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1.
Nature ; 622(7981): 130-138, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37730990

RESUMO

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD)1. However, achieving stable recovery is unpredictable2, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting3. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.


Assuntos
Estimulação Encefálica Profunda , Depressão , Transtorno Depressivo Maior , Humanos , Inteligência Artificial , Biomarcadores , Estimulação Encefálica Profunda/métodos , Depressão/fisiopatologia , Depressão/terapia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Eletrofisiologia , Resultado do Tratamento , Medida de Potenciais de Campo Local , Substância Branca , Lobo Límbico/fisiologia , Lobo Límbico/fisiopatologia , Expressão Facial
2.
Am J Physiol Gastrointest Liver Physiol ; 325(1): G80-G91, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37158470

RESUMO

Regulation of small intestinal epithelial growth by endogenous and environmental factors is critical for intestinal homeostasis and recovery from insults. Depletion of the intestinal microbiome increases epithelial proliferation in small intestinal crypts, similar to the effects observed in animal models of serotonin potentiation. Based on prior evidence that the microbiome modulates serotonin activity, we hypothesized that microbial depletion-induced epithelial proliferation is dependent on host serotonin activity. A mouse model of antibiotic-induced microbial depletion (AIMD) was employed. Serotonin potentiation was achieved through either genetic knockout of the serotonin transporter (SERT) or pharmacological SERT inhibition, and inhibition of serotonin synthesis was achieved with para-chlorophenylalanine. AIMD and serotonin potentiation increased intestinal villus height and crypt proliferation in an additive manner, but the epithelial proliferation observed after AIMD was blocked in the absence of endogenous serotonin. Using Lgr5-EGFP-reporter mice, we evaluated intestinal stem cell (ISC) quantity and proliferation. AIMD increased the number of ISCs per crypt and ISC proliferation compared with controls, and changes in ISC number and proliferation were dependent on the presence of host serotonin. Furthermore, Western blotting demonstrated that AIMD reduced epithelial SERT protein expression compared with controls. In conclusion, host serotonin activity is necessary for microbial depletion-associated changes in villus height and ISC proliferation in crypts, and microbial depletion produces a functional serotonin-potentiated state through reduced SERT protein expression. These findings provide an understanding of how changes to the microbiome contribute to intestinal pathology and can be applied therapeutically.NEW & NOTEWORTHY Antibiotic-induced microbial depletion of the murine small intestine results in a state of potentiated serotonin activity through reduced epithelial expression of the serotonin transporter. Specifically, serotonin-dependent mechanisms lead to increased intestinal surface area and intestinal stem cell proliferation. Furthermore, the absence of endogenous serotonin leads to blunting of small intestinal villi, suggesting that serotonin signaling is required for epithelial homeostasis.


Assuntos
Neoplasias Intestinais , Serotonina , Camundongos , Animais , Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Intestinos , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Neoplasias Intestinais/metabolismo , Proliferação de Células
3.
J Surg Res ; 239: 208-215, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30851520

RESUMO

BACKGROUND: Pilonidal, buttock, and perianal abscesses are common reasons for surgical consultation in the pediatric emergency department. Treatment typically includes a bedside incision and drainage, often followed by an abscess culture, and a course of oral antibiotics. We aimed to study the impact of culture data on changes in management and clinical outcomes. We hypothesized that management is unaffected by culture data, and therefore, fluid culture from pilonidal, buttock, and perianal abscesses in the pediatric population may represent an unnecessary laboratory test and cost. MATERIALS AND METHODS: A single institution's electronic medical record was searched between February 1, 2013 and August 1, 2017, identifying 249 pediatric patients meeting the inclusion criteria: age 0 to 18 y; diagnosis of pilonidal, buttock, or perianal abscess; bedside incision and drainage. Patients were divided into two different comparison groups for data analysis based on the presence or absence of culture and recurrence or no recurrence. RESULTS: Culture results directly altered management in only 5 patient encounters (2.7% of all cultured). When comparing groups by culture or no culture, no statistically significant difference in recurrence rate (P = 0.4) was noted. When comparing groups by recurrence versus no recurrence, we found no statistically significant difference between sex, resident type, vessel loop use, packing use, or antibiotic use (P > 0.05). CONCLUSIONS: We conclude that microbiological culture results are of limited utility in the management of pediatric pilonidal, buttock, and perianal abscesses as they do not appear to alter treatment, and omission of culture is not associated with failure of surgical management.


