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1.
J Public Health Manag Pract ; 30(2): 231-239, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38271105

RESUMO

CONTEXT: The Centers for Disease Control and Prevention (CDC) and the US Postal Service (USPS) consider anthrax to be a potential threat to USPS workers. A county health department-owned pharmacy supports local USPS response in the event of an exposure. The pharmacy team identified the need to review and update the local anthrax response plan. PROGRAM/POLICY: A Pharmacy Point-of-Dispensing Toolkit and response plan for initial 10-day post-exposure antibiotic prophylaxis was developed for use by a local health department in the event of a mass anthrax exposure at a US Post Office sorting facility. The pharmacist's role in medical countermeasures planning for anthrax exposure is also discussed to illustrate how pharmacists' medication expertise can be utilized. EVALUATION: The CDC's Public Health Preparedness Capabilities: National Standards for State and Local Planning framework and inputs from an interprofessional stakeholder team were used to develop a Medical Countermeasures Response Plan and Implementation Toolkit for mass point-of-dispensing (POD) in the event of an anthrax exposure. IMPLEMENTATION AND DISSEMINATION: Stakeholders attended a USPS Community Partner Training event where additional revisions to the toolkit were made. The toolkit and standing order are now implemented at the local health department to be reviewed and updated on a yearly basis by health department leadership. DISCUSSION: Pharmacists can use their medication expertise and experience with patient education to design emergency response plans focused on increasing patient safety and medication adherence. Pharmacists should be involved in emergency response and medical countermeasures planning that involve medications.


Assuntos
Antraz , Farmácia , Humanos , Antraz/tratamento farmacológico , Antraz/prevenção & controle , Profilaxia Pós-Exposição , Farmacêuticos , Saúde Pública
2.
Immunity ; 28(5): 621-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18450484

RESUMO

B lymphocytes perform somatic hypermutation and class-switch recombination (CSR) of the immunoglobulin locus to generate an antibody repertoire diverse in both affinity and function. These somatic diversification processes are catalyzed by activation-induced cytidine deaminase (AID), a potent DNA mutator whose expression and function are highly regulated. Here we show that AID was regulated posttranscriptionally by a lymphocyte-specific microRNA, miR-155. We found that miR-155 was upregulated in murine B lymphocytes undergoing CSR and that it targeted a conserved site in the 3'-untranslated region of the mRNA encoding AID. Disruption of this target site in vivo resulted in quantitative and temporal deregulation of AID expression, along with functional consequences for CSR and affinity maturation. Thus, miR-155, which has recently been shown to play important roles in regulating the germinal-center reaction, does so in part by directly downmodulating AID expression.


Assuntos
Linfócitos B/enzimologia , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Células Cultivadas , Switching de Imunoglobulina , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , MicroRNAs/genética , MicroRNAs/imunologia , Mutação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Hipermutação Somática de Imunoglobulina
3.
J Occup Environ Hyg ; 14(8): 634-641, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28718710

RESUMO

The aims of this study were to evaluate sound levels produced by compressed air guns in research and development (R&D) environments, replace conventional air gun models with advanced noise-reducing air nozzles, and measure changes in sound levels to assess the effectiveness of the advanced nozzles as engineering controls for noise. Ten different R&D manufacturing areas that used compressed air guns were identified and included in the study. A-weighted sound level and Z-weighted octave band measurements were taken simultaneously using a single instrument. In each area, three sets of measurements, each lasting for 20 sec, were taken 1 m away and perpendicular to the air stream of the conventional air gun while a worker simulated typical air gun work use. Two different advanced noise-reducing air nozzles were then installed. Sound level and octave band data were collected for each of these nozzles using the same methods as for the original air guns. Both of the advanced nozzles provided sound level reductions of about 7 dBA, on average. The highest noise reductions measured were 17.2 dBA for one model and 17.7 dBA for the other. In two areas, the advanced nozzles yielded no sound level reduction, or they produced small increases in sound level. The octave band data showed strong similarities in sound level among all air gun nozzles within the 10-1,000 Hz frequency range. However, the advanced air nozzles generally had lower noise contributions in the 1,000-20,000 Hz range. The observed decreases at these higher frequencies caused the overall sound level reductions that were measured. Installing new advanced noise-reducing air nozzles can provide large sound level reductions in comparison to existing conventional nozzles, which has direct benefit for hearing conservation efforts.


