Lymphocyte subsets in the small intestine of piglets fed with probiotic and zinc: a qualitative and quantitative micro-anatomical study.

BACKGROUND: Piglet mortality is a real concern to the pig farmers. The major cause is due to the late maturation of the immune system and dietary changes in postweaned piglets. The potential role of probiotic and zinc in the stimulation of the immune system is well established. Hence, the present study was undertaken to evaluate alterations of T and B cells in the small intestine after dietary inclusion of probiotic and zinc in pre and post-weaned piglets. MATERIALS AND METHODS: A total of 18 healthy Large White Yorkshire (LWY) piglets, irrespective of sex obtained from 3 litters at the age-group of 20, 30 and 60 days. They were divided into a control group fed with basal diet and a treatment group fed with probiotic and zinc supplement along with the basal diet, consisting of three animals in each group. The piglets were weaned at 28 days of age. After sacrificing the animals at day 20, 30 and 60 from both the groups, the abdominal cavity was opened and small intestinal tissue samples were collected, processed and stained by indirect immunofluorescence technique. The slides were evaluated under the fluorescent light microscope. The data were statistically analysed. RESULTS: The different T and B cell subsets were recorded in the lining epithelium, core of villus, crypt area of lamina propria and Peyer's patch area. The number of CD4+, CD8+, IgA+ and IgM+ cells was higher in the treated piglets than the control group of animals, irrespective of segments of intestine and age-group. CONCLUSIONS: It can be concluded that the dietary supplementation of probiotic and zinc was found to be good additives as they can stimulate the immune response in piglets, especially during the critical early post-weaning period.

Small intestinal mucosal cells in piglets fed with probiotic and zinc: a qualitative and quantitative microanatomical study.

BACKGROUND: Probiotics and zinc are commonly used and beneficial in pig production. This work aimed to assess the effects of probiotic and zinc on the mucosal cells of the small intestine in respect to digestive capacity and immunity in pre- and post-weaned piglets. MATERIALS AND METHODS: Eighteen Large White Yorkshire piglets were divided equally into control and treatment groups. The piglets were maintained in standard management conditions and were weaned at 28 days of age. The treatment group of piglets fed a mixture of probiotics orally at 1.25 × 109 CFU/day and zinc at 2000 ppm/day from birth to 10 days of age. At three different age-groups viz. day 20 (pre-weaning) and, day 30 and day 60 (post-weaning), the animals were sacrificed. For histomorphology, the tissue samples were processed and stained with Mayer's haematoxylin and eosin for routine study, combined periodic acid-Schiff-Alcian blue for mucopolysaccharides and Masson-Hamperl argentaffin technique for argentaffin cells. The stained slides were observed under the microscope. The samples were processed as per the standard procedure for scanning and transmission electron microscopy. The statistical analysis of the data using the appropriate statistical tests was also conducted. RESULTS: The mucosal epithelium of villi and crypts were lined by enterocytes, goblet cells, argentaffin cells, microfold (M-cell) cells, tuft cells and intraepithelial lymphocytes. The multipotent stem cells were located at the crypt base. The length of the enterocyte microvilli was significantly longer (p < 0.05) in the treatment group of piglets. The number of different types of goblet cells and argentaffin cells was more in treated piglets irrespective of segments of intestine and age. The intraepithelial lymphocytes were located in apical, nuclear and basal positions in the lining epithelium of both villus tip and base with their significant increase in the treatment group of piglets. The transmission electron microscopy revealed the frequent occurrence of tuft cells in the lining mucosa of the small intestine in treated piglets. CONCLUSIONS: Dietary supplementation of probiotic and zinc induced the number of different mucosal cells of villi and crypts in the small intestine that might suggest the greater absorptive capacity of nutrients and effective immunity in critical pre and post-weaned piglets.

Assessment of Reference Range of Serum Homocysteine from the Post-therapy Values of Cobalamin and Folate Deficiency Patients.

