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Background: Small-scale fishers of Indian Sundarbans depend on open-water fisheries for their livelihoods. They often face health, occupational, and safety issues in their profession due to environmental, socio-economic, and policy changes. The morbidity pattern and related risk factors are important indicators of well-being for any community, hence applicable to small-scale fishers of Sundarbans. The present study was designed to assess patterns of morbidities, associated risk factors including occupational health hazards, and treatment-seeking behavior of small-scale fishers in the Indian Sundarbans. Material and Methods: Household surveys, focused group discussions, and personal interviews were conducted through a predesigned pretested structured questionnaire. Associated risk factors and the nature of seeking treatment were considered during the data collection covering 650 individuals from 132 fishers' families. Results: Morbidities were more frequent in males (39.33%) than in females (28.5%). The fever (31%) was the most dominant reason for morbidities followed by ocular ailments (23%), musculoskeletal disorder (20%), dermatological ailments (17%), and respiratory illness (9%). The highest morbidities (25%) were recorded in the age group of 21-30 years in males while that was 20% in the 11-20 years age group in the case of the females. Physical labor for fishing activities predisposes to health ailments of the studied population. Conclusions: The prevalence of morbidity among the fishermen community was found to be 28.5%. The understanding of the morbidity profile of a population in general and specific age groups of both sexes in specific sheds light on the vulnerability of working groups that will help for effective healthcare planning and resource allocation. [ABSTRACT FROM AUTHOR]

Background: Agrawal and Shah modified CAST (Caries Assessment Spectrum and Treatment) is the novel index prepared specifically for the Indian population for the complete evaluation of the spectrum/range of dental caries described hierarchically. Objective: To assess the prevalence of dental caries and treatment needs in an adult Indian population using Agrawal and Shah modified CAST index. Materials and Methods: A cross-sectional transverse study was performed on 2000 adult patients in the age range of 19--70 years. All the adult patients were scored for caries presence by Agrawal and Shah modified CAST codes on a structured proforma. SPSS version 20 was used to analyze the data. Results: The prevalence of dental caries calculated using Agrawal and Shah modified CAST index was 85.6%. 5.2% (104) adults had sound dentition, 4.1% (82) adults had restorations, 2.1% (42) adults had non-cavitated lesions, 13.7% (274) adults had the presence of caries in the enamel, 19% (380) adults had the presence of caries in dentine, and pulpal involvement was observed in 27.7% (554) adults. 10.3% (206) adults had presented with a root surface and cervical caries. 13.6% (272) adults had lost at least one tooth due to caries, and 3% (60) adults had lost teeth due to any other reason except dental caries. 1.3% (26) adult patients do not show any caries-related diagnosis but were having predisposing conditions. Conclusion: Agrawal and Shah modified CAST index proved to be simple, useful, and appropriate in assessing dental caries prevalence in the Indian population along with the treatment needs of the Indian population. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a fatal vasculopathy that ultimately leads to elevated pulmonary pressure and death by right ventricular (RV) failure, which occurs in part due to decreased fatty acid oxidation and cytotoxic lipid accumulation. In this study, we tested the hypothesis that decreased fatty acid oxidation and increased lipid accumulation in the failing RV is driven, in part, by a relative carnitine deficiency. We then tested whether supplementation of l‐carnitine can reverse lipotoxic RV failure through augmentation of fatty acid oxidation. In vivo in transgenic mice harboring a human BMPR2 mutation, l‐carnitine supplementation reversed RV failure by increasing RV cardiac output, improving RV ejection fraction, and decreasing RV lipid accumulation through increased PPARγ expression and augmented fatty acid oxidation of long chain fatty acids. These findings were confirmed in a second model of pulmonary artery banding‐induced RV dysfunction. In vitro, l‐carnitine supplementation selectively increased fatty acid oxidation in mitochondria and decreased lipid accumulation through a Cpt1‐dependent pathway. l‐Carnitine supplementation improves right ventricular contractility in the stressed RV through augmentation of fatty acid oxidation and decreases lipid accumulation. Correction of carnitine deficiency through l‐carnitine supplementation in PAH may reverse RV failure. [ABSTRACT FROM AUTHOR]

Aims We previously reported that sodium-dependent glucose cotransporter 1 (SGLT1) is highly expressed in cardiomyocytes and is further up-regulated in ischaemia. This study aimed to determine the mechanisms by which SGLT1 contributes to ischaemia/reperfusion (I/R) injury. Methods and results Mice with cardiomyocyte-specific knockdown of SGLT1 (TGSGLT1-DOWN) and wild-type controls were studied. In vivo , the left anterior descending coronary artery was ligated for 30 min and reperfused for 48 h. Ex vivo , isolated perfused hearts were exposed to 20 min no-flow and up to 2 h reperfusion. In vitro , HL-1 cells and isolated adult murine ventricular cardiomyocytes were exposed to 1 h hypoxia and 24 h reoxygenation (H/R). We found that TGSGLT1-DOWN hearts were protected from I/R injury in vivo and ex vivo , with decreased infarct size, necrosis, dysfunction, and oxidative stress. 5'-AMP-activated protein kinase (AMPK) activation increased SGLT1 expression, which was abolished by extracellular signal-related kinase (ERK) inhibition. Co-immunoprecipitation studies showed that ERK, but not AMPK, interacts directly with SGLT1. AMPK activation increased binding of the hepatocyte nuclear factor 1 and specificity protein 1 transcription factors to the SGLT1 gene, and HuR to SGLT1 mRNA. In cells, up-regulation of SGLT1 during H/R was abrogated by AMPK inhibition. Co-immunoprecipitation studies showed that SGLT1 interacts with epidermal growth factor receptor (EGFR), and EGFR interacts with protein kinase C (PKC). SGLT1 overexpression activated PKC and NADPH oxidase 2 (Nox2), which was attenuated by PKC inhibition, EGFR inhibition, and/or disruption of the interaction between EGFR and SGLT1. Conclusion During ischaemia, AMPK up-regulates SGLT1 through ERK, and SGLT1 interacts with EGFR, which in turn increases PKC and Nox2 activity and oxidative stress. SGLT1 may represent a novel therapeutic target for mitigating I/R injury. [ABSTRACT FROM AUTHOR]

