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Anal fistula is a common disease of the anal region that can be treated using a cutting seton. The objective of this study was to investigate healing and recurrence outcomes of anal fistulas treated via cutting setons performed by a specialist colorectal surgery group at a single academic institution. This retrospective chart review study included 143 patients who underwent a cutting seton procedure at a single academic institution to treat their anal fistula between January 2013 and December 2018. The main outcomes measured in this study were healing rates, recurrences rates, incontinence rates, and infectious complication rates of anal fistulas being treated with a cutting seton. In total, 127 (88.8%) patients’ fistulas healed after treatment with a cutting seton. Fifteen (10.5%) patients had a fistula recurrence after treatment. Fourteen (9.8%) patients experienced an infectious complication after the cutting seton procedure while 8 (5.6%) patients developed some form of incontinence during the fistula healing period. Average healing time for fistulas after cutting seton treatment was 1.9 months (7–8 weeks). This study indicates that the cutting seton procedure is an effective and safe method for treating anal fistulas. Cutting setons lead to low rates of complications (like infections and incontinence) and good long-term outcomes when it comes to maintaining anal sphincter function after presence of a complicated and/or high anal fistula. This study suggests that the cutting seton remains an alternative to other procedures, which maybe more invasive and compromising.

Background The THUNDERBEAT is a multi-functional energy device which delivers both ultrasonic and bipolar energy, but there are no randomized trials which can provide more rigorous evaluation of the clinical performance of THUNDERBEAT compared to other energy-based devices in colorectal surgery. The aim of this study was to compare the clinical performance of THUNDERBEAT energy device to Maryland LigaSure in patients undergoing left laparoscopic colectomy. Methods Prospective randomized trial with two groups: Group 1 THUNDERBEAT and Group 2 LigaSure in a single university hospital. 60 Subjects, male and female, of age 18 years and above undergoing left colectomy for cancer or diverticulitis were included. The primary outcome was dissection time to specimen removal (DTSR) measured in minutes from the start of colon mobilization to specimen removal from the abdominal cavity. Versatility (composite of five variables) was measured by a score system from 1 to 5 (1 being worst and 5 the best), and adjusted/weighted by coefficient of importance with distribution of the importance as follow: hemostasis 0.275, sealing 0.275, cutting 0.2, dissection 0.15, and tissue manipulation 0.1. Other variables were: dryness of surgical field, intraoperative and postoperative complications, and mortality. Follow-up time was 30 days. Results 60 Patients completed surgery, 31 in Group 1 and 29 in Group 2. There was no difference in the DTSR between the groups, 91 min vs. 77 min (p = 0.214). THUNDERBEAT showed significantly higher score in dissecting and tissue manipulation in segment 3 (omental dissection), and in overall versatility score (p = 0.007) as well as versatility score in Segment 2 (retroperitoneal dissection p = 0.040) and Segment 3 (p = 0.040). No other differences were noted between the groups. Conclusions Both energy devices can be employed effectively and safely in dividing soft tissue and sealing mesenteric blood vessels during laparoscopic left colon surgery, with THUNDERBEAT demonstrating some advantages over LigaSure during omental dissection and tissue manipulation. ClinicalTrial.gov # NCT02628093.

The accumulation of neurofibrillary tangles (NFTs), which is composed of abnormally hyperphosphorylated tau aggregates, is the classic neuropathology associated with cognitive dysfunction in tauopathies such as Alzheimer’s disease (AD). However, there is an emerging theory suggesting that dysregulation in cerebral iron may contribute to NFT formation. Iron is speculated to bind to tau and induce conformational changes of the protein, potentially leading to subsequent aggregation and cognitive decline. Deferiprone (DFP) is a clinically available iron chelator, which has demonstrated potential therapeutic advantages of chelating iron in neurodegenerative disorders, and is currently in clinical trials for AD. However, its effect on tau pathology remains unclear. Here, we report the effects of short-term DFP treatment (4 weeks, 100 mg/kg/daily, via oral gavage) in a mixed-gender cohort of the rTg((tauP301L))4510 mouse model of tauopathy. Our results revealed that DFP improved Y-maze and open field performance, accompanied by a 28% decrease in brain iron levels, measured by inductively coupled plasma mass spectrometry (ICP-MS) and reduced AT8-labeled p-tau within the hippocampus in transgenic tau mice. This data supports the notion that iron may play a neurotoxic role in tauopathies and may be a potential therapeutic target for this class of disorders that can be modulated by the clinically available metal chelator DFP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-020-00972-w.

To evaluate patterns of use and outcomes of arteriovenous fistulas and prosthetic grafts within racial categories in a large population based cohort of hemodialysis (HD) patients in the United States.A retrospective analysis of white, black, and Hispanic patients in the prospectively maintained United States Renal Database System who had an autogenous fistula or prosthetic graft placed for HD access between January 2007 and December 2014 was performed. Analysis of variance, χThis study of 359,942 patients, composed of 285,781 autogenous fistulas (79.4%) and 74,161 prosthetic grafts (20.6%) placed in 213,877 white (59.4%), 115,727 black (32.2%), and 30,338 Hispanic (8.4%) patients. There was a 11% increase in the risk-adjusted odds of HD catheter use as bridge to autogenous fistula placement in blacks (adjusted odds ratio, 1.11; 95% confidence interval [CI], 1.08-1.14; P .001) and a 9% increase in Hispanics (adjusted odds ratio, 1.09; 95% CI, 1.05-1.14; P .001) compared with whites. Fistula maturation for HD access for whites vs blacks vs Hispanics was 77.0% vs 76.3% vs 77.8% (P = .35). After adjusting for covariates, fistula maturation was higher for blacks (adjusted hazard ratio, 1.09; 95% CI, 1.06-1.13; P .001) and Hispanics (adjusted hazard ratio, 1.13; 95% CI, 1.06-1.20; P .001) compared with whites. There was no significant difference in prosthetic graft maturation for blacks and Hispanics compared with whites. Primary, primary-assisted, and secondary patency were highest for Hispanic and least for black autogenous fistula recipients. Primary, primary-assisted, and secondary patency was also highest for Hispanic patients who received prosthetic grafts. Prosthetic grafts were associated with a decrease in patency and patient survival compared with fistulas in all racial categories. Mortality was lower for blacks and Hispanics relative to white patients. Initiation of HD with a catheter and conversion to autogenous fistula was associated with decrease in patency and patient survival compared with initiation with a fistula in all racial groups.Autogenous fistulas are associated with better patency and patient survival compared with prosthetic grafts for all races studied. The use of HD catheter before fistula placement is more prevalent in Hispanic and black patients and is associated with worse patency and patient survival irrespective of race. Fistula and graft patency is highest for Hispanic patients. Patient survival is higher for Hispanic and black patients relative to whites. These associations suggest potential benefit with initiation of HD via autogenous fistula and minimizing temporizing catheter use, irrespective of race.

