Anatomic TSA for B2 glenoids treated with asymmetric reaming has equivalent survivorship and patient outcomes compared to type A glenoids at mean 9 years follow-up.

BACKGROUND: Walch B2 glenoids can present a challenge to shoulder arthroplasty surgeons. Short-term studies have demonstrated that corrective reaming to 10° of retroversion in anatomic total shoulder arthroplasty (aTSA) can result in good outcomes, however there is little data reporting the long-term outcomes in this cohort. B2 glenoids treated with high-side reaming present a theoretical risk of early glenoid component failure as one may ream into the subchondral bone. This study aimed to demonstrate that 1) B2 glenoids treated with corrective reaming have durable results and 2) offer similar results to Walch A1/2 in long-term follow-up. METHODS: Patients who underwent aTSA by a single surgeon (E.L.F.) were identified from a shoulder arthroplasty registry. Inclusion criteria included Walch A1, A2 or B2 glenoid, a diagnosis of primary shoulder osteoarthritis, and a minimum radiographic and clinical follow-up of 5 years. 43 patients with B2 glenoids were compared to a cohort of 42 patients with A1 or A2 glenoids. Preoperative computed tomography (CT) and radiographs were utilized to assess deformity, glenoid version, and posterior subluxation of the humeral head. Postoperatively, patients were assessed with radiographs and patient-reported outcome measures including American Shoulder and Elbow Surgeons (ASES) score, Simple Shoulder Test (SST) score, and Visual Analog Scale (VAS). RESULTS: 85 shoulders (82 patients, 42 B2 and 43 A1/A2 glenoids) with an average follow-up of 9.4 years were included. In the B2 cohort, the average retroversion was 21.1° and posterior subluxation was 69.4% compared with 10.6°(p<0.001) and 57.5% (p<0.001) in the A1 or A2 cohort. The cohort demographics were similar except for male sex (B2 69.8% vs A1 or A2 37.2%, p=0.008). There was no difference between the cohorts in their improvement in ASES (p=0.807), SST (p=0.586), or VAS (p=0.930) scores. There was no difference in lateral humeral offset (p=0.889) or acromial humeral interval (p=0.468) between initial postoperative and final follow-up visits. Survivorship for B2 glenoids was 97.6%, 94.1% and 73.3% at 5, 10 and 15 years, respectively compared to 97.6%, 91.9% and 83.5% in type A glenoids. The revision rate was similar between the two groups (p=0.432). Lazarus score (p=0.682) and rates of humeral radiolucency (p=0.366) and humeral osteolysis (p=0.194) were similar between the two cohorts at final follow-up. CONCLUSION: Asymmetric reaming of patients with B2 glenoids is a reliable method of glenoid preparation with excellent mid- to long-term clinical results, patient reported outcomes, and low revision rates similar to their A1 and A2 counterparts.

Osteopontin/secreted phosphoprotein-1 behaves as a molecular brake regulating the neuroinflammatory response to chronic viral infection.

BACKGROUND: Osteopontin (OPN) as a secreted signaling protein is dramatically induced in response to cellular injury and neurodegeneration. Microglial inflammatory responses in the brain are tightly associated with the neuropathologic hallmarks of neurodegenerative disease, but understanding of the molecular mechanisms remains in several contexts poorly understood. METHODS: Micro-positron emission tomography (PET) neuroimaging using radioligands to detect increased expression of the translocator protein (TSPO) receptor in the brain is a non-invasive tool used to track neuroinflammation in living mammals. RESULTS: In humanized, chronically HIV-infected female mice in which OPN expression was knocked down with functional aptamers, uptake of TSPO radioligand DPA-713 was markedly upregulated in the cortex, olfactory bulb, basal forebrain, hypothalamus, and central grey matter compared to controls. Microglia immunoreactive for Iba-1 were more abundant in some HIV-infected mice, but overall, the differences were not significant between groups. TSPO+ microglia were readily detected by immunolabeling of post-mortem brain tissue and unexpectedly, two types of neurons also selectively stained positive for TSPO. The reactive cells were the specialized neurons of the cerebellum, Purkinje cells, and a subset of tyrosine hydroxylase-positive neurons of the substantia nigra. CONCLUSIONS: In female mice with wild-type levels of osteopontin, increased levels of TSPO ligand uptake in the brain was seen in animals with the highest levels of persistent HIV replication. In contrast, in mice with lower levels of osteopontin, the highest levels of TSPO uptake was seen, in mice with relatively low levels of persistent infection. These findings suggest that osteopontin may act as a molecular brake regulating in the brain, the inflammatory response to HIV infection.