Assuntos
Abscesso/terapia , Antibacterianos/administração & dosagem , Bactérias/isolamento & purificação , Análise Custo-Benefício , Drenagem , Abscesso/economia , Abscesso/microbiologia , Administração Oral , Adolescente , Canal Anal , Nádegas , Criança , Pré-Escolar , Técnicas de Cultura/economia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Seleção de Pacientes , Recidiva , Estudos Retrospectivos , Região Sacrococcígea , Resultado do Tratamento , Adulto Jovem
4.
J Urol ; 193(1): 48-52, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24960468

RESUMO

PURPOSE: Malignant voided cytology with normal endoscopic evaluation represents a diagnostic and therapeutic challenge in many patients with a history of nonmuscle invasive bladder cancer. Bladder biopsy is often advised but its efficacy is unclear. We evaluated the usefulness of bladder biopsy in patients with unexplained positive cytology and describe recurrence patterns in this unique patient subset. MATERIALS AND METHODS: From an institutional database we retrospectively identified patients with a history of nonmuscle invasive bladder cancer and surveillance cystoscopy from 2008 to 2012 who had malignant voided urine cytology but normal cystoscopy. Patients underwent systematic bladder biopsy or cystoscopic surveillance and were followed for recurrence and progression. RESULTS: Of 444 patients 343 were followed with surveillance only and 101 underwent a total of 118 biopsies of normal-appearing bladder mucosa. Three biopsies (2.5%) showed carcinoma in situ and none revealed invasive carcinoma. During the median 32-month followup recurrence developed in the bladder in 194 patients (44%), in the upper tract in 24 (5%) and in the prostatic urethra in 5 (1%) while 219 (49%) had no recurrence. A previous diagnosis of upper tract urothelial carcinoma and a history of bacillus Calmette-Guérin treatment were associated with an increased recurrence risk on multivariate analysis. Recurrence rates and patterns were similar in the biopsy and surveillance groups. CONCLUSIONS: Patients with malignant cytology despite normal cystoscopy have a high recurrence rate. Biopsy of normal-appearing bladder mucosa in this setting is rarely positive and does not alter the recurrence pattern.


Assuntos
Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Idoso , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/patologia , Invasividade Neoplásica , Estudos Retrospectivos
5.
J Exp Med ; 204(1): 129-39, 2007 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-17227908

RESUMO

For decades, in vitro expansion of transplantable hematopoietic stem cells (HSCs) has been an elusive goal. Here, we demonstrate that multipotent adult progenitor cells (MAPCs), isolated from green fluorescent protein (GFP)-transgenic mice and expanded in vitro for >40-80 population doublings, are capable of multilineage hematopoietic engraftment of immunodeficient mice. Among MAPC-derived GFP+CD45.2+ cells in the bone marrow of engrafted mice, HSCs were present that could radioprotect and reconstitute multilineage hematopoiesis in secondary and tertiary recipients, as well as myeloid and lymphoid hematopoietic progenitor subsets and functional GFP+ MAPC-derived lymphocytes that were functional. Although hematopoietic contribution by MAPCs was comparable to control KTLS HSCs, approximately 10(3)-fold more MAPCs were required for efficient engraftment. Because GFP+ host-derived CD45.1+ cells were not observed, fusion is not likely to account for the generation of HSCs by MAPCs.


Assuntos
Hematopoese , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Multipotentes/transplante , Animais , Linfócitos B/imunologia , Sobrevivência de Enxerto , Proteínas de Fluorescência Verde/genética , Hematopoese/imunologia , Sistema Hematopoético/citologia , Técnicas In Vitro , Tecido Linfoide/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Camundongos Transgênicos , Células-Tronco Multipotentes/imunologia , Especificidade de Órgãos , Proteínas Recombinantes/genética , Linfócitos T/imunologia
6.
J Law Biosci ; 10(2): lsad025, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901886

