Patient-reported outcomes and inflammatory biomarkers in patients with locally advanced/metastatic urothelial carcinoma treated with durvalumab in phase 1/2 dose-escalation study 1108.

BACKGROUND: Durvalumab has shown meaningful clinical activity in patients with metastatic urothelial carcinoma (mUC) in Study 1108 (NCT01693562). An important focus in treatment is health-related quality of life (HRQOL). Here, patient-reported outcomes (PROs) from Study 1108 and their relationship with inflammatory biomarkers are explored. METHODS: Disease-related symptoms, functioning, and HRQOL were assessed with the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). Relationships between PRO improvements and the best changes in the tumor size, albumin level, and neutrophil-lymphocyte ratio (NLR) were assessed with Spearman correlation analysis. RESULTS: The mean FACT-Bl total score improved from 107.5 (standard deviation [SD], 23.0) at the baseline to 115.4 (SD, 22.6) on day 113, with similar increases found for the Trial Outcome Index (TOI) and Bladder Cancer Subscale (BLCS) scores. The mean FACT-Bl total scores improved over time, and the FACT-Bl TOI scores significantly improved by day 113 (P < .05). The mean EORTC QLQ-C30 Global Health Status/Quality of Life score improved from 57.1 (SD, 24.8) at the baseline to 69.0 (SD, 21.4) on day 113; the functional scale and symptom scores (day 113) were higher than the baseline scores (P < .05) for EORTC Social Functioning. The FACT-Bl total, BLCS, and TOI scores improved in 32.6%, 34.9%, and 32.6% of the patients by day 113; 26.3% to 37.8% of the patients exhibited improvements in EORTC QLQ-C30 functional scores. The best tumor shrinkage and posttreatment improvements in serum albumin and NLR correlated with increases in FACT-Bl total, TOI, and BLCS scores and in EORTC Physical Functioning and Role Functioning scores (P < .05). CONCLUSIONS: Durvalumab was associated with improvements in disease-related symptoms, functioning, and HRQOL in patients with mUC. Improvements in systemic inflammation may contribute to PRO improvements in these patients.

Plasmonic Skyrmion Lattice Based on the Magnetoelectric Effect.

The physical mechanism of the plasmonic skyrmion lattice formation in a magnetic layer deposited on a metallic substrate is studied theoretically. The optical lattice is the essence of the standing interference pattern of the surface plasmon polaritons created through coherent or incoherent laser sources. The nodal points of the interference pattern play the role of lattice sites where skyrmions are confined. The confinement appears as a result of the magnetoelectric effect and the electric field associated with the plasmon waves. The proposed model is applicable to yttrium iron garnet and single-phase multiferroics and combines plasmonics and skyrmionics.

Efficacy of compositing with snail meat powder on protein nutritional quality of sorghum-wheat buns using a rat bioassay.

BACKGROUND: Protein energy malnutrition (PEM) is an important health burden in most developing countries mainly in sub-Saharan Africa, where it contributes to high rates of child morbidity and mortality. This study evaluated the efficacy of compositing with snail meat powder (SMP) on protein nutritional quality of sorghum-wheat buns using a rat bioassay. Nine diets -seven isonitrogenous diets, based on six variations of buns and a reference diet made using skimmed milk powder, in addition to the basal diet meant to estimate the endogenous nitrogen excretion and a 16% protein rehabilitation diet - were fed to male weanling albino rats. Protein efficiency ratio (PER), and food efficiency ratio (FER), net protein retention ratio (NPRR), apparent protein digestibility (APD), and true protein digestibility (TPD), protein digestibility corrected amino acid score (PDCAAS), and digestible indispensable amino acid score (DIAAS) indices of protein quality were determined. RESULTS: Fortification with SMP significantly (P < 0.05) enhanced PER from 0.21% to 2.70%, FER from 0.02% to 0.27%, APD from 81.17% to 88.28%, and TPD from 87.48% to 95.38%. PDCAAS and DIAAS increased from 45% to 78% and 44% to 69% respectively in unfortified buns to buns fortified with 25% SMP. CONCLUSION: Complementary diets fortified with SMP promote growth and rehabilitate emaciated rats, whereas unfortified diet did not support weight gain. Thus, supplementation of buns with SMP might enhance a faster recovery in children affected by PEM. © 2020 Society of Chemical Industry.

