Bisphenol-A and phthalate metabolism in children with neurodevelopmental disorders.

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine. HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers. METHODS: We measured the efficiency of glucuronidation in three groups of children, ASD (n = 66), ADHD (n = 46) and healthy controls (CTR, n = 37). The children were recruited from the clinics of Rutgers-NJ Medical School. A urine specimen was collected from each child. Multiple mass spectrometric analyses including the complete metabolome were determined and used to derive values for the efficiency of glucuronidation for 12 varied glucuronidation pathways including those for BPA and MEHP. RESULTS: (1) Both fold differences and metabolome analyses showed that the three groups of children were metabolically different from each other. (2) Of the 12 pathways examined, only the BPA and DEHP pathways discriminated between the three groups. (3) Glucuronidation efficiencies for BPA were reduced by 11% for ASD (p = 0.020) and 17% for ADHD (p<0.001) compared to controls. DEHP showed similar, but not significant trends. CONCLUSION: ASD and ADHD are clinically and metabolically different but share a reduction in the efficiency of detoxification for both BPA and DEHP with the reductions for BPA being statistically significant.

[Explaining radiation dose exposure : The role of the banana equivalent dose compared to the effective dose in patient communication]. / Strahlenexposition erklären : Die Rolle der Bananenäquivalentdosis im Vergleich zur effektiven Dosis im Rahmen der Patientenkommunikation.

BACKGROUND AND OBJECTIVES: Communicating the amount and effects of ionizing radiation to patients prior to an examination using x­rays is associated with challenges: first, calculating the expected dose prior to the examination and, second, quantifying and illustrating cancer risks. Analogies, such as comparing radiation exposure to accident risks, have limitations and may evoke unease. This study explores and compares two new approaches to discuss radiation exposure from common clinical examinations with patients: effective dose and exposure based on radioactive potassium-40 intake from the ingestion of bananas, the banana equivalent dose (BED). MATERIALS AND METHODS: The effective doses of the diagnostic reference levels (DRL) for computed tomography (CT) and X-ray examinations in adults were calculated using mean conversion factors for specific anatomic body regions. For the BED calculation of the diagnostic reference levels, the radiation dose from a conventional banana ingested over 50 years per becquerel was calculated. The outcomes were juxtaposed against an equivalent number of bananas and its respective radiation doses. RESULTS: The calculated doses, namely effective dose and BED, of the German DRL can serve as a reliable metric to discuss radiation exposure from medical imaging with patients prior to an examination. CONCLUSION: This is the first study to calculate the effective doses of the current DRL and to compare these with the pseudoscientific unit BED. While the BED serves as an interesting illustration to metaphorize radiation exposure, it is recommended to use the calculated effective dose of the DRL as the basis for educational consultations with patients.

Video Didactic Preparation Augments Problem-Based Learning for First Year Medical Students.

Problem-based learning (PBL) utilizes a self-directed strategy. This process relies on group participation to succeed. Students without a background in biology or medicine can feel overwhelmed by the complexity of the subject matter and unable to participate in the group learning process. We incorporated curated educational videos in the PBL curriculum to help address this situation. First year medical students participated in this study in the form of a typical PBL session. They were then assessed on basic and clinical science knowledge and their learning experience. Student basic science and clinical knowledge were similar between the student groups. However, the students given a list of suggested videos scored higher in their learning experience, perception of feeling prepared, and participating in the group PBL experience than students who were not given the video list. Results from this study indicate that videos can be utilized to enhance the PBL process.

Numeracy skills learning of children in Africa:-Are disabled children lagging behind?