RESUMO

Innovations in neurotechnologies have ignited conversations about ethics around the world, with implications for researchers, policymakers, and the private sector. The human rights impacts of neurotechnologies have drawn the attention of United Nations bodies; nearly 40 states are tasked with implementing the Organization for Economic Co-operation and Development's principles for responsible innovation in neurotechnology; and the United States is considering placing export controls on brain-computer interfaces. Against this backdrop, we offer the first review and analysis of neuroethics guidance documents recently issued by prominent government, private, and academic groups, focusing on commonalities and divergences in articulated goals; envisioned roles and responsibilities of different stakeholder groups; and the suggested role of the public. Drawing on lessons from the governance of other emerging technologies, we suggest implementation and evaluation strategies to guide practitioners and policymakers in operationalizing these ethical norms in research, business, and policy settings.

7.
PLoS One ; 17(3): e0266251, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35349599

RESUMO

Previous work demonstrated enhanced enterocyte proliferation and mucosal growth in gnotobiotic mice, suggesting that intestinal flora participate in mucosal homeostasis. Furthermore, broad-spectrum enteral antibiotics are known to induce near germ-free (GF) conditions in mice with conventional flora (CONV). We hypothesized that inducing near GF conditions with broad-spectrum enteral antibiotics would cause ordered small intestinal mucosal growth in CONV mice but would have no effect in GF mice with no inherent microbiome. C57BL/6J CONV and GF mice received either an antibiotic solution (Ampicillin, Ciprofloxacin, Metronidazole, Vancomycin, Meropenem) or a vehicle alone. After treatment, small intestinal villus height (VH), crypt depth (CD), mucosal surface area (MSA), crypt proliferation index (CPI), apoptosis, and villus and crypt cell types were assessed. Antibiotic-treated CONV (Abx-CONV) mice had taller villi, deeper crypts, increased CPI, increased apoptosis, and greater MSA compared to vehicle-treated CONV mice. Minor differences were noted in enterocyte and enterochromaffin cell proportions between groups, but goblet and Paneth cell proportions were unchanged in Abx-CONV mice compared to vehicle-treated CONV mice (p>0.05). Antibiotics caused no significant changes in VH or MSA in GF mice when compared to vehicle-treated GF mice (p>0.05). Enteral administration of broad-spectrum antibiotics to mice with a conventional microbiome stimulates ordered small intestinal mucosal growth. Mucosal growth was not seen in germ-free mice treated with antibiotics, implying that intestinal mucosal growth is associated with change in the microbiome in this model.


Assuntos
Intestino Delgado , Microbiota , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Vida Livre de Germes , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
8.
J Am Coll Surg ; 234(3): 352-358, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35213498

RESUMO

BACKGROUND: We aim to evaluate recurrence rates of gallstone pancreatitis in children undergoing early vs interval cholecystectomy. STUDY DESIGN: A multicenter, retrospective review of pediatric patients admitted with gallstone pancreatitis from 2010 through 2017 was performed. Children were evaluated based on timing of cholecystectomy. Early cholecystectomy was defined as surgery during the index admission, whereas the delayed group was defined as no surgery or surgery after discharge. Outcomes, recurrence rates, and complications were evaluated. RESULTS: Of 246 patients from 6 centers with gallstone pancreatitis, 178 (72%) were female, with mean age 13.5 ± 3.2 years and a mean body mass index of 28.9 ± 15.2. Most (90%) patients were admitted with mild pancreatitis (Atlanta Classification). Early cholecystectomy was performed in 167 (68%) patients with no difference in early cholecystectomy rates across institutions. Delayed group patients weighed less (61 kg vs. 72 kg, p = 0.003) and were younger (12 vs. 14 years, p = 0.001) than those who underwent early cholecystectomy. However, there were no differences in clinical, radiological, or laboratory characteristics between groups. There were 4 (2%) episodes of postoperative recurrent pancreatitis in the early group compared with 22% in the delayed group. More importantly, when cholecystectomy was delayed more than 6 weeks from index discharge, recurrence approached 60%. There were no biliary complications in any group. CONCLUSIONS: Cholecystectomy during the index admission for children with gallstone pancreatitis reduces recurrent pancreatitis. Recurrence proportionally increases with time when patients are treated with a delayed approach.


