An Automated Statistical Technique for Counting Distinct Multiple Sclerosis Lesions.

BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions. MATERIALS AND METHODS: MR imaging was used to assess the probability of a lesion at each location. The texture of this map was quantified using a novel technique, and clusters resembling the center of a lesion were counted. Validity compared with a criterion standard count was demonstrated in 60 subjects observed longitudinally, and reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites. RESULTS: The proposed count and the criterion standard count were highly correlated (r = 0.97, P < .001) and not significantly different (t59 = -.83, P = .41), and the variability of the proposed count across repeat scans was equivalent to that of lesion load. After accounting for lesion load and age, lesion count was negatively associated (t58 = -2.73, P < .01) with the Expanded Disability Status Scale. Average lesion size had a higher association with the Expanded Disability Status Scale (r = 0.35, P < .01) than lesion load (r = 0.10, P = .44) or lesion count (r = -.12, P = .36) alone. CONCLUSIONS: This study introduces a novel technique for counting pathologically distinct lesions using cross-sectional data and demonstrates its ability to recover obscured longitudinal information. The proposed count allows more accurate estimation of lesion size, which correlated more closely with disability scores than either lesion load or lesion count alone.

Volumetric Analysis from a Harmonized Multisite Brain MRI Study of a Single Subject with Multiple Sclerosis.

BACKGROUND AND PURPOSE: MR imaging can be used to measure structural changes in the brains of individuals with multiple sclerosis and is essential for diagnosis, longitudinal monitoring, and therapy evaluation. The North American Imaging in Multiple Sclerosis Cooperative steering committee developed a uniform high-resolution 3T MR imaging protocol relevant to the quantification of cerebral lesions and atrophy and implemented it at 7 sites across the United States. To assess intersite variability in scan data, we imaged a volunteer with relapsing-remitting MS with a scan-rescan at each site. MATERIALS AND METHODS: All imaging was acquired on Siemens scanners (4 Skyra, 2 Tim Trio, and 1 Verio). Expert segmentations were manually obtained for T1-hypointense and T2 (FLAIR) hyperintense lesions. Several automated lesion-detection and whole-brain, cortical, and deep gray matter volumetric pipelines were applied. Statistical analyses were conducted to assess variability across sites, as well as systematic biases in the volumetric measurements that were site-related. RESULTS: Systematic biases due to site differences in expert-traced lesion measurements were significant (P < .01 for both T1 and T2 lesion volumes), with site explaining >90% of the variation (range, 13.0-16.4 mL in T1 and 15.9-20.1 mL in T2) in lesion volumes. Site also explained >80% of the variation in most automated volumetric measurements. Output measures clustered according to scanner models, with similar results from the Skyra versus the other 2 units. CONCLUSIONS: Even in multicenter studies with consistent scanner field strength and manufacturer after protocol harmonization, systematic differences can lead to severe biases in volumetric analyses.

HIV-1-negative female sex workers sustain high cervical IFNɛ, low immune activation, and low expression of HIV-1-required host genes.

Sex workers practicing in high HIV endemic areas have been extensively targeted to test anti-HIV prophylactic strategies. We hypothesize that in women with high levels of genital exposure to semen changes in cervico-vaginal mucosal and/or systemic immune activation will contribute to a decreased susceptibility to HIV-1 infection. To address this question, we assessed sexual activity and immune activation status (in peripheral blood), as well as cellular infiltrates and gene expression in ectocervical mucosa biopsies in female sex workers (FSWs; n=50), as compared with control women (CG; n=32). FSWs had low-to-absent HIV-1-specific immune responses with significantly lower CD38 expression on circulating CD4(+) or CD8(+) T-cells (both: P<0.001) together with lower cervical gene expression of genes associated with leukocyte homing and chemotaxis. FSWs also had increased levels of interferon-ɛ (IFNɛ) gene and protein expression in the cervical epithelium together with reduced expression of genes associated with HIV-1 integration and replication. A correlative relationship between semen exposure and elevated type-1 IFN expression in FSWs was also established. Overall, our data suggest that long-term condomless sex work can result in multiple changes within the cervico-vaginal compartment that would contribute to sustaining a lower susceptibility for HIV-1 infection in the absence of HIV-specific responses.

Traumatic brain injury in Africa in 2050: a modeling study.