Assuntos
Ar Comprimido , Desenho de Equipamento , Ruído Ocupacional/prevenção & controle , Pesquisa/instrumentação
4.
Development ; 140(1): 31-42, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23154418

RESUMO

Understanding the molecular mechanisms of skeletal muscle regeneration is crucial to exploiting this pathway for use in tissue repair. Our data demonstrate that the MEF2A transcription factor plays an essential role in skeletal muscle regeneration in adult mice. Injured Mef2a knockout mice display widespread necrosis and impaired myofiber formation. MEF2A controls this process through its direct regulation of the largest known mammalian microRNA (miRNA) cluster, the Gtl2-Dio3 locus. A subset of the Gtl2-Dio3 miRNAs represses secreted Frizzled-related proteins (sFRPs), inhibitors of WNT signaling. Consistent with these data, Gtl2-Dio3-encoded miRNAs are downregulated in regenerating Mef2a knockout muscle, resulting in upregulated sFRP expression and attenuated WNT activity. Furthermore, myogenic differentiation in Mef2a-deficient myoblasts is rescued by overexpression of miR-410 and miR-433, two miRNAs in the Gtl2-Dio3 locus that repress sFRP2, or by treatment with recombinant WNT3A and WNT5A. Thus, miRNA-mediated modulation of WNT signaling by MEF2A is a requisite step for proper muscle regeneration, and represents an attractive pathway for enhancing regeneration of diseased muscle.


Assuntos
Carbocianinas/metabolismo , MicroRNAs/metabolismo , Músculo Esquelético/fisiologia , Fatores de Regulação Miogênica/fisiologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regeneração/fisiologia , Proteínas Wnt/metabolismo , Animais , Células COS , Linhagem Celular , Células Cultivadas , Chlorocebus aethiops , Receptores Frizzled/genética , Técnicas de Silenciamento de Genes , Humanos , Fatores de Transcrição MEF2 , Camundongos , Camundongos Knockout , Fatores de Regulação Miogênica/genética , Transdução de Sinais/fisiologia , Regulação para Cima/genética , Proteínas Wnt/fisiologia
5.
J Insect Sci ; 162016.
Artigo em Inglês | MEDLINE | ID: mdl-26936923

RESUMO

The universal mercury vapor black light trap is an effective device used for collecting moth specimens in a wide variety of habitats; yet, they can present challenges for researchers. The mercury vapor trap is often powered by a heavy automotive battery making it difficult to conduct extensive surveys in remote regions. The mercury vapor trap also carries a considerable financial cost per trap unit, making trapping challenging with low research budgets. Here, we describe the development and trapping properties of a lighter, simply constructed, and less expensive trap. The LED funnel trap consists of a funnel, soda bottles with plastic vanes, and is powered by rechargeable 9-V batteries. Two strips of low-wavelength LEDs are used as attractants. We tested the trapping parameters of this trap design compared to a standard mercury vapor trap over 10 trap nights in a suburban woodlot in the summer of 2015. The mercury vapor trap caught significantly more moth individuals than the LED trap (average of 78 vs 40 moths per trap night; P < 0.05), and significantly more species than the LED trap (23 vs 15 per trap night; P < 0.05); the mercury vapor trap caught a total of 104 macromoth species over the duration of the study, compared to a total of 87 by the LED trap. Despite the lower yields, the low cost of the LED trap (<$30 ea.) makes it superior to the mercury vapor trap in cost-acquisition per moth species and per moth individual trapped. The LED trap may be a viable alternative to the standard mercury vapor trap, facilitating insect trapping in more diverse settings.


