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1.
J Cardiothorac Surg ; 19(1): 401, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937775

RESUMO

BACKGROUND: The surgical evaluation and management of non-A non-B aortic dissections, in the absence of ascending aortic involvement, remains a grey area. It is in these scenarios when thorough evaluation of patient/family history, clinical presentation, but also overall lifestyle, is of immense importance when determining an optimal intervention. CASE PRESENTATION: We present a 38-year-old patient with a physically demanding lifestyle as a professional wrestler, uncontrolled hypertension due to history of medical non-adherence, and family history of aortic dissection who presented with acute non-A non-B aortic dissection. He was spared a total arch replacement by undergoing a hybrid approach of complete aortic debranching with antegrade Thoracic Endovascular Aortic Repair (TEVAR). The patient was able to benefit from reduced cardiopulmonary bypass (CPB) time, avoidance of aortic cross clamp, circulatory arrest, and hypothermic circulation. CONCLUSIONS: This patient's unique composition of a physically demanding lifestyle, personal history of medical non-adherence, family history of aortic dissection, and clinical presentation required a holistic approach to understanding an ideal intervention that would be best suited long-term. Due to this contextualization, the patient was able to be spared a total arch replacement, or suboptimal medical management, by instead undergoing a hybrid-approach with total aortic arch debranching with antegrade TEVAR.


Assuntos
Aorta Torácica , Aneurisma da Aorta Torácica , Dissecção Aórtica , Procedimentos Endovasculares , Humanos , Adulto , Masculino , Dissecção Aórtica/cirurgia , Procedimentos Endovasculares/métodos , Aneurisma da Aorta Torácica/cirurgia , Aorta Torácica/cirurgia , Implante de Prótese Vascular/métodos , Doença Aguda , Correção Endovascular de Aneurisma
2.
Am Surg ; : 31348241241728, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703074

RESUMO

BACKGROUND: Choledocholithiasis in children is commonly managed with an "endoscopy first" (EF) strategy (endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC) under a separate anesthetic). Endoscopic Retrograde Cholangiopancreatography is limited at the end of the week (EoW). We hypothesize that a "surgery first" (SF) approach with LC, intraoperative cholangiogram (IOC), and possible laparoscopic common bile duct exploration (LCBDE) can decrease length of stay (LOS) and time to definitive intervention (TTDI). METHODS: This is a retrospective single-center cohort study conducted between 2018 and 2023 in pediatric patients with suspected choledocholithiasis. Work week (WW) presentation included admission between Monday and Thursday. Time to definitive intervention was defined as time to LC. RESULTS: 88 pediatric patients were identified, 61 managed with SF (33 WW and 28 EoW) and 27 managed with EF (18 WW and 9 EoW). Both SF groups had shorter mean LOS for WW and EoW presentation (64.5 h, 92.4 h, 112.9 h, and 113.0 h; P < .05). There was a downtreading TTDI in the SF groups (SF: WW 24.7 h and EoW 21.7 h; EF: WW 31.7 h and EoW 35.9 h; P = .11). 44 patients underwent LCBDE with similar success rates (91.6% WW and 85% EoW; P = 1.0). All EF patients received 2 procedures; 69% of SF patients were definitively managed with one. CONCLUSION: Children with choledocholithiasis at the EoW have a longer LOS and TTDI. These findings are amplified when children enter an EF treatment pathway. An SF approach results in shorter LOS with fewer procedures, regardless of the time of presentation.