Correction to: Osteopontin/secreted phosphoprotein-1 behaves as a molecular brake regulating the neuroinflammatory response to chronic viral infection.

An amendment to this paper has been published and can be accessed via the original article.

Advancing basic and translational research to deepen understanding of the molecular immune-mediated mechanisms regulating long-term persistence of HIV-1 in microglia in the adult human brain.

Knowledge about the diversity microglia (MG) type and function in the rodent and human brain has advanced significantly in the last few years. Nevertheless, we have known for 40 years that MG, monocytes, and macrophages in the brain play crucial roles in the pathogenesis of the HIV-1 in all tissues. HIV enters and spreads in the brain early, long before the initiation of antiviral therapy. As a result, many people with HIV continue to experience neurologic and neuropsychiatric comorbid conditions collectively known as HIV-associated neurocognitive disorder (HAND). HIV pathogenic sequelae in the CNS pose a challenge for cure strategies. Detailed understanding at a mechanistic level of how low-level and latent HIV-1 infection in MG negatively impacts neuroglial function has remained somewhat elusive. Direct rigorous in vivo experimental validation that the virus can integrate into MG and assume a latent but reactivatable state has remained constrained. However, there is much excitement that human in vitro models for MG can now help close the gap. This review will provide a brief background to place the role of MG in the ongoing neurologic complications of HIV infection of the CNS, then focus on the use and refinement of human postmitotic monocyte-derived MG-like cells and how they are being applied to advance research on HIV persistence and proinflammatory signaling in the CNS. Critically, an understanding of myeloid plasticity and heterogeneity and rigorous attention to all aspects of cell handling is essential for reproducibility. Summary Sentence: This review focuses on human postmitotic monocyte-derived microglia-like cells as tools to advance research on HIV persistence and neuroinflammatory signaling.

Myeloid plasticity: The phenotype and function of myeloid cells (monocytes, macrophages, and microglia) are shaped and regulated by intercellular signals. These include cytokines, chemokines, and other cues from neighboring cells in the tissue microenvironment. In addition, paracrine and autocrine signals under the homeostatic state are altered with injury, stress, infection, or chronic disease conditions. In responding to these cues, myeloid cells undergo some or all of the following: morphologic changes, altered metabolism, variation of components released into the extracellular matrix, increased migration, cytokine/chemokine production, and phagocytosis. Human monocyte-derived microglia (hMMGS): Purified subpopulations of bone marrow-derived monocytes incubated in highly defined in vitro culture conditions that support the development of microglia-like cells. Their phenotype closely resembles primary cells (e.g., TMEM119, CXC3R1, P2YR12, PU.1, IRF8), and functionally, hMMGs are phagocytic and possess synaptic pruning and calcium signaling activity.

Surge-in-Place: Conversion of a Cardiac Catheterization Laboratory Into a COVID-19 Intensive Care Unit and Back Again.

In Spring 2020, the United States epicenter of COVID-19 was New York City, in which the borough of the Bronx was particularly affected. This Fall, there has been a resurgence of COVID-19 in Europe and the Midwestern United States. We describe our experience transforming our cardiac catheterization laboratories to accommodate an influx of COVID-19 patients so as to provide other hospitals with a potential blueprint. We transformed our pre/postprocedural patient care areas into COVID-19 intensive care and step-down units and maintained emergent invasive care for ST-segment elevation myocardial infarction using existing space and personnel.

Technique of laser calibration for wavelength-modulation spectroscopy with application to proton exchange membrane fuel cell measurements.

A diode laser sensor was developed for partial pressure and temperature measurements using a single water vapor transition. The Lorentzian half-width and line intensity of the transition were calibrated for conditions relevant to proton exchange membrane (PEM) fuel cell operation. Comparison of measured and simulated harmonics from wavelength-modulation spectroscopy is shown to yield accuracy of +/-2.5% in water vapor partial pressure and +/-3 degrees C in temperature despite the use of a single transition over a narrow range of temperatures. Collisional half-widths in air or hydrogen are measured so that calibrations can be applied to both anode and cathode channels of a PEM fuel cell. An in situ calibration of the nonlinear impact of modulation on laser wavelength is presented and used to improve the accuracy of the numerical simulation of the signal.

Osteopontin and Integrin Mediated Modulation of Post-Synapses in HIV Envelope Glycoprotein Exposed Hippocampal Neurons.