[Prevention of cardiovascular diseases]. / Prävention von Herz-Kreislauf-Erkrankungen.

The incidence of cardiovascular diseases can be reduced by the early detection and targeted treatment of risk factors and subclinical forms of the disease. Primary prevention provides several opportunities for successful interventions. In addition to a drug-based therapy, especially life style-modifying measures, such as physical activity, normalization of body weight, consistent nicotine abstinence and the consideration of psychosocial aspects represent core components of prevention programs. Healthcare data indicate that risk factors still often remain undetected and that the full potential of risk factor management has not yet been fully exploited at a population level. Especially motivation of patients and adherence to therapy represent key elements of successful prevention efforts.

Metabolomic analyses to evaluate the effect of drought stress on selected African Eggplant accessions.

BACKGROUND: Drought stress is one of the main abiotic stresses that affect crops. It leads to biochemical changes that can have adverse effects on plant growth, development and productivity. African eggplants are important vegetable and fruit crops reported to adapt and thrive well under drought stress. The diversified metabolites arising due to stress have not been well defined. A gas chromatographic-mass spectrometric metabolomic approach was applied to characterize the effect of drought stress on metabolites at different stages of growth. Nineteen accessions were selected for analysis and drought was imposed by withholding water until soil moisture reached 60% field capacity. Fresh leaf tissues were sampled before stress, 2 and 4 weeks after stress and metabolite profiling done. RESULTS: Significant changes in metabolite content were observed, and potentially important metabolites with respect to stress responses were characterized. Proline, glutamate, sucrose, fructose and tricarboxylic acid cycle metabolites were shown to be positively correlated with stress. Principal component analysis showed a clear discrimination between the different accessions, growth stages and stress/control conditions. CONCLUSION: The results illustrate that drought stress has a significant impact on the concentrations of some metabolites, such as amino acids, sugars and organic acids, which may contribute to drought stress effects and tolerance. © 2017 Society of Chemical Industry.

Herpes zoster and the search for an effective vaccine.

Primary infection with varicella zoster virus (VZV), an exclusively human neurotrophic alphaherpsesvirus, results in varicella, known more commonly as chickenpox. Like other alphaherpesviruses, VZV establishes latency in the sensory ganglia and can reactivate to cause herpes zoster (also known as shingles), a painful and debilitating disease, especially in elderly and immunocompromised individuals. The overall incidence of herpes zoster in Europe and the United States is three per 1000 people, but increases sharply after 60 years of age to 10 per 1000 people. Zostavax® is a vaccine approved by the Federal Drug Administration for the prevention of herpes zoster. Unfortunately, this vaccine reduces the incidence of disease by only 51% and the incidence of post-herpetic neuralgia by 66·5% when administered to those aged 60 and older. Moreover, it is contraindicated for individuals who are immunocompromised or receiving immunosuppressant treatments, although they are at higher risk for herpes zoster compared to immune-competent older individuals. This paper reviews VZV pathogenesis, host responses and current vaccines available to prevent herpes zoster.

Salivary, gingival crevicular fluid and serum levels of ghrelin and chemerin in patients with periodontitis and overweight.