Significant progress has been achieved in universal basic education in African countries since the late 1990s. This study provides empirical evidence on the within- and across-country variation in numeracy skills performance among children based on nationally representative data from eight African countries (DR Congo, The Gambia, Ghana, Lesotho, Sierra Leone, Togo, Tunisia, and Zimbabwe). We assess whether and to what extent children with disabilities lag in numeracy skills and how much it depends on their type of disabilities. More specifically, we explore whether disabled children benefit equally from better school system quality. The assessment is analysed as a natural experiment using the performance of non-disabled children as a benchmark and considering the different types of disabilities as random treatments. We first evaluate the variation in average numeracy skills in the eight African countries. They can roughly be divided into low- and high-numeracy countries. We apply Instrumental Variable (IV) methods to control the endogeneity of completed school years when assessing subjects' school performance and heterogeneous disability effects. Children with vision and hearing disabilities are not especially challenged in numeracy skills performance. The low numeracy skills among physically and intellectually disabled children are mainly attributable to their limited school attendance. Children with multiple disabilities are constrained both by low school attendance and by poor numeracy skills return to schooling. The average differences in school performance across the high- versus low-numeracy skill country groups are larger than the within-group average differences for disabled versus non-disabled kids. This indicates that school enrolment and quality are crucial for children's learning of numeracy skills, and that disabled children benefit equally from better school quality across these African countries.

An interactive feedback system for increasing hand antisepsis adherence in stationary intensive care.

BACKGROUND: Pathogens causing infections are in many cases transmitted via the hands of personnel. Thus, hand antisepsis has strong epidemiological evidence of infection prevention. Depending on various factors, hand antisepsis adherence ranges between 9.1% and 85.2%. AIM: To evaluate a new transponder system that reminded medical staff to use an alcohol-based hand rub based on indication by giving real-time feedback, to detect hand antisepsis adherence. METHODS: The monitoring system consisted of three components: a portable transponder detecting alcohol-based hand rub and able to give feedback; a beacon recognizing entries to and exits from the patient's surroundings; and a sensor placed at the hand-rub dispensers to count the number of hand rubs. With these components, the system provided feedback when hand antisepsis was not conducted although it was necessary according to moments 1, 4, and 5 of hand antisepsis. Adherence was measured in two use-cases with five phases, starting with the baseline measurement followed by intervention periods and phases without intervention to test the sustainability of the feedback. FINDINGS: Using the monitoring system, hand antisepsis adherence was increased by up to 104.5% in comparison to the baseline measurement. When the intervention ceased, however, hand antisepsis adherence decreased to less than or equal to the baseline measurement. CONCLUSION: A short-term intervention alone is not sufficient to lead to a long-term change in hand antisepsis adherence. Rather, permanent feedback and/or the integration in a multi-modal intervention strategy are necessary.

Young Individuals Are More Stable and Stand More Upright When Using Rollator Assistance During Standing up and Sitting Down.

Four-wheeled walkers or rollators are often used to assist older individuals in maintaining an independent life by compensating for muscle weakness and reduced movement stability. However, limited biomechanical studies have been performed to understand how rollator support affects posture and stability, especially when standing up and sitting down. Therefore, this study examined how stability and posture change with varying levels of rollator support and on an unstable floor. The aim was to collect comprehensive baseline data during standing up and sitting down in young participants. In this study, 20 able-bodied, young participants stood up and sat down both 1) unassisted and assisted using a custom-made robot rollator simulator under 2) full support and 3) touch support. Unassisted and assisted performances were analyzed on normal and unstable floors using balance pads with a compliant surface under each foot. Using 3D motion capturing and two ground-embedded force plates, we compared assistive support and floor conditions for movement duration, the relative timing of seat-off, movement stability (center of pressure (COP) path length and sway area), and posture after standing up (lower body sagittal joint angles) using ANOVA analysis. The relative event of seat-off was earliest under full support compared to touch and unassisted conditions under normal but not under unstable floor conditions. The duration of standing up and sitting down did not differ between support conditions on normal or unstable floors. COP path length and sway area during both standing up and sitting down were lowest under full support regardless of both floor conditions. Hip and knee joints were least flexed under full support, with no differences between touch and unassisted in both floor conditions. Hence, full rollator support led to increased movement stability, while not slowing down the movement, during both standing up and sitting down. During standing up, the full support led to an earlier seat-off and a more upright standing posture when reaching a stable stance. These results indicate that rollator support when handles are correctly aligned does not lead to the detrimental movement alterations of increased forward-leaning. Future research aims to verify these findings in older persons with stability and muscle weakness deficiencies.

Decreased Adiponectin Levels in Early Pregnancy Are Associated with High Risk of Prematurity for African American Women.

