Association of NOTCH4 and ACHE gene polymorphism in Alzheimer's disease of Gujarat cohort.

BACKGROUND: Alzheimer's Disease (AD) is the most common form of dementia, affecting cognitive and behavioral functions. AD is a complex disease resulting from the modest effect of gene interaction and environmental factors, as a result of which the exact pathogenesis is still unknown. AIM: The aim of the present study was to investigate the association between variants of 98 targeted genes with Alzheimer's disease phenotype. METHOD: A total of 98 genes from 32 AD cases and 11 controls were genotyped using the Haloplex target enrichment method and the PCR-RFLP approach.Association analysis was performed using the PLINK tool to identify the variant significantly associated with AD. Functional enrichment analysis and network analysis was performed using ClueGo and String database respectively. The Expression Quantitative Trait Loci (eQTL) analysis using the Genotype Tissue Expression (GTEx) dataset to explore the possible implication of the variant on the expression of one or more genes in different brain regions and whole blood. RESULT: Association analysis showed significant association of 19 variant assigned to 16 genes with Alzheimer's with p-value < 0.05 with rs367398/NOTCH4 only variant that passed multiple test corrections. Functional enrichment analysis showed association of these genes with AD. ClueGo and network analysis utilizing the String database suggested that genes are directly and indirectly linked to the AD pathogenesis. eQTL analysis revealed that the rs367398/NOTCH4 and rs1799806/ACHE variant showed significant eQTL for the neighbouring genes. CONCLUSION: The present study showed the possible role of 16 genes in AD pathogenesis, especially highlighting the role of rs367398/NOTCH4 and rs1799806/ACHE. However further investigation with large cohort is required to study and validate the implication of these variants in the AD pathogenesis.

The efficacy of oral ketamine in severely depressed patients at high risk of suicide.

BACKGROUND: Ketamine is most easily and inexpensively administered by the oral route and in racemic form. Oral racemic ketamine may be an important approach to the emergency management of suicide risk in clinical settings, especially in third world countries, that have a limited range of available healthcare resources. METHODS: In a prospective, uncontrolled, open-label investigation, we studied 30 severely depressed inpatients who consented to participate in a pilot hospital service offering ketamine for management of high suicide risk. Patients sipped a solution of racemic ketamine (150 mg) across 10-15 min in 3 alternate day sessions. Patients were assessed using the Modified Scale for Suicidal Ideation (MSSI), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Improvement-Severity (CGI-S) scale at baseline and 1 day after the last ketamine session. RESULTS: There was statistically and clinically significant improvement on all outcomes. Mean (standard deviation) MSSI scores dropped from 25.1(1.8) to 17.3(5.6), MADRS scores from 28.8(3.4) to 21.9(3.6), and CGI-S scores from 6.0(0.2) to 3.6(0.9). At endpoint, MSSI scores had dropped from severe to low or mild-to-moderate in 67% of patients. The 90 ketamine sessions were uneventful; the treatment was well tolerated and no patient dropped out. CONCLUSION: Oral racemic ketamine may be a useful and potentially life-saving approach to the emergency management of severely depressed patients at high risk of suicide.

Paclitaxel-loaded PEG-PE-based micellar nanopreparations targeted with tumor-specific landscape phage fusion protein enhance apoptosis and efficiently reduce tumors.

In an effort to improve the therapeutic index of cancer chemotherapy, we developed an advanced nanopreparation based on the combination of landscape phage display to obtain new targeting ligands with micellar nanoparticles for tumor targeting of water-insoluble neoplastic agents. With paclitaxel as a drug, this self-assembled nanopreparation composed of MCF-7-specific phage protein and polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles showed selective toxicity to target cancer cells rather than nontarget, non cancer cells in vitro. In vivo, the targeted phage micelles triggered a dramatic tumor reduction and extensive necrosis as a result of improved tumor delivery of paclitaxel. The enhanced anticancer effect was also verified by an enhanced apoptosis and reduced tumor cell proliferation following the treatment with the targeted micellar paclitaxel both in vitro and in vivo. The absence of hepatotoxicity and pathologic changes in tissue sections of vital organs, together with maintenance of overall health of mice following the treatment, further support its translational potential as an effective and safe chemotherapy for improved breast cancer treatment.

A case report on myxedema madness: curable psychosis.

Myxedema madness is a very rare but established entity. A psychotic patient having hypothyroid features should always be evaluated regarding same. A 30-year-old female without known significant past medical history had, for the past one and half year, continuous persecutory and referential delusions; second and third person auditory hallucinations, facial puffiness and Brief Psychiatric Rating Scale (BPRS) score of 41 on admission. Her thyroid profile was: Thyroid stimulating hormone - 63.71 mIU/L, Free tri iodo threonine (FT3) - 2.1 pg/ml, free tetra iodo thyronine (FT4) - 0.6 ng/ml with normal ultrasound-thyroid. Patient was started on thyroxin 100 µg with a low dose risperidone 2 mg. Risperidone was withdrawn over a week and the patient was discharged on thyroxin alone with BPRS score of 8 and absence of delusions and hallucinations.

