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1.
BMC Bioinformatics ; 20(1): 520, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653208

RESUMO

BACKGROUND: Due the computational complexity of sequence alignment algorithms, various accelerated solutions have been proposed to speedup this analysis. NVBIO is the only available GPU library that accelerates sequence alignment of high-throughput NGS data, but has limited performance. In this article we present GASAL2, a GPU library for aligning DNA and RNA sequences that outperforms existing CPU and GPU libraries. RESULTS: The GASAL2 library provides specialized, accelerated kernels for local, global and all types of semi-global alignment. Pairwise sequence alignment can be performed with and without traceback. GASAL2 outperforms the fastest CPU-optimized SIMD implementations such as SeqAn and Parasail, as well as NVIDIA's own GPU-based library known as NVBIO. GASAL2 is unique in performing sequence packing on GPU, which is up to 750x faster than NVBIO. Overall on Geforce GTX 1080 Ti GPU, GASAL2 is up to 21x faster than Parasail on a dual socket hyper-threaded Intel Xeon system with 28 cores and up to 13x faster than NVBIO with a query length of up to 300 bases and 100 bases, respectively. GASAL2 alignment functions are asynchronous/non-blocking and allow full overlap of CPU and GPU execution. The paper shows how to use GASAL2 to accelerate BWA-MEM, speeding up the local alignment by 20x, which gives an overall application speedup of 1.3x vs. CPU with up to 12 threads. CONCLUSIONS: The library provides high performance APIs for local, global and semi-global alignment that can be easily integrated into various bioinformatics tools.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31661898

RESUMO

Few studies examined the impact of maternal socioeconomic status and of its combined effects with environmental exposures on birthweight. Our goal was to examine the impact of maternal homelessness (mothers ever homeless or who lived in shelters during pregnancy) and participation in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) during pregnancy in conjunction with air pollution exposure on birthweight in the Boston-based Children's HealthWatch cohort from 2007 through 2015 (n = 3366). Birthweight was obtained from electronic health records. Information on maternal homelessness and WIC participation during pregnancy were provided via a questionnaire. Prenatal fine particulate matter (PM2.5) exposures, estimated at the subject's residential address, were calculated for each trimester. We fit linear regression models adjusting for maternal and child characteristics, seasonality, and block-group-level median household income and examined the interactions between PM2.5 and each covariate. Prenatal maternal homelessness was associated with reduced birthweight (-55.7 g, 95% CI: -97.8 g, -13.7 g), while participating in WIC was marginally associated with increased birthweight (36.1 g, 95% CI: -7.3 g, 79.4 g). Only average PM2.5 during the second trimester was marginally associated with reduced birthweight (-8.5 g, 95% CI: -19.3, 2.3) for a 1 µg/m3 increase in PM2.5. The association of PM2.5 during the second trimester with reduced birthweight was stronger among non-Hispanic Black mothers and trended toward significance among immigrants and single mothers. Our study emphasizes the independent and synergistic effects of social and environmental stressors on birthweight, particularly the potentially protective effect of participating in WIC for vulnerable populations.

3.
Nature ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31634902

RESUMO

Most genetic variants that contribute to disease1 are challenging to correct efficiently and without excess byproducts2-5. Here we describe prime editing, a versatile and precise genome editing method that directly writes new genetic information into a specified DNA site using a catalytically impaired Cas9 fused to an engineered reverse transcriptase, programmed with a prime editing guide RNA (pegRNA) that both specifies the target site and encodes the desired edit. We performed more than 175 edits in human cells including targeted insertions, deletions, and all 12 types of point mutation without requiring double-strand breaks or donor DNA templates. We applied prime editing in human cells to correct efficiently and with few byproducts the primary genetic causes of sickle cell disease (requiring a transversion in HBB) and Tay-Sachs disease (requiring a deletion in HEXA), to install a protective transversion in PRNP, and to insert various tags and epitopes precisely into target loci. Four human cell lines and primary post-mitotic mouse cortical neurons support prime editing with varying efficiencies. Prime editing offers efficiency and product purity advantages over homology-directed repair, complementary strengths and weaknesses compared to base editing, and much lower off-target editing than Cas9 nuclease at known Cas9 off-target sites. Prime editing substantially expands the scope and capabilities of genome editing, and in principle could correct about 89% of known pathogenic human genetic variants.

