Effect of Rat Strain Stereotactic Coordinates on Infarct Volume

Ischemic stroke makes up 87% of all hospital-admitted stroke cases annually; the primary treatment for these cases is intravenous administration of tPA within a 3.5 hour window from stroke onset. A long-term delayed ischemic stroke treatment proposed by this study was a combination of the pharmaceuticals Fluoxetine (SSRI), Simvastatin (statin), and ascorbic acid (Vitamin C). 51 adult rat subjects (10-12 months of age; 44 Sprague Dawley, 7 Long Evans) were given a combination of the drugs for 31 days. Drugs were given through voluntary oral administration via sugar cookie-dough balls to reduce inhibition of neurogenesis through stress-related glucocorticoid production. Drug combinations were as follows: FSA - 5 mg/kg fluoxetine, 0.5 mg/kg simvastatin and 20 mg/kg ascorbic acid; FS - 5 mg/kg fluoxetine, 0.5 mg/kg simvastatin; and the vehicle control. Endothelin-induced cortical stroke was administered using 2 different set of coordinates relative to bregma: Group 1 - (AP: 0.0 mm, ML: -2.5 mm) and (AP +1.5 mm; ML: -2.5 mm); Group 2 - (AP: 0.0 mm, ML: -2.5mm) and (AP +2.3; ML -2.5 mm). To analyze functional deficit, rats were subject to Montoya Staircase functional test once pre-stroke and twice post-stroke, and the Forelimb Asymmetry functional test once pre-stroke and thrice post-stroke. Results showed that Long Evans rats sustain a significantly larger infarct volume compared to Sprague Dawley rats using Group 2 coordinates; Group 1 cortical injection coordinates produced a larger infarct than Group 2 coordinates in FSA Sprague Dawley rats; drug treatment showed no effect on total infarct volume, however, this may be attributed to use of generic fluoxetine in Group 2 Sprague Dawley rats

Coronary angiographic profile characteristics in young patients with acute coronary syndrome and comparison with older patients with acute coronary syndrome

Background: CAD is a major cause of death worldwide. Indians are prone as a community to CAD at much younger age. This study examined the coronary angiographic profile characteristic in young (60 year).Methods: 192 patients with ACS aged less than 40 year and 200 patients with ACS aged more than 60 year were included in this study. Coronary angiographic profile characteristics were evaluated in young ACS patients and compared with that in older patients.Results: Young ACS patients often had angiographically normal coronary arteries, nonobstructive disease and single vessel disease than older patients (p value<0.05).Conclusions: Angiographically normal coronary arteries, nonobstructive disease, single vessel disease are more frequent in younger patients

Macroalgae as indicator species for shore platform zones of Dwarka, Gujarat, India

416-422Dwarka coast of Gujarat state in India has a stable shore platform. A study was carried out to identify indicator species among the sampled macroalgae to understand their spatial preferences on the shore platform zones. For this study, the shore platform was divided into three sections in north-south direction: Northern, central, and southern sections. These sections were further divided into three microzones in west-to-east direction based on their local geomorphology and tidal inundation characteristics for more detailed study. These microhabitat zones are: Cliff Base Zone (CBZ), Intertidal Mixed Zone (IMZ) and Subtidal Zone (STZ). To identify indicator species for each microzone, the shore platform was surveyed based on systematic random sampling for two years (April 2013 to April 2015). Line intercept transects and GPS-tagged photo quadrates were carried out from land to seaward as part of the sampling procedure. Indicator species were identified on the basis of a decision-rule when a single species belonged to only one microhabitat zone in all the three sections. Total 97 species of seaweeds were recorded in the shore platform of Dwarka. Out of these, 27 belonged to chlorophyta, 21 to phaeophyta and 49 to rhodophyta. Out of all these species, rhodophyta was found as the dominant group in the shore platform. Out of 97 species, only 12 species were identified as indicator species. Out of these, only one species was from phaeophyta group and eleven from rhodophyta group. This study shows indicator species of the microhabitat zones of the shore platform, with rhodophyta sp. as the prominent macroalgae group. Indicator species can act as proxy indicators of the microhabitats created by the local geomorphology and tidal regime on the shore platform

