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Background: There are limited studies pertaining to management of encephalocele in Nepal. So the present study seems justifiable to bridge the gap in the literature on encephalocele from Nepal on its clinical profile and early outcome. This study aims to characterize the clinical profile, management and outcome of largest series of encephalocele at tertiary care center in Nepal. Materials and Methods: A retrospective analysis of encephalocele, managed surgically at two tertiary care centers between 2015 and 2020, was performed. Results: Total of 25 cases was surgically managed in the present study. The median age of study population was 2.5 months. There were 11 male and 14 female with male to female ratio of 1:1.26. Occipital encephalocele was the most common variant. Lump in the head (n=11) was the commonest clinical presentation followed by hyperteliorism (n=10). One patient presented with cleft lip and one had CSF discharge in a case of occipital encephalocele. Bony defect was the common radiological findings. Excision and repair was the most common mode of surgery leading to good outcome. Mortality rate was 4% with morbidity of 20%. Conclusion: Early surgical excision and tight dural closure with repair of bony defect is the standard treatment with relatively good outcome.

IntroductionVentriculoperitoneal (VP) shunt is a commonly performed neurosurgical procedure in pediatric surgical practice. It results in a dramatic improvement in patient survival and neurological function but is associated with several complications requiring multiple shunt revisions throughout a patient’s lifetime. The main aimof the study was to evaluate the outcome especially complications of shunt surgery at our center.MethodsA single-institutional, retrospective observational study was conducted in 60 operated cases of congenital hydrocephalus with a minimum follow-up for up to 6 months. Parameters for analysis included demographic data, etiology of hydrocephalus, surgery time, and type of complications.ResultsOut of 86 patients, 60 patients who fulfilled the inclusion criteria were enrolled in the study. The mean age of the patients at the time of VP shunt placement was 3 months, range from 8 days to 15 years with male preponderance. The majority of the patients belonged to the 0-1-year age group (76.8%). Thecommonest etiology of hydrocephalus was congenital aqueduct stenosis. Fifteen patients (25%) developed complications within six months follow-up period. Eight patients (13.3%) developed clinical shunt infection with four cases having culture positive. Four (6.67%) had mechanical complications in the form of shuntobstruction. Three patients had ascites, subdural collection, and shunt extrusion from the anus. The shunt related mortality was 1.67%.ConclusionThe shunt infection and obstruction still remain the most important complications. Despite inherent problems, shunt surgery is the procedure of choice until a safer effective alternative is available.Keywords: Complications congenital hydrocephalus, ventriculoperitoneal shunt

Introduction: Microvascular complications such as diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy are associated with considerable medical and economic impact among persons with diabetes. In the UK Prospective Diabetes Study [UKPDS], 37% of patients with newly diagnosed type 2 diabetes developed at least one microvascular complication over a ten years period. Methodology: The procedure was told to the patients. 5.07 Simmes Weinstein monofilament consisted of a plastic handle supporting a nylon filament. The filament was placed perpendicular to the skin of the foot, and the pressure was applied until the filament buckles. The filament was held in place for approximately 1 second, then released. The patients were asked to elicit a ‘Yes/No’ response to monofilament pressure and correctly identify the site of contact. Inability to perceive the 10 g of force it applies was associated with clinically significant large fibre neuropathy. Like this 9 plantar sites and 1dorsal site were tested in each foot. Results: Statistical analysis of above obtained data reveals that patient with HbA1c ≥8% have 4.4 times higher risk of developing microvascular complications than patient with HbA1c ≤8%. This indicates HbA1c is a better predictor of microvascular complications in diabetics. Most of the patients had normal Blood urea and Serum creatinine levels. 25 patients had urea > 40mg/dl. 2 patient had creatinine > 2mg/dl. Conclusion: It is clear that significant increase in Blood urea and Serum creatinine levels which is indicative of renal involvement is less common at diagnosis of diabetes mellitus.

Background: Metabolic and bariatric surgery (MBS) is an effective treatment for adolescents with severe obesity. Objectives: This study examined the safety of MBS in adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This was a global, multicentre and observational cohort study of MBS performed between May 01, 2020, and October 10,2020, in 68 centres from 24 countries. Data collection included in-hospital and 30-day COVID-19 and surgery-specific morbidity/mortality. Results: One hundred and seventy adolescent patients (mean age: 17.75 ± 1.30 years), mostly females (n=122, 71.8%), underwent MBS during the study period. The mean pre-operative weight and body mass index were 122.16 ± 15.92 kg and 43.7± 7.11 kg/m2, respectively. Although majority of patients had pre-operative testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n=146; 85.9%), only 42.4% (n=72) of the patients were asked to self-isolate pre-operatively. Two patients developed symptomatic SARS-CoV-2 infection post-operatively (1.2%). The overall complication rate was 5.3% (n=9). There was no mortality in this cohort. Conclusions: MBS in adolescents with obesity is safe during the COVID-19 pandemic when performed within the context of local precautionary procedures (such as pre-operative testing). The 30-day morbidity rates were similar to those reported pre-pandemic. These data will help facilitate the safe re-introduction of MBS services for this group of patients.

Background Recent trauma guidelines recommend non-operative management for grade III splenic injury without contrast extravasation on computed tomography. Nevertheless, such recommendations rely on low-quality evidence, and practice variation characterizes clinical management for this type of injury. We aimed to identify the role of eleven selected clinical factors influencing the management of grade III splenic injury without contrast extravasation by expert consensus and a modified Delphi approach. Methods A questionnaire was developed with the endorsement of the World Society of Emergency Surgery (WSES). This was delivered and answered live by acute care surgeons attending the 6th WSES congress in Nijmegen in 2019. A dedicated mobile phone application was utilized to collect the answers. All answers were evaluated for areas of discrepancy with an 80% threshold for consensus between respondents. Results Three factors generated discrepancy in opinion for managing this pattern of injury: the patients’ injury severity, the presence of a bleeding diathesis, and an associated intra-abdominal injury. Agreement was obtained for the other eight factors. Conclusion Researchers should focus their efforts on the identified area of discrepancy. Clinicians should use additional care in the presence of the three factors for which discordant opinions were found.

IntroductionRecent advances hold promise of making personalized medicine a step closer to implementation in clinical settings. However, traditional sample preparation methods are not robust and reproducible. In this study, the TissueGrinder, a novel mechanical semi-automated benchtop device, which can isolate cells from tissue in a very fast and enzyme-free way is tested for cell isolation from surgically resected tumor tissues.Methods33 surgically resected tumor tissues from various but mainly pancreatic, liver or colorectal origins were processed by both novel TissueGrinder and explant method. An optimized processing program for tumors from pancreatic, liver or colorectal cancer was developed. The viability and morphological characteristics of the isolated cells were evaluated microscopically. Expression of pancreatic cancer markers was evaluated in cells isolated from pancreatic tumors. Finally, the effect of mechanical stress on the cells was evaluated by assessing apoptosis markers via western blotting.ResultsTissueGinder was more efficient in isolating cells from tumor tissue with a success rate of 75% when compared to explant method 45% in terms of cell outgrowth six weeks after processing. Cells isolated with TissueGinder had a higher abundance and were more heterogeneous in composition as compared to explant method. Mechanical processing of the cells with TissueGrinder does not lead to apoptosis but causes slight stress to the cells.DiscussionOur results show that TissueGrinder can process solid tumor tissues more rapidly and efficiently and with higher success rate compared to the conventionally used explant method. The results of the study suggest that the TissueGrinder might be a suitable method for obtaining cells, which is important for its application in individualized therapy. Due to the great variance in different tumor entities and the associated individual tissue characteristics, a further development of the dissociation protocol for other types of tumors and normal will be targeted.