The main purpose of a root canal treatment is to eliminate the bacteria and their products from the pulp space. Chemomechanical preparation (chemical—refers to irrigating solutions, i.e., either synthetic chemicals or herbal solutions and mechanical—refers to instrumentation of a root canals with endodontic files) of a root canal system plays a major role in obtaining the rationale of root canal treatment. Various synthetic chemicals known as endodontic irrigants play a major role in disinfection, but also have undesirable properties like allergic potential, toxicity, unacceptable taste, etc. Today there is a major change in trend towards the use of natural herbal medicines as a part of dental treatment due to its easy availability, less toxicity, and cost effectiveness. This article aims to provide a comprehensive review of various herbal endodontic irrigants evaluated for their effectiveness in the disinfection of a root canal system. This literature review is conducted using electronic databases "PubMed," "Google Scholar," and "Scopus," and articles were limited to those in the English language and published between 1980 and 2014. [ABSTRACT FROM AUTHOR]

Objective To describe our surgical technique and outcomes with robot-assisted laparoscopic repair of vesicovaginal fistula (VVF) in 10 patients. Methods From November 2010 to April 2014, a total of 10 patients with VVF underwent robot-assisted laparoscopic VVF repair. The principles of VVF repair were followed. The fistula tract was excised. The vagina defect and the cystotomy were closed with a flap of epiploica of sigmoid colon, a peritoneal inlay, or a bladder adventitia layer interposed between the bladder and vaginal suture lines. Perioperative patient characteristics, complications, operative data, and follow-up results were retrospectively reviewed with institutional review board approval. Results All 10 patients developed VVF as a result of previous elective hysterectomies for benign indications. Mean operative time was 214 minutes (range, 120-457 minutes). Longer operative times were caused by concomitant surgeries (3 ureteral reimplantations and 1 planned sigmoid colectomy). Median length of stay was 1 day (range, 1-5 days). There were no intraoperative complications. Perioperatively, there was 1 Clavien-Dindo grade 1 complication (ileus), and 2 grade 2 complications (readmission with Clostridium difficile infection and atelectasis). All patients were cured and were without VVF recurrence at a median follow-up close to 2 years. Conclusion Robot-assisted laparoscopic VVF repair is an effective approach to manage VVF even in complex medical scenarios. It is anticipated that an increasing number of VVF repairs will be undertaken with robot-assisted approach in the future, offering more patients who need VVF repair the advantages of minimally invasive surgery. [ABSTRACT FROM AUTHOR]

Introduction: An increasing number of obese patients (body mass index [BMI] >30 kg/m2]) with localized prostate cancer are presenting as candidates for robot-assisted radical prostatectomy (RARP), which can be carried out using the transperitoneal or the extraperitoneal (EP) approach. Morbidly obese (BMI >40 kg/m2) patients present as an especially challenging surgical cohort. We sought to evaluate the perioperative and pathologic outcomes associated with EP-RARP in morbidly obese men. Materials and Methods: In this institutional review board-approved study, our prospectively collected database (Cancer Information Systems [CAISIS]) was reviewed. One thousand six hundred sixty-three patients underwent EP-RARP for localized prostate cancer at our institution between July 2003 and December 2013 by a single surgeon. Forty patients were considered morbidly obese. A propensity score-matched analysis was performed using multivariate analysis incorporating 10 covariates to identify the comparable group of patients with a BMI of >40 kg/m2 and <40 kg/m2. Results: Apart from BMI, the two groups were matched (all p-values >0.05). Despite a higher total operating time and estimated blood loss (EBL) in the morbidly obese (238 vs 176 minutes, p<0.0001, and 235 vs 192 mL, p=0.003, respectively), there were no differences in the ability to perform nerve-sparing or pelvic lymphadenectomy, or the length of stay. While the morbidly obese had a higher rate of harboring more aggressive disease on final pathology (pT3 rates, 27.5 vs 7.5%, respectively), there were no differences in other postoperative pathologic parameters, such as prostate specimen weight, positive surgical margin status, and Gleason score sum. Moreover, there were no differences in intra- or postoperative complications between the two groups. Conclusions: The morbidly obese cohort harbored more aggressive disease with the difference in the proportion of pathologic T3 disease statistically significant. Apart from increased total operating time and EBL in the morbid obese, EP-RARP leads to comparable perioperative and pathologic outcomes to the nonmorbidly obese. Consideration should be given to added operating room time when operating on the morbidly obese. [ABSTRACT FROM AUTHOR]

Calorie restriction (CR) is the only proven regimen, which confers lifespan extension benefits across the various phyla right from unicellular organisms like yeast to primates. In a bid to elucidate the mechanism of calorie-restriction-mediated life span extension, the role of mitochondria in the process was investigated. In this study, we found that the mitochondrial content in CR cells remains unaltered as compared to cells grown on nonrestricted media. However, mitochondria isolated from CR cells showed increased respiration and elevated reactive oxygen species levels without augmenting adenosine triphosphate (ATP) generation. The antioxidant defense system was amplified in CR mitochondria, and in CR cells a cross protection to hydrogen-peroxide-induced stress was also observed. Moreover, we also documented that a functional electron transport chain was vital for the life span extension benefits of calorie restriction. Altogether, our results indicate that calorie restriction elicits mitohormetic effect, which ultimately leads to longevity benefit. [ABSTRACT FROM AUTHOR]

Urodeles and fetal mammals are capable of impressive epimorphic regeneration in a variety of tissues, whereas the typical default response to injury in adult mammals consists of inflammation and scar tissue formation. One component of epimorphic regeneration is the recruitment of resident progenitor and stem cells to a site of injury. Bioactive molecules resulting from degradation of extracellular matrix (ECM) have been shown to recruit a variety of progenitor and stem cells in vitro in adult mammals. The ability to recruit multipotential cells to the site of injury by in vivo administration of chemotactic ECM degradation products in a mammalian model of digit amputation was investigated in the present study. Adult, 6- to 8-week-old C57/BL6 mice were subjected to midsecond phalanx amputation of the third digit of the right hind foot and either treated with chemotactic ECM degradation products or left untreated. At 14 days after amputation, mice treated with ECM degradation products showed an accumulation of heterogeneous cells that expressed markers of multipotency, including Sox2, Sca1, and Rex1 (Zfp42). Cells isolated from the site of amputation were capable of differentiation along neuroectodermal and mesodermal lineages, whereas cells isolated from control mice were capable of differentiation along only mesodermal lineages. The present findings demonstrate the recruitment of endogenous stem cells to a site of injury, and/or their generation/proliferation therein, in response to ECM degradation products. [ABSTRACT FROM AUTHOR]

OBJECTIVE To report a large, single-centre experience with a continent, catheterizable abdominal conduit in adult patients. PATIENTS AND METHODS We retrospectively reviewed the case notes of all 65 patients who had surgery to create a continent catheterizable conduit based on the Mitrofanoff principle. Operations were carried out over a 13-year period. Data on surgical procedure, complications and final outcome were collected and analysed. RESULTS The mean age of the patients was 38.4 years and mean follow-up interval was 75.2 months. Patients with neuropathic lower urinary tracts accounted for the largest single indication for reconstruction (36 patients). The appendix was the conduit of choice and was available and suitable for use in 37 patients. There were 57 patients who continued to use their native bladder or had undergone an augmentation or substitution cystoplasty; 24.5% of these 57 individuals had also undergone closure of the bladder neck or urethra. There were postoperative complications requiring laparotomy in five (8%) patients. In all, 30 patients (46%) had catheterization problems, but most of these were easy to treat. Five patients (8%) had an incontinent conduit which was a more difficult problem to deal with. Two patients have died of unrelated cause and five patients have been converted to an ileal conduit. In all, 58 patients (92%) now have a Mitrofanoff conduit, of which 97% are catheterizable and 95% are continent. CONCLUSIONS Continent urinary diversion, based on the Mitrofanoff principle, has similar outcomes in adult urological practice to those described in published paediatric case series. There is good evidence to suggest that Mitrofanoff conduits are durable. However, patients should be aware of complications and the need for long-term follow-up. [ABSTRACT FROM AUTHOR]

Introduction. Many patients with Peyronie's disease (PD) have one or more risk factors (RFs) for atherosclerosis and endothelial dysfunction. It is well recognized that such RFs commonly lead to the development of systemic vascular abnormalities. While not necessarily so, this may implicate vascular dysfunction in its pathogenesis. The cause of PD remains obscure despite intense research over the years and investigating the role of vascular dysfunction in the pathogenesis of PD is a novel approach worth undertaking. Aim. To test our hypothesis that PD is associated with systemic vascular changes even in the absence of RFs for atherosclerosis and endothelial dysfunction. Methods. Vascular function was assessed using high-resolution brachial artery ultrasound in 23 PD patients (aged 30–65 years) without RFs for endothelial dysfunction and atherosclerosis, and 23 age-matched healthy controls. Endothelium-dependent, flow-mediated brachial artery dilation was measured in response to increased shear stress (reactive hyperemia induced by 5 minutes of forearm ischemia). This response was contrasted with that of 400 µg sublingual glyceryl trinitrate, an endothelium-independent vasodilator. Anthropometric characteristics, blood pressure, fasting lipids, and glucose were also measured. Main Outcome Measure. Endothelium-dependent, flow-mediated brachial artery dilation and glyceryl trinitrate-induced endothelium-independent vasodilation. Results. Endothelium-dependent flow-mediated dilation (FMD) was impaired in PD patients compared to controls (5.62 ± 0.58% vs. 7.46 ± 0.56%, P = 0.03). In contrast, responses to glyceryl trinitrate were similar in PD patients and controls as were blood pressure, lipid, and glucose values. FMD remained impaired after multivariable adjustment for potential confounders. Conclusion. Patients with Peyronie's disease have evidence of systemic vascular changes in the way of systemic conduit artery endothelial impairment even in the absence of RFs for atherosclerosis and endothelial dysfunction. These wider vascular abnormalities in PD are likely to be of clinical relevance and require further study. Agrawal V, Ellins E, Donald A, Minhas S, Halcox J, and Ralph DJ. Systemic vascular endothelial dysfunction in Peyronie's disease. J Sex Med 2008;5:2688–2693. [ABSTRACT FROM AUTHOR]