Assuntos
Entomologia/instrumentação , Mariposas , Animais , Custos e Análise de Custo , Entomologia/economia , Raios Ultravioleta
6.
J Virol ; 88(14): 7753-63, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24760885

RESUMO

The process of vaccination introduced by Jenner generated immunity against smallpox and ultimately led to the eradication of the disease. Procedurally, in modern times, the virus is introduced into patients via a process called scarification, performed with a bifurcated needle containing a small amount of virus. What was unappreciated was the role that scarification itself plays in generating protective immunity. In rabbits, protection from lethal disease is induced by intradermal injection of vaccinia virus, whereas a protective response occurs within the first 2 min after scarification with or without virus, suggesting that the scarification process itself is a major contributor to immunoprotection. importance: These results show the importance of local nonspecific immunity in controlling poxvirus infections and indicate that the process of scarification should be critically considered during the development of vaccination protocols for other infectious agents.


Assuntos
Vacina Antivariólica/imunologia , Varíola/prevenção & controle , Vacinação/métodos , Vaccinia virus/imunologia , Administração Cutânea , Animais , Feminino , Coelhos , Vacina Antivariólica/administração & dosagem
7.
Altern Ther Health Med ; 21(3): 36-44, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26026143

RESUMO

BACKGROUND: Female infertility is a complex issue encompassing a wide variety of diagnoses, many of which are caused or affected by adhesions. OBJECTIVES: The study intended to examine the rates of successful treatment of infertile women using a protocol of manual physical therapy to address underlying adhesive disease leading to infertility. Methods • The research team designed a retrospective chart review. SETTING: The study took place in a private physical therapy clinic. PARTICIPANTS: Participants were 1392 female patients who were treated at the clinic between the years of 2002 and 2011. They had varying diagnoses of infertility, including occluded fallopian tubes, hormonal dysfunction, and endometriosis, and some women were undergoing in vitro fertilization (IVF). Intervention • All patients underwent whole-body, patient-centered treatments that used a protocol of manual physical therapy, which focused on restoring mobility and motility to structures affecting reproductive function. OUTCOME MEASURES: Improvements demonstrated in the condition(s) causing infertility were measured by improvements in tubal patency and/or improved hormone levels or by pregnancy. Results • The results included a 60.85% rate of clearing occluded fallopian tubes, with a 56.64% rate of pregnancy in those patients. Patients with endometriosis experienced a 42.81% pregnancy rate. The success rate was 49.18% for lowering elevated levels of follicle stimulating hormone (FSH), with a 39.34% pregnancy rate in that group, and 53.57% of the women with polycystic ovarian syndrome (PCOS) achieved pregnancy. The reported pregnancy rate for patients who underwent IVF after the therapy was 56.16%. The results also suggested that the treatment was effective for patients with premature ovarian failure (POF). CONCLUSION: The manual physical therapy represented an effective, conservative treatment for women diagnosed as infertile due to mechanical causes, independent of the specific etiology.


Assuntos
Infertilidade Feminina/terapia , Modalidades de Fisioterapia , Adulto , Feminino , Humanos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
8.
Artigo em Inglês | MEDLINE | ID: mdl-25691329

RESUMO

Background • Female infertility is a complex issue encompassing a wide variety of diagnoses, many of which are caused or affected by adhesions. Objectives • The study intended to examine the rates of successful treatment of infertile women using a protocol of manual physical therapy to address underlying adhesive disease leading to infertility. Methods • The research team designed a retrospective chart review. Setting • The study took place in a private physical therapy clinic. Participants • Participants were 1392 female patients who were treated at the clinic between the years of 2002 and 2011. They had varying diagnoses of infertility, including occluded fallopian tubes, hormonal dysfunction, and endometriosis, and some women were undergoing in vitro fertilization (IVF). Intervention • All patients underwent whole-body, patient-centered treatments that used a protocol of manual physical therapy, which focused on restoring mobility and motility to structures affecting reproductive function. Outcome Measures • Improvements demonstrated in the condition(s) causing infertility were measured by improvements in tubal patency and/or improved hormone levels or by pregnancy. Results • The results included a 60.85% rate of clearing occluded fallopian tubes, with a 56.64% rate of pregnancy in those patients. Patients with endometriosis experienced a 42.81% pregnancy rate. The success rate was 49.18% for lowering elevated levels of follicle stimulating hormone (FSH), with a 39.34% pregnancy rate in that group, and 53.57% of the women with polycystic ovarian syndrome (PCOS) achieved pregnancy. The reported pregnancy rate for patients who underwent IVF after the therapy was 56.16%. The results also suggested that the treatment was effective for patients with premature ovarian failure (POF). Conclusion • The manual physical therapy represented an effective, conservative treatment for women diagnosed as infertile due to mechanical causes, independent of the specific etiology.

