An Unexpected Lymphoma: A Rare Case of Primary Gastric Burkitt's Lymphoma.

Primary gastric Burkitt's lymphoma is an aggressive non-Hodgkin's lymphoma that has been rarely reported in the literature. The majority of primary gastric lymphomas are diffuse large B-cell lymphomas and mucosa-associated lymphoid tissue (MALT) lymphomas. Patients with primary gastric Burkitt's lymphoma can present with abdominal pain, hematemesis, melena, perforation, and obstruction. Diagnosis is made with a combination of clinical, radiological, and pathological findings. Treatment data are limited due to the limited cases reported. We present a case of a 47-year-old female who presented with diffuse abdominal pain, melena, and coffee-ground emesis that was diagnosed with primary gastric Burkitt's lymphoma following biopsies taken from a gastric ulcerated mass found on upper endoscopy.

Decentralized Multisite VBM Analysis During Adolescence Shows Structural Changes Linked to Age, Body Mass Index, and Smoking: a COINSTAC Analysis.

There has been an upward trend in developing frameworks that enable neuroimaging researchers to address challenging questions by leveraging data across multiple sites all over the world. One such open-source framework is the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC) that works on Windows, macOS, and Linux operating systems and leverages containerized analysis pipelines to analyze neuroimaging data stored locally across multiple physical locations without the need for pooling the data at any point during the analysis. In this paper, the COINSTAC team partnered with a data collection consortium to implement the first-ever decentralized voxelwise analysis of brain imaging data performed outside the COINSTAC development group. Decentralized voxel-based morphometry analysis of over 2000 structural magnetic resonance imaging data sets collected at 14 different sites across two cohorts and co-located in different countries was performed to study the structural changes in brain gray matter which linked to age, body mass index (BMI), and smoking. Results produced by the decentralized analysis were consistent with and extended previous findings in the literature. In particular, a widespread cortical gray matter reduction (resembling a 'default mode network' pattern) and hippocampal increase with age, bilateral increases in the hypothalamus and basal ganglia with BMI, and cingulate and thalamic decreases with smoking. This work provides a critical real-world test of the COINSTAC framework in a "Large-N" study. It showcases the potential benefits of performing multivoxel and multivariate analyses of large-scale neuroimaging data located at multiple sites.

Lithium response in bipolar disorder correlates with improved cell viability of patient derived cell lines.

Lithium is an effective, well-established treatment for bipolar disorder (BD). However, the mechanisms of its action, and reasons for variations in clinical response, are unclear. We used neural precursor cells (NPCs) and lymphoblastoid cell lines (LCLs), from BD patients characterized for clinical response to lithium (using the "Alda scale" and "NIMH Retrospective Life chart method"), to interrogate cellular phenotypes related to both disease and clinical lithium response. NPCs from two biologically related BD patients who differed in their clinical response to lithium were compared with healthy controls. RNA-Seq and analysis, mitochondrial membrane potential (MMP), cell viability, and cell proliferation parameters were assessed, with and without in vitro lithium. These parameters were also examined in LCLs from 25 BD patients (16 lithium responders and 9 non-responders), and 12 controls. MMP was lower in both NPCs and LCLs from BD; but it was reversed with in vitro lithium only in LCLs, and this was unrelated to clinical lithium response. The higher cell proliferation observed in BD was unaffected by in vitro lithium. Cell death was greater in BD. However, LCLs from clinical lithium responders could be rescued by addition of in vitro lithium. In vitro lithium also enhanced BCL2 and GSK3B expression in these cells. Our findings indicate cellular phenotypes related to the disease (MMP, cell proliferation) in both NPCs and LCLs; and those related to clinical lithium response (cell viability, BCL2/GSK3B expression) in LCLs.

The 5-Hydroxytryptamine signaling map: an overview of serotonin-serotonin receptor mediated signaling network.