Associate Editor Michael G. Wyllie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands OBJECTIVE To assess men presenting with abnormalities of the penile suspensory ligament (PSL) and its correction. PATIENTS AND METHODS In all, 35 men presenting with abnormalities of the PSL that were subsequently repaired were included in this series. The causes included; sexual trauma (15 men), congenital absence of the PSL/congenital penile curvature (14), and two each with venogenic erectile dysfunction, Peyronie’s disease and penile dysmorphic disorder. The diagnosis was made clinically by the presence of a palpable gap between the symphysis pubis and the penis, together with medical history and examination of penile torsion or instability. The surgical repair used nonabsorbable sutures placed between the symphysis pubis and the tunica albuginea of the penis. RESULTS A ‘good’ surgical outcome was defined as correction of the penile deformity or instability and achieving normal sexual function. There was a good surgical outcome in 91% of men as defined, and 86% of the men were happy with the outcome. There were no significant complications, but three men needed a repeat PSL repair. CONCLUSION Men with abnormalities of the PSL can present with a variety of clinical symptoms, but when correctly diagnosed the repair is a simple technique with a successful cosmetic and functional outcome. [ABSTRACT FROM AUTHOR]

This article addresses and investigates the dual incorporation of daunorubicin (DR) and 6-mercaptopurine (6-MP) in liposomes for better chemotherapy. These drugs are potential candidates for interaction due to the quinone (H acceptor) and hydroxyl (H donor) groups on DR and 6-MP, respectively. Interactions between the two drugs in solution were monitored by UV/Vis and fluorescence spectroscopy. Interaction between the two drugs inside the liposomes was evaluated by HPLC (for 6-MP) and by fluorescence spectroscopy (for daunorubicin) after phospholipase-mediated liposome lysis. Our results provide evidence for the lack of interaction between the two drugs in solution and in liposomes. The entrapment efficiencies of 6-MP in the neutral Phosphatidyl choline (PC):Cholesterol (Chol):: 2:1 and anionic PC:Chol:Cardiolipin (CL) :: 4:5:1 single and double drug liposomes were found to be 0.4% and 1.5% (on average), respectively. The entrapment efficiencies of DR in the neutral and anionic double drug liposomes were found to be 55% and 31%, respectively. The corresponding entrapment of daunorubicin in the single drug liposomes was found to be 62% on average. Our thin layer chromatography (TLC) and transmission electron microscopy (TEM) results suggest stability of lipid and liposomes, thus pointing plausible existence of double drug liposomes. Cytotoxicity experiments were performed by using both single drug and double drug liposomes. By comparing the results of phase contrast and fluorescence microscopy, it was observed that the double drug liposomes were internalized in the jurkat and Hut78 (highly resistant cell line) leukemia cells as viewed by the fluorescence of daunorubicin. The cytotoxicity was dose dependent and had shown a synergistic effect when double drug liposome was used. [ABSTRACT FROM AUTHOR]

Abstract: Colony PCR is a convenient alternative to conventional plasmid isolation and restriction digestion for high-throughput screening of recombinant colonies. However, an insert carryover from the ligation mix, adhered to colony or agar plate, generates a substantial number of false positives. To avoid this, a simple single-tube technique involving pre-PCR nuclease incubation has been developed by optimizing a buffer system that provides nuclease action and PCR amplification sequentially. Results presented in this work provide a technique that is amenable for high-throughput screening of recombinant colonies. [Copyright &y& Elsevier]

We describe a case of recurrent scrotal arteriovenous malformation (AVM) in a young man secondary to pelvic fracture sustained during a road traffic accident. This was diagnosed as a lipoma on the ultrasound and clinical examination. To our knowledge, this is the first reported case of recurrent scrotal AVM secondary to trauma. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Associate Editor Michael G. Wyllie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands OBJECTIVE To assess whether the outcome of implanting penile prostheses is related to the number of prostheses implanted by surgeons, as several reports showed that the outcome of a urological procedure is directly related to the experience of the surgeon. METHODS We conducted a retrospective audit of 413 penile prostheses implanted over a 2-year period in the UK by 76 surgeons. RESULTS About 80% of the surgeons implanted only one or two prostheses per year, usually of the malleable type, and usually on patients in the private sector. Only four surgeons implanted >20 prostheses per year. The overall revision rate for implantation in the UK, at 24%, is far higher than the worldwide average. CONCLUSIONS Guidelines are needed on the number of prostheses a surgeon should implant per year so that revision rates will decline to more acceptable levels and patients will be offered a genuine choice of product. [ABSTRACT FROM AUTHOR]

Abstract: We describe a case of metastatic breast carcinoma involving the urinary bladder and causing bilateral hydronephrosis. Treatment consisted of bilateral renal decompression followed by chemoradiotherapy. The pertinent literature is reviewed. [Copyright &y& Elsevier]