9.
Am J Trop Med Hyg ; 109(1): 126-133, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37188338

RESUMO

Arthropods are vectors for many pathogens that significantly harm human and animal health globally, and research into vector-borne diseases is of critical public health importance. Arthropods present unique risks for containment, and therefore insectary facilities are essential to the safe handling of arthropod-borne hazards. In 2018, the School of Life Sciences at Arizona State University (ASU) began the process to build a level 3 arthropod containment (ACL-3) facility. Even with the COVID-19 pandemic, it took more than 4 years for the insectary to be granted a Certificate of Occupancy. At the request of the ASU Environmental Health and Safety team, Gryphon Scientific, an independent team with biosafety and biological research expertise, studied the project lifecycle through the design, construction, and commissioning of the ACL-3 facility with the goal of identifying lessons learned from the delayed timeline. These lessons learned convey insight into best practices for assessing potential facility sites, anticipating challenges with retrofitted construction, preparing for commissioning, equipping the project team with necessary expertise and expectations, and supplementing the gaps in available containment guidance. Several unique mitigations designed by the ASU team to address research risks not specifically addressed in the American Committee of Medical Entomology Arthropod Containment Guidelines are also described. Completion of the ACL-3 insectary at ASU was delayed, but the team thoroughly assessed potential risks and enabled appropriate practices for the safe handling of arthropod vectors. These efforts will enhance future ACL-3 construction by helping to avoid similar setbacks and streamlining progress from concept to operation.


Assuntos
Artrópodes , COVID-19 , Animais , Humanos , Pandemias/prevenção & controle , Vetores Artrópodes , Contenção de Riscos Biológicos
10.
J Virol ; 85(1): 550-67, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20943971

RESUMO

The importance of the 2'-5' oligoadenylate synthetase (OAS)/RNase L and double-stranded RNA (dsRNA)-dependent protein kinase (PKR) pathways in host interferon induction resulting from virus infection in response to dsRNA has been well documented. In poxvirus infections, the interactions between the vaccinia virus (VV) genes E3L and K3L, which target RNase L and PKR, respectively, serve to prevent the induction of the dsRNA-dependent induced interferon response in cell culture. To determine the importance of these host genes in controlling VV infections, mouse single-gene knockouts of RNase L and PKR and double-knockout mice were studied following intratracheal infection with VV, VVΔK3L, or VVΔE3L. VV caused lethal disease in all mouse strains. The single-knockout animals were more susceptible than wild-type animals, while the RNase L(-/-) PKR(-/-) mice were the most susceptible. VVΔE3L infections of wild-type mice were asymptomatic, demonstrating that E3L plays a critical role in controlling the host immune response. RNase L(-/-) mice showed no disease, whereas 20% of the PKR(-/-) mice succumbed at a dose of 10(8) PFU. Lethal disease was routinely observed in RNase L(-/-) PKR(-/-) mice inoculated with 10(8) PFU of VVΔE3L, with a distinct pathology. VVΔK3L infections exhibited no differences in virulence among any of the mouse constructs, suggesting that PKR is not the exclusive target of K3L. Surprisingly, VVΔK3L did not disseminate to other tissues from the lung. Hence, the cause of death in this model is respiratory disease. These results also suggest that an unanticipated role of the K3L gene is to facilitate virus dissemination.


