14, samples at three times during pregnancy) and their individual and combined classification efficiencies were evaluated. Quantitative, data-independent acquisition mass spectrometry was use to establish the protein profile in skeletal muscle biopsies from normal and GDM. Results A total of 2822 miRNAs were analyzed using a small RNA library, and a total of 563 miRNAs that significantly changed (p 90%. We identified a set of proteins in skeletal muscle biopsies from women with GDM associated with JAK-STAT signaling which could be targeted by the miRNA-92a-3p within circulating EVs. Interestingly, overexpression of miRNA-92a-3p in primary skeletal muscle cells increase insulin-stimulated glucose uptake. Conclusions During early pregnancy, differently-expressed, EV-associated miRNAs may be of clinical utility in identifying presymptomatic women who will subsequently develop GDM later in gestation. We suggest that miRNA-92a-3p within EVs might be a protected mechanism to increase skeletal muscle insulin sensitivity in GDM.

Preeclampsia (PE) is associated with long-term morbidity in mothers and lifelong morbidities for their children, ranging from cerebral palsy and cognitive delay in preterm infants, to hypertension, diabetes and obesity in adolescents and young adults. There are several processes that are critical for development of materno-fetal exchange, including establishing adequate perfusion of the placenta by maternal blood, and the formation of the placental villous vascular tree. Recent studies provide persuasive evidence that placenta-derived extracellular vesicles (EVs) represent a significant intercellular communication pathway, and that they may play an important role in placental and endothelial cell (both fetal and maternal) function. These functions are known to be altered in PE. EVs can carry and transport a wide range of bioactive molescules that have potential to be used as biomarkers and therapeutic delivery tools for PE. EV content is often parent cell specific, thus providing an insight or "thumbprint" of the intracellular environment of the originating cell (e.g., human placenta). EV have been identified in plasma under both normal and pathological conditions, including PE. The concentration of EVs and their content in plasma has been reported to increase in association with disease severity and/or progression. Placenta-derived EVs have been identified in maternal plasma during normal pregnancy and PE pregnancies. They contain placenta-specific proteins and miRNAs and, as such, may be differentiated from maternally-derived EVs. The aim of this review, thus, is to describe the potential roles of EVs in preecmpatic pregnancies, focussing on EVs secreted from placental cells. The biogenesis, specificity of placental EVs, and methods used to characterise EVs in the context of PE pregnancies will be also discussed.

The objective of this study was to quantify the differences in surface electromyogram (EMG) signal characteristics between affected and contralateral arm muscles of hemispheric stroke survivors. EMG signals were recorded from the biceps brachii muscles using single differential electrodes. Four chronic stroke subjects performed isometric elbow flexions at sub-maximal voluntary contraction levels on both the affected and contralateral limbs. The force generated on the contralateral side was matched to the force generated on the affected side. We observed different types of EMG activation on the affected side compared to the contralateral side.Specifically, two subjects showed lower RMS EMG activity on the affected side whereas two subjects showed greater EMG activity on the affected side compared to the contralateral side. Analysis of the peak amplitudes of the EMG activity showed greater number of peaks in the EMG on affected side compared to the contralateral side in all subjects. The histogram of the peak amplitudes showed greater number of smaller peak amplitudes in subjects with lower EMG activity on the affected side suggesting a reliance on smaller motor units. Our combined EMG signal analysis techniques on one set of recorded signals provides insight regarding potential mechanisms of weakness.Clinical Relevance- Decoding neural information from surface EMG signals without decomposition into individual motor units could provide clinicians with quick insight about disease progress and potential treatment.

Exosomes are membrane-bound extracellular vesicles secreted from a range of cells including human placental cells and contain specific cargo such as proteins, and miRNAs. The aim of this study was to determine the miRNA and protein profile in primary human trophoblast (PTH) and their secreted exosomes obtained from placentae from women with normal glucose tolerant (NGT) and gestational diabetes mellitus (GDM). Using quantitative proteomic analysis, 34 proteins were significantly different in PTH from GDM compared with NGT. Similarly, a specific set of proteins were significantly different in PTH exosomes from GDM compared with NGT. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from PTH and exosomes. We identified a set of miRNAs (miR-181, miR-151, miR-10a, miR-744, miR-1468 and miR-4507) which their expression varied in a consistent pattern in PTH and their secreted exosomes in GDM compared with NGT. Interestingly, a specific set of proteins and miRNAs were selectively enriched with exosomes and compared with their PTH of origin in NGT and GDM indicating a specific packaging of proteins and miRNAs into exosomes. We used Ingenuity Pathway Analysis (IPA) analysis to identify miRNA-gene interactions using the miRNA and proteomic data and created a network link with the down- and up-regulated pairs of miRNA-proteins. IPA core analysis showed that the top canonical pathway associated with these miRNAs were PI3/AKT signalling and glucose metabolism/insulin resistance, respectively. We proposed that exosomes are “fingerprints” of the releasing cells and their metabolic status. Exosomes released from placenta can modify the phenotype of target cells, inducing metabolic changes in GDM to contribute to changes in insulin sensitivity during pregnancy. Disclosure S. Nair: None. N. Jayabalan: None. D. Guanzon: None. A. Lai: None. D. McIntyre: Other Relationship; Self; Novo Nordisk A/S. M. Lappas: None. C. Salomon: None. Funding Diabetes Australia; Fondo Nacional de Desarrollo Científico y Tecnológico (1170809)