• Pulmonary vasculopathy is an important component of the multicompartmental lung pathology in Veterans with post-deployment respiratory syndrome (PDRS). • Although the clinical relevance of vascular pathology in PDRS remains incompletely characterized, we present evidence that pulmonary hypertension can develop in patients with PDRS. Exertional dyspnea has been documented in US military personnel after deployment to Iraq and Afghanistan. We studied whether continued exertional dyspnea in this patient population is associated with pulmonary vascular disease (PVD). We performed detailed histomorphometry of pulmonary vasculature in 52 Veterans with biopsy-proven post-deployment respiratory syndrome (PDRS) and then recruited five of these same Veterans with continued exertional dyspnea to undergo a follow-up clinical evaluation, including symptom questionnaire, pulmonary function testing, surface echocardiography, and right heart catheterization (RHC). Morphometric evaluation of pulmonary arteries showed significantly increased intima and media thicknesses, along with collagen deposition (fibrosis), in Veterans with PDRS compared to non-diseased (ND) controls. In addition, pulmonary veins in PDRS showed increased intima and adventitia thicknesses with prominent collagen deposition compared to controls. Of the five Veterans involved in our clinical follow-up study, three had borderline or overt right ventricle (RV) enlargement by echocardiography and evidence of pulmonary hypertension (PH) on RHC. Together, our studies suggest that PVD with predominant venular fibrosis is common in PDRS and development of PH may explain exertional dyspnea and exercise limitation in some Veterans with PDRS. [ABSTRACT FROM AUTHOR]

Carnitine is required to transport fatty acid across the mitochondrial membrane to undergo beta oxidation. In addition to disorders of fatty acid metabolism, a relative carnitine deficiency has been reported in pulmonary arterial hypertension (PAH). Here we performed an observational study in which food and supplement consumption were collected in an observation period followed by open label administration of a carnitine supplement to determine feasibility of increasing plasma carnitine levels in humans PAH. We confirmed that relative carnitine deficiency in PAH is not due to reduced dietary consumption and that plasma levels of carnitine can be increased in PAH patients with supplementation that is well tolerated. [ABSTRACT FROM AUTHOR]

Objective: Recent years have seen a steep rise in minimally invasive surgical therapy (MIST) for benign prostate hyperplasia (BPH). Prostatic urethral lift (UroLift) is a mechanical intervention aimed at reducing lower urinary tract symptoms, which affect patients with BPH. Material and methods: A narrative synthesis of all studies regarding UroLift is performed over the last decade, evaluating its impact on International Prostate Symptom Score (IPSS), quality of life (QoL), Qmax, Benign Prostate Hypertrophy Impact Index, and sexual health metrics. Results: The studies included have demonstrated significant improvements in the objective parameters mea-sured. UroLift has a low side-effect profile and is comparable to transurethral resection of the prostate in QoL changes and is superior with respect to recovery time and ejaculatory function. Conclusion: Our findings suggest that UroLift may be an appropriate treatment for individuals undergoing treatment for BPH who are concerned with sexual and ejaculatory functions. More studies are needed to deter-mine who is eligible for UroLift, as well as the long-term impact of UroLift on individuals with BPH. [ABSTRACT FROM AUTHOR]

Aims The lymphocyte adaptor protein (LNK) is a negative regulator of cytokine and growth factor signalling. The rs3184504 variant in SH2B3 reduces LNK function and is linked to cardiovascular, inflammatory, and haematologic disorders, including stroke. In mice, deletion of Lnk causes inflammation and oxidative stress. We hypothesized that Lnk−/− mice are susceptible to atrial fibrillation (AF) and that rs3184504 is associated with AF and AF-related stroke in humans. During inflammation, reactive lipid dicarbonyls are the major components of oxidative injury, and we further hypothesized that these mediators are critical drivers of the AF substrate in Lnk−/− mice. Methods and results Lnk−/− or wild-type (WT) mice were treated with vehicle or 2-hydroxybenzylamine (2-HOBA), a dicarbonyl scavenger, for 3 months. Compared with WT, Lnk−/− mice displayed increased AF duration that was prevented by 2-HOBA. In the Lnk−/− atria, action potentials were prolonged with reduced transient outward K+ current, increased late Na+ current, and reduced peak Na+ current, pro-arrhythmic effects that were inhibited by 2-HOBA. Mitochondrial dysfunction, especially for Complex I, was evident in Lnk−/− atria, while scavenging lipid dicarbonyls prevented this abnormality. Tumour necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) were elevated in Lnk−/− plasma and atrial tissue, respectively, both of which caused electrical and bioenergetic remodelling in vitro. Inhibition of soluble TNF-α prevented electrical remodelling and AF susceptibility, while IL-1β inhibition improved mitochondrial respiration but had no effect on AF susceptibility. In a large database of genotyped patients, rs3184504 was associated with AF, as well as AF-related stroke. Conclusion These findings identify a novel role for LNK in the pathophysiology of AF in both experimental mice and humans. Moreover, reactive lipid dicarbonyls are critical to the inflammatory AF substrate in Lnk−/− mice and mediate the pro-arrhythmic effects of pro-inflammatory cytokines, primarily through electrical remodelling. [ABSTRACT FROM AUTHOR]

