Association of Different Biochemical and Hemodynamic Characteristic with Type 2 Diabetes Mellitus and Hypertension in Nephrolithiasis Patients.

Background Although Nephrolithiasis is a common condition caused by a wide variety of metabolic or environmental disturbances, its being one of the major factor of morbidity. Incidence of kidney stone disease (KSD) is highly affected by metabolic disorders and change in blood pressure and glucose. Objective To find out association of different biochemical and hemodynamic parameters with various glycemic status and hypertension in kidney stone disease. Method A cross sectional study was conducted in patients diagnosed as nephrolithiasis by using re¬nal ultrasonography and underwent nephrectomy between January 2019 to January 2021 in Shahid Dharmabhakta National Transplant Centre (SDNTC). A total of 100 subjects with 60 male and 40 females were enrolled. Glycemic status was categorized based on criteria of American Diabetes Association (ADA) and hypertension was defined as BP ≥ 140/90 mm Hg in right arm supine position. All biochemical and hemodynamic profile was carried out following standard protocol. Result Out of 100 patients enrolled, pre-diabetes accounted for 31% followed by diabetes (4%). However, hypertension comprised of 66% in total subjects. Serum urea, cholesterol and triglyceride level were found to be increased by 84.6%, 67.7% and 64.7% respectively in diabetes followed by increase of 3.9%, 19.5% and 3.1% respectively in prediabetes when compared to normal glycemic condition in nephrolithiasis subjects. Serum fasting blood glucose, creatinine and uric acid level was observed significantly higher (p=0.003, p=0.004, p < 0.001 respectively) in hypertensive patients. Duration of hospital stay was also seen positively correlated with hypertension. Conclusion Not only diabetes, prediabetes also manifests the increased risk of kidney stone disease along with hypertension. There is significant impairment in renal function and lipid profile based on diabetes mellitus and hypertension. Early identifying these systemic diseases, different biochemical and hemodynamic parameters and proper treatment accordingly may minimize risk and prevent serious complication in these patients.

Correlation between Sonoelastographic, Doppler and Histopathological Findings in Chronic Kidney Disease Patients in Tertiary Care Centre.

Background Ultrasound (USG) with Doppler examination of intrarenal vessels is the imaging modality of choice employed in patients with renal failure and is commonly performed early in the clinical course. The pulsatility index (PI) and the resistive index (RI) of downstream renal artery have been found to correlate with renal vascular resistance, filtration fraction and effective renal plasma flow in chronic renal failure. Pathological process in any tissues alters their elastic properties which can be assessed non-invasively through newer technique like elastography. Objective To correlate the findings obtained by sonoelastographic, doppler and histopathological studies in chronic kidney disease patients. Method Study was done in 146 patients referred to Department of Radiodiagnosis and Imaging, TUTH for native renal biopsy. Renal sonographic morphology (length, echogenicity, cortical thickness), Sonoelastography (Young's modulus) and Doppler parameters (peak systolic velocity, resistive index) were assessed. The grading of estimated GFR (eGFR) was calculated based on chronic kidney disease (CKD) criteria. Result Among 146 patients, 63 (43.2%) were females and 83 (56.8%) were males. Maximum patients were in age group of 41-50 years (25.3%) followed by age group 51-60 years (24%). Mean age of patient was 42.06±14.70 for males and 39.57±12.54 females. Maximum mean Young's modulus was seen in eGFR stage G1 with 46.57±19.51 kPa followed by in stage G3a with 36.46±10.01 kPa and observed to be statistically non-significant (p=0.172). However, statistical significance difference was noted between the resistive index and elastographic measurement of Young's modulus (r=0.462, p=0.0001). Minimum mean cortical thickness was seen in eGFR stage G5 with 4.42±1.48 mm followed by stage G4 with 5.57±1.24 mm (p= 0.0001). Cortical thickness is decreasing as eGFR stage was increasing in our study (p=0.0001). Resistive index is increasing with decrease in renal size (r=-0.202, p=0.015). Conclusion Ultrasonography along with doppler study and elastography have limited role in diagnosing the pathology of chronic kidney disease, however, it has significant role in the disease progression.

Pulmonary tuberculosis at Patan Hospital, Nepal: One year audit.

