RESUMO
OBJECTIVE: This study aimed to characterize changes in firearm injuries at 5 level 1 trauma centers in Northern California in the 12âmonths following the start of the COVID-19 pandemic compared with the preceding 4âyears, accounting for regional variations and seasonal trends. SUMMARY AND BACKGROUND DATA: Increased firearm injuries have been reported during the early peaks of the COVID-19 pandemic despite shelter-in-place restrictions. However, these data are overwhelmingly from singlecenter studies, during the initial phase of the pandemic prior to lifting of shelter-in-place restrictions, or do not account for seasonal trends. METHODS: An interrupted time-series analysis (ITSA) of all firearm injuries presenting to 5 adult level 1 trauma centers in Northern California was performed (January 2016to February 2021). ITSA modeled the association of the onset of the COVID-19 pandemic (March 2020) with monthly firearm injuries using the ordinary least-squares method, included month indicators to adjust for seasonality, and specified lags of up to 12âmonths to account for autocorrelation. RESULTS: Prior to the start of COVID-19, firearm injuries averaged (±SD) of 86 (±16) and were decreasing by 0.5/month (P < 0.01). The start of COVID- 19 (March 2020) was associated with an alarming increase of 39 firearm injuries/month (P < 0.01) followed by an ongoing rise of 3.5/mo (P < 0.01). This resulted in an average of 130 (±26) firearm injuries/month during the COVID-19 period and included 8 of the 10 highest monthly firearm injury rates in the past 5âyears. CONCLUSIONS: These data highlight an alarming escalation in firearm injuries in the 12âmonths following the onset of the COVID-19 pandemic in Northern California. Additional studies and resources are needed to better understand and address this parallel public health crisis.
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COVID-19 , Armas de Fogo , Ferimentos por Arma de Fogo , Adulto , COVID-19/epidemiologia , California/epidemiologia , Humanos , Pandemias , Estudos Retrospectivos , Centros de Traumatologia , Ferimentos por Arma de Fogo/epidemiologiaRESUMO
Replication fork stalling can promote genomic instability, predisposing to cancer and other diseases. Stalled replication forks may be processed by sister chromatid recombination (SCR), generating error-free or error-prone homologous recombination (HR) outcomes. In mammalian cells, a long-standing hypothesis proposes that the major hereditary breast/ovarian cancer predisposition gene products, BRCA1 and BRCA2, control HR/SCR at stalled replication forks. Although BRCA1 and BRCA2 affect replication fork processing, direct evidence that BRCA gene products regulate homologous recombination at stalled chromosomal replication forks is lacking, due to a dearth of tools for studying this process. Here we report that the Escherichia coli Tus/Ter complex can be engineered to induce site-specific replication fork stalling and chromosomal HR/SCR in mouse cells. Tus/Ter-induced homologous recombination entails processing of bidirectionally arrested forks. We find that the Brca1 carboxy (C)-terminal tandem BRCT repeat and regions of Brca1 encoded by exon 11-two Brca1 elements implicated in tumour suppression-control Tus/Ter-induced homologous recombination. Inactivation of either Brca1 or Brca2 increases the absolute frequency of 'long-tract' gene conversions at Tus/Ter-stalled forks, an outcome not observed in response to a site-specific endonuclease-mediated chromosomal double-strand break. Therefore, homologous recombination at stalled forks is regulated differently from homologous recombination at double-strand breaks arising independently of a replication fork. We propose that aberrant long-tract homologous recombination at stalled replication forks contributes to genomic instability and breast/ovarian cancer predisposition in BRCA mutant cells.
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Proteína BRCA1/metabolismo , Replicação do DNA , Proteínas de Escherichia coli/metabolismo , Recombinação Homóloga , Animais , Proteína BRCA1/química , Proteína BRCA1/genética , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Quebras de DNA de Cadeia Dupla , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Éxons/genética , Conversão Gênica/genética , Instabilidade Genômica/genética , Síndrome Hereditária de Câncer de Mama e Ovário/genética , CamundongosRESUMO
Oral health is one of the most unmet health care needs of adolescents. Oral disease can have a profound effect on overall health, including pain, missed school, heart disease, and even death. Adolescents have specific needs pertaining to oral health in addition to the usual lifelong issues of caries management, sports injury prevention, and dental referrals. Teen years are a higher risk time for oral piercings, increased sugar intake, nicotine initiation, and orthodontic considerations. Adolescents need a unique approach to motivate them about their oral health issues. This is particularly important because lifelong health habits are created during these formative years, and prevention opportunities for sealants and varnish are only available at this age.