The relationship of low maternal serum adiponectin levels with preterm delivery among a multi-ethnic group has not been extensively investigated. We examined ethnic differences in cytokine/adipokine profiles and whether they contribute to several adverse pregnancy outcomes, particularly preterm delivery. Data and samples were from a large prospective observational cohort (n = 1776) of young, generally healthy pregnant women (African American 36.4%, Hispanic 48.0%, Caucasian 15.6%). Serum cytokine/adipokine concentrations were measured at entry (mean gestational age of 16.83 weeks) using the Liminex xMap Technology. Multivariable analyses were performed. A significant difference in adiponectin level was observed among ethnic groups. African Americans had a decreased adiponectin and increased resistin levels compared to Hispanics and Caucasians (p < 0.05 to p < 0.0001 for each). Decreased adiponectin (lowest quartile) was positively associated with preterm delivery independent of usual risk factors (adjusted odds ratio (AOR) 1.46, 95% confidence interval (CI) 1.05, 2.04 for all preterm and AOR 1.84, 95% CI 1.07, 3.17 for early preterm births). The results were unchanged when women with preeclampsia were excluded. Similar results were observed in African Americans. Decreased adiponectin levels were not related to preterm birth in either Hispanics or Caucasians. Lower adiponectin levels were also significantly associated with an increased risk of developing gestational diabetes (AOR 1.72, 95% CI 1.05, 2.84) and preeclampsia (AOR 1.45, 95% CI 1.00, 2.14) in the whole cohort and in Caucasians. We did not find any consistent relationships between the other markers with outcome variables. Dysregulation in maternal adiponectin at early gestation is associated with an increased risk of preterm delivery. An ethnic difference in adiponectin levels may contribute to a higher preterm delivery rate in African American women.

Preferences, trust, and performance in youth business groups.

We study how social preferences and norms of reciprocity are related to generalized (outgroup) and particularized (ingroup) trust among members of youth business groups in northern Ethiopia. The Ethiopian government promotes youth employment among land-poor rural youth by allocating them rehabilitated communal lands for the formation of sustainable businesses. The typical sustainable production activities that the groups can invest in include apiculture, forestry, horticulture, and livestock production. Our study used incentivized experiments to elicit social preferences, trust, and trustworthiness. We use data from 2427 group members in 246 functioning business groups collected in 2019. Altruistic and egalitarian preferences were associated with stronger norms to reciprocate, higher outgroup and ingroup trustworthiness and trust while spiteful and selfish preferences had opposite effects. The social preferences had both direct and indirect effects (through the norm to reciprocate) on trustworthiness and trust. Ingroup trust was positively correlated with a number of group performance indicators.

Involvement of the tuberomammillary nucleus of the hypothalamus in the modulation of nociception and joint edema in a model of monoarthritis.

AIMS: Investigate the involvement of the histaminergic projections from tuberomammillary nucleus (TMN) to the spinal cord in the modulation of nociception and peripheral edema in a model of monoarthritis. MAIN METHODS: Subacute monoarthritis was induced by an intraarticular injection of carrageenan followed by LPS 72 h later. Disability and joint edema were assessed at the 3rd hour after LPS and at every hour up to 6 h. KEY FINDINGS: Intrathecal administration of histamine potentiated joint incapacitation and edema, while the H1R antagonist cetirizine decreased both. The H3R agonist immepip decreased both incapacitation and edema, while the H3R antagonist thioperamide had the opposite effect. The microinjection of glutamate into the ventral TMN (vTMN) caused an increase of incapacitation and articular edema, whereas the blockade of this nucleus by cobalt chloride inhibited both parameters. Intrathecal administration of cetirizine prevented the increase of incapacitation and joint edema caused by glutamate microinjection into the vTMN. Similarly, an intrathecal injection of the NKCC1 cotransporter inhibitor bumetanide prevented the effects of glutamate microinjection into the vTMN, whereas coadministration of histamine with bumetanide only inhibited the potentiation of joint edema. A microinjection of orexin B into the vTMN potentiated incapacitation and joint edema, while coadministration of the OX1/2 receptor antagonist almorexant with orexin B did not. SIGNIFICANCE: These data support the notion that TMN participates in the modulation of a peripheral inflammatory process by means of histaminergic projections to the spinal cord, and the hypothalamus may trigger TMN activation by means of glutamate and orexin.