4.
Genet Med ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31578471

RESUMO

PURPOSE: Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved. METHODS: Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types of SOX5 alterations. Functional consequences of selected substitutions were investigated. RESULTS: Microdeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated. CONCLUSIONS: This study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features.

5.
PLoS One ; 14(9): e0222342, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509584

RESUMO

Perspective-taking is essential for improving intergroup relations. However, it is difficult to implement, especially in violent conflicts. Given that immersive virtual reality (VR) can simulate various points of view (POV), we examined whether it can lead to beneficial outcomes by promoting outgroup perspective-taking, even in armed conflicts. In two studies, Jewish-Israelis watched a 360° VR scene depicting an Israeli-Palestinian confrontation from different POVs-outgroup's, ingroup's while imagining outgroup perspective or ingroup's without imagined perspective-taking. Participants immersed in the outgroup's POV, but not those who imagined the outgroup's perspective, perceived the Palestinians more positively than those immersed in the ingroup's POV. Moreover, participants in the outgroup's POV perceived the Palestinian population in general more favorably and judged a real-life ingroup transgression more strictly than those in the ingroup's POV, even five months after VR intervention. Results suggest that VR can promote conflict resolution by enabling effective perspective-taking.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31548622

RESUMO

New methods are needed to efficiently characterize built environment attributes and residential behaviors to improve exposure assessment in epidemiologic research, given limitations of available databases and approaches. Window-opening and presence of air conditioning (AC) units predict indoor air quality and thermal comfort, but data are not widely available. In this study, we tested the utility of a GIS-based tool for rapidly assessing open windows and window/wall AC units in the city of Chelsea, Massachusetts using georeferenced street-level photographs and crowdsourced online surveys. We characterized open windows and window/wall AC units for 969 parcels in the winter and 1213 parcels in the summer, requiring ~40 person hours per season. In the winter, 21% of parcels surveyed had a window or wall AC unit and 19% had an open window. In the summer, 69% had a window or wall AC unit and 53% had an open window. We demonstrated an efficient method for rapidly characterizing open windows and window/wall AC units across an entire city. This tool can help to characterize exposures for epidemiological research, engage community members, and inform local land use planning and decision-making.

8.
Surg Endosc ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31376004

RESUMO

INTRODUCTION: Magnetic sphincter augmentation (MSA) is a promising antireflux surgical treatment. The cost associated with the device may be perceived as a drawback by payers, which may limit the adoption of this technique. There are limited data regarding the cost of MSA in the management of reflux disease. The aims of the study were to report the clinical outcome and quality of life measures in patients after MSA and to compare the pharmaceutical and procedure payer costs and the disease-related and overall expense of MSA compared to laparoscopic Nissen fundoplication (LNF) from a payer perspective. METHODS AND PROCEDURES: This prospective observational study was performed in conjunction with the region's largest health insurance company. Data were collected on patients who underwent MSA over a 2-year period beginning in September 2015 at the study network hospitals. The LNF comparison group was procured from members' claims data of the payer. Inclusion was predicated by patients having continuous coverage during study period. The total procedural reimbursement and the disease-related and overall medical claims submitted up to 12 months prior to surgery and up to 12 months following surgery were obtained. The payer reimbursement data are presented as allowed cost per member per month (PMPM). These values were then compared between groups. RESULTS: There were 195 patients who underwent MSA and 1131 that had LNF. MSA results in comparable symptom control, PPI elimination rate, and quality of life measures compared to values reported for LNF in the literature. The median (IQR) reimbursement of surgery was $13,522 (13,195-14,439) for those who underwent MSA and $13,388 (9951-16,261) for patients with LNF, p = 0.02. In patients who underwent MSA, the median reimbursement related to the upper gastrointestinal disease was $ 305 PMPM, at 12 months prior to surgery and $ 104 at 12 months after surgery, representing 66% decrease in cost. These values were $ 233 PMPM and $126 PMPM for patients who underwent LNF, representing a 46% decrease (p = 0.0001). At 12 months following surgery, the reimbursement for overall medical expenses had decreased by 10.7% in the MSA group and 1.4% in the LNF group when compared to the preoperative baseline reimbursement. The reimbursement for PPI use after surgery showed a 95% decrease in the MSA group and 90% among LNF group when compared to the preoperative baseline (p = 0.10). CONCLUSION: When compared with LNF, MSA results in a reduction of disease-related expenses for the payer in the year following surgery. While MSA is associated with a higher procedural payer cost compared to LNF, payer costs may offset due to reduction in the expenses after surgery.