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a complex heterogeneous condition with no proven therapies yet. Pulmonary hypertension (PH) and right ventricular dysfunction (RVD) are common in HFpEF, but prognostic and therapeutic implications of PH and RVD in HFpEF are incompletely understood. Hypothesis: We hypothesized that the presence of PH or RVD may worsen prognosis and potentially stratify treatment response in HFpEF cohorts. Methods: We evaluated the North American cohort of patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial who had echocardiographic data reported. Of 1767 patients, 647 patients had reported echocardiographic data. Of 647 patients, 389 patients reported measures of PH and 489 reported measures of RVD. PH was assessed by the RVSP estimate, and RVD was assessed by right ventricular fractional area change (RVFAC). Results: The presence of RVSP > 30 mmHg was associated with an increased risk of overall death (28.2% vs 16.5%, p = 0.006), heart failure hospitalization (30.3% vs 20.1%, p = 0.021), and non-cardiovascular hospitalization (50.8% vs 39.7%, p = 0.028). Spironolactone treatment resulted in decreased heart failure hospitalizations for patients with RVSP > 30 mmHg (Figure A). There was no significant effect of RVFAC on outcomes, but spironolactone treatment did significantly decrease the composite outcome of cardiovascular death, cardiac arrest, and heart failure hospitalization in patients with RVFAC greater than 0.5 (Figure B). Conclusions: Stratification of patients with HFpEF by the presence of PH or RVD informs both prognosis and treatment efficacy in TOPCAT cohort. Further studies are necessary to test these hypotheses prospectively. [ABSTRACT FROM AUTHOR]

Introduction: Identification of diastolic dysfunction (DD) in patients with PH has important prognostic and therapeutic implications. Right heart catheterization (RHC) with fluid challenge often identifies patients with occult DD. Non-invasive predictors of occult DD have not been identified. We hypothesized that non-invasive measures of diastolic function may predict occult DD in PH. Methods: We examined hemodynamic and echocardiographic data from consecutive patients referred for RHC with fluid challenge (500 mL saline over 10 min) from 2009-2017. Resting DD was defined by a pulmonary capillary wedge pressure (PCWP) >15 mmHg. A validation cohort comprised 52 patients who prospectively underwent simultaneous echocardiogram and RHC before and fluid challenge at Monaldi Hospital, Naples, Italy. Occult (post-fluid) DD by RHC was defined by PCWP > 18 mmHg after fluid challenge. Results: The Vanderbilt cohort comprised 126 patients (83% female, 56+14 years) with median interval to echo of 40 days. In total 27/126 (21%) had occult DD and 28 (22%) had resting DD. In multivariate analysis adjusting for tricuspid regurgitation velocity and left atrial volume index, E velocity (OR 1.8, 95% CI 1.1-2.9, p = 0.01) and E/e' (OR 1.9, 95% CI 1.1-3, p = 0.005) were associated with occult DD (Figure 1A). The optimal cutoff on Receiver Operating Curve (ROC) analysis was E/e' > 8.6 for occult DD (sensitivity 70%, specificity 64%). In the validation cohort, 11/52 (21%) had occult DD after fluid challenge. Univariate analysis confirmed resting E/e' (OR 8.75, 95% CI 2.3-33, p = 0.001) and E velocity (OR 7.7, 95% CI 2-29, p = 0.003) remained predictive of occult DD (Figure 1B). ROC suggested optimal cutoff for E/e' > 8 for occult DD (sensitivity 73%, specificity 90%). Conclusions: Among patients referred for RHC, E velocity and E/e' are associated with occult DD after fluid challenge. These findings suggest that routine echocardiographic measurements may help raise suspicion for PH due to DD. [ABSTRACT FROM AUTHOR]

OBJECTIVE To report the management of erectile dysfunction (ED) secondary to Klippel–Trenaunay syndrome (KTS), a rare congenital vascular disease. PATIENTS AND METHODS Three men (mean age 33 years) with vasogenic ED secondary to KTS underwent venous ligation surgery of the affected veins. These men had tried various treatments for their ED, including phosphodiesterase type 5 inhibitors and intracavernosal injection therapy, with little success. RESULTS There was abnormal penile venous drainage in all three men, probably associated with congenital vascular malformation from KTS. After venous ligation the men were followed for 5 years and all reported good quality erections satisfactory for sexual intercourse. CONCLUSION ED in men with KTS may be due to venous drainage anomalies and if confirmed, venous ligation surgery should be performed as this gives the best chance of a complete resolution. [ABSTRACT FROM AUTHOR]

Image-guided fiducial markers are being used in surgery, especially in spine and breast surgery, and radiotherapy, allowing localization of tumor sites precisely. We report a case of fiducial coil use in a man undergoing a robot-assisted laparoscopic resection of a metastatic nodule under the ipsilateral diaphragm after robot-assisted partial nephrectomy performed 2 years ago for a left upper pole renal tumor. The fiducial coil facilitated the localization of the lesion, which would otherwise have been challenging because of its small size and location. In addition, the fiducial coil was helpful to avoid cutting into the lesion directly. [ABSTRACT FROM AUTHOR]

Aims Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, microvascular dysfunction, and myocardial fibrosis with recent evidence implicating the immune system in orchestrating cardiac remodelling. Methods and results Here, we show the mouse model of deoxycorticosterone acetate (DOCA)-salt hypertension induces key elements of HFpEF, including diastolic dysfunction, exercise intolerance, and pulmonary congestion in the setting of preserved ejection fraction. A modified single-cell sequencing approach, cellular indexing of transcriptomes and epitopes by sequencing, of cardiac immune cells reveals an altered abundance and transcriptional signature in multiple cell types, most notably cardiac macrophages. The DOCA-salt model results in differential expression of several known and novel genes in cardiac macrophages, including up-regulation of Trem2, which has been recently implicated in obesity and atherosclerosis. The role of Trem2 in hypertensive heart failure, however, is unknown. We found that mice with genetic deletion of Trem2 exhibit increased cardiac hypertrophy, diastolic dysfunction, renal injury, and decreased cardiac capillary density after DOCA-salt treatment compared to wild-type controls. Moreover, Trem2-deficient macrophages have impaired expression of pro-angiogenic gene programmes and increased expression of pro-inflammatory cytokines. Furthermore, we found that plasma levels of soluble TREM2 are elevated in DOCA-salt treated mice and humans with heart failure. Conclusions Together, our data provide an atlas of immunological alterations that can lead to improved diagnostic and therapeutic strategies for HFpEF. We provide our dataset in an easy to explore and freely accessible web application making it a useful resource for the community. Finally, our results suggest a novel cardioprotective role for Trem2 in hypertensive heart failure. [ABSTRACT FROM AUTHOR]

