Perinatal fluoxetine exposure results in social deficits and reduced monoamine oxidase gene expression in mice.

Perinatal antidepressant drug exposure increases risk for autism spectrum disorder, yet the molecular and neurobehavioral effects of maternal antidepressant drug use on offspring remain poorly understood. In this study, we administered the selective serotonin reuptake inhibitor (SSRI) fluoxetine non-invasively to female mice throughout gestation and early lactation, and then examined social interaction behaviors in offspring. In addition, we measured whole brain gene expression levels of monoamine oxidase A (MAOA), the primary metabolizing enzyme for serotonin. We found deficits in sociability and social novelty-seeking behavior in the juvenile offspring of SSRI-treated mice, and these behaviors persisted into young adulthood. Furthermore, we found decreased MAOA expression in the brains of offspring of SSRI-treated mice. Our findings suggest that exposure to antidepressants during the prenatal and early postnatal period may negatively affect social development. Moreover, reduced MAOA expression may play a role in the mechanistic pathway linking SSRI exposure and behavioral deficits symptomatic of autism.

Incidence of variations in human cadaveric renal vessels.

BACKGROUND: Awareness of discrepancies of renal vasculature is crucial for some medical procedures. The present study investigated origin and course of aberrant and accessory renal vessels and any associated variations. MATERIALS AND METHODS: Renal blood vessels of 63 cadavers were examined. Number of renal veins and arteries, arrangement, location where the vasculature attached to the kidneys, and presence of variations were recorded. Incidence of renal vasculature variations was determined, and associations were tested with age at death, sex, and cause of death and whether variations were more common on a specific side. RESULTS: Variations were found in 7 (11%; 95% confidence interval [CI] 5-22%) cadavers. For renal veins, double, triple, and quadruple veins unilaterally (5; 8%) and veins that drained the superior pole (1; 2%) or inferior pole only (5; 8%) were found. For renal arteries, double and triple arteries unilaterally (3; 5%) and arteries attached to the superior pole only (1; 2%) or inferior pole only (2; 3%) were found. Other variations (polycystic kidney, variations in the common iliac or gonadal veins) were observed. Only renal failure as a cause of death was different between those with or without variations (4/7 [57%] vs. 1/56 [2%]; p < 0.001). CONCLUSIONS: The present study found many variations in renal vasculature. Awareness of such variations may be useful for physicians concerned with this region.

Appraisal of guidelines developed by the World Health Organization.

OBJECTIVE: To appraise the quality of guidelines developed by the World Health Organization (WHO) that were approved by its Guidelines Review Committee (GRC) and identify strengths and weaknesses in the guideline development process. STUDY DESIGN: Cross-sectional. METHODS: Three individuals independently assessed GRC-approved WHO guidelines using the Appraisal of Guidelines for Research and Evaluation II instrument (AGREE II). Scores were standardized across domains and overall quality was determined through consensus. RESULTS: 124 guidelines met inclusion criteria and were assessed. 58 guidelines were recommended for use, 58 were recommended with modifications and eight were not recommended. The highest scoring domains across guidelines were scope and purpose, and clarity of presentation. The recommended guidelines had higher rigor of development and applicability domain scores in comparison to other guidelines. 77% of the guidelines referenced an underlying evidence review and 49% used GRADE to assess the body of evidence or the strength of the recommendation. The domains in need of improvement included stakeholder engagement, editorial independence, and applicability. Guidelines not recommended for use were generally insufficient in their rigor of development. CONCLUSIONS: WHO guidelines need further improvement, most importantly in the rigor of their development (i.e., use of evidence reviews). Other areas for improvement include increased stakeholder engagement, a more explicit process for recommendation formulation and disclosure of interests, discussion of the facilitators, barriers, resource implications, and criteria for monitoring the outcomes of guideline implementation. WHO guidelines can improve through increased transparency, adherence to the WHO Handbook for Guideline Development, and better oversight by the GRC.

Pathology of experimental aerosol Zaire ebolavirus infection in rhesus macaques.