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Saúde do Adolescente , Promoção da Saúde/métodos , Saúde Bucal , Higiene Bucal/métodos , Educação de Pacientes como Assunto/métodos , Adolescente , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/terapia , Piercing Corporal/efeitos adversos , Cárie Dentária/prevenção & controle , Humanos , Boca/lesões , Ortodontia , Periodontite/prevenção & controle , Encaminhamento e Consulta , Uso de Tabaco/efeitos adversos , Uso de Tabaco/prevenção & controleRESUMO
Herein, we describe the synthesis of Pyk2 inhibitors via macrocyclization of FAK and dual Pyk2-FAK inhibitors. We identified macrocycle 25a as a highly potent Pyk2 inhibitor (IC50=0.7nM), with â¼175-fold improvement in Pyk2 potency as compared to its acyclic counterpart. In many cases, macrocyclization improved Pyk2 potency while weakening FAK potency, thereby improving the Pyk2/FAK selectivity ratio for this structural class of inhibitors. Various macrocyclic linkers were studied in an attempt to optimize Pyk2 selectivity. We observed macrocyclic atropisomerism during the synthesis of 19-membered macrocycles 10a-d, and successfully obtained crystallographic evidence of one atropisomer (10a-AtropB) preferentially bound to Pyk2.
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Quinase 2 de Adesão Focal/antagonistas & inibidores , Proteínas Tirosina Quinases/farmacologia , Animais , Ciclização , Cães , Relação Dose-Resposta a Droga , Quinase 2 de Adesão Focal/metabolismo , Humanos , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Camundongos , Modelos Moleculares , Estrutura Molecular , Proteínas Tirosina Quinases/síntese química , Proteínas Tirosina Quinases/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Erysipelothrix rhusiopathiae is the causative agent of animal erysipelas and, to a fewer occurrences, human erysipeloid. It is ubiquitous in nature and commensal in diverse species of animals, wild or domestic, from mammals and birds to reptiles and fish. Mechanisms of its virulence and pathogenicity are poorly understood. RESULTS: Making use of the complete genome sequencing of E. rhusiopathiae strain SY1027 and comparative genome analysis between the three highly pathogenic strains (SY1027, Fujisawa and ATCC19414), the genomic structure and putative functional elements, such as pathogenicity island (PAI)-like regions, potential virulence factors and horizontal transferring genes of the bacteria are identified. Strain SY1027 genome is 1,752,910 base pairs long, just 30 kilobases smaller than strain Fujisawa, with the same GC level of 36.36%. It contains 1,845 open reading frames (ORF) predicted by GLIMMER 3.02, of which 1,775 were annotated by PGAAP, 1,757 (~95.23%) were annotated by NCBI nr blast, 1,209 by COG database and 1,076 by KEGG database. 37 potential virulence factors were annotated in strain SY1027 by VFDB, while 19 (~51.35%) of them are common in the 2 strains, 7 of which are potentially related to antibiotic resistance and highly conserved (~98-100% match identity (ID)) amongst the three strains of E. rhusiopathiae and modestly homologous to other gastrointestinal tract-inhabiting Firmicutes (~40% match ID), e.g. Clostridium spp., Enterococcus spp. Genomic island- and pathogenicity island-like regions were also predicted, in which some showed association with tRNA and potential virulence factors. CONCLUSION: Complete genome sequencing of Erysipelothrix rhusiopathiae, the causative agent of animal erysipelas, was performed. Molecular identification of various genomic elements pave the way to the better understanding of mechanisms underlying metabolic capabilities, pathogenicity of swine erysipelas and prospective vaccine targets besides the widely used SpaA antigens.