Assuntos
Cálculos Biliares , Pancreatite , Adolescente , Criança , Colecistectomia/efeitos adversos , Feminino , Cálculos Biliares/complicações , Cálculos Biliares/cirurgia , Hospitalização , Humanos , Masculino , Pancreatite/etiologia , Pancreatite/cirurgia , Recidiva , Estudos Retrospectivos
9.
Blood ; 114(3): 693-701, 2009 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-19458354

RESUMO

Multipotent adult progenitor cells (MAPCs) are nonhematopoietic stem cells capable of giving rise to a broad range of tissue cells. As such, MAPCs hold promise for tissue injury repair after transplant. In vitro, MAPCs potently suppressed allogeneic T-cell activation and proliferation in a dose-dependent, cell contact-independent, and T-regulatory cell-independent manner. Suppression occurred primarily through prostaglandin E(2) synthesis in MAPCs, which resulted in decreased proinflammatory cytokine production. When given systemically, MAPCs did not home to sites of allopriming and did not suppress graft-versus-host disease (GVHD). To ensure that MAPCs would colocalize with donor T cells, MAPCs were injected directly into the spleen at bone marrow transplantation. MAPCs limited donor T-cell proliferation and GVHD-induced injury via prostaglandin E(2) synthesis in vivo. Moreover, MAPCs altered the balance away from positive and toward inhibitory costimulatory pathway expression in splenic T cells and antigen-presenting cells. These findings are the first to describe the immunosuppressive capacity and mechanism of MAPC-induced suppression of T-cell alloresponses and illustrate the requirement for MAPC colocalization to sites of initial donor T-cell activation for GVHD inhibition. Such data have implications for the use of allogeneic MAPCs and possibly other immunomodulatory nonhematopoietic stem cells for preventing GVHD in the clinic.


Assuntos
Apresentação de Antígeno/imunologia , Dinoprostona/biossíntese , Doença Enxerto-Hospedeiro/prevenção & controle , Células-Tronco Multipotentes/imunologia , Células-Tronco Adultas/imunologia , Células-Tronco Adultas/transplante , Animais , Transplante de Medula Óssea/métodos , Movimento Celular , Doença Enxerto-Hospedeiro/terapia , Ativação Linfocitária , Camundongos , Células-Tronco Multipotentes/transplante , Baço
10.
Cell Mol Gastroenterol Hepatol ; 12(3): 1093-1104, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34022423

RESUMO

Serotonin signaling is ubiquitous in the gastrointestinal (GI) system, where it acts as a neurotransmitter in the enteric nervous system (ENS) and influences intestinal motility and inflammation. Since its discovery, serotonin has been linked to cellular proliferation in several types of tissues, including vascular smooth muscle, neurons, and hepatocytes. Activation of serotonin receptors on distinct cell types has been shown to induce well-known intracellular proliferation pathways. In the GI tract, potentiation of serotonin signaling results in enhanced intestinal epithelial proliferation, and decreased injury from intestinal inflammation. Furthermore, activation of the type 4 serotonin receptor on enteric neurons leads to neurogenesis and neuroprotection in the setting of intestinal injury. It is not surprising that the mitogenic properties of serotonin are pronounced within the GI tract, where enterochromaffin cells in the intestinal epithelium produce 90% of the body's serotonin; however, these proliferative effects are attributed to increased serotonin signaling within the ENS compartment as opposed to the intestinal mucosa, which are functionally and chemically separate by virtue of the distinct tryptophan hydroxylase enzyme isoforms involved in serotonin synthesis. The exact mechanism by which serotonergic neurons in the ENS lead to intestinal proliferation are not known, but the activation of muscarinic receptors on intestinal crypt cells indicate that cholinergic signaling is essential to this signaling pathway. Further understanding of serotonin's role in mucosal and enteric nervous system mitogenesis may aid in harnessing serotonin signaling for therapeutic benefit in many GI diseases, including inflammatory bowel disease, malabsorptive conditions, and cancer.


