Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.

➤ Short bone-conserving femoral stems in total hip arthroplasty were designed to preserve proximal bone stock.➤ Given the distinct fixation principles and location of loading among these bone-conserving stems, a classification system is essential to compare clinical outcomes.➤ Due to the low quality of currently available evidence, only a weak recommendation can be provided for clinical usage of certain stem designs, while some other designs cannot be recommended at this time.➤ A high prevalence of stem malalignment, incorrect sizing, subsidence, and intraoperative fractures has been reported in a subset of these short stem designs.➤ Stronger evidence, including prospective multicenter randomized trials comparing standard stems with these newer designs, is necessary before widespread use can be recommended.

Successful total knee arthroplasty (TKA) has often been based on the restoration of the knee to neutral alignment postoperatively. Numerous reports have linked malaligned TKA components to increased wear, poor functional outcomes, and failure. There have been many different alignment philosophies and surgical techniques that have been established to attain the goal of proper alignment, which includes such techniques as computerized navigation, and custom cutting guides. In addition, these methods could potentially have the added benefit of leading to improved functional outcomes following total knee arthroplasty. In this report, we have reviewed and analyzed recent reports concerning mechanical, anatomic, and kinematic axis/alignment schemes used in total knee arthroplasty.

The effect of varying corticosteroid regimens on hip osteonecrosis incidence remains unclear. We performed a meta-analysis and systematic literature review to determine osteonecrosis occurrences in patients taking corticosteroids at varying mean and cumulative doses and treatment durations, and whether medical diagnoses affected osteonecrosis incidence. Fifty-seven studies (23,561 patients) were reviewed. Regression analysis determined significance between corticosteroid usage and osteonecrosis incidence. Osteonecrosis incidence was 6.7% with corticosteroid treatment of >2 g (prednisone-equivalent). Systemic lupus erythematosus patients had positive correlations between dose and osteonecrosis incidence. Each 10 mg/d increase was associated with a 3.6% increase in osteonecrosis rate, and >20 mg/d resulted in a higher osteonecrosis incidence. Clinicians must be wary of osteonecrosis in patients on high corticosteroid regimens, particularly in systematic lupus erythematosus.

Background Aseptic loosening is the most common cause for revisions after lower-extremity total joint arthroplasties, however studies differ regarding the degree to which host factors influence loosening. Questions/purpose We performed a systematic review to determine which host factors play a role in the development of clinical and/or radiographic failure from aseptic loosening after (1) THA and (2) TKA. Methods Two searches on THA and TKA, respectively, using four electronic databases (EMBASE, CINAHL Plus, PubMed, and Scopus) were conducted. We identified a total of 209 reports that encompassed nine potential host factors affecting aseptic loosening. Inclusion criteria for consideration of scientific clinical reports were that 20 or more patients were involved, with more than 1-year followup, with at least three studies pertaining to each factor, and at least six of the Methodological Index for Non-randomized Studies criteria met, and with raw data for odds ratio (OR) calculations. Twenty-one studies (16 THA studies with 45,779 hips and five TKA studies with 288 knees, respectively) were used to calculate weighted OR and CIs (using the random effects theory) and study heterogeneity for four different host factors in THAs (male sex, high activity level, obesity defined as BMI C 30 kg/m 2 , and current or former tobacco use) and one factor in TKA (BMI C 30 kg/m 2 ), which were placed in a forest plot. Results For THA, male sex (OR, 1.39; 95% CI, 1.22-1.58; p = 0.001) and high activity level (University of California Los Angeles [UCLA] activity score C 8 points; OR, 4.24; 95% CI, 2.46-7.31; p = 0.001) were associated with aseptic loosening. However, obesity (OR, 1.01; 95% CI, 0.73-1.40; p = 0.96), and tobacco use (OR, 1.96; 95% CI, 0.43-8.97; p = 0.39) were not associated with an increased risk of aseptic loosening after THA with the numbers available. For TKA, we found no host factors associated with loosening. In particular, obesity (BMI C 30 kg/m 2