9.
Environ Res ; 177: 108597, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401375

RESUMO

BACKGROUND: Land use regression (LUR) models have been widely used to estimate air pollution exposures at high spatial resolution. However, few LUR models were developed for rapidly developing urban cores, which have substantially higher densities of population and built-up areas than the surrounding areas within a city's administrative boundary. Further, few studies incorporated vertical variations of air pollution in exposure assessment, which might be important to estimate exposures for people living in high-rise buildings. OBJECTIVE: A LUR model was developed for the urban core of Lanzhou, China, along with a model of vertical concentration gradients in high-rise buildings. METHODS: In each of four seasons in 2016-2017, NO2 was measured using Ogawa badges for 2 weeks at 75 ground-level sites. PM2.5 was measured using DataRAM for shorter time intervals at a subset (N = 38) of the 75 sites. Vertical profile measurements were conducted on 9 stories at 2 high-rise buildings (N = 18), with one building facing traffic and another facing away from traffic. The average seasonal concentrations of NO2 and PM2.5 at ground level were regressed against spatial predictors, including elevation, population, road network, land cover, and land use. The vertical variations were investigated and linked to ground-level predictions with exponential models. RESULTS: We developed robust LUR models at the ground level for estimated annual averages of NO2 (R2: 0.71, adjusted R2: 0.67, and Leave-One-Out Cross Validation (LOOCV) R2: 0.64) and PM2.5 (R2: 0.77, adjusted R2: of 0.73, and LOOCV R2: 0.67) in the urban core of Lanzhou, China. The LUR models for the estimated seasonal averages of NO2 showed similar patterns. Vertical variation of NO2 and PM2.5 differed by windows orientation with respect to traffic, by season or by time of a day. Vertical variation functions incorporated the ground-level LUR predictions, in a form that could allow for exposure assessment in future epidemiological investigations. CONCLUSIONS: Ground-level NO2 and PM2.5 showed substantial spatial variations, explained by traffic and land use patterns. Further, vertical variation of air pollution levels is significant under certain conditions, suggesting that exposure misclassification could occur with traditional LUR that ignores vertical variation. More studies are needed to fully characterize three-dimensional concentration patterns to accurately estimate air pollution exposures for residents in high-rise buildings, but our LUR models reinforce that concentration heterogeneity is not captured by the limited government monitors in the Lanzhou urban area.