Background: An elevation in iron levels, together with an accumulation of α-synuclein within the oligodendrocytes, are features of the rare atypical parkinsonian disorder, Multiple System Atrophy (MSA). We have previously tested the novel compound ATH434 (formally called PBT434) in preclinical models of Parkinson’s disease and shown that it is brain-penetrant, reduces iron accumulation and iron-mediated redox activity, provides neuroprotection, inhibits alpha synuclein aggregation and lowers the tissue levels of alpha synuclein. The compound was also well-tolerated in a first-in-human oral dosing study in healthy and older volunteers with a favorable, dose-dependent pharmacokinetic profile. Objective: To evaluate the efficacy of ATH434 in a mouse MSA model. Methods: The PLP-α-syn transgenic mouse overexpresses α-synuclein, demonstrates oligodendroglial pathology, and manifests motor and non-motor aspects of MSA. Animals were provided ATH434 (3, 10, or 30 mg/kg/day spiked into their food) or control food for 4 months starting at 12 months of age and were culled at 16 months. Western blot was used to assess oligomeric and urea soluble α-synuclein levels in brain homogenates, whilst stereology was used to quantitate the number of nigral neurons and glial cell inclusions (GCIs) present in the substantia nigra pars compacta. Results: ATH434 reduced oligomeric and urea soluble α-synuclein aggregation, reduced the number of GCIs, and preserved SNpc neurons. In vitro experiments suggest that ATH434 prevents the formation of toxic oligomeric “species of synuclein”. Conclusion: ATH434 is a promising small molecule drug candidate that has potential to move forward to trial for treating MSA.

Coccidioidomycosis is a fungal disease endemic to the southwestern United States, Mexico, and Central and South America. Prevalence rates are increasing steadily, and new endemic areas of Coccidioides are emerging. Standard treatment is often administered for months to decades, and intolerance to medications and treatment failures are common. No new treatments for coccidioidomycosis have been approved in the United States in nearly 40 years. On 5 August 2020, the US Food and Drug Administration convened experts in coccidioidomycosis from academia, industry, patient groups, and other government agencies to discuss the disease landscape and strategies to facilitate product development for treatment of coccidioidomycosis. This article summarizes the key topics concerning drug development for coccidioidomycosis presented by speakers and panelists during the workshop, such as unmet need, trial designs, endpoints, incentives, research and development support, and collaborations to facilitate antifungal drug development.

Background Testicular germ cell cancer (TGCC) develops from pre-malignant germ neoplasia in situ (GCNIS) cells. GCNIS originates from fetal gonocytes (POU5F1+/MAGE-A4−), which fail to differentiate to pre-spermatogonia (POU5F1−/MAGE-A4+) and undergo malignant transformation. Gankyrin is an oncogene which has been shown to prevent POU5F1 degradation and specifically interact with MAGE-A4 in hepatocellular carcinoma (HCC) cells. We aimed to investigate the role of Gankyrin in progression from gonocyte to pre-invasive GCNIS and subsequent invasive TGCC. Methods We determined Gankyrin expression in human fetal testicular tissue (gestational weeks 9–20; n = 38), human adult testicular tissue with active spermatogenesis (n = 9), human testicular tissue with germ cell maturation delay (n = 4), testicular tissue from patients with pre-invasive GCNIS (n = 6), and invasive TGCC including seminoma (n = 6) and teratoma (n = 7). Functional analysis was performed in-vitro by siRNA knock-down of Gankyrin in the NTera2 cells (derived from embryonal carcinoma). Results Germ cell expression of Gankyrin was restricted to a sub-population of prespermatogonia in human fetal testes. Nuclear Gankyrin was also expressed in GCNIS cells of childhood and adult pre-invasive TGCC patients, and in GCNIS from seminoma and non-seminoma patients. Cytoplasmic expression was observed in seminoma tumour cells and NTera2 cells. Gankyrin knock-down in NTera2 cells resulted in an increase in apoptosis mediated via the TP53 pathway, whilst POU5F1 expression was unaffected. Furthermore, Gankyrin knock-down in NTera2 cells increased cisplatin sensitivity with an increase in cell death (13%, p Conclusions These results suggest that manipulation of Gankyrin expression may reduce the cisplatin dose required for the treatment of TGCC, with benefits in reducing dose-dependent side effects of chemotherapy. Further studies are required in order to assess the effects of modulating Gankyrin on GCNIS/TGCC using in vivo models.

OBJECTIVE To estimate the cost of delivering a hepatitis C virus care coordination program at 2 New York City health care provider organizations and describe a potential payment model for these currently nonreimbursed services. DESIGN An economic evaluation of a hepatitis C care coordination program was conducted using micro-costing methods compared with macro-costing methods. A potential payment model was calculated for 3 phases: enrollment to treatment initiation, treatment initiation to treatment completion, and a bonus payment for laboratory evidence of successful treatment outcome (sustained viral response). SETTING Two New York City health care provider organizations. PARTICIPANTS Care coordinators and peer educators delivering care coordination services were interviewed about time spent on service provision. De-identified individual-level data on study participant utilization of services were also used. INTERVENTION Project INSPIRE is an innovative hepatitis C care coordination program developed by the New York City Department of Health and Mental Hygiene. MAIN OUTCOME MEASURES Average cost per participant per episode of care for 2 provider organizations and a proposed payment model. RESULTS The average cost per participant at 1 provider organization was $787 ($522 nonoverhead cost, $264 overhead) per episode of care (5.6 months) and $656 ($429 nonoverhead cost, $227 overhead, 5.7 months) at the other one. The first organization had a lower macro-costing estimate ($561 vs $787) whereas the other one had a higher macro-costing estimate ($775 vs $656). In the 3-phased payment model, phase 1 reimbursement would vary between the provider organizations from approximately $280 to $400, but reimbursement for both organizations would be approximately $220 for phase 2 and approximately $185 for phase 3. CONCLUSIONS The cost of this 5.6-month care coordination intervention was less than $800 including overhead or less than $95 per month. A 3-phase payment model is proposed and requires further evaluation for implementation feasibility. Project INSPIRE's HCV care coordination program provides good value for a cost of less than $95 per participant per month. The payment model provides an incentive for successful cure of hepatitis C with a bonus payment; using the bonus payment to support HCV tele-mentoring expands HCV treatment capacity and empowers more primary care providers to treat their own patients with HCV.

Multiple System Atrophy (MSA) is a rare neurodegenerative synucleinopathy which leads to severe disability followed by death within 6-9 years of symptom onset. There is compelling evidence suggesting that biological trace metals like iron and copper play an important role in synucleinopathies like Parkinson's disease and removing excess brain iron using chelators could slow down the disease progression. In human MSA, there is evidence of increased iron in affected brain regions, but role of iron and therapeutic efficacy of iron-lowering drugs in pre-clinical models of MSA have not been studied. We studied age-related changes in iron metabolism in different brain regions of the PLP-αsyn mice and tested whether iron-lowering drugs could alleviate disease phenotype in aged PLP-αsyn mice. Iron content, iron-ferritin association, ferritin protein levels and copper-ceruloplasmin association were measured in prefrontal cortex, putamen, substantia nigra and cerebellum of 3, 8, and 20-month-old PLP-αsyn and age-matched non-transgenic mice. Moreover, 12-month-old PLP-αsyn mice were administered deferiprone or ceruloplasmin or vehicle for 2 months. At the end of treatment period, motor testing and stereological analyses were performed. We found iron accumulation and perturbed iron-ferritin interaction in substantia nigra, putamen and cerebellum of aged PLP-αsyn mice. Furthermore, we found significant reduction in ceruloplasmin-bound copper in substantia nigra and cerebellum of the PLP-αsyn mice. Both deferiprone and ceruloplasmin prevented decline in motor performance in aged PLP-αsyn mice and were associated with higher neuronal survival and reduced density of α-synuclein aggregates in substantia nigra. This is the first study to report brain iron accumulation in a mouse model of MSA. Our results indicate that elevated iron in MSA mice may result from ceruloplasmin dysfunction and provide evidence that targeting iron in MSA could be a viable therapeutic option.