OBJECTIVES: Ideally, the upper reference limit of plasma or serum homocysteine (Hcy) is to be defined from the studies done on individuals with normal cobalamin and folate status. It is difficult to separate the truly healthy (Cobalamin/Folate Replete) individuals from the randomly selected, apparently healthy individuals who are sub-clinically deficient of cobalamin/folate. The present study was aimed at defining the reference values for the serum homocysteine from individuals with normalized cobalamin and folate status. METHODS: In our study, 215 patients with cobalamin, folic acid deficiency were treated accordingly till complete restoration of clinical and laboratory abnormalities. The post-therapy serum Hcy values were used as reference values. RESULTS: Post-therapy serum Hcy values 12.56 µmol/L (95th percentile), 11.4 µmol/L (85th percentile), 9.8 µmol/L (67th percentile) were seen. The hyperhomocysteinemia was more visible (17.3% gain in prevalence) in the same patient group if interpreted using the post-therapy Hcy value (11.4 µmol/L) as the cut-off. There was no difference between the genders and age groups in the pre or post-therapy Hcy values. CONCLUSIONS: The benefit of the gain in prevalence of disease or the increase in the sensitivity of the test, though small, gets magnified in common diseases and in populous countries. Selection of the individuals is as important as the method or the reagent used in the method when a particular parameter is studied. Repleting the vitamin stores in the confirmed vitamin-deficient patients is more appropriate and easily feasible, since anyway they require treatment, than doing the same on the apparently healthy people. The data thus obtained can be better used as the reference value, for a more meaningful interpretation. The reference range can in turn be used to identify the sub-clinically deficient but asymptomatic people and managed accordingly.

Serum procalcitonin as a biomarker of bloodstream infection & focal bacterial infection in febrile patients.

Background & objectives: Bacteraemia is a serious form of infection in patients presenting with fever, thus, there is a necessity for a biomarker for rapid diagnosis of bacteraemia in such patients to make better therapeutic decisions. This study was conducted to measure the serum procalcitonin (PCT) levels at the time of initial presentation as a biomarker for identifying bacteraemia and as a predictor of mortality in patients admitted with acute fever. Methods: Four hundred and eighty patients, who presented with acute fever requiring admission to a tertiary care teaching hospital in south India, were prospectively studied. All patients were evaluated with a detailed history, physical examination, laboratory and imaging studies. Baseline serum PCT was measured for each patient within six hours of admission. Results: Among patients with single infectious cause (n=275), significantly higher median serum PCT levels were evident in bacteraemia compared to leptospirosis (P=0.002), dengue (P <0.001), scrub typhus (P <0.001) and evident focus of infection without bacteraemia (P=0.036). By receiver-operator characteristic curve analysis, at a cut-off value of >3.2 ng/ml, the sensitivity and specificity of serum PCT levels in predicting bacteraemia were 81.1 and 63.3 per cent, respectively. As per the worst-case scenario analysis, 91 (18.9%) patients had a poor outcome and these had significantly higher median serum PCT levels compared to survivors (n=389) [9.46 (2.03-44.4) vs. 1.23 (0.34-7.645); P <0.001]. At a cut-off value of >3.74 ng/ml, serum PCT levels at initial presentation predicted in-hospital mortality with a sensitivity and specificity of 67 and 67.5 per cent, respectively. Interpretation & conclusions: Our observations suggest that serum PCT level may be a useful biomarker for identifying bacteraemia as well as predicting mortality in patients with acute fever requiring admission to hospital.

Haemato-biochemical alterations and oxidative stress associated with naturally occurring porcine circovirus2 infection in pigs.

