Sisters of Charity Hospital

The authors studied 439 postmenopausal breast cancer cases, identified in hospitals throughout western New York, with an interview schedule that considered frequency and amount ingested of 172 foods and provided data for an estimate of total calories ingested. These were compared with age-matched controls comprising a random sample of the same communities as the cases. The extensive interviews, requiring 2.0 hours on average to administer, also covered alcohol ingestion, Quetelet index, and a wide variety of reproductive factors. The authors found, as have most investigators over the past 25 years, that risk increased with increases in age at first pregnancy, decreased with increases in numbers of children and pregnancies, and increased in those with history of benign breast disease and in those with female relatives previously affected with breast cancer. Risk adjusted for potential confounders was highest among women with the lowest ingestion of carotene or a substance correlated with its ingestion. Risk was not associated with retinol ingestion. It increased with increases in Quetelet index. Fat intake, whether studied in terms of quantity or the proportion of total calories derived from fat, was not associated with risk of breast cancer. Our analyses of these factors were adjusted for age, education, and the reproductive history traits described above.

The 70-gene signature (MammaPrint™) has been developed on retrospective series of breast cancer patients to predict the risk of breast cancer distant metastases. The microarRAy-prognoSTics-in-breast-cancER (RASTER) study was the first study designed to prospectively evaluate the performance of the 70-gene signature, which result was available for 427 patients (cT1-3N0M0). Adjuvant systemic treatment decisions were based on the Dutch CBO 2004 guidelines, the 70-gene signature and doctors' and patients' preferences. Five-year distant-recurrence-free-interval (DRFI) probabilities were compared between subgroups based on the 70-gene signature and Adjuvant! Online (AOL) (10-year survival probability <90% was defined as high-risk). Median follow-up was 61.6 months. Fifteen percent (33/219) of the 70-gene signature low-risk patients received adjuvant chemotherapy (ACT) versus 81% (169/208) of the 70-gene signature high-risk patients. The 5-year DRFI probabilities for 70-gene signature low-risk (n = 219) and high-risk (n = 208) patients were 97.0% and 91.7%. The 5-year DRFI probabilities for AOL low-risk (n = 132) and high-risk (n = 295) patients were 96.7% and 93.4%. For 70-gene signature low-risk-AOL high-risk patients (n = 124), of whom 76% (n = 94) had not received ACT, 5-year DRFI was 98.4%. In the AOL high-risk group, 32% (94/295) less patients would be eligible to receive ACT if the 70-gene signature was used. In this prospective community-based observational study, the 5-year DRFI probabilities confirmed the additional prognostic value of the 70-gene signature to clinicopathological risk estimations such as AOL. Omission of adjuvant chemotherapy as judged appropriate by doctors and patients and instigated by a low-risk 70-gene signature result, appeared not to compromise outcome.