A case series of percutaneous tension band wiring technique for fixation of fractures of olecranon and patella

There are several advantages in the treatment of fractures by means of closed reduction. Percutaneous fixation is a type of biological fixation. The aim and objectives of this study are to demonstrate the technique of percutaneous tension band wiring in cases of transverse, non- comminuted olecranon and patella fractures and to decrease the soft tissue dissection, blood loss, chances of infection and to ensure speedy mobilization using the innovative percutaneous fixation technique. This retrospective study includes ten patients of olecranon and ten patients of patella operated by the same surgeon. All patients were operated with percutaneous tension band wiring for olecranon and patella. There were six males and four females with olecranon fractures. There were seven males and three females who suffered patella fractures. The average duration of surgery was 55 minutes and average follow up was 24±6 weeks. The suture removal was done at 2 weeks. All patients had full range of movements at six weeks with significantly improved DASH score and Oxford knee score. None of the patients had any complications. Percutaneous fixation decreases the chances of bleeding secondary to unnecessary soft tissue dissection, thereby decreasing the post-operative morbidity. It also, convincingly, decreases the chances of post-operative infection and promotes early mobilization. Closed reduction with percutaneous fixation is believed to be an innovative, safe, reliable and efficient method of managing these difficult fractures

Comprehensive serial molecular profiling of an “N of 1” exceptional non-responder with metastatic prostate cancer progressing to small cell carcinoma on treatment

Abstract Importance Small cell carcinoma/neuroendocrine prostate cancer (NePC) is a lethal, poorly understood prostate cancer (PCa) subtype. Controversy exists about the origin of NePC in this setting. Objective To molecularly profile archived biopsy specimens from a case of early-onset PCa that rapidly progressed to NePC to identify drivers of the aggressive course and mechanisms of NePC origin and progression. Design, setting, and participants A 47-year-old patient presented with metastatic prostatic adenocarcinoma (Gleason score 9). After a 6-month response to androgen deprivation therapy, the patient developed jaundice and liver biopsy revealed exclusively NePC. Targeted next generation sequencing (NGS) from formalin-fixed paraffin-embedded (FFPE)-isolated DNA was performed from the diagnostic prostate biopsy and the liver biopsy at progression. Intervention Androgen deprivation therapy for adenocarcinoma followed by multiagent chemotherapy for NePC. Main outcomes and measures Identification of the mutational landscape in primary adenocarcinoma and NePC liver metastasis. Whether the NePC arose independently or was derived from the primary adenocarcinoma was considered based on mutational profiles. Results A deleterious somatic SMAD4 L535fs variant was present in both prostate and liver specimens; however, a TP53 R282W mutation was exclusively enriched in the liver specimen. Copy number analysis identified concordant, low-level alterations in both specimens, with focal MYCL amplification and homozygous PTEN, RB1, and MAP2K4 losses identified exclusively in the NePC specimen. Integration with published genomic profiles identified MYCL as a recurrently amplified in NePC. Conclusions and relevance NGS of routine biopsy samples from an exceptional non-responder identified SMAD4 as a driver of the aggressive course and supports derivation of NePC from primary adenocarcinoma (transdifferentiation).http://deepblue.lib.umich.edu/bitstream/2027.42/113670/1/13045_2015_Article_204.pd

Right ventricular shape and function: cardiovascular magnetic resonance reference morphology and biventricular risk factor morphometrics in UK Biobank