The monoamine neurotransmitter, 5-Hydroxytryptamine or serotonin, is derived from tryptophan and synthesized both centrally and systemically. Fourteen structurally and functionally distinct receptor subtypes have been identified for serotonin, each of which mediates the neurotransmitter's effects through a range of downstream signaling molecules and effectors. Although it is most frequently described for its role in the etiology of neuropsychiatric and mood disorders, serotonin has been implicated in a slew of fundamental physiological processes, including apoptosis, mitochondrial biogenesis, cell proliferation and migration. Its roles as the neurotransmitter have also emerged in pathogenic conditions ranging from anorexia nervosa to cancer. This has necessitated the understanding of the signaling mechanisms underlying the serotonergic system, which led us to construct a consolidative pathway map, which will provide as a resource for future biomedical investigation on this pathway. Using a set of stringent NetPath annotation criteria, we manually curated molecular reactions associated with serotonin and its receptors from publicly available literature; the reaction categories included molecular associations, activation/inhibition, post-translation modification, transport, and gene regulation at transcription and translational level. We identified 90 molecules in serotonin-serotonin receptor pathway. We submitted the curated data to NetPath, a publicly available database of human signaling pathways, in order to enable the wider scientific community to readily access data and contribute further to this pathway.

Genetic testing for clinically suspected spinocerebellar ataxias: report from a tertiary referral centre in India.

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative syndromes, characterized by a wide range of muscular weakness and motor deficits, caused due to cerebellar degeneration. The prevalence of the syndromes of SCA varies across the world and is known to be linked to the instability of trinucleotide repeats within the high-end normal alleles, along with susceptible haplotype. We estimated sizes of the CAG or GAA repeat expansions at the SCA1, SCA2, SCA3, SCA12 and frataxin loci among 864 referrals of subjects to genetic counselling and testing (GCAT) clinic, National Institute of Mental Health and Neurosciences, Bengaluru, India, with suspected SCA. The most frequent mutations detected were SCA1 (n = 100 (11.6%)) and SCA2 (n = 98 (11.3%)) followed by SCA3 (n = 40 (4.6%)), FRDA (n = 20 (2.3%)) and SCA12 (n = 8 (0.9%)).

Elevated serum adenosine deaminase levels in neuroleptic-naïve patients with recent-onset schizophrenia.

The present study examined serum levels of adenosine deaminase (ADA), an adenosine metabolizing enzyme, in neuroleptic-naive patients with recent-onset schizophrenia and age-matched healthy comparison subjects. ADA levels were found to be higher among patients, and revealed a possible link between evening rise and severity of auditory hallucinations as well as morning rise and severity of avolition-apathy in patients with schizophrenia. These findings suggest the potential utility of serum ADA as a peripheral biomarker of schizophrenia.

Evidence for schizophrenia susceptibility alleles in the Indian population: An association of neurodevelopmental genes in case-control and familial samples.

Schizophrenia is a severe psychiatric disorder with lifetime prevalence of ~1% worldwide. A genotyping study was conducted using a custom panel of Illumina 1536 SNPs in 840 schizophrenia cases and 876 controls (351 patients and 385 controls from North India; and 436 patients, 401 controls and 143 familial samples with 53 probands containing 37 complete and 16 incomplete trios from South India). Meta-analysis of this population of Indo-European and Dravidian ancestry identified three strongly associated variants with schizophrenia: STT3A (rs548181, p=1.47×10(-5)), NRG1 (rs17603876, p=8.66×10(-5)) and GRM7 (rs3864075, p=4.06×10(-3)). Finally, a meta-analysis was conducted comparing our data with data from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ) that supported rs548181 (p=1.39×10(-7)). In addition, combined analysis of sporadic case-control association and a transmission disequilibrium test in familial samples from South Indian population identified three associations: rs1062613 (p=3.12×10(-3)), a functional promoter variant of HTR3A; rs6710782 (p=3.50×10(-3)), an intronic variant of ERBB4; and rs891903 (p=1.05×10(-2)), an intronic variant of EBF1. The results support the risk variants observed in the earlier published work and suggest a potential role of neurodevelopmental genes in the schizophrenia pathogenesis.