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DNA Bacteriano/química , DNA Bacteriano/genética , Erysipelothrix/genética , Genoma Bacteriano , Análise de Sequência de DNA , Erisipela Suína/microbiologia , Animais , Erysipelothrix/isolamento & purificação , Anotação de Sequência Molecular , Dados de Sequência Molecular , Fases de Leitura Aberta , Suínos , Fatores de Virulência/genéticaRESUMO
Emus (Dromaius novaehollandiae) are farmed for their oil for pharmaceutical and cosmetic uses. This emu pituitary expressed sequence tag study was undertaken to identify novel transcripts in the emu pituitary to propel their identification and functional studies. By mapping reads derived from the Roche 454 GS Junior pyrosequencer to 8 reference species (human, mouse, chicken, zebra finch, fruit fly, turkey, round worm, and Carolina anole lizard) from the UniGene database, a total of 81,788 reads (53,312 mapped reads) were obtained and assembled with Reference Sequence (RefSeq). We annotated 6,676 potential emu genes by referencing 7 species (excluding lizard) and identified 1,232 potential genes common among 3 species (human, mouse, and chicken) with complete available reference genomes. Gene Ontology analysis revealed 376 Gene Ontology terms showing, with the highest counts, their involvements in biological processes, metabolism, and cellular components. These potential genes were detected to associate with 20 pathways including mitogen-activated protein kinase, insulin, neurotrophin signaling pathways, and carbohydrate digestion and absorption pathway. We also revealed a panel of tissue-specific genes including regulator of G-protein signaling protein (RGS), glucagon-like peptide receptor (GLPR), and growth hormone-inducible transmembrane protein (GHITM). Additionally, fatty acid binding protein (FABP), fatty acid desaturase (FAS), and stearoyl-coenzyme A desaturase (SCD), key enzyme genes in fat metabolism, were found to be also expressed in emu pituitary. This expressed sequence tag study represents the first step in functional characterization of emu pituitary gene expression and SNP identification for the improvement of fat production in the emu.
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Dromaiidae/genética , Dromaiidae/metabolismo , Etiquetas de Sequências Expressas , Técnicas de Amplificação de Ácido Nucleico/veterinária , Hipófise/metabolismo , Animais , Sequência de Bases , DNA/genética , Feminino , Perfilação da Expressão Gênica/veterinária , MasculinoRESUMO
BACKGROUND: Video feedback is a technique used in cognitive therapy for social anxiety disorder (CT-SAD) to update patients' negative self-perceptions of how they appear to others. Clients are supported to watch video of themselves engaging in social interactions. While typically undertaken in session with a therapist, this study aimed to investigate the effectiveness of remotely delivered video feedback embedded within an Internet-based cognitive therapy program (iCT-SAD). METHODS: We examined patients' self-perceptions and social anxiety symptoms before and after video feedback in two randomised controlled trials. Study 1 compared 49 iCT-SAD participants with 47 from face-to-face CT-SAD. Study 2 was a replication using data from 38 iCT-SAD participants from Hong Kong. RESULTS: In Study 1, ratings of self-perceptions and social anxiety showed significant reductions following video feedback, in both treatment formats. 92 % of participants in iCT-SAD, and 96 % in CT-SAD thought they looked less anxious compared to their predictions after viewing the videos. The change in self-perception ratings was larger in CT-SAD compared to iCT-SAD, but there was no evidence that the impact of video feedback on social anxiety symptoms around a week later differed between the two treatments. Study 2 replicated the iCT-SAD findings of Study 1. LIMITATIONS: The level of therapist support in iCT-SAD videofeedback varied with clinical need and was not measured. CONCLUSIONS: The findings indicate that video feedback can be delivered effectively online, and that its impact on social anxiety is not significantly different from in-person treatment delivery.
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Terapia Cognitivo-Comportamental , Fobia Social , Humanos , Fobia Social/terapia , Retroalimentação , Internet , Terapia Cognitivo-Comportamental/métodos , Autoimagem , Resultado do TratamentoRESUMO
Prostaglandins E (PGE) and F (PGF) mediate diverse physiological functions via their cell surface receptors - prostaglandin E receptor (EP) subtypes 1, 2, 3 and 4 (EP(1); EP(2); EP(3); EP(4)) and F receptor (FP). In teleost fishes, PGE was implicated in gill epithelium ion transport, while both PGE and PGF were involved in oocyte maturation, follicular rupture and coordination of reproductive behaviors. However, little is known about the mechanisms behind their actions. In present study, we first identified the full-length ORF cDNA clones of three zebrafish prostaglandin E receptor subtype 1 (zEP(1)) isoforms - zEP(1a), zEP(1b) and zEP(1c) - and FP (zFP) from adult ovary. RT-PCR showed that zEP(1a), zEP(1b) and zFP are widely expressed in adult tissues, while zEP(1c) mRNA expression is mainly confined in brain and kidney. Using a pGL3-NFAT-RE luciferase reporter system, both zEP(1a) and zEP(1b) expressed in DF-1 cells were shown to be activated by PGE(2) potently while zEP(1c) and zFP were activated by PGF(2a) effectively, suggesting that the four receptors are functionally coupled to intracellular Ca(2+)-signaling pathway. Furthermore, EP1a and EP1b, but not EP1c were suggested to couple to cAMP-PKA signaling pathway using a pGL3-CRE luciferase reporter assay. Although zEP(1c) might originate as a paralog to zEP(1a) and zEP(1b), its functional coupling to PGF(2α) instead of PGE(2) suggested that zEP(1) isoforms might have sub-functionalized in their ligand binding and G protein coupling specificity, in addition to differential tissue distribution. Characterization of these receptors undoubtedly furthered our understanding on the diverse yet highly target-specific responses of prostaglandins in teleosts.