3.
Front Glob Womens Health ; 5: 1359689, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784944

RESUMO

Introduction: Khat, a green leafy plant grown in East Africa and throughout the Arabian Peninsula, is chewed for its psychoactive and amphetamine-like effects, serving as a significant aspect of culture, economic livelihood, and global trade. Khat consumption during pregnancy has been associated with adverse effects, including anemia, premature rupture of membranes, and low birth weight, among others. Methods: This cross-sectional, explanatory sequential mixed methods study was conducted in the Haramaya District of eastern Ethiopia using a questionnaire and focus group discussions. Questionnaires assessed socio-demographic information, pregnancy history, and diet, including khat use. Data were analyzed using SPSS v28 to include descriptive statistics, proportions, odds ratios, binary logistic regression, and chi-square analysis. FGDs expanded on the knowledge, attitudes, and practices of khat in the region, including pregnant or lactating women from two different kebeles. Two independent reviewers conducted a qualitative content analysis to examine the qualitative findings from the FGDs. Transcripts from the focus groups were entered into NVivo 14 to aid in capturing salient themes. Results: A total of 444 pregnant women with a median age of 25 years completed the questionnaire. Two-thirds of the women, 66.9%, reported currently consuming khat while pregnant, and 72.7% of them reported daily consumption. The FGD analysis resulted in the discovery of five themes: Economic Livelihood, Maternal Significance, Medicinal Implications of Khat, Pesticide Use, and Social and Cultural Applications. Discussion: This study revealed an alarming high prevalence of khat consumption among pregnant women in the Haramaya District, highlighting the pressing need for long-term studies to assess the health consequences. The role of khat as both an economic staple and an energy source for daily activities underscores the challenges in curbing its use. The documented health risks associated with the chemicals used in khat cultivation, including cancer, call for interventions to enhance safe agricultural practices in households involved in khat farming.

4.
Support Care Cancer ; 32(5): 298, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639810

RESUMO

PURPOSE: Colorectal cancer (CRC) incidence and mortality are increasing among young adults (YAs) aged 18-39. This study compared quality of life (QOL) between YA and older adult CRC survivors in the ColoCare Study. METHODS: Participants were grouped by age (years) as follows: 18-39 (YA), 40-49, 50-64, and 65 + . Functional QOL (physical, social, role, emotional, cognitive) and global QOL were assessed with the EORTC-QLQ-C30 at enrollment, 3, 6, and 12 months. Average scores were compared between groups over time using longitudinal mixed-effect modeling. Proportions with clinically meaningful QOL impairment were calculated using age-relevant thresholds and compared between groups over time using logistic regression with mixed effects. RESULTS: Participants (N = 1590) were n = 81 YAs, n = 196 aged 40-49, n = 627 aged 50-64, and n = 686 aged 65 + . Average physical function was better among YAs than participants aged 50-64 (p = 0.010) and 65 + (p < 0.001), and average social function was worse among YAs than aged 65 + (p = 0.046). Relative to YAs, all age groups were less likely to report clinically meaningful social dysfunction (aged 40-49 OR = 0.13, 95%CI = 0.06-0.29; aged 50-64 OR = 0.10, 95%CI = 0.05-0.21; aged 65 + OR = 0.07, 95%CI = 0.04-0.15) and role dysfunction (aged 40-49 OR = 0.36, 95%CI = 0.18-0.75; aged 50-64 OR = 0.41, 95%CI = 0.22-0.78; aged 65 + OR = 0.32, 95%CI = 0.17-0.61). Participants aged 40-49 were also less likely to report physical dysfunction (OR = 0.42, 95%CI = 0.19-0.93). CONCLUSION: YA CRC survivors reported better physical and worse social function compared to older CRC survivors, and YA CRC survivors were more likely to report clinically meaningful social, role, and physical disfunction. Future work should further investigate QOL using age-relevant benchmarks to inform best practices for CRC survivorship care. TRIAL REGISTRATION: NCT02328677, registered December 2014.