Introduction: The worldwide prevalence of DM has risen dramatically over the past two decades, from an estimated 30 million cases in 1985 to 285 million in 2010. Based on current trends, the International Diabetes Federation projects that 438 million individuals will have diabetes by the year 2030. Although the prevalence of both type 1 and type 2 DM is increasing worldwide, the prevalence of type 2 DM is rising much more rapidly, presumably because of increasing obesity, reduced activity levels as countries become more industrialized, and the aging of the population. Methodology: Patients with newly diagnosed Diabetes mellitus presenting to department of medicine, were formed study subjects. They presented to physician either for routine checkup or have been admitted for some other illness and diabetes was detected by chance for first time. Known cases of diabetes mellitus under treatment were excluded from study. Results: It is clear that 34% of the patients at the time of diagnosis of diabetes mellitus had some infections (24% males and 10% females). 2% of the patients had cellulitis, 4% of them had UTI, 2% of them had tuberculosis, 10% of them had pneumonia, and 2% had gluteal abscess. Conclusion: 56% of the patients presented with classical symptoms of Diabetes and 32% of patients with symptoms due to complications. 12% of the patients were asymptomatic.

Diastomatomyelia (DM) is a clinical condition in which the spinal cord is split into two portions by either a bony or a fibrous spur. Depending on the type of dural involvement, it is divided into type 1 and type 2. We recently came across a 9-month old child with a lumbar DM with syringomyelia who was managed successfully at our institute. We discuss the management of this patient in detail along with the description of its etiology, embryology, neurological manifestations, relevant investigations, and treatment implications to both patients and parents. To the best of our knowledge, this is the first case report of DM from Nepal in an infant with minimal symptoms.

The motivation behind this study is to detect brain tumour and provide better treatment for the sufferings. The abnormal growths of cells in the brain are called tumours and cancer is a term used to represent malignant tumours. Usually CT or MRI scans are used for the detection of cancer regions in the brain. Positron Emission Tomography, Cerebral Arteriogram, Lumbar Puncture, Molecular testing are also used for brain tumour detection. In this study, MRI scan images are taken to analyse the disease condition. Objective this research works are i) identify the abnormal image ii) segment tumour region. Density of the tumour can be estimated from the segmented mask and it will help in therapy. Deep learning technique is employed to detect abnormality from MRI images. Multi level thresholding is applied to segment the tumour region. Number of malignant pixels gives the density of the affected region.

Introduction: Variation in Circle of Willis is a commonly encountered entity in patients undergoing computed tomography angiography, identification of which is crucial in the management of patients with vascular pathologies. The aim of the study was to find out the anatomical variations in the Circle of Willis in patients undergoing Computed Tomography cerebral angiography in a tertiary hospital in Nepal. Methods: This is a descriptive cross-sectional study involving 95 patients using convenient sampling techniques who were sent to the Department of Radiology and Imaging, Tribhuvan University Teaching hospital, for further evaluation of suspected vascular pathologies in the brain from April 2017 to September 2017. Ethical approval was taken from the Institutional Review Committee of the Institute of Medicine with reference number 326 (6-11-E). CT angiographic images of these patients were evaluated for the presence of variations in Circle of Willis, aneurysms, and other vascular pathologies. Data were analyzed using SPSS. Results: Among 95 subjects included in the study, the anatomical variations in the arteries of Circle of Willis was seen in 52 (54.7%) patients, hypoplastic posterior communicating artery being the most common variation 33 (34.7%). The aneurysm was seen in 22 (23.2%) of cases. Conclusions: CT Angiography is a commonly performed imaging modality for suspected cases of cerebral aneurysms and various other vascular pathologies. Multidetector computed tomography can effectively detect variations in arteries of Circle of Willis, recognition of which is crucial in operative management of vascular pathologies.

Introduction: Laparoscopic cholecystectomy, the gold-standard approach for cholecystectomy, has surprisingly variable outcomes and conversion rates. Only recently has operative grading been reported to define disease severity and few have been validated. This multicentre, multinational study assessed an operative scoring system to assess its ability to predict the need for conversion from laparoscopic to open cholecystectomy. Methods: A prospective, web-based, ethically approved study was established by WSES with a 10-point gallbladder operative scoring system; enrolling patients undergoing elective or emergency laparoscopic cholecystectomy between January 2016 and December 2017. Gallbladder surgery was considered easy if the G10 score < 2, moderate (2 ≦ 4), difficult (5 ≦ 7) and extreme (8 ≦ 10). Demographics about the patients, surgeons and operative procedures, use of cholangiography and conversion rates were recorded. Results: Five hundred four patients, mean age 53.5 (range 18-89), were enrolled by 55 surgeons in 16 countries. Surgery was performed by consultants in 70% and was elective in (56%) with a mean operative time of 78.7 min (range 15-400). The mean G10 score was 3.21, with 22% deemed to have difficult or extreme surgical gallbladders, and 71/504 patients were converted. The G10 score was 2.98 in those completed laparoscopically and 4.65 in the 71/504 (14%) converted. (p < 0.0001; AUC 0.772 (CI 0.719-0.825). The optimal cut-off point of 0.067 (score of 3) was identified in G10 vs conversion to open cholecystectomy. Conversion occurred in 33% of patients with G10 scores of ≥ 5. The four variables statistically predictive of conversion were GB appearance - completely buried GB, impacted stone, bile or pus outside GB and fistula. Conclusion: The G10 operative scores provide simple grading of operative cholecystectomy and are predictive of the need to convert to open cholecystectomy. Broader adaptation and validation may provide a benchmark to understand and improve care and afford more standardisation in global comparisons of care for cholecystectomy.