There is limited knowledge of the pathogenesis of human ebolavirus infections and no reported human cases acquired by the aerosol route. There is a threat of ebolavirus as an aerosolized biological weapon, and this study evaluated the pathogenesis of aerosol infection in 18 rhesus macaques. Important and unique findings include early infection of the respiratory lymphoid tissues, early fibrin deposition in the splenic white pulp, and perivasculitis and vasculitis in superficial dermal blood vessels of haired skin with rash. Initial infection occurred in the respiratory lymphoid tissues, fibroblastic reticular cells, dendritic cells, alveolar macrophages, and blood monocytes. Virus spread to regional lymph nodes, where significant viral replication occurred. Virus secondarily infected many additional blood monocytes and spread from the respiratory tissues to multiple organs, including the liver and spleen. Viremia, increased temperature, lymphocytopenia, neutrophilia, thrombocytopenia, and increased alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, total bilirubin, serum urea nitrogen, creatinine, and hypoalbuminemia were measurable mid to late infection. Infection progressed rapidly with whole-body destruction of lymphoid tissues, hepatic necrosis, vasculitis, hemorrhage, and extravascular fibrin accumulation. Hypothermia and thrombocytopenia were noted in late stages with the development of disseminated intravascular coagulation and shock. This study provides unprecedented insight into pathogenesis of human aerosol Zaire ebolavirus infection and suggests development of a medical countermeasure to aerosol infection will be a great challenge due to massive early infection of respiratory lymphoid tissues. Rhesus macaques may be used as a model of aerosol infection that will allow the development of lifesaving medical countermeasures under the Food and Drug Administration's animal rule.

Prevalence of Parkinson's disease-induced psychosis in a large U.S. managed care population.

Using 10 years' enrollment history, patients with non-drug-induced Parkinson's disease were identified, and the prevalence of Parkinson's disease-induced psychosis (PDP) was estimated using three different claims algorithms based on an expert working group criteria. The estimated prevalence of PDP ranged from 4 to 45/1,000 Parkinson's disease patients. PDP patients were just as likely to be male as female and were significantly older than Parkinson's disease patients without PDP. PDP patients more commonly had evidence of dementia and use of atypical antipsychotics. PDP occurs in up to 45,000 Parkinson's disease patients in the United States but represents a unique neuropsychiatric finding with important treatment implications.

Immediate cardiovascular effects of the Taser X26 conducted electrical weapon.

STUDY OBJECTIVES: To evaluate the immediate cardiac and cardiovascular effects of Taser X26 conducted electrical weapon (CEW) exposure in human volunteers, including heart rhythm, rate and blood pressure. METHODS: Volunteer police officers participating in CEW training and testing each underwent a 5, 3 and 1 s exposure to the Taser X26 CEW. Continuous electrocardiogram (ECG) monitoring was performed before, during and after each exposure. Blood pressures were measured at rest before and within 1 minute after each exposure. Paired sample t-test analysis and confidence interval calculations were performed. RESULTS: 84 Taser exposures were monitored among 28 subjects (24 men, four women) with an average age of 34 years (range 24-46, SD 5.6). No cardiac dysrhythmias or aberrantly conducted beats were seen. Mean heart rate increased by 10.9 beats per minute (bpm) (95% CI 8.2 to 13.7) from 121.7 to 132.6 (p<0.001). The QRS and QTc cardiac intervals did not change significantly. Mean blood pressure increased from 138.6/82.8 mm Hg at rest to 145.8/85.6 mm Hg after the standard 5-s CEW discharge. CONCLUSION: CEW exposure produced no detectable dysrhythmias and a statistically significant increase in heart rate. Overall, Taser CEW exposure appears to be safe and well tolerated from a cardiovascular standpoint in this population. This study increases the cumulative human subject experience of CEW exposure with continuous ECG monitoring and includes 28 full 5-s exposures.

Multiplexed PCR genotyping of HPVs from plantaris verrucae.

BACKGROUND: Plantaris verrucae are a common diagnosis in childhood, consume a significant amount of health-care resources, have many painful treatment options and many recurrences. OBJECTIVES: The objective of this study was to design and test a single site-anchored, multiplexed and expandable PCR assay for common types of cutaneous HPVs. STUDY DESIGN: Common forward and unique reverse primers were selected from the E2 open reading frames of five cutaneous HPV genotypes. These were analyzed for sensitivity and selectivity using pHPV plasmids and several control DNAs in an optimized multiplexed assay. This standardized assay was used to analyze human verruca plantaris tissue for genome type and to evaluate the effect of a commonly used treatment protocol. RESULTS: A sensitive, multiplexed PCR assay for human cutaneous HPV genotypes 1a, 2a and 4 was developed. Specific-unique primers and a consensus anchor primer were selected within the HPV E2 region to produce amplicons varying by greater than 100bp. In analytical sensitivity studies, fewer than 100 genome copies of HPV1a and 2a were detected, and fewer than 1000 copies of HPV4 were detected. The multiplexed assay did not amplify regions of human placenta, calf thymus, CaSki or SiHa DNA and E. coli, pBR322 or non-HPV virus DNAs. In combination with a forensic DNA extraction procedure, the multiplexed HPV assay detected and identified HPV types in 23 of 51 (45%) deep plantaris verrucae. Two patients were found with two different genotypes in single deep plantaris verruca. Detection of the HPV genome was followed as a function of tissue ablation and Mediplast treatment in one patient. In healing tissue, the genome content was reduced but had not totally disappeared. CONCLUSIONS: The multiplexed HPV assay can be used to determine genotype prevalence that may correlate with treatment efficacy.