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Receptores de Prostaglandina E Subtipo EP1/metabolismo , Receptores de Prostaglandina/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Feminino , Masculino , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Prostaglandina/genética , Receptores de Prostaglandina E Subtipo EP1/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Peixe-Zebra , Proteínas de Peixe-Zebra/genéticaRESUMO
Prostaglandin E and F regulate diverse physiological functions including gastrointestinal motility, fever induction and reproduction. This multitude of biological effects is mediated via their four E receptor subtypes (EP(1), EP(2), EP(3) and EP(4)) and F receptor (FP), respectively. Majority of these studies was performed in mammalian species, while investigations on their roles were impeded by inadequate information on their receptors in avian species. In present study, full-length cDNAs of chicken EP(3) (cEP(3)) and two isoforms of FP - cFPa and cFPb - were cloned from adult hen ovary. The putative cEP(3) and cFPa share high amino acid sequence identity with their respective orthologs, while the predicted cFPb is a novel middle-truncated splice variant which lacks 107 amino acids between transmembrane domains 4 and 6. RT-PCR showed that cEP(3), cFPa and cFPb are widely expressed in adult tissues examined, including ovary and oviduct. Using a pGL3-CRE luciferase reporter system, cEP(3)-expressing DF1 cells inhibited forskolin-induced luciferase activity (EC(50): <1.9 pM) upon PGE(2) treatment, suggesting that cEP(3) may functionally couple to Gi protein. Upon PGF(2α) addition, cFPa was shown to potentially couple to intracellular Ca(2+)-signaling pathway by pGL3-NFAT-RE reporter assay (EC(50): 2.9 nM), while cFPb showed no response. Using a pGL4-SRE reporter system, both cEP(3) and cFPa exhibited potential MAPK activation by PGE(2) and PGF(2α) at EC(50) 0.34 and 13 nM, respectively. Molecular characterization of these receptors paved the road to the better understanding of PGE(2) and PGF(2α) roles in avian physiology and comparative endocrinology studies.
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Galinhas/metabolismo , Receptores de Prostaglandina E Subtipo EP3/metabolismo , Receptores de Prostaglandina/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Galinhas/genética , Clonagem Molecular , Sequência Conservada , Dados de Sequência Molecular , Filogenia , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Receptores de Prostaglandina/química , Receptores de Prostaglandina/genética , Receptores de Prostaglandina E Subtipo EP3/química , Receptores de Prostaglandina E Subtipo EP3/genética , Alinhamento de SequênciaRESUMO
Background: Research is needed to determine the extent to which internet-delivered psychological therapies are effective when delivered in countries and cultures outside of where they were developed. Objective: This waitlist-controlled study evaluated the efficacy of a UK-developed, therapist-guided internet Cognitive Therapy programme for Social Anxiety Disorder (iCT-SAD) when delivered in Hong Kong by local therapists. Methods: Patients were randomized to iCT-SAD (n = 22) or a waitlist control group (n = 22). Assessments took place at weeks 0, 8, and 15 (posttreatment/postwait), with a further 3-month follow-up assessment for the iCT-SAD group. The primary outcome measure was the Liebowitz Social Anxiety Scale (self-report), and posttreatment/postwait diagnostic assessments were completed by independent assessors blind to condition. Trial Registration: ISRCTN11357117. Results: Compared with the waitlist group, iCT-SAD significantly reduced social anxiety symptoms (adjusted difference at posttreatment 55.36, 95%CI 44.32 to 66.39, p < 0.001; d Cohen 2.41). The treatment was also superior to waitlist on all secondary outcome measures. 86% of the iCT-SAD group demonstrated remission from SAD based on the LSAS, compared to 5% of the waitlist group. 73% no longer met diagnostic criteria at posttreatment, compared to 9% of the waitlist group. The gains made by the iCT-SAD group were maintained at three-month follow-up. Conclusions: iCT-SAD showed strong efficacy for the treatment of SAD in Hong Kong. As the clinical outcomes were similar to UK studies, this suggests the dissemination of the treatment into a different cultural setting did not result in a substantial loss of efficacy.
