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Human papillomaviruses (HPVs) belongs to the Papillomaviridae family, which is divided into high-risk (HR), and low-risk (LR) HPVs based on their disease-causing competence. HR-HPVs 16 and 18 are known to cause distinct carcinomas like cervical and head and neck, whereas LR-HPVs are commonly associated with the genital warts. We have developed an integrative platform; HPVomics dedicated to the potential therapeutic regimens targeting all HPV genes including oncoproteins E6, E7 and E5. We primarily focused on eighteen HR-HPVs and eleven LR-HPVs. It mainly deals with therapeutically imperative elements, i.e., vaccine epitopes, siRNAs, sgRNAs, and anti-viral peptides. Simultaneously, it also comprises of genome browser, whole-genome sequences and annotation of HPVs with searching and filtering capabilities. Moreover, we have also developed an integrated support vector machine (SVM) based computational algorithm " HPVepi " for the prediction of HPV epitome. We hope that HPVomics (http://bioinfo.imtech.res.in/manojk/hpvomics/) will assist the scientific community engaged in HPV research. • Human papillomaviruses (HPVs) play a cardinal role in diverse carcinomas. • HPVomics is an integrated resource dedicated to the HPV therapeutics and epitome. • Deliver therapeutically vital components i.e., vaccine epitopes, siRNAs, sgRNAs, etc. • HPVepi: HPV epitope prediction algorithm developed. • It is freely available at https://bioinfo.imtech.res.in/manojk/hpvomics/ [ABSTRACT FROM AUTHOR]

In December 2019, the Chinese city of Wuhan was the center of origin of a pneumonia-like disease outbreak with an unknown causative pathogen. The CDC, China, managed to track the source of infection to a novel coronavirus (2019-nCoV; SARS-CoV-2) that shares approximately 79.6% of its genome with SARS-CoV. The World Health Organization (WHO) initially declared COVID-19 as a Public Health Emergency of International Concern (PHEIC) and later characterized it as a global pandemic on March 11, 2020. Due to the novel nature of this virus, there is an urgent need for vaccines and therapeutics to control the spread of SARS-CoV-2 and its associated disease, COVID-19. Global efforts are underway to circumvent its further spread and treat COVID-19 patients through experimental vaccine formulations and therapeutic interventions, respectively. In the absence of any effective therapeutics, we have devised h bioinformatics-based approaches to accelerate global efforts in the fight against SARS-CoV-2 and to assist researchers in the initial phase of vaccine and therapeutics development. In this study, we have performed comprehensive meta-analyses and developed an integrative resource, "CoronaVR" (http://bioinfo.imtech.res.in/manojk/coronavr/). Predominantly, we identified potential epitope-based vaccine candidates, siRNA-based therapeutic regimens, and diagnostic primers. The resource is categorized into the main sections "Genomes," "Epitopes," "Therapeutics," and Primers." The genome section harbors different components, viz, genomes, a genome browser, phylogenetic analysis, codon usage, glycosylation sites, and structural analysis. Under the umbrella of epitopes, sub-divisions, namely cross-protective epitopes, B-cell (linear/discontinuous), T-cell (CD4+/CD8+), CTL, and MHC binders, are presented. The therapeutics section has different sub-sections like siRNA, miRNAs, and sgRNAs. Further, experimentally confirmed and designed diagnostic primers are earmarked in the primers section. Our study provided a set of shortlisted B-cell and T-cell (CD4+ and CD8+) epitopes that can be experimentally tested for their incorporation in vaccine formulations. The list of selected primers can be used in testing kits to identify SARS-CoV-2, while the recommended siRNAs, sgRNAs, and miRNAs can be used in therapeutic regimens. We foresee that this resource will help in advancing the research against coronaviruses. [ABSTRACT FROM AUTHOR]

Nipah virus (NiV) is an emerging and priority pathogen from the Paramyxoviridae family with a high fatality rate. It causes various diseases such as respiratory ailments and encephalitis and poses a great threat to humans and livestock. Despite various efforts, there is no approved antiviral treatment available. Therefore, to expedite and assist the research, we have developed an integrative resource NipahVR (http://bioinfo.imtech.res.in/manojk/nipahvr/) for the multi-targeted putative therapeutics and epitopes for NiV. It is structured into different sections, i.e. genomes, codon usage, phylogenomics, molecular diagnostic primers, therapeutics (siRNAs, sgRNAs, miRNAs) and vaccine epitopes (B-cell, CTL, MHC-I and -II binders). Most decisively, potentially efficient therapeutic regimens targeting different NiV proteins and genes were anticipated and projected. We hope this computational resource would be helpful in developing combating strategies against this deadly pathogen. Database URL: http://bioinfo.imtech.res.in/manojk/nipahvr/ [ABSTRACT FROM AUTHOR]

The outcomes of the elderly population on peritoneal dialysis (PD) in developing countries are less known. In this study, we intended to study the clinical characteristics and patient and technique survival of elderly patients on PD. In this study, data of 148 elderly patients with end-stage renal disease who initiated PD between January 2001 and December 2015 were collected. Baseline clinical characteristics and events during the study period were recorded. Overall patient and technique survival rates of diabetic and non-diabetic elderly patients on PD were analyzed. Around 128 patients who were initiated PD during the study period were included for final analysis. The mean age of the study group was 70.3 ± 5.1 years, and 94 (80%) were males. Among these, 79 (65.8%) had diabetes. At the end of the study period, only 20 (16.6%) patients were remained on PD. Eighty-four (70%) patients died during PD and 15 (12.5%) patients were transferred to hemodialysis during the study period. The main reasons for death were cardiovascular (56.6%) and sepsis due to peritonitis (18.8%). The mean patient survival time was 38.2 ± 2.6 months. The patient survival rates were 91.2%, 45.3%, and 22.8% at 1, 3, and 5 years, respectively. Predictors of mortality were increased serum phosphorus, peritonitis episodes, urine output <400 mL, and ultrafiltration <1000 mL/day at beginning of PD. The mean technique survival time was 92.0 ± 5.1 months. Technique survival rates at 1, 3, and 5 years were 94.8%, 85.3%, and 71.7%, respectively. None of the factors was found to be predictive of technique survival. We found no significant difference between diabetic and non-diabetic patients in terms of technique and patient survival. Mortality was higher in elderly patients on PD. Factors affecting mortality in elderly patients on PD are low urine output, low ultrafiltration at beginning of PD, high serum phosphorus, and presence of peritonitis episodes. Patient and technique survival rates were comparable between diabetic and non-diabetic elderly patients on PD. [ABSTRACT FROM AUTHOR]