Assuntos
Endorribonucleases/metabolismo , Interações Hospedeiro-Patógeno , Proteínas de Ligação a RNA/metabolismo , Vaccinia virus/patogenicidade , Vacínia/virologia , Proteínas Virais/metabolismo , eIF-2 Quinase/metabolismo , Animais , Linhagem Celular , Cricetinae , Endorribonucleases/genética , Perfilação da Expressão Gênica , Pulmão/metabolismo , Pulmão/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas/genética , Proteínas/metabolismo , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/imunologia , RNA de Cadeia Dupla/metabolismo , Proteínas de Ligação a RNA/genética , Doenças da Traqueia/patologia , Doenças da Traqueia/virologia , Vacínia/imunologia , Vacínia/patologia , Vaccinia virus/genética , Vaccinia virus/metabolismo , Proteínas Virais/genética , eIF-2 Quinase/genética
11.
Appl Biosaf ; 27(2): 64-78, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36035499

RESUMO

Introduction: Although the COVID-19 pandemic began over 2 years ago, responses from institutions have not been thoroughly documented. Because of constantly evolving guidance from regulatory and public health agencies, the traditional evidence-based risk assessment process was disrupted. It took time to obtain enough actionable information about the novel SARS-CoV-2 virus and its transmission to be able to inform decision making and consistently make accurate recommendations. Objectives: The primary objective of this article is to detail the actions in chronological order taken by the biosafety team at Arizona State University in response to the COVID-19 pandemic. Methods: This article includes a chronicling of actual experiences and observations with a retrospective review and analysis of the actions taken to document and share lessons learned to guard against future pandemics. Specific infection control practices, such as measuring saliva droplets from dropped test tubes, are described and different COVID-19 testing and vaccination site designs are evaluated. Results: The biosafety team helped collect more than 304,000 saliva samples, deliver 15,528 vaccinations, safely manage more than 170,000 gallons of biohazardous waste, and oversee the pandemic response inventory. The team also conducted inspections, developed safety procedures, and reviewed research protocols. Conclusions: The COVID-19 pandemic required safety professionals to re-envision how they perform their work, not only at their place of employment, but also within their communities and at their homes. This presented a challenge to balance inquiry and the scientific process against the urgent need for understanding changing pandemic dynamics and information and developing new best practices.

12.
J Biol Chem ; 285(12): 9202-10, 2010 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-20032458

RESUMO

Binding of the 4-1BB ligand (4-1BBL) to its receptor, 4-1BB, provides the T lymphocyte with co-stimulatory signals for survival, proliferation, and differentiation. Importantly, the 4-1BB-4-1BBL pathway is a well known target for anti-cancer immunotherapy. Here we present the 2.3-A crystal structure of the extracellular domain of human 4-1BBL. The ectodomain forms a homotrimer with an extended, three-bladed propeller structure that differs from trimers formed by other members of the tumor necrosis factor (TNF) superfamily. Based on the 4-1BBL structure, we modeled its complex with 4-1BB, which was consistent with images obtained by electron microscopy, and verified the binding site by site-directed mutagenesis. This structural information will facilitate the development of immunotherapeutics targeting 4-1BB.


Assuntos
Ligante 4-1BB/química , Ligante 4-1BB/fisiologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/fisiologia , Ligante 4-1BB/genética , Sítios de Ligação , Proliferação de Células , Clonagem Molecular , Cristalografia por Raios X/métodos , Dimerização , Citometria de Fluxo , Humanos , Microscopia Eletrônica/métodos , Modelos Moleculares , Conformação Molecular , Mutagênese Sítio-Dirigida , Ligação Proteica , Estrutura Terciária de Proteína , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/química
13.
Shock ; 55(2): 256-267, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32769821