Assuntos
Sobreviventes de Câncer , Neoplasias Colorretais , Idoso , Humanos , Adulto Jovem , Sobreviventes de Câncer/psicologia , Neoplasias Colorretais/terapia , Neoplasias Colorretais/psicologia , Emoções , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Adolescente , Adulto , Pessoa de Meia-Idade
5.
Am Surg ; : 31348241248698, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653577

RESUMO

INTRODUCTION: Unintentional injury is the leading cause of death among children. Much can be gleaned from the adult literature in understanding the characteristics that lead to recidivism in efforts to establish interventions for prevention. Our study aims to evaluate the rates, demographics, and features of pediatric trauma recidivism. METHODS: This was a retrospective single-institution review at a level-1 pediatric trauma center of children and young adults (ages 0-28) with traumatic injuries from January 2008 to April 2023. Patients with 1 or more prior visits to our institution's trauma center (recidivists) were identified and compared with those with single admissions. Chi-square tests were used to statistically analyze the two groups. RESULTS: Pediatric/young adult trauma recidivists were 4.4% of the total trauma population captured (n = 14,613). Of the total trauma group, 55% were under 18 years old. Recidivists had higher percentages of patients who were male (82% vs 69%, P < .01), African American (36% vs 24%, P < .01), involved in penetrating trauma (33% vs 17%, P < .01), self-pay/uninsured (17% vs 12%, P < .01), and have abuse reported (5% vs 4%, P = .04). The primary county for recidivism patients was Forsyth with most patients from a specific zip code in an urban area of the county. The average time between visits for recidivists was 1,066 days. CONCLUSIONS: Pediatric/young adult trauma recidivism is associated with specific characteristics including male, African American race, penetrating trauma, and uninsured status. Recidivists are primarily presenting from a zip code with low socioeconomic status. It is critical to develop targeted interventions to help this population in trauma prevention.

6.
Biomolecules ; 14(4)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38672472

RESUMO

Adversity during infancy can affect neurobehavioral development and perturb the maturation of physiological systems. Dysregulated immune and inflammatory responses contribute to many of the later effects on health. Whether normalization can occur following a transition to more nurturing, benevolent conditions is unclear. To assess the potential for recovery, blood samples were obtained from 45 adolescents adopted by supportive families after impoverished infancies in institutional settings (post-institutionalized, PI). Their immune profiles were compared to 39 age-matched controls raised by their biological parents (non-adopted, NA). Leukocytes were immunophenotyped, and this analysis focuses on natural killer (NK) cell populations in circulation. Cytomegalovirus (CMV) seropositivity was evaluated to determine if early infection contributed to the impact of an atypical rearing. Associations with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), two cytokines released by activated NK cells, were examined. Compared to the NA controls, PI adolescents had a lower percent of CD56bright NK cells in circulation, higher TNF-α levels, and were more likely to be infected with CMV. PI adolescents who were latent carriers of CMV expressed NKG2C and CD57 surface markers on more NK cells, including CD56dim lineages. The NK cell repertoire revealed lingering immune effects of early rearing while still maintaining an overall integrity and resilience.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Células Matadoras Naturais , Fator de Necrose Tumoral alfa , Células Matadoras Naturais/imunologia , Humanos , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Adolescente , Feminino , Masculino , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Citomegalovirus/imunologia , Interferon gama/metabolismo , Interferon gama/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Antígeno CD56/metabolismo , Antígenos CD57/metabolismo
7.
BMC Health Serv Res ; 24(1): 253, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38414045

