Feasibility and safety of redo laparoscopic repair of recurrent inguinal hernia following previous endolaparoscopic repair.

BACKGROUND: Laparoscopic redo inguinal hernia (LRIH) repairs are fraught with challenges as the pre-peritoneal space is violated due to previous surgery and the presence of mesh. The purpose of this study was to present the feasibility and safety of LRIH in a series of patients with recurrent inguinal hernia following previous endolaparoscopic repair and present technical experiences and clinical outcomes in this subset of patients. PATIENTS AND METHODS: This was a retrospective study from a prospective database of 16 patients who underwent LRIH between March 2014 and December 2020. The decision to do a redo laparoscopic surgery was undertaken after a detailed discussion with the patient. The operative details, challenges faced and tips to overcome difficulties have been explained in detail. RESULTS: Out of 16 patients (mean age 49.5 years, all men), 15 underwent laparoscopic redo trans-abdominal pre-peritoneal (TAPP) mesh repair and 1 underwent laparoscopic enhanced-view totally extra-peritoneal (eTEP) mesh repair. The mean operating time was 68.5 min for unilateral, 115 min for bilateral TAPP and 90 min for eTEP. The main contributing factors for recurrences were mesh migration, insufficient size of the mesh and inadequate fixation. There was no conversion to open repair. The duration of stay was 1-2 days. There was no documented re-recurrence during the follow-up period of 2-9 years. CONCLUSION: Based on our experience, redo laparoscopic inguinal hernia mesh repair after previous endolaparoscopic repair is feasible, effective and safe in experienced hands.

Formulation of cost-effective medium and optimization studies for enhanced production of rapamycin.

BACKGROUND: Enhancing rapamycin production using a cost-effective medium is crucial for wider accessibility, reduced manufacturing costs, sustainable pharmaceutical practices, and advancements in therapeutic applications. It promotes global health, biotechnological innovation, research collaboration, and societal well-being through affordable and effective treatments. This study focuses on the development of a novel cost-effective production medium for the synthesis of rapamycin from Streptomyces hygroscopicus. RESULTS: In the initial screening, more rapamycin production was observed in medium A. Initially, the organism produced 10 µg/mL rapamycin. Based on the OFT results, a novel cost-effective medium composition was designed, incorporating soyabean, sugarcane juice, and dried tomato components. Using RSM, soyabean and tomato was found to be more significant in rapamycin production than sugarcane. In the optimized medium, the production of rapamycin increased significantly to 24 µg/mL. Furthermore, a comparative analysis of the growth kinetics between the production normal medium (referred to as production medium A) and the newly optimized cost-effective production medium revealed that the optimized cost-effective production medium significantly enhanced the production of rapamycin. CONCLUSION: Overall, this study demonstrates the successful development of a cost-effective production medium for rapamycin synthesis from S. hygroscopicus. The findings highlight the potential of using a cost-effective medium to enhance the production of a valuable secondary metabolite, rapamycin, while reducing production costs.

Enhanced view totally extraperitoneal approach: A better alternative to transabdominal preperitoneal approach for irreducible inguinoscrotal and giant inguinal hernias!

The advantages of enhanced view totally extraperitoneal (eTEP) over TEP approach are well established in large inguinoscrotal, recurrent inguinal, patients with short pubis to umbilicus distance and in obese patients. Irreducible inguinoscrotal hernias (IISHs) and giant inguinal hernias (GIHs) pose a great challenge. GIHs are hernias which extend below the midpoint of the inner thigh with the patient in the standing position. Majority of these hernias are managed by open, hybrid or by transabdominal pre-peritoneal (TAPP) approach. TAPP was considered the optimal minimally invasive approach for these hernias as it provides a large working space and reduction of contents under vision. My practice of eTEP has been limited to IISH and GIH. I would like to share some technical tips to manage these cases by eTEP approach.

Persistent Müllerian duct syndrome: A surgical surprise and management during laparoscopic transabdominal pre-peritoneal repair.