RESUMO

ABSTRACT: Traumatic brain injury (TBI) can induce acute lung injury (ALI). The exact pathomechanism of TBI-induced ALI is poorly understood, limiting treatment options. Remote ischemic conditioning (RIC) can mitigate detrimental outcomes following transplants, cardiac arrests, and neurological injuries. In this study, we hypothesized that RIC would reduce TBI-induced ALI by regulating the sphingosine-1-phosphate (S1P)-dependent pathway, a central regulator of endothelial barrier integrity, lymphocyte, and myokine trafficking. Male mice were subjected to either diffuse TBI by midline fluid percussion or control sham injury and randomly assigned among four groups: sham, TBI, sham RIC, or TBI RIC; RIC was performed 1 h prior to TBI. Mice were euthanized at 1-h postinjury or 7 days post-injury (DPI) and lung tissue, bronchoalveolar lavage (BAL) fluid, and blood were collected. Lung tissue was analyzed for histopathology, irisin myokine levels, and S1P receptor levels. BAL fluid and blood were analyzed for cellularity and myokine/S1P levels, respectively. One-hour postinjury, TBI damaged lung alveoli and increased neutrophil infiltration; RIC preserved alveoli. BAL from TBI mice had more neutrophils and higher neutrophil/monocyte ratios compared with sham, where TBI RIC mice showed no injury-induced change. Further, S1P receptor 3 and irisin-associated protein levels were significantly increased in the lungs of TBI mice compared with sham, which was prevented by RIC. However, there was no RIC-associated change in plasma irisin or S1P. At 7 DPI, ALI in TBI mice was largely resolved, with evidence for residual lung pathology. Thus, RIC may be a viable intervention for TBI-induced ALI to preserve lung function and facilitate clinical management.


Assuntos
Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Lesões Encefálicas Traumáticas/complicações , Precondicionamento Isquêmico/métodos , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Distribuição Aleatória
14.
J Virol ; 83(18): 9223-36, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19570875

RESUMO

Many pathogenic orthopoxviruses like variola virus, monkeypox virus, and cowpox virus (CPXV), but not vaccinia virus, encode a unique family of ankyrin (ANK) repeat-containing proteins that interact directly with NF-kappaB1/p105 and inhibit the NF-kappaB signaling pathway. Here, we present the in vitro and in vivo characterization of the targeted gene knockout of this novel NF-kappaB inhibitor in CPXV. Our results demonstrate that the vCpx-006KO uniquely induces a variety of NF-kappaB-controlled proinflammatory cytokines from infected myeloid cells, accompanied by a rapid phosphorylation of the IkappaB kinase complex and subsequent degradation of the NF-kappaB cellular inhibitors IkappaBalpha and NF-kappaB1/p105. Moreover, the vCpx-006KO virus was attenuated for virulence in mice and induced a significantly elevated cellular inflammatory process at tissue sites of virus replication in the lung. These results indicate that members of this ANK repeat family are utilized specifically by pathogenic orthopoxviruses to repress the NF-kappaB signaling pathway at tissue sites of virus replication in situ.


Assuntos
Repetição de Anquirina , Movimento Celular/imunologia , Vírus da Varíola Bovina/patogenicidade , Inflamação/patologia , Subunidade p50 de NF-kappa B/antagonistas & inibidores , Proteínas Virais/fisiologia , Animais , Vírus da Varíola Bovina/química , Citocinas , Pneumopatias/patologia , Pneumopatias/virologia , Camundongos , Células Mieloides/virologia , Transdução de Sinais
15.
Shock ; 53(3): 284-292, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32045395

RESUMO

BACKGROUND: Sepsis is a potentially life-threatening complication of an underlying infection that quickly triggers tissue damage in multiple organ systems. To date, there are no established useful prognostic biomarkers for sepsis survival prediction. Sphingosine-1-phosphate (S1P) and its receptor S1P receptor 1 (S1PR1) are potential therapeutic targets and biomarkers for sepsis, as both are active regulators of sepsis-relevant signaling events. However, the identification of an S1PR1-related gene signature for prediction of survival in sepsis patients has yet to be identified. This study aims to find S1PR1-associated biomarkers which could predict the survival of patients with sepsis using gene expression profiles of peripheral blood to be used as potential prognostic and diagnostic tools. METHODS: Gene expression analysis from sepsis patients enrolled in published datasets from Gene Expression Omnibus was utilized to identify both S1PR1-related genes (co-expression genes or functional-related genes) and sepsis survival-related genes. RESULTS: We identified 62-gene and 16-gene S1PR1-related molecular signatures (SMS) associated with survival of patients with sepsis in discovery cohort. Both SMS genes are significantly enriched in multiple key immunity-related pathways that are known to play critical roles in sepsis development. Meanwhile, the SMS performs well in a validation cohort containing sepsis patients. We further confirmed our SMSs, as newly developed gene signatures, perform significantly better than random gene signatures with the same gene size, in sepsis survival prognosis. CONCLUSIONS: Our results have confirmed the significant involvement of S1PR1-dependent genes in the development of sepsis and provided new gene signatures for predicting survival of sepsis patients.


