The intron 4c allele of the NOS3 gene is associated with ischemic stroke in African Americans

Background  

Ischemic stroke is the most common cause of disability in North America and in addition to the generally accepted risk factors, there is increasing evidence for the potential pathophysiological role of genes. One of these genes, the endothelial nitric oxide synthase gene (NOS3) has been reported as a genetic risk factor for ischemic stroke. To independently confirm and extend the results of these previous reports, we investigated this gene as a risk factor for stroke in an ethnically diverse study population.     

Age-dependent variation of T1 and T2 relaxation times of adenocarcinoma in mice

The T1 and T2 values of adenocarcinoma EO 771 inoculated into the hind leg of mice are characterized and correlated with the histopathologic state of the tumor. Growth-dependent changes (indicated by a T1 of 630-910 msec and a T2 of 68-185 msec) can be separated into four characteristic phases. The increase in relaxation times in the early phases (A and B) is due to an increasing amount of viable tumor tissue relative to normal muscle tissue. In the later phases (C and D), a decline of the relaxation parameters is observed that is parallel to an increase in the fraction of necrotic tissue. By multiexponential analysis, two relaxation components (indicated by and, respectively) for T1 and T2 and the corresponding fractions alpha 1 and alpha 2 can be observed for both tumor and surrounding muscle tissue. A tissue criterion ("magnetic resonance fingerprint") is defined by a combination of these multiple parameters. This criterion allows separation of not only muscle and tumor tissue but also viable (early state) and necrotic (late state) tumor tissue.     

Physical activity,mental health and well-being of adults during initial COVID-19 containment strategies: A multi-country cross-sectional analysis

ObjectivesTo assess physical activity (PA), mental health and well-being of adults in the United Kingdom (UK), Ireland, New Zealand and Australia during the initial stages of National governments’ Coronavirus disease (COVID-19) containment responses.DesignObservational, cross-sectional.MethodsAn online survey was disseminated to adults (n = 8,425; 44.5 ± 14.8y) residing in the UK, Ireland, New Zealand and Australia within the first 2-6 weeks of government-mandated COVID-19 restrictions. Main outcome measures included: Stages of Change scale for exercise behaviour change; International Physical Activity Questionnaire (short-form); World Health Organisation-5 Well-being Index; and the Depression Anxiety and Stress Scale-9.ResultsParticipants who reported a negative change in exercise behaviour from before initial COVID-19 restrictions to during the initial COVID-19 restrictions demonstrated poorer mental health and well-being compared to those demonstrating either a positive-or no change in their exercise behaviour (p < 0.001). Whilst women reported more positive changes in exercise behaviour, young people (18-29y) reported more negative changes (both p < 0.001). Individuals who had more positive exercise behaviours reported better mental health and well-being (p < 0.001). Although there were no differences in PA between countries, individuals in New Zealand reported better mental health and well-being (p < 0.001).ConclusionThe initial COVID-19 restrictions have differentially impacted upon PA habits of individuals based upon their age and sex, and therefore have important implications for international policy and guideline recommendations. Public health interventions that encourage PA should target specific groups (e.g., men, young adults) who are most vulnerable to the negative effects of physical distancing and/or self-isolation.     

Prevention of graft rejection following bone marrow transplantation

Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.     

Origin and significance of diastolic Doppler flow signals in the left ventricular outflow tract

Diastolic Doppler flow signals (greater than or equal to 0.2 m/s) in the left ventricular outflow tract have not been well characterized, and their origin and significance remain controversial. Fifty-nine patients (55 +/- 16 years of age) with technically good Doppler echocardiographic studies were studied prospectively. There were 14 normal subjects, 21 patients with left ventricular hypertrophy, 10 with dilated cardiomyopathy and 14 with other cardiac disease. The rhythm was sinus in 55 and atrial fibrillation in 4. Two distinct Doppler flow signals were detected in the left ventricular outflow tract during diastole. These were termed E' (early) and A' (active) because they occurred 40 to 100 ms after higher velocity mitral inflow E (passive filling) and A (atrial contraction) signals. Among 59 patients, E' signals were present in 48 (81%) and had a mean velocity of 0.41 +/- 0.23 m/s. In 55 patients with normal sinus rhythm, A' signals were present in 52 (95%) and had a mean velocity of 0.52 +/- 0.24 m/s. No A' signals were present in the four patients with atrial fibrillation. The E' and A' velocities by pulsed wave Doppler ultrasound were low at the left ventricular apex and increased along the basal septum in the left ventricular outflow tract. Prominent A' velocities (greater than or equal to 0.45 m/s) were seen in 62% of patients with left ventricular hypertrophy, 50% of normal subjects and 10% of patients with dilated cardiomyopathy. The A' velocity was higher in patients with left ventricular hypertrophy (0.63 +/- 0.26 m/s) than in those with a normal heart (0.45 +/- 0.16 m/s; p less than 0.05) or dilated cardiomyopathy (0.25 +/- 0.13 m/s; p less than 0.01). The major determinants of diastolic outflow tract velocity were the mitral inflow E and A velocities and left end-diastolic dimension, particularly when combined (r = 0.64, p less than 0.0001 for E'; r = 0.72, p less than 0.0001 for A'). Distinctive E' and A' Doppler outflow tract signals result from mitral inflow and may be detected in most patients with normal heart size. These E' and A' velocities increase from apex to base and are more prominent in patients with a small, normally contracting heart or left ventricular hypertrophy.     