The advent of Human Immunodeficiency Virus (HIV) antiretrovirals have reduced the severity of HIV related neurological comorbidities but they nevertheless remain prevalent. Synaptic degeneration due to the action of several viral factors released from infected brain myeloid and glia cells and inflammatory cytokines has been attributed to the manifestation of a range of cognitive and behavioral deficits. The contributions of specific pro-inflammatory factors and their interplay with viral factors in the setting of treatment and persistence are incompletely understood. Exposure of neurons to chemokine receptor-4(CXCR4)-tropic HIV-1 envelope glycoprotein (Env) can lead to post-synaptic degradation of dendritic spines. The contribution of members of the extracellular matrix (ECM) and specifically, of perineuronal nets (PNN) toward synaptic degeneration, is not fully known, even though these structures are found to be disrupted in post-mortem HIV-infected brains. Osteopontin (Opn, gene name SPP1), a cytokine-like protein, is found in abundance in the HIV-infected brain. In this study, we investigated the role of Opn and its ECM integrin receptors, ß1- and ß3 integrin in modifying neuronal synaptic sculpting. We found that in hippocampal neurons incubated with HIV-1 Env protein and recombinant Opn, post-synaptic-95 (PSD-95) puncta were significantly increased and distributed to dendritic spines when compared to Env-only treated neurons. This effect was mediated through ß3 integrin, as silencing of this receptor abrogated the increase in post-synaptic spines. Silencing of ß1 integrin, however, did not block the increase of post-synaptic spines in hippocampal cultures treated with Opn. However, a decrease in the PNN to ßIII-tubulin ratio was found, indicating an increased capacity to support spine growth. From these results, we conclude that one of the mechanisms by which Opn counters the damaging impact of the HIV Env protein on hippocampal post-synaptic plasticity is through complex interactions between Opn and components of the ECM which activate downstream protective signaling pathways that help maintain the potential for effective post-synaptic plasticity.

An 8-Year-Old Boy With Fever, Splenomegaly, and Pancytopenia.

An 8-year-old boy with no significant past medical history presented to his pediatrician with 5 days of fever, diffuse abdominal pain, and pallor. The pediatrician referred the patient to the emergency department (ED), out of concern for possible malignancy. Initial vital signs indicated fever, tachypnea, and tachycardia. Physical examination was significant for marked abdominal distension, hepatosplenomegaly, and abdominal tenderness in the right upper and lower quadrants. Initial laboratory studies were notable for pancytopenia as well as an elevated erythrocyte sedimentation rate and C-reactive protein. Computed tomography (CT) of the abdomen and pelvis showed massive splenomegaly. The only significant history of travel was immigration from Albania 10 months before admission. The patient was admitted to a tertiary care children's hospital and was evaluated by hematology-oncology, infectious disease, genetics, and rheumatology subspecialty teams. Our multidisciplinary panel of experts will discuss the evaluation of pancytopenia with apparent multiorgan involvement and the diagnosis and appropriate management of a rare disease.

Association of human immunodeficiency virus and hepatitis C virus infection with long-term outcomes post-ST segment elevation myocardial infarction in a disadvantaged urban community.

BACKGROUND: HIV and HCV have been linked to an increased risk of cardiovascular disease (CVD). Their impact on long-term outcomes following ST-segment myocardial infarction (STEMI) has not been previously studied. METHODS: We leveraged data from a STEMI registry (n = 1208) at an inner-city health system to assess the influence of HIV and HCV on post-STEMI outcomes. Cox regression was used to compare HIV-monoinfected (n = 22), HCV-monoinfected (n = 26) and HIV-HCV-coinfected patients (n = 8) with the neither-infected group (n = 1152) with regard to death, death or any readmission, and death or CVD readmission. RESULTS: The cohort was majority black or Hispanic. Median follow-up was 4.3 years. Compared to the neither-infected group, the HIV-monoinfected group showed near-significantly higher risks of death or any readmission (HR = 1.62, 95% CI = 0.96, 2.74) and death or CVD readmission (HR = 1.82, 95% CI = 0.98, 3.39) after full adjustment. On similar comparison, the HCV-monoinfected group exhibited significantly higher risks of death (HR = 2.09, 95% CI = 1.05, 4.15) and death or any readmission (HR = 1.68, 95% CI = 1.07, 2.65), whereas the HIV-HCV-coinfected group showed higher risk of death (HR = 6.51, 95% CI = 2.28, 18.61). CONCLUSIONS: In this cohort composed mostly of race-ethnic minorities, HIV monoinfection tended to be associated with 1.6-to-1.8-fold higher risk of death or readmission for any cause or CVD over long-term follow-up compared to neither infection, whereas HCV monoinfection was associated with 1.7-to-2.1-fold higher risk of death and death or any readmission, and HIV-HCV coinfection with 6.5-fold higher risk of death. These associations require further study in larger populations, but highlight the importance of identifying and treating HIV and HCV in patients presenting with STEMI.