BACKGROUND AND PURPOSE: Our aim was to provide estimates of traumatic brain injury (TBI) in 2050 for the African population by region, sex and age strata. METHODS: A literature search was performed in October 2014 in PubMed for population-based studies of TBI in different geographical locations. Articles were selected from Kenya (model 1), New Zealand (model 2) and the USA (model 3). In model 1, rates of road traffic injury in Kenya were used to estimate TBI rates in the African continent. Models 2 and 3 used existing TBI incidence estimates from other locations to estimate the burden of TBI for Africa in 2050. The 2050 African population, as projected by the United Nations, was used as a base population. RESULTS: Based on rates from model 1, the estimated total TBI count in Africa in 2050 is 5.98 ± 0.03 million, with the highest count in eastern (2.04 ± 0.01 million) and lowest count in southern (0.15 ± 0.00 million) Africa. A higher TBI count is predicted by models 2 (14.25 ± 0.75 million) and 3 (10.40 ± 0.02 million). Estimated TBI count is highest for males aged 15-34 (5.47 ± 0.55 million in model 2 and 3.21 ± 0.13 million in model 3). CONCLUSIONS: Projected estimates of TBI in Africa are high, with a burden of anywhere between approximately 6 and 14 million new cases in 2050. This emphasizes the importance of developing accurate surveillance systems of TBI at a population level and public health measures to mitigate the risk and burden of TBI.

Canine hip dysplasia treated by juvenile pubic symphysiodesis. Part II: two year clinical results.

OBJECTIVES: To determine the clinical effects of juvenile pubic symphysiodesis (JPS) treatment in hip dysplasia-prone puppies with comparison to similar untreated control puppies. DESIGN: Controlled clinical case study. ANIMALS: Thirty-nine dysplastic puppies, of which six were part of the control group, with a positive Ortolani or hip distraction index (DI)≥0.40. PROCEDURES: The following eight clinical tests were evaluated preoperatively, and at one and two years postoperatively: Ortolani, hip reduction angle (HRA), gait evaluation, osteoarthritis, hip pain, and three Norberg angles (angle-extended mode [N-OFA], angle-compression mode [N-COM], and angle-distracted mode [N-DIS]). Juvenile pubic fusion (JPS) was performed by unipolar electro-cautery at 12 to 24 weeks of age; the control puppies received a sham operation. RESULTS: For the JPS puppies, the mean osteoarthritis level did not significantly increase (11%). There was a 74% reversal of preoperative positive Ortolani signs. Hip reduction angle, DI and N-DIS also improved significantly. Only N-DIS fully detected Norberg angle laxity. Within the control group, osteoarthritis increased significantly (55%) with no improvement in Ortolani incidence, N-OFA or N-COM angles. A decrease in HRA and DI was associated with increased osteoarthritis levels. Signs of hip pain increased by 33%, which was not significant. Dogs with initial severe hip laxity (DI≥0.70) experienced progressive osteoarthritis. CONCLUSIONS AND CLINICAL RELEVANCE: In JPS dogs with preoperative mild to moderate hip laxity (DI = 0.40-0.69), insignificant osteoarthritis occurred at two years. Juvenile pubic symphysiodesis surgery also improved other clinical criteria (Ortolani, HRA, hip pain, N-DIS). Osteoarthritis was generally not prevented by JPS in dogs with initial severely lax hips (DI≥0.70). Juvenile pubic symphysiodesis surgery at 12 to 24 weeks of age was an effective and safe pre-emptive bilateral treatment for mild to moderate hip dysplasia.

Canine hip dysplasia treated by juvenile pubic symphysiodesis. Part I: two year results of computed tomography and distraction index.

OBJECTIVES: To measure one and two year effects of juvenile pubic symphysiodesis (JPS) in puppies defined as 'at-risk' for canine hip dysplasia (CHD) using the following objective hip conformation criteria: Acetabular angle (AA), dorsal acetabular rim angle (DARA) and hip laxity (PennHIP© distraction index (DI). DESIGN: Controlled clinical case study. ANIMALS: Thirty-nine dysplastic puppies (six controls). PROCEDURES: The dogs were anaesthetised and acetabular angle, DARA, and DI values were obtained by computed tomography and radiography preoperatively. Electro-cautery fusion of the pubic symphysis was performed between 12 - 24 weeks of age. The imaging was repeated at one and two years of age. RESULTS: Significant hip improvements were seen at the two-year follow-up appointments for: AA (JPS dogs 31% increase, control 3%), DARA (JPS 38% decrease, control 15%) and DI (JPS 41% decrease in laxity, controls 20%) for all postoperative versus preoperative values. Pubic fusion occurred with minor morbidity. CONCLUSION: Juvenile pubic symphysiodesis resulted in significant improvements in hip conformation (AA and DARA), especially in mild to moderately lax hips (DI = 0.40-0.69). Most dogs with DI≥0.70 increased in osteoarthritis grade by two years of age. CLINICAL RELEVANCE: Juvenile pubic symphysiodesis surgery at 12-24 weeks of age significantly improved hip conformation and decreased laxity in at-risk CHD dogs. Early-age (12 to 16 week) recognition of hip laxity offered greater JPS benefits than surgery performed at 19- to 24-weeks-old. Dogs with severe laxity (DI≥0.70) continued to increase in osteoarthritis. An early (12-16 weeks) positive laxity test (Ortolani) should alert one to obtain objective laxity determinations (PennHIP© DI).