BACKGROUND AND OBJECTIVE: Nutrition and body weight are modifying factors for periodontitis. The purpose of this study was to quantify two molecules (ghrelin and chemerin), released in association with food intake and obesity, in periodontally healthy and diseased individuals with respect to different body mass categories. MATERIAL AND METHODS: The two main groups (patients with chronic periodontitis and periodontally healthy/gingivitis volunteers) were subdivided into groups of subjects with normal weight [body mass index (BMI) <25] and groups of overweight/obese subjects (BMI ≥25). Subgingival bacteria were analysed and the levels of acylated and total ghrelin, chemerin and interleukin-1ß (IL-1ß) were assessed in saliva, gingival crevicular fluid and serum. RESULTS: The amount of Treponema denticola present subgingivally was significantly higher in the groups of patients with chronic periodontitis as well as in periodontally healthy/gingivitis individuals with BMI ≥25 than in periodontally healthy/gingivitis individuals with BMI <25. The amount of total ghrelin in gingival crevicular fluid differed significantly between the groups, with the lowest levels found in the group of patients with chronic periodontitis and BMI ≥25. The levels of chemerin in gingival crevicular fluid were significantly higher in each chronic periodontitis group than in periodontally healthy/gingivitis individuals with BMI <25. However, the level of IL-1ß in the gingival crevicular fluid was most differentiating between the groups, with the highest levels found in the group of patients with chronic periodontitis and BMI <25 and the lowest levels in periodontally healthy/gingivitis individuals with BMI <25. No significant differences between any groups were seen for chemerin or for acylated ghrelin in the stimulated whole saliva, or for acylated and total ghrelin in peripheral blood serum. The BMI correlated with the serum level of chemerin. CONCLUSION: Low ghrelin and high chemerin levels in the gingival crevicular fluid might be linked to periodontal disease and overweight/obesity. However, unlike IL-1ß, the levels of chemerin and ghrelin in gingival crevicular fluid are not reliable indicators of periodontal destruction.

Ethnobotany, chemical constituents and biological activities of the flowers of Hydnora abyssinica A.Br. (Hydnoraceae).

Hydnora abyssinica A.Br. (Hydnoraceae), a holoparasitic herb, is for the first time recorded for Abyan governorate of South Yemen. Flowers of this species were studied for their ethnobotanical, biological and chemical properties for the first time. In South Yemen, they are traditionally used as wild food and to cure stomach diseases, gastric ulcer and cancer. Phytochemical analysis of the extracts showed the presence of terpenes, tannins, phenols, and flavonoids. The volatile components of the air-dried powdered flowers were identified using a static headspace GC/MS analysis as acetic acid, ethyl acetate, sabinene, α-terpinene, (+)-D-limonene and γ-terpinene. These volatile compounds that characterize the odor and taste of the flowers were detected for the first time in a species of the family Hydnoraceae. The flowers were extracted by n-hexane, dichlormethane, ethyl acetate, ethanol, methanol and water. With exception of the water extract all extracts demonstrated activities against Gram-positive bacteria as well as remarkable radical scavenging activities in DPPH assay. Ethyl acetate, methanol and water extracts exhibited good antifungal activities. The cytotoxic activity of the extracts against FL cells, measured in neutral red assay, was only weak (IC50 > 500 µg/mL). The results justify the traditional use of the flowers of Hydnora abyssinica in South Yemen.

Nationwide Effectiveness and Efficiency of the National Diabetes Prevention Policy Versus the Penny-per-Ounce Excise Tax Policy on Sugar-Sweetened Beverages.

Diabetes has reached epidemic levels in the United States (US). This review compared two nationwide diabetes prevention policies: the National Diabetes Prevention Program (DPP) and the Penny-per-Ounce Excise (POE) tax policy on sugar-sweetened beverages (SSBs) based on their efficiency and efficacy in reducing the number of new cases of diabetes in the US. The study made a recommendation for the implementation of one or both policies based on the comparison. The national DPP focuses on screening for prediabetes in overweight/obese individuals and having positive subjects participate in a potentially insured one-year weight loss program with CDC-approved coaches. The POE tax on SSBs on the other hand is based on taxing SSBs with the objective that it will reduce new cases of diabetes due to a lower consumption of these beverages, or a switch to healthier alternatives. Studies that predicted the impact of either policy at the national level were used to compare both policies. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference in net costs saved by the difference in net effectiveness (diabetes cases prevented per year); thereby comparing both policies in terms of costs saved for each diabetes case prevented per year. Using only nationwide US predictions, it has been estimated that the POE tax on SSB will produce the most cost savings with a greater impact on reducing new cases of diabetes if implemented; therefore, this tax should be recommended, in addition to the already implemented DPP.

Physicochemical properties of edible cricket oils: Implications for use in pharmaceutical and food industries.

The prevailing global market demands locally produced, sustainable oils for biomedical applications. This study focused on evaluating the quality of cricket-derived oils and meals from Scapsipedus icipe Hugel, Tanga, and Gryllus bimaculatus De Geer common delicacy in Africa, following standard methods for physicochemical properties, fatty acid composition, and phytochemicals (oxalates, phytates, tannins, and polyphenols). The cricket oils physicochemical properties aligned with Codex Alimentarius standards for edible oils, including low solidification temperature (< 2 °C), a high refractive index (1.46), and a specific gravity of 0.88. Notably, peroxide values (1.9 to 2.5 mg mEq O2/kg), acid values (1.1 to 2.2 mg KOH/g), and saponification values (234-246 mg KOH/g) all are indicative of lightness and unsaturated fatty acids. Nutritionally, cricket powder was rich in protein (56.8-56.9% -) and fat (31.7-33.5% -of dry matter), with significant amounts of essential omega-3 and omega-6 fatty acids. Predominant saturated and monounsaturated fatty acids were palmitic (23.9-31.2 mg/100 g-) and oleic acids (10.9-11.4 mg/100 g- of oil), respectively. Antioxidant values (48.0 to 65.0 mg/100 g), inferred from total polyphenols, suggests a stable oil with long shelf-life. These results highlight the promising and sustainable potential of cricket-derived oils for applications in the food and pharmaceutical industries.

Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31-32.

Primary pulmonary hypertension (PPH), an often fatal disease, is characterized by elevated pulmonary artery pressures in the absence of a secondary cause. Endovascular occlusion in the smallest pulmonary arteries occurs by proliferation of cells and matrix, with thrombus and vasospasm. Diagnosis is often delayed because the initial symptoms of fatigue and dyspnea on exertion are nonspecific and definitive diagnosis requires invasive procedures. The average life expectancy after diagnosis is two to three years with death usually due to progressive right heart failure. The aetiology of the disease is unknown. Although most cases appear to be sporadic, approximately 6% of cases recorded in the NIH Primary Pulmonary Hypertension Registry are inherited in an autosomal dominant manner with reduced penetrance. Following a genome-wide search using a set of highly polymorphic short tandem repeat (STR) markers and 19 affected individuals from six families, initial evidence for linkage was obtained with two chromosome 2q markers. We subsequently genotyped patients and all available family members for 19 additional markers spanning approximately 40 centiMorgans (cM) on the long arm of chromosome 2. We obtained a maximum two-point lod score of 6.97 at theta = 0 with the marker D2S389; multipoint linkage analysis yielded a maximum lod score of 7.86 with the marker D2S311. Haplotype analysis established a minimum candidate interval of approximately 25 cM.

Hepatic Dystrophic Calcification Secondary to Transarterial Chemoembolization: Case Report and Review of Literature.

Hepatocellular carcinoma (HCC) is a common malignancy usually treated with surgery. Patients who are not suitable for surgery undergo transarterial chemoembolization (TACE) which involves injecting anti-cancer drugs and embolizing agents into the hepatic artery. Although it is a relatively safe procedure with minor side effects, TACE can rarely cause dystrophic calcification in the liver. We report a case of a 58-year-old female who presented with right-sided chest pain. The patient had been previously treated for HCC with a TACE procedure. A chest x-ray revealed hepatic calcification which was likely secondary to the prior TACE. This case study emphasizes the significance of considering TACE as a potential cause of hepatic dystrophic calcification.

Outcomes of Portal Vein Thrombosis in Smokers With and Without Cirrhosis and Predictors of Mortality: A Nationwide Assessment.