Individual free fatty acids have unique associations with inflammatory biomarkers, insulin resistance and insulin secretion in healthy and gestational diabetic pregnant women.

Objective: We investigated the relationships of maternal circulating individual free fatty acids (FFA) with insulin resistance, insulin secretion and inflammatory biomarkers during mid-pregnancy. Research design and methods: The data were drawn from a prospective cohort of generally healthy pregnant women (n=1368, African-American 36%, Hispanic 48%, Caucasian 16%) in Camden, NJ. We quantitatively determined 11 FFAs, seven cytokine/adipokine, homeostatic model assessment of insulin resistance (HOMA-IR) and C-peptide levels from the fasting blood samples that were collected at 16 weeks of gestation. Multivariate analyses were performed along with separate analyses for each individual FFA. Results: High HOMA-IR (p<0.001) and C-peptide (p<0.0001) levels were positively associated with a twofold to fourfold increased risk for developing gestational diabetes mellitus (GDM). Negative relationships were found with specific FFAs (molecular percentage, palmitoleic, oleic, linolenic, myristic acids) and HOMA-IR and C-peptide levels (p<0.01 to p<0.0001). In contrast, palmitic, stearic, arachidonic, dihomo-γ-linolenic (DGLA) and docosahexaenoic acids were positively associated with HOMA-IR and C-peptide (p<0.01 to p<0.0001). The individual FFAs also predicted cytokine/adipokine levels. For example, women who had elevated DGLA (highest quartile) were twice as (adjusted OR 2.06, 95% CI 1.42 to 2.98) likely to have higher interleukin (IL)-8 (p<0.0001) levels. Conversely, women with high palmitoleic, oleic, and linolenic acid levels had reduced odds (≥2-fold, p<0.01 to p<0.001) for having higher IL-8, IL-6 or tumor necrosis factor-alpha levels. Conclusion: Our results suggest that maternal individual FFAs uniquely affect insulin resistance and secretion. The effects are either direct or indirect via modulation of the inflammatory response. Modifying the composition of FFAs may help in reducing the risk of GDM.

Modelling human pathology of traumatic brain injury in animal models.

Traumatic brain injury (TBI) is caused by a head impact with a force exceeding regular exposure from normal body movement which the brain normally can accommodate. People affected include, but are not restricted to, sport athletes in American football, ice hockey, boxing as well as military personnel. Both single and repetitive exposures may affect the brain acutely and can lead to chronic neurodegenerative changes including chronic traumatic encephalopathy associated with the development of dementia. The changes in the brain following TBI include neuroinflammation, white matter lesions, and axonal damage as well as hyperphosphorylation and aggregation of tau protein. Even though the human brain gross anatomy is different from rodents implicating different energy transfer upon impact, especially rotational forces, animal models of TBI are important tools to investigate the changes that occur upon TBI at molecular and cellular levels. Importantly, such models may help to increase the knowledge of how the pathologies develop, including the spreading of tau pathologies, and how to diagnose the severity of the TBI in the clinic. In addition, animal models are helpful in the development of novel biomarkers and can also be used to test potential disease-modifying compounds in a preclinical setting.

Anatomic ligament consolidation of the superior acromioclavicular ligament and the coracoclavicular ligament complex after acute arthroscopically assisted double coracoclavicular bundle stabilization.

PURPOSE: The consolidation of the acromioclavicular (AC) and coracoclavicular (CC) ligament complex after arthroscopically assisted stabilization of acute acromioclavicular joint (ACJ) separation is still under consideration. METHODS: Fifty-five consecutive patients after arthroscopically assisted double-CC-bundle stabilization within 14 days after acute high-grade ACJ separation were studied prospectively. All patients were clinically analysed preoperatively (FU0) and post-operatively (FU1 = 6 months; FU2 = 12 months). The structural MRI assessments were performed at FU0 (injured ACJ) and at FU2 bilateral (radiologic control group) and assessed separately the ligament thickness and length at defined regions for the conoid, trapezoid and the superior AC ligament. RESULTS: Thirty-seven patients were assessed after 6.5 months and after 16.0 months. The 16-month MRI analysis revealed for all patients continuous ligament healing for the CC-complex and the superior AC ligament with in the average hypertrophic consolidation compared to the control side. Separate conoid and trapezoid strands (double-strand configuration) were detected in 27 of 37 (73%) patients, and a single-strand configuration was detected in 10 of 37 (27%) patients; both configurations showed similar CCD data. The ligament healing was not influenced by the point of surgery, age at surgery and heterotopic ossification. The clinical outcome was increased (FU0-FU2): Rowe, 47.7-97.0 pts.; TAFT, 3.9-10.6 pts.; NAS pain, 8.9-1.4 pts. (all P < 0.05). CONCLUSION: The arthroscopically assisted double-CC-bundle stabilization within 14 days after acute high-grade ACJ separation showed 16 months after surgery sufficient consolidations of the AC and double-CC ligament complex in 73%. LEVEL OF EVIDENCE: III, Case series.

Cell-free cartilage repair in large defects of the knee: increased failure rate 5 years after implantation of a collagen type I scaffold.

INTRODUCTION: Cartilage defects of the knee remain a challenging problem in orthopedic surgery despite the ongoing improvements in regenerative procedures such as the autologous chondrocyte transplantation. Due to the lack of donor-site morbidity and the single-stage procedure cell-free scaffolds are an interesting alternative to cell-based procedures. But as currently mid- and long-term data are lacking, the aim of the present study was to present mid-term clinical, radiological and histological results of a cell-free collagen type I scaffolds for cartilage repair. MATERIALS AND METHODS: Twenty-eight patients were followed prospectively. Clinical evaluation using patient-reported outcome measures (KOOS, IKDC; VAS for pain, Tegner score for activity) as well as radiologic evaluation of the repair tissue (MOCART) was performed at 1 year, 2 years and 5 years. Histologic evaluation of the repair tissue was done in case of revision surgery using the ICRS II score for human cartilage repair. RESULTS: In these large cartilage defects with a mean defect size of 3.7 ± 1.9 cm2, clinical failure necessitating revision surgery was seen in 5 of 28 patients (18%). While the remaining patients showed good-to-excellent clinical results (KOOS, IKDC, VAS, Tegner), the radiologic appearance of the repair tissue showed a reduction of the MOCART score between the 2- and 5-year follow-up. Histologic evaluation of the repair tissue showed a cartilage-like appearance with no signs of inflammation or cell death but an overall medium tissue quality according to the ICRS II Score. CONCLUSION: The use of this cell-free collagen type I scaffold for large defects showed increased wear of the repair tissue and clinical failure in 18% of cases at 5-year follow-up.

[Combined posterior and anterior cruciate ligament reconstruction : Arthroscopic treatment with the GraftLink® system]. / Kombinierte Rekonstruktion des hinteren und vorderen Kreuzbandes : Arthroskopische Versorgung mit dem GraftLink®-System.

OBJECTIVE: Simultaneous arthroscopic reconstruction of the anterior and/or posterior cruciate ligament (ACL/PCL) using the GraftLink® system (Arthrex) to obtain stable treatment and good functional results. The transplant is protected by the safety belt like biomechanical GraftLink® principle, which is used to secure the intraoperatively obtained stability in the long term. INDICATIONS: ACL, PCL, or combined cruciate ligament rupture, especially multiligament injuries. Revision ACL and PCL reconstruction. CONTRAINDICATIONS: Preoperative fixed posterior tibial subluxation. Reduced range of motion (ROM) with an extension lag (extension/flexion 0­0-120° preoperatively required). Complex regional pain syndrome. High-grade atrophy of the quadriceps femoris muscle and osseous deformities. SURGICAL TECHNIQUE: Supine position with mobile leg and possible flexion of at least 120° allowing antegrade femoral bone tunnel replacement. Retrograde tunnel placement (e. g. using a retrocutter) is recommended in case of less than 120° knee flexion. Thigh tourniquet. Staging arthroscopy. Cruciate ligament reconstruction is realized by anatomic tunnel placement for the ACL/PCL using the GraftLink®. Recommended sequence of reconstruction: 1. tibial PCL tunnel, 2. femoral ACL tunnel, 3. femoral PCL tunnel, 4. tibial ACL tunnel. Hybrid fixation is recommended. Portals: High anteromedial, high anterolateral, posteromedial, posterolateral, small subvastus incision. POSTOPERATIVE MANAGEMENT: Combined cruciate ligament replacement: Gradual load and ROM increase in the PCL track. After postoperative week 5, increasing load up to full weight bearing, with extension/flexion 0­0-90° after week 7. Down training of the PCL track after week 13. Contact and competitive sports after 1 year. RESULTS: The GraftLink® system allows restoration of knee joint stability with good functional results. The procedure is especially suitable for complex situations like after knee dislocation with ACL and PCL reconstruction in 1 or 2 steps.

Return to sport after acute acromioclavicular stabilization: a randomized control of double-suture-button system versus clavicular hook plate compared to uninjured shoulder sport athletes.

PURPOSE: Traumatic high-grade acromioclavicular joint (ACJ) separations can be surgically stabilized by numerous anatomic and non-anatomic procedures. The return to sport (Maffe et al. in Am J Sports Med 23:93-98, 1995] and remaining sport-associated impairments after acute ACJ stabilization has not yet been investigated. METHODS: 73 consecutive athletes with acute high-grade ACJ separation were prospectively assigned into two groups (64.4% randomized, 35.6% intention-to-treat): open clavicular hook plate (cHP) implantation (GI) or arthroscopically assisted double double-suture-button (dDSB) implantation (GII). Patients were analyzed using shoulder sport-specific measurement tools for sport ability (ASOSS), sport activity (SSAS), and numerical analog scales: NASpain during sport, NASshoulder function in sport, and NASre-achievement of sport level. Four points of examination were established: preoperative evaluation (FU0) and first postoperative follow-up (FU1) at 6 months; FU2 at 12 months; and FU3 at 24 months after surgery. The control group (GIII) consisted of 140 healthy athletes without anamnesis of prior macro-injury or surgery. RESULTS: After surgical stabilization, 29 of 35 athletes in GI (82.9%; 38.6 ± 9.9 years) and 32 of 38 in GII (82.9%; 38.6 ± 9.9 years) were followed up for 24 months (FU3) (loss 17.8%). All operated athletes showed significantly increased scores compared to FU0 (p < 0.05). Compared to GI, GII showed significantly superior outcome data for sporting ability as well as for NASre-achievement of sport level (p < 0.05). While GII re-achieved GIII-comparable SSAS and ASOSS levels, GI remained at a significantly inferior level. Athletes after ACJ injury of Rockwood grade IV/V and overhead athletes benefited significantly from the dDSB procedure. CONCLUSION: The dDSB procedure enabled significantly superior sport-specific outcomes compared to the cHP procedure. Athletes after dDSB surgeries re-achieved the sporting ability and the sport activity levels of healthy athletes, whereas athletes after cHP implantation remained at significantly inferior levels. The more extensive dDSB procedure and the more restrictive rehabilitation are recommended for treatment of acute high-grade ACJ separations of functionally high-demanding athletes. LEVEL OF EVIDENCE: I.

Femoral tunnel widening is associated with tunnel malposition but not with clinical failure after medial patellofemoral ligament reconstruction with a free gracilis tendon graft.

