Osteomyelitis is a condition that disproportionately affects those with sickle cell anemia (SCA). Despite the frequency of osteomyelitis in this population, there are reports of increasing life ...expectancy and rates of Staphylococcus aureus infections, which contrasts the belief that Salmonella is the most common organism identified. The purpose of this systematic review is to determine the most commonly identified organism and identify whether age is associated with the development of Salmonella osteomyelitis in homozygous sickle cell patients.
A search of PubMed, EMBASE Cochrane and databases was performed for studies of all levels of evidence pertaining to osteomyelitis in SCA. Reasons for exclusion included non-English language, case reports, literature reviews, isolated septic arthritis without bony involvement and isolated oral-facial bony involvement.
The most common pathogen cultured was nontyphoid Salmonella , which occurred in 117 of 192 (60.9%) of cases identified. This was followed by S. aureus 41 of 192 (21.8%) and other enteric bacteria 14 of 192 (7.2%). Subgroup analysis demonstrated differences at the age of initial presentation with Salmonella cohort at 6.8 years and S. aureus cohort at 22.1 years ( P = 0.0001). On geographic analysis, African countries had an older average age of diagnosis at 13.1 years with decreased rates of Salmonella infections and increased rates of infections from other organisms compared with the US, Middle East and Europe.
This systematic review suggests that Salmonella is most commonly identified in patients with SCA (HbSS phenotype) especially those <12 years old presenting with acute osteomyelitis. Sub-Saharan African countries had later ages of diagnosis compared with the US, Middle East and Europe with bacterial profiles that favors a diagnosis of chronic osteomyelitis and missed acute initial presentation. Therefore, age of presentation is likely a surrogate for geographic and socioeconomic factors such as availability of medical screening and treatment.
Neuroanatomists have long speculated that expanded primate brains contain an increased morphological diversity of inhibitory neurons (INs)
, and recent studies have identified primate-specific ...neuronal populations at the molecular level
. However, we know little about the developmental mechanisms that specify evolutionarily novel cell types in the brain. Here, we reconstruct gene expression trajectories specifying INs generated throughout the neurogenic period in macaques and mice by analysing the transcriptomes of 250,181 cells. We find that the initial classes of INs generated prenatally are largely conserved among mammals. Nonetheless, we identify two contrasting developmental mechanisms for specifying evolutionarily novel cell types during prenatal development. First, we show that recently identified primate-specific TAC3 striatal INs are specified by a unique transcriptional programme in progenitors followed by induction of a distinct suite of neuropeptides and neurotransmitter receptors in new-born neurons. Second, we find that multiple classes of transcriptionally conserved olfactory bulb (OB)-bound precursors are redirected to expanded primate white matter and striatum. These classes include a novel peristriatal class of striatum laureatum neurons that resemble dopaminergic periglomerular cells of the OB. We propose an evolutionary model in which conserved initial classes of neurons supplying the smaller primate OB are reused in the enlarged striatum and cortex. Together, our results provide a unified developmental taxonomy of initial classes of mammalian INs and reveal multiple developmental mechanisms for neural cell type evolution.
Background:
Anterior shoulder instability is the pattern most commonly reported in the civilian population, but military servicemembers may represent a unique population. At 1.7 per 1000 ...person-years, servicemembers not only have a higher incidence of instability events compared with civilians (reported rate of 0.2-0.8), but the distribution of labral tears in the military may differ significantly as well.
Hypothesis:
The incidence of combined and posterior labral tears in the military population will be greater than numbers previously reported.
Study Design:
Cross-sectional study; Level of evidence, 3.
Methods:
The Wounded, Ill, and Injured Registry, a Department of Defense patient reported outcomes data collection platform that includes all military branches, was queried retrospectively for all patients who had undergone a primary arthroscopic or open shoulder stabilization procedure (Current Procedural Terminology codes 29806, 23455, 23462) between October 2016 and January 2019. Demographic information was obtained through intake forms completed by patients at the time of enrollment into the Military Orthopaedics Tracking Injuries and Outcomes Network. Tear location was determined arthroscopically and labeled as anterior, inferior, posterior, superior, or any combination thereof. Chi-square analysis was used to compare the percentage of patients with isolated anterior, isolated posterior, isolated inferior, or combined labral tears in the current study cohort with those in a previously reported cohort of patients with operative shoulder instability at a single military treatment facility.
Results:
A total of 311 patients were included who had undergone primary shoulder stabilization during the study period. Of these patients, 94 (30.2%) had isolated anterior tears, 76 (24.4%) had isolated posterior tears, and 136 (43.7%) had combined tears. We observed a higher percentage of combined tears in our data set than in a data set from a single military treatment facility (χ2(2) = 48.2; P < .00001). Chi-square analysis demonstrated that significantly more female patients had an isolated anterior labral tear (51.2%) compared with male patients (27.1%; χ2(2) = 9.4; P = .009).