Background The associations between cardiovascular disease (CVD) risk factors and the biventricular geometry of the right ventricle (RV) and left ventricle (LV) have been difficult to assess, due to subtle and complex shape changes. We sought to quantify reference RV morphology as well as biventricular variations associated with common cardiovascular risk factors. Methods A biventricular shape atlas was automatically constructed using contours and landmarks from 4329 UK Biobank cardiovascular magnetic resonance (CMR) studies. A subdivision surface geometric mesh was customized to the contours using a diffeomorphic registration algorithm, with automatic correction of slice shifts due to differences in breath-hold position. A reference sub-cohort was identified consisting of 630 participants with no CVD risk factors. Morphometric scores were computed using linear regression to quantify shape variations associated with four risk factors (high cholesterol, high blood pressure, obesity and smoking) and three disease factors (diabetes, previous myocardial infarction and angina). Results The atlas construction led to an accurate representation of 3D shapes at end-diastole and end-systole, with acceptable fitting errors between surfaces and contours (average error less than 1.5 mm). Atlas shape features had stronger associations than traditional mass and volume measures for all factors (p < 0.005 for each). High blood pressure was associated with outward displacement of the LV free walls, but inward displacement of the RV free wall and thickening of the septum. Smoking was associated with a rounder RV with inward displacement of the RV free wall and increased relative wall thickness. Conclusion Morphometric relationships between biventricular shape and cardiovascular risk factors in a large cohort show complex interactions between RV and LV morphology. These can be quantified by z-scores, which can be used to study the morphological correlates of disease

Detubularized isolated ureterosigmoidostomy in a complicated common cloaca: A case report

Urinary incontinence in a child secondary to a severe congenital anatomical disorder or due to complication of a previous surgery can be difficult to manage. Decisions can be especially hard when a redo procedure is being considered. We present one such case where a 6 year old girl previously operated for cloaca was brought with incontinence and after much consideration of options available, underwent a modified ureterosigmoidostomy to aid in her continence. The modification used was detubularized isolated ureterosigmoidostomy, described by Atta et al in 1996

Dolutegravir in pregnant mice is associated with increased rates of fetal defects at therapeutic but not at supratherapeutic levels

BACKGROUND: Dolutegravir (DTG) is a preferred regimen for all people with HIV including pregnant women, but its effects on the fetus are not fully understood. Periconceptional exposure to DTG has been associated with increased rates of neural tube defects (NTDs), although it is unknown whether this is a causal relationship. This has led to uncertainty around the use of DTG in women of reproductive potential. METHODS: Pregnant C57BL/6J mice were randomly allocated to control (water), 1x-DTG (2.5 mg/kg-peak plasma concentration ~3000 ng/ml - therapeutic level), or 5x-DTG (12.5 mg/kg-peak plasma concentration ~12,000 ng/ml - supratherapeutic level), once daily from gestational day 0.5 until sacrifice. DTG was administered with 50 mg/kg tenofovir+33.3 mg/kg emtricitabine. Fetal phenotypes were determined, and maternal and fetal folate levels were quantified by mass-spectrometry. FINDINGS: 352 litters (91 control, 150 1x-DTG, 111 5x-DTG) yielding 2776 fetuses (747 control, 1174 1x-DTG, 855 5x-DTG) were assessed. Litter size and viability rates were similar between groups. Fetal and placenta weights were lower in the 1x-DTG vs. control. Placental weight was higher in the 5x-DTG vs. control. Five NTDs were observed, all in the 1x-DTG group. Fetal defects, including microphthalmia, severe edema, and vascular/bleeding defects were more frequent in the 1x-DTG group. In contrast, defect rates in the 5x-DTG were similar to control. Fetal folate levels were similar between control and 1x-DTG, but were significantly higher in the 5x-DTG group. INTERPRETATION: Our findings support a causal relationship of DTG at therapeutic doses with increased risk for fetal defects, including NTDs at a rate that is similar that reported in the Tsepamo study for women exposed to DTG-based ART from conception. The non-monotonic dose-response relationship between DTG and fetal anomalies could explain the previous lack of fetal toxicity findings from pre-clinical DTG studies. The fetal folate levels suggest that DTG is unlikely to be an inhibitor of folate uptake. FUNDING: This project has been funded with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275201800001I