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1.
Prostate ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32201973

RESUMO

BACKGROUND: Radiotherapy and brachytherapy are common treatments for localized prostate cancer (PCa). However, very few studies evaluated the association of variations in DNA damage response genes and treatment outcomes and toxicity in brachytherapy-treated patients. PURPOSE: To evaluate the association of inherited germline variations in DNA repair-associated genes with tumor control and treatment toxicity in patients treated with low-dose-rate prostate brachytherapy (LDRB). MATERIAL AND METHODS: The cohort consists of 475 I-125 LDRB patients with a median follow-up of 51 months after seed implantation. Patients were genotyped for 215 haplotype tagging single nucleotide variations (htSNPs) in 29 candidate genes of DNA damage response and repair pathways. Their association with biochemical recurrence (BCR) was assessed using Cox regression models and Kaplan-Meier survival curves. Linear regressions and analysis of covariance (ANCOVA) between early and late International Prostate Symptom Score (IPSS) with htSNPs were used to evaluate the association with urinary toxicity. RESULTS: After adjustment for the established risk factors, six htSNPs in five genes were found to be significantly associated with an altered risk of BCR, with adjusted hazard ratios (HRadj. ) ranging between 3.6 and 11.1 (P < .05). Compared to carriers of the ERCC3 rs4150499C allele, patients homozygous for the T allele (n = 22) had a significant higher risk of BCR with a HR of 11.13 (IC95 = 3.9-32.0; P < .0001; q < 0.001). The Kaplan-Meier survival curve revealed a mean BCR-free survival time reduced from 213 ± 7 to 99 ± 12 months (log-rank P < .0001) for homozygous T carriers compare to noncarriers. For late IPSS (>6 months after treatment), htSNP rs6544990 from MSH2 showed a statistically significant b-coefficient of 1.85 ± 0.52 (P < .001; q < 0.1). Homozygous carriers of the MSH2 rs6544990C allele (n = 62) had a mean late IPSS 3.6 points higher than patients homozygous for the A allele (n = 132). This difference was significant when tested by ANCOVA using pretreatment IPSS as a covariate (P < .01). CONCLUSIONS: This study suggests an association of the intronic variants of the DNA nucleotide excision repair ERCC3 and DNA mismatch repair MSH2 genes with elevated risk of BCR and late urinary toxicity respectively after LDRB. Further validation is required before translational clinical advances.

2.
Sci Rep ; 10(1): 2759, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066827

RESUMO

Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the mouse orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. In this study we sought to address this problem using the Mouse Grimace Scale and a novel approach to the application of mechanical Von Frey hair stimuli. We use a dental pulp injury model that exposes the pulp to the outside environment, a procedure we have previously shown produces inflammation. Using RNAscope technology, we demonstrate an upregulation of genes that contribute to the pain state in the trigeminal ganglia of injured mice. We found that mice with dental pulp injury have greater Mouse Grimace Scores than sham within 24 hours of injury, suggestive of spontaneous pain. We developed a scoring system of mouse refusal to determine thresholds for mechanical stimulation of the face with Von Frey filaments. This method revealed that mice with a unilateral dental injury develop bilateral mechanical allodynia that is delayed relative to the onset of spontaneous pain. This work demonstrates that tooth pain can be quantified in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammatory pain and other forms of trigeminal pain.

3.
Sci Rep ; 10(1): 2176, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034228

RESUMO

The hyperthermal events of the Cenozoic, including the Paleocene-Eocene Thermal Maximum, provide an opportunity to investigate the potential effects of climate warming on marine ecosystems. Here, we examine the shallow benthic marine communities preserved in the late Cretaceous to Eocene strata on the Gulf Coastal Plain (United States). In stark contrast to the ecological shifts following the end-Cretaceous mass extinction, our data show that the early Cenozoic hyperthermals did not have a long-term impact on the generic diversity nor composition of the Gulf Coastal Plain molluscan communities. We propose that these communities were resilient to climate change because molluscs are better adapted to high temperatures than other taxa, as demonstrated by their physiology and evolutionary history. In terms of resilience, these communities differ from other shallow-water carbonate ecosystems, such as reef communities, which record significant changes during the early Cenozoic hyperthermals. These data highlight the strikingly different responses of community types, i.e., the almost imperceptible response of molluscs versus the marked turnover of foraminifera and reef faunas. The impact on molluscan communities may have been low because detrimental conditions did not devastate the entire Gulf Coastal Plain, allowing molluscs to rapidly recolonise vacated areas once harsh environmental conditions ameliorated.