Persistent Müllerian duct syndrome is an intersex disorder which occurs due to the failure of regression of Müllerian structures in genotypical and phenotypical males. It is a rare disorder of male internal pseudohermaphroditism with normal secondary sexual characters and XY karyotype. We report a male patient with the diagnosis of bilateral inguinoscrotal hernia with cryptorchidism scheduled for laparoscopic bilateral transabdominal pre-peritoneal (TAPP) mesh repair with bilateral orchidopexy. Intra-operatively, there was a rudimentary uterus with tubes on both sides. Bilateral testicular biopsy was taken to confirm the presence of testicular tissue and to exclude malignancy and ovarian tissue. Hernia surgery was deferred in the first stage. After 2 weeks, he underwent laparoscopic bilateral orchidopexy with TAPP mesh repair. At 6-year follow-up, there is no recurrence of hernia or features of malignancy in the retained testis.

Novel laparo-endoscopic hybrid technique of management of a rare case of duodeno-duodenal intussusception.

We herein report a rare case of duodeno-duodenal intussusception (IS) presenting with obstruction caused by tubulovillous adenoma in an adult with malrotation that was managed by a novel laparoendoscopic hybrid technique. This was done by passing transjejunal nasogastric tube (NG) through one of the ports and manoeuvring it towards the IS. Two hundred and fifty millilitre of saline was flushed by aseptosyringe with pressure connected to the NG. This hydrostatic reduction technique resulted in distension of the jejunal and duodenal loop achieving reduction of IS. Intraoperative endoscopy was performed to exactly localise the mass lesion. The duodenum was kocherised and was delivered through a 4-cm transverse incision. Anterior duodenotomy was performed; the mass was excised; and duodenotomy was closed transversely. An extensive literature search did not show any case report of duodenoduodenal IS being managed by this technique. The combination of novel retrograde decompression and intraoperative endoscopy helped us to manage this rare case by this novel technique.

Hepatocyte expression of the micropeptide adropin regulates the liver fasting response and is enhanced by caloric restriction.

The micropeptide adropin encoded by the clock-controlled energy homeostasis-associated gene is implicated in the regulation of glucose metabolism. However, its links to rhythms of nutrient intake, energy balance, and metabolic control remain poorly defined. Using surveys of Gene Expression Omnibus data sets, we confirm that fasting suppresses liver adropin expression in lean C57BL/6J (B6) mice. However, circadian rhythm data are inconsistent. In lean mice, caloric restriction (CR) induces bouts of compulsive binge feeding separated by prolonged fasting intervals, increasing NAD-dependent deacetylase sirtuin-1 signaling important for glucose and lipid metabolism regulation. CR up-regulates adropin expression and induces rhythms correlating with cellular stress-response pathways. Furthermore, adropin expression correlates positively with phosphoenolpyruvate carboxokinase-1 (Pck1) expression, suggesting a link with gluconeogenesis. Our previous data suggest that adropin suppresses gluconeogenesis in hepatocytes. Liver-specific adropin knockout (LAdrKO) mice exhibit increased glucose excursions following pyruvate injections, indicating increased gluconeogenesis. Gluconeogenesis is also increased in primary cultured hepatocytes derived from LAdrKO mice. Analysis of circulating insulin levels and liver expression of fasting-responsive cAMP-dependent protein kinase A (PKA) signaling pathways also suggests enhanced responses in LAdrKO mice during a glucagon tolerance test (250 µg/kg intraperitoneally). Fasting-associated changes in PKA signaling are attenuated in transgenic mice constitutively expressing adropin and in fasting mice treated acutely with adropin peptide. In summary, hepatic adropin expression is regulated by nutrient- and clock-dependent extrahepatic signals. CR induces pronounced postprandial peaks in hepatic adropin expression. Rhythms of hepatic adropin expression appear to link energy balance and cellular stress to the intracellular signal transduction pathways that drive the liver fasting response.

Receptor mapping using methoxy phenyl piperazine derivative: Preclinical PET imaging.