Portal vein thrombosis (PVT) is a rare condition that can lead to numerous complications, like variceal bleeding, hepatic encephalopathy, and chronic liver disease. PVT has various etiologies, including liver disease, infections, and hyper-coagulable disorders. Cirrhosis, a chronic progressive liver condition characterized by liver fibrosis, is one of the risk factors for the development of PVT. Secondly, smoking also increases the risk of PVT. The aim of this study is to identify outcomes in patients with PVT who smoked with and without cirrhosis. This study was performed using the National Inpatient Sample (NIS) database for the years 2016, 2017, and 2018. The study identified 33,314 patients diagnosed with PVT who smoked, of which 14,991 had cirrhosis, and 18,323 did not have cirrhosis. Patients with PVT and cirrhosis had significantly higher in-hospital mortality, upper gastrointestinal bleeds, acute kidney injury, and peritonitis compared to patients without cirrhosis. The results of the study show that patients with PVT and cirrhosis who smoke have a higher risk of unfavorable outcomes.

Induction of human ß-defensins and psoriasin in vulvovaginal human papillomavirus-associated lesions.

BACKGROUND: Infections with a low-risk type of human papillomavirus (HPV) may lead to genital warts. HPV targets the basal cell layer of epithelial cells. The first line of defense is the innate immune system, which provides nonspecific protection against a variety of pathogens. The antimicrobial peptides (AMPs) α- and ß-defensins, cathelicidins, psoriasin, and RNase7 are central mediators. METHODS: The expression of various α- and ß-defensins, cathelicidin LL-37, psoriasin, and RNase7 was studied in biopsy samples from 35 patients with genital warts and 25 healthy women using quantitative real-time polymerase chain reaction and immunohistochemical analysis. RESULTS: We found a significantly higher expression of the ß-defensins hBD-1 (P = .03), hBD-2 (P < 0.01), and hBD-3 (P < .001), and psoriasin (P = .001) in condylomata acuminata, compared with normal controls. The RNA and protein levels of RNase7 did not differ between infected and uninfected samples (P = .55). The α-defensins HNP 1-3, HD5, and HD6 and the cathelicidin LL-37 were scarcely detectable in normal and infected tissue. CONCLUSIONS: The differing expression of AMPs in HPV-infected, compared with noninfected, vulvovaginal biopsy samples suggests that these peptides are important in the local immune response. Curiously, hBD-1 shows a significant induction whereas RNase7 does not, which suggests differing regulation of AMPs over the course of bacterial and viral infections.

Excessive gluconeogenesis causes the hepatic insulin resistance paradox and its sequelae.

Background: Hepatic insulin signaling suppresses gluconeogenesis but promotes de novo lipid synthesis. Paradoxically, hepatic insulin resistance (HIR) enhances both gluconeogenesis and de novo lipid synthesis. Elucidation of the etiology of this paradox, which participates in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), cardiovascular disease, the metabolic syndrome and hepatocellular carcinoma, has not been fully achieved. Scope of review: This article briefly outlines the previously proposed hypotheses on the etiology of the HIR paradox. It then discusses literature consistent with an alternative hypothesis that excessive gluconeogenesis, the direct effect of HIR, is responsible for the aberrant lipogenesis. The mechanisms involved therein are explained, involving de novo synthesis of fructose and uric acid, promotion of glutamine anaplerosis, and induction of glucagon resistance. Thus, gluconeogenesis via lipogenesis promotes hepatic steatosis, a component of NAFLD, and dyslipidemia. Gluconeogenesis-centred mechanisms for the progression of NAFLD from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis are suggested. That NAFLD often precedes and predicts type 2 diabetes is explained by the ability of lipogenesis to cushion against blood glucose dysregulation in the earlier stages of NAFLD. Major conclusions: HIR-induced excessive gluconeogenesis is a major cause of the HIR paradox and its sequelae. Such involvement of gluconeogenesis in lipid synthesis rationalizes the fact that several types of antidiabetic drugs ameliorate NAFLD. Thus, dietary, lifestyle and pharmacological targeting of HIR and hepatic gluconeogenesis may be a most viable approach for the prevention and management of the HIR-associated network of diseases.

Dual-axis thrust stand for the direct characterization of electrospray performance.

