Can luteal regression be reversed?

The corpus luteum is an endocrine gland whose limited lifespan is hormonally programmed. This debate article summarizes findings of our research group that challenge the principle that the end of function of the corpus luteum or luteal regression, once triggered, cannot be reversed. Overturning luteal regression by pharmacological manipulations may be of critical significance in designing strategies to improve fertility efficacy

Prediction of function in daily life following multidisciplinary rehabilitation for individuals with chronic musculoskeletal pain; a prospective study

Background: The prevalence of chronic musculoskeletal pain is high, with widespread negative economic, psychological, and social consequences for the individual. It is therefore important to find ways to predict the outcome of rehabilitation programmes in terms of function in daily life. The aims of this study were to investigate the improvements over time from multidisciplinary rehabilitation in terms of pain and function, and analyse the relative impact of individual and psychosocial factors as predictors of function in daily life in individuals with chronic musculoskeletal pain. Methods: A prospective study was conducted among one hundred and forty three (N = 143) musculoskeletal pain patients. Measures of pain, function, and functional health status were obtained at baseline, after 5 weeks of intensive training, at the end of the 57-week rehabilitation programme, and at a 1 year follow-up, using validated self-administrated measures. Linear regression analysis was applied to investigate the relative impact of musculoskeletal pain, individual- , and psychosocial factors in function. Results: The participants studied showed a significant increase in function during the 57 weeks rehabilitation period. There was also a significant increase in function from the end of the rehabilitation period (57th week) to the one year follow-up measures. Pain intensity associated significantly with pain experience over all measurement periods. High levels of pain intensity (β = .42**) and pain experience (β = .37*), and poor psychological capacity (β = -.68*) at baseline, as well as poor physiological capacity (β = -.44**) and high levels of anxiety (β = .48**) and depression (β = .58***) at the end of the rehabilitation program were the most important prognostic factors of variance in functioning over the 4 measurement periods. Conclusion: The data suggest that physical capacity, emotional distress and coping skills should be priority areas in rehabilitation programmes to improve functioning in daily life

Dystropathology increases energy expenditure and protein turnover in the mdx mouse model of Duchenne muscular dystrophy

The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack functional dystrophin and undergo repeated bouts of necrosis, regeneration, and growth. These processes have a high metabolic cost. However, the consequences for whole body energy and protein metabolism, and on the dietary requirements for these macronutrients at different stages of the disease, are not well-understood. This study used juvenile (4- to 5- wk-old) and adult (12- to 14-wk-old) male dystrophic C57BL/10ScSn-mdx/J and age-matched C57BL/10ScSn/J control male mice to measure total and resting energy expenditure, food intake, spontaneous activity, body composition, whole body protein turnover, and muscle protein synthesis rates. In juvenile mdx mice that have extensive muscle damage, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were higher than in age-matched controls. Adaptations in food intake and decreased activity were insufficient to meet the increased energy and protein needs of juvenile mdx mice and resulted in stunted growth. In (non-growing) adult mdx mice with less severe dystropathology, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were also higher than in age-matched controls. Food intake was sufficient to meet their protein and energy needs, but insufficient to result in fat deposition. These data show that dystropathology impacts the protein and energy needs of mdx mice and that tailored dietary interventions are necessary to redress this imbalance. If not met, the resultant imbalance blunts growth, and may limit the benefits of therapies designed to protect and repair dystrophic muscles

Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma

Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca 2+ flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes. The inhibitors employed were the voltage gated Ca 2+ channel inhibitor Lomerizine (Lom), the Ca 2+ permeable AMPA receptor inhibitor YM872 and the P2X 7 receptor inhibitor oxATP. Results: Following partial optic nerve transection, hyper-phosphorylation of Tau and acetylated tubulin immunoreactivity were increased, and Nogo-A immunoreactivity was decreased, indicating that axonal changes occurred acutely. All combinations of ion channel inhibitors reduced hyper-phosphorylation of Tau and increased Nogo-A immunoreactivity at day 3 after injury. However, only Lom/oxATP or all three inhibitors in combination significantly reduced acetylated tubulin immunoreactivity. Most combinations of ion channel inhibitors were effective in restoring the lengths of the paranode and the paranodal gap, indicative of the length of the node of Ranvier, following injury. However, only all three inhibitors in combination restored to normal Ankyrin G length at the node of Ranvier. Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion channel inhibitors in combination. Conclusions: Data indicate that inhibiting any of a range of ion channels preserves certain elements of axon and node structure and limits some oxidative damage following injury, whereas ionic flux through all three channels must be inhibited to prevent lipid peroxidation and preserve Ankyrin G distribution and OPCs