Such as any field of medicine, it is imperative to stay current with the latest advances and treatment modalities in toxicology. With the absence of rigorous randomized controlled trials, many updated guidelines are created by expert consensus and/or case reports and clinical experience. Over the past 10 years, there have been several changes in the management of drug overdoses in light of new data available. Although this is not a comprehensive review of all available antidotes, this article will focus on several important interventions including the use of gastrointestinal decontamination, hyperinsulinemic–euglycemic therapy, methylene blue, intravenous lipid emulsion, hemodialysis, and extracorporeal membrane oxygenation. [ABSTRACT FROM AUTHOR]

Chest trauma is an important public health problem accounting for a substantial proportion of all trauma admissions and deaths. It directly account for 20-25 % of deaths due to trauma. Therefore, this study was conducted to analyze the presentation, patterns, and outcome of chest trauma in a level-1 urban trauma center. It was a prospective observational study of all patients presented with chest trauma to an urban level 1-trauma center over a period of 3 years. Demographic profile, mechanism of injury, injury severity scores (ISS), associated injuries, hospital stay, etc. were recorded. Morbidity and mortality rates were analyzed and compared with the published literature. Chest injuries comprised 30.9 % of all trauma admissions and the mechanism was blunt in majority (83.5 %) of the cases. Vehicular crashes (59.7 %) followed by assault were the most common modes of injury. Rib fracture was the most common chest injury seen in 724 of the 1258 patients while abdominal visceral injuries were the commonest associated injuries in polytrauma cases. Majority of the patients were managed non-operatively. Inter costal tube drainage (ICD) was the main stay of treatment in 75 % of the cases, whereas, thoracotomy was required only in 5.56 % of the patients. Overall mortality was 11 % and it was found to be significantly higher following blunt chest trauma. We observed that associated extra thoracic injuries resulted in higher mortality as compared to isolated chest injuries. Thoracic injuries can be readily diagnosed in the emergency department by meticulous and repeated clinical evaluation and majority require simple surgical procedures to prevent immediate mortality and long-term morbidity. [ABSTRACT FROM AUTHOR]

Introduction: Neck and thoracic trauma in children pose unforeseen challenges requiring variable management strategies. Here, we describe some unusual cases. Patients and Methods: Pediatric cases of unusual neck and thoracic trauma prospectively managed from April 2012 to March 2014 at a Level 1 trauma center were studied for management strategies, outcome, and follow-up. Results: Six children with a median age of 5.5 (range 2-10) years were managed. Mechanism of injury was road traffic accident, fall from height and other accidental injury in 2, 3 and 1 patient respectively. The presentation was respiratory distress and quadriplegia, exposed heart, penetrating injury in neck, dysphagia and dyspnea, and swelling over the chest wall in 1, 1, 1, 2 and 1 cases respectively. Injuries included lung laceration, open chest wall, vascular injury of the neck, tracheoesophageal fistula (2), and chest wall posttraumatic pyomyositis. One patient had a flare of miliary tuberculosis. Immediate management included chest wall repair; neck exploration and repair, esophagostomy, gastroesophageal stapling, and feeding jejunostomy (followed by gastric pull-up 8 months later). Chest tube insertion and total parenteral nutrition was required in one each. 2 and 4 patients required tracheostomy and mechanical ventilation. The patient with gastric pull-up developed a stricture of the esophagogastric anastomosis that was revised at 26-month follow-up. At follow-up of 40-61 months, five patients are well. One patient with penetrating neck injury suffered from blindness due to massive hemorrhage from the vascular injury in the neck and brain ischemia with only peripheral vision recovery. Conclusion: Successful management of neck and chest wall trauma requires timely appropriate decisions with a team effort. [ABSTRACT FROM AUTHOR]

Aim Treatment of hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) is difficult. Addition of ribavirin to pegylated-interferon (Peg-IFN) may help to improve the treatment response. Further, treatment duration could be shortened using a response-guided treatment (RGT) approach. Methods We retrospectively reviewed records of treatment-naïve adult patients with ESRD and chronic HCV infection who had been treated with Peg-IFN and low-dose ribavirin using a RGT approach. Rapid responders (undetectable HCV-RNA at 4 weeks) received treatment for 12 weeks, and slow responders (HCV-RNA detectable at 4 weeks, but undetectable or with >2.0 log10 reduction at week 12) for 24 (genotype 3; GT3) or 48 (genotype 1; GT1) weeks. In those without such reduction (null responders), treatment was discontinued. Results Of 26 non-cirrhotic patients (GT1 15, GT3 11) treated, four (15%; GT1 3, GT3 1) were null responders. Twenty-two (85%) patients had either rapid ( n = 14 (54%); GT1 10, GT3 4) or slow response ( n = 8 (31%); GT1 2, GT3 6). Of them, 21 patients had undetectable RNA at the end of treatment; one could not complete the treatment and was lost thereafter. There were no deaths during treatment. Three patients relapsed and three others died in 6 months after stopping treatment. Overall, 15/26 (58%) patients attained SVR24. Fourteen patients underwent transplantation beginning one month after treatment completion, and all were relapse-free after 17 (14-24) months of follow-up. Conclusion RGT using Peg-IFN and ribavirin was effective in ESRD patients on maintenance dialysis. Renal transplant was safely done within one month of completing such treatment. [ABSTRACT FROM AUTHOR]