This study aimed at assessing 2-methoxyphenyl piperazine derivative for its binding specificity and suitability in mapping metabotropic glutamate receptor subtype 1, which is implicated in several neuropsychiatric disorders. N-(2-(4-(2-Methoxyphenyl)piperazin-1-yl)ethyl)-N-methylpyridin-2-amine was synthesised and evaluated for brain imaging subsequent to radiolabelling with [11C] radioisotope via methylation process in 98.9% purity and 52 ± 6% yield (decay corrected). The specific activity was in the range of 72-93 GBq/µmol. The haemolysis of blood was 2-5% for initial 4 hr and remained < 10% after 24 h of incubation indicating low toxicity. In vitro autoradiograms after coincubation with unlabelled ligand confirmed the high uptake of the PET radioligand in the mGluR1 receptor rich regions. The PET as well as biodistribution studies also showed high activity in the brain with a direct correlation between receptor abundance distribution pattern and tracer activity. The biodistribution analyses revealed initial high brain uptake (4.18 ± 0.48). The highest uptake was found in cerebellum (SUV 4.7 ± 0.2), followed by thalamus (SUV 3.5 ± 0.1), and striatum (SUV 3 ± 0.1). In contrast, pons had negligible tracer activity. The high uptake observed in all the regions with known mGluR1 activity indicates suitability of the ligand for mGluR1 imaging.

Metal based imaging probes of DO3A-Act-Met for LAT1 mediated methionine specific tumors: synthesis and preclinical evaluation.

PURPOSE: Tumor cells are known to have an elevated requirement for methionine due to increased protein synthesis and trans-methylation reactions. A methionine based macrocyclic tumor imaging system, DO3A-Act-Met, has been designed to provide a novel platform for tumor imaging via modalities, PET/MRI using metal ions, (68)Ga and (157)Gd. METHODS: Synthesis of DO3A-Act-Met was confirmed through NMR and mass spectrometric techniques. Cytotoxicity of complexes was evaluated using MTT assay whereas receptor binding and trans-stimulation studies were performed on EAT and U-87 MG cell lines. Tumor targeting was assessed through imaging and biodistribution experiments on U-87 MG xenograft model. RESULTS: DO3A-Act-Met was synthesized and radiolabeled with (68)Ga in high radiochemical purity (85-92%). The receptor binding assay on EAT cells predicted high binding affinity with Kd of 0.78 nM. Efflux of (35)S-L-methionine trans-stimulated by extracellular DO3A-Act-Met on U-87MG cells suggested an L-system transport. MR studies revealed a longitudinal relaxivity of 4.35 mM(-1) s(-1) for Gd-DO3A-Act-Met and a 25% signal enhancement at tumor site. The biodistribution studies in U-87MG xenografts validated tumor specificity. CONCLUSION: DO3A-Act-Met, a methionine conjugated probe is a promising agent for targeted molecular imaging, exhibiting high specificity towards tumor owing to its essential role in proliferation of cancer cells mediated through LAT1.

Recurrent Subdural Hematoma: An Institutional Experience.

Background Chronic subdural hematoma (CSDH) is a common neurosurgical problem, which offers a good outcome following surgery. In many cases, burr hole irrigation and drainage under local anesthesia can provide satisfactory results. However, recurrence can be a cause for concern for both the surgeon and the patient. While recurrence is not a frequent phenomenon, studies have reported rates of up to 31.6%. Aims and objectives In this study, our objective is to examine a comprehensive range of potential risk factors and provide valuable insights into identifying patients at a higher risk of recurrence to aid in surgical decision-making. Methodology This study employed a prospective and retrospective design, conducted between 2017 and 2021, at Sri Ramachandra Institute of Higher Education and Research. The study received ethical approval from the Institutional Ethics Committee. The research aimed to assess patients who underwent surgery for CSDH, with a particular focus on those who experienced recurrence. Results The average age of patients with recurrence was 71.5 years compared to 65.2 years in the no-recurrence group, but this difference did not show a significant statistical correlation. A significant male predominance was observed, with 27 men and four women affected (out of a total of 147 men and 73 women in the study), resulting in a statistically significant p-value of 0.01. On multivariate analysis, heterogenous subtypes were a significant predictor of recurrence (OR: 8.88, 95% CI: 6.96-16.54, p = 0.01). The mean midline shift in those with recurrence was 11.4 mm compared to 7.09 mm in those without recurrence. This was a statistically significant correlation with a p-value of 0.02. Regarding those with recurrence, 24 patients underwent evacuation using two burr holes, with one placed in the frontal region and another in the parietal region. All of these patients had a subdural drain placed, which was removed on postoperative day 2. The remaining eight patients underwent a mini-craniotomy for evacuation. We had four cases of refractory CSDH, all of whom underwent the second evacuation using burr holes. Three of them underwent evacuation via craniotomy, while the family of the fourth patient did not give consent for the procedure. Conclusion Patient-related factors such as gender, bilateral presentation, and the presence of hypertension and radiological factors such as the presence of heterogenous subtype and a significant midline shift are clues toward a higher chance of recurrence.