High-flexion mobile-bearing knees: impact on patellofemoral outcomes in 159 patients.

Ethnic cultural demands of the patient have encouraged surgeons to use high-flexion designs. It has been speculated that these high-flexion designs may produce higher incidence of patellofemoral complications over conventional designs. We wish to report 5- to 7-year follow-up of this design with special emphasis on patellofemoral outcomes. We performed a prospective study involving 159 patients who underwent computer-assisted simultaneous bilateral total knee arthroplasty (TKA) with high-flexion design. Patients were evaluated clinically using Knee Society score (KSS), Western Ontario and McMaster University Osteoarthritis (WOMAC) score, and Hospital for Special Surgery patella score with a minimum follow-up period of 5 years. At last follow-up, mean scores were KSS (88.7), WOMAC (48.5), and HSS (86.7). All the scores improved postoperatively. Average preoperative range of motion was 108 degrees, which improved to 132 degrees postoperatively. There was no evidence of loosening or spin out in our study. Our study shows that TKA done using high-flexion rotating platform design results in near normal patellofemoral tracking patterns with improvement in function. The level of evidence of the study is IV.

High-flexion posterior-stabilized total knee prosthesis: is it worth the hype?

High-flexion knee prosthesis was introduced with the aim of obtaining higher degree of flexion and good survivorship in patients with high functional demands or those requiring squatting, kneeling, etc., which is more common in Asians. Based on all the research and experience with this prosthesis, it was concluded that high flexion designs meet the need of deeper degrees of flexion in selected sets of patients only. Results were equal and comparable to the traditional standard posterior-stabilized total knee arthroplasty design and superior to it in terms of gaining more flexion and fulfilling activities, such as squatting, kneeling, and sitting cross-legged.

Multiple myeloma presenting as gingival hyperplasia.

Multiple myeloma is a malignant neoplasm that is characterized by a monoclonal proliferation of plasma cells. Oral and maxillofacial manifestations as an initial sign or symptom of multiple myeloma are rare. A 58-year-old male patient presented with generalized gingival enlargement for last 6 months. Based on clinical presentation, a diagnosis of gingival hyperplasia was made. After Phase I therapy, excisional biopsy was taken in anterior mandibular region and excised tissue was sent for histopathological examination. The histopathology report revealed a lining of stratified squamous epithelium with foci of ulceration. The subepithelial zone showed infiltration by sheets of mainly binucleate and multinucleate plasma cells, few cells being less differentiated. Rounded cytoplasmic inclusion bodies were identified in many of these cells. After a series of clinical investigations, a case of "multiple myeloma" was diagnosed. Patient presenting with generalized gingival hyperplasia should be worked up for systemic disease like multiple myeloma.

Simultaneous bilateral total knee replacement: a prospective study of 150 patients.

PURPOSE: To evaluate the safety of simultaneous bilateral total knee replacement (TKR). METHODS: 124 women and 26 men (mean age, 66 years) underwent simultaneous bilateral TKR for tricompartmental osteoarthritis using a posteriorstabilised, high-flexion implant. All patients underwent dobutamine stress echocardiography for detection of any silent cardiac comorbidity by a cardiologist. None had any adverse effect after testing. Five patients had positive outcome and underwent coronary angiography to detect any significant coronary blockage. Functional outcome was evaluated using the Knee Society Score (KSS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC). Tranexamic acid was given intravenously to reduce peri-operative blood loss. Femoral blocks and patient-controlled analgesia were used to facilitate early recovery. Aggressive physiotherapy was allowed. Patients were followed up at months 3, 6, and 12, and yearly thereafter. RESULTS: At the 2-year follow-up, the mean range of motion improved from 95º to 129º (p=0.032), the mean KSS from 120 to 158 (p<0.001), and the WOMAC from 51 to 88 (p=0.002). One patient developed patellar crepitus at week 6, which resolved with conservative treatment. Another patient developed infection in both knees at month 6. Despite salvage procedures, infection recurred after 3 months and the patient underwent bilateral arthrodesis. No patient developed deep vein thrombosis or pulmonary embolism, myocardial infarction, atrial fibrillation, or other cardiac event. CONCLUSION: Simultaneous bilateral TKR is safe for properly selected patients.