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Galanin is a multi-functional neuropeptide that is widely distributed in the mammalian central nervous system and peripheral tissues. It exerts multiple physiological functions through interaction with 3 known G protein-coupled receptors (GPCR), namely, galanin type I, II and III (GalR1, 2 and 3) receptors, which have only been identified in mammals. In this study, we reported the cloning and characterization of chicken galanin type I receptor (GalR1) and a novel galanin receptor with considerable homology to chicken GalR1, which herein is designated as galanin type I-like receptor (GalR1-L). Chicken GalR1 and GalR1-L full-length cDNAs were cloned from chicken brain and small intestine tissue, respectively. The former encodes a protein of 357 amino acids that shares 84-86% amino acid sequence identities with its mammalian counterparts, whereas the latter encodes a 363-amino acid protein with comparatively lower identities (55-56%) to the mammalian GalR1. Using reverse transcription (RT)-PCR assays, we examined the expression of both receptors in adult chicken tissues. Both receptors were found to be widely distributed in the tissues examined, including brain, small intestine, kidney, ovary, pancreas, pituitary and spleen. Interestingly, cGalR1 expression was detected in different regions of chicken oviduct, while cGalR1-L expression was restricted to the vagina. Using a pGL3-CRE luciferase reporter system, chicken galanin peptide (1-29) was demonstrated to inhibit both basal and forskolin-stimulated luciferase activities, in dose-dependent manners, through the cAMP-mediated signaling pathway in Chinese hamster ovary (CHO) cells expressing either cGalR1 or cGalR1-L, thus suggesting the functional couplings of both receptors to G(i) proteins. Together, the characterization of chicken GalR1 and GalR1-L provides a better understanding of the physiological roles of galanin in avian species.
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Proteínas Aviárias/genética , Galinhas/genética , Receptores de Galanina/genética , Sequência de Aminoácidos , Animais , Proteínas Aviárias/química , Proteínas Aviárias/metabolismo , Sequência de Bases , Células CHO , Galinhas/metabolismo , Clonagem Molecular , Cricetinae , Cricetulus , DNA Complementar/química , Dados de Sequência Molecular , RNA Mensageiro , Receptores de Galanina/química , Receptores de Galanina/metabolismo , Alinhamento de Sequência , Análise de Sequência de Proteína , Transdução de SinaisRESUMO
BACKGROUND: Mortality in hypotensive patients requiring laparotomy is reported to be 46% and essentially unchanged in 20 years. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been incorporated into resuscitation protocols in an attempt to decrease mortality, but REBOA can have significant complications and its use in this patient group has not been validated. This study sought to determine the mortality rate for hypotensive patients requiring laparotomy and to evaluate the mortality risk related to the degree of hypotension. Additionally, this study sought to determine if there was a presenting systolic blood pressure (SBP) that was associated with a sharp increase in mortality to target the appropriate patient group most likely to benefit from focused interventions such as REBOA. METHODS: The trauma registry at a level I trauma center was reviewed for patients undergoing emergent laparotomy from January 2007 to June 2020. Data included demographics, mechanism of injury, physiological data, Injury Severity Score, blood products transfused, and outcomes. Group comparisons were based on initial SBP (0 to 50 mm Hg, 60 to 69 mm Hg, 70 to 79 mm Hg, 80 to 89 mm Hg, and ≥90 mm Hg). RESULTS: During the study period, 52 016 trauma patients were treated and 1174 required laparotomy within 90 min of arrival; 424 had an initial SBP of <90 mm Hg. The overall mortality rate was 18%, but mortality increased as SBP decreased (≥90=9%, 80 to 89=20%, 70 to 79=21%, 60 to 69=48%, 0 to 59=66%). Mortality increased sharply with SBP of <70 mm Hg. DISCUSSION: Mortality rate increases with worsening hypotension and increases sharply with an SBP of <70 mm Hg. Further study on focused interventions such as REBOA should target this patient group. LEVEL OF EVIDENCE: Therapeutic/care management, level III.
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OBJECTIVES: To prevent the future development of insomnia in at-risk adolescents. METHODS: A randomized controlled trial comparing 4 weekly insomnia prevention program with a nonactive control group. Subjects were assessed at baseline, postintervention, and 6 and 12 months after intervention. Assessors were blinded to the randomization. Analyses were conducted on the basis of the intention-to-treat principles. RESULTS: A total of 242 adolescents with family history of insomnia and subthreshold insomnia symptoms were randomly assigned to an intervention group (n = 121; mean age = 14.7 ± 1.8; female: 51.2%) or control group (n = 121; mean age = 15.0 ± 1.7; female: 62.0%). There was a lower incidence rate of insomnia disorder (both acute and chronic) in the intervention group compared with the control group (5.8% vs 20.7%; P = .002; number needed to treat = 6.7; hazard ratio = 0.29; 95% confidence interval: 0.12-0.66; P = .003) over the 12-month follow-up. The intervention group had decreased insomnia symptoms (P = .03) and reduced vulnerability to stress-related insomnia (P = .03) at postintervention and throughout the 12-month follow-up. Decreased daytime sleepiness (P = .04), better sleep hygiene practices (P = .02), and increased total sleep time (P = .05) were observed at postintervention. The intervention group also reported fewer depressive symptoms at 12-month follow-up (P = .02) compared with the control group. CONCLUSIONS: A brief cognitive behavioral program is effective in preventing the onset of insomnia and improving the vulnerability factors and functioning outcomes.
Assuntos
Terapia Cognitivo-Comportamental/métodos , Distúrbios do Sono por Sonolência Excessiva/prevenção & controle , Distúrbios do Início e da Manutenção do Sono/prevenção & controle , Adolescente , Intervalos de Confiança , Depressão/epidemiologia , Depressão/prevenção & controle , Feminino , Humanos , Incidência , Análise de Intenção de Tratamento , Masculino , Números Necessários para Tratar , Risco , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Fatores de TempoRESUMO
In this study, a full-length cDNA encoding a prolactin-like protein (PRL-L) was cloned from chicken brain tissues using RT-PCR. This putative PRL-L precursor has 225 amino acids in length and shares 30-35% amino acid sequence identity with prolactin (PRL) of chicken, zebrafish, Xenopus, rat and human. Using RT-PCR, the mRNA expression of PRL-L in chicken tissues was further examined. Unlike the predominant expression of PRL in pituitary, PRL-L was found to be widely expressed in adult chicken extra-pituitary tissues with only minimal expression detected in pituitary. In day-7 chicken embryos, the expression of PRL-L, but not PRL, was also detected in all extra-pituitary tissues examined. In line with this finding, the 5'-flanking region of chicken PRL-L (cPRL-L) gene, but not PRL gene, displayed a strong promoter activity in cultured DF-1 cell (a chicken embryo fibroblast cell line), suggesting that the basal expression of PRL-L gene is controlled by a transcriptional regulatory mechanism different from that of PRL gene. As the same findings in chickens, PRL-like protein(s), which share high amino acid sequence (42-86%) identity with chicken PRL-L, was identified in several non-mammalian vertebrate species including zebra finch, tiger puffer, green puffer and zebrafish. RT-PCR assay demonstrated that zebrafish PRL-L, similar to chicken PRL-L, is expressed in extra-pituitary tissues including brain, gill, muscle, ovary and testis. Taken together, these findings strongly suggest that a novel PRL-like protein exists in some non-mammalian vertebrates and may play an important role in target tissues, such as extra-pituitary tissues of chickens and zebrafish.
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Galinhas , Prolactina/genética , Peixe-Zebra , Sequência de Aminoácidos , Animais , Sequência de Bases , Encéfalo/metabolismo , Linhagem Celular , Embrião de Galinha , Mapeamento Cromossômico , Feminino , Tentilhões , Brânquias/metabolismo , Humanos , Masculino , Dados de Sequência Molecular , Músculos/metabolismo , Ovário/metabolismo , Hipófise/metabolismo , Regiões Promotoras Genéticas , Ratos , Alinhamento de Sequência , Testículo/metabolismo , TetraodontiformesRESUMO
BACKGROUND: Rib fractures are common among trauma patients and analgesia remains the cornerstone of treatment. Intercostal nerve blocks provide analgesia but are limited by the duration of the anesthetic. This study compares outcomes of epidural analgesia with intercostal nerve block using liposomal bupivacaine for the treatment of traumatic rib fractures. METHODS: A retrospective chart review was used to identify patients who received either epidural analgesia or intercostal nerve block with liposomal bupivacaine for the treatment of traumatic rib fractures. Patients were matched in a 1:1 ratio on age, Injury Severity Score, and number of rib fractures. Outcomes included intubations, mechanical ventilation days, ICU length of stay (LOS), hospital LOS, and mortality. RESULTS: After matching, 116 patients were included in the study. Patients receiving intercostal nerve blocks with liposomal bupivacaine were less likely to require intubation (3% vs 17%; p = 0.015), had shorter hospital LOS (mean ± SD 8 ± 6 days vs 11 ± 9 days; p = 0.020) and ICU LOS (mean ± SD 2 ± 5 days vs 5 ± 6 days; p = 0.007). There were no differences in ventilator days or mortality. Minor complications occurred in 26% of patients that received an epidural catheter for rib fractures. No complications occurred in the patients receiving intercostal nerve block. CONCLUSIONS: Patients who received intercostal nerve blocks with liposomal bupivacaine required intubation less frequently and had shorter ICU and hospital LOS compared with epidural analgesia patients. These results suggest that intercostal nerve blocks with liposomal bupivacaine might be equal or superior to epidural analgesia.