4.
Nanoscale ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32080696

RESUMO

Although common in nature, the self-assembly of small molecules at sold-liquid interfaces is difficult to control in artificial systems. The high mobility of dissolved small molecules limits their residence at the interface, typically restricting the self-assembly to systems under confinement or with mobile tethers between the molecules and the surface. Small hydrogen-bonding molecules can overcome these issues by exploiting group-effect stabilization to achieve non-tethered self-assembly at hydrophobic interfaces. Significantly, the weak molecular interactions with the solid makes it possible to influence the interfacial hydrogen bond network, potentially creating a wide variety of supramolecular structures. Here we investigate the nanoscale details of water and alcohols mixtures self-assembling at the interface with graphite through group-effect. We explore the interplay between inter-molecular and surface interactions by adding small amounts of foreign molecules able to interfere with the hydrogen bond network and systematically varying the length of the alcohol hydrocarbon chain. The resulting supramolecular structures forming at room temperature are then examined using atomic force microscopy with insights from computer simulations. We show that the group-based self-assembly approach investigated here is general and can be reproduced on other substrates such as molybdenum disulphide and graphene oxide, potentially making it relevant for a wide variety of systems.

5.
J Proteome Res ; 19(4): 1592-1619, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32050077

RESUMO

Pain and emotional distress have a reciprocal relation. The amygdala has been implicated in emotional processing. The central nucleus of the amygdala (CeA) receives nociceptive information from the dorsal horn of spinal cord and is responsible for the central plasticity in chronic pain. Neuropathic pain is a type of severe chronic pain and can be strongly influenced by emotional components. Plastic changes in the CeA may play a key role in the development or maintenance or both of neuropathic pain. We studied the expression levels of proteins in the CeA of spinal nerve transection (SNT) model rats. Total tissue lysate proteins were separated by two-dimensional-gel electrophoresis (2D-PAGE). Gels from different time points were compared using Progenesis SameSpot software, and the spots with Fold Change greater than 2 were excised for protein identification by mass spectrometry. We identified more than 50 cytosolic proteins as significantly altered in their expression levels in the CeA of SNT rats, and most of these changes have been validated at mRNA levels by qRT-PCR. We also identified more than 40 membrane proteins as notably up- or down-regulated in the CeA of SNT model rats relative to a control using stable isotope dimethyl labeling nano-LC-MS/MS based proteomics and found that one such protein, doublecortin (DCX), a microtubule-associated protein expressed by neuronal precursor cells during development, is specifically localized in the membrane fraction without changes in total amount of the protein. Immunohistochemistry showed that doublecortin is expressed in processes in the CeA of rats 7 and 21 days after SNT surgery, suggesting that doublecortin is one of the proteins that may contribute to the plastic changes, namely, redevelopment or rewiring of neural networks, in the CeA in the neuropathic pain model. These dysregulated proteins may play roles in reciprocal relationships between pain and psychological distress in the amygdala and contribute to central sensitization. Data are available via ProteomeXchange with identifier PXD017473.