RESUMO

BACKGROUND: Germline cancer genetic testing has become a standard evidence-based practice, with established risk reduction and screening guidelines for genetic carriers. Access to genetic services is limited in many places, which leaves many genetic carriers unidentified and at risk for late diagnosis of cancers and poor outcomes. This poses a problem for childhood cancer survivors, as this is a population with an increased risk for subsequent malignant neoplasms (SMN) due to cancer therapy or inherited cancer predisposition. The ENGaging and Activating cancer survivors in Genetic services (ENGAGE) study evaluates the effectiveness of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic testing in childhood cancer survivors compared to usual care options for genetic testing. METHODS: The ENGAGE study is a 3-arm randomized hybrid type 1 effectiveness and implementation study within the Childhood Cancer Survivor Study population which tests a clinical intervention while gathering information on its delivery during the effectiveness trial and its potential for future implementation among 360 participants. Participants are randomized into three arms. Those randomized to Arm A receive genetic services via videoconferencing, those in Arm B receive these services by phone, and those randomized to Arm C will receive usual care services. DISCUSSION: With many barriers to accessing genetic services, innovative delivery models are needed to address this gap and increase uptake of genetic services. The ENGAGE study evaluates the effectiveness of an adapted model of remote delivery of genetic services to increase the uptake of recommended genetic testing in childhood cancer survivors. This study assesses the uptake in remote genetic services and identify barriers to uptake to inform future recommendations and a theoretically-informed process evaluation which can inform modifications to enhance dissemination beyond this study population and to realize the benefits of precision medicine. TRIAL REGISTRATION: This protocol was registered at clinicaltrials.gov (NCT04455698) on July 2, 2020.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Criança , Neoplasias/genética , Testes Genéticos
11.
J Biol Chem ; 299(6): 104773, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37142225

RESUMO

The bacterial RadD enzyme is important for multiple genome maintenance pathways, including RecA DNA strand exchange and RecA-independent suppression of DNA crossover template switching. However, much remains unknown about the precise roles of RadD. One potential clue into RadD mechanisms is its direct interaction with the single-stranded DNA binding protein (SSB), which coats single-stranded DNA exposed during genome maintenance reactions in cells. Interaction with SSB stimulates the ATPase activity of RadD. To probe the mechanism and importance of RadD-SSB complex formation, we identified a pocket on RadD that is essential for binding SSB. In a mechanism shared with many other SSB-interacting proteins, RadD uses a hydrophobic pocket framed by basic residues to bind the C-terminal end of SSB. We found that RadD variants that substitute acidic residues for basic residues in the SSB binding site impair RadD:SSB complex formation and eliminate SSB stimulation of RadD ATPase activity in vitro. Additionally, mutant Escherichia coli strains carrying charge reversal radD changes display increased sensitivity to DNA damaging agents synergistically with deletions of radA and recG, although the phenotypes of the SSB-binding radD mutants are not as severe as a full radD deletion. This suggests that cellular RadD requires an intact interaction with SSB for full RadD function.


Assuntos
Proteínas de Ligação a DNA , Escherichia coli , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Reparo do DNA/genética , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , Proteínas de Ligação a DNA/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Ligação Proteica , Mutação , Sítios de Ligação , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Modelos Moleculares , Estrutura Quaternária de Proteína
12.
BMC Cancer ; 23(1): 300, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013476

RESUMO

BACKGROUND: Physical activity and BMI have been individually associated with cancer survivorship but have not yet been studied in combinations in colorectal cancer patients. Here, we investigate individual and combined associations of physical activity and BMI groups with colorectal cancer survival outcomes. METHODS: Self-reported physical activity levels (MET hrs/wk) were assessed using an adapted version of the International Physical Activity Questionnaire (IPAQ) at baseline in 931 patients with stage I-III colorectal cancer and classified into 'highly active' and'not-highly active'(≥ / < 18 MET hrs/wk). BMI (kg/m2) was categorized into 'normal weight', 'overweight', and 'obese'. Patients were further classified into combined physical activity and BMI groups. Cox-proportional hazard models with Firth correction were computed to assess associations [hazard ratio (HR), 95% profile HR likelihood confidence interval (95% CI) between individual and combined physical activity and BMI groups with overall and disease-free survival in colorectal cancer patients. RESULTS: 'Not-highly active' compared to 'highly active' and 'overweight'/ 'obese' compared to 'normal weight' patients had a 40-50% increased risk of death or recurrence (HR: 1.41 (95% CI: 0.99-2.06), p = 0.03; HR: 1.49 (95% CI: 1.02-2.21) and HR: 1.51 (95% CI: 1.02-2.26), p = 0.04, respectively). 'Not-highly active' patients had worse disease-free survival outcomes, regardless of their BMI, compared to 'highly active/normal weight' patients. 'Not-highly active/obese' patients had a 3.66 times increased risk of death or recurrence compared to 'highly active/normal weight' patients (HR: 4.66 (95% CI: 1.75-9.10), p = 0.002). Lower activity thresholds yielded smaller effect sizes. CONCLUSION: Physical activity and BMI were individually associated with disease-free survival among colorectal cancer patients. Physical activity seems to improve survival outcomes in patients regardless of their BMI.