Assuntos
Trato Gastrointestinal/metabolismo , Mitógenos/metabolismo , Receptores de Serotonina/metabolismo , Serotonina/metabolismo , Animais , Proliferação de Células , Sobrevivência Celular , Motilidade Gastrointestinal , Humanos , Transdução de Sinais
11.
J Pediatr Surg ; 56(9): 1495-1499, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33745746

RESUMO

INTRODUCTION: Fundoplication for gastro-esophageal reflux disease (GERD) has been commonly performed by pediatric surgeons, however there are no recent data documenting fundoplication trends. Changes in fundoplication volume impact pediatric surgical training and may reflect changes in care for children with severe GERD. MATERIALS & METHODS: The Pediatric Health Information System (PHIS) was queried from 2010-2019 for children with ICD-9/ICD-10 codes for GERD, fundoplication, and gastrostomy. Institutional surgical volume and patient demographics were examined over time. A secondary analysis using the Accreditation Council for Graduate Medical Education case logs for pediatric surgery fellows was performed across the same years to assess effects upon surgical volume for trainees. RESULTS: Mean institutional fundoplication case volume decreased from 50 in 2010 to 17 in 2019. Trends were similar between institutions with and without fellowship programs when corrected by total operative volume. Patient characteristics were relatively unchanged between 2010 and 2019. Fundoplication volume reported in fellow case logs decreased from 46 in 2010 to 26 in 2019, mirroring national data. CONCLUSIONS: Institutional volume for fundoplication in children with GERD has seen a 3-fold decrease over the last decade, mirrored by an almost 2-fold decrease in case volume reported by pediatric surgery fellows.


Assuntos
Esofagoplastia , Refluxo Gastroesofágico , Laparoscopia , Especialidades Cirúrgicas , Criança , Fundoplicatura , Refluxo Gastroesofágico/cirurgia , Gastrostomia , Humanos , Resultado do Tratamento
12.
J Pediatr Surg ; 56(11): 2016-2021, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33549307

RESUMO

INTRODUCTION: Inguinal hernia repairs (IHR) are commonly performed by pediatric surgeons in the United States. The operative approach depends on surgeon preference with no definitive prospective studies comparing laparoscopic inguinal hernia repair (LIHR) versus traditional inguinal hernia repair (TIHR). We aim to assess current practice, hypothesizing that laparoscopy is increasingly used for pediatric IHR. MATERIAL & METHODS: The Children's Hospital Association (CHA) Pediatric Health Information System was queried for IHRs performed between 01/01/2009 and 12/31/2018. Demographics, procedure type, hernia laterality, and cost were obtained. Patients were grouped by procedure type (laparoscopic/traditional). RESULTS: 125,249 IHRs were performed at 32 CHA hospitals during the ten-year study period. 115,782 (92.4%) were TIHR and 9467 (7.6%) LIHR. Use of laparoscopy increased 5-fold from 3% to 15% over the study period. When comparing laparoscopic to traditional IHR groups, there were more females (28.3% vs 12.6%), African-Americans (19.7% vs 14.4%), government-insured (50% vs 45.2%), younger patients (4.2 vs 4.4 years), bilateral IHRs (11.4% vs 7.9%), and higher adjusted total hospital cost ($3,791 vs $2995) in the laparoscopic group (p<0.0001, all comparisons). CONCLUSIONS: Laparoscopy for pediatric IHR is increasing at CHA hospitals where nearly 1 in 6 children currently undergoes a laparoscopic repair. The long-term outcomes with laparoscopic repair are worthy of future study.


Assuntos
Hérnia Inguinal , Laparoscopia , Criança , Feminino , Hérnia Inguinal/cirurgia , Herniorrafia , Hospitais Pediátricos , Humanos , Estudos Prospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia
13.
JPEN J Parenter Enteral Nutr ; 45(6): 1249-1258, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797633

RESUMO

BACKGROUND: Pediatric intestinal rehabilitation (PIR) programs are associated with improved outcomes in children with intestinal failure but remain heterogeneous nationally. This study characterizes PIR program components to aid those seeking to establish or expand a program. METHODS: Members of the Children's Hospital Association reporting a PIR program to the US News and World Report completed a 14-item questionnaire using the Qualtrics Online Survey Software. Programs were categorized as small or large (≤50 vs >50 patients) and new or established (≤10 vs >10 years). RESULTS: Seventy-one programs were identified and 61 surveys were returned for a response rate of 86%. Majority of programs had gastroenterology, surgery, nutrition, nursing, and social work services involved. Large programs (n = 34; 59%) were more likely to serve as referral centers; have greater participation by nursing, social work, and primary care; have more dedicated time by gastroenterology, surgery, nursing, nutrition, and social work; have more frequent meetings; and have various funding sources (P < .05). CONCLUSION: Critical components of a PIR program include gastroenterology, surgery, and nutrition services with strong nursing and social work support. These data document the components of modern PIR programs, though further studies on the relationship between program structure and patient outcomes are warranted.