7.
Adv Radiat Oncol ; 4(4): 631-640, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673656

RESUMO

Purpose: To compare health-related quality of life (HRQOL) of high-dose-rate brachytherapy (HDRB) versus low dose-rate brachytherapy (LDRB) for localized prostate cancer in a multi-institutional phase 2 randomized trial. Methods and Materials: Men with favorable-risk prostate cancer were randomized between monotherapy brachytherapy with either Iodine-125 LDRB to 144 Gy or single-fraction Iridium-192 HDRB to 19 Gy. HRQOL and urinary toxicity were recorded at baseline and at 1, 3, 6, and 12 months using the Expanded Prostate Cancer Index Composite (EPIC)-26 scoring and the International Prostate Symptom Score (IPSS). Independent samples t test and mixed effects modeling were performed for continuous variables. Time to IPSS resolution, defined as return to its baseline score ±5 points, was calculated using Kaplan-Meier estimator curves with the log-rank test. A multiple-comparison adjusted P value of ≤.05 was considered significant. Results: LDRB and HDRB were performed in 15 and 16 patients, respectively, for a total of 31 patients. At 3 months, patients treated with LDRB had a higher IPSS score (mean, 15.5 vs 6.0, respectively; P = .003) and lower EPIC urinary irritative score (mean, 69.2 vs 85.3, respectively; P = .037) compared with those who received HDRB. On repeated measures at 1, 3, 6, and 12 months, the IPSS (P = .003) and EPIC urinary irritative scores (P = .019) were significantly better in the HDR arm, translating into a lower urinary toxicity profile. There were no significant differences in the EPIC urinary incontinence, sexual, or bowel habit scores between the 2 groups at any measured time point. Time to IPSS resolution was significantly shorter in the HDRB group (mean, 2.0 months) compared with the LDRB group (mean, 6.0 months; P = .028). Conclusions: HDRB monotherapy is a promising modality associated with a lower urinary toxicity profile and higher HRQOL in the first 12 months compared with LDRB.

8.
Transl Vis Sci Technol ; 8(4): 21, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31404399

RESUMO

Purpose: Manufacturers of surgical instrumentation have increasingly sought to decrease the size of ophthalmic surgical instruments. We have used finite element modeling to model the stress and strain present in a fragmatome as a function of driving frequency and fragmatome dimensions. Methods: Finite element calculations using the COMSOL Multiphysics system v3.5 were used to elucidate the influence of wall thickness, length, and excitation frequency on a titanium fragmatome tube with outer diameters of 20, 23, 25, and 27 gauge. Results: By coupling structural mechanics, fluid mechanics, and acoustical physics, we were able to determine the eigenfrequencies (resonant frequencies) as well as parameters in which the von Mises stress in a fragmatome tube exceeds the yield strength, leading to destruction of the instrument. Conclusion: Solid fragmatomes have far fewer possible failure modes than fragmatomes with a standard wall thickness. Eigenfrequency analysis and finite element calculations can be critical in predicting potentially catastrophic designs in modern surgical instruments. Translational Relevance: Instruments developed for microsurgical applications cannot always simply be scaled down versions of conventional instruments. Such an approach can lead to potentially dangerous intraoperative failures, such as a fragmatome shattering inside the eye. Modern engineering techniques are increasingly necessary to investigate potential instrument failure mechanisms and to optimize device performance in a design in silico before in vivo testing.

9.
Brachytherapy ; 18(5): 598-605, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31230941

RESUMO

PURPOSE: Interstitial brachytherapy (ISBT) can be effective for vaginal tumors due to its ability to deliver conformal treatment with 3D planning. As there is no consensus for 3D vaginal brachytherapy (BT) contouring, the goals of this study are to evaluate the variability in practices and contouring, and to develop consensus concepts on target definitions. METHODS: A survey/contouring study was conducted with 16 radiation oncologists from 10 Canadian academic centers. The study included three vaginal ISBT cases. Participants were provided staging, prebrachytherapy (pre-BT), and BT MRIs. Participants responded to a questionnaire and contoured on the provided images. Agreement between contours was analyzed. A meeting was held to develop consensus definitions of targets. RESULTS: Median ISBT experience was 3.5 years. All 16 participants regularly contour with MRI, whereas three also plan on MRI. For the three cases, there was variation into how CTVHR and CTVIR was defined. Kappa statistics showed higher agreement with bulky tumors (mean 0.59) as compared with small residual tumors (mean 0.29). For all cases, kappa was highest in pre-BT GTVres as compared with BT GTVres (mean 0.58, 0.46). Consensus concepts to define targets were developed. CONCLUSIONS: Variations exist in how ISBT targets are defined for vaginal tumors. Highest contouring variability was seen with small residual at BT. Contouring is more consistent on pre-BT MRI as compared with BT MRI suggesting a needle distortion effect. Consensus CTVHR and CTVIR definitions have been developed and further work is warranted to establish international standards.