Conclusion:
The incidence of combined and posterior labral tears in the military population is greater than numbers previously reported in both military and civilian populations.
Study objective Community-associated methicillin-resistant Staphylococcus aureus is now the leading cause of uncomplicated skin abscesses in the United States, and the role of antibiotics is ...controversial. We evaluate whether trimethoprim-sulfamethoxazole reduces the rate of treatment failures during the 7 days after incision and drainage and whether it reduces new lesion formation within 30 days. Methods In this multicenter, double-blind, randomized, placebo-controlled trial, we randomized adults to oral trimethoprim-sulfamethoxazole or placebo after uncomplicated abscess incision and drainage. Using emergency department rechecks at 2 and 7 days and telephone follow-up, we assessed treatment failure within 7 days, and using clinical follow-up, telephone follow-up, and medical record review, we recorded the development of new lesions within 30 days. Results We randomized 212 patients, and 190 (90%) were available for 7-day follow-up. We observed a statistically similar incidence of treatment failure in patients receiving trimethoprim-sulfamethoxazole (15/88; 17%) versus placebo (27/102; 26%), difference 9%, 95% confidence interval –2% to 21%; P =.12. On 30-day follow-up (successful in 69% of patients), we observed fewer new lesions in the antibiotic (4/46; 9%) versus placebo (14/50; 28%) groups, difference 19%, 95% confidence interval 4% to 34%, P =.02. Conclusion After the incision and drainage of uncomplicated abscesses in adults, treatment with trimethoprim-sulfamethoxazole does not reduce treatment failure but may decrease the formation of subsequent lesions.
•Organoids offer a window into genetic and cellular mechanisms underlying brain evolution.•Organoids capture cell diversity and interactions that occur during development.•Organoid modeling could be ...applied to study specialized traits linked to cognition.
Primate brains vary dramatically in size and organization, but the genetic and developmental basis for these differences has been difficult to study due to lack of experimental models. Pluripotent stem cells and brain organoids provide a potential opportunity for comparative and functional studies of evolutionary differences, particularly during the early stages of neurogenesis. However, many challenges remain, including isolating stem cell lines from additional great ape individuals and species to capture the breadth of ape genetic diversity, improving the reproducibility of organoid models to study evolved differences in cell composition and combining multiple brain regions to capture connectivity relationships. Here, we describe strategies for identifying evolved developmental differences between humans and non-human primates and for isolating the underlying cellular and genetic mechanisms using comparative analyses, chimeric organoid culture, and genome engineering. In particular, we focus on how organoid models could ultimately be applied beyond studies of progenitor cell evolution to decode the origin of recent changes in cellular organization, connectivity patterns, myelination, synaptic development, and physiology that have been implicated in human cognition.
Human pluripotent stem cells hold significant promise for regenerative medicine. However, long differentiation protocols and immature characteristics of stem cell-derived cell types remain challenges ...to the development of many therapeutic applications. In contrast to the slow differentiation of human stem cells in vitro that mirrors a nine-month gestation period, mouse stem cells develop according to a much faster three-week gestation timeline. Here, we tested if co-differentiation with mouse pluripotent stem cells could accelerate the differentiation speed of human embryonic stem cells. Following a six-week RNA-sequencing time course of neural differentiation, we identified 929 human genes that were upregulated earlier and 535 genes that exhibited earlier peaked expression profiles in chimeric cell cultures than in human cell cultures alone. Genes with accelerated upregulation were significantly enriched in Gene Ontology terms associated with neurogenesis, neuron differentiation and maturation, and synapse signaling. Moreover, chimeric mixed samples correlated with in utero human embryonic samples earlier than human cells alone, and acceleration was dose-dependent on human-mouse co-culture ratios. The altered gene expression patterns and developmental rates described in this report have implications for accelerating human stem cell differentiation and the use of interspecies chimeric embryos in developing human organs for transplantation.