Assuntos
Neoplasias Colorretais , Obesidade , Humanos , Índice de Massa Corporal , Obesidade/complicações , Sobrepeso/complicações , Sobrepeso/epidemiologia , Exercício Físico , Fatores de Risco
13.
J Gastrointest Surg ; 27(3): 573-584, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36469282

RESUMO

INTRODUCTION: Parastomal hernia is a debilitating complication of stoma creation. Parastomal hernia repair with mesh reduces recurrence rates in open and laparoscopic settings. Recent comparative studies conflict with previously pooled data on optimal mesh repair technique. The objective of this study is to examine parastomal hernia recurrence rates after Sugarbaker and keyhole repairs by performing an updated systematic review and meta-analysis of comparative studies. METHODS: A systematic review of PubMed, MEDLINE, EMBASE, the Cochrane database, SCOPUS, and the PROSPERO registry was performed according to PRISMA 2020 guidelines (PROSPERO ID: CRD42021290483). Studies comparing parastomal hernia recurrences after Sugarbaker and keyhole repairs were included. Studies with overlapping patient cohorts (duplicate data), non-comparative studies, studies that did not report the primary outcome of interest, and studies not in the English language were excluded. Study bias was assessed using the Newcastle-Ottawa scale. Pooled mean differences (MD), odds ratios (OR), and risk ratios (RR) with 95% confidence intervals (CI) were calculated. Heterogeneity was assessed using the I2 statistic. Forest plots and funnel plots were generated. Study quality was analyzed using MINORS. Additional subgroup analysis of modern studies was performed. RESULTS: Ten comparative studies published between 2005 and 2021 from 5 countries were included for analysis comprising 347 Sugarbaker repairs and 246 keyhole repairs. There were no differences in patient age, sex, or BMI between the groups. There was no difference between the groups regarding surgical site infection (OR 0.78; CI 0.31-1.98; P = 0.61) or post-operative bowel obstruction (OR 0.76; CI 0.23-2.56; P = 0.66). Sugarbaker repairs were significantly less often associated with parastomal hernia recurrence when compared to keyhole repairs (OR 0.38; CI 0.18-0.78; P = 0.008). There was no significant heterogeneity among the studies comparing parastomal hernia recurrence (I2 = 32%; P = 0.15). Quality analysis revealed a median MINORS score of 11 (range 6-16). Subgroup analysis of studies performed after the previously published pooled analysis (2015-2021) revealed no significant difference in parastomal hernia recurrence between the two groups (OR 0.58; CI 0.24-1.38; P = 0.22) with a significant subgroup effect (P = 0.05). CONCLUSIONS: Though there were lower rates of parastomal hernia recurrence with Sugarbaker repairs on overall analysis, this phenomenon disappeared on subgroup analysis of modern studies. Randomized controlled trials with contemporary cohorts would help further evaluate these repairs and minimize potential bias.