Assuntos
Braquiterapia/métodos , Imagem por Ressonância Magnética , Padrões de Prática Médica , Radioterapia Guiada por Imagem , Neoplasias Vaginais/radioterapia , Adulto , Idoso , Consenso , Feminino , Humanos , Masculino , Radioterapia (Especialidade) , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Inquéritos e Questionários , Terminologia como Assunto , Carga Tumoral , Neoplasias Vaginais/patologia
10.
Geriatr Orthop Surg Rehabil ; 10: 2151459318825199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31041114

RESUMO

Introduction: A periprosthetic joint infection (PJI) is a potentially devastating complication following an arthroplasty procedure. There are many organisms that commonly cause this complication; in this case report, we will discuss a PJI caused by an unusual bacteria found in the mouths of domestic pets. Objective: To present a case report of a patient with a periprosthetic hip infection from Capnocytophaga canimorsus and review the literature. Methods: We present a case of C canimorsus PJI in an immunocompetent woman who had undergone a total hip arthroplasty. The patient was doing well postoperatively for many years until she was bitten on the foot by a domestic canine. Patient diagnosed using Musculoskeletal Infection Society criteria, then treated with explant of the hip prosthesis, irrigation and debridement, placement of an antibiotic cement spacer, and a 6-week course of intravenous antibiotics. Results: Unfortunately, while awaiting replant, this patient had a massive myocardial infarction and died. Discussion: Current literature suggests treating canine bites with amoxicillinas well as a discussion with patients pre-/postoperatively from a lower extremity arthroplasty specialist. Conclusion: Capnocytophaga canimorsus is a rare cause of infection, even more unusual in an immunocompetent patient. This study highlights the importance of considering C canimorsus as a cause of PJI, regardless of the immunologic status of the patient.

11.
Geobiology ; 17(5): 523-535, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31120196

RESUMO

Thrombolite and stromatolite habitats are becoming increasingly recognized as important refuges for invertebrates during Phanerozoic Oceanic Anoxic Events (OAEs); it is posited that oxygenic photosynthesis by cyanobacteria in these microbialites provided a refuge from anoxic conditions (i.e., the "microbialite refuge" hypothesis). Here, we test this hypothesis by investigating the distribution of ~34, 500 benthic invertebrate fossils found in ~100 samples from a microbialite succession that developed following the latest Permian mass extinction event on the Great Bank of Guizhou (South China), representing microbial (stromatolites and thrombolites) and non-microbial facies. The stromatolites were the least taxonomically diverse facies, and the thrombolites also recorded significantly lower diversities when compared to the non-microbial facies. Based on the distribution and ornamentation of the bioclasts within the thrombolites and stromatolites, the bioclasts are inferred to have been transported and concentrated in the non-microbial fabrics, that is, cavities around the microbial framework. Therefore, many of the identified metazoans from the post-extinction microbialites are not observed to have been living within a microbial mat. Furthermore, the lifestyle of many of the taxa identified from the microbialites was not suited for, or even amenable to, life within a benthic microbial mat. The high diversity of oxygen-dependent metazoans in the non-microbial facies on the Great Bank of Guizhou, and inferences from geochemical records, suggests that the microbialites and benthic communities developed in oxygenated environments, which disproves that the microbes were the source of the oxygenation. Instead, we posit that microbialite successions represent a taphonomic window for exceptional preservation of the biota, similar to a Konzentrat-Lagerstätte, which has allowed for diverse fossil assemblages to be preserved during intervals of poor preservation.


Assuntos
Biodiversidade , Fósseis , Invertebrados/classificação , Animais , China , Sedimentos Geológicos/análise
12.
Radiother Oncol ; 133: 62-67, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30935583

RESUMO

BACKGROUND AND PURPOSE: To compare bDFS and toxicity outcomes in a population of intermediate risk prostate cancer patients treated using I-125 LDR brachytherapy with or without DIL boost based on multiple core biopsy maps. MATERIALS AND METHODS: Between January 2005 and December 2013, all our intermediate risk prostate cancer patients treated with LDR I-125 brachytherapy were reviewed. All patients were given 144 Gy to the prostate. A pathologic DIL distribution (defined by sextant biopsy) was contoured prospectively prior to planning, to be covered by the 150% isodose line. Of the 165 patients treated, 55 received a DIL boost. Patients completed prospectively the IPSS questionnaire, a sexual and bowel function questionnaire. Gastro-intestinal toxicities were graded according to CTCAE v4.03. A patient was considered to have erectile dysfunction if he was unable to achieve erection to perform intercourse. BDFS was determined according to the Phoenix consensus definitions. RESULTS: The median follow-up was 78 months. The estimated 7-year bDFS rate was 96% (95% CI, 74-99%) in the DIL group versus 89% (95% CI, 79-94%) in the control group (p = 0.188). There was no difference between groups in urinary, gastro-intestinal or sexual toxicities up to 5 years of follow-up. There was no difference in urinary obstruction with catheterization between DIL versus control groups (3,6 vs 2,8 %, p = 1.00). Only 1 patient in the DIL group had ≥grade 3 toxicity (TURP) and none in the control group. CONCLUSIONS: Boost to DIL defined by sextant biopsy with permanent seed prostate implant shows a trend toward improvement of biochemical control in intermediate risk prostate cancer patient without increasing toxicity.