Objective: To compare oral mifepristone (400 mg) with trans-cervical balloon catheter for induction of labor (IOL) in post date women with previous one cesarean section (CS).Methods: In this randomized trial, post date pregnant women (gestation 40 weeks 5 days), with previous one low segment CS (no previous vaginal delivery) were induced either with oral mifepristone (400 mg) or balloon catheter [Foley's catheter (16 Fr); bulb filled with 30 ml normal saline]. They were re-assessed 24 and 48 h later. If at any time Bishop Score was >6; amniotomy was done, followed by oxytocin infusion. Primary outcome of the study was labor onset after first manoeuvre. Secondary outcomes were cervical ripening, need of oxytocin, vaginal delivery and CS, in two groups.Results: From June 2012 to September 2015, we enrolled 107 women. Out of these, 57 received oral tablet mifepristone (400 mg) and 50 were inserted with balloon catheter. Labor onset after first manoeuvre was statistically significantly more in mifepristone group (37/57 vs. 13/50, respectively; p value 0.000). Bishop Score after 24 h was better in balloon catheter (p value 0.000). More women with balloon catheter required oxytocin for IOL (37/50 vs. 20/57, respectively; p value 0.000) along with higher dose [840 (320) mU vs 560 (120) mU, respectively, p value 0.000]. Failure of induction was statistically significantly higher in balloon catheter group (8 out of 50 vs. 2 out of 57, respectively, p value 0.043). There was no statistically significant difference in normal delivery or CS in either group (p value 0.242 and 0.331, respectively).Conclusion: Oral mifepristone (400 mg) is associated with statistically significantly higher incidence of labor onset in post date pregnant women with previous one CS, as compared to balloon catheter. Both methods are primarily for cervical ripening and oxytocin should not be delayed in the absence of onset of labor.Clinical Trial Registration: Clinical Trials Registry-India, www.ctri.nic.in , CTRI/2012/05/003634. [ABSTRACT FROM AUTHOR]

Purpose: Ursolic acid (UA), a pentacyclic triterpenoid extracted from plants, shows promising inhibitory effect in different tumor bearing cell lines. In the present study we fabricated UA loaded PLGA nanoparticles (UA-NPs) as the drug carrier and thoroughly evaluated in vitro and in vivo the differential tumor targeting effects of UA and UA-NPs in B16F10 melanoma cells. Methods: Ursolic acid loaded PLGA nanoparticles were prepared by emulsion solvent evaporation technique and evaluated for particle size, polydispersity, zeta potential and drug release potency. MTT assay as well as flow cytometric and confocal microscopic analyses were done in B16F10 mouse melanoma cell lines. Formulations were labeled with technetium-99m to evaluate the biodistribution and perform scintigraphic imaging studies following intravenous administration in tumor bearing mice model. Results: Single emulsification technique produced smooth spherical nanoparticles of small size with relatively narrow size distribution (154 ± 4.56 nm). On B16F10 cell line, the formulation showed higher cytotoxicity compared to the free drug due to increased in vitro cellular uptake. The formulation was successfully radiolabeled and remained substantially (>90%) stable when incubated (37°C, 6 h) separately in normal saline or freshly collected rat serum or histidine solution. The radiolabeled UA-NPs exhibited slower blood clearance and comparatively high uptake in tumor region as evidenced by biodistribution and scintigraphic studies. Conclusions: The in vitro and in vivo studies have proved the tumor targeting potential of UA-NPs in B16F10 melanoma cell lines. [ABSTRACT FROM AUTHOR]

Background: Lymphocytic esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations.Aim: The aim of this study was to characterize patients with LyE, compare them to non-LyE controls, and identify risk factors.Methods: We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000, and June 1, 2012. Archived pathology slides were re-reviewed, and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls.Results: Twenty-seven adults were diagnosed with LyE, and the majority were female (63 %). The most common symptom was dysphagia (70 %). Fifty-two percentage had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37 %), erosive esophagitis (33 %), rings (26 %), and hiatal hernia (26 %); 33 % of patients required dilation. After histology re-review, 78 % of LyE patients were found to have more than 20 lymphs/hpf. In comparison with the normal, reflux and EoE controls, patients with LyE tended to be nonwhite (p < 0.01), were more commonly tobacco users (p = 0.02) and less likely to have seasonal allergies (p = 0.02).Conclusion: LyE commonly presents with dysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE, whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is an infectious disease that can involve any organ system of the body. Abdominal TB can be gastrointestinal, lymph-nodal, visceral or peritoneal. Gall bladder (GB) is rarely involved as a primary organ in abdominal TB. On extensive research, the literature on gall bladder TB is limited to case reports. There has been no review on this rare abdominal pathology. The GB tuberculosis is difficult to diagnose preoperatively. It is a rare differential among the more common gall bladder pathologies like cholelithiasis, or a gall bladder malignancy. Standard histopathology of a resected specimen helps in this rare diagnosis. Subjecting every specimen to histopathological examination followed by medical treatment offers a chance to cure. Through this review the authors have tried to provide an insight into this entity. [ABSTRACT FROM AUTHOR]