Diabetic foot ulcers are a major health care concern with limited effective therapies. Mesenchymal stem cell (MSC)-based therapies are promising treatment options due to their beneficial effects of immunomodulation, angiogenesis, and other paracrine effects. We investigated whether a bioengineered scaffold device containing hypoxia-preconditioned, allogeneic human MSCs combined with the beta-adrenergic antagonist timolol could improve impaired wound healing in diabetic mice. Different iterations were tested to optimize the primary wound outcome, which was percent of wound epithelialization. MSC preconditioned in 1 μM timolol at 1% oxygen (hypoxia) seeded at a density of 2.5 × 105 cells/cm2 on Integra Matrix Wound Scaffold (MSC/T/H/S) applied to wounds and combined with daily topical timolol applications at 2.9 mM resulted in optimal wound epithelialization 65.6% (24.9% ± 13.0% with MSC/T/H/S vs 41.2% ± 20.1%, in control). Systemic absorption of timolol was below the HPLC limit of quantification, suggesting that with the 7-day treatment, accumulative steady-state timolol concentration is minimal. In the early inflammation stage of healing, the MSC/T/H/S treatment increased CCL2 expression, lowered the pro-inflammatory cytokines IL-1B and IL6 levels, decreased neutrophils by 44.8%, and shifted the macrophage ratio of M2/M1 to 1.9 in the wound, demonstrating an anti-inflammatory benefit. Importantly, expression of the endothelial marker CD31 was increased by 2.5-fold with this treatment. Overall, the combination device successfully improved wound healing and reduced the wound inflammatory response in the diabetic mouse model, suggesting that it could be translated to a therapy for patients with diabetic chronic wounds.

Introduction : Traumatic brain injury (TBI) is one of the major cause of severe disability and death world wide.The mortality rate in these patients largely depends on initial severity of trauma. In TBI, initial level of consciousness is most important prognostic indicator. The commonest scale is the Glasgow Coma Scale (GCS). Despite its widespread use, the GCS has some significant limitations, including variations in inter rater reliability and predictive validity. In order to overcome deficiencies of the GCS, an alternative scale called FOUR (Full Outline of Unresponsiveness score) has been developed and validated in several neurosurgical centers in North America. This study was an attempt to validate this score in Nepalese Setting. This study was carried out in the Department of Neurosurgery at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. The main objective ofthe study was to compare the FOUR with GCS in predicting outcome in patients with Traumatic brain injury.MATERIAL AND METHODS: Patients with moderate to severe head injury aged 2: 16 years admitted in the Department ofNeurosurgery were eligible to participate in the study.The GCS and FOUR score were measured at the earliest possible time during admission by the single observer. Glasgow Outcome Scale (GOS) was measured at discharge and at 3 months follow up. Mortality was used as the primary outcome measure.RESULTS: Total of 122 patients were included in the study. The mean age of the study population was 38.7 ± 18 years. Mean GCS score among survivors was higher than that among non-survivors which was statistically significant (10.9 ± 2 vs. 6 ± 1.12 (p

Background: Brain abscess in pediatric population is serious life threatening problem. Many risk factors are associated with this entity like congenital heart disease, ear infection and immunocompromised state. Early diagnosis and treatment with minimal invasive procedure has good outcome. Materials and Methods: This is a hospital based cross-sectional study conducted at institute of Medicine (IOM), Tribhuvan University Teaching Hospital Kathmandu, Nepal over the period of 3 years between September 2014 to August 2017. Clinical profile, management and outcome were analyzed. Results: A total of 27 cases were taken for the surgical management in the present study. There were 18 male and 9 female with the male to female ratio of 2:1. Mean age of the study population was 7.08 years. Otogenic Abscess was the most common 37.03% (n=10) and the temporal lobe was the most common site (37.5%). Headache was the most common clinical presentation seen in 74.07 %. All the cases were initially managed with the burrhole and aspiration. Only 14.8 %( n=4) of cases subsequently required surgical excision of the abscess wall. Only18.5 %( n=5) of the cases required multiple session aspiration. Positive culture was seen in 25.9% (n=7). Pseudomonas aeruginosa and E.coli were the commonest organisms grown. Mortality rate was 3.7%.Conclusion: Modern advances in radio imaging and multidisciplinary team involvement has decreased the morbidity and mortality.Keywords: otogenic brain abscess; pediatric brain abscess; tubercular abscess.

Introduction: Computed tomography (CT) is the ‘gold standard’ for detecting subarachnoid hemorrhage (SAH) and digital subtraction angiography (DSA) for visualizing the vascular pathology. There is some correlation between the pattern (based on Fisher grading) and location of bleed on CT scan and eventual location of cerebral aneurysm(s). Our aim was to assess the correlation between distribution of hemorrhage on the initial CT scan and eventual site of the ruptured aneurysm at our institution. Methods: This retrospective review of prospectively collected data consisted of 50 patients with SAH over 8 months period. CT scan of patients performed within 72 hours after the ictus with suspected SAH were included in the study. Four neurosurgeons, who had at least three years of experience after being qualified, who were blind to the imaging studies, analyzed and scored independently the quantity and distribution of the hemorrhage on CT. Their prediction of the site of the ruptured aneurysm was recorded and this was correlated with the CT angiography (CTA) and/ or DSA findings. Results: Overall accuracy of prediction was 71.6 % (68.2-75%). Parenchymal cerebral hematoma was an excellent predictor for the site of a ruptured aneurysm but was present in only a few cases (16%). The next valid predictor was blood distribution on CT for ruptured anterior communicating artery (ACom) and middle cerebral artery (MCA) aneurysms (89.4% and 85% respectively). Pattern of blood on CT together with CTA/DSA findings was found to be reliable for identifying the ruptured aneurysm in patients with multiple aneurysms in all cases. Conclusion: The quantity and pattern of the blood on CT is a fairly reliable and quick tool for locating a ruptured MCA or ACom aneurysms. It is not, however, reliable for locating other ruptured aneurysms.

Background: After surgical resection, ionizing radiation alone or in combination with chemotherapy is the main treatment modality for brain tumors including glioblastoma (GBM). Although the effect of radiation-induced (RI) damage improves the patient survival ratio, injury to the neural stem and progenitor cell (NSPC) compartments and damage to NSPC populations is hypothesized to be central to the pathogenesis of RI cognitive decline in the patients. Studies on sensitivity of neural cell populations to radiation have shown that mature neurons and astrocytes have substantial radio resistance; in contrast, NSPC are highly sensitive to radiation, as exposure induces DNA double-strand breaks that when unrepaired can lead to cell death. Therefore, protection of NPCs is an important countermeasure against radiotherapy in normal tissues. Rapamycin, a small molecule inhibitor of mammalian target of rapamycin (mTOR), has been shown to exert a profoundly protective effect on epithelial and hematopoietic stem cells upon exposure to radiation therapy. Recently, several pharmacokinetically improved rapamycin analogs have secured FDA approval. In this study we investigate the potential of Everolimus as radio-protector for NSPCs in a GBM environment. Materials and Methods: NSPCs generated from healthy donors and GBM cells were treated with different doses of Everolimus 24 h before and after a single dose 4 Gy irradiation. Survival was monitored using Cell Titer Glo assay. Western Blots, qPCR and immunofluorescence were used to assess mTOR pathway activation and NPC differentiation in 2D and 3D culture. Co-culture of NSPCs and GFP-tagged GBM cells were treated with Everolimus and irradiated with subsequent followup by confocal imaging to check the relative survival of these cells. Results: Low doses of Everolimus restored survival and proliferation of irradiated NSPCs, while GBM cells remained radiosensitive. qPCR analysis of Nestin, SOX2 and FOXG1 revealed that NSPCs maintained their stemness after treatment. MAP2 and βIII tubulin analysis demonstrated that irradiated NSPCs were able to differentiate to neurons upon treatment. Everolimus treatment also reduced γH2A and phospho-PP2A levels and promoted phosphorylation of Akt suggesting that mTOR inhibition with Everolimus could activate DNA repair in irradiated NPCs. Conclusions: Our findings suggest that pretreatment with low-dose Everolimus may protect NSPCs from radiation induced injuries after radiation therapy, while maintaining radiation sensitivity to GBM cells. This study suggests low-dose Everolimus as a potential radio-protector for clinical treatment of glioblastoma and other brain malignancies. Citation Format: Tithi Ghosh Halder, Ryan Rodriguez del Villar, Jerome Lacombe, Kevin Drenner, Serina Ng, Trason Thode, Alexis Weston, Mohan Kaadige, Raffaella Soldi, Sunil Sharma. Everolimus mediated Radioprotection on surrounding healthy tissue in glioblastoma microbrain models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3068.