Tunable luminescence and electrical properties of cerium doped strontium aluminate (SrAl2O4:Ce3+) phosphors for white LED applications.

In new research growth long after glow material is a potential candidate due to its physical properties, chemical stability and wide application in modern solid-state lightning (LED), display devices, dosimetry and sensors. A cerium doped strontium aluminate phosphor (SrAl2O4:Ce3+) was synthesized by conventional solid-state reaction method. The crystal structure and morphology of phosphors, while doping rare earth metal and lithium metal ion was investigated by using X-ray diffraction, Raman spectroscopy and field emission scanning electron microscopy. Fourier transformed infrared spectrum results of the synthesized phosphor composition conforms the characteristic vibration bands of synthesized phosphor. Surface composition analysis of the prepared samples was examined using X-ray photoelectron spectroscopy. Photoluminescence emission band observed at ∼420 nm, ∼490 nm and ∼610 nm region under the excitation wavelength of 256 nm. Wight light emission was confirmed using the Commission Internationale de L'Eclairage (CIE) chromatic coordinate graph. The correlated colour temperature (CCT) value of 0.5% Ce3+ doped SAO of phosphors was calculated is in the range of 1543 K, which is indicated the synthesized phosphors performance as warm white light source. The obtained phosphor has a high dielectric constant and low loss tangent which is useful to optoelectronic devices.

Biochemical and Radiological Factors for Prognostication of Traumatic Brain Injury: An Institutional Experience.

Introduction Traumatic brain injury (TBI) necessitates identifying patients at risk of fatal outcomes. Classic biomarkers used clinically today in other organ systems are quantitative in nature. This aspect largely restricts the prognostic ability of a theoretical quantitative brain biomarker. This study aimed to explore biochemical markers and imaging findings reflecting the severity of cerebral damage to predict outcomes. Methodology In this study, 61 TBI cases with moderate to severe brain injury were prospectively observed, and various indices including random blood sugar (RBS), hemoglobin, international normalized ratio (INR), lactate dehydrogenase (LDH), cortisol, and CT findings were assessed. Glasgow Outcome Scores (GOS) determined the outcomes. Statistical analysis was carried out to assess correlations.  Results The mean RBS level of those who did not survive was 259.58 mg/dL, whereas in those who survived the value was 158.48 mg/dL. Analysis indicated that patients with high RBS value on admission had a higher risk of mortality (p=0.000). We noted that the mean serum cortisol levesl on both Days 1 and 5 were higher in patients who died and were able to establish a statistically significant correlation between both the values and outcome. A statistically significant negative correlation between Day 1 and Day 5 serum LDH levels and outcomes was evident from our study (p=0.000 for both). Among the components of the Rotterdam score, the presence of intraventricular hemorrhage (IVH) in the CT scan had a significant association with unfavorable outcomes (p=0.01) while midline shift was significantly associated with a low GCS (p=0.04). Conclusion Biochemical markers such as INR, RBS, serum cortisol, and LDH at admission can serve as valuable indicators of prognosis in TBI patients. Furthermore, a persistent increase in LDH and cortisol levels between Days 1 and 5, along with the Glasgow Coma Scale and Rotterdam Scoring system, are good predictors of mortality.

Obesity accelerates thymic aging.

As the expanding obese population grows older, their successful immunologic aging will be critical to enhancing the health span. Obesity increases risk of infections and cancer, suggesting adverse effects on immune surveillance. Here, we report that obesity compromises the mechanisms regulating T-cell generation by inducing premature thymic involution. Diet-induced obesity reduced thymocyte counts and significantly increased apoptosis of developing T-cell populations. Obesity accelerated the age-related reduction of T-cell receptor (TCR) excision circle bearing peripheral lymphocytes, an index of recently generated T cells from thymus. Consistent with reduced thymopoiesis, dietary obesity led to reduction in peripheral naive T cells with increased frequency of effector-memory cells. Defects in thymopoiesis in obese mice were related with decrease in the lymphoid-primed multipotent progenitor (Lin-Sca1+Kit+ Flt3+) as well as common lymphoid progenitor (Lin-Sca1+CD117(lo)CD127+) pools. The TCR spectratyping analysis showed that obesity compromised V-beta TCR repertoire diversity. Furthermore, the obesity induced by melanocortin 4 receptor deficiency also constricted the T-cell repertoire diversity, recapitulating the thymic defects observed with diet-induced obesity. In middle-aged humans, progressive adiposity with or without type 2 diabetes also compromised thymic output. Collectively, these findings establish that obesity constricts T-cell diversity by accelerating age-related thymic involution.