IMPORTANCE: Full-term neonates born between 37 and 41 weeks' gestational age have been considered a homogeneous, low-risk group. However, recent evidence from studies based on mode of delivery has pointed toward increased morbidity associated with early-term cesarean section births (37-38 weeks) compared with term neonates (39-41 weeks). OBJECTIVE: To compare the short-term morbidity of early-term vs term neonates in a county-based birth cohort using the primary objective of admission to a neonatal intensive care unit (NICU) or neonatology service. DESIGN, SETTING, AND PARTICIPANTS: Retrospective population-based 3-year birth cohort study (January 1, 2006-December 31, 2008) at all major birth hospitals in Erie County, New York. All full-term live births comprised the birth cohort; this information was obtained from the hospitals' perinatal databases, and data pertaining to NICU or neonatology service admissions were extracted from individual medical records. EXPOSURE: Gestational age of early term (37(0/7)-38(6/7) weeks) vs term (39(0/7)-41(0/7) weeks). MAIN OUTCOMES AND MEASURES: Admission to the NICU or neonatology service. RESULTS: There were 33,488 live births during the 3-year period, of which 29,741 had a gestational age between 37 and 41 weeks. Of all live births, 9031 (27.0%) were early term. Compared with term infants, early-term neonates had significantly higher risks for the following: hypoglycemia (4.9% vs 2.5%; adjusted odds ratio [OR], 1.92), NICU or neonatology service admission (8.8% vs 5.3%; adjusted OR, 1.64), need for respiratory support (2.0% vs 1.1%; adjusted OR, 1.93), requirement for intravenous fluids (7.5% vs 4.4%; adjusted OR, 1.68), treatment with intravenous antibiotics (2.6% vs 1.6%; adjusted OR, 1.62), and mechanical ventilation or intubation (0.6% vs 0.1%; adjusted OR, 4.57). Delivery by cesarean section was common among early-term births (38.4%) and increased the risk for NICU or neonatology service admission (12.2%) and morbidity (7.5%) compared with term births. Among vaginal deliveries, early-term neonates (6.8%) had a significantly higher rate of NICU or neonatology service admission compared with term neonates (4.4%). CONCLUSIONS AND RELEVANCE: Early-term births are associated with high neonatal morbidity and with NICU or neonatology service admission. Evaluation of local prevalence data will assist in implementation of specific preventive measures and plans, as well as prioritize limited health care resources.

BACKGROUND AND PURPOSE: Transcarotid artery revascularization (TCAR) is comprised of carotid artery stent placement with cerebral protection via proximal carotid artery clamping and reversal of cerebral arterial flow. The aim of the present study was to evaluate the safety and efficacy of TCAR performed by a broad group of physicians with variable TCAR experience. METHODS: The ROADSTER 2 study is a prospective, open label, single arm, multicenter, postapproval registry for patients undergoing TCAR. Patients considered at high risk for complications from carotid endarterectomy with symptomatic stenosis ≥50% or asymptomatic stenosis ≥80% were included. The primary end point was procedural success, which encompassed technical success plus the absence of stroke, myocardial infarction, or death within the 30-day postoperative period. Secondary end points included technical success and individual/composite rates of stroke, death, and myocardial infarction (MI). All patients underwent independent neurological assessments before the procedure, within 24 hours, and at 30 days after TCAR. An independent clinical events committee adjudicated all major adverse events. RESULTS: Between 2015 and 2019, 692 patients (Intent to Treat Population) were enrolled at 43 sites. Sixty cases had major protocol violations, leaving 632 patients adhering to the Food and Drug Administration-approved protocol (per-protocol population). The majority (81.2%) of operators were TCAR naïve before study initiation. Patients underwent TCAR for neurological symptoms in 26% of cases, and all patients had high-risk factors for carotid endarterectomy (anatomic-related 44%; physiological 32%; both 24%). Technical success occurred in 99.7% of all cases. The primary end point of procedural success rate in the Intent to Treat population was 96.5% (per-protocol 97.9%). The early postoperative outcomes in the Intent to Treat population included stroke in 13 patients (1.9%), death in 3 patients (0.4%), and MI in 6 patients (0.9%). The composite 30-day stroke/death rate was 2.3%, and stroke/death/MI rate was 3.2%. In the per-protocol population, there were strokes in 4 patients (0.6%), death in one patient (0.2%), and MI in 6 patients (0.9%) leading to a composite 30-day stroke/death rate of 0.8% and stroke/death/MI rate of 1.7%. CONCLUSIONS: TCAR results in excellent early outcomes with high technical success combined with low rates of postprocedure stroke and death. These results were achieved by a majority of operators new to this technology at the start of the trial. Adherence to the study protocol and peri-procedural antiplatelet therapy optimizes outcomes. Longer-term follow-up data are needed to confirm these early outcomes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02536378.