BACKGROUND: Globally, Tuberculosis (TB) is one of the top 10 causes of death. In Nepal, poverty and malnutrition aggravate the burden of TB. To identify Mycobacterium tuberculosis sputum is the best sample to identify the bacterium which is helpful for diagnosis. The aim of this study is to identify the situation, burden and challenges of pulmonary tuberculosis in low-middle income country like Nepal. METHOD: A retrospective-audit with reliable-secondary-data of one year was collected (n = 4131). Descriptive-analysis was performed using frequency, percentage and analytical using chi-square-test. Level of significance was set at p < 0.05. Ethical Approval was obtained from IRC-PAHS. RESULT: The prevalence of notified/suspected cases was highest among the patients having >60 years of age 1344(32.54%) and least among the patients with ≤15 years of age 239(5.79%). The male had 1.67 times more smear-positive pulmonary TB cases. Among the AFB-positive cases, smear 3+ was seen in most of the cases 69(38.54%) followed by smear 1+ and smear 2+ in 56(31.28%) and 54(30.16%) respectively. CONCLUSION: The prevalence of smear-positive pulmonary TB case is higher in male. Smear 3+ is seen in most of the followed by smear 1+ and smear 2+. The Burden of Pulmonary TB is more among adult and old-age-people and its control is a challenge for developing and low-middle income countries like Nepal.

3D Convolutional Neural Networks for Event-Related Potential detection.

Deep learning techniques have recently been successful in the classification of brain evoked responses for multiple applications, including brain-machine interface. Single-trial detection in the electroencephalogram (EEG) of brain evoked responses, like event-related potentials (ERPs), requires multiple processing stages, in the spatial and temporal domains, to extract high level features. Convolutional neural networks, as a type of deep learning method, have been used for EEG signal detection as the underlying structure of the EEG signal can be included in such system, facilitating the learning step. The EEG signal is typically decomposed into 2 main dimensions: space and time. However, the spatial dimension can be decomposed into 2 dimensions that better represent the relationships between the sensors that are involved in the classification. We propose to analyze the performance of 2D and 3D convolutional neural networks for the classification of ERPs with a dataset based on 64 EEG channels. We propose and compare 6 conv net architectures: 4 using 3D convolutions, that vary in relation to the number of layers and feature maps, and 2 using 2D convolutions. The results support the conclusion that 3D convolutions provide better performance than 2D convolutions for the binary classification of ERPs.

Hepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate.

The aim of our study was to determine which microsomal cytochrome P450 isozyme(s) were responsible for the microsomal oxidation of indole to indoxyl, an important intermediate in the information of the uremic toxin indoxyl sulfate. Indole was incubated together with an NADPH-generating system and rat liver microsomes. Formation of indigo, an auto-oxidation product of indoxyl, was used to determine the indole-3-hydroxylation activity. Apparent Km and Vmax values of 0.85 mM and 1152 pmol min(-1) mg(-1) were calculated for the formation of indoxyl from indole using rat liver microsomes. The effects of various potential inducers and inhibitors on the metabolism of indole to indoxyl by rat liver microsomes were studied to elucidate the enzymes responsible for metabolism. Studies with general and isozyme-specific P450 inhibitors demostrated that P450 enzymes and not FMO are responsible for the formation of indoxyl. In the induction studies, rate of indoxyl formation in the microsomes from untreated vs induced rats correlated nearly exactly with the CYP2E1 activity (4-nitrophenol 2-hydroxylation). These results suggests that CYP2E1 is the major isoform for the microsomal oxidation of indole to indoxyl.

Homozygosity mapping to the USH2A locus in two isolated populations.

Usher syndrome is a group of autosomal recessive disorders characterised by progressive visual loss from retinitis pigmentosa and moderate to severe sensorineural hearing loss. Usher syndrome is estimated to account for 6-10% of all congenital sensorineural hearing loss. A gene locus in Usher type II (USH2) families has been assigned to a small region on chromosome 1q41 called the UHS2A locus. We have investigated two families with Usher syndrome from different isolated populations. One family is a Norwegian Saami family and the second family is from the Cayman Islands. They both come from relatively isolated populations and are inbred families suitable for linkage analysis. A lod score of 3.09 and 7.65 at zero recombination was reached respectively in the two families with two point linkage analysis to the USH2A locus on 1q41. Additional homozygosity mapping of the affected subjects concluded with a candidate region of 6.1 Mb. This region spans the previously published candidate region in USH2A. Our study emphasises that the mapped gene for USH2 is also involved in patients from other populations and will have implications for future mutation analysis once the USH2A gene is cloned.

