The musculoskeletal consequences of latissmus dorsi breast reconstruction in women following mastectomy for breast cancer

INTRODUCTION: Current evidence suggests that patients who have latissimus dorsi (LD) breast reconstruction following mastectomy for breast cancer can experience long-term shoulder dysfunction. However, as there is no standardised assessment or follow-up period within the literature, findings are conflicting. This research aimed to investigate the impact on daily living of immediate and delayed LD breast reconstruction in women following mastectomy for breast cancer.METHODS: Both qualitative and quantitative methods of enquiry were used. A focus group study explored the musculoskeletal consequences of surgery as perceived by the women (n = 15) and their healthcare professionals (n = 11). A questionnaire survey was administered (n = 159), including a range of outcome measures to quantify both the physical and psychosocial impact of LD breast reconstruction. Dyad interviews were also conducted in order to determine the impact of surgery on function and activities of daily living (ADL) from the woman's perspective and that of her significant other (n = 8).RESULTS: The qualitative studies highlighted a lack of preparedness and unrealistic expectations regarding functional recovery among women and their significant others'. Post-surgery it was apparent that women weighed up reduced shoulder function against survival, demonstrating resilience in their approach to coping with this adaptive way of living. The survey identified low to moderate effect on the outcomes assessed (n = 159), however, node removal significantly impacted certain aspects of quality of life (p&lt;0.05) and disability (p = 0.04).CONCLUSIONS: Breast reconstruction using the LD had an impact on shoulder function and some ADL, which impacted not only on the women but also family and significant others. Despite the functional implications associated with surgery, findings would suggest that shoulder dysfunction is not their main concern. This work identified that women and their significant other require further information to clarify expectation regarding recovery, highlighting the changing priorities of women throughout their journey from diagnosis into long-term recovery.</p

Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Radically open-dialectical behavior therapy for adult anorexia nervosa: feasibility and outcomes from an inpatient program

Background Anorexia Nervosa (AN) is a highly life-threatening disorder that is extremely difficult to treat. There is evidence that family-based therapies are effective for adolescent AN, but no treatment has been proven to be clearly effective for adult AN. The methodological challenges associated with studying the disorder have resulted in recommendations that new treatments undergo preliminary testing prior to being evaluated in a randomized clinical trial. The aim of this study was to provide preliminary evidence on the effectiveness of a treatment program based on a novel adaptation of Dialectical Behavior Therapy (DBT) for adult Anorexia Nervosa (Radically Open-DBT; RO-DBT) that conceptualizes AN as a disorder of overcontrol. Methods Forty-seven individuals diagnosed with Anorexia Nervosa-restrictive type (AN-R; mean admission body mass index = 14.43) received the adapted DBT inpatient program (mean length of treatment = 21.7 weeks). Results Seventy-two percent completed the treatment program demonstrating substantial increases in body mass index (BMI; mean change in BMI = 3.57) corresponding to a large effect size (d = 1.91). Thirty-five percent of treatment completers were in full remission, and an additional 55% were in partial remission resulting in an overall response rate of 90%. These same individuals demonstrated significant and large improvements in eating-disorder related psychopathology symptoms (d = 1.17), eating disorder-related quality of life (d = 1.03), and reductions in psychological distress (d = 1.34). Conclusions RO-DBT was associated with significant improvements in weight gain, reductions in eating disorder symptoms, decreases in eating-disorder related psychopathology and increases in eating disorder-related quality of life in a severely underweight sample. These findings provide preliminary support for RO-DBT in treating AN-R suggesting the importance of further evaluation examining long-term outcomes using randomized controlled trial methodology

Comparison of the caries-protective effect of fluoride varnish with treatment as usual in nursery school attendees receiving preventive oral health support through the Childsmile oral health improvement programme - the Protecting Teeth@3 Study:a randomised controlled trial