An equitable approach by the American College of Medical Genetics and Genomics (ACMG) has recently recommended carrier screening for genes associated with moderate to severe autosomal recessive ...conditions with a carrier frequency of ≥1/200 in the Genome Aggregation Database exomes (gnomADv2.0.2). We analyzed carrier frequencies in gnomADv3.1.1 genomes representing diverse populations. ClinVar data on 35 996 pathogenic/likely pathogenic variants in 419 genes were used to estimate the gnomAD frequency of heterozygous carriers. We found that ninety‐two genes had a carrier frequency of ≥1/200, of which 63 were shared between v3.1.1 and v2.0.2 and 29 were new in v3.1.1. Addition of new populations (Amish, Finnish and Middle Eastern) increased the number of new genes with a carrier frequency of ≥1/200 to 71. Changes in carrier frequencies were attributed to new gnomAD populations, different sample sizes, new ClinVar data, and technical differences between exomes and genomes. This study highlights the dynamic changes in carrier frequencies due to new datasets from diverse populations and provides updated carrier frequencies based on the combined data from 184 352 genomes and exomes in gnomAD. We recommend a periodic review for inclusion of new population data to update carrier screening panels in the future.
Updated carrier frequencies of autosomal recessive conditions are provided using the combined data from 184 352 genomes and exomes in gnomAD. We highlight the dynamic changes in carrier frequencies as genome data from new diverse populations become available and provide a bioinformatic framework for future comparative analyses of population databases.
Hip Injuries in the Adolescent Athlete Schroeder, Paul B; Nicholes, Marc A; Schmitz, Matthew R
Clinics in sports medicine
40, Številka:
2
Journal Article
Recenzirano
This article provides concise and up-to-date information on the most common hip pathologies that affect adolescent athletes. We cover the evaluation and treatment of avulsion injuries, stress ...fractures, slipped capital femoral epiphysis (SCFE), femoroacetabular impingement, developmental dysplasia of the hip, Legg-Calve-Perthes disease, and coxa saltans focusing on minimizing advanced imaging and using conservative therapy when applicable. Although this is not an all-encompassing list of disorders, it is key to understand these hip pathologies because these injuries occur commonly and can also have detrimental complications if not diagnosed and addressed early, especially SCFE and femoral neck stress fractures.
Central estrogen signaling coordinates energy expenditure, reproduction, and in concert with peripheral estrogen impacts skeletal homeostasis in females. Here, we ablate estrogen receptor alpha (ERα) ...in the medial basal hypothalamus and find a robust bone phenotype only in female mice that results in exceptionally strong trabecular and cortical bones, whose density surpasses other reported mouse models. Stereotaxic guided deletion of ERα in the arcuate nucleus increases bone mass in intact and ovariectomized females, confirming the central role of estrogen signaling in this sex-dependent bone phenotype. Loss of ERα in kisspeptin (Kiss1)-expressing cells is sufficient to recapitulate the bone phenotype, identifying Kiss1 neurons as a critical node in this powerful neuroskeletal circuit. We propose that this newly-identified female brain-to-bone pathway exists as a homeostatic regulator diverting calcium and energy stores from bone building when energetic demands are high. Our work reveals a previously unknown target for treatment of age-related bone disease.
Background: Acetabular labral tears as a source of potential hip pain have received a great deal of attention in recent literature. The gold standard for identifying acetabular labral tears is hip ...arthroscopy, but recent advances in optimized, noncontrast magnetic resonance imaging (MRI) have proven effectiveness in identifying intra-articular hip pathological changes without the invasive nature of hip arthroscopy or gadolinium-enhanced arthrography. There are little data in the literature on imaging results in an asymptomatic population.
Purpose: The objective of this study was to use an optimized, noncontrast 1.5-T MRI protocol to identify hip abnormalities, including paralabral cysts, in asymptomatic volunteers.
Study Design: Case series (prevalence); Level of evidence, 4.
Methods: In this study, 42 hips in asymptomatic patients with an average age of 34 years (range, 27-43 years) were prospectively imaged with optimized, noncontrast 1.5-T MRI scans. Two fellowship-trained musculoskeletal radiologists interpreted the scans at 2 different points in time and commented on the presence of labral abnormalities including paralabral cysts. The results were analyzed for both interobserver and intraobserver reliability.
Results: Acetabular paralabral cysts were identified in 11 of 42 (26.2%) and 9 of 42 (21.4%) hips by the 2 respective radiologists, with an interobserver reliability of 90.5% (κ = .74) and intraobserver reliability of 95.2% (κ = .87). In addition, acetabular labral tears were identified in 36 of 42 (85.7%) and 34 of 42 (80.9%) hips, with an interobserver reliability of 90.5% (κ = .70) and intraobserver reliability of 95.2% (κ = .83).
Conclusion: Utilizing an optimized, noncontrast 1.5-T MRI protocol, we report the previously undescribed prevalence of acetabular labral pathological abnormalities and paralabral cysts in a young, asymptomatic population. This emphasizes the importance of correlating patient symptoms with history and physical examination when evaluating patients with hip pain and radiographic abnormalities as defined by MRI criteria. These data demonstrate that labral tears can occur without symptoms.
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