Strength of medial structures of the knee joint are decreased by isolated injury to the medial collateral ligament and subsequent joint immobilization.

Past studies of the healing of the medial collateral ligament (MCL) in animal models have been conducted over a variety of healing intervals, some as early as 1 week. One concern with testing at early healing intervals is the difficulty in identifying and isolating the tissues that carry load. The purpose of this study was to determine if isolation of the MCL and healing time are critical factors in the assessment of structural strength in this model. Furthermore, the effect of immobilization on these critical factors was investigated. Our approach was to calculate the load-sharing ratio between the MCL and the MCL plus capsule. A 4 mm gap was created in the midsubstance of both hindlimb MCLs of 52 female New Zealand White rabbits (n=104). Of these, 29 rabbits had their right hindlimb pin immobilized (immobilized group), leaving the left hindlimb non-immobilized. Testing was performed at 3 (n=12), 6 (n=22), and 14 (n=24) weeks. The remaining 23 rabbits, which had both limbs non-immobilized (non-immobilized group), were tested at 3 (n=10), 6 (n=12), 14 (n=12), and 40 (n=12) weeks. For both groups, half of the specimens at each healing interval were used to test the MCL alone and half to test the MCL plus capsule, except for 3 week immobilized joints where only the MCL plus capsule was tested. Additionally, MCL (n=12), MCL plus capsule (n=6), and capsule alone (n=5) were tested from normal animals. The load-sharing ratio at MCL failure for the normal joint was 89%, suggesting an MCL-dominated response. For the non-immobilized group, the load-sharing ratio was 24% at 3 weeks of healing, suggesting a capsule-dominated response. At and after 6 weeks of healing, an MCL-dominated response was observed, with the ratio being 68% or greater. Thus, at less than 6 weeks of healing, the structural strength capabilities of the joint may be better represented by the medial structures rather than the isolated MCL. Immobilization delayed the transition from a capsule-dominated response to an MCL-dominated response in this model.

Shape control of near-field probes using dynamic meniscus etching.

Dynamic etching methods for fabricating fibre optic tips are explored and modelled. By vertically translating the fibre during etching by an HF solution under an organic protective layer, a variety of tip shapes were created. The probe taper lengths, cone angles and geometrical probe shapes were measured in order to evaluate the dynamic meniscus etching process. Fibre motion, etching rate, meniscus distortion and etching time were all found to be important variables that can be used to control the final probe shape.

Clinical efficacy of flunixin, carprofen and ketoprofen as adjuncts to the antibacterial treatment of bovine respiratory disease.

Three non-steroidal anti-inflammatory drugs (NSAIDs), flunixin, ketoprofen and carprofen, were used in conjunction with ceftiofur, in the treatment of naturally occurring bovine respiratory disease. Sixty-six mixed-breed beef cattle weighing on average 197 kg met the inclusion criteria of pyrexia of at least 40 degrees C, an illness score indicating at least moderate illness and at least moderate dyspnoea. They were allocated randomly to four treatment groups. All the groups received ceftiofur for three days at a dose rate of 1.1 mg/kg by intramuscular injection, and three groups received, in addition, a single dose of either flunixin (2.2 mg/kg by intravenous injection) or ketoprofen (3 mg/kg by intravenous injection) or carprofen (1.4 mg/kg by subcutaneous injection). During the first 24 hours of the study, the pyrexia of the three groups treated with a NSAID was reduced significantly more than the pyrexia of the group treated with ceftiofur alone, and two and four hours after treatment the reduction in pyrexia was significantly greater in the groups treated with flunixin and ketoprofen than in the group treated with carprofen. There were no statistically significant differences between the four groups with respect to depression, illness scores, dyspnoea or coughing. There was less lung consolidation in the three groups treated with a NSAID than in the animals treated with ceftiofur alone, but the difference was significant only in the group treated with flunixin.