Proliferating human granulosa-lutein cells in long term monolayer culture: expression of aromatase, cholesterol side-chain cleavage, and 3 beta-hydroxysteroid dehydrogenase

The development of long term culture conditions with which to study the regulation of expression of aromatase, cholesterol side-chain cleavage enzyme, and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in human granulosa-lutein cells is described in this report. Conditions have been established for the dispersal, growth, freezing, and storage of functional human granulosa cells isolated from preovulatory follicles of women undergoing laparoscopy for gamete intrafallopian tube transfer and in vitro fertilization procedures. Optimal growth conditions for human granulosa-lutein cells were determined by plating cells at a low density and testing the capacity of a variety of culture conditions to support growth. A combination of fetal bovine serum (FBS), horse serum, and the serum substitute UltroSer G was found to increase cell number to maximal levels, 8- to 10-fold higher than with sera alone. Human granulosa-lutein cells grown under these conditions had a doubling rate of 36-40 h and were morphologically distinct from human theca interna cells grown under similar conditions. Human granulosa-lutein cells treated with forskolin retracted and rounded up, whereas cultures of human ovarian theca interna cells or human fibroblasts treated similarly did not retract. Human granulosa-lutein cells were grown for successive passages and transferred to serum-free medium containing forskolin, LH, hCG, or cholera toxin. Addition of these agents resulted in a time- and dose-dependent increase in aromatase activity and progesterone secretion. In these studies FSH treatment was found not to increase aromatase activity. In a study of the time course of 3 beta HSD activity in the absence of forskolin under serum-free conditions, it was found that 3 beta HSD activity increased 3-fold during the 72-h treatment period. Forskolin-stimulated 3 beta HSD activity also increased in a time-dependent manner, with levels in treated cells 3-fold higher than those in control cells. Northern analysis performed on total RNA obtained from forskolin- or hCG-stimulated granulosa-lutein cells confirmed that the increase in aromatase activity was associated with a corresponding increase in levels of mRNA specific for aromatase cytochrome P-450. Levels of mRNA encoding cholesterol side-chain cleavage cytochrome P-450 were similarly increased in cells treated with forskolin compared with unstimulated values at each of the time points investigated. Under serum-free conditions in the absence of stimulation, the 3.4-kilobase band of aromatase cytochrome P-450 mRNA was detectable.(ABSTRACT TRUNCATED AT 400 WORDS)     

The β-tubulin gene of Epichloë typhina from perennial ryegrass (Lolium perenne)

Summary Epichloë typhina is a biotrophic fungal pathogen which causes choke disease of pooid grasses. The anamorphic state, Acremonium typhinum, is placed in the section Albo-lanosa along with related, mutualistic, seeddisseminated endophytes. As an initial study of gene structure and evolution in Epichloë and related endophytes, the -tubulin gene, tub2, of the perennial ryegrass choke pathogen (EtPRG) was cloned and sequenced. The coding sequence and the predicted -tubulin amino acid sequence were highly homologous to the Neurospora crassa homologs, and to one of the two -tubulin genes of Emericella nidulans. However, two introns characteristic of the N. crassa and Em. nidulans genes were absent in the E. typhina gene. Furthermore, one of the remaining introns possessed the uncommon 5 splice junction, GC. In contrast to published observations concerning other Ascomycetes, a mutant of EtPRG, selected for resistance to methyl-2-benzimidazole carbamate (benomyl), possessed no alteration of its -tubulin coding sequence.     