BACKGROUND The normal blood platelet count is 1,50,000-4,50,000/μL. Thrombocytopenia results from decreased production, increased destruction and/or sequestration. Although, the bleeding risk varies somewhat by the reason for the thrombocytopenia, bleeding rarely occurs in isolated thrombocytopenia at counts

Introduction: Neural tube defects are among the most common congenital malformations and a major cause of health problems in surviving children, especially in developing countries. Although the incidence of spinal dysraphism has significantly decreased over the last few decades, all over the world; however, the incidence is much higher in developing countries with poor socioeconomic status. The social and economic impact of this disease is not well documented; however, up to 75% of adult survivors may be dependent on parents or other care providers.Aims and Objectives: The aim of this study is to review the demographic profile, clinical pretentions, surgical management and short term outcome of patients presenting with spinal dysraphism Methodology: This is a prospective observational study of cases of spinal dysraphism managed surgically over the period of 2 years from March 2014 to February 2016 in Department of Neurosurgery at Tribhuvan University Teaching Hospital (TUTH), Kathmandu Nepal.Results: Out of total 97 cases, there was male preponderance. In about 40% of population there was no history of proper ANC visit and most of them were from low economic status. Lump on the back was the commonest clinical findings. Lumbar Myelomeningocele was the commonest anatomical location of dysraphism. More than one third of patients needed CSF diversion postoperatively.Conclusion: Myelomeningocele is a common NTDs. Open dysraphism may not always present as a lump. Delay in seeking medical attention may be due to illiteracy. None of the mother had taken folic acid prior to conception.Nepal Journal of Neuroscience, Volume 14, Number 1, 2017, Page: 2-6

Available with full text.Nepal Journal of Neuroscience, Volume 14, Number 1, 2017, Page: 28-31

Introduction: Mental disorders are common and major source of disability around the world. Though Nepal lacks national data on the prevalence of mental disorders, many studies have been conducted in specific groups of people. The Thakali community is one of the indigenous communities of Nepal. We aim to look at the prevalence of mental disorders in this group. Materials and Methods: This is a cross-sectional study with multiphasic sampling conducted in the Thakali community in six distinct geographical regions of Nepal. The first stage was a household survey done by field researchers using screening questionnaires to detect a probable diagnosis of mental disorders. The second stage was detailed clinical assessment and diagnosis (ICD-10) by two independent psychiatrists. Results: Among the 917 participants, after the first phase, a probable diagnosis (as per the screening questionnaire) was found to be 12.5%. After the psychiatrists' assessment and addition of already diagnosed cases, the prevalence was 6.1%. In both the cases, prevalence of alcohol use disorder was comparatively higher (34.8% and 31.9%, respectively). Conclusion: Despite many shortcomings, this study has provided an estimate of the prevalence and pattern of mental disorders among an indigenous Nepalese community. We emphasize the need of validation of tools for Nepal and estimation of prevalence at the national level.

Osteoarthritis (OA) is a chronic disease of articular joints that leads to degeneration of both cartilage and subchondral bone. These degenerative changes are further aggravated by proinflammatory cytokines including IL-1β and TNF-α. Previously, we have reported that IL-3, a cytokine secreted by activated T cells, protects cartilage and bone damage in murine models of inflammatory and rheumatoid arthritis. However, how IL-3 protects cartilage degeneration is not yet known. In this study, we investigated the role of IL-3 on cartilage degeneration under both in vitro and in vivo conditions. We found that both mouse and human chondrocytes show strong expression of IL-3R at gene and protein levels. IL-3 increases the expression of mouse chondrocyte-specific genes, Sox9 and collagen type IIa, which were downregulated by IL-1β. Moreover, IL-3 downregulated IL-1β– and TNF-α–induced expression of matrix metalloproteinases in both mouse and human chondrocytes. Interestingly, IL-3 reduces the degeneration of articular cartilage and subchondral bone microarchitecture in a mouse model of human OA. Moreover, IL-3 showed the preventive and therapeutic effects on cartilage degeneration induced by IL-1β in micromass pellet cultures of human mesenchymal stem cells. Thus, to our knowledge, we provide the first evidence that IL-3 has therapeutic potential in amelioration of degeneration of articular cartilage and subchondral bone microarchitecture associated with OA.

Central nervous system (CNS) tumors are the most common cause of cancer-related death in children. Little is known about the demographics and treatment of pediatric brain tumors in low- and middle-income countries (LMICs).We performed a retrospective chart review of all pediatric patients who presented to the neurosurgical service at Tribhuvan University Teaching Hospital in Kathmandu, Nepal from 2009-2014 and collected information on patients18 years old who received a diagnosis of a CNS tumor. We analyzed age, gender, clinical presentation, extent of surgical resection, histopathology, and length of hospital stay. We also conducted a literature review using specific terminology to capture studies of pediatric neuro-oncologic epidemiology conducted in LMICs. Study location, length of study, sample size, study type, and occurrence of 4 common pediatric brain tumors were extracted.We identified 39 cases of pediatric CNS tumors, with 62.5% observed in male children. We found that male children (median = 13 years) presented later than female children (median = 8 years). The most frequently observed pediatric brain tumor type was ependymoma (17.5%), followed by astrocytoma (15%) and medulloblastoma (15%). Surgical resection was performed for 80% of cases, and gross total resection reported in 62.9% of all surgeries. More than half (54.1%) of patients had symptoms for more than 28 days before seeking treatment. Symptomatic hydrocephalus was noted in 57.1% of children who presented with CNS tumors. The literature review yielded studies from 18 countries. Study length ranged from 2-20 years, and sample sizes varied from 35-1948. Overall, we found more pronounced variation in the relative frequencies of the most common pediatric brain tumors, compared with high-income countries.We present the first operative series of childhood CNS tumors in Nepal. Children often had delayed diagnosis and treatment of a tumor, despite symptoms. More comprehensive data are required to develop improved treatment and management algorithms in the context of a given country's demographics and medical capabilities for childhood CNS tumors.

In an agriculture based economy like Nepal farm related accidents are not uncommon. Indigenous farm machinery like winnowing fan is common in our villages. Five cases of fan related head injuries presenting to the Department of Surgery, Tribhuvan University Teaching Hospital in a single month of winnowing season are discussed.JSSN 2015; 18 (1), Page: 29-31

Purpose: Adrenocortical carcinoma (ACC) is a rare and aggressive disease with poor prognosis. The first line of treatment is surgery followed by chemotherapy (Mitotane), though these therapies still result in a dismal 15-44% survival rate after 5 years. Currently, there is no effective second line of treatment. Efforts have been made to treat ACC with immune therapy agents such as Avelumab, a PD-L1 antibody, but a recent study showed that there was only an overall response rate of 6% in a phase 1 clinical trial, further exhibiting a need for the development of novel therapeutics. Further research suggests that the current first line ACC treatments may benefit from the addition of immune therapies that induce an Interferon Beta (IFN-β) response in the tumor microenvironment. Previous studies have shown that treatment with IFN-β induces cell death and sensitizes human ACC lines to Mitotane, implying that combination of therapies that induce an IFN-β response may improve the anti-tumor response to Mitotane. Recently, inhibition of Lysine-Specific histone Demethylase 1 (LSD-1) was shown to stimulate an IFN-dependent anti-tumor response driven by the expression of Endogenous Retroviral Elements (ERVs) in a variety of cancer types. In addition, PD-L1 expression has also been shown to increase after LSD-1 inhibition. Yang, et al. reported that SP-2509, a preclinical analog of SP-2577 (Seclidemstat, currently in clinical phase I trials, Salarius Pharmaceuticals, Houston, TX) was able to induce the expression and release of interferons and cytokines in triple negative breast cancer models. In this study we investigate the ability of SP-2577 to promote the expression of IFN-β in human ACC cell lines, resulting in an anti-tumor immune response. Experimental Design: qRT-PCR was performed on ACC cell lines H295R and SW-13 at 48 and 72 hours post treatment to verify the ability of SP-2577 to promote IFN-β expression. ACC cells were co-cultured with peripheral blood mononuclear cells (PBMCs) in a 3D platform to evaluate lymphocyte infiltration following SP-2577 treatment. Interferons, chemokines, and cytokines were quantified in the culture supernatant after treatment with SP-2577 using the Meso Scale Discovery platform. Results: qRT-PCR showed that SP-2577 promotes ERV-mediated immune response in ACC cell lines via the expression and release of interferons, chemokines, and cytokines. Additionally, SP-2577 stimulates lymphocyte infiltration in an ACC derived 3D-spheroid platform further resulting in a cytotoxic effect. Conclusion: Our data suggests that the LSD-1 inhibitor SP-2577 can be used as a single agent in ACC patients to promote immune response and can potentially sensitize the tumor to first line of therapy, Mitotane. This study was supported by funding from the TGen Foundation. Citation Format: Sunil Sharma, Raffaella Soldi, Alexis Weston, Samuel Sampson, Sherin Daniel Ampanattu, Scott Celinski, Haiyong Han, Mohan Kaadige, Michael Berens, Jeffrey Trent. Inhibition of LSD1 using the reversible inhibitor SP2577 promotes Interferon dependent anti-tumor response in adrenocortical carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6681.

The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fat mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.

Osteoblastoma is a rare and benign osteoid producing primary bone tumor that affects mainly the long bones. It makes 5% of spinal tumors, mostly arising within the posterior elements of the spine within the second and 3rd decades of life. We managed an 18 year old patient with osteoblastoma of C6 vertebra.Nepal Journal of Neuroscience 13:51-53, 2016

Subdural Hematoma (SDH) or effusion following Ventriculoperitoneal (VP) shunt for hydrocephalous is not an unusual complication. However, we rarely come across organized chronic subdural hematoma (CSDH) following shunts. We present a case of organized CSDH in a four-year-old female child who presented with seizure three and half year after the VP Shunt placement for obstructive hydrocephalus due to aqueductal stenosis. The child was managed with craniotomy and evacuation of hematoma with membranectomy. We report this unusual case and review the relevent literature.Nepal Journal of Neuroscience 12:46-48, 2015

Lysine-Specific Demethylase 1 (LSD1) over-expression correlates with poorly differentiated neuroblastoma and predicts poor outcome despite multimodal therapy. We have studied the efficacy of reversible and specific LSD1 inhibition with HCI-2509 in neuroblastoma cell lines and particularly the effect of HCI-2509 on the transcriptomic profile in MYCN amplified NGP cells. Cell survival assays show that HCI-2509 is cytotoxic to poorly differentiated neuroblastoma cell lines in low micromole or lower doses. Transcriptional profiling of NGP cells treated with HCI-2509 shows a significant effect on p53, cell cycle, MYCN and hypoxia pathway gene sets. HCI-2509 results in increased histone methyl marks and p53 levels along with cell cycle arrest in the G2/M phase and inhibition of colony formation of NGP cells. Our findings indicate that LSD1 inhibition with HCI-2509 has a multi-target effect in neuroblastoma cell lines, mediated in part via p53. MYCN-amplified neuroblastoma cells have a targeted benefit as HCI-2509 downregulates the MYCN upregulated gene set.

Human hydatid disease or cystic echinococcosis (CE), caused by the larval form of cestode Echinococcus granulosus still continues to a common problem in health care environments as different as Europe/North America and resource poor countries of the South America and the East. The Liver is the most frequently parasatized organ in humans. While ultrasonography remains the main diagnostic tool, computed tomography and serology improve the accuracy of diagnosis in Liver hydatid cysts (LHC). Although surgery is the only modality applicable over the entire spectrum of the disease, systemic chemotherapy and percutaneous drainage have evolved as alternative therapies in the last three decades. Various laparoscopic techniques have also been described for safe and optimal management of this entity. In this paper, we review the current management procedures of LHC with particular emphasis on the evidence base and setting specific problems.

Deregulated glucose metabolism fulfills the energetic and biosynthetic requirements for tumor growth driven by oncogenes. Because inhibition of oncogenic BRAF causes profound reductions in glucose uptake and a strong clinical benefit in BRAF-mutant melanoma, we examined the role of energy metabolism in responses to BRAF inhibition. We observed pronounced and consistent decreases in glycolytic activity in BRAF-mutant melanoma cells. Moreover, we identified a network of BRAF-regulated transcription factors that control glycolysis in melanoma cells. Remarkably, this network of transcription factors, including hypoxia-inducible factor-1α, MYC, and MONDOA (MLXIP), drives glycolysis downstream of BRAFV600, is critical for responses to BRAF inhibition, and is modulated by BRAF inhibition in clinical melanoma specimens. Furthermore, we show that concurrent inhibition of BRAF and glycolysis induces cell death in BRAF inhibitor (BRAFi)–resistant melanoma cells. Thus, we provide a proof-of-principle for treatment of melanoma with combinations of BRAFis and glycolysis inhibitors. Significance: BRAFis suppress glycolysis and provide strong clinical benefit in BRAFV600 melanoma. We show that BRAF inhibition suppresses glycolysis via a network of transcription factors that are critical for complete BRAFi responses. Furthermore, we provide evidence for the clinical potential of therapies that combine BRAFis with glycolysis inhibitors. Cancer Discov; 4(4); 423–33. ©2014 AACR. See related commentary by Haq, p. 390 This article is highlighted in the In This Issue feature, p. 377