Assuntos
Braquiterapia/métodos , Radioisótopos do Iodo/administração & dosagem , Neoplasias da Próstata/radioterapia , Idoso , Biópsia/métodos , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Estudos Retrospectivos
13.
ACS Med Chem Lett ; 10(3): 367-373, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30891142

RESUMO

A new phenyl (3-phenylpyrrolidin-3-yl)sulfone series of RORγt inverse agonists was discovered utilizing the binding conformation of previously reported bicyclic sulfonamide 1. Through a combination of structure-based design and structure-activity relationship studies, a polar set of amides at N1-position of the pyrrolidine ring and perfluoroisopropyl group at para-position of the 3-phenyl group were identified as critical structural elements to achieve high selectivity against PXR, LXRα, and LXRß. Further optimization led to the discovery of (1R,4r)-4-((R)-3-((4-fluorophenyl)sulfonyl)-3-(4-(perfluoropropan-2-yl)phenyl)pyrrolidine-1-carbonyl)cyclohexane-1-carboxylic acid (26), which displayed excellent selectivity, desirable liability and pharmacokinetic properties in vitro, and a good pharmacokinetic profile in mouse. Oral administration of 26 demonstrated dose-dependent inhibition of IL-17 production in a mouse IL-2/IL-23-induced pharmacodynamic model and biologic-like efficacy in an IL-23-induced mouse acanthosis model.

14.
Neuroscientist ; 25(3): 208-226, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30014771

RESUMO

Ca2+ is an essential trigger for most forms of synaptic plasticity. Ca2+ signaling occurs not only by Ca2+ entry via plasma membrane channels but also via Ca2+ signals generated by intracellular organelles. These organelles, by dynamically regulating the spatial and temporal extent of Ca2+ elevations within neurons, play a pivotal role in determining the downstream consequences of neural signaling on synaptic function. Here, we review the role of three major intracellular stores: the endoplasmic reticulum, mitochondria, and acidic Ca2+ stores, such as lysosomes, in neuronal Ca2+ signaling and plasticity. We provide a comprehensive account of how Ca2+ release from these stores regulates short- and long-term plasticity at the pre- and postsynaptic terminals of central synapses.


Assuntos
Sinalização do Cálcio , Plasticidade Neuronal , Neurônios/metabolismo , Sinapses/metabolismo , Animais , Espinhas Dendríticas/metabolismo , Retículo Endoplasmático/metabolismo , Humanos , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Terminações Pré-Sinápticas/metabolismo
15.
Sci Signal ; 11(558)2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482851

RESUMO

Acidic organelles, such as endosomes and lysosomes, store Ca2+ that is released in response to intracellular increases in the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP). In neurons, NAADP and Ca2+ signaling contribute to synaptic plasticity, a process of activity-dependent long-term potentiation (LTP) [or, alternatively, long-term depression (LTD)] of synaptic strength and neuronal transmission that is critical for neuronal function and memory formation. We explored the function of and mechanisms regulating acidic Ca2+ store signaling in murine hippocampal neurons. We found that metabotropic glutamate receptor 1 (mGluR1) was coupled to NAADP signaling that elicited Ca2+ release from acidic stores. In turn, this released Ca2+-mediated mGluR1-dependent LTP by transiently inhibiting SK-type K+ channels, possibly through the activation of protein phosphatase 2A. Genetically removing two-pore channels (TPCs), which are endolysosomal-specific ion channels, switched the polarity of plasticity from LTP to LTD, indicating the importance of specific receptor store coupling and providing mechanistic insight into how mGluR1 can produce both synaptic potentiation and synaptic depression.


Assuntos
Canais de Cálcio/fisiologia , Sinalização do Cálcio , Cálcio/metabolismo , Hipocampo/fisiologia , Potenciação de Longa Duração , NADP/análogos & derivados , Receptores de Glutamato Metabotrópico/metabolismo , Animais , Células Cultivadas , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , NADP/farmacologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologia , Ratos , Ratos Wistar
16.
Geriatr Orthop Surg Rehabil ; 9: 2151459318803843, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30377549

RESUMO

Introduction: As life expectancy increases, the incidence of shoulder arthroplasty continues to increase as well. There are few shoulder arthroplasty studies investigating perioperative complication, readmission, and mortality. Furthermore, with bundled payments on the horizon, the cost of shoulder arthroplasty has become a significant issue. Clarifying risk factors for the need for postdischarge acute care will be critical information due to the high cost of such care. The goal of this study was to compare discharge disposition, length of stay (LOS), perioperative complications, readmission, and mortality in elderly and nonelderly cohorts to determine whether age is a risk factor for shoulder arthroplasty. Materials and Methods: We retrospectively compared 89 elderly patients (80 years or older) and 86 nonelderly patients (79 years or younger) who underwent hemiarthroplasty, total shoulder arthroplasty, reverse total shoulder arthroplasty, or revision shoulder arthroplasty from 2007 to 2015. Baseline characteristics were compared between the 2 cohorts. We then compared discharge disposition, LOS, 90-day complication rate, readmission, and mortality between the 2 cohorts. Results: Average length of hospitalization and percentage of patients with greater than 2 days of hospitalization were significantly higher in the elderly cohorts. Forty-four percent of the elderly cohorts were discharged to a skilled nursing facility compared to 6% in the nonelderly cohorts (P < .0001). There were no significant differences found in 90-day major complication rate, readmission, or mortality. Discussion: Shoulder arthroplasty is a valuable surgery for various indications in the elderly population. However, the likelihood of a patient to need a prolonged hospitalization or skilled nursing facility care after surgery are important questions that need to be answered. Our study shows that age over 80 years is a risk factor for prolonged hospitalization and need for skilled nursing facility care after shoulder arthroplasty. Conclusion: We conclude that elderly patients who undergo shoulder arthroplasty are significantly more likely to have extended hospitalizations and to be discharged to skilled nursing facilities compared to nonelderly patients.

17.
Curr Biol ; 28(20): 3267-3272.e3, 2018 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-30270190

RESUMO

Organisms can often benefit by distinguishing between different classes of individuals. An example is kin recognition, whereby individuals preferentially associate with or aid genetic relatives that bear matching recognition cues but reject others. Despite its potential benefits, however, kin recognition using genetically based cues is often weak or absent [1-4]. A general explanation, termed "Crozier's effect," is that when individuals interact randomly, rarer cue alleles less often match cues of other individuals, and so are involved predominantly in "reject"-type interactions. If such interactions are more costly, positive frequency-dependent selection will erode the cue diversity upon which discrimination depends [4, 5]. Although widely cited [1, 2, 4, 6-9], this idea lacks rigorous testing in the field. Here, we show how Crozier's effect applies to interactions between hosts and conspecific parasites, and measure it using field data. In the wasp we studied, conspecific parasitism fits a key assumption of Crozier's model: the same females act as both hosts and parasites. By exchanging offspring between nests experimentally, we find no evidence that females respond to genetically based cues associated with foreign offspring. Through measuring costs and benefits, however, we demonstrate a strong Crozier effect: because more parental investment is wasted when foreign offspring are rejected, interactions involving rejection have substantially lower payoffs than interactions involving acceptance. Costly rejection can thus eliminate cue diversity by causing selection against rare cue alleles, consistent with the absence of genetically based recognition that we observe. Females instead appear to rely on non-genetic cues that enable them to detect less than half of parasitic offspring.