Porcine circovirus2 (PCV2) infection in pigs is one of the major causes of economic loss to the farmers in terms of low production, slow growth and increase post-weaning mortality rate. The effect of PCV2 infection on haemogram, serum biochemical profile and oxidant/anti-oxidant status is not well established in pigs. In the present study, haemogram, serum biochemical profile and oxidant/anti-oxidant status were assessed in pigs confirmed positive for PCV2 infections as evidenced by commercially available enzyme-linked immunosorbent assay kit (n = 151) and polymerase chain reaction (PCR) (n = 42) among a total of 306 number of pigs included in the study. Non-infected healthy pigs (n = 6) served as healthy control. The total erythrocyte count (TEC), haemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), differential leukocyte count (DLC) and thrombocyte count were measured. The levels of total protein, albumin, globulin, total bilirubin, direct bilirubin, blood urea nitrogen (BUN), creatinine and glucose and enzymes viz. alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were measured. Oxidative stress indicators such as plasma malondialdehyde (MDA) and total anti-oxidant activity (TAOA) were measured using commercially available kits. The mean values of TLC, lymphocytes and thrombocyte count were significantly (P < 0.05) low in PCV2-infected pigs. The levels of globulin, AST, GGT, BUN and creatinine were significantly increased (P < 0.05) whereas levels of albumin and glucose significantly (P < 0.05) decreased in PCV2-infected pigs. The significant increase (P < 0.05) in MDA level and significant decrease (P < 0.05) in TAOA level were noticed in PCV2-infected animals as compared with healthy control. The present study supports immunosuppression, possible multiple organ damage and oxidative stress associated with naturally occurring PCV2 infection in pigs. Timely vaccination and managemental practices can reduce PCV2 infection in farms. In spite of many research studies, there is still paucity of detailed systemic study on haemato-biochemical alteration and oxidative stress associated with PCV2 infection.

Characterization of drug resistance and genetic diversity of Plasmodium falciparum parasites from Tripura, Northeast India.

Monitoring of anti-malarial drug resistance is vital in Northeast India as this region shares its international border with Southeast Asia. Genetic diversity of Plasmodium parasites regulates transmission dynamics, disease severity and vaccine efficacy. P. falciparum chloroquine resistance transporter (Pfcrt), multidrug resistance-1 (Pfmdr-1) and kelch 13 propeller (PfK-13) genes which govern antimalarial drug resistance and three genetic diversity markers, merozoite surface protein 1 and 2 (Pfmsp-1, Pfmsp-2) and glutamate rich protein (Pfglurp) were evaluated from Tripura, Northeast India using molecular tools. In the Pfcrt gene, 87% isolates showed triple mutations at codons M74I, N75E and K76T. 12.5% isolates in Pfmdr-1 gene showed mutation at N86Y. No polymorphism in PfK-13 propeller was found. Polyclonal infections were observed in 53.85% isolates and more commonly in adults (p = 0.0494). In the Pfmsp-1 locus, the K1 allelic family was predominant (71.2%) followed by the 3D7/IC family (69.2%) in the Pfmsp-2 locus. RII region of Pfglurp exhibited nine alleles with expected heterozygosity of 0.85. The multiplicity of infection for Pfmsp-1, Pfmsp-2 and Pfglurp were 1.56, 1.31 and 1.06 respectively. Overall, the study demonstrated a high level of chloroquine resistance and extensive parasite diversity in the region, necessitating regular surveillance in this population group.

An unusual case of Cheyletiellosis in a Persian cat and its therapeutic management.

A male Persian cat was presented with a history of alopecia at the dorsal tail region, with mild pruritus, flaking of skin and the owner's complaint of pruritus on herself and her family members. All the vital signs of the cat were found within the normal reference range. Skin scraping and hair samples were found to be negative for Demodex spp. and Sarcoptes spp. of mites, pediculosis and fungal infestation. Physical examination of the whole body revealed absence of fleas or flea eggs. Further, food hypersensitivity was ruled out by gradually changing the previous wheat based diet to a commercial cat food. However, eggs of Cheyletiella spp. were seen on microscopic examination of skin scraping and the lesions on the owner's body were indicative of infestation by Cheyletiella spp. as it's zoonotic in nature. A treatment protocol was initiated that included Ivermectin and bath with a shampoo containing selenium sulphide. Owners were advised to apply Calamine lotion on their lesions. Both the owner and patient recovered uneventfully 3 months post-therapy.