AIMS: The aim of this study was to determine whether intermittent ambulatory treatment with levosimendan would improve functional capacity, quality of life, and event-free survival in patients with advanced heart failure. METHODS AND RESULTS: This was a prospective, randomized, double-blind, placebo-controlled, multicentre, parallel-group trial of pulsed infusions of levosimendan in 120 outpatients with advanced heart failure (EF ≤35%, NYHA class III or IV). The study was conducted at 11 centres in Austria, Greece, and Germany. Levosimendan (0.2 µg/kg/min) or placebo was administered for 6 h at 2-week intervals over 6 weeks, in addition to standard care therapy. The primary outcome was the proportion of patients with a ≥20% improvement in the 6 min walk test and a ≥15% score increase on the Kansas City Cardiomyopathy Questionnaire at the end of the 24-week study period. Secondary outcomes included event-free survival after 24 weeks. Analyses were performed on an intention-to-treat basis. The primary endpoint was reached in 19% of patients receiving levosimendan and 15.8% of patients receiving placebo (odds ratio 1.25; 95% confidence interval 0.44-3.59; P = 0.810). Cardiac death (four vs. one), heart transplants (two vs. one), and acute heart failure (14 vs. nine) were more frequent with placebo as compared with levosimendan. The incidence of side effects was comparable between groups. CONCLUSION: Intermittent ambulatory treatment with levosimendan in patients with advanced heart failure did not improve significantly functional capacity or quality of life as compared with placebo. An adequately powered, event-driven trial is warranted to enlarge on our findings. TRIAL REGISTRATION: NCT01065194.

During a 1-year period, 7620 elective surgical admissions were given multiple laboratory screening (SMA-18) determinations. Of these, 11 healthy patients, aged 10 to 54, with a pretest classification of ASA 1 (no systemic disease) were found to have clearly abnormal elevations of the SGOT, SGPT, and LDH levels. The proposed elective surgical procedures and anesthesia were canceled. All 11 patients proved to have overt liver pathology by further testing, and 3 later became clinically jaundiced. No cases of unexplained postsurgical jaundice occurred in any of the other 7609 operated cases during the 1-year study. The incidence of clearly elevated enzyme levels in voluntary hospital surgical admissions is approximately 1/700 and the incidence of clinical jaundice is approximately 1/2540. There appears to be a seasonal variation, with the preponderance of elevated enzyme levels in the winter and spring months.

BACKGROUND: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. METHODS: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers’ discretion. RESULTS: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P &amp;lt; .0001). Respiratory outcomes up to 28 days of age were no different. CONCLUSIONS: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.

Hyperbaric oxygen has been advocated, both as an adjunctive or primary form of treatment, for a variety of disorders, including gas gangrene, osteoradionecrosis, and carbon monoxide poisoning. It has also been used to improve ischemic wounds before skin grafting and to support ischemic flaps. In this review, we analyze the available literature that investigates the use of hyperbaric oxygen for composite grafts, skin grafts, random flaps, distant flaps, and free flaps. An appraisal of the level of evidence for each of these uses of hyperbaric oxygen is offered. Although there are a significant amount of animal data supporting the application of hyperbaric oxygen for grafts and flaps, there is very little clinical information other than case reports and series to sustain its choice over other modalities of therapy. Multicenter prospective clinical studies are clearly needed comparing hyperbaric oxygen to other mechanical or pharmacologic interventions to improve wound healing for grafting or to support flap survival.

Olfactory neuroblastoma is a malignant neoplasm with a varied biological behavior. Its clinical course is unpredictable and there is no correlation between its microscopic features and biological behavior. The present study deals with light and ultrastructural characteristics of two cases of olfactory neuroblastoma of the nasal cavity. In one patient, the definitive diagnosis was established on the basis of ultrastructural features of the lesion. The most consistent fine structural findings were the presence of intracytoplasmic densecored neurosecretory granules, "true" and "pseudo-" rosettes, and the neuritic processes emanating from the tumor cells. On the basis of their biochemical, histochemical, and ultrastructural characteristics, olfactory neuroblastomas are similar to neuroblastomas arising from the adrenals or sympathetic nervous system. These findings, therefore, support the hypothesis that olfactory neuroblastomas are most likely of neural crest origin and thus belong to a group of neoplasms collectively known as "apudomas" or neurocristomas. The literature review strongly favors combined surgery and postradiation as the most effective treatment of olfactory neuroblastoma.

Relapse after stem cell transplantation for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remains a significant challenge. In this systematic review, we compare survival outcomes of second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib with first-generation TKI imatinib when these agents are used after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Ph+ ALL. In addition, we review the literature on TKI use to prevent relapse in patients who proceed to allo-HSCT beyond first complete response (>CR1). We performed database searches (inception to January 2018) using PubMed, Cochrane Library, and Embase. After exclusions, 17 articles were included in this analysis. Imatinib was used post-transplant either prophylactically or preemptively in 12 studies, 7 prospective studies and 5 retrospective studies. Overall survival (OS) for most prospective studies at 1.5 to 3 and 5 years ranged between 62% to 92% and 74.5% to 86.7%. Disease-free survival at 1.5 to 5 years was 60.4% to 92%. Additionally, imatinib failed to show survival benefit in patients who were >CR1 at the time of allo-HSCT. The cumulative OS for most retrospective studies using imatinib at 1 to 2 and 3 to 5 years was 42% to 100% and 33% to 40% respectively. Event-free survival at 1 to 2 and 3 to 5 years was 33.3% to 67% and 20% to 31% respectively. Dasatinib was used as maintenance treatment in 3 retrospective studies (n = 34). The OS for patients with Ph+ ALL using dasatinib as maintenance regimen after allo-HSCT at 1.4 to 3 years was 87% to 100% and disease-free survival at 1.4 to 3 years was 89% to 100%. Ninety-three percent of patients with minimal residual disease (MRD) positive status after allo-HSCT became MRD negative. Three prospective studies used nilotinib. In 2 studies where investigators studied patients with advanced chronic myeloid leukemia and Ph+ ALL, the cumulative OS and event-free survival at 7.5 months to 2 years were 69% to 84% and 56% to 84%, respectively. In the third study (n = 5) in patients with Ph+ ALL, nilotinib use resulted in OS at 5 years of 60%. Our review showed that use of TKIs (all generations) after allo-HSCT for patients in CR1 improved OS when given as a prophylactic or preemptive regimen. Limited data suggest that second-generation TKIs (ie, dasatinib) have a better OS, especially in patients with MRD-positive status. Imatinib did not improve OS in patients who were >CR1 at the time of allo-HSCT; for this population, no data were available with newer generation TKIs. The evaluation of survival benefit with newer generation TKIs and their efficacy in patients in >CR1 needs further study in large randomized clinical trials.

A total of 283 epithelial ovarian cancer families from the United Kingdom (UK) and the United States (US) were screened for coding sequence changes and large genomic alterations (rearrangements and deletions) in the BRCA1 and BRCA2 genes. Deleterious BRCA1 mutations were identified in 104 families (37%) and BRCA2 mutations in 25 families (9%). Of the 104 BRCA1 mutations, 12 were large genomic alterations; thus this type of change represented 12% of all BRCA1 mutations. Six families carried a previously described exon 13 duplication, known to be a UK founder mutation. The remaining six BRCA1 genomic alterations were previously unreported and comprised five deletions and an amplification of exon 15. One of the 25 BRCA2 mutations identified was a large genomic deletion of exons 19-20. The prevalence of BRCA1/2 mutations correlated with the extent of ovarian and breast cancer in families. Of 37 families containing more than two ovarian cancer cases and at least one breast cancer case with diagnosis at less than 60 years of age, 30 (81%) had a BRCA1/2 mutation. The mutation prevalence was appreciably less in families without breast cancer; mutations were found in only 38 out of 141 families (27%) containing two ovarian cancer cases only, and in 37 out of 59 families (63%) containing three or more ovarian cancer cases. These data indicate that BRCA1 and BRCA2 are the major susceptibility genes for ovarian cancer but that other susceptibility genes may exist. Finally, it is likely that these data will be of clinical importance for individuals in families with a history of epithelial ovarian cancer, in providing accurate estimates of their disease risks.

Studies of the histopathology of ovarian cancer arising in patients with germline mutations in BRCA1 or BRCA2 have shown inconsistent findings. We analyzed the large number of tumors from women enrolled in the Gilda Radner Familial Ovarian Cancer Registry for correlations between histopathology and BRCA mutation status. Histopathology slides and reports were reviewed for histology, grade, and stage for cancers of the ovary or peritoneum in 220 women from 126 Gilda Radner Familial Ovarian Cancer Registry families. At least one affected member of each family was analyzed for mutations in the BRCA1 and BRCA2 genes, and tumors from mutation-positive families were compared with those from mutation-negative families. Of 70 patients from 38 BRCA1-positive families, 69 had epithelial ovarian carcinoma and one had a dysgerminoma. Fifteen of 16 patients from nine BRCA2-positive families had epithelial ovarian cancer, and one had a primary peritoneal cancer. Of 134 patients from 79 BRCA-negative families, 118 had epithelial ovarian carcinoma, 11 had ovarian borderline tumors, three had nonepithelial tumors, and two had primary peritoneal carcinoma. There were fewer grade 1 (p < 0.001) and stage I (p = 0.005) cancers in patients from BRCA-positive families than in patients from BRCA-negative families. Neither mucinous nor borderline tumors were found in the BRCA-positive families. In conclusion, ovarian cancers arising in women from BRCA-positive families are more likely to be high-grade and have extraovarian spread than tumors arising in women from BRCA-negative families. Borderline and mucinous tumors do not appear to be part of the phenotype of families with germline mutations in the BRCA genes.

BACKGROUND: The two-hit hypothesis for the genesis of cancer predicts that cancer can develop when the wild-type allele of a tumor suppressor gene is lost in an individual with a germline mutation in that gene. Neither loss of heterozygosity (LOH) for BRCA1 nor mutations of the TP53 (also known as p53) gene have been documented prior to invasion in ovarian cancers arising in women with germline BRCA1 mutations. Such documentation is difficult because lesions are rarely identified in ovarian epithelium. We, therefore, looked for LOH at microsatellite polymorphisms linked to the BRCA1 and TP53 tumor suppressor loci in an incidental carcinoma in situ of the ovary removed prophylactically from a woman with a germline BRCA1 mutation. METHODS: By use of laser-capture microdissection, we obtained pure populations of atypical ovarian epithelial cells and normal stromal cells. DNA was extracted, amplified with primers flanking polymorphic microsatellites linked to BRCA1 (D17S855 and D17S579) and TP53 (TP53 and D17S786), and analyzed for LOH at these microsatellites. We also tested for p53 expression in the abnormal epithelium by immunohistochemistry. RESULTS: Both of the markers linked to TP53 showed LOH, as did an intragenic BRCA1-linked marker (D17S855). The other microsatellite marker for BRCA1 was uninformative. Immunohistochemical staining with an antibody to p53 showed strong immunoreactivity confined to the atypical epithelium. CONCLUSIONS: BRCA1, as well as TP53, can undergo LOH prior to stromal invasion in BRCA1-associated ovarian cancer. Strong immunoreactivity for p53 suggests the presence of mutated p53 in these cells as well. These findings suggest that loss of function of these two tumor suppressor genes occurs early in ovarian carcinogenesis in BRCA1 mutation carriers.

Abstract From 1957 through 1977, a total of 714 patients with malignant melanoma were treated by chemotherapy administered by isolated regional perfusion of the limbs, and 56 patients were treated by intra‐arterial infusion . Excisional surgery and adjunctive perfusion in 286 patients with stage I disease resulted in cumulative survival rates of 87% at 5 years and 75% at 10 and 15 years. With recurrent or metastatic regional disease treated by perfusion alone or in combination with surgical excision, the survival rates were 36%, 34%, and 31% at 5, 10, and 15 years, respectively. Even in the least favorable group, those with nodal and soft tissue involvement, the survival rates were 27% at 5 years and 22.5% at 10 and 15 years. Analysis of 121 patients with stage I melanoma according to level of dermal invasion showed recurrence in 2 of 42 (4%) patients with level III lesions, 11 of 75 (15%) with level IV tumors, and 2 of 4 (50%) with level V lesions. Recurrence rates by pathologic type were 2 of 49 (4%) patients with superficial spreading melanoma, 6 of 30 (20%) with nodular melanoma, and 5 of 14 (36%) with acral lentiginous melanoma, the latter including subungual, plantar, or palmar lesions . Chemotherapy by intra‐arterial infusion is a technique useful in treating regional disease not amenable to isolation‐perfusion. Of 36 patients having measurable lesions, there were 4 complete responses. Objective responses occurred in 50–80% of patients treated, depending on the agent used . As an adjunct to surgical treatment, chemotherapy by isolation‐perfusion offers improved survival rates without prolonged treatment or the risks associated with systemic chemotherapy. As primary therapy for advanced regional disease, chemotherapy by perfusion produces survival rates superior to those obtained by surgery alone or systemic chemotherapy .

In the past 3 years, five patients with lung carcinoma were found to have enlarged adrenal glands without any evidence of distant metastasis. The patients were treated with adrenalectomy. The cases are presented in order to discuss optimal methods of diagnosis and treatment for this condition.

BACKGROUND: The purpose of this study was to evaluate socio-demographic characteristics of clients claiming genetic counseling for hereditary breast and ovarian cancer (HBOC) in Austria. Furthermore, changes of these parameters before and after Angelina Jolie's (AJ) disclosure of carrying a BRCA mutation were evaluated. METHODS: In this prospective, nonrandomized study 268 consecutive clients seeking genetic counseling for HBOC at the Medical University of Vienna, Department of Obstetrics and Gynecology, Vienna, Austria between June 2012 and June 2014 were included. Socio-demographic data and source of information about HBOC and genetic counseling were evaluated. First, socio-demographic parameters were compared to the general Austrian population. Second, changes in these parameters after AJ's public disclosure of carrying a BRCA mutation were analyzed. RESULTS: Subjects were more frequent female, younger and higher educated in comparison to Austria's general population (p < 0.001). Furthermore, level of education in participants was higher before than after AJ's disclosure (p = 0.046). Most clients were informed about genetic counseling by physicians. As expected, after AJ's public announcement patients were more frequent advised to genetic counseling by social media (p = 0.043) and family or friends (p = 0.010) than before. CONCLUSIONS: In this present study we could demonstrate that particularly younger and female participants with high educational level attended significantly more often genetic counseling for HBOC. Increased presence of HBOC in media since AJ's disclosure of carrying a BRCA mutation had lead that information and awareness about HBOC was obtained by a wider audience from different social background.

Metastatic involvement of the gallbladder in melanoma is rare, but constitutes the most common metastatic lesion involving this organ. Two cases of metastatic melanoma to the gallbladder with radiographic evidence of gallbladder abnormality prior to surgery are presented. These cases are compared to the nine previously reported cases of metastatic melanoma to the gallbladder with abnormal cholecystograms. All eleven cases presented with signs and symptoms compatible with cholecystitis. Nine of the eleven patients had a previous melanoma primary and most had other extrabiliary metastases. Associated cholelithiasis appeared to be only incidental. In addition, nine reported cases of "primary" biliary melanoma were reviewed. Clinical and pathologic presentations in the latter cases were similar to the former cases with metastases. Seventy-eight percent had extrabiliary sites of metastasis at some time in the course of their disease, tending to refute the impression of "primary" biliary melanoma. Melanoma in the gallbladder is much more likely to have metastasized from a regressed skin primary than to have arisen de novo. The two reported cases and the 18 cases from the literature indicate that the physician must consider gallbladder metastasis in melanoma patients presenting with symptoms compatible with cholecystitis.

Bioterrorism is an emerging public health and infection control threat. Potential biological agents include smallpox, anthrax, plague, tularemia, botulinum toxin, brucellosis, Q fever, viral encephalitis, hemorrhagic fever, and staphylococcal enterotoxin B. An understanding of the epidemiology, clinical manifestations, and management of the more likely candidate agents is critical to limiting morbidity and mortality from a biological event. Effective response requires an increased index of suspicion for unusual diseases or syndromes, with prompt reporting to health authorities to facilitate recognition of an outbreak and subsequent intervention. Hospital epidemiology programs will play a crucial role in this effort.

Several hypotheses exist for the etiology of decubitus ulcers, with external pressures exceeding internal capillary pressures over bony prominences claimed to be the major factor. This investigation evaluated the mechanical changes that occurred in human skin as a result of its exposure to static versus cyclic normal pressures of the magnitudes earlier recorded for the heels of human subjects on various support surfaces. The skin was characterized through uniaxial tensile testing. Static pressure alone altered the tissue's mechanical properties more than dynamic pressure cycles. Tissue subjected to pressure prior to uniaxial tensile testing always was less stiff than control tissue. Damage to the initially randomly oriented tissue collagen fiber bundles in the fibrous matrix, which may occur as a result of sustained compression, may be the cause of a decrease in stiffness of tissue subjected to prior pressure loading. This is the first report of compressive-pre-load-induced strain softening (Mullins effect) of a biological material.

OBJECTIVE: Obesity and type 2 diabetes are associated with an increase in the incidence and prevalence of Alzheimer's disease (AD) and an impaired cognitive function. Because peripheral blood mononuclear cells (MNC) express amyloid precursor protein (APP), the precursor of β-amyloid, which forms the pathognomonic plaques in the brain, we hypothesized that APP expression diminishes after the marked caloric restriction and weight loss associated with Roux-en-Y gastric bypass (RYGB) surgery. RESEARCH DESIGN AND METHODS: Fifteen type 2 diabetic patients with morbid obesity (body mass index, 52.1 ± 13 kg/m(2)) underwent RYGB, and the expression of inflammatory and AD-related genes was examined before and after 6 months in plasma and in MNC. RESULTS: Body mass index fell to 40.4 ± 11.1 kg/m(2) at 6 months after RYGB. There was a significant fall in plasma concentrations of glucose and insulin and in homeostasis model of assessment for insulin resistance. The expression of APP mRNA fell by 31 ± 9%, and that of protein fell by 36 ± 14%. In addition, there was a reduction in the expression of other AD-related genes including presinilin-2, ADAM-9, GSK-3β, PICALM, SORL-1, and clusterin (P < 0.05 for all). Additionally, the expression of c-Fos, a subunit of the proinflammatory transcription factor AP-1, was also suppressed after RYGB. These changes occurred in parallel with reductions in other proinflammatory mediators including C-reactive protein and monocyte chemoattractant protein-1. CONCLUSIONS: Thus, the reversal of the proinflammatory state of obesity is associated with a concomitant reduction in the expression of APP and other AD-related genes in MNC. We conclude that obesity and caloric intake modulate the expression of APP in MNC. If indeed, this effect also occurs in the brain, this may have implications for the pathogenesis and the treatment of AD. It is relevant that cognitive function has been shown to improve with weight loss following bariatric surgery.