Background: The Scottish Government set out its policy on addressing the poor oral health of Scottish children in 2005. This led to the establishment of Childsmile, a national programme designed to improve the oral health of children in Scotland. One element of the programme promotes daily tooth brushing in all nurseries in Scotland (Childsmile Core). A second targeted component (Childsmile Nursery) offers twice-yearly application of fluoride varnish to children attending nurseries in deprived areas. Studies suggest that fluoride varnish application can reduce caries in both adult and child populations. This trial aims to explore the effectiveness and cost-effectiveness of additional preventive value fluoride varnish application compared to Childsmile Core. Methods/Design: The Protecting Teeth@3 Study is an ongoing 2 year parallel group randomised treatment as usual controlled trial. Three-year-old children attending the ante pre-school year are randomised (1:1) to the intervention arm (fluoride varnish &#38; treatment as usual) or the control arm (treatment as usual). Children in the intervention arm will have Duraphat® fluoride varnish painted on the primary tooth surfaces and will continue to receive treatment as usual: the core Childsmile Nursery intervention. Children in the treatment as usual arm will receive the same series of contacts, without the application of varnish and will also continue with the Childsmile Core intervention. Interventions are undertaken by Childsmile trained extended duty dental nurses at six-monthly intervals. Participants receive a baseline dental inspection in nursery and an endpoint inspection in Primary 1 at the age of 5 years old. We will use primary and secondary outcome measures to compare the effectiveness of Duraphat® fluoride varnish plus treatment as usual with treatment as usual only in preventing any further dental decay. We will also undertake a full economic evaluation of the trial

The behaviour of repeat visitors to museums: Review and empirical findings

This study presents a theoretical and operational framework for analysing repeat visit to museums. Starting from the literature on repeat visit in tourism, the specificities of these cultural attractions are made explicit through a review of theoretical and applied works. Consistently with previous contributors, the paper suggests that the analysis of actual past behaviours has to be preferred to the one of attitudes. The application of proper econometric models is also remarked in order to put into account individual profiles. Information coming from three techniques is then used in an integrated way in order to provide a more comprehensive view of the phenomenon. Evidence from an ad hoc survey suggests the necessity to give a greater attention to perceived cultural value during the visit, promoting cultural events during the week and addressed to children, and taking care of those visitors that come from far places also through an integrated tourist supply. © 2013 Springer Science+Business Media Dordrecht

A basal lithostrotian titanosaur (Dinosauria: Sauropoda) with a complete skull: Implications for the evolution and paleobiology of titanosauria

We describe Sarmientosaurus musacchioi gen. et sp. nov., a titanosaurian sauropod dinosaur from the Upper Cretaceous (Cenomanian - Turonian) Lower Member of the Bajo Barreal Formation of southern Chubut Province in central Patagonia, Argentina. The holotypic and only known specimen consists of an articulated, virtually complete skull and part of the cranial and middle cervical series. Sarmientosaurus exhibits the following distinctive features that we interpret as autapomorphies: (1) maximum diameter of orbit nearly 40% rostrocaudal length of cranium; (2) complex maxilla - lacrimal articulation, in which the lacrimal clasps the ascending ramus of the maxilla; (3) medial edge of caudal sector of maxillary ascending ramus bordering bony nasal aperture with low but distinct ridge; (4) ´tongue-like´ ventral process of quadratojugal that overlaps quadrate caudally; (5) separate foramina for all three branches of the trigeminal nerve; (6) absence of median venous canal connecting infundibular region to ventral part of brainstem; (7) subvertical premaxillary, procumbent maxillary, and recumbent dentary teeth; (8) cervical vertebrae with ´strut-like´ centroprezygapophyseal laminae; (9) extremely elongate and slender ossified tendon positioned ventrolateral to cervical vertebrae and ribs. The cranial endocast of Sarmientosaurus preserves some of the most complete information obtained to date regarding the brain and sensory systems of sauropods. Phylogenetic analysis recovers the new taxon as a basal member of Lithostrotia, as the most plesiomorphic titanosaurian to be preserved with a complete skull. Sarmientosaurus provides a wealth of new cranial evidence that reaffirms the close relationship of titanosaurs to Brachiosauridae. Moreover, the presence of the relatively derived lithostrotian Tapuiasaurus in Aptian deposits indicates that the new Patagonian genus represents a ´ghost lineage´ with a comparatively plesiomorphic craniodental form, the evolutionary history of which is missing for at least 13 million years of the Cretaceous. The skull anatomy of Sarmientosaurus suggests that multiple titanosaurian species with dissimilar cranial structures coexisted in the early Late Cretaceous of southern South America. Furthermore, the new taxon possesses a number of distinctive morphologies - such as the ossified cervical tendon, extremely pneumatized cervical vertebrae, and a habitually downward- facing snout - that have rarely, if ever, been documented in other titanosaurs, thus broadening our understanding of the anatomical diversity of this remarkable sauropod clade. The latter two features were convergently acquired by at least one penecontemporaneous diplodocoid, and may represent mutual specializations for consuming low-growing vegetation.Fil: Martínez, Rubén Darío. Universidad Nacional de la Patagonia; ArgentinaFil: Lamanna, Matthew C.. Carnegie Museum Of Natural History; Estados UnidosFil: Novas, Fernando Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "bernardino Rivadavia"; ArgentinaFil: Ridgely, Ryan C.. Ohio University College Of Osteopathic Medicine; Estados UnidosFil: Casal, Gabriel. Universidad Nacional de la Patagonia; ArgentinaFil: Martínez, Javier E.. Hospital Regional de Comodoro Rivadavia; ArgentinaFil: Vita, Javier R.. Resonancia Magnética Borelli; ArgentinaFil: Witmer, Lawrence M.. Ohio University College Of Osteopathic Medicine; Estados Unido

Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation

Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin

Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women

IMPORTANCE: A recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for SCZ tend to have children at an earlier or later age. OBJECTIVE: To determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets. DESIGN, SETTING, AND PARTICIPANTS: This investigation used multiple independent genome-wide association study data sets. The SCZ sample comprised 18 957 SCZ cases and 22 673 controls in a genome-wide association study from the second phase of the Psychiatric Genomics Consortium, and the AFB sample comprised 12 247 genotyped women measured for AFB from the following 4 community cohorts: Estonia (Estonian Genome Center Biobank, University of Tartu), the Netherlands (LifeLines Cohort Study), Sweden (Swedish Twin Registry), and the United Kingdom (TwinsUK). Schizophrenia genetic risk for each woman in the AFB community sample was estimated using genetic effects inferred from the SCZ genome-wide association study. MAIN OUTCOMES AND MEASURES: We tested if SCZ genetic risk was a significant predictor of response variables based on published polynomial functions that described the relationship between maternal age and SCZ risk in offspring in Denmark. We substituted AFB for maternal age in these functions, one of which was corrected for the age of the father, and found that the fit was superior for the model without adjustment for the father's age. RESULTS: We observed a U-shaped relationship between SCZ risk and AFB in the community cohorts, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for the age of the father. We confirmed that SCZ risk profile scores significantly predicted the response variables (coefficient of determination R2 = 1.1E-03, P = 4.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014. CONCLUSIONS AND RELEVANCE: This study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers

Nurse-Led Medicines' Monitoring for Patients with Dementia in Care Homes: A Pragmatic Cohort Stepped Wedge Cluster Randomised Trial

People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines' monitoring.Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines' monitoring versus usual care.Five UK private sector care homes.41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine.Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step.Problems addressed and changes in medicines prescribed.Information was collected from participants' notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site.Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57-4.11, P <0.001. For example, pain was more likely to be treated (adjusted Odds Ratio [aOR] 3.84, 1.78-8.30), and more patients attended dentists and opticians (aOR 52.76 [11.80-235.90] and 5.12 [1.45-18.03] respectively). Profile use was associated with reduction in mental health medicines (aOR 4.45, 1.15-17.22).The WWADR Profile for Mental Health Medicines can improve the quality and safety of care, and warrants further investigation as a strategy to mitigate the known adverse effects of prescribed medicines.ISRCTN 48133332