Assuntos
Sepse/genética , Sepse/mortalidade , Receptores de Esfingosina-1-Fosfato/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Transdução de Sinais , Taxa de Sobrevida , Transcriptoma
16.
J Am Chem Soc ; 131(49): 17777-9, 2009 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-19916553

RESUMO

Biophysical studies of membrane proteins are often impeded by the requirement for a membrane mimicking environment. Detergent micelles are the most common choice, but the denaturing properties make them unsatisfactory for studies of many membrane proteins and their interactions. In the present work, we explore phospholipid bilayer nanodiscs as membrane mimics and employ electron microscopy and solution NMR spectroscopy to characterize the structure and function of the human voltage dependent anion channel (VDAC-1) as an example of a polytopic integral membrane protein. Electron microscopy reveals the formation of VDAC-1 multimers, an observation that is consistent with results obtained in native mitochondrial outer membranes. High-resolution NMR spectroscopy demonstrates a well folded VDAC-1 protein and native NADH binding functionality. The observed chemical shift changes upon addition of the native ligand NADH to nanodisc-embedded VDAC-1 resemble those of micelle-embedded VDAC-1, indicating a similar structure and function in the two membrane-mimicking environments. Overall, the ability to study integral membrane proteins at atomic resolution with solution NMR in phospholipid bilayers, rather than in detergent micelles, offers exciting novel possibilities to approach the biophysical properties of membrane proteins under nondenaturing conditions, which makes this technology particular suitable for protein-protein interactions and other functional studies.


Assuntos
Bicamadas Lipídicas/química , Nanoestruturas/química , Canal de Ânion 1 Dependente de Voltagem/química , Dimiristoilfosfatidilcolina/química , Humanos , Tamanho da Partícula , Conformação Proteica , Propriedades de Superfície
17.
World J Gastroenterol ; 24(19): 2108-2119, 2018 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-29785079

RESUMO

AIM: To compare (1) quality of life and (2) rate of recurrent small bowel obstructions (SBO) for patients treated with novel manual physiotherapy vs no treatment. METHODS: One hundred and three subjects (age 19-89) with a history of recurrent adhesive SBO were treated with a manual physiotherapy called the Clear Passage Approach (CPA) which focused on decreasing adhesive crosslinking in abdominopelvic viscera. Pre- and post-therapy data measured recurring obstructions and quality of life, using a validated test sent 90 d after therapy. Results were compared to 136 untreated control subjects who underwent the same measurements for subjects who did not receive any therapy, which is the normal course for patients with recurring SBO. Comparison of the groups allowed us to assess changes when the physiotherapy was added as an adjunct treatment for patients with recurring SBO. RESULTS: Despite histories of more prior hospitalizations, obstructions, surgeries, and years impacted by bowel issues, the 103 CPA-treated subjects reported a significantly lower rate of repeat SBO than 136 untreated controls (total obstructions P = 0.0003; partial obstructions P = 0.0076). Subjects treated with the therapy demonstrated significant improvements in five of six total domains in the validated Small Bowel Obstruction Questionnaire (SBO-Q). Domains of diet, pain, gastrointestinal symptoms, quality of life (QOL) and pain severity when compared to post CPA treatment were significantly improved (P < 0.0001). The medication domain was not changed in the CPA treated group (P = 0.176). CONCLUSION: CPA physical therapy was effective for patients with adhesive SBO with significantly lower recurrence rate, improvement in reported symptoms and overall quality of life of subjects.


