Geographic contiguity and genetic affinity among five ethnic populations of Manipur,India: further molecular studies based on VNTR and STR loci

Background : Apart from traditional markers studied among a few numerically small, geographically defined surveys among Mongoloid populations in northeastern parts of India, very little is known about their genomic diversity at the molecular level. Primary objective : This study seeks to investigate how best the variable number tandem repeat (VNTR) and short tandem repeat (STR) loci together can detect the patterns of the genetic affinity among five geographically contiguous, linguistically and socio-culturally diverse Mongoloid-affiliated populations of Manipur in northeastern regions of India. Subject and methods : Blood samples were collected from unrelated and randomly selected volunteers of five ethnic populations (Meitei, Kuki, Naga, Hmar and Manipuri Muslim) from different parts of the state. Allelic variation in four minisatellite loci (D1S7, D4S139, D5S110 and D17S79) and three STR loci (vWA, FESFPS and F13AO1) was studied. Results : Average heterozygosity values among the five groups for the minisatellite range from 68% to 94%, while the hypervariable three STR loci were between 60% and 88%. In the populations, all the studied loci were highly polymorphic, with almost no departure from Hardy-Weinberg equilibrium. The gene differentiation for the VNTR loci was lower and moderate ( G st = 0.030) in comparison with microsatellites ( G st = 0.043). The neighbour-joining method of clustering based on both type of molecular markers reveals a close cluster for the tribal groups of Kuki, Naga and Hmar, while Manipur Muslim stand distinct in both the trees. The clustering pattern obtained from the combined DNA marker loci matches more closely the pattern from STR loci than that obtained from VNTR loci. Conclusions : The results reinforce that using both VNTR and STR loci in detecting regional genetic affinity among the populations is more effective than using VNTR or STR independently, and also confirm the results obtained from the serological and electrophoretic data. However, the clustering pattern obtained from combined DNA markers is more in conformity with the pattern obtained by STR loci rather than with VNTR loci. Despite linguistic, geographical and cultural barriers, the populations show genetic affinity among the four populations except in the case of the migrant Manipur Muslim group.     

Use of Street Methadone in Italian Heroin Addicts Presenting for Opioid Agonist Treatment

ABSTRACT

It is commonly assumed that people who are addicted to certain substances would abuse any substance. This position has never been supported by validly collected and analyzed research data. In this study, the authors examine the use of street methadone by heroin addicts seeking their first agonist opioid treatment in a clinical setting. Fifty-four heroin addicts who resorted to street methadone use were compared by socio-demographic, current clinical, and disease-related variables to 251 peers who do not use street methadone. Heroin addicts who resort to street methadone use are more likely to be females and to have a higher degree of education, are less likely to engage in polyabuse (use of more than three substances), are less severely ill, have been addicted for a shorter period of time, and have been seeking treatment sooner in the course of their disease. Also, they suffer from a wider range of psychopathological distress symptoms. In Italy, resorting to street methadone does not seem to be a surrogate form of heroin addiction, but rather represents means of harm reduction, with treatment seeking occurring shortly after its initiation. This should be accounted for when deciding on take-home policies and issues of potential methadone diversion.     

Nutritional Status of Individuals with Autism Spectrum Disorders: Do We Know Enough?

The incidence of individuals with autism spectrum disorders (ASDs) is on the rise; therefore, well-timed screening is important. Given that this is a nutritionally vulnerable population, it is imperative to conduct a detailed nutritional assessment so that timely and intensive interventions can be recommended. This review article summarizes the research, focusing on the nutritional status of individuals with ASDs based on their anthropometric measurements, biomarkers, and dietary assessments. Research examining anthropometric measurements reveals an abnormally accelerated rate of growth among children with autism but shows inconsistent findings on the prevalence of overweight/obesity in comparison with typically growing children. Although dysregulated amino acid metabolism, increased homocysteine, and decreased folate, vitamins B-6 and B-12, and vitamin D concentrations have been proposed as possible biomarkers for an early diagnosis of ASDs, research investigating their association with age, gender, severity, and other comorbid psychiatric/nonpsychiatric disorders is lacking. There is consensus that children with autism have selective eating patterns, food neophobia, limited food repertoire, and sensory issues. Although inadequate micronutrient but adequate macronutrient intakes are increasingly reported, there are inconsistent results about the extent and type of nutrient deficiencies. Identification and development of nutritional assessment indicators that serve as early warning signs during routine practice beginning at birth and extending throughout the child’s growth are necessary. With this population aging, there is also a dire need to study the adult population. A more vigorous role by nutrition professionals is warranted because management of potential comorbidities and contributory factors may be particularly problematic.     