Necrotising enterocolitis (NEC) is a serious infection of the bowel that predominantly affects preterm infants and is a leading cause for mortality and morbidity in preterm infants. It involves a spectrum of pathology including widespread inflammation of the intestinal mucosa, invasion of the immature gut by enteric gas forming bacteria, dissection of the gut wall and portal veins by this gas, often culminating in ischemic necrosis of the intestine. This article provides an overview of the incidence, etio-pathological risk factors, preventive strategies and medical management of NEC. [ABSTRACT FROM AUTHOR]

Background: Sphingobacterium spiritivorum is a microorganism that is ubiquitously found in the environment. However, it is rarely isolated from human clinical specimens. There are few reports to date of Sphingobacterium spiritivorum causing disease in humans. Case report: We describe a case of Sphingobacterium spiritivorum infection in a patient on haemodialysis, which to our knowledge, has not been described before. Further testing revealed this strain was sensitive to multiple antimicrobials. Conclusion: Despite interrupted courses of several antibiotics, our patient clinically made a good recovery and continued to receive haemodialysis. [ABSTRACT FROM AUTHOR]

Purpose Platinum based chemotherapy is widely used for bladder cancer but is associated with vascular toxicity, especially thromboembolism. We evaluated the short-term (less than 1 year) and intermediate-term (2 to 5 years) vascular toxicity of platinum agents in older patients with bladder cancer. Materials and Methods We identified Medicare beneficiaries 66 to 94 years old diagnosed with stage II-III bladder cancer from 1998 to 2007 in the SEER-Medicare database. We measured the association between platinum based chemotherapy and vascular events (thromboembolic and nonthromboembolic) using Cox proportional hazard regression models. Results The sample included 5,057 patients, of whom 21.3% received platinum based chemotherapy. Patients receiving platinum based chemotherapy were more likely to be younger and male with less comorbidity than those not receiving any chemotherapy. During the first year after diagnosis the patients who received platinum based chemotherapy had a higher risk of a thromboembolic event (19.8% vs 11.6%, AHR 1.43, 95% CI 1.17–1.75) compared to those who did not receive chemotherapy. The likelihood of having a thromboembolic outcome was similar whether platinum chemotherapy was cisplatin based (21.1%, AHR 1.56, 95% CI 1.22–2.00) or carboplatin based (18.9%, AHR 1.35, 95% CI 1.07–1.71). During years 2 to 5 after diagnosis there was no significant association between platinum chemotherapy and the risk of thromboembolic events. The risk of nonthromboembolic vascular events was not increased with platinum chemotherapy in either period. Conclusions Patients receiving platinum based chemotherapy were at higher risk for thromboembolism but not other vascular events, particularly in the first year after diagnosis. This risk of thromboembolism is similar for cisplatin and carboplatin. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is an infectious disease that can affect any organ system of the body. Abdominal TB can be gastrointestinal, lymph nodal, visceral or peritoneal. The gallbladder (GB) is rarely involved in abdominal TB as a primary organ. Extensive research literature on gallbladder TB is limited to case reports. There has been no review on this rare abdominal pathology. GB tuberculosis is a difficult diagnosis preoperatively. It is a rare differential among the more common gallbladder pathologies such as cholelithiasis, or a gallbladder malignancy. Typical histopathology of the resected specimen helps to establish this rare diagnosis. Subjecting every specimen to histopathological examination followed by medical treatment offers the chance of cure. Through this review, the authors attempt to provide an insight into this disease entity. [ABSTRACT FROM AUTHOR]

We present 2 cases of Trigeminal neuralgia (TN) refractory to medicinal therapy. The patients had pain that was unilateral along distribution of the trigeminal nerve trunk, particularly the second and third trunk. Peripheral glycerol injection is a "minimally invasive therapy" that can be considered for patients refractory to medicinal treatment. Ease of administration and repeatability favors its use in a clinical setup. Both the patients responded very well to the treatment and 6 month follow up showed no recurrence of TN. [ABSTRACT FROM AUTHOR]

Purpose Patients with good risk nonseminomatous germ cell tumors received induction chemotherapy with 4 cycles of etoposide and cisplatin (EPx4) or 3 cycles of bleomycin, etoposide and cisplatin (BEPx3). We report the histological results at post-chemotherapy retroperitoneal lymph node dissection after induction chemotherapy in patients treated with etoposide and cisplatin or bleomycin, etoposide and cisplatin for good risk nonseminomatous germ cell tumors. Materials and Methods Post-chemotherapy retroperitoneal lymph node dissection was performed in 579 patients after induction chemotherapy. Of these patients 505 were treated with EPx4 and 74 were treated with BEPx3 or BEPx4. Clinical and pathological features are reported. Results No difference in the frequency of viable residual cancer was observed with bleomycin, etoposide and cisplatin vs etoposide and cisplatin (5% vs 6%, respectively, p=not significant). Teratoma was more prevalent in the bleomycin, etoposide and cisplatin group vs etoposide and cisplatin group (57% vs 34%, respectively, p <0.001). On multivariate analysis patients who received induction bleomycin, etoposide and cisplatin had a twofold greater risk of harboring teratoma at post-chemotherapy retroperitoneal lymph node dissection (OR 2.0; 95% CI 1.0, 4.0; p=0.04). When excluding patients from analysis who received BEPx4, those who received BEPx3 still had a 3.7-fold increased risk of teratoma in the retroperitoneum (OR 3.7; 95% CI 1.5, 8.9; p=0.004). Relapse-free and disease specific survival was not different between the 2 regimens. Conclusions Viable cancer was equally uncommon after treatment with both regimens. Overall, relapse-free and disease specific survival did not differ between the groups. The discrepancy between regimens in the frequency of teratoma is not explained but may be due to an unrecognized selection bias rather than an effect of the regimen. [ABSTRACT FROM AUTHOR]