Adipose tissue exosomal miRNAs (exomiRs) serve as a signalling molecule that is involved in conveying intercellular message signalling. In this study, we aimed to profile the adipose tissue exomiRs in patients with normal glucose tolerant (NGT) and gestational diabetes mellitus (GDM). Omentum were obtained from BMI-matched NGT (n=10) and GDM (n=10) women at delivery (>37 weeks gestation). Isolated exosomes were characterised based on size distribution and protein enrichment. Total exosomal RNA was isolated by miRNeasy (Qiagen) according to manufacturer’s instructions. Illumina TrueSeq Small RNA kit was used to construct a small RNA library. Finally, the resulting sequencing FASTQ files were analysed using miRDeep2 to identify both known and novel miRNAs. A selected exomiR mimic was overexpressed in the human primary trophoblast (PHT) cells and its effect on glucose uptake was evaluated using 2-NBDG. We identified a total of 1209 miRNAs with 18 miRNAs were significantly differentially expressed in GDM exosomes. Comparatively, 12 miRNAs were upregulated while 6 were downregulated in the exosomes from GDM pregnancy compared to normal pregnancy. Consequently, has-miR-515-5p was selected to be investigated in further functional studies, following validation of its expression using real-time PCR. The QRT-PCR analysis of placental tissue showed a significant increase in the expression of GDM placenta compared to NGT placenta. In PHT cells, the overexpression of miR-515-5p significantly stimulated the glucose uptake (p Disclosure N. Jayabalan: None. D. Guanzon: None. A. Lai: None. D. McIntyre: Other Relationship; Self; Novo Nordisk A/S. M. Lappas: None. C. Salomon: None. Funding Diabetes Australia; Fondo Nacional de Desarrollo Científico y Tecnológico (1170809)

Several studies have assessed the safety and feasibility of single port robot-assisted radical prostatectomy using different and custom built robotic-assisted technology. In part due to the non-standardized nature of these approaches, single site robotic prostatectomy has not been widely adopted. With the recent approval of the da Vinci (Intuitive Surgical, Sunnyvale CA) Single Port (SP) platform, there has been a renewed interest in single site robotic-assisted prostatectomy and several institutions have begun reporting their initial experiences with this technique. In this systematic review, we sought to assess and summarize the literature regarding patient outcomes for single site robotic-assisted prostatectomy and evaluate its role in surgical treatment of prostate cancer. This systematic review was structured using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies describing the use of any robotic platform, including da Vinci Si, Xi or SP platforms for robotic single-port or single site radical prostatectomy between 2000 and July 15, 2019 were eligible for inclusion in this systematic review. Studies were excluded if they included combined cases with other organ resection, represented use in a non-clinical setting (such as a cadaveric model), or described results for a simple prostatectomy technique. Data was extracted by two authors with concerns resolved by consensus. Primary outcomes were mean operative times, estimated blood loss (mL), and hospital length of stay (days). Secondary outcomes included intraoperative conversion to open surgery, and intraoperative and postoperative complications. Variables of interest included sample size (n), mean age (years), mean prostate size (mL), prostate specific antigen (PSA, ng/mL), Gleason score, clinical and pathological TNM staging [American Joint Commission on Cancer (AJCC)], lymph nodes (n) and perioperative complications as available. A total of 217 studies were reviewed by title and abstract, with 28 selected for full-text review; ultimately, 12 studies were included, with available data from 145 patients. Primary outcomes and preoperative characteristics varied greatly amongst patients and across studies. One patient (0.7%) required conversion to a multi-port approach and there were no conversions to an open technique. No intraoperative complications were reported, and no Clavien grade III or greater postoperative complications have been described in the initial 81 radical prostatectomies performed with the SP platform. Single Port techniques appear to represent a safe and feasible approach for performing the minimally invasive radical prostatectomy. The current available literature on the single port radical prostatectomy is weak and consists of single center studies with small sample sizes, short-term follow up and limited functional data. More rigorous multi-center trials with standardized metrics for reporting functional outcomes as well as long-term cancer specific survival are necessary to validate these initial studies.

Chemoresistance is one of the major obstacles in the treatment of cancer patients. It poses a fundamental challenge to the effectiveness of chemotherapy and is often linked to relapse in patients. Chemoresistant cells can be identified in different types of cancers; however, ovarian cancer has one of the highest rates of chemoresistance-related relapse (50% of patients within 5 years). Resistance in cells can either develop through prolonged cycles of treatment or through intrinsic pathways. Mechanistically, the problem of drug resistance is complex mainly because numerous factors are involved, such as overexpression of drug efflux pumps, drug inactivation, DNA repair mechanisms and alterations to and/or mutations in the drug target. Additionally, there is strong evidence that circulating miRNAs participate in the development of chemoresistance. Recently, miRNAs have been identified in exosomes, where they are encapsulated and hence protected from degradation. These miRNAs within exosomes (exo-miRNAs) can regulate the gene expression of target cells both locally and systemically. Exo-miRNAs play an important role in disease progression and can potentially facilitate chemoresistance in cancer cells. In addition, and from a diagnostic perspective, exo-miRNAs profiles may contribute to the development of predictive models to identify responder and non-responder chemotherapy. Such model may also be used for monitoring treatment response and disease progression. Exo-miRNAs may ultimately serve as both a predictive biomarker for cancer response to therapy and as a prognostic marker for the development of chemotherapy resistance. Therefore, this review examines the potential role of exo-miRNAs in chemotherapy in ovarian cancer.