Outcome of subvastus approach in elderly nonobese patients undergoing bilateral simultaneous total knee arthroplasty: A randomized controlled study.

BACKGROUND: Subvastus approach in total knee arthroplasty (TKA) spares the quadriceps and may assist in faster rehabilitation. The present randomised controlled study was conducted to determine if the subvastus approach results in early recovery, faster mobilization, shorter hospital stay, and improved function. MATERIALS AND METHODS: 100 patients undergoing simultaneous bilateral TKA were randomized into two groups: subvastus group and medial parapatellar group. The patients were assessed clinically using VAS, time to straight leg raise, ability to stand with walker, ability to use a commode chair, ability to climb stairs, flexion at discharge, and day of discharge. Perioperative blood loss and duration of surgery were also compared. The patient were kept on same pain management and physiotherapy protocol. The evaluation was done at day 0,1,3 and at discharge. Statistical analyses tested the null hypotheses of no differences in patients treated with either group at 95% significance level (P < 0.05). RESULTS: The VAS score was significantly lower in subvastus group on day 1 and day 3. Also mean hospital stay was 2.04 days less in subvastus group. Patients with subvastus approach were able to perform straight leg raising 0.44 days earlier. Though time to stand with walker was same for both groups, the ability to use commode chair, and climb stairs was significantly early (P < 0.05) in the subvastus group. The average flexion at the time of discharge in subvastus and parapatellar group were 100.8 and 96.8°, respectively. The mean perioperative blood loss in subvastus group and parapatellar group were 343 ml and 372 ml, respectively. Average surgical time required for subvastus approach and parapatellar approach were 108.5 and 94.3 min, respectively. CONCLUSIONS: Subvastus approach produce appreciably less pain and faster mobilization due to lesser insult to quadriceps, thus assisting in early rehabilitation, shorter hospital stay, less expenditure, and more patient satisfaction.

Silent cardiac comorbidity in arthroplasty patients: an unusual suspect?

We studied 109 patients who were subjected to dobutamine stress echocardiography (DSE) for preoperative cardiac risk assessment before undergoing elective primary hip and knee arthroplasty. Patients were selected for DSE based on several criteria. There were 16 patients with history of ischemic heart disease and 93 patients without. Seven of the 93 patients showed a positive DSE test result, of which 5 developed postoperative cardiac events (P = .00). This study clearly shows that serious "silent" cardiac comorbidity can exist even in so-called healthier patients undergoing routine hip and knee arthroplasty. We believe that identifying these patients and treating them before arthroplasty can significantly improve the overall outcome of the surgery.

Duration of reappearance of gingival melanin pigmentation after surgical removal - A clinical study.

BACKGROUND: In dentistry, esthetics has a special place. Although gingival melanin pigmentation does not present a medical problem, clinicians are often faced with a challenge of achieving gingival esthetics. MATERIALS AND METHODS: A method of de-epithelialization of the pigmented gingiva using Kirkland's gingivectomy knife is described. Twenty patients who were conscious about their gingival melanin pigmentation were selected. The gingiva of the whole of the arch was abraded until the entire visible pigmentation was removed. Clinical observations for intensity of pigmentation were recorded at baseline and then after surgery at monthly intervals over a period of 9 months according to Dummett-Gupta Oral Pigmentation Index scoring criteria proposed by Dummett C. O. in 1964. RESULTS: The mean gingival melanin pigmentation score came down to 0.407 after 9 months as compared to preoperative score, which was 2.24. No repigmentation occurred in fair-complexioned persons. In persons with wheatish complexion, repigmentation was seen in 85.71% of the cases, but scores came down to 0.38 postoperatively as compared to 2.27 preoperatively. In dark-complexioned persons, repigmentation occurred in all cases, but the mean scores were 0.93 as compared to 2.40 preoperatively. The difference between preoperative and postoperative mean scores for each segment was put to statistical analysis by applying paired t test and was found to be significant. CONCLUSION: As this method has shown statistically significant results, it can be used in patients who are conscious of pigmented gingiva and want an esthetically satisfactory color.