Endotheliotropic herpesvirus infection in Asian elephants (Elephas maximus) of Assam, India.

BACKGROUND AND AIM: Elephant endotheliotropic herpesvirus (EEHV) is an emerging disease of elephant. Therefore, a study was conducted to know the actual status of the disease in Assam State of India. MATERIALS AND METHODS: A total of 289 Asian elephants of Assam were screened during 2 years of study from April 2017 to March 2019. The clinical symptoms of diseased as well as gross and histopathological changes of dead elephants were recorded for the diagnosis of the disease. Virus involved in the occurrence of the disease was confirmed by polymerase chain reaction (PCR). RESULTS: In the present study, a total of three elephant calves out of 22 were found positive to EEHV1A. On the other hand, three adult asymptomatic elephants were also found positive for EEHV1 on screening 267 captive Asian elephants of Assam. The amplified PCR product showed band size of 520, 600, and 930 bp. The PCR amplified product with size 600 bp had shown the gene sequence for EEHV1U77/HEL. Gross lesions include congested blood vessels of the liver and intestinal mucosa, foci of petechiae in the spleen, and heart and focal ulceration in the dorsal surface of the tongue. Microscopically, the kidneys showed intertubular edema and focal areas of degeneration associated with coagulative necrosis of the tubular epithelium. The liver showed hydropic degeneration and fatty changes of the hepatocytes. There was a massive proliferation of fibroblasts in the interlobular spaces which penetrated the necrosed areas of the hepatic lobules. CONCLUSION: A total of three wild rescued elephant calves and three asymptomatic adults were found positive for EEHV1A during the 2 years of study. The PCR amplified product with size 600 bp had shown the gene sequence for EEHV1U77/HEL.

Retraction Note to: Therapeutic management of trypanosomosis with ophthalmic involvement in a dog.

[This retracts the article DOI: 10.1007/s12639-017-0953-z.].

A Randomized, Double Blind, Placebo Controlled, Crossover Study to Assess the Safety and Beneficial Effects of Cassia Tora Supplementation in Healthy Adults.

OBJECTIVE: The current clinical trial was aimed at evaluating the safety and beneficial effect of Cassia tora (C. tora) supplementation in healthy adults. DESIGN: A randomized, double blind, placebo controlled study with a crossover design was done on 60 healthy normal weight adults (age range: 20-55 yrs). The study consisted of 2 treatment phases of 24 weeks each with a washout period of 4 weeks between the phases. 30 subjects randomly allocated to the 'Placebo first' group and 30 to 'C. tora first' group and assigned to receive a dose of C. tora (330 mg) or matched placebo three times a day. Safety markers were measured at base line and at the end of both the treatment phases. Body mass index, blood pressure, fasting blood sugar, glycated hemoglobin, lipid profile and antioxidants were measured at baseline and at every three months interval. Repeated measures analysis was applied to assess the period and carryover effects of the drug over placebo on biochemistries. RESULTS: C. tora supplementation was well tolerated and no apparent changes were observed in safety markers. The net effect of C. tora in natural units over placebo was 0.83 [0.57, 1.09]- high density lipoprotein cholesterol; 27.63 [24.39, 30.88]- superoxide dismutase; 0.32 [0.28, 0.36]- catalase; 0.68 [0.56, 0.80]- glutathione peroxidase; 0.25 [0.22, 0.29]- glutathione s-transferase; 0.32 [0.29, 0.36]- glutathione and -1.08 [-1.63, -0.54]- low density lipoprotein cholesterol. CONCLUSION: The findings advocate that C. tora supplementation is safe and beneficial in elevating high density lipoprotein cholesterol and antioxidants and hence advised for consumption.

Antifolate drug resistance: Novel mutations and haplotype distribution in dhps and dhfr from Northeast India.