Objectives To review the evidence for the use of various biomarkers in the detection of chemotherapy associated cardiac damage. Design and methods Pubmed.gov was queried using the search words chemotherapy and cardiac biomarkers with the filters of past 10 years, humans, and English language. An emphasis was placed on obtaining primary research articles looking at the utility of biomarkers for the detection of chemotherapy-mediated cardiac injury. Results Biomarkers may help identify patients undergoing treatment who are at high risk for cardiotoxicity and may assist in identification of a low risk cohort that does not necessitate continued intensive screening. cTn assays are the best studied biomarkers in this context and may represent a promising and potentially valuable modality for detecting cardiac toxicity in patients undergoing chemotherapy. Monitoring cTnI levels may provide information regarding the development of cardiac toxicity before left ventricular dysfunction becomes apparent on echocardiography or via clinical symptoms. A host of other biomarkers have been evaluated for their utility in the field of chemotherapy related cardiac toxicity with intermittent success; further trials are necessary to determine what role they may end up playing for prediction and prognostication in this setting. Conclusions Biomarkers represent an exciting potential complement or replacement for echocardiographic monitoring of chemotherapy related cardiac toxicity which may allow for earlier realization of the degree of cardiac damage occurring during treatment, creating the opportunity for more timely modulation of therapy. [ABSTRACT FROM AUTHOR]

This science advisory focuses on the need to better understand the epidemiology, pathophysiology, and treatment of pulmonary hypertension in patients with heart failure with preserved ejection fraction. This clinical phenotype is important because it is common, is strongly associated with adverse outcomes, and lacks evidence-based therapies. Our goal is to clarify key knowledge gaps in pulmonary hypertension attributable to heart failure with preserved ejection fraction and to suggest specific, actionable scientific directions for addressing such gaps. Areas in need of additional investigation include refined disease definitions and interpretation of hemodynamics, as well as greater insights into noncardiac contributors to pulmonary hypertension risk, optimized animal models, and further molecular studies in patients with combined precapillary and postcapillary pulmonary hypertension. We highlight translational approaches that may provide important biological insight into pathophysiology and reveal new therapeutic targets. Last, we discuss the current and future landscape of potential therapies for patients with heart failure with preserved ejection fraction and pulmonary vascular dysfunction, including considerations of precision medicine, novel trial design, and device-based therapies, among other considerations. This science advisory provides a synthesis of important knowledge gaps, culminating in a collection of specific research priorities that we argue warrant investment from the scientific community. [ABSTRACT FROM AUTHOR]

Aging is associated with increased production of reactive oxygen species (ROS) and oxidation-induced damage to intracellular structures and membranes. Caloric restriction (CR) has been demonstrated to delay aging in a variety of species. Although the mechanisms of CR remain to be clearly elucidated, reductions in oxidative damage have been shown to increase lifespan in several model systems. Contrary to the general belief that ROS production is reduced in CR, this article provides evidence that not only oxygen consumption but ROS production is enhanced in the calorie restricted condition. To understand the biological mechanism underlying the anti aging action of CR, the role of scavenging enzymes was studied. It was found that super oxide dismutase (SOD1 and SOD2), catalase and glutathione peroxidase (GPx) all are over expressed in CR. We further investigated the role of Sir2, a potential effector of CR response in the activation of scavenging enzymes. No marked difference was found in CR mediated activation of SOD and catalase in the absence of Sir2. Our results suggest that in CR scavenging enzymes are activated by a Sir2 independent manner. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 35-year-old female patient, who visited a dental clinic for complaints of discoloration and pus drainage of her upper right central incisor of the mouth.

Subglottic stenosis is a known complication of a traumatic and prolonged intubation. In a child, subglottic area is narrower and more prone to damage by an oversized or overinflated endotracheal tube. The stenosis can present with complaints of change in voice, croup, or respiratory obstruction. Those presenting with respiratory obstruction require immediate diagnosis under direct laryngoscopy and timely corrective intervention under general anesthesia. A 4-year-old child came to the emergency department with severe respiratory obstruction. His medical history revealed invasive ventilatory management for aspiration pneumonitis 2 months back. Under direct laryngoscopy, we found severe narrowing of the subglottic area due to subglottic web. Since the subglottic area was so stenosed, intubation was impossible. Hence, emergency tracheostomy was performed to secure patient airway, followed by microlaryngeal surgery to remove the subglottic web. Acquired subglottic stenosis in a child can be a life-threatening situation which requires immediate airway management. It should be suspected in any child in severe respiratory obstruction with a history of prolonged intubation. [ABSTRACT FROM AUTHOR]