Central nervous system melanocortin-3 receptors are required for synchronizing metabolism during entrainment to restricted feeding during the light cycle.

Melanocortin-3 receptors (Mc3rs) in the central nervous system are involved in expression of anticipatory rhythms and synchronizing clocks maintaining circadian rhythms during restricted feeding (RF) [mice housed under a 12-h light-dark cycle with lights on between zeitgeber time (ZT) 0 to ZT12 fed 60% of normal calories between ZT7 and ZT11]. Because the systems governing circadian rhythms are important for adaptation to RF, we investigated whether Mc3rs are required for metabolic adaption to RF. Mc3r(-/-) mice subjected to RF exhibited normal weight loss; however, they developed hyperinsulinemia, glucose intolerance, increased expression of lipogenic genes, and increased ketogenesis relative to controls. Rhythmic expression of transcription factors regulating liver clock activity and energy metabolism (Bmal1, Rev-erbalpha, Pgc1, Foxo1, Hnf4alpha, and Pck1) was severely compromised in Mc3r(-/-) mice during RF. Inhibition of neural melanocortin receptors by agouti-related peptide also attenuated rhythmicity in the hepatic expression of these genes during RF. Collectively, these data suggest that neural Mc3rs are important for adapting metabolism and maintaining rhythms of liver metabolism during periods when feeding is restricted to the light cycle.-Sutton, G. M., Begriche, K., Kumar, K. G., Gimble, J. M., Perez-Tilve, D., Nogueiras, R., McMillan, R. P., Hulver, M. W., Tschöp, M. H., Butler, A. A. Central nervous system melanocortin-3 receptors are required for synchronizing metabolism during entrainment to restricted feeding during the light cycle.

Leave Against Medical Advice amongst Pediatric Patients Admitted in a Tertiary Teaching Hospital in Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: Leave against medical advice has a potentially deleterious effect on the health of a child. This is particularly alarming in case of pediatric patients as they are unable to understand the implications of it and rely on parents to make decisions regarding their health. This study was undertaken to find out the prevalence of leave against medical advice among pediatric patients admitted in a tertiary teaching hospital in Nepal. METHODS: A descriptive cross-sectional study was conducted in the Department of Pediatrics, Manipal Teaching Hospital between August 2019 and July 2020. Ethical clearance was obtained from the Institutional Review Committee (Ref: 256). Convenient sampling method was used. Data entry and analysis was done on Statistical Package for Social Sciences version 23. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: Out of 1608 pediatric admissions taken in our study, the prevalence of leave against medical advice was found to be 67 (4.2%) at 95% Confidence Interval (3.22-5.18). Maximum 22 (33%) and minimum 6 (9%) patients respectively belonged to the age group from birth to 7 days and more than 10 years. Out of 67 cases, there were 36 (54%) males and 31 (46%) females. CONCLUSIONS: The prevalence of leave against medical advice among admitted pediatric patients in our study was similar to that of other studies. It is a social health problem which can be prevented by increasing the awareness and facilitating the use of health insurance schemes. More effective communication is required between the treating physicians and the parents to prevent this detrimental practice.

Increased physical activity cosegregates with higher intake of carbohydrate and total calories in a subcongenic mouse strain.