Effect of chronic fenvalerate (synthetic pyrethroid) intoxication on the immune response of goats to Brucella abortus strain 19 vaccine.

Fenvalerate, a widely used pesticide, was administered orally to goats at a dose rate of 15 mg/kg body weight, daily for 270 days. After 90 days of dosing, the animals, together with appropriate controls, were vaccinated with Brucella abortus strain 19. The fenvalerate reduced both the humoral and cell-mediated immune responses, as assessed by the standard tube agglutination test and delayed hypersensitivity test, respectively.

Immunosuppression due to chronic Lantana camara, L. toxicity in sheep.

Five sheep were intoxicated with powdered L. camara, leaves at the rate of 200 mg/kg body weight daily for 110 days and another group of four sheep were drenched with distilled water daily for equal number of days which acted as control. The cell mediated immunity of intoxicated and control sheep was assessed with the help of 2,4-dinitrofluorobenzene skin sensitivity test and graft-versus-host reaction and the antibody forming potential of both the groups of animals was measured by haemagglutination against chicken red blood cells antigen. In addition, the phagocytic activity of splenic reticulo-endothelial cells was analysed by nitro blue tetrazolium test. The results indicated significant reduction of both cellular and humoral immunity due to L. camara toxicity. The non-specific phagocytic activity of splenic reticulo-endothelial cells also showed significant reduction due to L. camara, L. intoxication. The present communication constitutes the first report of in vivo immunosuppression due to chronic lantana poisoning in sheep.

Suppression of cell-mediated immunity by purified aflatoxin B1 in broiler chicks.

The effect of purified aflatoxin B1 on cell-mediated immunity (CMI) in broiler chicks was assessed using doses of 0.3 and 1 mg/kg feed from hatching to 6 weeks of age. Total lymphocyte and T lymphocyte counts and the 2,4-dinitrofluorobenzene skin sensitivity test, graft-versus-host reaction and nitroblue tetrazolium salt reduction tests were used to evaluate CMI. Both doses of aflatoxin B1, including the apparently nontoxic dose of 0.3 mg/kg feed, caused a significant (P less than 0.05) decline in CMI. The functional activity of splenic macrophages was decreased significantly (P less than 0.05) by both doses of the toxin.

In vivo and in vitro measurement of cell mediated immunity in Marek's disease: role of reticuloendothelial system.

Dinitrofluorobenzene (DNFB) contact-sensitivity test and leucocyte adherence inhibition (LAI) test were performed in this study as in vivo and in vitro tests to measure the cell-mediated immunity (CMI) in chickens subjected to stimulation of reticuloendothelial (RE) system, depletion of RE system and other experimental groups after being challenged with Marek's disease (MD) virus. It was found that CMI was lower in the birds with depleted RE system and infected control birds, whereas CMI was higher in the birds with activated RE system and vaccinated birds as revealed by DNFB contact-sensitivity test. In cases of LAI test, the number of LAI-positive birds were highest in the chicks with depleted RE system particularly in 3rd and 4th month of age, when the incidence of MD was also maximum.

Immunosuppression due to chronic ochratoxicosis in broiler chicks.

Crystalline ochratoxin A (OA) was added to the feed of broiler chicks at 0.5 ppm and 2.0 ppm, and humoral and cell-mediated immunity (CMI) were studied. CMI was assessed by skin sensitivity testing, graft versus host (GVH) reaction and T lymphocyte count. Humoral immunity was examined by measuring the haemagglutinin (HA) response to sheep RBC (SRBC). In addition, total lymphocyte counts, total serum protein, albumin and globulin were determined and the phagocytic activity of splenic macrophages was measured in the nitroblue tetrazolium test (NBT). The weights of lymphoid organs were also recorded at post-mortem examination of the birds. Highly significant reductions in CMI were indicated by diminished skin sensitivity, GVH reactions and T lymphocyte counts. On the other hand, only the overall HA titres differed significantly between the various treatment groups. Total lymphocyte counts, total serum protein, serum albumin and serum globulin were significantly depressed on the 21st day of intoxication. The number of NBT-positive cells was drastically reduced in both the intoxicated groups compared with controls (P less than 0.05) and the weights of thymus, bursa of Fabricius and spleen of intoxicated birds were significantly reduced. The study illustrated the immunosuppressive effects of ochratoxicosis in broiler chicks.