Abstract: Biologic scaffolds composed of extracellular matrix (ECM) are commonly used repair devices in preclinical and clinical settings; however the use of these scaffolds for peripheral and central nervous system (CNS) repair has been limited. Biologic scaffolds developed from brain and spinal cord tissue have recently been described, yet the conformation of the harvested ECM limits therapeutic utility. An injectable CNS-ECM derived hydrogel capable of in vivo polymerization and conformation to irregular lesion geometries may aid in tissue reconstruction efforts following complex neurologic trauma. The objectives of the present study were to develop hydrogel forms of brain and spinal cord ECM and compare the resulting biochemical composition, mechanical properties, and neurotrophic potential of a brain derived cell line to a non-CNS-ECM hydrogel, urinary bladder matrix. Results showed distinct differences between compositions of brain ECM, spinal cord ECM, and urinary bladder matrix. The rheologic modulus of spinal cord ECM hydrogel was greater than that of brain ECM and urinary bladder matrix. All ECMs increased the number of cells expressing neurites, but only brain ECM increased neurite length, suggesting a possible tissue-specific effect. All hydrogels promoted three-dimensional uni- or bi-polar neurite outgrowth following 7 days in culture. These results suggest that CNS-ECM hydrogels may provide supportive scaffolding to promote in vivo axonal repair. [Copyright &y& Elsevier]

Objectives To determine retrospectively, the outcome of vasectomies performed by five urologists over a six year period in terms of achievement of azoospermia on post vasectomy semen analysis (PVSA) and to compare the effect of the type of suture material used for ligation of the vas deferens on the vasectomy success. Methods Review of PVSA results of 3005 consecutive vasectomies done in a district general hospital between November 1998 and October 2004. Patient records and vasectomy logs were reviewed and data analysed. The main outcome measure was achievement of azoospermia on PVSA. Results The age distribution of men between the two study groups was similar. Overall compliance to provide at least two semen samples for PVSA was 73.8% and was similar between the two groups. Failure to achieve azoospermia on PVSA was seen in 3.5% men (36/1038) in the chromic catgut group and 10.1% men (110/1088) in the Vicryl® group (p < 0.0001). Also, the vasectomy failure rates for individual urologists increased significantly following introduction of Vicryl®. Conclusions In our study we noticed a three fold increase in failure to achieve azoospermia on PVSA with Vicryl® as compared to chromic catgut. This study demonstrates that the type of suture material used for ligation of the vas deferens does affect the vasectomy success. [ABSTRACT FROM AUTHOR]

Radiation force-based techniques have been developed by several groups for imaging the mechanical properties of tissue. Acoustic Radiation Force Impulse (ARFI) imaging is one such method that uses commercially available scanners to generate localized radiation forces in tissue. The response of the tissue to the radiation force is determined using conventional B-mode imaging pulses to track micron-scale displacements in tissue. Current research in ARFI imaging is focused on producing real-time images of tissue displacements and related mechanical properties. Obstacles to producing a real-time ARFI imaging modality include data acquisition, processing power, data transfer rates, heating of the transducer, and patient safety concerns. We propose a parallel receive beamforming technique to reduce transducer heating and patient acoustic exposure, and to facilitate data acquisition for real-time ARFI imaging. Custom beam sequencing was used with a commercially available scanner to track tissue displacements with parallel-receive beamforming in tissue-mimicking phantoms. Using simulations, the effects of material properties on parallel tracking are observed. Transducer and tissue heating for parallel tracking are compared to standard ARFI beam sequencing. The effects of tracking beam position and size of the tracked region are also discussed in relation to the size and temporal response of the region of applied force, and the impact on ARFI image contrast and signal-to-noise ratio are quantified. [ABSTRACT FROM AUTHOR]

Radicular fractures are very challenging to address due to various complications like periodontal communication, increased mobility, and continued pulpal infection leading to necrosis and its long term sequelae like root resorption and pulp canal obliteration. This paper present a case of a long standing horizontal mid root fracture with root resorption and pulp canal obliteration, which was preserved functionally and aesthetically by surgical approach using MTA (mineral trioxide aggregate) and PRF (platelet rich fibrin). [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is a known consequence of bone morphogenetic protein type II receptor (BMPR2) mutations seen in pulmonary arterial hypertension (PAH). However, standard 2D cell culture models fail to mimic the mechanical environment seen in the pulmonary vasculature. Hydrogels have emerged as promising platforms for 3D disease modeling due to their tunable physical and biochemical properties. In order to recreate the mechanical stimuli seen in the pulmonary vasculature, we have created a novel 3D hydrogel-based pulmonary vasculature model ("artificial arteriole") that reproduces the pulsatile flow rates and pressures seen in the human lung. Using this platform, we studied both Bmpr2R899X and WT endothelial cells to better understand how the addition of oscillatory flow and physiological pressure influenced gene expression, cell morphology, and cell permeability. The addition of oscillatory flow and pressure resulted in several gene expression changes in both WT and Bmpr2R899X cells. However, for many pathways with relevance to PAH etiology, Bmpr2R899X cells responded differently when compared to the WT cells. Bmpr2R899X cells were also found not to elongate in the direction of flow, and instead remained stagnant in morphology despite mechanical stimuli. The increased permeability of the Bmpr2R899X layer was successfully reproduced in our artificial arteriole, with the addition of flow and pressure not leading to significant changes in permeability. Our artificial arteriole is the first to model many mechanical properties seen in the lung. Its tunability enables several new opportunities to study the endothelium in pulmonary vascular disease with increased control over environmental parameters. [ABSTRACT FROM AUTHOR]