10.
Environ Health Perspect ; 127(8): 87008, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31449464

RESUMO

BACKGROUND: Children born near New Bedford, Massachusetts, have been prenatally exposed to multiple environmental chemicals, in part due to an older housing stock, maternal diet, and proximity to the New Bedford Harbor (NBH) Superfund site. Chemical exposure measures are not available for all births, limiting epidemiologic investigations and potential interventions. OBJECTIVE: We linked biomonitoring data from the New Bedford Cohort (NBC) and birth record data to predict prenatal exposures for all contemporaneous area births. METHODS: We used prenatal exposure biomarker data from the NBC, a population-based cohort of 788 mother-infant pairs born during 1993­1998 to mothers living near the NBH, linked to their corresponding Massachusetts birth record data, to build predictive models for cord serum polychlorinated biphenyls (expressed as a sum, [Formula: see text]), [Formula: see text] (DDE), hexachlorobenzene (HCB), cord blood lead (Pb), and maternal hair mercury (Hg). We applied the best fit models (highest pseudo [Formula: see text]), with multivariable smooths of continuous variables, to predict exposure biomarkers for all 10,270 births during 1993­1998 around the NBH. We used 10-fold cross validation to validate the exposure models and the bootstrap method to characterize sampling variability in the exposure predictions. RESULTS: The 10-fold cross-validated [Formula: see text] for the [Formula: see text], DDE, HCB, Pb, and Hg exposure models were 0.54, 0.40, 0.34, 0.46, and 0.40, respectively. For each exposure model, multivariable smooths of continuous variables improved the fit compared with linear models. Other variables with significant effects on exposure estimates were paternal education, maternal race/ethnicity, and maternal ancestry. The resulting exposure predictions for all births had variability consistent with the NBC measured exposures. CONCLUSIONS: Predictive models using multivariable smoothing explained reasonable amounts of variance in prenatal exposure biomarkers. Our analyses suggest that prenatal chemical exposures can be predicted for all contemporaneous births in the same geographic area by modeling available biomarker data for a subset of that population. https://doi.org/10.1289/EHP4849.

11.
J Shoulder Elbow Surg ; 28(11): 2128-2138, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31272889

RESUMO

BACKGROUND: The incidence of medial calcar resorption has been shown to be common after uncemented total shoulder arthroplasty (TSA). With etiologies including stress shielding, debris-induced osteolysis, and infection, the clinical impact of medial calcar resorption has not been specifically examined. The purpose of this study was to determine whether resorption is associated with inferior outcomes or higher rates of radiographic loosening in TSA patients. METHODS: We conducted a retrospective review of TSA patients with minimum 2-year clinical follow-up. Patient-reported and functional outcome measures were recorded preoperatively and postoperatively. Postoperative radiographs were evaluated for glenoid and humeral component loosening. A new calcar resorption grading system was introduced to quantify the degree of resorption and assess the progression. RESULTS: A total of 171 patients met the inclusion criteria, with average clinical and radiographic follow-up periods of 50 and 46 months, respectively. Calcar resorption was identified in 110 patients (64.3%). No significant overall differences were observed between the patients with and without calcar resorption. Subgroup analysis showed that patients with grade 3 resorption had a higher incidence of glenoid radiolucencies (50%, P = .001) and patients with a progression from grade 1 to grade 3 had higher incidences of glenoid (50%, P = .003) and humeral (9%, P = .039) radiolucencies. CONCLUSION: Medial calcar resorption following TSA with a standard-length press-fit humeral component is common. Overall, no differences in patient-reported outcome measures or radiographic loosening were found compared with patients without calcar resorption. However, grade 3 calcar resorption and more dramatic progression of resorption should raise the suspicion of prosthetic loosening.

12.
Nat Biotechnol ; 37(9): 1070-1079, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31332326

RESUMO

Base editors use DNA-modifying enzymes targeted with a catalytically impaired CRISPR protein to precisely install point mutations. Here, we develop phage-assisted continuous evolution of base editors (BE-PACE) to improve their editing efficiency and target sequence compatibility. We used BE-PACE to evolve cytosine base editors (CBEs) that overcome target sequence context constraints of canonical CBEs. One evolved CBE, evoAPOBEC1-BE4max, is up to 26-fold more efficient at editing cytosine in the GC context, a disfavored context for wild-type APOBEC1 deaminase, while maintaining efficient editing in all other sequence contexts tested. Another evolved deaminase, evoFERNY, is 29% smaller than APOBEC1 and edits efficiently in all tested sequence contexts. We also evolved a CBE based on CDA1 deaminase with much higher editing efficiency at difficult target sites. Finally, we used data from evolved CBEs to illuminate the relationship between deaminase activity, base editing efficiency, editing window width and byproduct formation. These findings establish a system for rapid evolution of base editors and inform their use and improvement.