Malaria is a major public health concern in Northeast India with a preponderance of drug-resistant strains. Until recently the partner drug for artemisinin combination therapy (ACT) was sulphadoxine pyrimethamine (SP). Antifolate drug resistance has been associated with the mutations at dihydropteroate synthase (dhps) and dihydrofolatereductase (dhfr) genes. This study investigated antifolate drug resistance at the molecular level. A total of 249 fever cases from Arunachal Pradesh, NE India, were screened for malaria, and of these, 75 were found to be positive for Plasmodium falciparum. Samples were sequenced and analysed with the help of BioEdit and ClustalW. Three novel point mutations were found in the dhps gene with 10 haplotypes along with the already reported mutations. A single haplotype having quadruple mutation was found in the dhfr gene. The study reports higher degree of antifolate drug resistance as evidenced by the presence of multiple point mutations in dhps and dhfr genes. The findings of this study strongly discourage the use SP as a partner drug in ACT.

Therapeutic management of trypanosomosis with ophthalmic involvement in a dog.

The present report communicates a case of canine trypanosomosis with ophthalmic involvement, its diagnosis, hemato-biochemistry and therapeutic management in a 2 year old dog. The dog had history of bilateral corneal opacity and impaired vision since last 4 weeks. On the basis of history and clinical signs, a presumptive diagnosis of canine trypanosomosis was made followed by confirmation with Giemsa stained buffy coat smear examination. Therapeutic regimen was comprised of Diminazine aceturate @ 3.5 mg/kg deep IM for two occasions 24 h apart along with parenteral fluids, hematinics, NSAID and multivitamins which yielded favourable response by third day post-therapy. Haemato-biochemical parameters took nearly 14 days of time to return to near normal levels. Improvement with respect to corneal opacity took 6 weeks of time and the animal was followed up to 3 months without any recurrence.

Diabetes in pregnancy: worse medical outcomes in type 1 diabetes but worse psychological outcomes in gestational diabetes.

BACKGROUND: Women with diabetes experience an increased risk of adverse pregnancy outcomes. AIM: We aim to describe and quantify the psychological impact of the diagnosis of diabetes in pregnant women with type 1 diabetes and gestational diabetes mellitus (GDM) compared to each other and to their counterparts without diabetes. DESIGN: This is a survey-based study with prospective collection of pregnancy outcome data. METHODS: A total of 218 pregnant women (50% with diabetes) were administered questionnaires relating to psychological health. Maternal and neonatal characteristics and pregnancy outcomes were collected. Associations between key psychometric and health outcome variables were examined. RESULTS: At least 25% of women in all three pregnancy groups had scores indicating affective distress in at least one domain. Compared to those with type 1 diabetes, women with GDM evidenced a greater number of uplifts in pregnancy (U = 94, P = 0.041), but also higher levels of overall anxiety (U = 92, P = 0.03) and stress (U = 82, P < 0.01). Women with GDM also had significantly elevated overall depression scores, compared with the control group (U = 34, P = 0.02). Both groups of women with diabetes had clinically elevated levels of diabetes-related distress. There were no associations between maternal psychological variables and pregnancy outcomes. CONCLUSIONS: This work highlights a potential role for targeted psychological interventions to address and relieve symptoms of anxiety and depression among pregnant women with diabetes.

Study of the structure and functioning of referral mechanism of patients receiving treatment and records linkage under Revised National Tuberculosis Control Programme (RNTCP) of Government of India.

BACKGROUND: The reliable and successful performance of the Revised National Tuberculosis Control Programme (RNTCP) "referral mechanism" is profoundly important in the medical college scenario, and it is an important requirement of the programme to have feedback status report of the referred patients. METHODS: An observational study on tuberculosis (TB) patients referred from Directly Observed Treatment (DOT) Centre, Sri Venkateswara Institute of Medical Sciences (SVIMS) was conducted during the years 2010 to 2012 (n=622). Subjects referred to other TUs within the District but failed to report there within 45 days constituted "cases" and subjects, who obtained treatment from the TUs they were referred to "controls". The initial information or confirmation of registration for treatment status feedback were obtained from patient/Senior Treatment Supervisor (STS)/District Tuberculosis Centre (DTC) levels respectively both before using intervention (Phase I, year 2010) and after using intervention (Phase II, years 2011 and 2012) by sending day-to-day text messaging of referral details of patients to the STS and District Tuberculosis Officer (DTO). RESULTS: During Phase I, the distribution of subjects (n=242) in the ages ≤25, 26-50, and ≥51 years was similar in both the cases and control subjects (p=0.054). Further, there was no statistically significant difference in the median age of the cases and controls [34.5 (interquartile range, IQR 31-51) vs 39 (30-54); p=0.319]. There was no statistically significant difference in other parameters, such as gender distribution (p=0.9748); availability of phone numbers (p=0.9614); type of disease (p=0.8395); and type of case (p=0.0793). In Phase II, the effect of intervention on feedback related parameters showed statistically significant improvement in all the parameters such as initial feedback levels obtained within 15 days (p=0.0077); within 45 days (p<0.0001); above 45 days (p<0.0001); registration status confirmation within 45 days (p=0.0343); mismatch of feedback received by observer (p<0.0001); and telephone number of patients recorded (p<0.0001). CONCLUSION: Our findings suggest that text messaging reminders may be an important tool to achieve optimal feedback response in resource-limited settings.

Comparison of Disease Activity Score in 28 joints with ESR (DAS28), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) & Routine Assessment of Patient Index Data with 3 measures (RAPID3) for assessing disease activity in patients with rheumatoid arthritis at initial presentation.

BACKGROUND & OBJECTIVES: In patients with rheumatoid arthritis (RA), disease severity assessment is done using Disease Activity Score in 28 joints with ESR (DAS28). Computing DAS28 is time-consuming, requires laboratory testing and an online calculator. There is a need to validate rapid methods of disease severity assessment for routine daily use. This study was conducted to compare DAS28, Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) and Routine Assessment of Patient Index Data with 3 measures (RAPID3) to assess the disease activity in patients with RA. METHODS: We prospectively studied the utility of CDAI, HAQ-DI and RAPID3 scoring in 100 consecutive newly diagnosed, disease modifying antirheumatic drugs (DMARDs) naïve adult patients with RA seen during January 2013 and June 2014 at a tertiary care teaching hospital in south India. RESULTS: The mean age of the patients was 42.1±11.6 yr, there were 82 females. The median [interquartile range (IQR)] symptom duration was 6 (range 4-12) months. The median (IQR) DAS28, CDAI, HAQ-DI and RAPID3 scores at presentation were 7 (6-7), 36 (28-43), 2 (1-2) and 17 (13-19), respectively. A significant positive correlation was observed between DAS28 and CDAI (r=0.568; P<0.001); DAS28 and HAQ-DI (r=0.304; P=0.002) and DAS28 and RAPID3 (r=0.404; P<0.001). A 'slight-to-fair' agreement was observed in between DAS28 and CDAI (kappa-statistic=0.296). The agreement between DAS28 and HAQ-DI (kappa-statistic=0.007) and RAPID3 (kappa-statistic=0.072) was less robust. INTERPRETATION & CONCLUSIONS: In adult patients with RA, in the setting where illiteracy is high, CDAI emerged as the preferred choice for rapid assessment of severity of disease at the time of initial presentation.

Provider-initiated HIV testing & counselling in incident tuberculosis cases under National TB Programme conditions at a tertiary care teaching hospital in Tirupati, south India.