BACKGROUND: Intramedullary interlocking is currently considered the treatment of choice for femoral shaft fractures, with high rates of fracture union, advantage of early stabilization which decreases the morbidity and mortality rate in patients, allows early mobilization, reduces the incidence of infection, malunion, non-union or implant failure. AIMS: To assess the time taken for fracture union and the functional outcome in patients with fracture shaft of femur. METHODS AND MATERIALS: We studied a total of 30 patients of fracture shaft of femur admitted in the Orthopedic Department of Kempegowda Institute of Medical sciences Bangalore treated with closed intramedullary interlocking nailing. 23 patients were male and 7 were females and age group ranged from 18-49 years with mean age 30 Yrs. right side fractures encountered in 18 cases and 12 left side. 24 fractures were closed and 6 fractures were open type. 5 fractures were in proximal third, 19 fractures were in the middle third and 6 in distal third of femur. Duration of study was 2 years. RESULTS: Duration between injury and surgery was

BACKGROUND AND OBJECTIVE : Tibial plateau fractures are one of the commonest intra-articular fractures. It results from indirect coronal or direct axial compressive forces. It comprises of 1% of all fractures. These fractures encompass many and varied fracture configurations that involve medial, lateral or both plateaus with many degrees of articular depressions and displacements. Being one of the major weight bearing joints of the body, fractures around it will be of paramount importance. METHODS : 30 cases of tibial plateau fractures treated by various modalities were studied from September 2009 to september 2011 at Kempegoda Institute of Medical Sciences and followed for minimum of 6 months. RESULTS : The selected patients evaluated thoroughly clinically and radiologically, after the relevant lab investigations, were taken for surgery. The indicated fractures treated as per the SCHATZKER'S types, accordingly with CRIF with percutaneous cannulated cancellous screws, MIPPO with LCP/ Butress plate and screw, ORIF with buttress plate/ LCP and screw. Early range of motion started soon after the surgery. No weight bearing upto 6 weeks. The full weight bearing deferred until 12 weeks or complete fracture union. Immobilization in insecurely fixed fractures continued for 3-6 weeks by POP cast. The knee range of motion was excellent to very good, gait and weight bearing after complete union was satisfactory. Infection in two cases and stiffness in 2 cases were seen and there was no non-union in our cases. CONCLUSION: Surgical management of tibial condylar fractures will give excellent anatomical reduction and rigid fixation to restore articular congruity, facilitate early motion, hence to achieve optimal knee INTRODUCTION: Tibial plateau fractures are one of the commonest intra-articular fractures. It results from indirect coronal or direct axial compressive forces. It comprises of 1% of all fractures. These fractures encompass many and varied fracture configurations that involve medial, lateral or both plateaus with many degrees of articular depressions and displacements. Each fracture type has its own characteristic morphology and response to the treatment. It is essential to determine the force of injury since high-energy trauma is associated with considerable soft tissue and neurovascular damage. Apart from tibial plateau bony injury, meniscal tear and ligament injuries should also be assessed.1 The stationary lower limb may be struck by a moving object; this is the common pedestrian injury, the so called "BUMPER FRACTURE", since the bumper of most vehicles being placed roughly at knee height. The exposed knee joint may be subjected to angulation, rotation or shearing strains and when the subject is upright, his body weight assists in the injury and he falls over. Fractures of the upper tibia are difficult to treat, apart from the usual problems of confining patients to bed. Conservative treatment at any age, may be complicated by knee stiffness, malunion

Patient: Male, 59 Final Diagnosis: Pleural and pericardial effusion from a Streptococcus pneumonia Symptoms: Chest pain • chills • cough • fever • shortness of breath Medication: — Clinical Procedure: Pericardiocentesis • pericardial window Specialty: Cardiology Objective: Rare disease Background: Although pericardial effusion with afib is not rare, the combination of purulent pericardial effusion presenting as afib is not a common occurrence particularly in the developing world. The more common symptoms associated with purulent pericardial effusion are fever, dyspenia, and tachycardia. Without prompt recognition followed by antibiotics and surgical drainage, tamponade, and shock can potentially lead to death. Case Report: A 59-year-old male was transferred to our hospital for evaluation of afib with rapid rate associated with cough and dyspenia. He reported fevers, chills, cough and sputum for 1 week. Complaints included chest pain with relief upon lying down. Patient was afebrile with a pulse of 101 and blood pressure of 119/89. WBC 39,200 cells/ml. Chest X-RAY showed right lower lobe pneumonia and EKG revealed afib, rapid ventricular response, and secondary ST changes inferolaterally. Pericardial effusion and thickened pericardium were eveident on echo. Patient was treated for community acquired pneumonia, along with heparin and IV amiodarone. Both sputum cultures and pericardiocentesis revealed S. Pneumoniae. Cardioversion reestablished sinus mechanism. Intially pericardial effusion resolved, but later reaccumulated at which point it was decided to perform a subxiphoid pericardial window. Follow up showed no effusion and patient was asymptomatic. Conclusions: Purulent pericardial effusion with atrial fibrillation and rapid ventricular rate needs to be recognized promptly. Because friction fub and chest pain are not present in every case, prompt management in the setting of pneumonia and minor hemodynamic derangements can aid in the treatment of this potentially life threating disease.

This is an executive summary of the 2019 update of the 2004 guidelines and levels of care for PICU. Since previous guidelines, there has been a tremendous transformation of Pediatric Critical Care Medicine with advancements in pediatric cardiovascular medicine, transplant, neurology, trauma, and oncology as well as improvements of care in general PICUs. This has led to the evolution of resources and training in the provision of care through the PICU. Outcome and quality research related to admission, transfer, and discharge criteria as well as literature regarding PICU levels of care to include volume, staffing, and structure were reviewed and included in this statement as appropriate. Consequently, the purposes of this significant update are to address the transformation of the field and codify a revised set of guidelines that will enable hospitals, institutions, and individuals in developing the appropriate PICU for their community needs. The target audiences of the practice statement and guidance are broad and include critical care professionals; pediatricians; pediatric subspecialists; pediatric surgeons; pediatric surgical subspecialists; pediatric imaging physicians; and other members of the patient care team such as nurses, therapists, dieticians, pharmacists, social workers, care coordinators, and hospital administrators who make daily administrative and clinical decisions in all PICU levels of care.