Assuntos
Adenosina Desaminase/metabolismo , Evolução Molecular Direcionada , Edição de Genes , Adenosina Desaminase/genética , Animais , Sequência de Bases , Sistemas CRISPR-Cas , Linhagem Celular , Regulação Enzimológica da Expressão Gênica , Marcação de Genes , Humanos , Mutação INDEL , Camundongos
14.
Environ Res ; 176: 108544, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271923

RESUMO

Blood pressure is a leading risk factor for cardiovascular disease, influenced by chemical and non-chemical stressors. Exposure reduction strategies can potentially improve public health, but there are analytical challenges in developing quantitative models of health benefits, including the need for detailed multi-stressor exposure models, corresponding health evidence, and methods to simulate changes in exposure and resultant health benefits. These challenges are pronounced in low-income urban communities, where residents are often simultaneously exposed to numerous chemical and non-chemical stressors. For New Bedford (Massachusetts, USA), a low-income community near a Superfund site, we simulated geographically-resolved individual data, and applied previously published structural equation models developed from National Health and Nutrition Examination Survey (NHANES) data. These models simultaneously predict exposures to multiple chemicals (e.g., lead (Pb), cadmium (Cd), and polychlorinated biphenyls (PCBs)) and non-chemical factors (e.g., socioeconomic status), and determine their combined effects on blood pressure. We then modeled counterfactual scenarios reducing exposures and estimated the resulting changes in blood pressure distribution in the community. Results indicated small shifts in mean blood pressure and percentage of normotensive individuals with a reduction of Pb and/or PCB exposure. For example, a reduction in PCB to the lowest 10th percentile exposure in the NHANES resulted in a 2.4 mm Hg shift in systolic blood pressure (SBP), corresponding with 3% fewer individuals with SBP in the Stage 2 hypertension category [SBP ≥140]. Our model also emphasized the importance of the multi-stressor framework by simulating benefits of reductions in smoking rates, given positive associations with Pb and Cd but inverse associations with body mass index and blood pressure. This research demonstrates the ability to jointly consider chemical and non-chemical exposures and their impact on cardiovascular health, using approaches generalizable to other cumulative risk assessment applications.

15.
Hum Mutat ; 40(11): 1993-2000, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31230393

RESUMO

Human retrocopies, that is messenger RNA transcripts benefitting from the long interspersed element 1 machinery for retrotransposition, may have specific consequences for genomic testing. Next genetration sequencing (NGS) techniques allow the detection of such mobile elements but they may be misinterpreted as genomic duplications or be totally overlooked. We report eight observations of retrocopies detected during diagnostic NGS analyses of targeted gene panels, exome, or genome sequencing. For seven cases, while an exons-only copy number gain was called, read alignment inspection revealed a depth of coverage shift at every exon-intron junction where indels were also systematically called. Moreover, aberrant chimeric read pairs spanned entire introns or were paired with another locus for terminal exons. The 8th retrocopy was present in the reference genome and thus showed a normal NGS profile. We emphasize the existence of retrocopies and strategies to accurately detect them at a glance during genetic testing and discuss pitfalls for genetic testing.