C57BL/6 J (B6) and CAST/EiJ (CAST), the inbred strain derived from M. musculus castaneus, differ in nutrient intake behaviors, including dietary fat and carbohydrate consumption in a two-diet-choice paradigm. Significant quantitative trait loci (QTLs) for carbohydrate (Mnic1) and total energy intake (Kcal2) are present between these strains on chromosome (Chr) 17. Here we report the refinement of the Chr 17 QTL in a subcongenic strain of the B6.CAST-( D17Mit19-D17Mit91 ) congenic mice described previously. This new subcongenic strain possesses CAST Chr 17 donor alleles from 4.8 to 45.4 Mb on a B6 background. Similar to CAST, the subcongenic mice exhibit increased carbohydrate and total calorie intake per body weight, while fat intake remains equivalent. Unexpectedly, this CAST genomic segment also confers two new physical activity phenotypes: 22% higher spontaneous physical activity levels and significantly increased voluntary wheel-running activity compared with the parental B6 strain. Overall, these data suggest that gene(s) involved in carbohydrate preference and increased physical activity are contained within the proximal region of Chr 17. Interval-specific microarray analysis in hypothalamus and skeletal muscle revealed differentially expressed genes within the subcongenic region, including neuropeptide W (Npw); glyoxalase I (Glo1); cytochrome P450, family 4, subfamily f, polypeptide 1 (Cyp4f15); phospholipase A2, group VII (Pla2g7); and phosphodiesterase 9a (Pde9a). This subcongenic strain offers a unique model for dissecting the contributions and possible interactions among genes controlling food intake and physical activity, key components of energy balance.

Uveitis in Patients with Retinitis Pigmentosa: 30 Years' Consecutive Data.

PURPOSE: To describe the clinical pattern of uveitis in patients with retinitis pigmentosa (RP) at a tertiary care eye hospital over a period of 30 years. METHODS: The medical records of 32 eyes of 22 patients of RP with uveitis were included in this study. Collected data included age, subsets of uveitis, best corrected visual acuities (BCVA), detailed laboratory investigations, and treatment. RESULTS: Mean age at presentation was 53.4 ± 18.8 years, and mean age of diagnosis of RP was 39.2 ± 21.4 years. Uveitis was bilateral in 10 (45.5%) patients. The most common of uveitis in current study was anterior uveitis (56.2%), followed by intermediate uveitis (43.8%). Cataract developed in 12 (37.5%) eyes, and three eyes had raised intraocular pressure. Ten patients (45.5%) required oral steroid, and one patient required oral methotrexate. CONCLUSIONS: Uveitis in RP patients is rare, but not uncommon. Coexistence of these disorders might support the inflammatory pathway in etiology of RP.

Morbidities and Outcome of a Neonatal Intensive Care in Western Nepal.

BACKGROUND: Neonatal mortality rate of developing countries is declining over decades. In the recent years increasing number of preterm and high risk neonates have facilities for tertiary care treatment. The aim of the study was to assess the morbidities and outcome of neonatal intensive care admissions. METHODS: It was a retrospective observational study carried out in neonatal intensive care unit of the Manipal Teaching Hospital, Pokhara, Nepal from January 2014 to December 2015. Neonatal details including place of delivery, birth weight, gestation, diagnosis at admission, hospital course and final outcome were recorded in predesigned proforma. Risk of mortality was calculated using odds ratio and 95% confidence interval. RESULTS: There were total 1708 admission during study period and inborn as well as out born neonates were equally admitted. Neonatal hyperbilirubinemia (37.1%), neonatal sepsis 532 (31.2%), prematurity, 314 (18.4%) perinatal asphyxia 112 (6.6%), meconium aspiration syndrome 79 (4.6%) and intrauterine growth restriction 49 (2.8%) were main indications for hospitalization. A total of 1410 (82.6%) the patients were discharged after treatment, 167 (9.7) left against medical advice, 115 (6.7%) died in hospital and 16 (1%) cases were referred. Preterm neonates had twice the risk of mortality than term neonates (OR =2.1664). Birth weight < 2500 grams had three times more risk of neonatal mortality than normal birth weight (OR =3.0783). CONCLUSIONS: Neonatal hyperbilirubinemia, prematurity and neonatal sepsis were common morbidities inneonatal intensive care unit.

Time trend of neurocysticercosis in children with seizures in a tertiary hospital of western Nepal.

