Genetic analysis of the postsynaptic transmembrane X-linked neuroligin 3 gene in autism

Autism is a complex neurodevelopmental disorder, the prevalence of which has increased drastically in India in recent years. Neuroligin is a type I transmembrane protein that plays a crucial role in synaptogenesis. Alterations in synaptic genes are most commonly implicated in autism and other cognitive disorders. The present study investigated the neuroligin 3 gene in the Indian autistic population by sequencing and in silico pathogenicity prediction of molecular changes. In total, 108 clinically described individuals with autism were included from the North Karnataka region of India, along with 150 age-, sex-, and ethnicity-matched healthy controls. Genomic DNA was extracted from peripheral blood, and exonic regions were sequenced. The functional and structural effects of variants of the neuroligin 3 protein were predicted. One coding sequence variant (a missense variant) and four non-coding variants (two 5'-untranslated region [UTR] variants and two 3'-UTR variants) were recorded. The novel missense variant was found in 25% of the autistic population. The C/C genotype of c.551T>C was significantly more common in autistic children than in controls (p = 0.001), and a significantly increased risk of autism (24.7-fold) was associated with this genotype (p = 0.001). The missense variant showed pathogenic effects and high evolutionary conservation over the functions of the neuroligin 3 protein. In the present study, we reported a novel missense variant, V184A, which causes abnormal neuroligin 3 and was found with high frequency in the Indian autistic population. Therefore, neuroligin is a candidate gene for future molecular investigations and functional analysis in the Indian autistic population.

Mutation analysis and characterisation of F9 gene in haemophilia- B population of India

Background@#Hemophilia B (HB) is an X-linked bleeding disorder resulting from coagulation factor IX defects. Over 3,000 pathogenic, HB-associated mutations in the F9 gene have been identified. We aimed to investigate the role of F9 variants in 150 HB patients using sequencing technology. @*Methods@#F9 gene sequences were amplified from peripheral blood-derived DNA and sequenced on an Applied Biosystems (ABI) 3500 Sanger sequencing platform. Functional and structural predictions of mutant FIX were analyzed. @*Results@#Among 150 HB patients, 102 (68%), 30 (20%), and 18 (12%) suffered from severe, moderate, and mild HB, respectively. Genetic analysis identified 16 mutations, including 3 novel mutations. Nine mutations (7 missense and 2 stop-gain) were found to be pathogenic.Only 3 mutations (c.127C＞T, c.470G＞A, and c.1070G＞A) were associated with different severities. While 2 mutations were associated with mild HB cases (c.304C＞T and c.580A＞G), 2 (c.195G＞A and c.1385A＞G) and 3 mutations (c.223C＞T, c.1187G＞A, and c.1232G＞A) resulted in moderate and severe disease, respectively. Additionally, 1 mutation each was associated with mild-moderate (c.*1110A＞G) and mild-severe HB disease (c.197A＞T), 4 mutations were associated with moderate-severe HB cases (c.314A＞G, c.198A＞T, c.676C＞T, and c.1094C＞A). FIX concentrations were lower in the mutated group (5.5±2.5% vs. 8.0±2.5%). Novel p.E66D and p.S365 mutations were predicted to be pathogenic based on changes in FIX structure and function. @*Conclusion@#Novel single nucleotide polymorphisms (SNPs) largely contributed to the pathogenesis of HB. Our study strongly suggests that population-based genetic screening will be particularly helpful to identify risk prediction and carrier detection tools for Indian HB patients.

Prosthetic rehabilitation of a partially edentulous patient with maxillary acquired defect by a two-piece hollow bulb obturator [using a dentogenic concept]

Patients may face functional, aesthetic, and social distress because of the palatal defects. Prosthetic rehabilitation of maxillectomy or developmental defect can be challenging for prosthodontists. Prognosis of the prosthetic appliances can be affected not only by patients' own ability to adapt to the prosthesis but also by the factors like the remaining teeth, bony structure, and existing mucosa. Maxillary defects are usually developed by surgical intercession of the benign or malignant conditions and trauma cases. Speech, mastication and aesthetics can be hampered by any extent of palatal defect. During obturation of palatal/maxillectomy defects, the primary intent of the prosthodontist should be the shutting of the maxillectomy defect and parting of the oral cavity from the sinonasal openings by use of different bulb designs. In the present case, dentogenic concept has been applied while fabricating the two-piece hollow bulb obturator for restoration of the defect. Well known fact about the gravitational force is that it acts on maxillary obturator and reduces its retentive qualities, this can be counteracted to some extent by making the obturator hollow. Dentogenic concept is the skill, training, and procedure of generating the chimera of natural teeth in artificial teeth during prosthodontic restorations

Study on validity of a rapid diagnostic test kit versus light microscopy for malaria diagnosis in Ahmedabad city, India

Light microscopy of blood smears for diagnosis of malaria in the field has several limitations, notably delays in diagnosis. This study in Ahmedabad in Gujarat State, India, evaluated the diagnostic performance of a rapid diagnostic test for malaria [SD Bioline Malaria Ag P.f/Pan] versus blood smear examination as the gold standard. All fever cases presenting at 13 urban health centres were subjected to rapid diagnostic testing and thick and thin blood smears. A total of 677 cases with fever were examined; 135 [20.0%] tested positive by rapid diagnostic test and 86 [12.7%] by blood smear. The sensitivity of the rapid diagnostic test for malaria was 98.8%, specificity was 91.5%, positive predictive value 63.0% and negative predictive value 99.8%. For detection of Plasmodium falciparum the sensitivity of rapid diagnostic test was 100% and specificity was 97.3%. The results show the acceptability of the rapid test as an alternative to light microscopy in the field setting

Intrathecal morphine in two patients undergoing deep hypothermic circulatory arrest during aortic surgery: A case report / 대한마취과학회지

We retrospectively report the first use of intrathecal morphine prior to incision in two male patients undergoing a complex aortic reconstruction, who required complete circulatory arrest under deep hypothermia for intraoperative and postoperative pain control. We administered intrathecal morphine to two male patients undergoing circulatory arrest and deep hypothermia. Patients were fully heparinized prior to cardiopulmonary bypass. Deep hypothermic circulatory arrest was performed by cooling the patients to 18degrees C. Following the surgery, the neurologic status was monitored. The management of postoperative pain is a quality standard in health care. During the first 24 hours after surgery, we observed excellent analgesia without the associated side effects, thus, reducing the time required for pain control by the nursing staff. A successful analgetic strategy not only enhances the patient satisfaction, but may improve the postoperative outcome. However, complications, such as increased risk of epidural hematoma formation, are of special concern in cardiac surgery.

Present and future biochemical markers of cardiac diseases

Biochemical markers play an important role in the diagnosis of myocardial injuries and adopting a therapy that would improve clinical outcome. The earliest biomarkers, such as alanine aminotransferase and lactate dehydrogenase, have become redundant with the development of more sensitive and specific assays for latest cardiac markers. This development of assays for new marker proteins has contributed to a greater understanding of the pathophysiology of the disease spectrum of many myocardial diseases