Assuntos
Interações Hospedeiro-Parasita , Comportamento de Nidação , Vespas/fisiologia , Vespas/parasitologia , Animais , Sinais (Psicologia) , Feminino , Reprodução , Especificidade da Espécie
18.
Proc Biol Sci ; 285(1889)2018 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-30355705

RESUMO

The Late Triassic and Early Toarcian extinction events are both associated with greenhouse warming events triggered by massive volcanism. These Mesozoic hyperthermals were responsible for the mass extinction of marine organisms and resulted in significant ecological upheaval. It has, however, been suggested that these events merely involved intensification of background extinction rates rather than significant shifts in the macroevolutionary regime and extinction selectivity. Here, we apply a multivariate modelling approach to a vast global database of marine organisms to test whether extinction selectivity varied through the Late Triassic and Early Jurassic. We show that these hyperthermals do represent shifts in the macroevolutionary regime and record different extinction selectivity compared to background intervals of the Late Triassic and Early Jurassic. The Late Triassic mass extinction represents a more profound change in selectivity than the Early Toarcian extinction but both events show a common pattern of selecting against pelagic predators and benthic photosymbiotic and suspension-feeding organisms, suggesting that these groups of organisms may be particularly vulnerable during episodes of global warming. In particular, the Late Triassic extinction represents a macroevolutionary regime change that is characterized by (i) the change in extinction selectivity between Triassic background intervals and the extinction event itself; and (ii) the differences in extinction selectivity between the Late Triassic and Early Jurassic as a whole.


Assuntos
Organismos Aquáticos , Evolução Biológica , Mudança Climática , Extinção Biológica , Temperatura Alta , Fósseis , Modelos Biológicos , Paleontologia
19.
ACS Appl Mater Interfaces ; 10(40): 34265-34271, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30221928

RESUMO

Methanol occupies a central role in chemical synthesis and is considered an ideal candidate for cleaner fuel storage and transportation. It can be catalyzed from water and volatile organic compounds, such as carbon dioxide, thereby offering an attractive solution for reducing carbon emissions. However, molecular-level experimental observations of the catalytic process are scarce, and most existing catalysts tend to rely on empirically optimized, expensive, and complex nanocomposite materials. This lack of molecular-level insights has precluded the development of simpler, more cost-effective alternatives. Here, we show that graphite immersed in ultrapure water is able to spontaneously catalyze methanol from volatile organic compounds in ambient conditions. Using single-molecule resolution atomic force microscopy (AFM) in liquid, we directly observe the formation and evolution of methanol-water nanostructures at the surface of graphite. These molecularly ordered structures nucleate near catalytically active surface features, such as atomic step edges, and grow progressively as further methanol is being catalyzed. Complementary nuclear magnetic resonance analysis of the liquid confirms the formation of methanol and quantifies its concentration. We also show that electric fields significantly enhance the catalysis rate, even when as small as that induced by the natural surface potential of the silicon AFM tip. These findings could have a significant impact on the development of organic catalysts and on the function of nanoscale carbon devices.

20.
Int Physiol J ; 1(1): 1, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30123889

RESUMO

Following ocular trauma and retinal detachment, gliotic changes in the retina may develop over the subsequent month, a process known as PVR (proliferative vitreoretinopathy). There have been no successful therapeutic interventions to inhibit PVR. The protein CTGF (Connective Tissue Growth Factor) has been associated with retinal PVR and other fibrotic diseases of the retina in clinical studies but the mechanistic link between different pathologies and retinal gliosis has not been determined. In addition, CTGF has been previously noted to be associated, in some cases, with YAP/TAZ (Yes-associated protein and Tafazzin protein complex), transcriptional regulatory proteins that change subcellular localization in response to mechanical cues, such as the stiffness of the underlying material. We have previously shown that the mRNA for CTGF is markedly (100-fold) upregulated in retinal Müller cells grown on soft substrates. In order to evaluate if the mechanism by which mechanotransduction modulating CTGF production in retinal Müller cells involves the YAP/TAZ complex, this study tests the influence of substrate stiffness on the time dependence of CTGF protein expression, as well as subcellular localization of YAP/TAZ using a conditionally-immortalized mouse retinal Müller cell line plated on laminin-coated, polyacrylamide substrates of varying elastic modulus. Changes were assayed using immunohistochemistry and ELISA (Enzyme-Linked ImmunoSorbent Assay). In retinal Müller cells, the relationship between elastic modulus and the pattern of CTGF protein expression was bimodal, with CTGF levels rising more rapidly for cells on hard substrates and more slowly for cells grown on soft substrates. In addition, nuclear localization of YAP/TAZ corresponded directly to the maximum CTGF expression.

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