Assuntos
Obstrução Intestinal/reabilitação , Intestino Delgado/patologia , Manipulações Musculoesqueléticas/métodos , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Doença Crônica/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
18.
Protein Sci ; 16(9): 1977-83, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17766390

RESUMO

Human phospholamban (PLN), a 30 kDa homopentamer in the sarcoplasmic reticulum (SR) membrane, controls the magnitude of heart muscle contraction and relaxation by regulating the calcium pumping activity of the SR Ca(2+)-ATPase (SERCA). When PLN is not phosphorylated, it binds and inhibits SERCA. Phosphorylation of PLN at S16 or T17 releases such inhibitory effect. It remains a matter of debate whether phosphorylation perturbs the structure of PLN, which in turn affects its interaction with SERCA. Here we examine by NMR spectroscopy the structure and dynamics of PLN pentamer with a physiologically relevant, phosphorylation-mimicking mutation, S16E. Based on extensive NMR data, including NOEs, dipolar couplings, and solvent exchange of backbone amides, we conclude that the phosphorylation-mimicking mutation does not perturb the pentamer structure. However, (15)N R(1) and R(2) relaxation rates and (15)N((1)H) NOEs suggest subtle differences in the dynamics of the extramembrane portion of the protein.


Assuntos
Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/metabolismo , Substituição de Aminoácidos , Proteínas de Ligação ao Cálcio/genética , Humanos , Peso Molecular , Ressonância Magnética Nuclear Biomolecular , Fosforilação , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Serina/metabolismo , Relação Estrutura-Atividade
19.
J Diabetes Complications ; 21(1): 63-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17189876

RESUMO

A 57-year-old Caucasian man presented with diaphragmatic paralysis and type 2 diabetes. He had severe orthopnea that remained unchanged for 1 year. He was later diagnosed with distal symmetric polyneuropathy and was started on topiramate. Within 26 weeks of treatment, the patient showed improvement in diaphragmatic function and regrowth of intraepidermal nerve fibers, accompanied by improvement in respiratory and peripheral neuropathy symptoms. Topiramate may prove to be an effective agent in the treatment of nonremitting diaphragmatic paralysis and regrowth of intraepidermal nerve fibers.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/fisiopatologia , Frutose/análogos & derivados , Fármacos Neuroprotetores/uso terapêutico , Paralisia/tratamento farmacológico , Nervo Frênico/fisiopatologia , Neuropatias Diabéticas/diagnóstico por imagem , Frutose/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Topiramato , Resultado do Tratamento , Capacidade Vital
20.
Psychol Assess ; 29(6): 639-651, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28594208

RESUMO

Offenders with high levels of both psychopathy and deviant sexual interests are often described as being more prone to recidivate than other sexual offenders, and many forensic evaluators report considering this psychopathy and sexual deviance interaction when coming to conclusions about sex offender risk. However, empirical support for the interaction comes from studies using sexual deviance measures that are rarely used in the field. We examined the ability of Psychopathy Checklist-Revised (PCL-R) field scores and possible field measures of sexual deviance (e.g., paraphilia diagnosis, offense characteristics) to predict sexual recidivism among 687 offenders released after being evaluated for postrelease civil commitment (M follow-up = 10.5 years). PCL-R total scores and antisocial personality diagnoses were predictive of a combined category of violent or sexual recidivism, but not sexual recidivism. Paraphilia diagnoses and offense characteristics were not associated with an increased likelihood of reoffending. There was no evidence that those with high levels of both psychopathy and sexual deviance were more likely than others to reoffend. Although the psychopathy and sexual deviance interaction findings from prior studies are large and compelling, our findings highlight the need for research examining the best ways to translate those findings into routine practice. (PsycINFO Database Record


Assuntos
Transtorno da Personalidade Antissocial/epidemiologia , Criminosos/estatística & dados numéricos , Transtornos Parafílicos/epidemiologia , Escalas de Graduação Psiquiátrica/normas , Reincidência/estatística & dados numéricos , Medição de Risco/normas , Delitos Sexuais/estatística & dados numéricos , Adulto , Transtorno da Personalidade Antissocial/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Parafílicos/diagnóstico , Texas/epidemiologia
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