A technique for intraoperative creation of patient-specific titanium mesh implants

Prefabricated, patient-specific alloplastic implants for cranioplasty reduce surgical complexity, decrease operative times, minimize exposure and risk of contamination, and have resulted in improved aesthetic results. However, in creating a prefabricated custom implant using a patient’s computed tomography data, a stable, unalterable defect must be clearly defined before surgery. In the event that an intraoperative modification of an exiting skull defect is required, or in cases of tumour resection in which the size of the skull defect is unknown preoperatively, these prefabricated implants cannot be used. The ideal method for alloplastic cranioplasty would enable cost-effective creation of a patient-specific implant with the capacity for intraoperative modification.The present article describes a novel technique of cranioplasty that uses a patient’s computed tomography data to create a custom forming tool (ie, mold), enabling intraoperative creation of a patient-specific titanium mesh implant. The utility of these implants in creating a custom reconstructive solution in cases in which the size of the skull defect is unknown preoperatively will be demonstrated using two case presentations.     

Predictors and prevalence of patients undergoing additional kyphoplasty procedures after an initial kyphoplasty procedure

Background context

Vertebral cement augmentation, including kyphoplasty, has been shown to be a successful treatment for pain relief for vertebral compression fracture (VCF). Patients can sustain additional symptomatic VCFs that may require additional surgical intervention.

Purpose

To examine the prevalence and predictors of patients who sustain additional symptomatic VCFs that were treated with kyphoplasty.

Study design

A retrospective review of patients who previously underwent kyphoplasty for VCFs and had additional VCFs that were treated with kyphoplasty.

Patient sample

A total of 256 patients underwent kyphoplasty for VCFs from 2000 to 2007 at a single medical center.

Outcome measures

The outcome measure of interest was the need for an additional kyphoplasty procedure for a symptomatic VCF.

Methods

Risk factors such as age, sex, smoking status, and steroid use were assessed, as well as bisphosphonate use. Sagittal spinal alignment via Cobb angles for thoracic, thoracolumbar, and lumbar regions was assessed.

Results

About 22.2% of the patients had an additional symptomatic VCF that was treated with a kyphoplasty procedure. Steroid use was the only significant risk factor for predicting patients with additional symptomatic VCFs who underwent additional kyphoplasty. The average time to the second VCF was 33 days. Adjacent-level VCFs were most common in the thoracic and thoracolumbar spine. Bisphosphonate use was not shown to be protective of preventing additional VCFs during this follow-up period.

Conclusion

This is the first single-center review of a large cohort of patients who underwent additional-level kyphoplasty for symptomatic VCFs after an index kyphoplasty procedure. Our results suggest that patients with a VCF who use chronic oral steroids should be carefully monitored for the presence of additional symptomatic VCFs that may need surgical intervention. Patients with prior thoracic VCFs who have additional back pain should be reevaluated for a possible adjacent-level fracture.     

Are vitamin B12 and folate deficiency clinically important after roux-en-Y gastric bypass?

Although iron, vltamm B₁₂, and folate deficiency have been well documented after gastric bypass operations performed for morbid obesity, there is surprisingly little information on either the natural course or the treatment of these deficiencies in Roux-en-Y gastric bypass (RYGB) patients Durmg a l0-year period, a complete blood count and serum levels of iron, total iron-binding capacity, vltamin B₁₂, and folate were obtained in 348 patients preoperatively and postoperatively at 6-month intervals for the first 2 years, then annually thereafter The principal objectives of this study were to determine how readily patients who developed metabolic deficiencies after Roux-en-Y gastric bypass responded to postoperative supplements of the deficient micronutrient and to learn whether the risk of developmg these deficiencies decreases over time Hemoglobin and hematocrit levels were slgnificantly decreased at all postoperative intervals in comparison to preoperative values Moreover, at each successive interval through 5 years, hemoglobin and hematocrit were decreased signifiantly compared to the preceding interval Folate levels were significantly increased compared to preoperative levels at all time intervals Iron and vltamin B₁₂ levels were lower than preoperative measurements and remained relatively stable postoperatively Half of the low hemoglobin levels were not associated with iron deficiency Taking multivltamin supplements resulted in a lower incidence of folate deficiency but did not prevent iron or vitamin B₁₂ deficiency Oral supplementation of iron and vitamin B₁₂ corrected defiaencies in 43% and 81% of cases, respectively Folate deficiency was almost always corrected with multivitamins alone No patient had symptoms that could be attributed to either vitamin B₁₂ or folate deficiency Conversely, many patients had symptoms of iron deficiency and anenua Lack of symptoms of vitamin B₁₂ and folate deficiency suggests that these deficiencies are not clinically important after RYGB Conversely, iron deficiency and anemia are potentially serious problems after RYGB, particularly in younger women Hence we recommend prophylactic oral iron supplements to premenopausal women who undergo RYGB