BACKGROUND & OBJECTIVES: : As sparse published data are available regarding burden of human immunodeficiency virus (HIV) infection in incident tuberculosis (TB) cases at tertiary care teaching hospitals under National TB Programme conditions from India, the present study was designed to assess the proportion of referred registered TB patients who had actually undergone HIV testing and HIV-seropositivity in these. METHODS: : This was a study of provider-initiated HIV testing and counselling in patients registered for the treatment under Revised National TB Control Programme (RNTCP) of Government of India at a tertiary care teaching hospital in Tirupati, south India, during 2012-2013. RESULTS: : Between January 2012 and June 2013, 610 adult patients registered under RNTCP who were referred to Integrated Counselling and Testing Centre for HIV testing, were prospectively studied. Of these, 458 patients (75%) [mean age: 38.6±16.3 yr; 295 (64.4%) males] underwent HIV testing; HIV-co-infection was present in 21 (4.6%) patients. A significantly higher proportion of HIV co-infection was evident in PTB compared with EPTB [13/179 (7.2%) vs 8/279 (2.8%); respectively, P=0.038] and in previously treated patients compared to new patients [6/51 (11.8%) vs 15/407 (3.7%); respectively, P=0.009]. INTERPRETATION & CONCLUSIONS: : The findings of this study showed that a higher proportion of TB patients underwent HIV testing (75%) compared to the national figure of 63 per cent in 2013-2014. HIV seropositivity (4.6%) in TB patients who underwent HIV testing was similar to the five per cent figure observed at national level during 2013-2014. The HIV status of 25 per cent of patients with incident TB still remained unknown, suggesting a need for better integration and co-ordination for effective management of HIV-TB co-infection.

Concomitant infestation of Toxocara cati and Ancylostoma tubaeforme in a mongrel cat.

A 3½ years old mongrel female cat was brought with the history of inappetence, seizure and lateral recumbency since 4 days and motion sickness since 2 days. Faecal examination confirmed Toxocara cati and Ancylostoma tubaeforme along with un-hatched live Toxocara cati larvae. Treatment has been initiated with Pyrantel pamoate and along with supportive therapy.

Assessment of human abuse potential of dasotraline compared to methylphenidate and placebo in recreational stimulant users.

AIMS: The aim of this study was to evaluate the abuse potential of dasotraline, a novel dopamine and norepinephrine reuptake inhibitor with slow absorption (tmax, 10-12h) and elimination (t1/2=47-77 h) that is in development for the treatment of attention deficit hyperactivity disorder (ADHD). METHODS: Recreational stimulant users (N=48) who had specific experience with cocaine, and who were able to distinguish methylphenidate (60 mg) versus placebo in a qualification session, were randomized, in a 6-period, double-blind, crossover design, to receive single doses of dasotraline 8 mg, 16 mg, and 36 mg, methylphenidate (MPH) 40 mg and 80 mg, and placebo. The primary endpoint was the Drug Liking Visual Analog Scale (VAS) score at the time of peak effect (Emax). RESULTS: There were no significant differences between the 3 doses of dasotraline and placebo on the drug liking VAS at Emax, and on most secondary endpoints. Both doses of MPH had significantly higher VAS-drug liking scores at Emax relative to both placebo (P<0.001 for all comparisons) and dasotraline 8 mg (P<0.001), 16 mg (P<0.001) and 36 mg (P<0.01). The increase in heart rate for MPH and dasotraline 36 mg showed a time-course that closely matched subject-rated measures such as Any Effects VAS. CONCLUSIONS: In this study, dasotraline was found to have low potential for abuse, which may be, in part, related to its established pharmacokinetics (PK) profile, which is characterized by slow absorption and gradual elimination.

Binary classification using multivariate receiver operating characteristic curve for continuous data.

The classification scenario needs handling of more than one biomarker. The main objective of the work is to propose a multivariate receiver operating characteristic (MROC) model which linearly combines the markers to classify them into one of the two groups and also to determine an optimal cut point. Simulation studies are conducted for four sets of mean vectors and covariance matrices and a real dataset is also used to demonstrate the proposed model. Linear and quadratic discriminant analysis has also been applied to the above datasets in order to explain the ease of the proposed model. Bootstrapped estimates of the parameters of the ROC curve are also estimated.