INTRODUCTION: Neurocysticercosis is a common cause of seizure disorders in children of Western Nepal. The clinical presentation is variable. The incidence varies depending on the food habits and ethnicity of the population. The present study was undertaken with the objective of studying the mode of presentation, radiological findings and to determine the recent trend of the disease in children of Western Nepal. METHODS: Records from the Department of Pediatrics, Manipal Teaching Hospital, Pokhara, Nepal of children aged 0-17 years admitted from 2003 to 2015 and with the discharge diagnosis of seizure and neurocysticercosis (NCC) were reviewed. The diagnosis was primarily based on clinical features, neurological involvement and CT and MRI studies. Seizures due to other CNS pathologies were excluded. Patients with NCC were treated with Albendazole15mg/kg/day for 28 days with supportive treatments for seizures and raised intracranial pressure. Patients were followed up for one year after the completion of the treatment. RESULTS: There were 1355 cases of seizure disorders, out of which 229 (16.90%) were NCC. There were 99 (43.23%) in the age group 6-10 years followed by 91 (41.09%) in the age group of 11-15 years. Seizures were the most common presenting symptom in 88.65%, followed by raised ICP in 9.61%. Neuropsychiatric changes were noted in 38 cases (16.59%). CT scan findings revealed single lesion in 78.16% and multiple lesions in 21.83%. Poisson regression analysis showed statistically significant decline of year-wise incidence of NCC cases (p<0.05) from 2003 to 2015. CONCLUSION: The decline in the incidence of NCC in recent years is most probably attributed to improved hygiene with the construction of household toilets to avoid open defecation and biannual deworming with Albendazole as a part of School Health and Nutrition Project.

DNA vaccine (P1-2A-3C-pCDNA) co-administered with Bovine IL-18 gives protective immune response against Foot and Mouth Disease in cattle.

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals causing considerable economic loss in the affected countries. Presently used tissue culture inactivated vaccine protects the vaccinated animals for a short duration. DNA vaccines along with appropriate adjutants is one of the approach for the development of alternative vaccine. In the present study, we constructed P1-2A-3CpCDNA (containing P1-2A-3C coding sequences of FMDV Asia-1 Ind 63/72) and bovine IL-18 pCDNA plasmids and evaluated in cattle. Four groups of calves each group containing six calves were vaccinated with 200µg of plasmid DNA vaccine P1-2A-3CpCDNA, P1-2A-3CpCDNA+ bIL-18pCDNA and inactivated vaccine respectively where as fourth group was unvaccinated. P1-2A-3CpCDNA+bIL-18pCDNA vaccinated animals have shown higher levels of neutralizing antibodies and specific T-cell proliferation responses. Higher levels of CD4(+) and CD8(+) cells were observed in these animals. Similarly, IL-18 adjuvanted group has shown increased Th1 and Th2 cytokine responses. All the vaccinated animals were challenged with cattle adapted FMD homologous Asia1 virus two weeks after the booster dose. IL18 co administered DNA vaccine construct has protected four out of six animals challenged with homologous virus.

Short chain acyl-CoA dehydrogenase deficiency and short-term high-fat diet perturb mitochondrial energy metabolism and transcriptional control of lipid-handling in liver.

BACKGROUND: The liver is an important site of fat oxidation, which participates in the metabolic regulation of food intake. We showed previously that mice with genetically inactivated Acads, encoding short-chain acyl-CoA dehydrogenase (SCAD), shift food consumption away from fat and toward carbohydrate when tested in a macronutrient choice paradigm. This phenotypic eating behavior suggests a link between fat oxidation and nutrient choice which may involve an energy sensing mechanism. To identify hepatic processes that could trigger energy-related signals, we have now performed transcriptional, metabolite and physiological analyses in Acads-/- mice following short-term (2 days) exposure to either high- or low-fat diet. METHODS AND RESULTS: Metabolite analysis revealed 25 acylcarnitine species that were altered by diet and/or genotype. Compared to wild-type mice, phosphorylated AMP-activated protein kinase was 40 % higher in Acads-/- mice after short-term high-fat diet, indicating a low ATP/AMP ratio. Metabolite analyses in isolated liver mitochondria from Acads-/- mice during ADP-linked respiration on butyrate demonstrated a reduced oxygen consumption rate (OCR) compared to wild-type, an effect that was not observed with succinate or palmitoylcarnitine substrates. Liver transcriptomic responses in Acads-/- mice fed high- vs. lowfat diet revealed increased RXR/PPARA signaling, up-regulation of lipid handling pathways (including beta and omega oxidation), and increased mRNA expression of Nfe2l2 target genes. CONCLUSIONS: Together, these results point to an oxidative shortage in this genetic model and support the hypothesis of a lower hepatic energy state associated with SCAD deficiency and high-fat diet.