Total Knee Arthroplasty Prehabilitation: Clinical Decisions related to Bony Malalignment, Neurologic Complexities, and Getting to Know a Patient

Background: The benefits of pre-operative habilitation or “prehabilitation” for total knee arthroplasty outcomes have been documented and researched over the last twenty years. However, the majority of these studies do not describe prehabilitation programs for patients with complex neurologic comorbidities. Purpose: The purpose of this case report is to describe clinical decisions made during the course of a prehabilitation program for a patient with a cerebellar disorder and bony malformation at her knee. Case Description: The patient was diagnosed with excessive tibial torsion when she was 60 years old and a year later diagnosed with uterine cancer and paraneoplastic cerebellar degeneration. The patient currently shows significant genu valgum at her right lower extremity and ambulates using a four wheeled walker, bilateral knee braces donned, and has an ataxic gait. Her goals for therapy are to improve her strength as she anticipates having a total knee arthroplasty, improve her balance, and stay active. Outcome Measures: Timed Up and Go (TUG), Berg Balance Scale, Dynamometer, as well as mass of weights lifted were used as outcome measures. Discussion: Low-load, high repetition and open kinetic chain movements were optimal means of strengthening for this particular patient, addressing both bony malformation and neurologic deficits. Additionally, the patient’s Timed Up and Go and Berg Balance Scale showed meaningful changes, possibly in part because the patient had good afferent signaling, but also because of the large amounts of time the patient dedicated to rehabilitation

Population policies, programmes and the environment

Human consumption is depleting the Earth's natural resources and impairing the capacity of life-supporting ecosystems. Humans have changed ecosystems more rapidly and extensively over the past 50 years than during any other period, primarily to meet increasing demands for food, fresh water, timber, fibre and fuel. Such consumption, together with world population increasing from 2.6 billion in 1950 to 6.8 billion in 2009, are major contributors to environmental damage. Strengthening family-planning services is crucial to slowing population growth, now 78 million annually, and limiting population size to 9.2 billion by 2050. Otherwise, birth rates could remain unchanged, and world population would grow to 11 billion. Of particular concern are the 80 million annual pregnancies (38% of all pregnancies) that are unintended. More than 200 million women in developing countries prefer to delay their pregnancy, or stop bearing children altogether, but rely on traditional, less-effective methods of contraception or use no method because they lack access or face other barriers to using contraception. Family-planning programmes have a successful track record of reducing unintended pregnancies, thereby slowing population growth. An estimated $15 billion per year is needed for family-planning programmes in developing countries and donors should provide at least$5 billion of the total, however, current donor assistance is less than a quarter of this funding target

Meta-Analysis of the Alzheimer\u27s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models.

We present a consensus atlas of the human brain transcriptome in Alzheimer\u27s disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington\u27s disease, amyotrophic lateral sclerosis, and aging. Other human coexpression modules, including those implicated in proteostasis, are not activated in AD models but rather following other, unexpected genetic manipulations. Our results comprise a cross-species resource, highlighting transcriptional networks altered by human brain pathophysiology and identifying correspondences with mouse models for AD preclinical studies

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder:The ENIGMA adventure

International audienc

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Beyond the Global Brain Differences:Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and globalbrain differences compared with noncarriers. However, interpreting regional differences is challenging if a globaldifference drives the regional brain differences. Intraindividual variability measures can be used to test for regionaldifferences beyond global differences in brain structure.METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n =30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matchednoncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual’sregional difference and global difference, were used to test for regional differences that diverge from the globaldifference.RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differedmore than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thicknessin regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal andsomatosensory cortex differed more than the global difference in cortical thickness.CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanismsinvolved in altered neurodevelopment