Complex fractures of the distal humerus in the elderly: Is primary total elbow arthroplasty a valid treatment alternative? A series of 20 cases

SummaryIntroductionDistal humerus fractures are fairly rare. But as our population ages, these fractures become more complex and the choice of treatment more delicate. Poor bone quality results in many technical problems and the fixation hardware stability remains at risk. The goal of this study was to evaluate the functional recovery and morbidity of complex distal humerus fractures in elderly patients when treated with elbow prosthesis.HypothesisGood functional recovery can be achieved with a total joint replacement.Patients and methodsThis series consisted of 20 patients (18 women and two men) having an average age of 80years (range 65–93, median 80). Based on the AO classification, there were two Type A2 fractures, two Type B fractures, 15 Type C fractures and one fracture that could not be classified because of previous rheumatoid disease history at this elbow. Two fractures were open. In two cases, the olecranon was also fractured. Treatment consisted of the implantation of a Coonrad-Morrey, hinge-type total elbow prosthesis (Zimmer®, Warsaw, IN, USA). The Mayo Clinic surgical approach was used 17 times and the transolecranon approach was used three times. Primary arthroplasty was performed in 19 cases and the surgery was performed after six weeks of conservative treatment (diagnostic delay) in one case. Unrestricted motion was allowed after surgery, but a maximum of 0.5kg could be carried during the first 3months; this was subsequently increased to 2.5kg.ResultsFifteen of the 20 patients were available for reevaluation with an average follow-up of 3.6years (range 1.7–5.5, median 3.4). Four patients had died and one was lost to follow-up. The average range of motion was 97° (range 60–130°), comprising an average flexion of 130° (range 110–140°) and average loss of extension of 33° (range 0–80°). Pronation and supination were normal. The average Mayo Elbow Performance Score (MEPS) was 83 (range 60–100, median 80). X-rays revealed seven cases of radiolucent lines, with two being progressive. There was no visible wear of the polyethylene bushings at the hinge. Six patients had moderate periarticular heterotopic ossification. The two cases of olecranon osteotomy and one case of olecranon fracture had healed. There were no surgical site infections but two cases of ulnar compression, one of which required neurolysis. There was one case of humeral component loosening after 6years, but the implant was not changed.DiscussionThe clinical range of motion results were comparable to published data. The functional scores were slightly lower, mainly because of the pain factor. The initial results were encouraging and consistent with published data as long as the indications were well-chosen. Based on this retrospective study, total elbow arthroplasty can be a valid alternative in the surgeon's treatment armamentarium for complex distal humerus fractures in elderly patients who have moderate functional demands. Our results support our hypothesis, since we found good functional recovery without associated morbidity.Level of evidenceLevel IV retrospective study without comparator

Early prediction of femoral head avascular necrosis following neck fracture

SummaryFemoral neck fracture puts at risk functional prognosis in young patients and can be life-threatening in the elderly. The present study reviews methods of femoral head vascularity assessment following neck fracture, to address the following issues: what is the risk of osteonecrosis? And what, in the light of this risk, is the best-adapted treatment to avoid iterative surgery? Femoral head vascularity depends on retinacular vessels and especially the lateral epiphyseal artery, which contributes from 70 to 80% of the femoral head vascular supply. Fracture causes vascular lesions, which are in turn the prime cause of necrosis. Other factors combine with this: hematoma tamponade effect, reduced joint space and increased pressure due to lower extremity positioning in extension/internal rotation/abduction during surgery. Head deformity is not due to direct cell death but to the repair process originating from the surrounding living bone. In post-traumatic necrosis, proliferation rapidly invades the head, with significant osteogenesis. Pathologic fractures occur at the boundary between the new and dead bone. Many techniques have been reported to help assess residual hemodynamics and risk of necrosis. Some are invasive: superselective angiography, intra-osseous oxygen pressure measurement, or Doppler-laser hemodynamic measurement; others involve imaging: scintigraphy, conventionnal or dynamic MRI. The future seems to lie with dynamic MRI, which allows a new classification of femoral neck fractures, based on a non-invasive assessment of femoral head vascularity

Molecular basis for PrimPol recruitment to replication forks by RPA

DNA damage and secondary structures can stall the replication machinery. Cells possess numerous tolerance mechanisms to complete genome duplication in the presence of such impediments. In addition to translesion synthesis (TLS) polymerases, most eukaryotic cells contain a multi-functional replicative enzyme called Primase-Polymerase (PrimPol) that is capable of directly bypassing DNA damage by TLS, as well as repriming replication downstream of impediments. Here, we report that PrimPol is recruited to reprime through its interaction with RPA. Using biophysical and crystallographic approaches, we identify that PrimPol possesses two RPA-binding motifs and ascertained the key residues required for these interactions. We demonstrate that one of these motifs is critical for PrimPolʼs recruitment to stalled replication forks in vivo. In addition, biochemical analysis reveals that RPA serves to stimulate the primase activity of PrimPol. Together, these findings provide significant molecular insights into PrimPolʼs mode of recruitment to stalled forks to facilitate repriming and restart

Human Innate Mycobacterium tuberculosis–Reactive αβTCR+ Thymocytes

The control of Mycobacterium tuberculosis (Mtb) infection is heavily dependent on the adaptive Th1 cellular immune response. Paradoxically, optimal priming of the Th1 response requires activation of priming dendritic cells with Th1 cytokine IFN-γ. At present, the innate cellular mechanisms required for the generation of an optimal Th1 T cell response remain poorly characterized. We hypothesized that innate Mtb-reactive T cells provide an early source of IFN-γ to fully activate Mtb-exposed dendritic cells. Here, we report the identification of a novel population of Mtb-reactive CD4− αβTCR+ innate thymocytes. These cells are present at high frequencies, respond to Mtb-infected cells by producing IFN-γ directly ex vivo, and display characteristics of effector memory T cells. This novel innate population of Mtb-reactive T cells will drive further investigation into the role of these cells in the containment of Mtb following infectious exposure. Furthermore, this is the first demonstration of a human innate pathogen-specific αβTCR+ T cell and is likely to inspire further investigation into innate T cells recognizing other important human pathogens

Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins

PrimPol is a recently identified polymerase involved in eukaryotic DNA damage tolerance, employed in both re-priming and translesion synthesis mechanisms to bypass nuclear and mitochondrial DNA lesions. In this report, we investigate how the enzymatic activities of human PrimPol are regulated. We show that, unlike other TLS polymerases, PrimPol is not stimulated by PCNA and does not interact with it in vivo. We identify that PrimPol interacts with both of the major single-strand binding proteins, RPA and mtSSB in vivo. Using NMR spectroscopy, we characterize the domains responsible for the PrimPol-RPA interaction, revealing that PrimPol binds directly to the N-terminal domain of RPA70. In contrast to the established role of SSBs in stimulating replicative polymerases, we find that SSBs significantly limit the primase and polymerase activities of PrimPol. To identify the requirement for this regulation, we employed two forward mutation assays to characterize PrimPol's replication fidelity. We find that PrimPol is a mutagenic polymerase, with a unique error specificity that is highly biased towards insertion-deletion errors. Given the error-prone disposition of PrimPol, we propose a mechanism whereby SSBs greatly restrict the contribution of this enzyme to DNA replication at stalled forks, thus reducing the mutagenic potential of PrimPol during genome replication

A Novel Resource Polymorphism in Fish, Driven by Differential Bottom Environments: An Example from an Ancient Lake in Japan

Divergent natural selection rooted in differential resource use can generate and maintain intraspecific eco-morphological divergence (i.e., resource polymorphism), ultimately leading to population splitting and speciation. Differing bottom environments create lake habitats with different benthos communities, which may cause selection in benthivorous fishes. Here, we document the nature of eco-morphological and genetic divergence among local populations of the Japanese gudgeon Sarcocheilichthys (Cyprinidae), which inhabits contrasting habitats in the littoral zones (rocky vs. pebbly habitats) in Lake Biwa, a representative ancient lake in East Asia. Eco-morphological analyses revealed that Sarcocheilichthys variegatus microoculus from rocky and pebbly zones differed in morphology and diet, and that populations from rocky environments had longer heads and deeper bodies, which are expected to be advantageous for capturing cryptic and/or attached prey in structurally complex, rocky habitats. Sarcocheilichthys biwaensis, a rock-dwelling specialist, exhibited similar morphologies to the sympatric congener, S. v. microoculus, except for body/fin coloration. Genetic analyses based on mitochondrial and nuclear microsatellite DNA data revealed no clear genetic differentiation among local populations within/between the gudgeon species. Although the morphogenetic factors that contribute to morphological divergence remain unclear, our results suggest that the gudgeon populations in Lake Biwa show a state of resource polymorphism associated with differences in the bottom environment. This is a novel example of resource polymorphism in fish within an Asian ancient lake, emphasizing the importance and generality of feeding adaptation as an evolutionary mechanism that generates morphological diversification

Postnatal Cytomegalovirus Exposure in Infants of Antiretroviral-Treated and Untreated HIV-Infected Mothers

HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV transmission may impact growth and disease progression in HIV-exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA load and postnatal transmission, its impact on milk CMV load is unclear. We examined the relationship between milk CMV and HIV-1 load (4-6 weeks postpartum) and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian women and assessed the relationship between milk CMV load and postnatal growth in HIV-exposed, breastfed infants through six months of age. Despite an association between milk HIV-1 RNA and CMV DNA load (0.39 log 10 rise CMV load per log 10 rise HIV-1 RNA load, 95% CI 0.13-0.66), milk CMV load was similar in antiretroviral-treated and untreated women. Higher milk CMV load was associated with lower length-for-age (−0.53, 95% CI: −0.96, −0.10) and weight-for-age (−0.40, 95% CI: −0.67, −0.13) Zscore at six months in exposed, uninfected infants. As the impact of maternal antiretroviral therapy on the magnitude of postnatal CMV exposure may be limited, our findings of an inverse relationship between infant growth and milk CMV load highlight the importance of defining the role of perinatal CMV exposure on growth faltering of HIV-exposed infants

Understanding young adult physical activity, alcohol and tobacco use in community colleges and 4-year post-secondary institutions: A cross-sectional analysis of epidemiological surveillance data

<p>Abstract</p> <p>Background</p> <p>Young adults experience many adverse health behavior changes as they transition from adolescence into adulthood. A better understanding of the relationships between health promoting and risky health behaviors may aid in the development of health promotion interventions for various types of young adult post-secondary students. Therefore, the purpose of this study was to examine associations between alcohol and tobacco use and physical activity among 2-year and 4-year college students.</p> <p>Methods</p> <p>Cross-sectional analyses were conducted using 2007 survey data, collected as part of an on-going post-secondary health surveillance system in Minnesota. Students were randomly selected to participant from 14 Minnesota colleges and universities (six 2-year community and/or technical colleges, eight 4-year post-secondary institutions). The 2007 surveillance data included 9,931 respondents.</p> <p>Results</p> <p>The prevalence of demographic characteristics and health behaviors (e.g., physical activity, tobacco use) differed between young adults attending 2-year and 4-year post-secondary institutions; in general, those attending 2-year institutions are representative of more at-risk populations. Overall, higher levels of moderate, vigorous and strengthening physical activity were associated with higher levels of alcohol consumption and lower levels of smoking. In general, despite the disparities in the prevalence of these risk behaviors, the associations between the behaviors did not differ substantially between 2-year and 4-year post-secondary populations.</p> <p>Conclusions</p> <p>These findings illustrate links between leading risk behaviors. Interventions targeting multiple risk behaviors among young adults may warrant further consideration. Overall, future research is needed to support and inform young adult health promotion efforts that may be implemented in a wide array of post-secondary institutions.</p

Factors associated with early menarche: results from the French Health Behaviour in School-aged Children (HBSC) study

<p>Abstract</p> <p>Background</p> <p>Puberty is a transition period making physiological development a challenge adolescents have to face. Early pubertal development could be associated with higher risks of poor health. Our objective was to examine risk behaviours, physical and psychological determinants associated with early menarche (<11 years).</p> <p>Methods</p> <p>Early menarche was assessed in the Health Behaviour in School-aged Children French cross-sectional survey. Data were collected in 2006 by anonymous self-reported standardized questionnaire from a nationally representative sample of 1072 15 years old girls in school classrooms. Family environment, school experience, physical and psychological factors, risk behaviours (substance use and sexual initiation) were recorded. Logistic regression models were applied (analysing for crude and adjusted relationships between early menarche and risk behaviours controlled for family context).</p> <p>Results</p> <p>Median age at menarche was 13.0 years; 57 girls (5.3%) were early-matured. Controlled for familial environment, early menarche was associated with having had more than two life-drunkenness episodes (adjusted OR = 2.5 [1.3-4.6]), early sexual initiation (adjusted OR = 2.8 [1.3-6.0]) and overweight (adjusted OR = 7.3 [3.6-14.9]).</p> <p>Conclusion</p> <p>Early-maturing girls may affiliate with older adolescents, hence engage in risk behaviours linked to their appearance rather than their maturity level. Factors associated with early menarche highlight the need to focus attention on early-matured girls to prevent further health problems linked to risk behaviours.</p