Inguinal hernia repair using mesh is one of the most frequently performed operations in general surgery. The mesh can be placed using an open technique or by laparoscopic approach. Many studies have highlighted the merits and risks of laparoscopic approach for the repair of inguinal hernia, the final sentence still remains to be written as majority of trials are too small to show clear benefits of one technique over another. To compare laparoscopic mesh repair with open method in management of inguinal hernia. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? Lymphovascular invasion ( LVI) is an important step in systemic cancer cell dissemination. LVI has been shown to be an independent predictor of disease recurrence and cancer-specific survival in urothelial carcinoma of the bladder ( UCB) for patients with carcinoma invading bladder muscle., Patients with final pathological stage T1 N0 UCB who underwent radical cystectomy ( RC) have not been separately analysed for influence of LVI on outcomes. Our study shows that LVI predicts disease recurrence and cancer-specific survival in patients with final stage T1 UCB after RC., Objective To determine the outcomes of patients with final pathological stage T1 N0 disease after radical cystectomy ( RC) for urothelial carcinoma of the bladder ( UCB) and to determine whether lymphovascular invasion ( LVI) is an independent predictor of prognosis in these patients., Patients and Methods Records of 958 consecutive patients who underwent RC at three academic centres were reviewed., A total of 101 patients with negative lymph nodes and with final stage (the higher of the pre- RC clinical/transurethral resection [ TUR] and post- RC pathological stages) T1 UCB were identified., The median (range) follow-up was 38 (0.4-177) months and the median (range) number of nodes examined was 19 (9-80)., Results Overall, 12/101 (11.9%) patients experienced cancer recurrence and 7/101 (6.9%) died from their cancer. The 3-year recurrence-free survival probability (SD) was 0.89 (0.04) and 3-year cancer-specific survival probability (SD) was 0.96 (0.02)., Six of 101 (6%) patients had LVI, of whom four experienced disease recurrence and three died from bladder cancer., All recurrences and deaths occurred in patients who had either LVI and/or concomitant carcinoma in situ., On multivariable analysis, LVI (hazard ratio [ HR] 4.9, P = 0.01) and higher pathological stage ( HR 8.5, P = 0.04) predicted cancer recurrence and LVI ( HR 6.7, P = 0.01) predicted cancer-specific survival., Conclusions LVI helps identify patients with final pathological T1 N0 UCB who are at significantly increased risk of bladder cancer recurrence and death., These patients should be considered for close monitoring after cystectomy. [ABSTRACT FROM AUTHOR]

Chylothorax is known for its rarity, and its diagnosis following blunt chest trauma is exceptional. Only a small number of cases have been reported in the literature. Severe consequences, such as cardiopulmonary abnormalities and metabolic, nutritional, and immunologic disorders, can result from chylothorax. Management of chylothorax is challenging. It can either be managed nonoperatively or surgically. Surgical treatment is required in cases of persistent or high output fistulae. We report here in three cases of blunt trauma chest following road traffic crash associated with chylothorax. All of them were successfully managed nonoperatively with inter costal tube drainage and supportive treatment sans need of any operative intervention. [ABSTRACT FROM AUTHOR]

Background: The purpose of the present study was to determine the etiology, management, and outcome of acute pancreatitis (AP) in children in an endemic area of hepatobiliary ascariasis (HBA). Methods: This was a prospective, hospital-based study over a 9-year period that included 156 children younger than 12 years of age who had a diagnosis of AP. Results: Of the 156 patients, 71 were boys and 85 were girls with a mean age of 8.4 ± 1.5 years (range 3-12 years). The various factors contributing to AP were biliary ascariasis in 93 cases (60 %), gallstones 16 (10 %), trauma 5 (3 %), choledochal cyst 4 (3 %), impacted bile duct stone 3 (2 %), and gallbladder sludge 2 (1 %). Idiopathic group 33 cases (21 %). Diagnosis was based on clinical picture, abdominal ultrasonography, and elevated serum amylase level. Pancreatitis was mild in 113 (72 %) patients and severe in 43 (28 %). With conservative therapy, 123 patients (79 %) improved, whereas the remaining 33, who had intractable abdominal pain, cholangitis, or worsening cholecystitis, underwent emergency endoscopic retrograde cholangiopancreatography for removal of worms (26 patients) and stones in the bile duct (7 patients). Bile duct stones were extracted in all 7 patients with that condition, and worms were extracted from 23 of the 26 patients with ascariasis. Emergency surgery was performed in five patients. Three patients died. Pancreatitis recurred in 16 patients due to HBA. Conclusions: Pancreatitis is not uncommon in children. Ascariasis is a leading cause of AP in endemic areas. Patients usually respond to conservative management, but endoscopic treatment is effective. Surgery is rarely required. [ABSTRACT FROM AUTHOR]

Background. The putative genetic regulation of multidrug resistance gene-1 (MDR-1) gene expression and P-glycoprotein function has not yet been clearly delineated in patients with nephrotic syndrome (NS). We undertook this study to examine the distribution of three most frequent MDR-1 exonic polymorphisms G3435C, G2677T/A and C1236T in patients with NS and control children to investigate their usefulness as markers of responsiveness of the disease to steroids.Methods. Two hundred and sixteen children with NS and 216 healthy controls were genotyped for three exonic MDR-1 polymorphisms (G3435C, G2677T/A and C1236T) by using the polymerase chain reaction–restriction fragment length polymorphism technique. The frequency distribution of genotypes/alleles was compared between patients with NS and controls and also between steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS) patients.Results. Of the total 216 cases of NS (median age of onset 5 years, 165 males), 137 had SSNS, and 79 had SRNS. Homozygous mutants of C3435T (TT versus CC, P = 0.034) and G2677T/A (TT + AA versus GG), P = 0.030) were significantly higher in patients with NS compared to controls. The frequency distribution of homozygous mutant TT + AA compared to wild genotype GG was significantly higher in SRNS than SSNS patients (P = 0.011) for G2677T/A, while the mutant genotypes for C3435T and C1236T were not different between SRNS and SSNS patients. The combination-bearing mutant genotype either of C3435T or G2677T/A exhibited a significantly higher frequency of mutant genotypes distribution in SRNS patients. MDR-1 haplotypes did not differ significantly between SSNS and SRNS patients.Conclusions. Patients with NS carrying homozygous mutants of single nucleotide polymorphism (SNP) G2677T/A are prone to develop SRNS. The synergistic effect of mutant genotypes of SNPs G2677T/A and C3435T in different combinations increase the risk of developing steroid resistance in patients with NS. [ABSTRACT FROM PUBLISHER]

Purpose: Women have been associated with adverse outcomes after radical cystectomy for lower tract urothelial carcinoma. We evaluated the prognostic value of gender in an international cohort of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods: We retrospectively studied 754 patients treated with RNU for UTUC without neoadjuvant chemotherapy at nine centers located in Asia, Canada, and Europe. Univariable and multivariable Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. Median follow-up was 40 months (interquartile range: 18-75). Results: The majority of patients was of men (516, 68.4%). Women were older than men at the time of RNU (median: 69.2 vs. 66.5 years; P = 0.0003). Women were less likely to have high-grade disease, undergo lymph node dissection, and to receive adjuvant chemotherapy. Gender was not associated with pathologic stage, lymph node metastasis, lymphovascular invasion, concomitant CIS, tumor architecture, or tumor necrosis. On univariable Cox regression analyses, there was no association between gender and cancer recurrence ( P = 0.76) or cancer-specific mortality ( P = 0.30). On multivariable Cox regression analyses that adjusted for the effects of clinicopathologic features, gender was not associated with disease recurrence ( P = 0.47) or cancer-specific survival ( P = 0.15). Conclusions: We found no difference in histopathologic features and outcomes between men and women treated with RNU for UTUC. Nevertheless, epidemiologic and mechanistic molecular studies should be encouraged to design, analyze, and report gender-specific associations to aid in our understanding of gender impact on UTUC incidence, progression, and metastasis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to assess the association of concomitant carcinoma in situ (CIS) with disease recurrence and cancer-related death in a multi-institutional series of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods: We collected retrospectively the data of 772 patients treated with RNU and ipsilateral bladder cuff excision at 9 international institutions in Asia, Europe, and Northern America from 1987 to 2008. Surgical specimens were processed according to standard pathologic procedures at each institution. Univariable and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality. Results: Concomitant CIS was present in 88 patients (11.4%); it was associated with more advanced pathologic stage, higher tumor grade, and presence of lymphovascular invasion (all P-values < 0.05). The five-year recurrence-free (RFS) and cancer-specific survival (CSS) estimates were 74.4 and 76.3%, respectively, in the absence of CIS compared with 56.4 and 59.9%, respectively, in the presence of CIS ( P-values < 0.0001 for RFS and 0.002 for CSS, respectively). On multivariable Cox regression analyses, concomitant CIS was an independent predictor of both RFS (hazard ratio (HR): 1.9; P = 0.007) and CSS (HR: 1.7, P = 0.048). Similar findings were reconfirmed in subgroups analyses limited to T2, organ confined, and N0/Nx UTUC, or patients who did not receive adjuvant chemotherapy. Conclusions: Presence of concomitant CIS is an independent predictor of both RFS and CSS in patients treated with RNU for UTUC. This information may be useful in risk stratification of UTUC patients for follow-up and additional therapy. [ABSTRACT FROM AUTHOR]

Abstract: Various putative theories involved in the development of chronic fatigue syndrome revolve around the role of stress, infection and oxidative stress. Scientific evidence highlighting the protective role of nutritional supplements in chronic fatigue syndrome is lacking. Based on these assumptions, the present study was designed to evaluate the effect of olive extract in a mouse model of immunologically-induced fatigue, wherein purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigen were used as immunogens. The assessment of chronic fatigue syndrome was based on immobility period during chronic water-immersion stress test for 10min daily. The stress-induced hyperalgesia was measured by tail withdrawal latency. Mice challenged with LPS or BA for 19days showed significant increase in the immobility time, hyperalgesia and oxidative stress on the 19th day. Serum tumor necrosis factor-alpha (TNF-α) levels were also markedly increased with LPS or BA challenge. Concurrent treatment with olive extract resulted in a significant decrease in the immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as serum TNF-α levels. The results of the present study strongly indicate the role of oxidative stress and immunological activation in the pathophysiology of chronic fatigue syndrome and highlight the valuable role of olive extract in combating chronic fatigue syndrome. [Copyright &y& Elsevier]

Purpose: We determined the relevance of the biomechanical properties of freshly harvested vaginal tissue during large cystocele repair on clinical outcome at a minimum 1-year followup. Materials and Methods: With institutional review board approval we prospectively studied the biomechanical properties of full thickness vaginal wall tissue from postmenopausal women with symptomatic Baden-Walker prolapse undergoing anterior vaginal wall suspension with cystocele repair from 2002 to 2005. A standardized biomechanical protocol was applied with stress-strain curves for Young''s modulus obtained by blinded investigators. Failed repair was defined as recurrence on examination or reoperation for recurrent anterior prolapse. Results: A total of 32 patients (median age 72 years) had a median followup of 34 months (range 12 to 62). Median Young''s modulus was statistically different in tissue samples transported in immersed vs moistened media (median 3.8 vs 7.6, p = 0.008). Associations between Young''s modulus and clinical variables were described. On followup 7 patients experienced failure of the repair. After controlling for tissue transport protocol no association was seen between Young''s modulus and failures (HR 1.1, p = 0.34). Conclusions: This study found no association between Young''s modulus and clinical results at long-term followup. This finding suggests that retropubic scarring and pelvic floor muscle properties may be more important for a successful reparative outcome than the intrinsic properties of the vaginal wall. [Copyright &y& Elsevier]

Basal cell carcinoma of the penis is an extremely rare entity, accounting for less than 0.03% of all basal cell carcinomas. Fortunately, wide local excision of such lesions is generally curative. Fewer than 25 cases have been reported in the literature describing penile basal cell carcinoma. Here we report a case of penile basal cell carcinoma cured with wide local excision. [ABSTRACT FROM AUTHOR]

A five year old male dog presented with generalized patchy alopecia, erythema, papules, pustules, pruritus and skin scales on most body parts. Cigar shaped demodex mites in deep skin scrapping from lesions confirmed generalised demodicosis. Culture of superficial skin scrapping revealed presence of Trichophyton mentagrophytes. The dog was treated with daily oral Ivermectin @ 0.5 mg/kg body weight along with topical Amitraz @ 0.05% twice in a week until two consecutive skin scrapings resulted in cure. Antimicrobial therapy along with Ketoconazole treated concurrent bacterial and fungal infection. [ABSTRACT FROM AUTHOR]

Eight New Zealand white rabbits were presented with clinical signs of pruritus, alopecia, scab and crust formation and llchenification Initially on upper lip which later extended to full face, ear pinnae, eyelids, lower jaw and limbs. Skin scrapping revealed mixed infestations of Sarcoptes cuniculi and Psoroptes cuniculi. Subcutaneous injection of ivermectin at weekly intervals for four weeks resulted In remission of clinical signs and improvement. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of good quality evidence regarding the best therapeutic option for acute control of blood pressure during acute hypertensive emergency of pregnancy.Objective: We sought to compare the efficacy of intravenously administered hydralazine and oral nifedipine for acute blood pressure control in acute hypertensive emergency of pregnancy.Study Design: In this double-blind, randomized, controlled trial, pregnant women (≥24 weeks period of gestation) with sustained increase in systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥110 mm Hg were randomized to receive intravenous hydralazine injection in doses of 5, 10, 10, and 10 mg and a placebo tablet or oral nifedipine (10 mg tablet up to 4 doses) and intravenous saline injection every 20 minutes until the target blood pressure of 150 mm Hg systolic and ≤100 mm Hg diastolic was achieved. Crossover treatment was administered if the initial treatment failed. The primary outcome of the study was time necessary to achieve target blood pressure. The secondary outcomes were the number of dosages required, adverse maternal and neonatal effects, and perinatal outcome.Results: From December 2014 through September 2015, we enrolled 60 patients. The median time to achieve target blood pressure was 40 minutes in both groups (intravenous hydralazine and oral nifedipine) (interquartile interval 5 and 40 minutes, respectively, P = .809). The median dose requirement in both groups was 2 (intravenous hydralazine and oral nifedipine) (interquartile range 1 and 2 doses, respectively, P = .625). Intravenous hydralazine was associated with statistically significantly higher occurrence of vomiting (9/30 vs 2/30, respectively, P = .042). No serious adverse maternal or perinatal side effects were witnessed in either group.Conclusion: Both intravenous hydralazine and oral nifedipine are equally effective in lowering of blood pressure in acute hypertensive emergency of pregnancy. [ABSTRACT FROM AUTHOR]

A eighteen months old German Shepherd dog was examined with complaint of recurrent inappetence, weakness and vomiting. Hematology showed leucocytosis with neutrophilia. Increase of ALT, ALP and GGT supported diagnosis of hepatobiliary disease. Abdominal ultrasound evaluation showed diffuse hepatic tissue lesions associated with cholangitis. The dog responded to rehydration and anti-bacterials along with ursodeoxycholic acid and silymarin assisting speedy recovery. [ABSTRACT FROM AUTHOR]

Uremic pruritus is one of the most troublesome symptom associated with uremia. There are reports of significant relief with use of Gabapentin in refractory uremic pruritus. But many patients experience sedation and dizziness with use this agent. Incidence of such side effects is less with pregabalin. There is paucity of information about efficacy of pregabalin in uremic pruritus. Therefore we conducted this study to evaluate efficacy of pregabalin in patients of end stage renal disease (ESRD) with refractory pruritus. Materials and Methods: Study group comprised of 21 patients on maintenance hemodialysis (MHD) They had severe pruritus refractory to traditional measures like charcoal, antihistaminics and xylocaine etc. They received 75 mg pregabalin daily. Their pruritus score was calculated before starting therapy. It was calculated 7 days and 14 days after treatment. VAS score was also calculated on same visits on 10 mm line. Besides this their demographic profile, dialysis dose, S.Calcium, S.Phosphorus, S.PTH were also recorded. Any side effect like dizziness, sedation or weight gain was also recorded. Results: Mean age of patients was 42±18.2 years. Gender ratio was 2.2: 1(M:F). Causes of ESRD were DM 38% (n= 8), Chronic glomerulonephritis 23.8% (n= 5), Chronic interstitial nephritis 19% (n=4) and others 19% (n=4). All patients were on maintenance hemodialysis. Their mean kt|v was 1.28±.12. Their mean S. Ca, S. P were 8.98±1.21 mg% and 4.9±1.13 mg% respectively. Their mean S. PTH was 164±36.4 pg/ml. Mean duration of hemodialysis was 10+ 4 months. Their pruritus score before treatment was 16.4±1.99 (range 14-19). The pruritus score was 13.76±1.76 (range 10-16) after 1 week of therapy and it was 10.28±1.24 (range 7-12) after 2 weeks of therapy. We compared baseline pruritus score to score at I week (P=0.003) and at 2 weeks (P=0.003). VAS score also showed significant improvement from baseline. The VAS score before treatment was 6.94.1.6. It was 4.84.1.9 after 1 week of treatment and score was 3.8 4.1.7 after 4 weeks of treatment. 3 patients complained of dizziness and vertigo during treatment and they were managed by increasing the dose interval of drug to 36 hours. Significant weight gain was not observed in any patient. Conclusion: Use of pregabalin is associated with significant symptomatic relief in refractory uremic pruritus and no significant side effects were observed. [ABSTRACT FROM AUTHOR]