Purpose: Many cancers are addicted to oncogenic super-enhancers that drive expression of oncogenes such as Myc. Super-enhancers are a class of regulatory regions that are associated with a strong enrichment of transcriptional coactivators (MED1, BRD4) and chromatin marks (H3K27Ac). Importantly, majority of super-enhancers depend on the ability of cyclin-dependent kinase 7 (CDK7) to initiate transcription by phosphorylating the C-terminal domain of RNA Pol II. Recent reports have shown that high level of CDK7 is associated with poor prognosis in breast, gastric, ovarian cancer, pancreatic, SCLC and AML cancers. Targeting transcriptional machinery of super-enhancer binding proteins is an active therapeutic strategy and we have focused our efforts on developing a selective and reversible small molecule inhibitor of CDK7. Methods: With the application of in-house fragment library screening utilizing the crystal structure of hCDK7 (PDB: 1UA2) and iterative optimization within the ATP binding pocket, candidate criteria, and synthesis led to the identification of lead CDK7 inhibitor TGN-1062. In vitro kinase assays were performed using ADP-GloTMkinase assay kit (Promega). Cell viability assays were performed in a panel of cancer cell lines using CellTiter-Glo assay kit (Promega). RNA Pol II phosphorylation and total c-Myc protein levels were determined by Western Blotting. Results: Here we report the identification of novel, orally available reversible CDK7 inhibitor TGN-1062, through fragment-based and CDK7 kinase screening strategies. TGN-1062 demonstrated promising selectivity against CDK7 with an IC50 of 33 nM (Ki=19 nM) and IC50 values were 6- and 23- fold higher for CDK2 and CDK5, respectively. Our in vitro studies showed that pancreatic cancer cell lines were sensitive to TGN-1062 with GI50 of less than 0.4 µM. In addition, phosphorylation of RNA Pol II and expression of c-Myc were suppressed by TGN-1062 in the MiaPaca2 pancreatic cancer cells. Mouse pharmacokinetic analysis of TGN-1062 demonstrated an oral bioavailability of 62.5%. Further optimization within TGN-1062 series led to the discovery of TGN-1069 that retained the potency against CDK7 with an IC50 of 38 nM (Ki=22 nM) and showed a selectivity of 64- and 122- fold towards CDK2 and CDK5, respectively. Conclusion: In summary, we have developed a novel reversible, selective and an orally available inhibitor of CDK7. The preclinical lead candidate TGN-1069 is currently under investigation for kinome profiling, super-enhancer binding protein activities, ADME-Tox and efficacies. Citation Format: Trason Thode, Zhaoliang Li, Alexis Weston, Raffaella Soldi, Mohan Rao Kaadige, Hariprasad Vankayalapti, Sunil Sharma. Targeting CDK7-dependent transcriptional addiction with novel, orally available small molecule inhibitor shows efficacy in pancreatic cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-107.

Toll-like receptor-4 (TLR4) is a sentinel pathogen recognition receptor with a pivotal role in inflammation, tissue injury, diabetes and its complications. The aim of the study was to examine the contribution of TLR4 expression and activation to the prolonged inflammation observed in diabetic wounds. Diabetes was induced in male C57BL/6J and TLR4 knockout (KO) mice using streptozotocin (STZ) with matching non-diabetic mice as control. After 2 weeks of persistent hyperglycemia in the mice, full-thickness excision wounds were made on the backs aseptically. Total RNA and protein were subjected to real-time PCR and western blot analyses. Wound sizes were measured using digital planimetry. TLR4 mRNA and protein expression increased significantly in wounds of diabetic mice compared with non-diabetic mice (P

Perforation of a Meckel's diverticulum is a rare complication. This case report is about a 9yr old child who presented to our emergency department with diffuse abdominal pain, vomiting and fever. He had leucocytosis and free fluid in the peritoneal cavity on USG. Erect x-ray abdomen shows gas under the diaphragm. A perforated appendix or a bowel perforation was suspected and a diagnosis of a ruptured MD was finally made by laparotomy. INTRODUCTION: MD is a true intestinal diverticulum that results from the failure of the vitelline duct (omphalomesenteric duct) to obliterate during the 5 th week of fetal development 1 . MD is the most common congenital abnormality occurring in about 2% of the population. Meckel diverticulum is typically lined by ileal mucosa, but other tissue types are also found with varying frequency. The heterotopic mucosa is most commonly gastric (present in 50% of all MD's) and pancreatic mucosa is encountered in about 5% of diverticula; less commonly, these diverticula may harbour colonic mucosa 2 . This is important because peptic ulceration of this or adjacent mucosa can lead to painless bleeding, perforation, or both. CASE PRESENTATION: A 9 year old, previously healthy child, presented at the emergency room of Dept. of Surgery, AIMS, Bellur, with abdominal pain, that started in the left iliac fossa 24 hrs ago and progressed to be diffuse, accompanied with vomiting and high grade fever. Physical examination showed the patient to be pale and febrile (body temperature of 102 F) with diffuse tenderness along with rebound tenderness in the right iliac fossa. Guarding was noted in all the quadrants. Laboratory tests showed anemia (10.0g %) with leukocytosis (13000cells/cu mm) accompanied with polymorphonuclear predominance (89%) and normal blood biochemistry analysis. Erect X-ray abdomen showed gas under the diaphragm. USG abdomen revealed echogenic free fluid in the peritoneal cavity with few septations in the RIF-? Pyoperitoneum. These findings led to the diagnosis of a bowel perforation. A laparotomy incision made and pyoperitoneum confirmed. Appendix was inflamed and the bowel inspected. A perforated MD found and resection anastomosis of ileum along with appendectomy done. The patient recovered uneventfully and 7 days later was discharged in a fine condition. Histopathological examination showed Meckel's diverticulitis with ectopic gastric tissue forming an adenoma.

The cystic swellings of scrotum are one among the common surgical problem in all age group. Objective of this study is to identify the cause, mode of presentation, various modalities of management and outcome of these with least complications. A total of 50 cases of cystic swellings of scrotum fulfilling the methodology criteria were subjected to preformatted study. Final diagnosis was made with clinical examination and ultrasound. All 50 cases were treated surgically. Most of the patients were in age group of 31-40 years (28%), common presenting feature being scrotal swelling in 60% of cases, majority of them were right sided(64%), most of them presented within a year of development of symptoms. Primary vaginal hydrocele was the commonest cystic swelling (60%), followed by epididymal cyst, sebaceous cyst, haematocoele, pyocoele. Most of the patients were discharged around 8th Post-operative day. All of the cystic swellings were treated surgically with good results. INTRODUCTION: Cystic swellings of the scrotum are a common problem encountered in surgery OPD. Cystic swellings of scrotum affect the physical well being of the patient and present with varied etiology. Since scrotum is placed outside the lower abdomen they are easily noticed by the patient himself and is also easily accessible for clinical examination by the treating doctor. This spectrum of disease consists of hydrocoele (commonest cause), epididymal cysts, spermatocoele, haematocoele, pyocoele, chylocoele, and sebaceous cysts. Cystic swellings of scrotum are usually painless and can attain a very big size without causing much discomfort to patient. Hydrocoele is an abnormal collection of serous fluid in some part of the processus vaginalis, usually the tunica1. It is divided into simple (scrotal) and communicating2. Secondary hydrocoele occur secondary to disease of the testes and epididymis and its management mainly consists of treatment of the underlying cause. Filarial hydrocoele and chylocoele account for