INTRODUCTION: MPFL reconstruction is widely and successfully used for treating patella instability, either as a standalone procedure or in combination. Although different techniques allow for MPFL reconstruction, the use of a free tendon graft is one of the most commonly used. The phenomenon of tunnel widening or tunnel enlargement is well described in ACL reconstruction, but so far only little effort has been put into evaluating this phenomenon after MPFL reconstruction. MATERIALS AND METHODS: Patients who received an MPFL reconstruction with a free gracilis tendon graft were identified by review of patient files. Additional clinical examination and magnetic resonance imaging were performed to assess tunnel enlargement and clinical outcome. RESULTS: Fifty-one knees of 49 patients (34 female, 17 male) with a mean follow-up of 3.0 ± 1.4 years were included in this study. Mean age at the time of surgery was 22.6 ± 8.5 years. Mean Tegner score decreased from preoperative 5.3 ± 2.0 to 4.0 ± 1.4 postoperative. Postoperative IKDC and Kujala scores were 74 ± 16 and 80 ± 15, respectively. Twenty-three patients showed a tunnel enlargement at follow-up examination. Of these 23 patients, 20 showed a tunnel that was positioned too proximal, whereas only 13 of the 28 patients showing no enlargement had a tunnel that was positioned too proximal (p = 0.0033). Interestingly, patients showing a tunnel enlargement at follow-up examination also showed significantly better Kujala (84 ± 12 vs. 75 ± 16; p = 0.03) and IKDC scores (80 ± 7 vs. 70 ± 19; p = 0.02) when compared to the non-enlarged group. CONCLUSION: Tunnel enlargement after MPFL reconstruction with a free gracilis tendon graft seems to be connected to mechanical overload due to a proximal malposition of the femoral tunnel. Interestingly, this did not influence clinical outcome as patients with tunnel enlargement showed better Kujala and IKDC scores.

Geographical differences in survival of dogs with non-Hodgkin lymphoma treated with a CHOP based chemotherapy protocol.

BACKGROUND: In humans geographical differences in the incidence and presentation of various cancers have been reported. However, much of this information has not been collected in veterinary oncology. AIM: The purpose of this study was to determine if a geographic difference in progression free survival exists for dogs with lymphoma treated within the US. MATERIALS AND METHODS: Medical records of 775 cases of canine lymphoma from 3 US regions (west, south and north), treated with CHOP chemotherapy, were retrospectively evaluated. Cases were collected from referral institutions and were required to have received at least one doxorubicin treatment and have follow up information regarding time to progression. RESULTS: Significant differences in sex (p = 0.05), weight (p = 0.049), stage (p < 0.001), immunophenotype (p = <0.001), and number of doxorubicin doses (p = 0.001) were seen between regions. Upon univariate analysis, progression free survival (PFS) differed by region (p = 0.006), stage (p = 0.009), sub-stage (p = 0.0005), and immunophenotype (p = 0.001). A multivariable Cox regression model showed that dogs in the western region had a significantly shorter PFS when compared to the south and east. CONCLUSION: PFS was significantly affected by stage, sub-stage and phenotype.

A quantitative study of tau pathology in 11 cases of chronic traumatic encephalopathy.

AIMS: To quantify tau pathology of chronic traumatic encephalopathy (CTE) and investigate influence of dot-like lesions (DL), brain region, comorbidity and sporting career length. METHODS: Densities of neurofibrillary tangles (NFT), astrocytic tangles (AT), DL, oligodendroglial inclusions (GI), neuropil threads (NT), vacuoles, neurons and enlarged neurons (EN) were measured in tau-immunoreactive sections of upper cortical laminae of frontal and temporal lobes, hippocampus (HC), amygdala and substantia nigra (SN) in 11 cases of CTE. RESULTS: DL were a consistent finding in CTE. Densities of NFT, NT and DL were greatest in sectors CA1 and CA2 of the HC. Densities of AT were lower than NFT, small numbers of GI were recorded in temporal lobe and low densities of vacuoles and EN were consistently present. ß-Amyloid-containing neuritic plaques (NP) also occurred at low density. Densities of NFT, NT, DL and AT were greater in sulci than gyri, while vacuole density was greater in gyri. Principal components analysis (PCA) suggested that sporting career length and densities of NFT in entorhinal cortex, NT in CA2 and SN and vacuolation in the DG were significant sources of variation among cases. CONCLUSION: DL are frequent in CTE suggesting affinity with argyrophilic grain disease (AGD) and Parkinson's disease dementia (PD-Dem). Densities of AT in all regions and NT/DL in sectors CA2/4 were consistent features of CTE. The 11 cases are neuropathologically heterogeneous which may result from genetic diversity, and variation in anatomical pathways subjected to trauma.

Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.

An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells.