Citations

Abstract Notch and its ligands have been implicated in the regulation and differentiation of various CD4+ T-helper cells. Regulatory T cells (Tregs), which express the transcription factor Foxp3, suppress aberrant immune responses that are typically associated with autoimmunity or excessive inflammation. Previous studies have shown that transforming growth factor beta (TGFβ1) induces Foxp3 expression and a regulatory phenotype in peripheral T cells. Here, we show that pharmacologic inhibition of Notch signaling using γ-secretase inhibitor (GSI) treatment blocks (1) TGFβ1-induced Foxp3 expression, (2) the up-regulation of Foxp3-target genes, and (3) the ability to suppress naive T-cell proliferation. In addition, the binding of Notch1, CSL, and Smad to conserved binding sites in the foxp3 promoter can be inhibited by treatment with GSI. Finally, in vivo administration of GSI results in reduced Foxp3 expression and development of symptoms consistent with autoimmune hepatitis, a disease previously found to result from dysregulation of TGFβ signaling and regulatory T cells. Together, these findings indicate that the Notch and TGFβ signaling pathways cooperatively regulate Foxp3 expression and regulatory T-cell maintenance both in vitro and in vivo.

Midline abdominal incisional hernias are common following open repair of abdominal aortic aneurysms. These may be caused by the weakness of connective tissue. This study sought to determine the prevalence of diastasis recti among unoperated Caucasian males with abdominal aortic aneurysm compared to a control group with atherosclerotic lower extremity peripheral arterial disease. Forty-two consecutive white males referred for evaluation of abdominal aortic aneurysm (n = 18) or peripheral arterial disease (n = 24) were examined by a single examiner at the Mayo Clinic. Both groups were similar in terms of age and smoking history, 2 major risk factors for both abdominal aortic aneurysm and peripheral arterial disease. Abdominal aortic aneurysm patients ranged in age from 59 to 89 (mean, 73.2) years. Seventeen of 18 (94.4%) had a history of smoking. Peripheral arterial disease patients ranged in age from 52 to 93 (mean, 70.8) years. Twenty-one of 24 (87.5%) had a history of smoking. Diastasis recti were present in 12 of 18 (66.7%) subjects with abdominal aortic aneurysm versus 4 of 24 (16.7%) subjects with peripheral arterial disease ( P = .001, 2-tailed Fisher exact test). Diastasis recti are significantly more common in males with abdominal aortic aneurysm than peripheral arterial disease and may provide an important clue to screen for abdominal aortic aneurysm in those at risk.

Study Design and SettingA two‐center prospective case series analysis.PatientsOne hundred fourteen patients with previously treated laryngeal or pharyngeal squamous cell carcinoma who underwent salvage transoral laser microsurgery (TLM).InterventionsTLM in 114 patients, neck dissection in 22 (19%) patients, adjuvant radiotherapy in 12 (11%) patients.ResultsNinety‐one (80%) patients had recurrent primary tumors whereas 23 (20%) patients had second primary tumors occur within a previously irradiated field. The minimum follow‐up was 1 year (median, 3 years). The distribution of tumor location was oropharynx 52 (46%), glottic and subglottic larynx 44 (39%), supraglottic larynx 11 (10%), and pyriform/hypopharynx 7 (6%). Overall, three‐year local and locoregional control estimates were 70 percent and 67 percent, respectively; and three‐year survival and disease‐free survival estimates were 62 percent and 64 percent, respectively. The average duration of hospitalization was 2.3 days. Four (3.5%) patients had significant postoperative bleeding. Two (<2%) patients had treatment‐related deaths.ConclusionsTransoral laser microsurgery offers select patients an attractive alternative salvage surgical therapy to the recurrent and second primary tumor site.

Abstract Base excision repair and nucleotide excision repair are vital responses to multiple types of DNA damage, including damage from tobacco exposure. Single-nucleotide polymorphisms (SNP) in these pathways may affect DNA repair capacity and therefore influence risk for cancer development. We performed a clinic-based, case-control study comprising 481 consecutive patients with confirmed pancreatic adenocarcinoma and 625 healthy controls. Allele and genotype frequencies for 16 SNPs in DNA repair genes ERCC1, XPD/ERCC2, XPC, XPF/ERCC4, OGG1, and XRCC1 were compared after adjusting for age, sex, and smoking history. Subgroup analysis by sex and smoking history was performed. Carriers of one or two XPF/ERCC4 minor alleles at R415Q had decreased risk of pancreatic adenocarcinoma compared with those who had two major alleles [odds ratio (OR), 0.59; 95% confidence interval (95% CI), 0.40–0.85]. Heavy smokers (&gt;40 pack-years) had increased risk for cancer if they were carriers of at least one minor allele for XPD/ERCC2 at D312N (OR, 2.78; 95% CI, 1.28–6.04) or D711D (OR, 2.19; 95% CI, 1.01–4.73). No other significant differences in risk were identified. Minor alleles in DNA repair genes XPF/ERCC4 and XPD/ERCC2 were associated with altered risk for pancreatic cancer. [Cancer Res 2008;68(12):4928–35]

This work presents a theory for the acoustic radiation force exerted on a solid sphere by an arbitrary spatially distributed beam. The theory is developed for an sphere suspended in an ideal fluid. We assume that the acoustic beam can be decomposed in a set of plane waves with same frequency, propagating in different directions. The sphere radius is considered to be much smaller than the wavelength of the beam. Bulk properties of the sphere such as shear and compressional sound speed are taken into account. The radiation force is obtained by solving the linear acoustic scattering problem for the sphere. Theoretically, the radiation force depends on the sphere cross section area, the radiation force function, and the vector energy flux upon the sphere. The radiation force function is related to the sphere scattering properties. We apply the developed theory to study the radiation force produced by an spherical concave transducer. The generated radiation force can be decomposed into two components, namely, axial and transverse with respect to the wave propagation direction. The ratio between the transverse and axial components of the force depends on the transducer F-number and wave frequency. Results show that this ratio for a 2 MHz transducer with 3.5 F-number on the focal plane is less than 5%.

ABSTRACT Introduction Sexual function through pregnancy and the postpartum period is an important aspect of quality of life. Despite this, prospective studies are limited, and the impact of body image on sexual function has not been explored. Aim To prospectively assess the effects of pregnancy on sexual function, and explore causative factors for sexual function alterations such as body image and pelvic floor symptoms. Materials and Methods Pregnant women completed the questionnaires in the first and third trimester and at 6 months postpartum. These included general information, questions regarding sexual activity and practices, and five validated indices: the Female Sexual Function Index (FSFI), the Body Exposure during Sexual Activities Questionnaire, short forms of Urogenital Distress Inventory and Incontinence Impact Questionnaire, and the Fecal Incontinence Quality of Life Scale. Main Outcome Measures An assessment of the FSFI domains through the 6 months postpartum and relationships between sexual function, body image, and pelvic floor symptoms. Results One hundred seven women were enrolled, 63 completed the final questionnaire. Sexual function declined through pregnancy and was not recovered by postpartum (P = 0.017); sexual frequency was highest prior to becoming pregnant (P &lt; 0.0005). Sexual practices changed during pregnancy but returned to early pregnancy levels in the postpartum period. Although body image during sexual functioning did not significantly change during pregnancy, it worsened in the postpartum period (P = 0.01). In early pregnancy, low sexual function was associated with impaired body image, while in the postpartum period, worse urinary symptoms correlated with poor FSFI. Conclusion Sexual function worsens during pregnancy and is not recovered by the 6 months postpartum; poor scores may be attributable to low body image and urinary complaints.