Assuntos
Hérnia Ventral , Hérnia Incisional , Laparoscopia , Estomas Cirúrgicos , Humanos , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Estomas Cirúrgicos/efeitos adversos , Herniorrafia/métodos , Infecção da Ferida Cirúrgica , Laparoscopia/métodos , Telas Cirúrgicas/efeitos adversos , Hérnia Ventral/cirurgia , Hérnia Ventral/complicações
14.
PLoS Genet ; 17(12): e1009972, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34936656

RESUMO

The RarA protein, homologous to human WRNIP1 and yeast MgsA, is a AAA+ ATPase and one of the most highly conserved DNA repair proteins. With an apparent role in the repair of stalled or collapsed replication forks, the molecular function of this protein family remains obscure. Here, we demonstrate that RarA acts in late stages of recombinational DNA repair of post-replication gaps. A deletion of most of the rarA gene, when paired with a deletion of ruvB or ruvC, produces a growth defect, a strong synergistic increase in sensitivity to DNA damaging agents, cell elongation, and an increase in SOS induction. Except for SOS induction, these effects are all suppressed by inactivating recF, recO, or recJ, indicating that RarA, along with RuvB, acts downstream of RecA. SOS induction increases dramatically in a rarA ruvB recF/O triple mutant, suggesting the generation of large amounts of unrepaired ssDNA. The rarA ruvB defects are not suppressed (and in fact slightly increased) by recB inactivation, suggesting RarA acts primarily downstream of RecA in post-replication gaps rather than in double strand break repair. Inactivating rarA, ruvB and recG together is synthetically lethal, an outcome again suppressed by inactivation of recF, recO, or recJ. A rarA ruvB recQ triple deletion mutant is also inviable. Together, the results suggest the existence of multiple pathways, perhaps overlapping, for the resolution or reversal of recombination intermediates created by RecA protein in post-replication gaps within the broader RecF pathway. One of these paths involves RarA.


Assuntos
Adenosina Trifosfatases/genética , Proteínas de Bactérias/genética , Proteínas de Ligação a DNA/genética , Epistasia Genética/genética , Proteínas de Escherichia coli/genética , RecQ Helicases/genética , Dano ao DNA/genética , Reparo do DNA/genética , Replicação do DNA/genética , DNA de Cadeia Simples , Escherichia coli/genética , Exodesoxirribonucleases , Recombinação Homóloga/genética , Recombinação Genética/genética , Mutações Sintéticas Letais/genética
15.
JCI Insight ; 6(16)2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34283808

RESUMO

BACKGROUNDEpicardial adipose tissue (EAT) directly overlies the myocardium, with changes in its morphology and volume associated with myriad cardiovascular and metabolic diseases. However, EAT's immune structure and cellular characterization remain incompletely described. We aimed to define the immune phenotype of EAT in humans and compare such profiles across lean, obese, and diabetic patients.METHODSWe recruited 152 patients undergoing open-chest coronary artery bypass grafting (CABG), valve repair/replacement (VR) surgery, or combined CABG/VR. Patients' clinical and biochemical data and EAT, subcutaneous adipose tissue (SAT), and preoperative blood samples were collected. Immune cell profiling was evaluated by flow cytometry and complemented by gene expression studies of immune mediators. Bulk RNA-Seq was performed in EAT across metabolic profiles to assess whole-transcriptome changes observed in lean, obese, and diabetic groups.RESULTSFlow cytometry analysis demonstrated EAT was highly enriched in adaptive immune (T and B) cells. Although overweight/obese and diabetic patients had similar EAT cellular profiles to lean control patients, the EAT exhibited significantly (P ≤ 0.01) raised expression of immune mediators, including IL-1, IL-6, TNF-α, and IFN-γ. These changes were not observed in SAT or blood. Neither underlying coronary artery disease nor the presence of hypertension significantly altered the immune profiles observed. Bulk RNA-Seq demonstrated significant alterations in metabolic and inflammatory pathways in the EAT of overweight/obese patients compared with lean controls.CONCLUSIONAdaptive immune cells are the predominant immune cell constituent in human EAT and SAT. The presence of underlying cardiometabolic conditions, specifically obesity and diabetes, rather than cardiac disease phenotype appears to alter the inflammatory profile of EAT. Obese states markedly alter EAT metabolic and inflammatory signaling genes, underlining the impact of obesity on the EAT transcriptome profile.FUNDINGBarts Charity MGU0413, Abbott, Medical Research Council MR/T008059/1, and British Heart Foundation FS/13/49/30421 and PG/16/79/32419.