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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Pharmacokinetics of cysteamine bitartrate following intraduodenal delivery

Cysteamine is approved for the treatment of cystinosis and is being evaluated for Huntington's disease and non‐alcoholic fatty liver disease. Little is known about the bioavailability and biodistribution of the drug. The aim was to determine plasma, cerebrospinal fluid (CSF), and tissue (liver, kidney, muscle) cysteamine levels following intraduodenal delivery of the drug in rats pretreated and naïve to cysteamine and to estimate the hepatic first‐pass effect on cysteamine. Healthy male rats (n = 66) underwent intraduodenal and portal (PV) or jugular (JVC) venous catheterization. Half were pretreated with cysteamine, and half were naïve. Following intraduodenal cysteamine (20 mg/kg), serial blood samples were collected from the PV or the JVC. Animals were sacrificed at specific time points, and CSF and tissue were collected. Cysteamine levels were determined in plasma, CSF, and tissue. The C_max was achieved in 5–10 min from PV and 5–22.5 min from JVC. The PV‐C_max (P = 0.08), PV‐AUC_0–t (P = 0.16), JVC‐C_max (P = 0.02) and JVC‐AUC_0–t (P = 0.03) were higher in naive than in pretreated animals. Plasma cysteamine levels returned to baseline in ≤120 min. The hepatic first‐pass effect was estimated at 40%. Peak tissue and CSF cysteamine levels occurred ≤22.5 min, but returned to baseline levels ≤180 min. There was no difference in CSF and tissue cysteamine levels between naïve and pretreated groups, although cysteamine was more rapidly cleared in the pretreated group. Cysteamine is rapidly absorbed from the small intestine, undergoes significant hepatic first‐pass metabolism, crosses the blood brain barrier, and is almost undetectable in plasma, CSF, and body tissues 2 h after ingestion. Sustained‐release cysteamine may provide prolonged tissue exposure.     

Gas geyser syndrome: An important preventable cause of disabling neurological events

To bring to light the greatly hazardous effects of the use of flue less gas geysers in the domestic setting. Over a period of two years (2008 to 2010) twenty six cases were documented as presenting with unexplained neurological events while bathing in an ill ventilated bathroom with a functional flue less gas geyser. The cases were mainly of three distinct prototypes namely seizure like episodes seen in 11 patients, carbon monoxide intoxication in 13 patients with near cardiac arrest in 4, and as a precipitating factor for epilepsy as seen in 2 cases. Out of the 13 cases presenting as carbon monoxide intoxication 4 had subtle cognitive defects and 2 developed early Parkinsonian features on follow up. To increase awareness regarding gas geyser induced epilepsy and associated carbon monoxide intoxication, both of which are entirely preventable conditions. We also wish to emphasize the importance of stringent and universal implementation of gas geyser usage and installation laws.     

Granulomatous and lymphocytic hypophysitis – are they immunologically distinct?

Hypophysitis includes three histopathologically distinct entities – granulomatous, lymphocytic and xanthomatous forms. Etiopathogenesis and the immunological differences among these is not well characterized. This study aims to explore the immunopathogenesis of granulomatous and lymphocytic forms of hypophysitis. Demographic, clinical, endocrine function and radiological features of 33 histologically confirmed cases of hypophysitis were reviewed. Immunophenotyping of inflammatory component was performed in 13/33 cases. Visual disturbances (46%), headache (36%), polyuria/polydipsia (6%), menstrual disturbance (6%) and galactorrhoea (6%) were the frequent presenting symptoms. Endocrine abnormalities were noted in 11/18 cases evaluated (61%). Hypothyroidism was the most common endocrine abnormality (33.33%) followed by hyperprolactinaemia (22%) and hypocortisolism (16.66%). On neuroimaging, sellar mass with variable contrast enhancement was observed. On histology, granulomatous hypophysitis (GH) was more common (84.84%) than lymphocytic hypophysitis (LH) (15.15%). In GH, the infiltrate had almost equal proportions of CD3+ T cells and CD68+ histiocytes. Cytotoxic T cells (CD8+) predominated [CD4:CD8 < 1]. CD20+ B cell component ranged from <5% to 50%. Fibrosis, necrosis and giant cells accompanied GH. LH in contrast, had CD4+ T‐helper cell predominance [CD4: CD8 > 1]. CD68+ histiocytes constituted <20% and CD20+ B cells, 5–40% of the infiltrates. In conclusion, GH revealed cytotoxic T cell and histiocyte rich infiltrate in contrast to CD4+ T‐cell predominance in LH suggesting that the two forms have distinct immunological mechanisms in evolution, an autoimmune process in LH and type IV hypersensitivity response in GH.     

Standard immunosuppressive therapy of immune-mediated glomerular diseases

Glomerulonephritis (GN) accounts for 10%–20% of the total incident cases of end stage renal disease (ESRD), and is the third most common cause of ESRD after diabetes and hypertension in western countries. The pathogenesis of glomerulonephritis is prevalently immune mediated: humoral and cell-mediated immunity are involved, although the rationale for an etiological treatment is still lacking. In the last forty years, empirical treatment based upon the use of corticosteroids and/or immunosuppressive drugs have obtained excellent results in improving survival of both the patient and the kidney. Almost 95% of children affected by minimal change disease (MCD) achieve remission of proteinuria within 4 to 8 weeks of prednisone administration. In adults with focal segmental glomerulosclerosis (FSGS), prednisone induces complete or partial remission in the majority of patients, but a longer period of steroid treatment or the combination of calcineurin inhibitors or cytotoxic drugs can be needed. A percentage of 65%–70% of patients with idiopathic membranous nephropathy (MN) reach complete or partial remission with a 6-month course of therapy alternating glucocorticoids with alkylating agents. Glucocorticoids plus cyclophosphamide, and, on occasion, plasmapheresis are effective in 70%–90% of patients with ANCA-associated vasculitis (AAV). Fifty percent of responders relapse within the 3–5 years and currently, the mortality of AAV at 1 year exceeds 15%.This article is aimed to analyze the risk-to-benefit balance of steroids and conventional immunosuppressive regimens, focusing, for a sake of brevity, on idiopathic nephrotic syndrome (INS) and ANCA associated vasculitis.