Purpose: Coronavirus-19 disease (COVID-19) has been associated with a high risk of thrombotic complications. Here, we report the case of a patient who developed simultaneous bilateral retinal artery occlusion following COVID-19 infection.Case Report: A 42-year-old male with no systemic co-morbidities presented with sudden, painless loss of vision in both eyes. Fundoscopy showed retinal edema and cherry-red spots in both eyes. Fluorescein angiography showed reperfusion, absence of choroidal ischemia, and Optical Coherence Tomography showed thickened inner retinal layers suggestive of retinal edema and the outer retinal layers appeared intact. Blood investigations for vasculitis, coagulation profile, lipids, and homocysteine level were within normal limits.Conclusion: COVID-19 patients may develop a systemic coagulopathy and acquired thrombophilia characterized by a tendency for venous, arterial, and microvascular thrombosis. This hypercoagulable state is believed to be a hyperinflammatory response; physicians and ophthalmologists, alike, should be aware of these possible long-term sequelae.

Due to the immediate need for social distancing, as well as widespread disruption in clinical practices, brought on by the novel severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic, medical student education rapidly shifted to a virtual format, which resulted in a variety of innovative and remotely accessible practices to address new restrictions on face-to-face education. Educators approached curriculum design seeking to replicate as much of the in-person experience as possible, and were faced with overcoming the challenges of replacing the innately hands-on nature of surgery with virtual operative and skills experiences. Restrictions on in-person visiting electives expedited the role of virtual education as a notable opportunity for medical student education and recruitment, with a variety of approaches to engaging undergraduate medical learners, including the use of live-streaming operative cases, virtual didactic curricula, and a rise in podcasts; web-based conferences; and virtual journal clubs. In addition to education, virtual outreach to medical students has become an essential tool in trainee recruitment and selection, and ongoing application of novel educational platforms will allow for new opportunities in multi-institutional collaboration and exchange with a multitude of benefits to future vascular surgery trainees. Our aim was to outline the resources and practices used to virtually teach and recruit medical students and the benefits of virtual rotations to the program and students.

Background: Pancreatic surgery is associated with considerable morbidity and, consequently, offers a large and complex field for research. To prioritize relevant future scientific projects, it is of utmost importance to identify existing evidence and uncover research gaps. Thus, the aim of this project was to create a systematic and living Evidence Map of Pancreatic Surgery. Methods: PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for all randomized controlled trials and systematic reviews on pancreatic surgery. Outcomes from every existing randomized controlled trial were extracted, and trial quality was assessed. Systematic reviews were used to identify an absence of randomized controlled trials. Randomized controlled trials and systematic reviews on identical subjects were grouped according to research topics. A web-based evidence map modeled after a mind map was created to visualize existing evidence. Meta-analyses of specific outcomes of pancreatic surgery were performed for all research topics with more than 3 randomized controlled trials. For partial pancreatoduodenectomy and distal pancreatectomy, pooled benchmarks for outcomes were calculated with a 99% confidence interval. The evidence map undergoes regular updates. Results: Out of 30, 860 articles reviewed, 328 randomized controlled trials on 35, 600 patients and 332 systematic reviews were included and grouped into 76 research topics. Most randomized controlled trials were from Europe (46%) and most systematic reviews were from Asia (51%). A living meta-analysis of 21 out of 76 research topics (28%) was performed and included in the web-based evidence map. Evidence gaps were identified in 11 out of 76 research topics (14%). The benchmark for mortality was 2% (99% confidence interval: 1%–2%) for partial pancreatoduodenectomy and

It is very well observed that offshore sites mostly contain soft/loose soils may be of sand or clay or may be multiple layer of soil mixture under saturated condition. This particular soil undergoes large deformation on the installation of any offshore structure like jack up. It is also observed that jack up may tilt or sink under its own weight without any lateral load or hydrodynamic pressure or any natural hazard like liquefaction or hurricane. It may undergo punching shear failure due to the presence of soft soil. It may suffer failure due to jack up leg and foundation element connection failure. It gets affected by rotational stiffness, foundation fixity parameters. To overcome this situation, several techniques had been proposed by various researchers. Spudcan, anchors, mud mat, bucket foundation, suction caisson foundation, etc., are used to overcome such difficulties. These techniques of mitigation subsequently affect bearing capacity failure zones of soil. Sinking and tilting effects are due to overlapping of bearing capacity failure zones. Hence, by advancing changing in shape and spacing of jack up legs, sinking and tilting effects can be considerably reduced. In particular research paper, an attempt has been made to investigate the effects of various mitigation techniques by previous researchers. All field and laboratory studies along with soft computing with FEM-based software had been discussed. Considerable researchers had shown that provision of mud mat in jack up bottom increases stability of jack up structure. To visualize the various effects, FEM-based Plaxis 3D program had also been used.

OBJECTIVE: While up to 35% of children with asthma have evidence of sleep disordered breathing (SDB), it is unclear if nocturnal symptoms stem from asthma itself or SDB. The Pediatric Sleep Questionnaire (PSQ) is a validated tool for identifying SDB in childhood asthma. We hypothesize children with asthma and abnormal PSQ demonstrate decreased asthma control and are at higher risk of obstructive sleep apnea (OSA). METHODS: We performed a retrospective, chart review of children and young adults referred to our tertiary children’s hospital severe asthma clinic. Data collection included age, gender, BMI percentile, spirometry, PSQ, asthma control questionnaires, asthma severity, control, and impairment. These data were evaluated in the context of polysomnography, when available. RESULTS: 205 inner-city children were included; 37.2% female, median age 6.4y, and mean BMI of 71.3%ile. Rhinitis (p=0.028), eczema (p=0.002), and reflux (p=0.046) were associated with abnormal PSQ; however, overweight/obese status, spirometry, asthma severity, and serologic markers were not. After correcting for comorbidities, abnormal PSQ score was associated with poor asthma control based on validated measures (p

AimsHeart valve disease attributed to serotonin (5HT) has been observed with 5HT-secreting carcinoid tumors and in association with medications, such as the diet drug, Dexfenfluoramine, a serotonin transporter (SLC6A4) inhibitor and 5HT receptor (HTR) 2B agonist. HTR2B signaling upregulates TGFβ-1 resulting in increased production of extracellular matrix proteins. SLC6A4 internalizes 5HT, limiting HTR signaling. Selective 5HT reuptake inhibitors (SSRI), widely used antidepressants, target SLC6A4, thus enhancing HTR signaling. However, 5HT and SLC6A4 mechanisms have not been previously associated with degenerative mitral regurgitation (MR). The present studies investigated the hypothesis that both dysregulation of SLC6A4 and inhibition of SLC6A4 contribute to the pathophysiology of MR.Methods and ResultsHere we report SLC6A4 related studies of 225 patients with MR requiring surgery. A multivariate analysis showed that SSRI use in MR patients was associated with surgery at a younger age, indicating more rapidly progressive MR (p=0.0183); this was confirmed in a national dataset (pConclusionsDown regulation and inhibition of SLC6A4 influences MR through enhanced HTR signaling. SSRI may further influence MR through inhibition and down regulation of SLC6A4, upregulation of HTR2B, and increased platelet release of 5HT.Translational PerspectiveDegenerative mitral valve regurgitation (MR) affects millions, and there is no medical therapy for this disease. MR becomes progressively worse, and for severe MR, the only option is cardiac surgery. Serotonin (5HT) is best known as a neurotransmitter. However, 5HT secreting carcinoid tumors cause a cardiac valve disorder in many cases, and 5HT related medications, such as the diet drug Fenfluoramine, have been associated with the development of cardiac valve disease. The present paper presents evidence that diminished serotonin transporter (SLC6A4) expression and inhibition, lead to increased 5HT receptor signaling, contributing to the progression of MR.