Mitogenomic phylogenetic analyses of the Delphinidae with an emphasis on the Globicephalinae

BACKGROUND: Previous DNA-based phylogenetic studies of the Delphinidae family suggest it has undergone rapid diversification, as characterised by unresolved and poorly supported taxonomic relationships (polytomies) for some of the species within this group. Using an increased amount of sequence data we test between alternative hypotheses of soft polytomies caused by rapid speciation, slow evolutionary rate and/or insufficient sequence data, and hard polytomies caused by simultaneous speciation within this family. Combining the mitogenome sequences of five new and 12 previously published species within the Delphinidae, we used Bayesian and maximum-likelihood methods to estimate the phylogeny from partitioned and unpartitioned mitogenome sequences. Further ad hoc tests were then conducted to estimate the support for alternative topologies. RESULTS: We found high support for all the relationships within our reconstructed phylogenies, and topologies were consistent between the Bayesian and maximum-likelihood trees inferred from partitioned and unpartitioned data. Resolved relationships included the placement of the killer whale (Orcinus orca) as sister taxon to the rest of the Globicephalinae subfamily, placement of the Risso's dolphin (Grampus griseus) within the Globicephalinae subfamily, removal of the white-beaked dolphin (Lagenorhynchus albirostris) from the Delphininae subfamily and the placement of the rough-toothed dolphin (Steno bredanensis) as sister taxon to the rest of the Delphininae subfamily rather than within the Globicephalinae subfamily. The additional testing of alternative topologies allowed us to reject all other putative relationships, with the exception that we were unable to reject the hypothesis that the relationship between L. albirostris and the Globicephalinae and Delphininae subfamilies was polytomic. CONCLUSION: Despite their rapid diversification, the increased sequence data yielded by mitogenomes enables the resolution of a strongly supported, bifurcating phylogeny, and a chronology of the divergences within the Delphinidae family. This highlights the benefits and potential application of large mitogenome datasets to resolve long-standing phylogenetic uncertainties

European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce

Neuropathic pain in a rehabilitation setting after spinal cord injury: an interpretative phenomenological analysis of inpatients’ experiences

Study design Qualitative, semi-structured interviews. Objectives Neuropathic pain (NP) can be psychologically and physically debilitating, and is present in approximately half of the spinal cord injured (SCI) population. However, under half of those with NP are adherent to pain medication. Understanding the impact of NP during rehabilitation is required to reduce long-term impact and to promote adherence to medication and psychoeducation recommendations. Setting United Kingdom. Methods Five males and three females with SCI and chronic NP, resident in rehabilitation wards at a specialist SCI center in the United Kingdom, took part. Semi-structured interviews were conducted with participants less than 15 months post-SCI (mean = 8.4 months). Verbatim transcripts were subject to interpretative phenomenological analysis (IPA). Results Three super-ordinate themes were identified, mediating pain and adherence: (1) the dichotomy of safety perceptions; (2) adherence despite adversity; and (3) fighting the future. Analyses suggest that experience of the rehabilitation setting and responsiveness of care shapes early distress. Attitudes to medication and psychosocial adjustment are relevant to developing expectations about pain management. Conclusions Enhancing self-efficacy, feelings of safety in hospital, and encouraging the adoption of adaptive coping strategies may enhance psychosocial and pain-related outcomes, and improve adherence to medication. Encouraging adaptive responses to, and interpretation of, pain, through the use of interventions such as coping effectiveness training, targeted cognitive behavioral pain management, and acceptance-based interventions such as mindfulness, is recommended in order to reduce long-term reliance on medication

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion