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1.
N Engl J Med ; 387(21): 1935-1946, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36351262

RESUMO

BACKGROUND: In February 2022, Massachusetts rescinded a statewide universal masking policy in public schools, and many Massachusetts school districts lifted masking requirements during the subsequent weeks. In the greater Boston area, only two school districts - the Boston and neighboring Chelsea districts - sustained masking requirements through June 2022. The staggered lifting of masking requirements provided an opportunity to examine the effect of universal masking policies on the incidence of coronavirus disease 2019 (Covid-19) in schools. METHODS: We used a difference-in-differences analysis for staggered policy implementation to compare the incidence of Covid-19 among students and staff in school districts in the greater Boston area that lifted masking requirements with the incidence in districts that sustained masking requirements during the 2021-2022 school year. Characteristics of the school districts were also compared. RESULTS: Before the statewide masking policy was rescinded, trends in the incidence of Covid-19 were similar across school districts. During the 15 weeks after the statewide masking policy was rescinded, the lifting of masking requirements was associated with an additional 44.9 cases per 1000 students and staff (95% confidence interval, 32.6 to 57.1), which corresponded to an estimated 11,901 cases and to 29.4% of the cases in all districts during that time. Districts that chose to sustain masking requirements longer tended to have school buildings that were older and in worse condition and to have more students per classroom than districts that chose to lift masking requirements earlier. In addition, these districts had higher percentages of low-income students, students with disabilities, and students who were English-language learners, as well as higher percentages of Black and Latinx students and staff. Our results support universal masking as an important strategy for reducing Covid-19 incidence in schools and loss of in-person school days. As such, we believe that universal masking may be especially useful for mitigating effects of structural racism in schools, including potential deepening of educational inequities. CONCLUSIONS: Among school districts in the greater Boston area, the lifting of masking requirements was associated with an additional 44.9 Covid-19 cases per 1000 students and staff during the 15 weeks after the statewide masking policy was rescinded.


Assuntos
COVID-19 , Política de Saúde , Máscaras , Serviços de Saúde Escolar , Precauções Universais , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Incidência , Pobreza/estatística & dados numéricos , Instituições Acadêmicas/legislação & jurisprudência , Instituições Acadêmicas/estatística & dados numéricos , Estudantes/legislação & jurisprudência , Estudantes/estatística & dados numéricos , Política de Saúde/legislação & jurisprudência , Máscaras/estatística & dados numéricos , Serviços de Saúde Escolar/legislação & jurisprudência , Serviços de Saúde Escolar/estatística & dados numéricos , Categorias de Trabalhadores/legislação & jurisprudência , Categorias de Trabalhadores/estatística & dados numéricos , Precauções Universais/legislação & jurisprudência , Precauções Universais/estatística & dados numéricos , Massachusetts/epidemiologia , Controle de Doenças Transmissíveis/legislação & jurisprudência , Controle de Doenças Transmissíveis/estatística & dados numéricos
2.
Proc Natl Acad Sci U S A ; 118(37)2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34433692

RESUMO

The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, correlating with poor outcomes. These Tregs showed a distinct transcriptional signature, with overexpression of several suppressive effectors, but also proinflammatory molecules like interleukin (IL)-32, and a striking similarity to tumor-infiltrating Tregs that suppress antitumor responses. Most marked during acute severe disease, these traits persisted somewhat in convalescent patients. A screen for candidate agents revealed that IL-6 and IL-18 may individually contribute different facets of these COVID-19-linked perturbations. These results suggest that Tregs may play nefarious roles in COVID-19, by suppressing antiviral T cell responses during the severe phase of the disease, and by a direct proinflammatory role.


Assuntos
COVID-19/etiologia , Linfócitos T Reguladores/fisiologia , Adulto , Idoso , Linfócitos T CD4-Positivos/virologia , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Inflamação/metabolismo , Inflamação/virologia , Interleucina-18/genética , Interleucina-18/metabolismo , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Linfócitos do Interstício Tumoral/fisiologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/virologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
3.
J Pediatr Gastroenterol Nutr ; 77(4): 486-490, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37490618

RESUMO

Genetic variations, in specific COMT , OPRM1 , and MAO-A polymorphisms, have been associated with hypnotizability in adults. The aim of this exploratory study was to investigate whether these polymorphisms are also associated with response to hypnotherapy (HT) in children. Patients (8-18 years, n = 260) diagnosed with a functional abdominal pain disorder (FAPD) from a previous trial assessing HT efficacy were approached for participation and 144 agreed to collect a buccal sample. Primary aim was to explore the association between COMT , OPRM1 , and MAO-A polymorphisms with treatment success (TS) after 3-month HT. Additionally, associations between these polymorphisms and adequate relief, anxiety, depression, quality of life, somatization, hypnotic susceptibility, expectations, pain beliefs, and coping strategies were evaluated. Participants with different variations of COMT , MAO-A , and OPRM1 achieved similar TS levels ( P > 0.05). No associations were found between these polymorphisms and secondary outcomes. This suggest that in pediatric patients with FAPDs, COMT , OPRM1 , and MAO-A polymorphisms do not predict HT response.


Assuntos
Hipnose , Qualidade de Vida , Adulto , Humanos , Criança , Polimorfismo de Nucleotídeo Único , Dor Abdominal/genética , Dor Abdominal/terapia , Monoaminoxidase/genética
4.
J Clin Nurs ; 32(21-22): 7812-7821, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37658646

RESUMO

AIM: To investigate the self-reported levels of social support from friends and family and from nurses as mediators of the relationship between self-rated physical and psychological condition in hospitalised patients. DESIGN: Cross-sectional study of adult inpatients at a large tertiary-care hospital in the northeast United States. METHODS: Multiple mediation analysis of survey data. RESULTS: In surveys received from 324 inpatients, one fourth of the variation in patients' self-rated psychological condition was explained by self-rated physical condition. Social support from family and friends mediated a significant proportion (11.0%) of the relationship between self-rated physical and psychological condition, however social support from nurses did not. CONCLUSION: Social support from family and friends can positively influence the psychological health of inpatients, but nurses are not an adequate replacement for the social support provided by family and friends. IMPLICATIONS FOR NURSING: Although nurses cannot replace the social support provided by family and friends, the assessment of social isolation and care planning of interventions to support patients is a fundamental nursing role. Technology to connect patients with friends and family should be used to mitigate isolation for hospitalised patients unable to receive in-person visits from loved ones. IMPACT: The influence of social support from family and friends and nurses was addressed. The study found social support from family and friends, but not nurses, to influence the relationship between physical and psychological ratings. This finding has implications for the role of nurses in the hospital setting. REPORTING METHOD: Strengthening the Reporting of Observational Studies in Epidemiology guidelines were followed.

6.
BMC Med Res Methodol ; 20(1): 228, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917141

RESUMO

BACKGROUND: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic. RESULTS: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. CONCLUSIONS: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Manejo de Espécimes/métodos , Adolescente , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Feminino , Desenvolvimento Fetal , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , SARS-CoV-2
7.
Curr Psychiatry Rep ; 22(11): 55, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32845375

RESUMO

PURPOSE OF THE REVIEW: This review will examine the current, although limited, literature on the development of healthy sexuality for sex offenders, as well as some of the related controversies surrounding sex offender specific therapies. RECENT FINDINGS: Over the last decade, the definition of healthy sexuality has remained elusive while the boundary delineating unhealthy sexuality has radically changed. These changes are not reflected in current approaches to sex offender treatment which continue to focus on suppression of offenders' sexuality. Our attention to the management of sexual behaviors has led to a diminished, and perhaps impoverished, curiosity and understanding of what is driving problematic sexual behavior and also moves us further from an understanding of what leads to "healthy" sexual behavior. It is our contention that a consideration of sex offending behavior through the lens of early childhood trauma will lead to an improvement in our ability to assist these offenders in the development of sexually happier and more fulfilling lives while being able to function within the parameters of society's standards for legal behavior. The sex positive perspective of sex therapy will allow for a broader consideration of what defines and promotes healthy sexual behavior in an offender population.


Assuntos
Criminosos , Delitos Sexuais , Criança , Pré-Escolar , Humanos , Comportamento Sexual , Sexualidade
8.
Eur Heart J ; 40(41): 3385-3392, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31228190

RESUMO

AIMS: Efficacy of aspirin in primary prevention of cardiovascular disease (CVD) may be influenced by a common allele in guanylate cyclase GUCY1A3, which has been shown to modify platelet function and increase CVD risk. METHODS AND RESULTS: We investigated whether homozygotes of the GUCY1A3 rs7692387 risk (G) allele benefited from aspirin in two long-term, randomized placebo-controlled trials of aspirin in primary CVD prevention: the Women's Genome Health Study (WGHS, N = 23 294) and a myocardial infarction (MI, N = 550) and stroke (N = 382) case-control set from the Physician's Health Study (PHS, N = 22 071). Bleeding risk was evaluated in the WGHS. In the placebo group of the WGHS, the GUCY1A3 risk (G) allele was confirmed to increase CVD risk [hazard ratio 1.38; 95% confidence interval (CI) 1.08-1.78; P = 0.01]. Random-effects meta-analysis of the WGHS and PHS revealed that aspirin reduced CVD events among risk allele homozygotes [G/G: odds ratio (OR) 0.79; 95% CI 0.65-0.97; P = 0.03] but increased CVD events among non-risk allele carriers (e.g. G/A: OR 1.39; 95% CI 1.03-1.87; P = 0.03) thus implying an interaction between genotype stratum and aspirin intake (Pinteraction = 0.01). Bleeding associated with aspirin increased in all genotype groups, with higher risks in heterozygotes. CONCLUSION: In two randomized placebo-controlled trials in the setting of primary prevention, aspirin reduced the incidence of CVD events in individuals homozygous for the GUCY1A3 risk (G) allele, whereas heterozygote individuals had more events when taking aspirin.


Assuntos
Aspirina , Doenças Cardiovasculares , Doença da Artéria Coronariana , Guanilil Ciclase Solúvel/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/prevenção & controle , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Prevenção Primária
9.
Am J Geriatr Psychiatry ; 27(1): 1-8, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30424994

RESUMO

OBJECTIVE: Catechol-O-methyltransferase (COMT), a key enzyme in degrading catecholamines associated with the stress response, may influence susceptibility to delirium. Individuals with the COMT (rs4680) Val/Val genotype (designated "warriors") withstand the onset of neuropsychiatric disorders and cognitive decline, whereas individuals with Met/Met and Val/Met genotypes ("nonwarriors") are more susceptible to these conditions. We evaluated whether COMT genotype modifies the established association between acute phase reactant (stress marker) C-reactive protein (CRP) and postoperative delirium. METHODS: This was a prospective cohort study conducted at two academic medical centers. The study involved 547 patients aged 70 or older undergoing major noncardiac surgery. We collected blood, extracted DNA, and performed COMT genotyping using allele-specific polymerase chain reaction assays, considering warriors versus nonwarriors. High plasma CRP, measured on postoperative day 2 using enzyme-linked immunosorbent assay, was defined by the highest sample-based quartile (≥234.12 mg/L). Delirium was determined using the Confusion Assessment Method, augmented by a validated chart review. We used generalized linear models adjusted for age, sex, surgery type, and race/ethnicity, stratified by COMT genotype, to determine whether the association between CRP and delirium differed by COMT. RESULTS: Prevalence of COMT warriors was 26%, and postoperative delirium occurred in 23%. Among COMT warriors, high CRP was not associated with delirium (relative risk [RR] 1.0, 95% confidence interval [CI] 0.4-2.6). In contrast, among nonwarriors, we found the expected relationship of high CRP and delirium (RR 1.5, 95% CI 1.1-2.2). CONCLUSION: COMT warriors may be protected against the increased risk of delirium associated with high CRP on postoperative day 2. With further confirmation, COMT genotype may help target interventions for delirium prevention in the vulnerable nonwarrior group.


Assuntos
Proteína C-Reativa , Catecol O-Metiltransferase/genética , Delírio , Predisposição Genética para Doença/genética , Complicações Pós-Operatórias , Idoso , Idoso de 80 Anos ou mais , Delírio/sangue , Delírio/genética , Delírio/fisiopatologia , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/genética , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos
10.
Support Care Cancer ; 27(6): 2179-2187, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30298411

RESUMO

PURPOSE: Cancer-related fatigue (CRF) is a common and challenging late effect for many cancer survivors. Clinical trials demonstrate robust placebo effects on CRF in blinded trials. Recently, open-label placebo (OLP) has been shown to improve a variety of symptoms in other populations. We conducted a randomized controlled trial to investigate the effect of OLP on CRF in cancer survivors, and to explore biologic and psychological correlates of placebo efficacy. METHODS: Forty cancer survivors (92.5% female; mean age 47.3 years) were randomized to OLP or no treatment control. OLP participants were prescribed two placebo tablets twice daily, for 3 weeks. All participants completed assessments at Baseline, Day 8, and Day 22. The primary endpoint was change in CRF (FACIT-F), and secondary outcomes included exercise frequency, mood, and quality of life. We examined whether personality characteristics or a genetic variation important in dopamine catabolism (catechol-O-methyltransferase; COMT) affected the placebo response. RESULTS: The OLP group reported significantly improved CRF at both Day 8 (p = 0.005) and Day 22 (p = .02), while the control group did not (ps > .05). CRF improvement differed by COMT genotype, but was not associated with personality characteristics. Marginal improvements were noted in the placebo group for some secondary outcomes (exercise frequency and quality of life), but not in the control group. CONCLUSIONS: Results demonstrate that even when administered openly, placebos improve CRF in cancer survivors and dopaminergic systems may be associated with this response. This novel research has meaningful implications for the use of OLP in symptom management for cancer survivors.


Assuntos
Sobreviventes de Câncer/psicologia , Fadiga/terapia , Qualidade de Vida/psicologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Projetos de Pesquisa , Resultado do Tratamento , Adulto Jovem
11.
Surg Endosc ; 33(8): 2657-2662, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30390161

RESUMO

INTRODUCTION: The use of non-narcotic modalities for postoperative analgesia may decrease exposure to opioids, thereby limiting their deleterious effects. The objective of this study was to determine the effectiveness of a liposomal bupivacaine transverse abdominis plane (TAP) block prior to laparoscopic sleeve gastrectomy (LSG) and laparoscopic gastric bypass (LRYGB). The primary outcome was total postoperative morphine equivalents. METHODS: A single-surgeon, IRB-approved retrospective chart review was performed on consecutive patients who underwent LRYGB or LSG from 2010 to 2016. Patients were grouped according to those who received TAP blocks immediately preoperatively with rescue opioids (TAP group) and those who received PCA only (PCA group). Total parenteral morphine equivalents (PME) were calculated. Numerical pain scores were collected immediately following surgery, 12 h postoperatively, and on the day of discharge. Median length of stay (LOS) and 30-day readmissions were also calculated. RESULTS: There were 440 patients who met inclusion criteria. The TAP group had significantly less opioid use (total PME) than the PCA, irrespective of surgical approach (70.4 ± 2.7 PCA LRYGB and 26.5 ± 1.5 TAP block LRYGB, p value ≤ 0.0001; 60.0 ± 3.5 PCA LSG vs. and 24.1 ± 2.0 TAP block LSG, p value < 0.0001). Median LOS was 2.0 days for both PCA groups, whereas LOS decreased to 1.0 day for both groups of patients receiving TAP blocks (p < 0.0001). Pain scores immediately following and 12 h after surgery were significantly elevated in the TAP LRYGB versus PCA LRYGB (p < 0.05) and immediately following surgery for PCA versus TAP block for LSG (p = 0.0109). CONCLUSIONS: TAP blocks with liposomal bupivacaine lead to significantly less use of parenteral morphine equivalents and decreased LOS compared to PCA alone. Pain scores were higher in the TAP LRYGB group compared to the LRYGB PCA group, with no differences in pain scores noted in the LSG groups.


Assuntos
Analgésicos não Narcóticos/administração & dosagem , Bupivacaína/administração & dosagem , Gastrectomia , Derivação Gástrica , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Músculos Abdominais/inervação , Adulto , Analgesia Controlada pelo Paciente , Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Bupivacaína/uso terapêutico , Feminino , Gastrectomia/métodos , Derivação Gástrica/métodos , Humanos , Laparoscopia , Tempo de Internação/estatística & dados numéricos , Lipossomos , Masculino , Pessoa de Meia-Idade , Morfina/uso terapêutico , Medição da Dor , Dor Pós-Operatória/diagnóstico , Estudos Retrospectivos
12.
Ophthalmic Plast Reconstr Surg ; 34(3): 213-216, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28472009

RESUMO

PURPOSE: The authors describe a cadaver feasibility study investigating a minimally invasive technique for corneal neurotization with the supraorbital nerve harvested endoscopically. METHODS: A cadaver study was performed to investigate the technical feasibility of corneal neurotization via endoscopic supraorbital nerve transfer to the corneoscleral limbus. RESULTS: Endoscopic corneal neurotization was successfully performed on each cadaveric hemiface. CONCLUSION: The use of an endoscope allows for a minimally invasive approach to corneal neurotization with the supraorbital nerve.


Assuntos
Nervos Cranianos/transplante , Endoscopia/métodos , Transferência de Nervo/métodos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Cadáver , Estudos de Viabilidade , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
14.
J Nat Prod ; 79(8): 1929-37, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27419263

RESUMO

Four bicyclic and three pentacyclic guanidine alkaloids (1-7) were isolated from a French Polynesian Monanchora n. sp. sponge, along with the known alkaloids monalidine A (8), enantiomers 9-11 of known natural product crambescins, and the known crambescidins 12-15. Structures were assigned by spectroscopic data interpretation. The relative and absolute configurations of the alkaloids were established by analysis of (1)H NMR and NOESY spectra and by circular dichroism analysis. The new norcrambescidic acid (7) corresponds to interesting biosynthetic variation within the pentacyclic core. All compounds exhibited antiproliferative and cytotoxic efficacy against KB, HCT116, HL60, MRC5, and B16F10 cancer cells, with IC50 values ranging from 4 nM to 10 µM.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Axinella/química , Guanidinas/isolamento & purificação , Guanidinas/farmacologia , Alcaloides/química , Animais , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Guanidinas/química , Células HCT116 , Células HL-60 , Humanos , Concentração Inibidora 50 , Células KB , Biologia Marinha , Ressonância Magnética Nuclear Biomolecular , Polinésia
15.
Anesth Analg ; 122(2): 393-401, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26569427

RESUMO

BACKGROUND: Nonintubated patients receiving sevoflurane have slower protective airway reflex recovery after anesthesia compared with patients receiving desflurane. We asked whether this difference would remain significant among intubated patients receiving rocuronium or whether the impact of variable neuromuscular recovery would predominate and thus minimize differences between anesthetics. METHODS: After obtaining written informed consent, patients were randomly assigned to receive sevoflurane (n = 41) or desflurane (n = 40), with neuromuscular monitoring by quantitative train-of-four (TOF) method using accelerometry. Intubation was facilitated by administration of 1 mg/kg rocuronium. Neuromuscular block was produced, with the goal of maintaining 10% to 15% of baseline function. After surgery, neostigmine 70 µg/kg + glycopyrrolate 14 µg/kg was administered. When TOF ratio reached ≥ 0.7, anesthetic was discontinued and fresh gas flow was raised to 15 L/m. The time of first response to command was noted, after which patients were given a 20-mL water swallowing test at 2, 6, 14, 22, 30, and 60 minutes. The following average time intervals were compared between the 2 intervention groups: anesthetic discontinuation to first response to command (T1); first response to command to first successful passing of swallow test (T2); and anesthetic discontinuation to first successful passing of swallow test (T3). We also compared the rates of successful swallow tests at 2 minutes after first response to command in the 2 groups, first categorizing as failures all those who were unable to take the test at 2 minutes, and then excluding 10 patients unable to take the test at this time for reasons other than somnolence (n = 10). RESULTS: Patients receiving desflurane passed the swallowing test at shorter time intervals after first response to command than did patients receiving sevoflurane (Wilcoxon-Mann-Whitney odds = 1.60; 95% confidence interval [CI], 1.01-2.69; P = 0.054). Two minutes after the first response to command, among all 81 patients, the chance of passing the swallowing test was higher after desflurane compared with sevoflurane anesthesia (relative risk = 1.6; 95% CI, 1.0-2.5; P = 0.04). Of the 71 patients (as above), we observed a significantly higher chance of passing at 2 minutes after first response to command (relative risk = 1.8; 95% CI, 1.2-2.7; P = 0.006) in patients receiving desflurane (25/33) compared with those receiving sevoflurane (16/38). In 18 of 81 and 16 of 71 patients, the neuromuscular monitoring and reversal protocols were not followed (neostigmine underdosed, extubation at TOF <0.7, or reliance on tactile as opposed to quantitative TOF measurement). In both the total cohort and the subset of 71, neuromuscular protocol adherence increased the chance of passing the swallow test, independent of anesthetic assignment in multivariable logistic regression (P = 0.02 and P = 0.006, respectively), demonstrating significant effect on airway reflex recovery independent of chosen anesthetic. CONCLUSIONS: Compared with sevoflurane, desflurane allowed faster recovery of airway reflexes after anesthesia in intubated patients. Clinical management of neuromuscular block, including full reversal and the use of quantitative TOF, affects airway reflex recovery-an effect that may be at least as profound as the choice of potent inhaled anesthetic.


Assuntos
Anestesia por Inalação , Anestésicos Inalatórios , Isoflurano/análogos & derivados , Éteres Metílicos , Bloqueio Neuromuscular/métodos , Reflexo/efeitos dos fármacos , Acelerometria , Adolescente , Adulto , Idoso , Procedimentos Cirúrgicos Ambulatórios , Androstanóis , Período de Recuperação da Anestesia , Deglutição/efeitos dos fármacos , Desflurano , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Fármacos Neuromusculares não Despolarizantes , Rocurônio , Sevoflurano , Adulto Jovem
16.
Proc Natl Acad Sci U S A ; 110(51): 20645-50, 2013 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-24297902

RESUMO

Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome.


Assuntos
Adaptação Fisiológica/fisiologia , Boidae , Evolução Molecular , Regulação da Expressão Gênica/fisiologia , Genoma/fisiologia , Transcrição Gênica/fisiologia , Animais , Boidae/genética , Boidae/metabolismo , Ciclo Celular/fisiologia , Humanos , Especificidade de Órgãos/fisiologia
17.
Arterioscler Thromb Vasc Biol ; 34(9): 2160-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25035343

RESUMO

OBJECTIVE: Catechol-O-methyltransferase (COMT), a key enzyme in catecholamine metabolism, is implicated in cardiovascular, sympathetic, and endocrine pathways. This study aimed to confirm preliminary association of COMT genetic variation with incident cardiovascular disease (CVD). It further aimed to evaluate whether aspirin, a commonly used CVD prevention agent, modified the potential association of COMT with incident CVD. APPROACH AND RESULTS: We examined COMT polymorphism rs4680 (MAF [minor allele frequency], 0.47), encoding a nonsynonymous methionine-to-valine substitution, in the Women's Genome Health Study (WGHS), a large population-based cohort of women with randomized allocation to aspirin or vitamin E when compared with placebo and 10-year follow-up. Rs4680 effects were confirmed with COMT polymorphism rs4818 and also examined in Coronary ARtery DIsease Genome-wide Replication and Meta-analysis/The Coronary Artery Disease Genetics Consortium, consortia for genome-wide association studies of coronary artery disease. Among WGHS women allocated to placebo (135 events/n=5811), the rs4680 valine allele was protective against incident CVD relative to the methionine (hazard ratio [HR; 95% confidence interval {CI}], 0.66 [0.51-0.84]; P=0.0007); an association also observed in Coronary ARtery DIsease Genome-wide Replication and Meta-analysis and The Coronary Artery Disease Genetics Consortium (combined P=2.4×10(-5)). In the WGHS, the rs4680 association was abolished by randomized allocation to aspirin, such that valine/valine women experienced higher CVD rates with aspirin allocation when compared with placebo (HR [95% CI], 1.85 [1.05-3.25]; P=0.033), whereas methionine/methionine women experienced lower rates (HR [95% CI], 0.60 [0.39-0.93]; P=0.023). Allocation to vitamin E also conferred higher but nonsignificant CVD rates on valine/valine (HR [95% CI], 1.50 [0.83-2.70]; P=0.180) when compared with significantly lower rates on methionine/methionine (HR [95% CI], 0.53 [0.34-0.84]; P=0.006) women. Rs4818 results were similar. CONCLUSIONS: Common COMT polymorphisms were associated with incident CVD, and this association was modified by randomized allocation to aspirin or vitamin E. Replication of these findings is required.


Assuntos
Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Catecol O-Metiltransferase/genética , Polimorfismo de Nucleotídeo Único , Substituição de Aminoácidos , Aspirina/farmacologia , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Feminino , Seguimentos , Estudo de Associação Genômica Ampla , Humanos , Incidência , Metanálise como Assunto , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Vitamina E/farmacologia , Vitamina E/uso terapêutico
18.
Syst Parasitol ; 92(1): 1-11, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26249517

RESUMO

Species of the faustulid genus Antorchis Linton, 1911 of the tropical Indo-West Pacific are reviewed. We recognise five species in the region, including a novel form. Antorchis nasonis n. sp. is described from Naso annulatus (Quoy & Gaimard) and N. tonganus (Valenciennes) on the southern Great Barrier Reef (GBR). We interpret specimens reported from Naso hexacanthus (Bleeker) from Japan as the same species. This species appears to be the only faustulid known from acanthurid fishes and differs from all other species in the genus in having the prominent dorsal genital invagination close to the posterior end of the body. In addition, new host and locality records are reported for two described species of Antorchis, A. pomacanthi (Hafeezullah & Siddiqi, 1970) and A. tsushimaensis (Machida, 1971). The wide distribution of A. pomacanthi was further demonstrated by the generation of identical ITS2 rDNA sequences for specimens from Ningaloo Reef off Western Australia, off Lizard and Heron Islands (GBR) and off New Caledonia, localities separated by up to 5,300 km. The host-specificity of the genus is considered.


Assuntos
Trematódeos/classificação , Animais , DNA Espaçador Ribossômico/genética , Peixes/parasitologia , Especificidade de Hospedeiro , Oceano Índico , Oceano Pacífico , Especificidade da Espécie , Trematódeos/anatomia & histologia , Trematódeos/genética
19.
Zootaxa ; (3814): 451-77, 2014 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-24943442

RESUMO

Extensive surveys of the biodiversity on the seafloor of the inter-reef regions of the Great Barrier Reef, Australia, have resulted in the collection of large numbers of sponges, many of which are likely new to science. Identification of these sponges, however, was made difficult by the absence in some specimens of key diagnostic characters, such as megascleres. We used an integrated approach to the taxonomy of these sponges, incorporating morphological examination by SEM, analysis of DNA sequence data (using the COI barcoding fragment of mtDNA) and preliminary studies of the chemistry of the sponges, to describe the new species, which were found to contain no native spicules other than acanthose microrhabds. Here, we propose two new species of Theonella Gray, 1868: Theonella deliqua n. sp. (found in association with a single unidentified species of siliquariid mollusc) and Theonella maricae n. sp. from the Great Barrier Reef. Further, we propose the new combination of Theonella xantha (Sutcliffe, Hooper and Pitcher 2010) n. comb. for another microrhabd-only-bearing species. On the basis of our gene trees, we recognise Theonella (and Theonellidae Lendenfeld, 1903) within Astrophorida Sollas, 1887. We discuss the potential for chemotaxonomic and DNA-based insights into the origins and radiation of species of Theonella and explore the evolutionary significance of the reduced morphology of the three additional species recognised here.


Assuntos
Poríferos/classificação , Distribuição Animal , Estruturas Animais/anatomia & histologia , Animais , Austrália , Evolução Biológica , DNA Mitocondrial/genética , Ecossistema , Dados de Sequência Molecular , Filogenia , Poríferos/anatomia & histologia , Poríferos/genética
20.
J Virol ; 86(9): 5380-5, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22345476

RESUMO

During human adenovirus type 3 (Ad3) infection, an excess of penton base and fiber proteins are produced which form dodecahedral particles composed of 12 pentamers of penton base and 12 trimers of fiber protein. No biological functions have yet been ascribed to Ad3 dodecahedra. Here, we show that dodecahedra compete with Ad3 virions for binding to the cell surface and trigger cell remodeling, giving new insights into possible biological functions of dodecahedra in the Ad3 infectious cycle.


Assuntos
Adenovírus Humanos/fisiologia , Proteínas do Capsídeo/metabolismo , Interações Hospedeiro-Patógeno , Linhagem Celular , Membrana Celular/metabolismo , Desmogleína 2/metabolismo , Humanos , Ligação Proteica , Ligação Viral
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