Patients with neuromuscular disease (NMD) experience weakened cough due to progressive respiratory muscle weakness. Peak cough flow (PCF) measurements derived from adult populations are used to recommend initiation of assisted cough therapies. The objective of this study was to characterize PCF values among pediatric patients with NMD. Retrospective chart review was performed for patients seen in the multidisciplinary pediatric muscular dystrophy clinic from 2010 to 2016. Clinical and demographic variables included age, gender, ambulation status, and PCF measurements. 366 patients with an established diagnosis of NMD (median age 11.8 years) were included in this study. 102 (27.8%) out of the 366 patients were affected by Duchenne muscular dystrophy (DMD), 42 (11.5%) by congenital muscular dystrophy (CMD), 42 (11.5%) by Charcot Marie Tooth disease (CMT) and 24 (6.5%) by Becker’s muscular dystrophy (BMD). The mean PCF values in DMD (255.8 L/min) and CMD (249.1 L/min) were lower than CMT (321.5 L/min) with p-values of 0.007 and 0.02, respectively. The mean PCF of BMD (333.3 L/min) was higher than that of DMD and CMD but the difference was not statistically significant. PCFs were not statistically different between ambulatory and non-ambulatory status (263.0 L/min versus 290.8 L/min, p = 0.12). Children under 10 years of age had lower PCF relative to older subjects (179.5 L/min versus 300.9 L/min, p

Male genital emergencies relating to the penis and scrotum are rare and require prompt investigation and surgical intervention. Clinicians are often unfamiliar with the management of these conditions and may not work in a specialist centre with on-site expertise in genitourethral surgery. A series of consensus statements have been developed by an expert consensus committee comprising members of the BAUS Section of Andrology and Genitourethral Surgery together with experts from urology units throughout the UK. Priapism requires prompt assessment and treatment and these consensus statements provide guidance for UK practice.

Male genital emergencies relating to the penis and scrotum are rare and require prompt investigation and surgical intervention. Clinicians are often unfamiliar with the management of these conditions and may not work in a specialist centre with on-site expertise in genitourethral surgery. A series of consensus statements have been developed by an expert consensus comprising British Association of Urological Surgeons (BAUS) Section of Andrology and Genitourethral Surgery together with experts from units throughout the UK. Testicular trauma requires prompt investigation and treatment in order to prevent the development of subfertility or hypogonadism. This series of consensus statements provide guidance for UK practice.

Male genital emergencies relating to the penis and scrotum are rare and require prompt investigation and surgical intervention. Clinicians are often unfamiliar with the management of these conditions and may not work in a specialist centre with on-site expertise in genitourethral surgery. A series of consensus statements have been developed by an expert consensus committee comprising members of the British Association of Urological Surgeons (BAUS) Section of Andrology and Genitourethral Surgery together with experts from urology units throughout the UK. Penile amputation is a rare genital emergency, which requires prompt intervention and microsurgical reconstruction. The consensus statements will outline the management of these cases for non-specialist units, as well as recommendations for reconstruction for specialists.

Relapsing polychondritis (RP) is a rare episodic and progressive inflammatory disease of presumed autoimmune etiology. The estimated incidence is 3.5 cases per million. Of these only 10% affect pediatric populations.

OBJECTIVES: To determine the antibiotic prescribing practices of pediatric residents and assess how they acquire knowledge leading to prescribing behaviors. METHODS: We performed a cross-sectional electronic survey of all pediatric residents at the Children’s National Medical Center and Nicklaus Children’s Hospital, assessing antibiotic prescribing patterns for common pediatric infections, use of antibiograms, and factors influencing antibiotic choice. RESULTS: Eighty-five surveys (45%) were returned complete and included in the analysis. Increased deviations from clinical guideline recommendations were observed for antibiotic treatments of sinusitis and community-acquired pneumonia as compared with otitis media and group A streptococcal pharyngitis. Only 57% of residents reported having used antibiograms. General pediatric inpatient attending physicians were identified as the most influential source for house staff antibiotic knowledge. CONCLUSIONS: Results illustrate the need for better promotion and integration of clinical guidelines with antibiograms when developing antibiotic education programs for residents in training. In addition, pediatric hospitalists should play an active role in the implementation of these programs and can provide valuable insight into the development of educational programs in conjunction with graduate medical education divisions.

Abtbract Ethnopharmacological relevance Aconite root is very poisonous; causes cardiac arrhythmias, ventricular fibrillation and ventricular tachycardia. There is no specific antidote for aconite poisoning. In Ayurveda, dehydrated borax is mentioned for management of aconite poisoning. Aim of the study The investigation evaluated antidotal effect of processed borax against acute and sub-acute toxicity, cardiac toxicity and neuro-muscular toxicity caused by raw aconite. Materials and methods For acute protection Study, single dose of toxicant (35 mg/kg) and test drug (22.5 mg/kg and 112.5 mg/kg) was administered orally, and then 24 h survival of animals was observed. The schedule was continued for 30 days in sub-acute protection Study with daily doses of toxicant (6.25 mg/kg), test drug (22.5 mg/kg and 112.5 mg/kg) and vehicle. Hematological and biochemical tests of blood and serum, histopathology of vital organs were carried out. The cardiac activity Study was continued for 30 days with daily doses of toxicant (6.25 mg/kg), test drug (22.5 mg/kg), processed borax solution (22.5 mg/kg) and vehicle; ECG was taken after 1 h of drug administration on 1TB, 15th and on 30th day. For neuro-muscular activity Study, the leech dorsal muscle response to 2.5 µg of acetylcholine followed by response of toxicant at 25 µg and 50 µg doses and then response of test drug at 25 µg dose were recorded. Results Protection index indicates that treated borax gave protection to 50% rats exposed to the lethal dose of toxicant in acute protection Study. Most of the changes in hematological, biochemical parameters and histopathological Study induced by the toxicant in sub-acute protection Study were reversed significantly by the test drug treatment. The ventricular premature beat and ventricular tachyarrhythmia caused by the toxicant were reversed by the test drug indicate reversal of toxicant induced cardio-toxicity. The acetylcholine induced contractions in leech muscle were inhibited by toxicant and it was reversed by test drug treatment. Conclusion The processed borax solution is found as an effective protective agent to acute and sub-acute aconite poisoning, and aconite induced cardiac and neuro-muscular toxicity. Processed borax at therapeutic dose (22.5 mg/kg) has shown better antidotal activity profile than five times more than therapeutic dose (112.5 mg/kg).

Male genital emergencies relating to the penis and scrotum are rare and require prompt investigation and surgical intervention. Clinicians are often unfamiliar with the management of these conditions and may not work in a specialist centre with on-site expertise in genitourethral surgery. The aim of these consensus statements is to provide best practice guidance for urological surgeons based in the UK which are developed by an expert consensus. Penile fracture is a rare emergency and in most cases requires prompt exploration and repair to prevent erectile dysfunction and penile curvature.

The New York City Department of Health and Mental Hygiene (DOHMH) implemented Project INSPIRE, an integrated model of hepatitis C care coordination and telementoring services, from 2014 to 2017. We evaluated the use of chronic care management (CCM) codes to sustain the intervention. DOHMH data were collected as part of a Healthcare Innovation Award from the Centers for Medicare & Medicaid Services (CMS). A retrospective cohort medical billing study was conducted by assigning INSPIRE activities to procedure codes in both facility and nonfacility settings. Rates for procedures were extracted from the CMS's 2018 fee schedules and added across the eligibility periods for Medicare enrollees. Reimbursement was adjusted on the basis of expected patient attrition and compared to costs. The minimum number needed to treat (NNT) to break even was calculated in each setting. Facility reimbursement was higher than costs, whereas nonfacility reimbursement was lower (both P < .01). The NNT was 23 patients in facilities and 33 patients in nonfacilities; 24 patients per care coordinator were treated annually in INSPIRE. CCM fees alone were insufficient to fully reimburse the costs in either setting. Implementation of an appropriate risk financing strategy is necessary to mitigate financial shortfalls when providing CCM services in facility settings.