Internet addiction and its correlates among high school students: a preliminary study from Ahmedabad, India.

PURPOSE: Internet addiction (IA) is an upcoming and less researched entity in psychiatry, especially in low and middle income countries. This is the first such effort to study IA amongst Indian school students of class 11th and 12th and to find its correlation with socio-educational characteristics, internet use patterns and psychological variables, namely depression, anxiety and stress. METHODS: Six hundred and twenty one students of six English medium schools of Ahmedabad participated, of which 552 (88.9%) who completed forms were analyzed. Young's Internet Addiction Test and 21 item Depression Anxiety and Stress Scale were used to measure IA and psychological variables respectively. Logistic regression analysis was applied to find the predictors of IA. RESULTS: Sixty-five (11.8%) students had IA; it was predicted by time spent online, usage of social networking sites and chat rooms, and also by presence of anxiety and stress. Age, gender and self-rated academic performance did not predict IA. There was a strong positive correlation between IA and depression, anxiety and stress. CONCLUSIONS: IA may be a relevant clinical construct, and needs extensive research even in developing nations. All high school students suffering from depression, anxiety and stress must be screened for IA, and vice versa.

Alternative Psychosis - Is it a Defined Clinical Entity?

Following seizure control with antiepileptic drugs and normalization of electroencephalogram, behavioral problem may appear for the first time in an epileptic patient. This phenomenon has been termed 'alternative psychosis'. However, it remains poorly understood in absence of any definite diagnostic criteria, and there are no specific guidelines to treat the condition. Here we report a case of an untreated patient of epilepsy of 13 years duration, who had onset of first episode non-specific aggressive behavior within 1 week after starting treatment with sodium valproate, which responded adequately to a short course of low dose risperidone. We conclude that alternative psychosis may have a variable clinical presentation and may respond favorably to antipsychotic drugs.

Intraventricular chordoid meningioma in a child: fever of unknown origin, clinical course, and response to treatment.

The authors present the case of an 11-year-old boy with an intraventricular chordoid meningioma, which is a rare presentation of prolonged fever of unknown origin due to a rare tumor in a rare location. The fever resolved after excision of the lesion. Subsequent imaging revealed recurrence at 1 year. After a repeat excision and fractionated radiotherapy, the patient has remained disease free 5 years after the first surgery. Very few cases of intraventricular chordoid meningioma have been reported to date. The pathological features and clinical course are described. A review of the literature describing management options for this tumor type, recently found to have a higher recurrence rate, is described herein.

Isolated intracranial Rosai Dorfman disease.

Rosai Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a benign histiocytic proliferative disorder mainly affecting the lymph nodes. Although several cases of extra-nodal involvement have been reported previously, central nervous system involvement, particularly in the absence of nodal disease is extremely rare. We report a case of isolated intracranial RDD occurring in a relatively elder patient, which was shown by histological examination to have a dura-based involvement.

Mycetoma: Nonvenereal perineal lesions.

Mycetoma is a chronic, granulomatous disease of the skin, and subcutaneous tissue, which sometimes involves muscle, bones, and neighboring organs. It is characterized by tumefaction, abscess formation, and fistulae with discharge of grains from sinuses. Mycetoma can be caused by various species of fungi (eumycetoma) and aerobic actinomycetes (actinomycetoma), which occur as saprophytes in soil or plants. A tentative diagnosis sufficient to initiate treatment may be made on the basis of grain color. For instance, melanoid grains are always caused by fungi and ochroid or pale grains by actinomycetes. Although this is not the thumbrule, there are exceptional reports too. As trauma favors infection, most lesions are on the foot and lower leg but they may occur anywhere on the body mimicking actinomycosis. However, lab investigations and culture are important tool to differentiate apart from the clinical picture. We are reporting atypical case with unusual site of presentation (perineum and thigh) of mycetoma.

Primary chondrosarcoma of the heart.

Primary cardiac chondrosarcoma is extremely rare with very few cases reported in the literature. Most cardiac chondrosarcomas described in the literature are secondary. We report herein a case of 22-year-old man who presented with easy fatigability, which the general practitioner diagnosed as mitral stenosis clinically. Echocardiography showed left atrial mass, possibly myxoma. The histopathology of the excised mass revealed mesenchymal chondrosarcoma, confirmed by immunohistochemistry. Clinical and radiological studies did not reveal any other neoplasm.