Diabetes is a mutifactorial metabolic disorder that leads to a number of complications. Diabetes is estimated to affect 36 million people in the U.S.A., and the prevalence of diagnosed and undiagnosed diabetes is at 9.3% and continues to rise. Evidence from experimental animal models as well as humans has indicated that systemic inflammation plays a role in the pathophysiological processes of diabetes and is facilitated by innate immune responses. TLRs (Toll-like receptors) are key innate immune receptors that recognize conserved PAMPs (pathogen-associated molecular patterns), induce inflammatory responses essential for host defences and initiate an adaptive immune response. Although TLR expression is increased in a plethora of inflammatory disorders, the effects of metabolic aberrations on TLRs and their role in diabetes and its complications is still emerging. In the present paper, we provide a systematic review on how TLRs play a detrimental role in the pathogenic processes [increased blood sugar, NEFAs (non-esterified ‘free’ fatty acids), cytokines and ROS (reactive oxygen species)] that manifest diabetes. Furthermore, we will highlight some of the therapeutic strategies targeted at decreasing TLRs to abrogate inflammation in diabetes that may eventually result in decreased complications.

IL-3, a cytokine secreted by Th cells, functions as a link between the immune and the hematopoietic system. We previously demonstrated the potent inhibitory role of IL-3 on osteoclastogenesis, pathological bone resorption, and inflammatory arthritis. In this study, we investigated the novel role of IL-3 in development of regulatory T (Treg) cells. We found that IL-3 in a dose-dependent manner increases the percentage of Foxp3+ Treg cells indirectly through secretion of IL-2 by non-Treg cells. These IL-3–expanded Treg cells are competent in suppressing effector T cell proliferation. Interestingly, IL-3 treatment significantly reduces the severity of arthritis and restores the loss of Foxp3+ Treg cells in thymus, lymph nodes, and spleen in collagen-induced arthritis mice. Most significantly, we show that IL-3 decreases the production of proinflammatory cytokines IL-6, IL-17A, TNF-α, and IL-1 and increases the production of anti-inflammatory cytokines IFN-γ and IL-10 in collagen-induced arthritis mice. Thus, to our knowledge, we provide the first evidence that IL-3 play an important role in modulation of Treg cell development in both in vitro and in vivo conditions, and we suggest its therapeutic potential in the treatment of rheumatoid arthritis and other autoimmune diseases.

About 15 % of war injuries involve the chest. Fortunately 85% of patients sustaining chest injuries that reach medical facility will require clinical observation or a simple procedure like tube thoracostomy. Only one in six patients has life-threatening injuries that necessitate urgent operative repair. Early deaths are caused by airway obstruction, major respiratory problems such as tension pneumothorax or massive hemothorax, and cardiac tamponade. These conditions are easily managed if recognized promptly. Diagnosis and management of various components of chest injury requires clear judgment and indepth knowledge of pathophysiological mechanisms involved. The therapeutic goal in the war scenario is to restore normal physiology and thereby to restore cardiac and pulmonary function and evacuate the patient after stabilization.

BACKGROUND C-reactive protein (CRP) inhibits the activity of the endothelial isoform of nitric oxide synthase (eNOS) via uncoupling of the enzyme both in vitro and in vivo. eNOS activity appears to be related in part to its interaction with other cellular proteins, including heat shock protein 90 (Hsp90), caveolin-1, and porin. In this study, we examined the effect of CRP treatment of human aortic endothelial cells (HAECs) on eNOS interaction with caveolin-1, Hsp90, and porin. METHODS We incubated HAECs with CRP (0, 12.5, and 25 mg/L) for 1, 6, or 24 h and assessed the interaction of these proteins with eNOS by immunoprecipitation and western blotting. RESULTS CRP treatment (12.5 and 25 mg/L) of HAECs for 24 h significantly increased eNOS binding to caveolin-1 (40% and 54% increase, respectively; P < 0.05) and decreased binding to Hsp90 (33% and 66% decrease, respectively; P < 0.05). CRP (25 mg/L) also significantly decreased the binding of porin to eNOS (11% decrease, P < 0.05). Similar results were seen when HAECs were treated with CRP for 6 h. CONCLUSIONS These negative protein–protein interactions of eNOS were able to partly explain the CRP-induced decreases in the activity of this critical enzyme, which caused endothelial dysfunction.

The diabetic state confers an increased propensity to accelerated atherogenesis. Inflammation is pivotal in atherosclerosis; in addition to the established risk factors, inflammation appears to play a pivotal role in diabetes and its complications. Evidence for increased inflammation includes: increased levels of plasma C-reactive protein, the prototypic marker of inflammation; increased levels of plasminogen-activator inhibitor; increased monocyte superoxide and proinflammatory cytokine release (IL-1, IL-6 and TNF-alpha); increased monocyte adhesion to endothelium; increased NF-kappaB activity; and increased Toll-like receptor 2 and 4 expression and activity in diabetes. Thus, it appears that both Type 1 and Type 2 diabetes are proinflammatory states and that these could contribute to increased diabetic vasculopathies.

OBJECTIVE Individuals with type 2 diabetes have a myriad of metabolic aberrations including increased inflammation, increasing their cardiovascular risk. Toll-like receptors (TLRs) and their ligands play a key role in insulin resistance and atherosclerosis. However, there is a paucity of data examining the expression and activity of TLRs in type 2 diabetes. Thus, in the present study, we examined TLR2 and TLR4 mRNA and protein expression, their ligands, and signaling in monocytes of recently diagnosed type 2 diabetic patients. RESEARCH DESIGN AND METHODS TLR mRNA, protein expression, TLR ligands, and TLR signaling were measured in freshly isolated monocytes from healthy human control subjects (n = 23) and type 2 diabetic subjects (n = 23) using real-time RT-PCR, Western blot, and flow cytometric assays. RESULTS Type 2 diabetic subjects had significantly increased TLR2, TLR4 mRNA, and protein in monocytes compared with control subjects (P < 0.05). Increased TLR2 and TLR4 expression correlated with BMI, homeostasis model assessment–insulin resistance (HOMA-IR), glucose, A1C, Nε-(carboxymethyl) lysine (CML), and free fatty acid (FFA). Ligands of TLR2 and TLR4, namely, HSP60, HSP70, HMGB1, endotoxin, and hyaluronan levels, were elevated in type 2 diabetic subjects and positively correlated with TLR2 and TLR4. Type 2 diabetic subjects showed increased MyD88, phosphorylated IRAK-1, Trif, TICAM-1, IRF-3, and NF-κB p65 expression in monocytes compared with control subjects. Furthermore, TLR-MyD88-NF-κB signaling resulted in elevated levels of cytokines (P < 0.05), but increased interleukin (IL)-1β, interferon (IFN)-γ, and endotoxin were not significant when adjusted for BMI. CONCLUSIONS In this comprehensive study, we make the novel observation that TLR2 and TLR4 expression and their ligands, signaling, and functional activation are increased in recently diagnosed type 2 diabetes and contribute to the proinflammatory state.