Detection of mammaglobin in the sera of patients with breast cancer.

Current procedures for the diagnosis of breast cancer are cumbersome and invasive, making detection of this disease difficult. A rapid screening test for early detection of breast cancer would allow for better management of this deadly disease. In this report, we show that, with the exception of the skin, mammaglobin mRNA is specifically expressed in mammary tissue and commonly overexpressed in breast cancer. Mammaglobin is not expressed in other types of cancer including colon, lung, ovarian, and prostate cancer. Breast-specific expression of mammaglobin protein was shown using immunohistochemical methods. Mammaglobin is secreted from both established breast cancer cell lines and primary breast carcinoma cells cultured in vitro. Using a monoclonal antibody-based assay for monitoring the presence of mammaglobin in serum, elevated levels of mammaglobin were detected in sera of patients with breast cancer, but not in healthy women. Thus, mammaglobin, which is overexpressed and secreted from breast carcinoma cells, is detectable in sera of patients with breast cancer and may provide a rapid screening test for the diagnosis and management of breast cancer.

Sibling adjustment to pediatric traumatic brain injury: a case-controlled pilot study.

OBJECTIVE: To assess depressive symptoms, self-concept, and behavior in non-affected siblings of children with severe pediatric traumatic brain injury (TBI). DESIGN: Cross-sectional study with case controls. SETTING: Children's hospital tertiary care center. PARTICIPANTS: Twelve siblings of children consecutively admitted to an inpatient rehabilitation unit after a severe TBI. Case controls were randomly selected from the sibling's classmates. MAIN OUTCOME MEASURES: The Child Behavior Checklist (CBCL), the Teacher's Report Form of the CBCL (TRF-CBCL), the Self-Perception Profile for Children and the Children's Depression Inventory (CDI). RESULTS: No statistical differences were found in depressive symptoms, self-concept, or behavior between the siblings and their classmates 3 to 18 months after injury. Poorer functional outcomes in the child with a TBI were found to correlate significantly with lower self-concept and more symptoms of depression in the siblings. CONCLUSIONS: Further research is needed to evaluate the potential impact on sibling adjustment after pediatric TBI.

A prospective investigation of the impact of smoking bans on tobacco cessation and relapse.

BACKGROUND AND OBJECTIVES: To examine the long term impact of workplace smoking bans on employee smoking cessation and relapse. Over three years we studied a total of 1033 current or former smokers (intervention group) employed in smoke-free hospitals and 816 current or former smokers (comparison group) employed in non-smoke-free workplaces. The design of this natural experiment is a prospective cohort study. We randomly selected both hospitals and employees from 12 strata based on hospital size and state tobacco regulations, and sampled employees in the same communities. Main outcome measures were post-ban quit ratio and relapse rate. RESEARCH DESIGN: Between groups comparisons were conducted using the Cochran-Mantel-Haenszel statistic for general association, stratified Cox proportional hazards models, and the CMH analysis of variance statistic based on ranks. McNemar's test and the sign test were used to test for changes over time within each group. RESULTS: Differences in the post-ban quit ratio were observed between intervention and comparison groups (p < or = 0.02). For employees whose bans were implemented at least seven years before survey, the post-ban quit ratio was estimated at 0.256, compared with 0.142 for employees in non-smoke-free workplaces (p = 0.02). After controlling for a variety of factors, time to quit smoking was shorter for the hospital employees (p < 0.001), with an overall relative risk of quitting of 2.3. Contrary to expectations, relapse rates were similar between the groups. CONCLUSION: Employees in workplaces with smoking bans have higher rates of smoking cessation than employees where smoking is permitted, but relapse is similar between these two groups of employees. The results of this investigation have international applicability for policy makers, clinicians, employers, and employees. Countries should review smoking policies in workplaces in light of their own smoking patterns and efforts to deal with environmental tobacco smoke.

The effects of a lumbar support on repositioning error in subjects with low back pain.

