Reserpine modulates neurotransmitter release to extend lifespan and alleviate age-dependent Aβ proteotoxicity in Caenorhabditis elegans

Aging is a debilitating process often associated with chronic diseases such as diabetes, cardiovascular and neurodegenerative diseases like Alzheimer's disease (AD). AD occurs at a very high incidence posing a huge burden to the society. Model organisms such as C. elegans become essential to understand aging or lifespan extension - the etiology, molecular mechanism and identification of new drugs against age associated diseases. The AD model, manifesting Aβ proteotoxicity, in C. elegans is well established and has provided valuable insights. Earlier, we have reported that Reserpine, an FDA-approved antihypertensive drug, increases C. elegans lifespan with a high quality of life and ameliorates Aβ toxicity in C. elegans. But reserpine does not seem to act through the known lifespan extension pathways or inhibition of its known target, vesicular monoamine transporter, VMAT. Reserpine's mode of action and the pathways it activates are not known. Here, we have evaluated the presynaptic neurotransmitter(s) release pathway and identified acetylcholine (ACh) as the crucial player for reserpine's action. The corroborating evidences are: i) lack of lifespan extension in the ACh loss of function (hypomorphic) - synthesis (cha-1) and transport (unc-17) mutants; ii) mitigation of chronic aldicarb effect; iii) lifespan extension in dopamine (cat-2) and dopamine and serotonin (bas-1) biosynthetic mutants; iv) no rescue from exogenous serotonin induced paralysis in the AD model worms; upon reserpine treatment. Thus, modulation of acetylcholine is essential for reserpine's action.     

A rare presentation of hepatic and splenic cystic malignant fibrous histiocytoma: A case report and literature review

INTRODUCTIONMalignant fibrous histiocytoma is one of the most common soft tissue sarcomas in late adult life. But primary visceral malignant fibrous histiocytoma is a very rare entity. In peripheries, it is known to have an aggressive behavior but its biological pattern when involving liver and spleen is not well understood due to the rarity of its occurrence.PRESENTATION OF CASEA case of malignant fibrous histiocytoma of the liver and spleen as multiple cystic lesions in a 30 years old man is reported. The patient presented with hepatosplenomegaly resulting in central abdominal distention. Pre-operative investigations pointed toward the diagnosis of malignant cystic disease. The tumor presented as multiple hepatic cysts with massive hepatomegaly and splenomegaly. These cysts contained hemorrhagic fluid. Biopsy revealed highly cellular pleomorphic spindle cells fascicles arranged in storiform pattern at places with frequent mitoses. Immunohistochemistry revealed viamentin positivity. The tumor is compared with previous case reports.DISCUSSIONMalignant fibrous histiocytoma of liver and spleen has been mentioned in the literature as isolated case reports and most of these present as solid lesions but presentation as multiple cysts is also a possibility as was seen in this patient. It can be confirmed only on histo-pathology supported by immunohistochemistry. The disease carries guarded prognosis due to its rapid progression and diagnostic dilemma pre-operatively.CONCLUSIONThis rare malignancy affecting the viscera can be diagnosed only with high index of suspicion and awareness regarding its presentation can help surgeons deal with it.     

Ethnic density,cultural congruity and mental illness in migrants

Migration is now well understood to be associated with mental illness in many parts of the world. However, the cause and effects of migration that are associated with mental illness continue to be a point of debate. The Ethnic Density concepts give a plausible explanation. On further elaboration, we conclude that a move from a sociocentric society to an egocentric one leads to more distress and more mental illness. Cultural incongruity faced by a migrant in an alien culture has a similar impact. Several theories on migratory distress have tried to explain psychiatric morbidity: high morbidity at source, individual predisposition, stress, misdiagnosis and racial discrimination. We hypothesise that the impact of ethnic density and cultural congruity occurs in a social context.     

Prevalence of thoracic scoliosis in adults 25 to 64 years of age detected during routine chest radiographs

Purpose

To investigate the prevalence of thoracic scoliosis and determine the effect of both age and gender on coronal curve magnitude among asymptomatic adults aged 25–64 years old, using standing posterior-anterior chest radiographs.