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Analgesia Epidural/métodos , Bupivacaína/administração & dosagem , Nervos Intercostais/efeitos dos fármacos , Bloqueio Nervoso/métodos , Manejo da Dor/métodos , Fraturas das Costelas/terapia , Adolescente , Adulto , Anestésicos Locais/administração & dosagem , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: A low cortisol level has been shown to occur soon after trauma, and is associated with increased mortality. The purpose of this study was to investigate the impact of low cortisol levels in acute critically ill trauma patients. We hypothesized that patients would require increase vasopressor use, have a greater blood product administration, and increased mortality rate. METHODS: A blinded, prospective observational study was performed at an American College of Surgeons verified Level I trauma center. Adult patients who met trauma activation criteria, received initial treatment at Community Regional Medical Center and were admitted to the intensive care unit were included. Total serum cortisol levels were measured from the initial blood draw in the emergency department. Patients were categorized according to cortisol ≤15 µg/dL (severe low cortisol, SLC), 15.01-25 µg/dL (relative low cortisol, RLC), or >25 µg/dL (normal cortisol, NC) and compared on demographics, injury severity score, initial vital signs, blood product usage, vasopressor requirements, and mortality. RESULTS: Cortisol levels were ordered for 280 patients; 91 were excluded and 189 were included. Penetrating trauma accounted for 19% of injuries and blunt trauma for 81%. 22 patients (12%) had SLC, 83 (44%) had RLC, and 84 (44%) had NC. This study found patients with admission SLC had higher rates of vasopressor requirements, required more units of blood, and had a higher mortality rate than both the RLC and NC groups. CONCLUSION: Low cortisol level can be identified acutely after severe trauma. Trauma patients with SLC had larger blood product requirements, vasopressor use, and increase mortality. Initial cortisol levels are useful in identifying these high-risk patients. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.
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BACKGROUND: Base Deficit (BD) and lactate have been used as indicators of shock and resuscitation. This study was done to evaluate the utility of BD and lactate in identifying shock and resuscitative needs in trauma patients. METHODS: A prospective observational study was performed from 3/2014-12/2018. Data included demographics, admission systolic BP, ISS, BD, lactate, blood transfusion, and outcomes. BD and lactate were modeled continuously and categorically and compared. RESULTS: 2271 patients were included. BD and lactate were moderately correlated (r2 = 0.63 p < 0.001). On univariate regression, BD and lactate were associated with transfusion requirement and mortality (p < 0.001), but on multivariate regression, only BD was associated with transfusion requirement and mortality (OR = 1.2, p < 0.001; OR = 1.1, p < 0.001, respectively). BD discriminated better than lactate for hypotension, higher ISS, increased transfusion requirements and mortality. CONCLUSIONS: Admission BD and lactate levels are correlated following injury, but BD is superior to lactate in identifying shock, resuscitative needs and mortality in severely injured trauma patients.