OBJECTIVE: To determine whether a lumbar support improves trunk repositioning error (RE), an aspect of proprioception. DESIGN: RE was measured with and without a lumbar support. SETTING: Outpatient clinic. PARTICIPANTS: Twenty subjects with chronic low back pain (LBP) and 20 control subjects. INTERVENTIONS: Subjects wore the lumbar support for 2 hours and then testing was repeated. MAIN OUTCOME MEASURES: Standing with legs and pelvis immobilized, subjects moved to a predetermined target position and then attempted to replicate the position. The 3-dimensional position of the trunk was measured with a 3Space Tracker. RE was calculated as the absolute difference between the actual target position and the subject-perceived target position. Testing was performed with and without a lumbar support both before and after wearing the support for 2 hours. RESULTS: In subjects with LBP, RE was significantly lower with a support in flexion, extension, and right lateral bending. In control subjects, RE was significantly lower when wearing the support in left bending only, and RE was significantly higher in control subjects after wearing the support for 2 hours. CONCLUSION: A lumbar support improves trunk RE. In subjects with LBP, this result was significant in the sagittal plane and in right lateral bending, whereas in control subjects, it was significant only in left lateral bending.

Immunomodulation therapy for feline leukemia virus infection.

Clinically ill feline leukemia virus (FeLV)-infected cats, treated with Staphylococcus protein A (SPA) or oral interferon alpha (IFN), or both, were compared with cats treated with saline (SAL). Nine cats received SPA/SAL, nine received SPA/IFN, 10 received SAL/IFN, and eight received SAL/SAL. Twelve cats survived and completed the 100-week therapy. Significantly more owners of cats treated with SPA/SAL thought their cat's health improved during treatment compared to owners of cats treated with SAL/SAL (P=0.05, pair-wise comparison) or SPA/IFN (P=0.05, pair-wise comparison). No significant differences in body weight, temperature, hematocrit, red blood cell counts, mean corpuscular hemoglobin concentration, reticulocyte counts, white blood cell or neutrophil numbers, lymphocyte concentrations, bone-marrow cytopathology, FeLV status, survival time, activity, or appetite scores were observed. No significant differences in the owners' subjective assessment of their cat's health following treatment with SAL/IFN, SPA/IFN, or SAL/SAL were seen. Therapy with SPA as a single agent results in the owners' subjective impression of improved health of their FeLV-infected cats.

A probabilistic approach to space-group determination from powder diffraction data.

An algorithm for the determination of the space-group symmetry of a crystal from powder diffraction data, based upon probability theory, is described. Specifically, the relative probabilities of different extinction symbols are assessed within a particular crystal system. In general, only a small number of extinction symbols are relatively highly probable and a single extinction symbol is often significantly more probable than any other. Several examples are presented to illustrate this approach.

Quantification of measurement of femoral head coverage and Norberg angle within and among four breeds of dogs.

OBJECTIVE: To report values for percentage coverage of the femoral head (PC) and Norberg angle (NA) in 4 common breeds of dogs and to determine values for each that distinguish between normal and dysplastic hip status on the basis of Orthopedic Foundation for Animals (OFA) hip evaluation. ANIMALS: 1,841 dogs 24 to 48 months of age that were Labrador Retrievers (455), Golden Retrievers (423), Rottweilers (545), or German Shepherd Dogs (418). PROCEDURE: Retrospective analysis of NA and PC measured from standard OFA ventrodorsal pelvic radiographs from 4 breeds of dog. RESULTS: Norberg angle ranged from 67.4 to 124.4 degrees for Labrador Retrievers, 59.7 to 128.6 degrees for Rottweilers, 70.2 to 119.4 degrees for Golden Retrievers, and 55.3 to 121.3 degrees for German Shepherd Dogs. The PC ranged from 6.5 to 79.9% for Labrador Retrievers, 5.7 to 79.5% for Rottweilers, 8.3 to 79.3% for Golden Retrievers, and 5.4 to 83.7% for German Shepherd Dogs. On the basis of logistic regression modeling for determining normal versus abnormal hip status for all 4 breeds, cutoff points for NA were <105 degrees and PC were <50%. CONCLUSIONS AND CLINICAL RELEVANCE: Results of our study indicate that cutoff points of NA of 105 degrees and PC of 50% do not differentiate normal versus dysplastic hip status. Each of the 4 breeds had different values for NA and PC that distinguished normal from dysplastic hip status.

Nonlinear chemical imaging microscopy: near-field third harmonic generation imaging of human red blood cells.

Third harmonic generation (THG) imaging using a near-field scanning optical microscope (NSOM) is demonstrated for the first time. A femtosecond, tunable near-infrared laser was used to generate both nonresonant and resonantly enhanced third harmonic radiation in human red blood cells. We show that resonantly enhanced THG is a chemically specific bulk probe in NSOM imaging by tuning the excitation source onto and off of resonance with the Soret transition of oxyhemoglobin. Additionally, we provide evidence that tightly focused, nonresonant, far-field THG imaging experiments do not produce contrast that is truly surface specific.