16.
J Shoulder Elbow Surg ; 28(10): 1948-1955, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31227465

RESUMO

BACKGROUND: Ideal management of severe glenoid retroversion during anatomic total shoulder arthroplasty (TSA) remains controversial, as previous reports have suggested that severe retroversion may negatively impact clinical outcomes. The purpose of this study was to evaluate the impact of severe glenoid retroversion on clinical and radiographic TSA outcomes using a standard glenoid component, as well as to compare outcomes among patients with less severe retroversion. METHODS: A case-control study was performed comparing 40 patients treated with TSA with more than 20° of glenoid retroversion preoperatively (average follow-up, 53 months) vs. a matched cohort of 80 patients with less than 20° of retroversion (average follow-up, 49 months). In all patients, the surgical technique, implant design, and postoperative rehabilitation protocol were identical. Patients were matched based on sex, age, indication, and prosthetic size. Comparisons were made regarding patient-reported outcome measures (PROMs), motion, postoperative radiographic loosening, and the presence of medial calcar resorption. RESULTS: Preoperatively, both groups demonstrated similar PROMs and measured motion, except for preoperative Single Assessment Numeric Evaluation scores and American Shoulder and Elbow Surgeons total scores, which were higher for the severe retroversion group (44.4 vs. 31.3 [P = .012] and 34.9 vs. 29.4 [P = .048], respectively). Postoperative PROMs and motion were also similar between the 2 cohorts. No significant differences were observed for postoperative radiographic findings. Medial calcar resorption was identified in 74 patients (61.7%). Calcar resorption and individual resorption grades were not found to differ significantly. CONCLUSION: At midterm follow-up, preoperative severe glenoid retroversion does not appear to influence clinical or radiographic outcomes of TSA using a standard glenoid component.

17.
Dev Cogn Neurosci ; 38: 100658, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31121480

RESUMO

Early life stress carries long-term negative consequences for children's well-being and maturation of the social brain. Here, we utilize a unique cohort to test its effects on mothers' social brain, targeting mothers' neural empathic response in relation to caregiving and child empathic abilities. Mother-child dyads living in a zone of repeated war-related trauma were followed from early childhood and mother-child behavioral synchrony was repeatedly observed. At pre-adolescence(11-13 years) children's empathic abilities were assessed and mothers(N = 88, N = 44 war-exposed) underwent magnetoencephalography(MEG) while exposed to vicarious pain. All mothers showed alpha suppression in sensorimotor regions, indicating automatic response to others' pain. However, trauma-exposed mothers did not exhibit gamma oscillations in viceromotor cortex, a neural marker of mature empathy which utilizes interoceptive mechanisms for higher-order understanding and does not emerge before adulthood. Mother-child synchrony across the first decade predicted mothers' viceromotor gamma, and both synchrony and maternal viceromotor gamma mediated the relations between war-exposure and child empathic abilities, possibly charting a cross-generational pathway from mothers' mature neural empathy to children's empathic capacities. Our findings are first to probe the maternal social brain in adolescence in relation to parenting and underscore the need for targeted interventions to mothers raising children in contexts of chronic stress.

18.
J Comp Neurol ; 527(17): 2875-2884, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31071232

RESUMO

Chemosensitivity is a key mechanism for the regulation of breathing in vertebrates. The retrotrapezoid nucleus is a crucial hub for respiratory chemoreception within the brainstem. It integrates chemosensory information that are both peripheral from the carotid bodies (via the nucleus of the solitary tract) and central through the direct sensing of extracellular protons. To date, the location of a genetically defined RTN has only been ascertained in rodents. We first demonstrated that Phox2b, a key determinant for the development of the visceral nervous system and branchiomotor nuclei in the brainstem including the RTN, had a similar distribution in the brainstem of adult macaques compared to adult rats. Second, based on previous description of a specific molecular signature for the RTN in rats, and on an innovative technique for duplex in situ hybridization, we identified parafacial neurons which coexpressed Phox2b and ppGal mRNAs. They were located ventrally to the nucleus of the facial nerve and extended from the caudal part of the nucleus of the superior olive to the rostral tip of the inferior olive. Using the previously described blockface technique, deformations were corrected to allow the proper alignment and stacking of digitized sections, hence providing for the first time a 3D reconstruction of the macaque brainstem, Phox2b distribution and the primate retrotrapezoid nucleus. This description should help bridging the gap between rodents and humans for the description of key respiratory structures in the brainstem.