Evaluation of cell-mediated immunity during chronic organophosphate pesticide intoxication in mice and goats.

The status of cell-mediated immunity (CMI) after pesticide exposure was assessed in mice with the help of skin sensitivity and graft versus host reaction tests. It was observed that at 24 hours post-challenge CMI values did not differ significantly from the control, indicating no effect of quinalphos treatment in mice. Goats receiving monocrotophos at a dose rate of 1.0 mg kg-1 body mass for 40 days gave a similar result when CMI was tested with the help of the chemical sensitizer dinitrofluorobenzene (DNFB). Thus the results clearly indicate that the tested organophosphates do not interfere with cellular immunity in the intoxicated animals.

The role of the reticuloendothelial system in the immunopathology of Marek's disease.

The role of macrophages in immunity against Marek's disease (MD) was studied. Chickens of one group were subjected to depletion of macrophages using repeated doses of Francil amorphous silica and those of another group were subjected to activation of macrophages using repeated doses of brewer's thioglycollate broth. Chickens of a third group were vaccinated with herpesvirus of turkeys FC 126 vaccine followed by depletion of macrophages. Chickens of these three groups, as well as groups of healthy unvaccinated and healthy vaccinated chickens, were challenged with virulent MD virus. A sixth group of healthy uninfected chickens was kept as a control. The results, based on clinical signs, gross and histopathological studies and agar gel precipitation test (AGPT) for antibodies, indicated that activation of macrophages enhanced immunity against MD and depletion of macrophages had the opposite effect. The protective effect of vaccination against MD was also lowered by depletion of macrophages. The results of AGPT indicated retardation of MD virus replication by macrophage activation and the reverse on depletion.

In vivo immunosuppression by synthetic pyrethroid (cypermethrin) pesticide in mice and goats.

Cypermethrin toxicity was produced in mice by intra-peritoneal injection of the pesticide at 50 mg/kg body weight per day for 26 days, and in goats by drenching with cypermethrin at 41.6 mg/kg body weight per day for 30 days. The status of cell-mediated immunity (CMI) was assessed by the 2,4-dinitrofluorobenzene (DNFB) skin sensitivity test. The results indicated significant depression of CMI in the cypermethrin-treated mice and goats. In addition, the humoral immune reaction of the goats intoxicated with cypermethrin was estimated by enumeration of the plaque-forming B-lymphocytes. The rate of plaque formation in the lymphocyte suspension of cypermethrin-treated goats was significantly reduced and the diameter of the plaques was also significantly lower than in that of control animals. The results indicated that cypermethrin suppressed both CMI and the antibody-forming ability of lymphocytes. This immunosuppressive action of cypermethrin is being reported for the first time.

Histopathology of the duodenum and rumen of goats during experimental infections with Paramphistomum cervi.

On microscopic examination after experimental infection with Paramphistomum cervi, tissue reactions in the duodenum were more pronounced during early stages of the infection (20th day post-infection (DPI)). Immature parasites were seen migrating to the muscularis layer, and focal infiltration of macrophages and lymphocytes was observed in the lamina propria and in the interstitial tissue of Brunner's gland. At places, there was cystic dilatation of Brunner's gland. At 40 DPI, the parasite was not present in the duodenal sections, and cellular infiltration was more diffuse and consistent. With the passage of time, the tissue reactions and cellular infiltration in the duodenum became less pronounced, but at 80 days parasites were attached to the villi of the rumen. Infiltration of mononuclear cells in the supporting connective tissue of the rumen was also observed. Thus, it is concluded that the immature forms of Paramphistomum cervi caused more severe damage in the duodenal tissue, whereas the adult form inflicted mild tissue damage in the rumen of the experimental kids.

Bone growth during chronic aldrin intoxication in goats.

Microscopic examination of the costochondral junction of goats after chronic aldrin intoxication revealed a drastic reduction in the width of proliferating, maturing and degenerating cartilage cells. The zone of provisional calcification was almost negligible in aldrin treated animals. In contrast, the control animals showed an orderly sequence of endochondral bone formation. Appositional bone growth studied by the tetracycline labelling technique also showed a marked reduction following chronic aldrin intake. It was concluded that decrease in the rate of appositional bone growth at endosteal periosteal and osteonic surfaces might be due to poor synthesis of bone matrix by the osteoblasts.