Deep learning using tumor HLA peptide mass spectrometry datasets improves neoantigen identification.

Neoantigens, which are expressed on tumor cells, are one of the main targets of an effective antitumor T-cell response. Cancer immunotherapies to target neoantigens are of growing interest and are in early human trials, but methods to identify neoantigens either require invasive or difficult-to-obtain clinical specimens, require the screening of hundreds to thousands of synthetic peptides or tandem minigenes, or are only relevant to specific human leukocyte antigen (HLA) alleles. We apply deep learning to a large (N = 74 patients) HLA peptide and genomic dataset from various human tumors to create a computational model of antigen presentation for neoantigen prediction. We show that our model, named EDGE, increases the positive predictive value of HLA antigen prediction by up to ninefold. We apply EDGE to enable identification of neoantigens and neoantigen-reactive T cells using routine clinical specimens and small numbers of synthetic peptides for most common HLA alleles. EDGE could enable an improved ability to develop neoantigen-targeted immunotherapies for cancer patients.

A Fully Customized Baseline Removal Framework for Spectroscopic Applications.

The task of proper baseline or continuum removal is common to nearly all types of spectroscopy. Its goal is to remove any portion of a signal that is irrelevant to features of interest while preserving any predictive information. Despite the importance of baseline removal, median or guessed default parameters are commonly employed, often using commercially available software supplied with instruments. Several published baseline removal algorithms have been shown to be useful for particular spectroscopic applications but their generalizability is ambiguous. The new Custom Baseline Removal (Custom BLR) method presented here generalizes the problem of baseline removal by combining operations from previously proposed methods to synthesize new correction algorithms. It creates novel methods for each technique, application, and training set, discovering new algorithms that maximize the predictive accuracy of the resulting spectroscopic models. In most cases, these learned methods either match or improve on the performance of the best alternative. Examples of these advantages are shown for three different scenarios: quantification of components in near-infrared spectra of corn and laser-induced breakdown spectroscopy data of rocks, and classification/matching of minerals using Raman spectroscopy. Software to implement this optimization is available from the authors. By removing subjectivity from this commonly encountered task, Custom BLR is a significant step toward completely automatic and general baseline removal in spectroscopic and other applications.

Matrix Effects in Quantitative Analysis of Laser-Induced Breakdown Spectroscopy (LIBS) of Rock Powders Doped with Cr, Mn, Ni, Zn, and Co.

Obtaining quantitative chemical information using laser-induced breakdown spectroscopy is challenging due to the variability in the bulk composition of geological materials. Chemical matrix effects caused by this variability produce changes in the peak area that are not proportional to the changes in minor element concentration. Therefore the use of univariate calibrations to predict trace element concentrations in geological samples is plagued by a high degree of uncertainty. This work evaluated the accuracy of univariate minor element predictions as a function of the composition of the major element matrices of the samples and examined the factors that limit the prediction accuracy of univariate calibrations. Five different sample matrices were doped with 10-85 000 ppm Cr, Mn, Ni, Zn, and Co and then independently measured in 175 mixtures by X-ray fluorescence, inductively coupled plasma atomic emission spectrometry, and laser-induced breakdown spectroscopy, the latter at three different laser energies (1.9, 2.8, and 3.7 mJ). Univariate prediction models for minor element concentrations were created using varying combinations of dopants, matrices, normalization/no normalization, and energy density; the model accuracies were evaluated using root mean square prediction errors and leave-one-out cross-validation. The results showed the superiority of using normalization for predictions of minor elements when the predicted sample and those in the training set had matrices with similar SiO2 contents. Normalization also mitigates differences in spectra arising from laser/sample coupling effects and the use of different energy densities. Prediction of minor elements in matrices that are dissimilar to those in the training set can increase the uncertainty of prediction by an order of magnitude. Overall, the quality of a univariate calibration is primarily determined by the availability of a persistent, measurable peak with a favorable transition probability that has little to no interference from neighboring peaks in the spectra of both the unknown and those used to train it.

Isotope ratios of H, C, and O in CO2 and H2O of the martian atmosphere.

Stable isotope ratios of H, C, and O are powerful indicators of a wide variety of planetary geophysical processes, and for Mars they reveal the record of loss of its atmosphere and subsequent interactions with its surface such as carbonate formation. We report in situ measurements of the isotopic ratios of D/H and (18)O/(16)O in water and (13)C/(12)C, (18)O/(16)O, (17)O/(16)O, and (13)C(18)O/(12)C(16)O in carbon dioxide, made in the martian atmosphere at Gale Crater from the Curiosity rover using the Sample Analysis at Mars (SAM)'s tunable laser spectrometer (TLS). Comparison between our measurements in the modern atmosphere and those of martian meteorites such as ALH 84001 implies that the martian reservoirs of CO2 and H2O were largely established ~4 billion years ago, but that atmospheric loss or surface interaction may be still ongoing.