Assuntos
Gastroenterologia , Intestinos , Criança , Humanos , Estado Nutricional , Apoio Social , Inquéritos e Questionários , Estados Unidos
14.
J Surg Educ ; 78(2): 412-421, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32768380

RESUMO

OBJECTIVE: Describe the early impact of the COVID-19 pandemic on general surgery residency training nationwide. DESIGN: A 31-question electronic survey was distributed to general surgery program directors. Qualitative data underwent iterative coding analysis. Quantitative data were evaluated with summary statistics and bivariate analyses. PARTICIPANTS: Eighty-four residency programs (33.6% response rate) with representation across US geographic regions, program affiliations, and sizes. RESULTS: Widespread changes were observed in the surgical training environment. One hundred percent of programs reduced the number of residents on rounds and 95.2% reduced the size of their in-hospital resident workforce; on average, daytime staffing decreased by nearly half. With telehealth clinics (90.5%) and remote inpatient consults (26.2%), both clinical care and resident didactics (86.9%) were increasingly virtual, with similar impact across all program demographics. Conversely, availability of some wellness initiatives was significantly higher among university programs than independent programs, including childcare (51.2% vs 6.7%), housing (41.9% vs 13.3%), and virtual mental health services (83.7% vs 53.3%). CONCLUSIONS: Changes in clinical care delivery dramatically reduced in face-to-face learning opportunities for surgical trainees during the COVID-19 pandemic. While this effect had equal impact across all program types, sizes, and geographies, the same cannot be said for wellness initiatives. Though all programs initiated some strategies to protect resident health, the disparity between university programs and independent programs may be cause for action.


Assuntos
COVID-19/epidemiologia , Educação de Pós-Graduação em Medicina/tendências , Cirurgia Geral/educação , Admissão e Escalonamento de Pessoal/tendências , Humanos , Internato e Residência , Pandemias , SARS-CoV-2 , Inquéritos e Questionários , Estados Unidos/epidemiologia
15.
J Immunol ; 181(12): 8767-75, 2008 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-19050298

RESUMO

CD4(+)CD25(+) regulatory T cells (Tregs) play an essential role in controlling autoimmunity and allograft rejection. Several ex vivo activation and expansion protocols have been developed to amplify cell numbers and suppressor function of murine and human Tregs. We demonstrate in this study that ex vivo activation and expansion of murine Tregs resulted in an enrichment of a CD4(low/neg)CD25(+) T cell population that was more than 20-fold more potent than expanded conventional Tregs in suppressing an in vitro CD4(+)CD25(-) T cell response to allo-Ag. The generation of CD4(low/neg)CD25(+) T cells was independent of the presence of Tregs in the culture, and suppressor function was acquired only after activation and expansion. CD4(low/neg)CD25(+) T cells expressed either an alphabeta or gammadelta TCR, had an activated phenotype, and did not express the transcription factor FoxP3. Despite expressing the cell surface Ags lymphocyte activation gene-3 (CD223) and CD103, neither was essential for suppressor cell function. Suppression by CD4(low/neg)CD25(+) T cells was prevented by a semipermeable membrane and was independent of IL-10 and TGF-beta. In summary, we describe in this study CD4(low/neg)CD25(+) FoxP3(neg) T cells with highly potent suppressor cell function derived from cultures of an enriched population of CD4(+)CD25(+) T cells that may contribute to the suppressor activity of ex vivo expanded bone fide Tregs.