Macroscopic and microvascular blood supply of the canine common calcaneal tendon.

Chronic tendinopathy injuries to the canine common calcaneal tendon are relatively common in large breed dogs and typically affect the distal portion of the tendon. In humans, poor blood supply, biomechanical faults, poor training methods and fluoroquinolone administration have all been linked with the development of Achilles tendinopathy. The most common sites for Achilles tendinopathy in humans seem to correspond with areas of poor blood supply within the tendon. The aim of this study was to evaluate the blood supply of the canine common calcaneal (Achilles) tendon to determine if variations occur along the tendon. The null hypothesis was that there would be no difference in the microvascular blood supply at varying points along the tendon. Paired pelvic limbs were collected from 12 large breed dog cadavers. A 50% barium sulphate and 50% saline solution was infused into the femoral artery of one limb from each dog and radiographs were taken to outline the blood supply to the common calcaneal tendon. Indian ink was infused into the contralateral limb. The common calcaneal tendon was removed, fixed and sectioned at 1 cm intervals, from calcaneal insertion to musculotendinous junction. The ink-filled arteries and arterioles in each section were counted. Radiographs revealed fine branches from the caudal saphenous artery entering the mid-body of the tendon along its cranial border. The musculotendinous junction had additional branches from the gastrocnemius muscles. Distally, vessels radiated proximally from the calcaneus 2 to 3 cm into the tendon. Mean total vessel counts at the insertion (138.54 +/- SD 31.06) were significantly higher than all other sections (p <0.001). The mid-body had significantly lower total vessel counts. When the cross sectional area of the tendon was taken into account, only the insertion had a significantly higher mean vessel count/cm2 than the mid-body of the tendon. There were no other significant differences in mean vessel count/cm2. Areas of poorer blood supply did not correspond with the most commonly reported site for chronic common calcanean tendinopathies, suggesting that inherent poor blood supply at the site of injury may not play a role in the pathogenesis. Atraumatic handling and minimal manipulation should be used during the surgical approach and debridement to preserve the remaining blood supply in ruptured tendons.

Osteocyte apoptosis and osteoclast presence in chicken radii 0-4 days following osteotomy.

Osteocyte apoptosis caused by load-induced microdamage is followed by osteoclastic bone remodeling, and a causal link between apoptosis and repair has been suggested. The objectives of the present study were to use a chick model to examine the incidence of osteocyte apoptosis and the presence of osteoclasts during the first 96 hours following an osteotomy, prior to extensive callus mineralization. Osteotomies were performed on the right radii of 24 chicks at 23-24 days of age. The left radii served as controls. Radii were collected and processed at six time points following surgery (0, 12, 24, 48, 72, and 96 hours). Decalcified bone tissue sections were stained either for apoptosis using a modified TUNEL procedure or for tartrate-resistant acid phosphatase to identify osteoclasts in the intracortical and periosteal envelopes. The percentage of apoptotic osteocytes, as well as osteoclast counts (n/mm or n/mm2) were quantified in four regions (0-1, 1-2, 2-4, and 4-8 mm from the site of the osteotomy; regions 1-4, respectively) in the osteotomized radii and in the same measured areas in the control radii. Data for osteocyte apoptosis and osteoclasts in the control limb were subtracted from the osteotomized limb data to identify differences due to surgical influence. The incidence of osteocyte apoptosis was significantly higher at 12, 24, 48, and 72 hours versus 0 hours following osteotomy, and the response was highest in region 1; however, there was no interaction between time and region. Intracortical osteoclast counts (n/mm2) were elevated after 48 hours, and the response was similar in all regions. The data demonstrate that osteocyte apoptosis occurs within 24 hours in response to an osteotomy and temporally precedes an increase in osteoclast presence. Hence, osteocyte apoptosis may play a role in signaling during the bone healing process.

Spinal meningeal cyst in a dog: a case report and literature review.

A two-year-old, female Chinese shar pei was presented with a one-year history of ataxia involving the pelvic limbs. The neurological lesion was localized to the thoracolumbar region of the spinal cord. A cyst involving the dorsal subarachnoid space at the level of the 12th thoracic vertebral body was identified with myelography. The diagnosis of a meningeal cyst was made, and surgical treatment consisting of a dorsal laminectomy and cyst fenestration was performed. The pelvic-limb ataxia improved, and the owners considered the dog to be normal three months after surgery. The classification, etiology, clinical signs, diagnostic techniques, treatment, and histology of meningeal cysts are reviewed.