Purpose The purpose of this prospective study was to evaluate the feasibility of positron emission tomography/computed tomography (PET/CT)-guided biopsy of Ga-68 avid lesions using an automated robotic arm and determine the diagnostic yield of this technique. Material and methods Patients who underwent Ga-68 labelled tracers imaging followed by PET/CT-guided biopsies of tracer-avid lesions were prospectively included. Biopsies were performed using a dedicated automated-robotic-arm assisted PET/CT-guided biopsy device on the same-day of diagnostic PET/CT-imaging. The tissue samples were retrieved after confirming the position of needle-tip in the target lesion. Procedure-related complications and radiation exposure of the interventionist were recorded. Histopathological reports were reviewed for diagnostic yield. Results A total of 25 patients (19 men, six women) with a mean age of 50.8 ± 17.3 (SD) years (range: 17-83 years) were included. The biopsies were performed after PET/CT using Ga-68 DOTANOC (n = 16) or Ga-68 PSMA (n = 8) and Ga-68 chemokine-analogue (n = 1). The biopsy samples were obtained from the liver (n = 9), bone (n = 8), lymph-nodes (n = 3), lung (n = 1), pancreas (n = 1), anterior mediastinal lesion (n = 1), peritoneal-deposit (n = 1) and thigh-lesion (n = 1). No immediate or delayed procedure-related complications were documented in any patient. PET/CT-guided molecular sampling was technically successful in all the patients. Histopathology revealed malignancies in all the biopsied specimens without the need for repeat sampling or further invasive-diagnostic workup, with a diagnostic yield of 100%. The estimated absorbed-radiation dose was 566.7 μSv/year for the interventionist. Conclusion PET/CT-guided molecular biopsy using Ga-68 labelled radiotracers is feasible and can be performed safely and accurately with a high-diagnostic yield. It is helpful in accurately staging the disease when tracer-avid isolated distant lesion evident on imaging and highly practical in patients with previous inconclusive sampling.

Background: Triphala is one of the most easily available and commonly used medicine which contains fine powder of three fruits viz. Terminalia chebula Retz . (Haritaki) , Terminalia bellerica Roxb . (Bibhitaki) and Embilica officinalis Gaertn . (Amalaki) and is indicated as one of the drugs for management of disorders of Kapha and Meda. Due to bitter and astringent taste of Triphala in the powder form is a major complaint of the patients. So, to discover that form of Triphala , which is easy to take, effective in low dose, has long shelf life and simple to dispense is the need. For assurance of quality of herbal compounds pharmacognostical and pharmaceutical analysis should be done. Methods: Triphala Kajjali was subjected to microscopic evaluation for pharmacognostical, physiochemical analysis like hardness, weight variation, loss on drying, ash value, acid insoluble extract, pH value, water soluble extract, alcohol soluble extract and high-performance thin layer chromatography (HPTLC). Results: Pharmacognostical study showed the presence of certain identifying characters of all of the ingredients of Triphala Kajjali that is Haritaki , Bibhitaki and Amalaki. In pharmaceutical study, preliminary physiochemical analysis showed that hardness of the tablet was 2.05 kg/cm 2 , ash value 4.03%w/w, loss on drying 5.5%w/w, water soluble extract 5.89%w/w, alcohol soluble extract 25.96%w/w and HPTLC showed 7 spots in 254 nm and 7 spots in 366 nm. Conclusions: Pharmacognostical and physico-chemical observations revealed the specific characters of all active constituents of Triphala Kajjali and confirmed the purity and genuinity of the drug.

One of the approaches to address the issues of the cost of production, recovery and reusability of the extremozymes can be immobilization. In this report, we describe immobilization of an α-amylase from Laceyella sacchari TSI-2 and characterization of the immobilized enzyme. The enzyme was immobilized on 6 different matrices using entrapment, ionic binding and surface adsorption. The DEAE cellulose with glutaraldehyde crosslinking appeared most effective for the immobilization with high operational stability. While the temperature optima and thermal stability of the immobilized α-amylase shifted from 60 to 70°C with increased half-life, the pH optima remain unaltered while pH stability was shifted from 6 to 7. The stability of the immobilized enzyme improved in solvents. The enzyme catalysis in surfactants enhanced, while the Km and Vmax were reduced after immobilization. The structural features of the immobilized enzyme as probed by FT-IR established the role of aliphatic amines, esters and alkenes in immobilization. The starch hydrolysis efficiency of the immobilized enzyme was 15.55%. The immobilized enzyme in various detergents was highly efficient in removing the starch stain from cotton cloth. Taken together, the α-amylase turned more stable after immobilization and can be a favored choice for applications.

A thermophilic actinobacterium, Laceyella sacchari TSI-2 from a hot spring was characterized for its morphological and cultural features. It optimally produced α-amylase at 50 °C and pH 7. The enzyme was purified by 55-fold with 12.23% yield and 4215.91 U/mg specific activity. The molecular weight, Km, Vmax and Kcat were 31 kD, 2.71 mg ml−1, 7.589 μmoles min−1 per mg of the protein and 4.31 × 10−2 s−1, respectively. Optimum catalysis and stability occurred at 70 °C and pH 7. A stabilizing effect of thiourea was evident, while metal ions and chelators inhibited the enzyme. The enzyme was highly stable in various surfactants. Kd, t1/2, ΔH*, ΔS* and ΔG* supported thermal stability reflected by the structural integrity and substrate affinity. The HPTLC analysis of the end products suggested the formation of malto-oligosaccharides as intermediate products along with maltose confirming the enzyme as α-amylase. The FT-IR revealed significant role of the triple bonds in thermal stability, while CD spectroscopy suggested changes in the secondary structure of the native and denatured enzymes. The enzyme was highly efficient in removing starch stains from the cotton cloth. Stability at high temperatures, alkaline pH and in surfactants suggests potential of the amylase in various applications.

Background: Punarnava Guggulu is a polyherbal formulation mentioned in Bhaishajya Ratnavali containing various Ayurvedic medicinal drugs and specially indicated for the treatment of Amavata and Vatarakta. For assurance of quality of herbal compounds pharmacognostical and pharmaceutical analysis should be done. Methods: Punarnava Guggulu was subjected to microscopic evaluation for Pharmacognostical study, physiochemical analysis like hardness, weight variation, loss on drying, ash value, acid insoluble extract, pH value, water soluble extract, alcohol soluble extract, high performance thin layer chromatography (HPTLC). Results: Pharmacognostical study showed the presence of certain identifying characters of all of the ingredients of Punarnava Guggulu that is Punarnava , Erandamula , Shunthi , Guggulu , Eranda Tail , Trivruta , Danti , Guduchi , Haritaki , Bibhitaki , Amalaki , Maricha , Pippali , Chitraka , Bhallataka and Vidanga . In pharmaceutical study, preliminary physiochemical analysis showed that hardness of the Vati was 4.05 Kg/cm2, ash value 12.84% w/w, acid insoluble ash value 1.56% w/w, loss on drying 1.6% w/w, water soluble extract 35.93% w/w, alcohol soluble extract 22.14% w/w and HPTLC showed 13 spots in 254nm and 8 spots in 366nm. Conclusions: Present work was carried out to standardize the polyherbal formulation Punarnava Guggulu in terms of its identity, quality and purity. Pharmacognostical and physico-chemical observations revealed the specific characters of all active constituents in the preparation were present in it.