A meta-analysis examining clinical test utility for assessing superior labral anterior posterior lesions.

BACKGROUND: The reported accuracy of clinical tests for superior labral anterior posterior lesions is extremely variable. Pooling results from multiple studies of higher quality is necessary to establish the best clinical tests to use. HYPOTHESIS: Certain clinical tests are superior to others for diagnosing the presence or absence of a superior labral anterior posterior lesion. STUDY DESIGN: Meta-analysis. METHODS: A literature search of MEDLINE (1966-2007), CINAHL (1982-2007), and BIOSIS (1995-2007) was performed for (labrum OR labral OR SLAP OR Bankart) AND (shoulder OR shoulder joint OR glenoid) AND (specificity OR sensitivity AND specificity). Identified articles were reviewed for inclusion criteria. Sensitivity and specificity values were recorded from each study and used for meta-analysis. RESULTS: Six of 198 identified studies satisfied the eligibility criteria. Active compression, anterior slide, crank, and Speed tests were analyzed using receiver operating characteristic curves. The accuracy of the anterior slide test was significantly inferior to that of the active compression, crank, and Speed tests. There was no significant difference in test accuracy found among active compression, crank, and Speed tests. Between studies, methodological scores did not significantly affect sensitivity and specificity values. CONCLUSION: The anterior slide test is a poor test for detecting the presence of a labral lesion in the shoulder. Active compression, crank, and Speed tests are more optimal choices. Clinicians should choose the active compression test first, crank second, and Speed test third when a labral lesion is suspected.

The effectiveness of thoracic spine manipulation for the management of musculoskeletal conditions: a systematic review and meta-analysis of randomized clinical trials.

Thoracic spine manipulation (TSM) is an intervention practiced by different professions, and recently an incursion of research using TSM has been published. The purpose of this review was to examine the effectiveness of TSM for the management of musculoskeletal conditions and the quality of trials that included TSM techniques. A comprehensive search of online databases was performed, and first authors of studies identified were contacted. Thirteen randomized clinical trials were included in the final review. The methodological quality of all studies was assessed using the 10-point PEDro scale. Seven of the 13 studies were of high quality. Three studies looked at TSM for treatment of shoulder conditions; however, there is limited evidence to support the use of TSM for shoulder conditions. Nine studies used TSM for the management of neck conditions. The meta-analysis identified a subset of homogeneous studies evaluating neck pain. The value of the pooled estimator (1.33) was statistically significant for the treatment effect of TSM in the studies with researcher effect removed (95 % confidence interval: 1.15, 1.52). This analysis suggests there is sufficient evidence to support the use of TSM for specific subgroups of patients with neck conditions. This review also identifies the need for further studies to examine the effectiveness of TSM to treat shoulder conditions and the effectiveness of TSM on neck conditions with long-term follow-up studies.

A meta-analysis examining clinical test utilities for assessing meniscal injury.

OBJECTIVE: To systematically review the most recent literature with meta-analysis to summarize the accuracy of clinical tests for assessing meniscal lesions of the knee. METHODS AND MEASURES: A computerized database search was performed to identify eligible articles. Identified articles were reviewed to determine eligibility and methodological quality. Sensitivity, specificity, likelihood ratios and diagnostic odd ratios were reproduced or recorded from each study. Meta-analysis was performed using the reported study sensitivity and specificity values. RESULTS: Three tests - joint line tenderness, McMurray's and Apley's - were compared in the meta-analysis. The methodological quality of the studies was found to have a significant effect on both the test sensitivities and specificities. Summary receiver operating characteristic (ROC) curves, sensitivity values, mean likelihood ratios and diagnostic odd ratios (DOR) uniformly show joint line tenderness (DOR = 10.98) to be the best ;common' test, followed by McMurray's (DOR = 3.99) and Apley's (DOR = 2.2). Thessaly's test reported the strongest DOR of 227, but samples were smaller (n = 410), than those for joint line tenderness (n = 1354), McMurray's (n = 1232) and Apley's (n = 479). CONCLUSION: Methodological quality varied from poor to fair among studies, affecting test performance. Future studies should, where possible, utilize larger samples of individuals without meniscal lesions to better estimate test specificity and thus more accurately identify optimal clinical tests.