Assuntos
Desequilíbrio Ácido-Base/sangue , Ácido Láctico/sangue , Ressuscitação , Choque/sangue , Choque/terapia , Ferimentos e Lesões/sangue , Ferimentos e Lesões/terapia , Biomarcadores/sangue , Transfusão de Sangue , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Estudos Prospectivos , Choque/mortalidade , Índices de Gravidade do Trauma , Ferimentos e Lesões/mortalidadeRESUMO
BACKGROUND: The number of trauma patients on prehospital novel oral anticoagulants (NOACs) is increasing. After an initial negative computed tomography of the head (CTH), practice patterns are variable for obtaining repeat CTH to evaluate for delayed intracranial hemorrhage (ICH-d). However, the risks and outcomes of ICH-d for patients on NOACs are unclear. We hypothesized that, for these patients, the incidence of ICH-d is low, similar to that of warfarin, and when it occurs, it does not result in clinically significant worse outcomes. METHODS: Five level 1 trauma centers in Northern California participated in a retrospective review of anticoagulated trauma patients. Patients were included if their initial CTH was negative. Primary outcomes were incidence of ICH-d, neurosurgical intervention, and death. Patient factors associated with the outcome of ICH-d were determined by multivariable regression. RESULTS: From 2016 to 2018, 777 patients met the inclusion criteria (NOAC, n = 346; warfarin, n = 431), 54% of whom received a repeat CTH. Delayed intracranial hemorrhage incidence was 2.3% in the NOAC group and 4% in the warfarin group (p = 0.31). No NOAC patient with ICH-d required neurosurgical intervention or died because of their head injury. Two warfarin patients received neurosurgical intervention, and three died from their head injury. Head Abbreviated Injury Scale ≥3 was associated with increased odds of developing ICH-d (adjusted odds ratio, 32.70; p < 0.01). CONCLUSION: The incidence of ICH-d in patients taking NOAC is low. In this study, patients on NOACs who developed ICH-d after an initial negative CTH did not need neurosurgical intervention or die from their head injury. Repeat CTH in this patient population does not appear necessary. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.Therapeutic, level IV.
Assuntos
Anticoagulantes/uso terapêutico , Traumatismos Craniocerebrais/diagnóstico por imagem , Hemorragias Intracranianas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Administração Oral , Anticoagulantes/efeitos adversos , California/epidemiologia , Traumatismos Craniocerebrais/complicações , Humanos , Incidência , Hemorragias Intracranianas/epidemiologia , Hemorragias Intracranianas/etiologia , Padrões de Prática Médica , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Procedimentos Desnecessários , Varfarina/efeitos adversos , Varfarina/uso terapêuticoRESUMO
BACKGROUND: Research describing the splenic capsule and its effect on non-operative management of splenic injuries is limited. The aim of this study is to identify the current beliefs about the splenic capsule thickness and investigate changes in the splenic capsule with age. METHODS: Trauma Medical Directors were surveyed on their beliefs regarding splenic capsule thickness changes with age. Thicknesses of cadaveric splenic capsule samples were measured. RESULTS: The majority of trauma medical directors (59%) believe the capsule thickness decreases with age. There were 94 splenic specimens obtained. The splenic capsules of infants were thin and had a uniform layer of elastin fibers. With aging, the capsule becomes thick and develops a collagen layer. CONCLUSION: Most trauma directors believe the splenic capsule thickness decreases with age. However, our results demonstrate that the splenic capsule thickness increases during childhood but remains constant in adulthood.
Assuntos
Envelhecimento/patologia , Baço/patologia , Ruptura Esplênica/patologia , Traumatismos Abdominais/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Acute cholecystitis presents in a spectrum of severity, where acute disease may be complicated by severe inflammation, gangrene, and perforation. The goal of this study is to outline an evidence-based grading scale that predicts patient outcomes after laparoscopic cholecystectomy (LC). METHODS: A retrospective review of all patients with a preoperative diagnosis of acute cholecystitis who underwent LC from August 2011 until June 2015 at a tertiary-level hospital was performed. Patients who underwent elective cholecystectomy, incidental cholecystectomy, a planned open cholecystectomy, had gallstone pancreatitis or choledocholithiasis, and those admitted to a non-surgical service were excluded. Severity of disease was obtained from operative and pathology reports, and patients were classified according to the following grading scale:Grade I: symptomatic cholelithiasis.Grade II: acute/chronic cholecystitis.Grade III: gangrenous/necrotizing cholecystitis.Grade IV: gallbladder perforation or abscess.The groups were compared on age, gender, body mass index, severity of gallbladder disease, presence of preoperative systemic inflammatory response syndrome, hospital length of stay, length of operation, complications within 30 days, conversion to open rate, and cost of hospitalization. RESULTS: During the study period, 1252 patients who underwent laparoscopic cholecystectomy were analyzed; 677 met inclusion criteria. The most common grade was grade 2, which was present in 80% of patients, followed by grade 3, which was found in 16% of patients. Grade 4 cholecystitis occurred in 1.2% of patients and grade 1 occurred in 3.2% of patients. There were statistically significant increases in age, presence of preoperative systemic inflammatory response syndrome, hospital length of stay, conversion to open rate, cost of hospitalization, and length of operation with increased cholecystitis grade. CONCLUSIONS: The proposed grading scale is an accurate predictor of duration of operation, conversion to open rate, hospital length of stay, and cost of hospitalization. LEVEL OF EVIDENCE: III. STUDY TYPE: Prognostic.