There are limited data on the impact of carotid angioplasty and stenting (CAS)-related changes in blood pressure, heart rate, and preprocedural medications on periprocedural stroke in contemporary, real-world practice. This study evaluates the risk attributable to the CAS-related hemodynamic events and the impact preprocedural medications have on mitigating this risk in a large, population-based cohort.We studied all patients in the Vascular Quality Initiative who underwent CAS between January 2006 and December 2016. Kaplan-Meier, multivariable logistic, and Cox regression analyses were used to evaluate the impact of periprocedural hypertension, hypotension, bradycardia, and medication use on immediate periprocedural stroke (IPPS), 30-day, and 1-year stroke.Of the 13,698 CAS procedures studied, 1239 (9.1%), 1824 (13.3%), and 1333 (9.7%) patients experienced periprocedural hypertension, hypotension, and bradycardia, respectively. IPPS was 3.2% vs 2.1% vs 0.65% (P .001), comparing patients with periprocedural hypertension vs hypotension vs normotension and 1.4 vs 1.0% (P = .19) for bradycardic vs nonbradycardic patients. Periprocedural hypertension was associated with a four-fold increase in IPPS (adjusted odd ratio [aOR], 3.97; 95% confidence interval [CI], 2.63-5.99; P .001). periprocedural hypotension and bradycardia were associated with 5.5-fold (aOR, 5.56; 95% CI, 3.24-9.52; P .001) and 2.3-fold (aOR, 2.31; 95% CI, 1.26-4.25; P = .007) increases in IPPS among patients with carotid symptoms. There was 76% decrease in IPPS for patients who did not experience a periprocedural hemodynamic event (aOR, 0.24; 95% CI, 0.16-0.35; P .001). Unlike preprocedural beta-blockers and angiotensin-converting enzyme inhibitors, prophylactic antibradyarrhythmic agents conferred a 58% reduction in IPPS among patients with carotid symptoms (aOR, 0.42; 95% CI, 0.23-0.78; P = .006). The periprocedural hemodynamic events were also associated with 7.7-fold increase in myocardial infarction (aOR, 7.70; 95% CI, 4.77-12.45; P .001), a 2.2-fold increase in 30-day mortality (aOR, 2.24; 95% CI, 1.61-3.12; P .001), and a 16% increase in length of stay (aOR, 1.16; 95% CI, 0.04-2.28; P = .042). The occurrence of these hemodynamic events is higher in patients with prior cardiac disease and the difference in periprocedural outcomes extended to 1 year.Periprocedural hemodynamic events are associated with an increase in periprocedural stroke, myocardial infarction, death, and length of stay. Periprocedural hypertension in all patients; hypotension and bradycardia in patients with symptomatic carotid disease are associated with significant increase in IPPS. Prophylactic antibradyarrhythmic agents are associated with decrease in bradycardia and IPPS. These results heighten the need to anticipate and promptly address these CAS-related hemodynamic events, especially in susceptible patients.

Hepatitis C (HCV) is a viral infection that if left untreated can severely damage the liver. Project INSPIRE was a 3 year HCV care coordination programme in New York City (NYC) that aimed to address barriers to treatment initiation and cure by providing patients with supportive services and health promotion. We examined whether enrolment in Project INSPIRE was associated with differences in HCV treatment and cure compared with a demographically similar group not enrolled in the programme. INSPIRE participants in 2015 were matched with a cohort of HCV-infected persons identified in the NYC surveillance registry, using full optimal matching on propensity scores and stratified by INSPIRE enrolment status. Conditional logistic regression was used to assess group differences in the two treatment outcomes. Two follow-up sensitivity analyses using individual pair-matched sets and the full unadjusted cohort were also conducted. Treatment was initiated by 72% (790/1130) of INSPIRE participants and 36% (11 960/32 819) of study-eligible controls. Among initiators, 65% (514/790) of INSPIRE participants compared with 47% (5641/11 960) of controls achieved cure. In the matched analysis, enrolment in INSPIRE increased the odds of treatment initiation (OR: 5.25, 95% CI: 4.47-6.17) and cure (OR: 2.52, 95% CI: 2.00-3.16). Results from the sensitivity analyses showed agreement with the results from the full optimal match. Participation in the HCV care coordination programme significantly increased the probability of treatment initiation and cure, demonstrating that care coordination for HCV-infected individuals improves treatment outcomes.

Kasa is well-defined clinical condition in Brihadtrayi, clearly correlate with cough and its pathophysiology exactly correlates with the mechanism of cough reflex in contemporary medical science. Everywhere, Paediatric Outdoor Patients Department (OPD) has more than half of the total patients having respiratory tract complaints. So, to treat the disease Kasa, Vyaghri Haritaki Avaleha (VHA) was taken from Bhaishajya Ratnavali. The present work was carried out to standardize the raw drugs and finished product-VHA with comparing API standards and previous research work done in same institute to conform its identity, quality and purity of the final product. The pharmacognostical work reveals that presence of Epidermis, Cork, Pericycle, Phloem etc. from Kantakari; Lignified fibre, Stone cells etc. of Haritaki; Aluerone grains, Prismatic crystals etc. of Shunthi observed microscopically. Organoleptic features of VHA made out of the crude drugs were within the standard range. The pH value of VHA was 4.5, Water soluble extract was 71.9 %w/w, Loss on drying was 30.41 %w/w, Reducing sugar was 27.92 %w/w and High Performance Thin Layer Chromatography (HPTLC) at 254nm and 366nm resulted into 2 and 5 spots respectively

Background Laparoscopic surgical treatment of T4 cancers remains a concern that is mostly associated with technical feasibility, high conversion rate, inadequate oncologic clearance, and surgical outcome. Objective The purpose of this work was to evaluate the short- and long-term clinical and oncologic outcomes after laparoscopic and open surgeries for T4 colon cancers. Design This was a retrospective study of patients with T4 colon cancer without metastasis (M0) who had laparoscopic or open surgery from 2003 to 2011. Setting The study was conducted at a single institution. Patients A total of 83 patients with pT4 colon cancer were included. Main outcome measures R0 resection rate, morbidity and mortality within 30 postoperative days, overall survival, and disease-free survival were measured. Results Laparoscopic surgery was performed on 61 and open surgery on 22 patients. The groups were similar in overall staging (p = 0.461), with 35 (42%) of the patients at stage 2 and 48 (58%) at stage 3. A complete R0 resection was achieved in 61 (100%) of the patients who underwent laparoscopic surgery and in 21 (96%) of the patients who underwent open surgery (p = 0.265). The average number of lymph nodes harvested was 21 in the laparoscopic group and 24 in the open group (p = 0.202). Thirty-day morbidity rate was similar between the groups (p = 0.467), and the mortality rate was 0. The length of hospital and postsurgical stay was significantly shorter in the laparoscopic group (p = 0.002 and p = 0.008). The 3-year overall survival rates between the groups were 82% (range, 71%-93%) for patients who underwent laparoscopic surgery and 81% (range, 61%-100%) for those who underwent open surgery (p = 0.525), and disease-free survival was 67% (range, 54%-79%) for laparoscopic surgery and 64% (range, 43%-86%) for open surgery (p = 0.848). The follow-up time was 40 ± 25 in months in the laparoscopic group and 34 ± 26 months in the open surgery group (p = 0.325). Limitations This was a retrospective study at a single institution. Conclusions The study shows that laparoscopic surgery is feasible in T4 colon cancers. With comparable clinical and oncologic outcomes, this study suggests that laparoscopy may be considered as an alternative approach for T4 colon cancers with the advantage of faster recovery (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A156).

