Vitamin D metabolites are associated with musculoskeletal injury in young adults: a prospective cohort study

The relationship between vitamin D metabolites and lower body (pelvis and lower limb) overuse injury is unclear. In a prospective cohort study, we investigated the association between vitamin D metabolites and incidence of lower body overuse musculoskeletal and bone stress injury in young adults undergoing initial military training during all seasons. In 1637 men and 530 women (age, 22.6 ± 7.5 years; BMI, 24.0 ± 2.6 kg∙m-2 ; 94.3% white ethnicity), we measured serum 25-hydroxyvitamin D (25(OH)D) and 24,25- dihydroxyvitamin D (24,25(OH)2D) by high-performance liquid chromatography tandem mass spectrometry, and 1,25-dihydroxyvitamin D (1,25(OH)2D) by immunoassay during week 1 of training. We examined whether the relationship between 25(OH)D and 1,25(OH)2D:24,25(OH)2D ratio was associated with overuse injury. During 12 weeks training, 21.0% sustained ≥1 overuse musculoskeletal injury, and 5.6% sustained ≥1 bone stress injury. After controlling for sex, BMI, 2.4 km run time, smoking, bone injury history, and Army training course (Officer, standard, or Infantry), lower body overuse musculoskeletal injury incidence was higher for participants within the second lowest versus highest quartile of 24,25(OH)2D (OR: 1.62 [95%CI 1.13–2.32; P = 0.009]) and lowest versus highest cluster of 25(OH)D and 1,25(OH)2D:24,25(OH)2D (OR: 6.30 [95%CI 1.89–21.2; P = 0.003]). Lower body bone stress injury incidence was higher for participants within the lowest versus highest quartile of 24,25(OH)2D (OR: 4.02 [95%CI 1.82–8.87; P < 0.001]) and lowest versus highest cluster of 25(OH)D and 1,25(OH)2D:24,25(OH)2D (OR: 22.08 [95%CI 3.26–149.4; P = 0.001]), after controlling for the same covariates. Greater conversion of 25(OH)D to 24,25(OH)2D, relative to 1,25(OH)2D (i.e., low 1,25(OH)2D:24,25(OH)2D), and higher serum 24,25(OH)2D were associated with a lower incidence of lower body overuse musculoskeletal and bone stress injury. Serum 24,25(OH)2D may have a role in preventing overuse injury in young adults undertaking arduous physical training

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Ethanol-Induced Face-Brain Dysmorphology Patterns Are Correlative and Exposure-Stage Dependent

Prenatal ethanol exposure is the leading preventable cause of congenital mental disability. Whereas a diagnosis of fetal alcohol syndrome (FAS) requires identification of a specific pattern of craniofacial dysmorphology, most individuals with behavioral and neurological sequelae of heavy prenatal ethanol exposure do not exhibit these defining facial characteristics. Here, a novel integration of MRI and dense surface modeling-based shape analysis was applied to characterize concurrent face-brain phenotypes in C57Bl/6J fetuses exposed to ethanol on gestational day (GD)7 or GD8.5. The facial phenotype resulting from ethanol exposure depended upon stage of insult and was predictive of unique patterns of corresponding brain abnormalities. Ethanol exposure on GD7 produced a constellation of dysmorphic facial features characteristic of human FAS, including severe midfacial hypoplasia, shortening of the palpebral fissures, an elongated upper lip, and deficient philtrum. In contrast, ethanol exposure on GD8.5 caused mild midfacial hypoplasia and palpebral fissure shortening, a shortened upper lip, and a preserved philtrum. These distinct, stage-specific facial phenotypes were associated with unique volumetric and shape abnormalities of the septal region, pituitary, and olfactory bulbs. By demonstrating that early prenatal ethanol exposure can cause more than one temporally-specific pattern of defects, these findings illustrate the need for an expansion of current diagnostic criteria to better capture the full range of facial and brain dysmorphology in fetal alcohol spectrum disorders

Strategies to prevent HIV transmission among heterosexual African-American women

BACKGROUND: African-American women are disproportionately affected by HIV, accounting for 60% of all cases among women in the United States. Although their race is not a precursor for HIV, the socioeconomic and cultural disparities associated with being African American may increase their risk of infection. Prior research has shown that interventions designed to reduce HIV infection among African-American women must address the life demands and social problems they encounter. The present study used a qualitative exploratory design to elicit information about strategies to prevent HIV transmission among young, low-income African-American women. METHODS: Twenty five low income African American women, ages 18–29, participated in five focus groups of five women each conducted at a housing project in Houston, Texas, a large demographically diverse metropolitan area that is regarded as one of the HIV/AIDS epicenters in the United States. Each group was audiotaped, transcribed, and analyzed using theme and domain analysis. RESULTS: The participants revealed that they had most frequently placed themselves at risk for HIV infection through drugs and drinking and they also reported drug and alcohol use as important barriers to practicing safer sex. The women also reported that the need for money and having sex for money to buy food or drugs had placed them at risk for HIV transmission. About one-third of the participants stated that a barrier to their practicing safe sex was their belief that there was no risk based on their being in a monogamous relationship and feeling no need to use protection, but later learning that their mate was unfaithful. Other reasons given were lack of concern, being unprepared, partner's refusal to use a condom, and lack of money to buy condoms. Finally, the women stated that they were motivated to practice safe sex because of fear of contracting sexually transmitted diseases and HIV, desire not to become pregnant, and personal experience with someone who had contracted HIV. CONCLUSION: This study offers a foundation for further research that may be used to create culturally relevant HIV prevention programs for African-American women

Nitric Oxide Signalling Augments Neuronal Voltage-Gated L-Type (CaV1) and P/Q-Type (CaV2.1) Channels in the Mouse Medial Nucleus of the Trapezoid Body

Nitric Oxide (NO) is a diffusible second messenger that modulates ion channels, intrinsic excitability and mediates synaptic plasticity. In light of its activity-dependent generation in the principal neurons of the medial nucleus of the trapezoid body (MNTB), we have investigated its potential modulatory effects on native voltage-gated calcium channels (CaV) within this nucleus. Whole-cell patch recordings were made from brain slices from P13–15 CBA mice. Slices were incubated with the inhibitor of neuronal nitric oxide synthase (nNOS) 7-nitroindazole (10 µM) and pharmacological blockers used to isolate Ca2+ current subtypes. Unpaired observations in the presence and absence of the NO-donors sodium nitroprusside (SNP, 100 µM) or Diethyl-ammonium-nonoate (DEA, 100 µM) were made to elucidate NO-dependent modulation of the expressed CaV subtypes. A differential effect of NO on the calcium channel subtypes was observed: CaV1 and CaV2.1 (L+R- and P/Q+R-type) conductances were potentiated, whereas N+R-type (CaV2.2) and R-type (CaV2.3) current amplitudes were unaffected. L+R-type currents increased from 0.36±0.04 nA to 0.64±0.11 nA and P/Q+R-type from 0.55±0.09 nA to 0.94±0.05 nA, thereby changing the balance and relative contribution of each subtype to the whole cell calcium current. In addition, N+R-type half-activation voltage was left shifted following NO exposure. NO-dependent modulation of P/Q+R and N+R-type, but not L+R-type, channels was removed by inhibition of soluble guanylyl cyclase (sGC) activity. This data demonstrates a differential effect of NO signalling on voltage-gated calcium entry, by distinct NO-dependent pathways

EGFR, CD10 and proliferation marker Ki67 expression in ameloblastoma: possible role in local recurrence

<p>Abstract</p> <p>Background</p> <p>Ameloblastoma is an odontogenic neoplasm characterized by local invasiveness and tendency towards recurrence.</p> <p>Aims</p> <p>Studying the role played by EGFR, CD10 and Ki67 in the recurrence of ameloblastoma.</p> <p>Methods</p> <p>This study was carried out on 22 retrospective cases of mandibular ameloblastoma from the period from Jan 2002 to Jan 2008 with follow up period until Jan 2011 (3 to 8 years follow up peroid). Archival materials were obtained from pathology department, Mansoura university. Paraffin sections of tumor tissue from all cases were submitted for routine H&E stains and immunohistochemistry using EGFR, CD10 and Ki67 monoclonal antibodies. Statistical analysis using of clinical data for all patients, tumor type, EGFR, CD10 and Ki67 expression in relation to recurrence were evaluated.</p> <p>Results</p> <p>Among the 22 cases, 10 cases were males and 12 were females with sex ratio 1:1.2. Age ranged from 34 to 59 years old with a mean age 44.18 year. Five cases showed local recurrence within studied period and proved by biopsy. No statistically significant relation was found between local recurrence and patient age, tumor size, tumor type, EGFR expression. There was a significant relation between CD10 expression as well as Ki67 labelling index and recurrence (P value = 0.003, 0.000 respectively).</p> <p>Conclusion</p> <p>Evaluation of CD10 and Ki67 status together with conventional histological evaluation can help in providing more information about the biologic behavior of the tumor, while EGFR could be a target of an expanding class of anticancer therapies.</p> <p>Since ameloblastomas are EGFR-positive tumors, anti-EGFR agents could be considered to reduce the size of large tumors and to treat unresectable tumors that are in close proximity to vital structures.</p> <p>Virtual Slides</p> <p>The virtual slide(s) for this article can be found here:</p> <p><url>http://www.diagnosticpathology.diagnomx.eu/vs/1902106905645651</url></p