Methods

This was a retrospective, cross-sectional study evaluating 500 randomly selected digital posterior-anterior chest radiographs taken at a single institution on an outpatient basis between January 2010 and December 2011. Males (n = 184) and females (n = 316) ranged in age from 25 to 64 years. Patients with symptoms of back pain; including a history of back pain, spinal instrumentation, or known pre-existing spinal disease were excluded. Radiographs were evaluated using Centricity PACS Web Diagnostic 2.1 system (General Electric Co. Fairfield, CT). Coronal Cobb angle measurements of the thoracic spine were quantified by the authors, with scoliosis defined as coronal curves greater than 10°. Curvatures were subdivided into groups: a control group with coronal curves less than 10°, curves measuring 10° to 19°, 20° to 29°, and greater than 30°. The effect of age and gender on curve magnitude was examined using Pearson correlation analysis and linear regression analysis.

Results

There was a 13.4 % (67 patients) prevalence of thoracic scoliosis. The prevalence among asymptomatic males was 10.9 %, while the prevalence among asymptomatic females was 14.9 %. 11.6 % demonstrated a coronal curvature between 10° and 19° (58 patients), 1.6 % between 20° and 29° (8 patients), and 0.2 % greater than 30° (1 patient). Age and gender were not found to be significant independent predictors of curve severity.

Conclusions

We found a 13.4 % prevalence of thoracic scoliosis among asymptomatic adults aged 25–64 years on routine outpatient chest radiographs. 11.6 % of patients demonstrated a coronal curvature between 10° and 19°. Unlike prior studies evaluating asymptomatic thoracic curves in elderly patients, age and gender did not significantly affect curve magnitude in our younger cohort. These data may provide a reference point to help clinicians counsel asymptomatic patients diagnosed with thoracic scoliosis on routine chest radiographs.

     

Melioidosis: a review of orthopedic manifestations, clinical features, diagnosis and management

Melioidosis is an infectious disease caused by gram-negative soil-dwelling bacillus Burkholderia pseudomallei. Musculoskeletal melioidosis mimics other infections both clinically and radiologically. An extensive literature review has been performed over musculoskeletal melioidosis through various search engines such as Pubmed, Embase, Medscape, Altavista and Google. Diagnosis requires a high index of clinical suspicion and is dependent on microbiological confirmation. Prompt treatment with long-term combination antibiotics in high dosages and surgical drainage of abscesses improves survival.     

Etiology-Based Classification of Adjacent Segment Disease Following Lumbar Spine Fusion

Background

Adjacent segment disease (ASDz) is a potential complication following lumbar spinal fusion. A common nomenclature based on etiology and ASDz type does not exist and is needed to assist with clinical prognostication, decision making, and management.

Questions/Purposes

The objective of this study was to develop an etiology-based classification system for ASDz following lumbar fusion.

Methods

We conducted a retrospective chart review of 65 consecutive patients who had undergone both a lumbar fusion performed by a single surgeon and a subsequent procedure for ASDz. We established an etiology-based classification system for lumbar ASDz with the following six categories: “degenerative” (degenerative disc disease or spondylosis), “neurologic” (disc herniation, stenosis), “instability” (spondylolisthesis, rotatory subluxation), “deformity” (scoliosis, kyphosis), “complex” (fracture, infection), or “combined.” Based on this scheme, we determined the rate of ASDz in each etiologic category.

Results

Of the 65 patients, 27 (41.5%) underwent surgery for neurogenic claudication or radiculopathy for adjacent-level stenosis or disc herniation and were classified as “neurologic.” Ten patients (15.4%) had progressive degenerative disc pathology at the adjacent level and were classified as “degenerative.” Ten patients (15.4%) had spondylolisthesis or instability and were classified as “instability,” and three patients (4.6%) required revision surgery for adjacent-level kyphosis or scoliosis and were classified as “deformity.” Fifteen patients (23.1%) had multiple diagnoses that included a combination of categories and were classified as “combined.”

Conclusion

This is the first study to propose an etiology-based classification scheme of ASDz following lumbar spine fusion. This simple classification system may allow for the grouping and standardization of patients with similar pathologies and thus for more specific pre-operative diagnoses, personalized treatments, and improved outcome analyses.