Assuntos
Tecido Adiposo/imunologia , Diabetes Mellitus/epidemiologia , Obesidade/epidemiologia , Pericardite/epidemiologia , Pericárdio/patologia , Imunidade Adaptativa , Tecido Adiposo/citologia , Tecido Adiposo/patologia , Idoso , Fatores de Risco Cardiometabólico , Comorbidade , Ponte de Artéria Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/cirurgia , Diabetes Mellitus/sangue , Diabetes Mellitus/imunologia , Diabetes Mellitus/metabolismo , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/imunologia , Obesidade/metabolismo , Pericardite/imunologia , Pericardite/patologia , Pericárdio/cirurgia , RNA-Seq
16.
Clin Colon Rectal Surg ; 34(2): 121-126, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33642952

RESUMO

Diverticular disease affects a large percentage of the US population, affecting over 30% among those older than 45 years old. It is responsible for ∼300,000 hospitalizations per year in the United States and can lead to serious complications such as hemorrhage, obstruction, abscess, fistulae, or bowel perforation. 2 It is an extremely common reason for emergency room and outpatient visits and evaluations by general and colorectal surgeons. In the US, patients usually present with sigmoid diverticulitis in the setting of a normal immune system so surgeons will follow well-established practice guidelines for treatment. However, there may be special circumstances in which the management of diverticulitis is not as straightforward. In this article, we will address patients who present with multifocal disease, giant colonic diverticulum, right-sided diverticulitis, and diverticulitis in the setting of immunosuppression and hopefully provide guidance for treatment in these special circumstances.

17.
Mol Microbiol ; 115(6): 1122-1137, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33247976

RESUMO

Most, but not all, homologous genetic recombination in bacteria is mediated by the RecA recombinase. The mechanistic origin of RecA-independent recombination has remained enigmatic. Here, we demonstrate that the RarA protein makes a major enzymatic contribution to RecA-independent recombination. In particular, RarA makes substantial contributions to intermolecular recombination and to recombination events involving relatively short (<200 bp) homologous sequences, where RecA-mediated recombination is inefficient. The effects are seen here in plasmid-based recombination assays and in vivo cloning processes. Vestigial levels of recombination remain even when both RecA and RarA are absent. Additional pathways for RecA-independent recombination, possibly mediated by helicases, are suppressed by exonucleases ExoI and RecJ. Translesion DNA polymerases may also contribute. Our results provide additional substance to a previous report of a functional overlap between RecA and RarA.


Assuntos
Adenosina Trifosfatases/genética , Proteínas de Ligação a DNA/genética , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Recombinação Homóloga/genética , Recombinases Rec A/genética , Adenosina Trifosfatases/metabolismo , Proteínas de Bactérias/genética , DNA Helicases/metabolismo , Reparo do DNA/genética , DNA Bacteriano/genética , Exodesoxirribonucleases/genética
18.
Int J Surg Case Rep ; 72: 524-527, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32698280

RESUMO

INTRODUCTION: Enterocele is a herniation of the small bowel through the cul-de-sac. It is uncommon and most often seen in elder females. Large enterocele manifesting as rectal prolapse is exceedingly rare and only few cases are reported previously. Due to it rarity, the best surgical treatment is not yet established especially in male patients. We present a case of enterocele causing rectal prolapse in a male patient that was treated surgically. PRESENTATION OF CASE: A 47-year-old African American male with chronic constipation and straining presented with manually reducible rectal prolapse. A defecography revealed a large enterocele prolapsing through the anterior rectal wall. The patient underwent an open posterior suture rectopexy with peritoneoplasty. His symptoms completely resolved after surgery, and repeat defecography three months after the procedure showed no sign of recurrence. DISCUSSION & CONCLUSION: Extraperineal enterocele in male is a rare disease. Rectopexy with peritoneoplasty can provide a great symptom relieve and improvement on defecography. Long-term outcome should be evaluated.