A New Anti-Depressive Strategy for the Elderly: Ablation of FKBP5/FKBP51

The gene FKBP5 codes for FKBP51, a co-chaperone protein of the Hsp90 complex that increases with age. Through its association with Hsp90, FKBP51 regulates the glucocorticoid receptor (GR). Single nucleotide polymorphisms (SNPs) in the FKBP5 gene associate with increased recurrence of depressive episodes, increased susceptibility to post-traumatic stress disorder, bipolar disorder, attempt of suicide, and major depressive disorder in HIV patients. Variation in one of these SNPs correlates with increased levels of FKBP51. FKBP51 is also increased in HIV patients. Moreover, increases in FKBP51 in the amygdala produce an anxiety phenotype in mice. Therefore, we tested the behavioral consequences of FKBP5 deletion in aged mice. Similar to that of naïve animals treated with classical antidepressants FKBP5−/− mice showed antidepressant behavior without affecting cognition and other basic motor functions. Reduced corticosterone levels following stress accompanied these observed effects on depression. Age-dependent anxiety was also modulated by FKBP5 deletion. Therefore, drug discovery efforts focused on depleting FKBP51 levels may yield novel antidepressant therapies

Timing of immune escape linked to success or failure of vaccination

Successful vaccination against HIV should limit viral replication sufficiently to prevent the emergence of viral immune escape mutations. Broadly directed immunity is likely to be required to limit opportunities for immune escape variants to flourish. We studied the emergence of an SIV Gag cytotoxic T cell immune escape variant in pigtail macaques expressing the Mane-A*10 MHC I allele using a quantitative RT-PCR to measure viral loads of escape and wild type variants. Animals receiving whole Gag expressing vaccines completely controlled an SIVmac251 challenge, had broader CTL responses and exhibited minimal CTL escape. In contrast, animals vaccinated with only a single CTL epitope and challenged with the same SIVmac251 stock had high levels of viral replication and rapid CTL escape. Unvaccinated na&iuml;ve animals exhibited a slower emergence of immune escape variants. Thus narrowly directed vaccination against a single epitope resulted in rapid immune escape and viral levels equivalent to that of na&iuml;ve unvaccinated animals. These results emphasize the importance of inducing broadly directed HIV-specific immunity that effectively quashes early viral replication and limits the generation of immune escape variants. This has important implications for the selection of HIV vaccines for expanded human trials.<br /

Longitudinal In Vivo Imaging of Retinal Ganglion Cells and Retinal Thickness Changes Following Optic Nerve Injury in Mice

Retinal ganglion cells (RGCs) die in sight-threatening eye diseases. Imaging RGCs in humans is not currently possible and proof of principle in experimental models is fundamental for future development. Our objective was to quantify RGC density and retinal thickness following optic nerve transection in transgenic mice expressing cyan fluorescent protein (CFP) under control of the Thy1 promoter, expressed by RGCs and other neurons.A modified confocal scanning laser ophthalmoscopy (CSLO)/spectral-domain optical coherence tomography (SD-OCT) camera was used to image and quantify CFP+ cells in mice from the B6.Cg-Tg(Thy1-CFP)23Jrs/J line. SD-OCT circle (1 B-scan), raster (37 B-scans) and radial (24 B-scans) scans of the retina were also obtained. CSLO was performed at baseline (n = 11) and 3 (n = 11), 5 (n = 4), 7 (n = 10), 10 (n = 6), 14 (n = 7) and 21 (n = 5) days post-transection, while SD-OCT was performed at baseline and 7, 14 and 35 days (n = 9) post-transection. Longitudinal change in CFP+ cell density and retinal thickness were computed. Compared to baseline, the mean (SD) percentage CFP+ cells remaining at 3, 5, 7, 10, 14 and 21 days post-transection was 86 (9)%, 63 (11)%, 45 (11)%, 31 (9)%, 20 (9)% and 8 (4)%, respectively. Compared to baseline, the mean (SD) retinal thickness at 7 days post-transection was 97 (3)%, 98 (2)% and 97 (4)% for the circle, raster and radial scans, respectively. The corresponding figures at 14 and 35 days post-transection were 96 (3)%, 97 (2)% and 95 (3)%; and 93 (3)%, 94 (3)% and 92 (3)%.Longitudinal imaging showed an exponential decline in CFP+ cell density and a small (≤8%) reduction in SD-OCT measured retinal thickness post-transection. SD-OCT is a promising tool for detecting structural changes in experimental optic neuropathy. These results represent an important step towards translation for clinical use

Substance abuse and intimate partner violence: treatment considerations

Given the increased use of marital- and family-based treatments as part of treatment for alcoholism and other drug disorders, providers are increasingly faced with the challenge of addressing intimate partner violence among their patients and their intimate partners. Yet, effective options for clinicians who confront this issue are extremely limited. While the typical response of providers is to refer these cases to some form of batterers' treatment, three fundamental concerns make this strategy problematic: (1) most of the agencies that provide batterers' treatment only accept individuals who are legally mandated to complete their programs; (2) among programs that do accept nonmandated patients, most substance-abusing patients do not accept such referrals or drop out early in the treatment process; and (3) available evidence suggests these programs may not be effective in reducing intimate partner violence. Given these very significant concerns with the current referral approach, coupled with the high incidence of IPV among individuals entering substance abuse treatment, providers need to develop strategies for addressing IPV that can be incorporated and integrated into their base intervention packages