Assuntos
Antígenos CD4 , Proliferação de Células , Tolerância Imunológica , Subunidade alfa de Receptor de Interleucina-2 , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Animais , Complexo CD3/biossíntese , Antígenos CD4/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Células Cultivadas , Células Clonais , Feminino , Imunofenotipagem , Interleucina-2/fisiologia , Subunidade alfa de Receptor de Interleucina-2/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/biossíntese , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo
16.
Minn Med ; 93(8): 39-44, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20862878

RESUMO

Prostate cancer is the second leading cause of cancer death among men. Because it has been thought that identifying the disease earlier leads to better outcomes, there has been a great deal of interest in screening for the disease. Since the late 1980s, testing for elevated prostate-specific antigen (PSA) levels in blood has been the most prominent screening tool. Despite widespread adoption of PSA testing, however, it remains controversial. It has been shown that elevated PSA levels do not always indicate cancer and low PSA levels do not ensure that cancer is absent. In addition, there has been conflicting evidence about whether definitive treatment of prostate cancer is always indicated. As a result of the conflicting evidence on the efficacy of PSA testing as a screening tool and the necessity of treatment of prostate cancer in all cases, national organizations have issued various guidelines for screening. Thus, the decision to screen or not to screen remains in the court of the individual patient and physician. This article reviews the current thinking about PSA testing, highlights relevant research findings, and discusses possible changes to screening and treatment that may appear in the near future.


Assuntos
Biomarcadores Tumorais/sangue , Programas de Rastreamento/tendências , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Minnesota , Valor Preditivo dos Testes , Neoplasias da Próstata/mortalidade , Taxa de Sobrevida
17.
Life Sci ; 260: 118428, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32931798

RESUMO

AIMS: The benefits of utilizing laboratory mice include low cost, ease of maintenance, and accessibility of molecular tools. However, the ages of experimental mice in the literature vary drastically. We hypothesized that there exists age-related variation in the murine small intestine across developmental stages. MATERIALS AND METHODS: Segments of small intestine were harvested from C57BL/6J mice of varying ages (E17 to 24 weeks; n = 3-4/group). Slides were analyzed for morphometric parameters, cell types, and crypt proliferation index (CPI). Secondary analysis comparing age-matched males and females (n = 4/group) was performed. Means were compared with Student's t-test and variance of proportions with the Chi-squared test to a significance of p < 0.05. KEY FINDINGS: There were small but significant differences including regional variation in villus height, which abolished when examining the small intestine as a whole. Sexually immature mice had increased CPI compared to mature animals. The most dramatic differences were seen in mice at weaning, which demonstrated shallower crypts, increased CPI, fewer Paneth and goblet cells, and more enterochromaffin cells. Examination of embryonic intestine revealed an underdeveloped mucosa lacking differentiated cells. There were minimal differences when comparing age-matched males and females. SIGNIFICANCE: Small, but statistically significant differences in villus height, crypt depth, and crypt proliferation are present in mice across early developmental stages. Mice at weaning exhibit variation in crypt-villus cell composition compared to older animals, which may explain the propensity for certain intestinal conditions in the very young. Investigators studying the GI mucosa should employ consistent age-matching in order to allow direct comparison between studies.


Assuntos
Mucosa Intestinal/citologia , Mucosa Intestinal/crescimento & desenvolvimento , Intestino Delgado/crescimento & desenvolvimento , Fatores Etários , Animais , Feminino , Mucosa Intestinal/embriologia , Intestino Delgado/citologia , Intestino Delgado/embriologia , Masculino , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura
18.
Semin Pediatr Surg ; 29(4): 150939, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32861443

RESUMO

Liver and biliary pathology in the neonate are rare and include a broad range of structural, neoplastic, infectious, genetic, and metabolic diseases. While most conditions present postnatally, antenatal detection is increasing given recent advances in antenatal imaging capabilities. In certain structural or obstructive liver diseases, antenatal detection now proves essential to help guide treatment and prevent morbidity. We review the epidemiology, pathophysiology, common antenatal diagnostic findings, and recommendations for surgical liver and biliary pathology in the neonate.


Assuntos
Doenças Biliares/diagnóstico , Doenças Fetais/diagnóstico , Doenças do Recém-Nascido/diagnóstico , Hepatopatias/diagnóstico , Diagnóstico Pré-Natal , Doenças Biliares/epidemiologia , Doenças Biliares/patologia , Doenças Biliares/terapia , Feminino , Doenças Fetais/epidemiologia , Doenças Fetais/patologia , Doenças Fetais/terapia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/patologia , Doenças do Recém-Nascido/terapia , Hepatopatias/epidemiologia , Hepatopatias/patologia , Hepatopatias/terapia , Gravidez
19.
J Surg Educ ; 77(3): 499-507, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31889695

RESUMO

OBJECTIVE: Physician burnout, including surgical trainees, is multidimensional. Input variables used to predict burnout include grit, exhaustion, and financial stress. Each instrument has intrinsic limitations of scope and strength. We hypothesize that bioinformatics methods borrowed from oncogenetics may allow meta-analysis of existing predictive tools to improve identification of subpopulations at highest risk of burnout. DESIGN: A composite survey was created using widely accepted instruments: demographic factors, burnout using the Single-Item Maslach Burnout Inventory Emotional Exhaustion Measure, grit using the Duckworth Grit Scale, occupational fatigue using the Occupational Fatigue Exhaustion/Recovery Scale, financial well-being, perceptions of physician leadership, and attitudes towards robotic surgery. Surveys were analyzed using k-means analysis and supervised/unsupervised clustering. SETTING: Yale General Surgery Residency. PARTICIPANTS: Survey participants consisted of Yale General Surgery residents. Of 70 residents, 53 responded (75.7%). Males comprised 57.1% and each postgraduate year had majority representation, 68.8% to 100%. RESULTS: Unsupervised hierarchical clustering showed heterogeneous resident answer patterns and suggested clusters of responders. To define groups of dissimilar responders, we performed k-means clustering, testing 15 iterations with 50 attempts. The analysis revealed 3 discrete clusters of responders with differential risk for burnout (p = 0.021). The highest risk group demonstrated the lowest grit score, low interest in innovation and leadership, higher financial stress, and concordantly, the highest rates of anxiety, dread, and self-reported burnout. (p = 0.0004; 0.0014; 0.1217; 0.0625; 0.021; 0.0011; 0.0224) CONCLUSIONS: The limited scope of common tools aiming to predict burnout constrains their utility. The machine-learning technique of cluster analysis organizes compound data to describe complex outcomes such as oncologic risks. We apply this analysis technique to create a composite predictor of burnout among surgical residents. Our method determines subgroups of residents sharing unique traits predictive of burnout. Residencies can use this tool to allocate resources to best support resident well-being.


Assuntos
Esgotamento Profissional , Internato e Residência , Médicos , Esgotamento Profissional/diagnóstico , Esgotamento Profissional/epidemiologia , Biologia Computacional , Feminino , Humanos , Masculino , Inquéritos e Questionários
20.
Int J Surg Case Rep ; 65: 349-353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31770712

RESUMO

INTRODUCTION: Anorectal malformations (ARM) in newborns classically present with the absence of a normal anus or an abnormally located anus. In a male infant with a high ARM, an initial diverting colostomy is later followed by a definitive posterior sagittal anorectoplasty (PSARP). Prior to definitive surgery an augmented-pressure colostogram is performed to identify the location of the fistula between the rectum and urogenital tract. However, on occasion, the augmented-pressure colostogram fails to identify the location of the fistula tract. We present a case of ARM where augmented-pressure colostogram failed to identify a fistula tract, thus requiring an alternative diagnostic approach. PRESENTATION OF CASE: A newborn male presented with a high anorectal malformation and suspected rectourinary fistula on initial augmented-pressure colostogram. The patient ultimately underwent a laparoscopic assisted PSARP after cystoscopy with air colostogram identified the exact location of the fistulous connection in the prostatic urethra. DISCUSSION: Augmented-pressure colostogram remains the gold standard in diagnosing rectourinary fistulae in cases of ARM. However, a number of alternative and adjunctive techniques have been proposed in recent years. We provide a brief review of the literature in addition to a case presentation highlighting the potential benefits of pre-operative cystoscopy-assisted air colostogram in male patients with ARM. CONCLUSION: Cystoscopy-assisted air colostogram via a distal mucous fistula can be utilized as an alternative diagnostic modality, especially when the augmented-pressure distal colostogram fails to identify rectourinary fistulae in high anorectal malformations.

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