Purpose To compare the demarcation line depth after contact lens–assisted corneal crosslinking (CXL) for progressive keratoconus using dextran-based and hydroxypropyl methylcellulose (HPMC)-based riboflavin solutions. Setting Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Design Retrospective case series. Methods Patients with preoperative epithelium-on (epi-on) minimum corneal thickness between 350 μm and 450 μm having contact lens–assisted CXL for progressive keratoconus were crosslinked with isoosmolar 0.1% riboflavin in 20% dextran 500 or HPMC 1.1%. The primary outcome measure was the mean demarcation line depth measured 1 month postoperatively on anterior-segment optical coherence tomography. The secondary outcome measure was change in endothelial cell density (ECD) 6 months from baseline. Results The study comprised 21 patients (21 eyes, 9 in the HPMC group and 12 in the dextran group). The mean demarcation line depth was deeper in the HPMC group (308.22 μm ± 84.19 [SD]) than in the dextran group (235.33 ± 64.87 μm) ( P < .04). This difference remained significant ( P = .02) even after controlling for the preoperative lesser epi-on minimum corneal thickness in the HPMC group (385.56 ±13.81 μm) versus the dextran group (413.08 ± 29.58 μm) ( P < .02). The ECD 6 months after contact lens–assisted CXL was comparable to the baseline levels in both groups ( P = .19 and P = .09, respectively). Conclusion During contact lens–assisted CXL, HPMC-based riboflavin seemed to be associated with a deeper demarcation line than dextran-based riboflavin, although both solutions were safe for the endothelium at 6 months. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate safety and visual outcomes in surgically aphakic children undergoing secondary intraocular lens (IOL) implantation. DESIGN: Retrospective, consecutive, interventional case series. METHODS: One hundred seventy-four eyes of 104 children (70 bilateral, 34 unilateral) who underwent secondary IOL implantation for aphakia after congenital cataract surgery at L. V. Prasad Eye Institute, Hyderabad, India, were analyzed. A minimum of 3 months of follow-up after surgery was required for inclusion in the study. Eyes with aphakia after surgery for traumatic cataracts and other associated ocular comorbidities were excluded. Main outcome measures were intraoperative and postoperative complications and visual outcome at the last follow-up. RESULTS: Mean age at secondary IOL implantation was 6.08 ± 3.75 years. The mean follow-up was 25.7 ± 24.9 months. Mean best-corrected visual acuity improved from 1.08 ± 0.65 in aphakic children to 0.55 ± 0.51 logarithm of the minimal angle of resolution in pseudophakic children at last follow-up (P < .0001). Overall, 51 eyes (35%) attained a final best-corrected visual acuity of 20/ 40 (0.3 logarithm of the minimal angle of resolution) or better, whereas only 2 eyes (8.7%) attained a final bestcorrected visual acuity of 20/40 (0.3 logarithm of the minimal angle of resolution) or better in children who underwent secondary IOL implantation for unilateral aphakia. The most common postoperative complications were secondary membrane formation (17 eyes; 9.77%), optic capture (15 eyes; 8.6%), IOL decentration (9 eyes; 5.17%), and secondary glaucoma (11 eyes; 5%). CONCLUSIONS: Secondary sulcus IOL implantation in children is a relatively safe procedure and leads to favorable visual postoperative outcomes. [ABSTRACT FROM AUTHOR]

Allele-specific siRNAs (ASP-siRNAs) have emerged as promising therapeutic molecules owing to their selectivity to inhibit the mutant allele or associated single-nucleotide polymorphisms (SNPs) sparing the expression of the wild-type counterpart. Thus, a dedicated bioinformatics platform encompassing updated ASP-siRNAs and an algorithm for the prediction of their inhibitory efficacy will be helpful in tackling currently intractable genetic disorders. In the present study, we have developed the ASPsiRNA resource (http://crdd.osdd.net/servers/aspsirna/) covering three components viz (i) ASPsiDb, (ii) ASPsiPred, and (iii) analysis tools like ASP-siOffTar. ASPsiDb is a manually curated database harboring 4543 (including 422 chemically modified) ASP-siRNAs targeting 78 unique genes involved in 51 different diseases. It furnishes comprehensive information from experimental studies on ASP-siRNAs along with multidimensional genetic and clinical information for numerous mutations. ASPsiPred is a two-layered algorithm to predict efficacy of ASP-siRNAs for fully complementary mutant (Effmut) and wild-type allele (Effwild) with one mismatch by ASPsiPredSVM and ASPsiPredmatrix, respectively. In ASPsiPredSVM, 922 unique ASP-siRNAs with experimentally validated quantitative Effmut were used. During 10-fold cross-validation (10nCV) employing various sequence features on the training/testing dataset (T737), the best predictive model achieved a maximum Pearson's correlation coefficient (PCC) of 0.71. Further, the accuracy of the classifier to predict Effmut against novel genes was assessed by leave one target out cross-validation approach (LOTOCV). ASPsiPredmatrix was constructed from rule-based studies describing the effect of single siRNA:mRNA mismatches on the efficacy at 19 different locations of siRNA. Thus, ASPsiRNA encompasses the first database, prediction algorithm, and off-target analysis tool that is expected to accelerate research in the field of RNAibased therapeutics for human genetic diseases. [ABSTRACT FROM AUTHOR]