Background: Rivea hypocrateriformis (Desr.) Choisy is known to be the source plant of Phanji , a classically delineated leafy vegetable which is till date used by some hill dwelling Kandha tribes of Odisha. Though it is in use since a long time, it is not yet evaluated for its nutritive value. Aim: The leaves of R. hypocrateriformis were evaluated for its nutritive value and antioxidant potential. Materials and Methods: The in vitro antioxidant properties of the leaf of R. hypocrateriformis were screened through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and total antioxidant capacity. Phytochemicals, crude protein, fat, carbohydrate, energy value, and mineral content of the leaves of the plant were evaluated with standard procedures. Results: In phytochemical analysis, tannin, alkaloids, flavonoids, and carbohydrates were present in leaf powder of R. hypocrateriformis . Energy content was found to be highest (331.54 kcals/100 g). Carbohydrate, fat, protein, calcium, magnesium, phosphorous, and zinc were present in 57.63%, 2.66%, 19.27%, 0.99%, 0.34%, 0.32%, and 0.011%, respectively. The IC50 values of the extract and ascorbic acid were found to be 254 ± 5.29 μg/ml and 11.67 ± 0.58 μg/ml, respectively. Percentage scavenging of DPPH radical was found to rise with increasing concentration of the crude extract. Total antioxidant capacity of the extract was found to be 111.30 ± 0.003 mcg. Conclusion: The results of this study indicate that the leaves of R. hypocrateriformis contain secondary metabolites such as tannin and possess mild antioxidant properties. Nutritional analysis indicates the presence of energy in highest amount, carbohydrates, proteins, fats, calcium, phosphorous, zinc, and magnesium.

The pancreatico-enteric anastomosis has widely been regarded as the ‘Achilles heel’ of the modern day, single-stage, pancreatoduodenectomy (PD). A review of the literature was carried out to address the evolution of the pancreatico-enteric anastomosis following PD, the spectrum of anastomoses performed around the world, and finally present the current evidence in support of each anastomosis. Pancreaticogastrostomy (PG) and pancreaticojejunostomy (PJ) are the most common forms of pancreatico-enteric reconstruction following PD. There is no difference in postoperative pancreatic fistula (POPF) rates between PG and PJ, as well as individual variations, except in a high-risk anastomosis where performance of a PJ may be preferred. The routine use of glue, trans-anastomotic stents or omental wrapping is of no proven benefit. Externalised trans-anastomotic stents may have a role in mitigating the risk of a clinically relevant POPF in high-risk anastomoses. Pancreatico-enteric anastomosis is an important component of reconstruction following PD even though it is fraught with the risk of development of a POPF. Adherence to the tenets of anastomotic reconstruction and performance of a safe and reproducible anastomosis with a low clinically-relevant POPF rate remain the mainstay of achieving the best outcomes. Appropriate selection and opportune use of fistula mitigation strategies may help provide optimal outcomes when faced with the need to perform a high-risk pancreatico-enteric anastomosis.

Developments in assisted reproductive techniques (ART) have transformed the management of male factor infertility and the advent of intracytoplasmic sperm injection (ICSI) in 1993 was a landmark in the management of the infertile male. While this has been an undoubted success, it has led to a shift away from understanding and correcting the potential reversible causes of male factor infertility, to one that simply overcomes it with assisted reproductive techniques (ART). The aetiology of male infertility can broadly be divided into impaired spermatogenesis, or impaired sperm transport within the genital tract. The most challenging of these is male infertility due to azoospermia, which affects approximately 10-15% of infertile men (2.7million men in Europe). This article is protected by copyright. All rights reserved.

There is an increasing prevalence of obesity globally. Implications of the global obesity epidemic are far-reaching and have become a major public health issue. Strikingly, the incidence of obesity is growing fastest among the pediatric population. Complications of childhood obesity are multifactorial with effects on psychosocial, pulmonary, gastrointestinal, renal, musculoskeletal, neurological, cardiovascular, and endocrine systems. The following chapter discusses the pulmonary complications of obesity as body habitus has a significant impact, not only on the mechanics of the respiratory system but by interfering with several immunopathologic and endocrine mechanisms as well.

SummaryOne of the biggest surprises since the sequencing of the human genome has been the discovery of thousands of long noncoding RNAs (lncRNAs)1–6. Although lncRNAs and mRNAs are similar in many ways, they differ with lncRNAs being more nuclear-enriched and in several cases exclusively nuclear7,8. Yet, the RNA-based sequences that determine nuclear localization remain poorly understood9–11. Towards the goal of systematically dissecting the lncRNA sequences that impart nuclear localization, we developed a massively parallel reporter assay (MPRA). Unlike previous MPRAs12–15 that determine motifs important for transcriptional regulation, we have modified this approach to identify sequences sufficient for RNA nuclear enrichment for 38 human lncRNAs. Using this approach, we identified 109 unique, conserved nuclear enrichment regions, originating from 29 distinct lncRNAs. We also discovered two shorter motifs within our nuclear enrichment regions. We further validated the sufficiency of several regions to impart nuclear localization by single molecule RNA fluorescence in situ hybridization (smRNA-FISH). Taken together, these results provide a first systematic insight into the sequence elements responsible for the nuclear enrichment of lncRNA molecules.

Background: Time (Kala) of collection is an important criterion responsible for the quality of crude drugs of herbal origin. According to their parts used, the guidelines for rutuwise (seasonal) collection of crude plant drugs has been well documented in various treatise of Ayurveda. Among various parts used of medicinal plants, Kshira (latex) of Arka and Shwetarka finds a wide usage in various pharmaceutical processes and formulations in classical literature. The latex has been quoted to be procured in Sharada rutu (September- October) but the scientific reason behind this still remains unexplored. Materials and Methods: The fresh crude latex of both C. gigantean (CG) and C. procera (CP) were collected in clean glass vials regularly in all the six rutu i.e Vasanta (March-April), Grishma (May-June), Varsha (July- August), Sharada (September- October), Hemanta (November- December) and Shishira (January- February). The collection was done for 4 days in each rutu and 3 times in a day i.e. before sunrise (BS), 3 hrs. after sunrise (3AS) and 6 hrs. after sunrise (6AS) from three different tender and fresh parts of the plant i.e. twig, petiole and peduncle. The observations regarding volume, girth of plant parts, pH, viscosity, specific gravity along with preliminary phytochemical analysis of latex was carried out in samples of crude latex collected in six seasons. Results: Grishma rutu was very well differentiated from other rutus in terms of volume and girth. Also, a peculiar presence of alkaloids and proteins was observed in Sharada rutu in both the species supports the classical collection protocol in Agneya period.