19.
Clin Orthop Relat Res ; 477(9): 2097-2108, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31107323

RESUMO

BACKGROUND: The first-generation, lateral-center-of-rotation reverse shoulder arthroplasty (RSA) modular design has demonstrated durable early-, mid-, and long-term outcomes. The second-generation monoblock implant shares a similar design but eliminates the modular junction and facilitates inset placement within the metaphysis to avoid humeral-sided junctional failures and facilitate metaphyseal press-fit. However, no paper has specifically examined the radiographic findings and improvements in pain and function after the use of this next generation design. QUESTIONS/PURPOSES: (1) After second-generation, lateral-center-of-rotation monoblock RSA, what are the improvements in shoulder scores, general health scores, and ROM at a minimum of 2 years of followup? (2) Are the differences in shoulder scores, health scores, and ROM associated with fixation (cemented versus cementless components)? (3) How frequently do complications occur (defined as humeral loosening, dislocation, baseplate failure, scapular notching, acromial fractures, and revision surgery) after inset monoblock RSA? METHODS: We retrospectively studied patients undergoing primary RSA between 2010 and 2015 with preoperative data and a minimum of 2 years of clinical followup. Of the 329 primary RSA performed during this period, 125 were excluded based on the use of a different generation humeral stem of the same design, three based on need for a nickel-free implant, and 39 due to a lack of preoperative shoulder scores. Of the remaining 162 patients, 137 patients (85%) met the inclusion criteria with a mean age of 74 years (range, 46-90 years). The predominant indications were osteoarthritis with a massive rotator cuff tear (74%) and fracture sequelae (16%). During the study, humeral implants were typically inserted using an uncemented press-fit technique (85%), with only 21 patients requiring a cemented humeral stem. The mean clinical and radiographic followup period was 37 months (range, 24-82 months). Patient-reported outcome measures (PROMs) including the Simple Shoulder Test, American Shoulder and Elbow Surgeons Total, VAS for pain, SF-12, Single Assessment Numeric Evaluation, and measured active motion (forward elevation and external and internal rotation) were recorded at pre- and postoperative intervals. Postoperative radiographs were evaluated for baseplate failure, glenoid and humeral loosening, scapular notching, and acromion fractures. Complications were recorded in the longitudinally maintained institutional repository. RESULTS: At the most recent followup examination, there were improvements in measured motion, general health outcomes, and all PROMs. There were no differences between the cemented and press-fit techniques. Complications observed included 17 of 137 patients (12%) with scapular notching, six postoperative acromion fractures (4%), and two revision procedures (1%). No patients experienced gross humeral loosening or baseplate failure. CONCLUSIONS: Primary RSA using a second-generation monoblock inset humeral component resulted in improvements in pain and functional outcomes as well as low rates of acromion fractures, humeral radiolucency, and complications. Future studies are needed to provide a more definitive analysis on the use of an uncemented technique for humeral stem fixation and the effect of an inset stem on postoperative acromion fractures. LEVEL OF EVIDENCE: Level IV, therapeutic study.

20.
Nat Commun ; 10(1): 1905, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015471

RESUMO

Empathy is a core human social ability shaped by biological dispositions and caregiving experiences; yet the mechanisms sustaining maturation of the neural basis of empathy are unknown. Here, we followed eighty-four children, including 42 exposed to chronic war-related adversity, across the first decade of life, and assessed parenting, child temperament, and anxiety disorders as contributors to the neural development of empathy. At preadolescence, participants underwent magenetoencephalography while observing others' distress. Preadolescents show a widely-distributed response in structures implicating the overlap of affective (automatic) and cognitive (higher-order) empathy, which is predicted by mother-child synchrony across childhood. Only temperamentally reactive young children growing in chronic adversity, particularly those who later develop anxiety disorders, display additional engagement of neural nodes possibly reflecting hyper-mentalizing and ruminations over the distressing stimuli. These findings demonstrate how caregiving patterns fostering interpersonal resonance, reactive temperament, and chronic adversity combine across early development to shape the human empathic brain.


Assuntos
Encéfalo/fisiologia , Empatia/fisiologia , Relações Mãe-Filho/psicologia , Poder Familiar/psicologia , Teoria da Mente/fisiologia , Exposição à Guerra , Adolescente , Desenvolvimento do Adolescente , Encéfalo/anatomia & histologia , Mapeamento Encefálico , Criança , Desenvolvimento Infantil , Pré-Escolar , Feminino , Humanos , Israel , Masculino , Percepção Social
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