Gingival tuberculosis.

Tuberculosis is a chronic specific granulomatous disease and a major cause of death in developing countries. The clinical presentation of tuberculosis lesions of oral cavity varies widely, including ulceration, diffuse inflammatory lesions, granulomas and fissures. Oral lesions usually appear as secondary to primary tuberculosis infection elsewhere, although primary infection of the oral mucosa by Mycobacterium tuberculosis has been described. We report a case of tuberculosis of gingiva, manifesting as gingival enlargement. Diagnosis was based on histopathological examination, complete blood count, X-ray chest and immunological investigations with detection of antibodies against Mycobacterium tuberculosis. Anti-tuberculous therapy was carried out for over six months. This case report emphasizes the need for dentists to include tuberculosis in the differential diagnosis of various types of gingival enlargements.

Duchenne muscular dystrophy: a clinical, histopathological and genetic study at a neurology tertiary care center in Southern India.

BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy that affects young boys and the dystrophin gene on the X chromosome has been found to be associated with the disorder. MATERIALS AND METHODS: In this prospective study, 112 clinically diagnosed DMD patients had muscle biopsy and were tested for exon deletions. Genotyping was also carried out at STR44, STR45, STR49 and STR 50 markers in 15 families. RESULTS: Of the 112 clinically suspected DMD patients, the diagnosis of DMD was confirmed by histopathology and/or genetics in 101 patients. The mean age of onset was 3.1+/-1.44 years (1-6 years) and the mean age at presentation was 8.0+/-3.1 years (1.1-18.0 years). Delayed motor milestones were present in 63 (62.3%) patients. The mean creatine kinase value was 11822.64+/-8206.90 U/L (1240-57,700). Eighty-four patients had muscle biopsy and immunohistochemistry was done in 60 muscle samples, all of which demonstrated absence of dystrophin staining. Of the 60 dystrophin-negative cases, 73% showed deletion of at least one exon. Single exon deletion was found in 20.4%. Distal hotspot Exons 45, 47, 49 and 50 were the commonly deleted xenons and the deletion rates were 36%, 35%, 33.7% and 38.5% respectively. CONCLUSIONS: In this study population in south India the deletion rate was 73% and were more frequent in the distal end exon. With the availability of genetic analysis, the first investigation of choice in DMD should be genetic studies and muscle biopsy should be considered only if the genetic tests are negative or not available.

Characterization of hnRNP K protein-RNA interactions.

The heterogeneous nuclear ribonucleoprotein K protein is an RNA-binding protein found in several subcellular compartments where it is thought to be involved in signaling multiple processes that compose gene expression. K protein contains three K homology (KH) domains that mediate RNA-binding. We used a serial analysis of gene expression (SAGE)-based strategy, yeast three-hybrid screen, RNA pull-down assays and computational analysis to characterize K protein-associated RNAs. We demonstrate that K protein interacts with many sense and antisense nuclear and mitochondrial transcripts through both direct and indirect binding. The highly specific direct binding of transcripts to K protein is mediated by a consensus sequence comprising three C-rich patches. Structural analysis suggests a three-prong interaction model whereby each of the three KH domains binds one of the C-rich patches. Genome-wide and yeast three-hybrid clone analysis revealed that these sequences are located preferentially in the 3' untranslated regions, which are known to regulate mRNA translation and processing.