Despite the increasing prevalence of obesity and colonic diseases, the impact of obesity on short-term and oncologic outcomes of laparoscopic colorectal surgery still remains unclear.Seventy-six consecutive obese patients with body mass index (BMI) ≥30 kg/m(2) who underwent laparoscopic colectomy were matched with 76 nonobese patients with BMI30 kg/m(2). Perioperative parameters and oncologic outcomes were analyzed in the two groups.Obesity was associated with greater operative time (obese vs nonobese, 182 ± 59 vs 157 ± 55 min, P = .0084) and multivariate analysis identified BMI (hazard ratio 2.11, 95% confidence interval 0.64-3.56, P = .0049) as an independent predicting factor for operative time together with cancer location (hazard ratio 28.6, 95% confidence interval 14.62-42.51, P .0001). Obesity had no adverse influence on overall morbidity (25 vs 21%, P = .563), however, or postoperative duration of stay (median 6.0 vs 5.5 days, P = .22). Furthermore, the rate of conversion to open procedure was similar between the two groups (9 vs 9%, P .99). Regarding oncologic outcomes, there was no statistical difference in overall and disease-free survival between the two groups (5-year overall survival rate 86 vs 89%, P = .72, 5-year disease survival rate 70 vs 77%, P = .70).Laparoscopic colonic resection, when performed for selected patients, appears to be a safe and reasonable option in obese patients with colon cancer resulting in similar short-term and oncologic outcomes as nonobese patients.

The aim of this prospective human trial was to evaluate the clinical performance of a novel THUNDERBEAT (TB) energy device in laparoscopic colon surgery. This study reports the first human trial in USA with this combined energy device in colon surgery. This is a prospective pilot study with 30 subjects undergoing left or right laparoscopic colon resection for neoplasm in a single institution. All soft tissue dissections and all vessel ligations were performed using TB. No other energy device was used within the abdomen. Recorded end-points were dissection time (from the start of colon mobilization to specimen removal), surgical procedure time, the number of times TB taken out of the abdominal cavity, intraoperative complications (bleeding at the time of mesenteric dissection or vessel ligation, thermal injury during surgery, injury of other organs), technical device problems, postoperative complications (bleeding, delayed thermal injuries, other complications within 30 days), length of hospital stay, and mortality. Thirty subjects (15 males) were enrolled in the study with median age and range 68.5 (21–86) and BMI kg/m2 25.5 (20–35). Twelve subjects underwent right and 18 left laparoscopic hemicolectomy. The mean surgical procedure time was 163 ± 86 min and for dissection using TB device 80.6 ± 35 min. Major vessel ligation was successful in all subjects. The median number of TB applications to seal inferior mesenteric artery was 3 (2–8). TB was taken out of the abdominal cavity during dissection for tip cleaning a medium number of two times/per case. No intraoperative or postoperative complications (bleeding, thermal injuries, etc.) related to use of TB were noted. The TB device demonstrated efficient and successful performance at tissue dissection and vessel ligation in left and right colectomies. TB technology can be employed in complex abdominal surgery and may save time through faster dissection but comparative studies with other energy devices are needed to confirm this.

Purpose. The purpose of the study was to evaluate the feasibility and safety of performing laparoscopic intestinal surgery using local anesthesia and intravenous sedation with instruments 2 pneumoperitoneum was maintained using pressure of 3 to 5 mm Hg. Commercially available instruments, sizes 2 insufflation pressure under local anesthesia and intravenous sedation. This methodology holds promise in the development of new approaches to intestinal surgery and disease diagnosis.

Background: Keshanjana (collyrium) is a well known Ayurvedic preparation prepared out of Keshamasi (ash prepared by scalp hairs) mixed with Goghrita (cow's ghee). This medicine is indicated for the treatment of Shushkakshipaka (dry eye syndrome) in the classical literature of Ayurveda; hence, it was under taken for standardization and clinical evaluation in an extra-mural research project from Central Council for Research in Ayurvedic Sciences, Department of AYUSH, New Delhi. Aim: To develop standard quality parameters for the Keshamasi, Keshanjana and Keshamasi ointment. Materials and Methods: Scalp hairs of male and females collected from saloons were converted to classical Masi Kalpana and mixed with cow ghee and petrolatum in the ratio of 1:5 to prepare the Keshanjana and Keshamasi ointment respectively. Standard Operation Procedure (SOP) were adopted and recorded accordingly. The raw material, furnished products and plain Goghrita were subjected for quality control parameters i.e., physico-chemical evaluation, anti-microbial study, particle size analysis, heavy metal analysis through inductive couple plasma spectroscopy with high performance thin layer liquid chromatography fingerprints. Results: Rancidity was negative in all the samples, indicating that the physico-chemical parameters are in acceptable range. Lead and zinc were present in most of the samples; while all samples are were free from microbial contamination. Conclusion: As no standards are available to compare the results of the current study, the observations cannot be compared. Thus the profile generated in the current study can be considered as standard to refer in future studies.

Background HIV and HCV are both treatable viruses for which routine screening among specific age cohorts is recommended. New York State requires patient consent prior to screening for HIV but not HCV. To estimate the impact of the consent requirement, we compared rates of HIV and HCV screening. Methods We performed a retrospective study of all adult patients admitted to a tertiary-care hospital in the Bronx, NY, between April 2015 and June 2016. During the study period, automated prompts in the electronic medical record facilitated screening for HIV among patients ages 21–64, and for HCV among patients born between1945-1965. We compared the proportions of patients qualifying for screening for HIV, HCV, or both who were appropriately screened prior to discharge to calculate an adjusted risk difference between performance of HIV and HCV screening. Using the local prevalence of undiagnosed HIV, we estimated the number of missed HIV diagnoses attributable to the difference in screening rates. Results A total of 21,413 unique hospitalized patients ages 21–64 and/or born between 1945–1965 were analyzed. Among those qualifying for screening for HIV alone or HCV alone, 39.7% and 58.6% were screened prior to discharge, respectively. Among those qualifying for both HIV and HCV screening, 6.7% were screened for HIV alone, 29.3% were screened for HCV alone, and 30.3% were screened for both. The risk difference between HCV and HIV screening adjusted for patient and admission characteristics was 22.0% (95% CI 20.6%-23.4%). Using an estimated prevalence of undiagnosed HIV of 0.2%, this risk difference corresponds to approximately four (95% CI 3.6–4.1) missed cases of HIV during the study period. Conclusion There was a large difference in the number of patients appropriately screened for HIV compared with HCV. While the requirement for consent was the only operational difference in performing routine screening for HIV compared with HCV, differences in how the two viruses are perceived may also have contributed to the observed difference in screening rates. Nevertheless, our findings suggest that removing the requirement for consent prior to HIV screening may increase the number of cases of previously undiagnosed HIV identified by routine screening. Disclosures All authors: No reported disclosures.

Aim The natural history and appropriate management of anastomotic sinus has not been clearly defined. The aim of this study was to evaluate the incidence, management and outcomes of anastomotic sinus. Method The medical records of all patients who underwent a low anterior resection (LAR) or an ileal pouch– anal anastomosis (IPAA) with a diverting loop ileostomy (LI) and with contrast enema performed before planned stoma closure between 2001 and 2011 were retrospectively reviewed. The radiological features of the sinus tract, treatment and outcome of anastomotic sinus were studied. Results Twenty patients (8.2%) were found to have anastomotic sinuses out of the total of 244 patients who had undergone LAR (n = 146) or IPAA (n = 98) with LI. Of these, 13 (65%) had prior symptomatic leaks, while seven did not. Twelve patients (60%) were found to have simple sinus tracts, while eight had complex sinuses (associated with either pelvic cavities or severe strictures). Five patients with simple tracts were treated with observation alone. Fifteen patients underwent surgical interventions. Overall, with a median follow-up of 28 (6–73) months, 16 patients (80%) had resolution of their sinuses. All of 12 patients (100%) with simple sinus tracts and four of eight patients (50%) with complex sinuses underwent successful stoma reversals after 8 (3.5–24) months following the initial surgery (P = 0.01). Conclusion Patients with simple tracts are significantly more likely to have complete resolution of sinuses than patients with complex sinuses. Persistent sinus associated with either a pelvic cavity or severe stricture despite surgical intervention is likely to lead to a permanent