19.
Nucleic Acids Res ; 48(15): 8445-8460, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32644157

RESUMO

DNA lesions or other barriers frequently compromise replisome progress. The SF2 helicase RecG is a key enzyme in the processing of postreplication gaps or regressed forks in Escherichia coli. A deletion of the recG gene renders cells highly sensitive to a range of DNA damaging agents. Here, we demonstrate that RecG function is at least partially complemented by another SF2 helicase, RadD. A ΔrecGΔradD double mutant exhibits an almost complete growth defect, even in the absence of stress. Suppressors appear quickly, primarily mutations that compromise priA helicase function or recA promoter mutations that reduce recA expression. Deletions of uup (encoding the UvrA-like ABC system Uup), recO, or recF also suppress the ΔrecGΔradD growth phenotype. RadD and RecG appear to avoid toxic situations in DNA metabolism, either resolving or preventing the appearance of DNA repair intermediates produced by RecA or RecA-independent template switching at stalled forks or postreplication gaps. Barriers to replisome progress that require intervention by RadD or RecG occur in virtually every replication cycle. The results highlight the importance of the RadD protein for general chromosome maintenance and repair. They also implicate Uup as a new modulator of RecG function.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Adenosina Trifosfatases/genética , Reparo do DNA/genética , Replicação do DNA/genética , Proteínas de Escherichia coli/genética , DNA Bacteriano/genética , Proteínas de Ligação a DNA/genética , Escherichia coli/genética , Mutação/genética , Recombinação Genética/genética
20.
Vet Comp Oncol ; 18(4): 519-527, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32012432

RESUMO

Thyroid carcinoma is the most common endocrine malignancy in dogs. Thyroidectomy and radiation therapy control local disease, yet are not always feasible, and efficacious medical therapies need to be identified. Toceranib phosphate has been reported to provide clinical benefit (CB) in dogs with thyroid carcinoma, while its role in treatment-naïve thyroid tumours has not been well-described. The objective of this study was to describe the use of toceranib in the management of thyroid carcinomas in dogs in both the naïve-disease and prior therapy- settings. A medical record search identified 42 dogs diagnosed with thyroid carcinoma and treated with toceranib, of which 26 and 16 dogs were in settings of naïve-disease and after prior therapy, respectively. Twenty-three (88.4%) and twelve (75%) dogs experienced CB in the naïve and prior therapy settings, respectively. The median [95% confidence interval] progression free interval (PFI) for dogs in the naïve and prior therapy settings were 206 [106,740] and 1015 [92,1015] days, respectively. The median overall survival time (OST) for dogs in the naïve and prior therapy settings were 563 [246,916] and 1082 [289,1894] days, respectively. Overall, the data provided no evidence for differences in overall PFI (P > .20) or OST (P = .15) between settings. However, when asymptomatic at the time of diagnosis, dogs in the naïve setting showed poorer survival prognosis (estimated hazard ratio 17.2 [1.8, 163]) relative to dogs in the prior therapy setting. This study characterizes PFI, OST and CB with minimal AE in dogs with thyroid carcinoma treated with toceranib in both the naïve and prior therapy settings.


Assuntos
Antineoplásicos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Indóis/uso terapêutico , Pirróis/uso terapêutico , Neoplasias da Glândula Tireoide/veterinária , Animais , Antineoplásicos/efeitos adversos , Doenças do Cão/patologia , Cães , Indóis/efeitos adversos , Pirróis/efeitos adversos , Sobrevida , Neoplasias da Glândula Tireoide/tratamento farmacológico
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