A dual-axis torsional thrust stand was successfully demonstrated at the Air Force Research Laboratory, enabling direct simultaneous thrust and mass loss measurement for the Air Force Electrospray Thruster Series 2 passively fed electrospray thruster. The dual-axis system is effectively two nulled torsional thrust stands sharing a single dual-axis gimbal with a thrust and mass resolution of ±0.2 µN and ±0.04 mg, respectively. The development of this system was inspired by a need for direct efficiency characterization of electrosprays via in situ mass measurements, and performance was compared to thruster masses measured pre- and post-testing using an analytical balance. Mass consumption data captured via the dual-axis stand, which is calibrated to a traceable uncertainty of 1.6%, varied between -5% and 18% as compared to analytical balance measurements throughout a multi-month testing effort highlighting the limitations in pre/post-weighing as a method for capturing propellant consumption due to absorption of atmospheric moisture when thrusters are removed from vacuum. Thrust stand tests were limited to short term operation with a daily available testing window of ∼5 h due to thrust stand drift following the 24 h cyclic temperature variations of the testing facility. A thorough investigation into the root cause of ambient thermal drift suggests that the thermal response of commercial flex-pivot bearings is directly producing spurious torques on the order of 10 µN m/°C. Additionally, unresolved charging effects on thrust stand hardware currently limit thrust stand operation to tests operating with a positive thruster polarity. Further development and long duration test stability require both a targeted investigation into flex-pivot thermal response and minimization of facility effects.

Effect of incorporation of snail meat powder on sensory attributes and consumer acceptability of sorghum-wheat buns.

Formulation of foods from -low-lysine cereals fortified with animal protein is a potentially sustainable approach to enhance protein quality in diet due to nutritional compensation while buns are valuable vehicles to deliver nutrients to human body because of their relatively noble eating quality and extended shelf life. The aim of this study was to evaluate the sensory attributes and consumer acceptability of sorghum-wheat buns containing snail meat powder (SMP). Buns were prepared by replacing 5, 10, 15, 20, and 25% of sorghum-wheat composite flour with SMP. Principal component analysis (PCA) revealed 99% total variation of 23 attributes for buns scored by a descriptive sensory panel, of which 98% was due to the proportion of SMP that replaced sorghum-wheat composite flour in buns and the remainder 1% was due to the buns' physical appearance. Compositing sorghum-wheat buns with SMP imparted positive consumer attributes of fine crumb, sponginess, and crumby texture. It also resulted in buns with reasonably high sensory acceptability as evaluated by 8- to 9-year-old school children. The buns can serve as supplementary rich sources of protein for alleviating the menace of protein energy malnutrition in sub-Saharan Africa.

Effect of Comorbidities on Inflammatory Bowel Disease-Related Colorectal Cancer: A Nationwide Inpatient Review.

Introduction  The risk of inflammatory bowel disease-associated colorectal cancer (IBD-CRC) is known to increase with primary sclerosing cholangitis (PSC) and a family history of CRC. However, the impact of comorbidities such as liver disease, obesity, diabetes, chronic lung, heart, and renal disease, and psychiatric illness on the risk of IBD-CRC remains unclear. We evaluated the effect of these comorbidities on the risk of IBD-CRC. Methods A retrospective review from 2009 to 2014 was conducted using the National Inpatient Sample data for adults 18 years and older. Patients with IBD (360,892), of whom 2,831 had CRC were identified using the International Classification of Diseases, Ninth Revision codes (ICD-9). Data on comorbidities were also obtained. Adjusted odds ratios (aOR) and confidence intervals (CI) were computed via logistic regression to evaluate the effect of comorbidities on the risk of IBD-CRC; the p-value was set at <0.05. Results The mean age of IBD patients in this study was 52.36±0.03. A majority of the patients with IBD-CRC were white and were significantly older compared to those without cancer (60 vs 52 years, p<0.05). The risk of colon cancer in IBD was increased by having a non-cholestatic liver disease (aOR 1.51, CI 1.23-1.86, p<0.01). Also, patients younger than 50 years with liver disease were at an increased risk of IBD-associated colon cancer in comparison to older patients (aOR 1.83 vs 1.34, p<0.05). Notably, diabetes, chronic pulmonary disease, renal failure, psychiatric illnesses, and rheumatoid diseases, were inversely associated with the risk of IBD-CRC (p<0.05). After stratifying by IBD subtypes, non-cholestatic liver disease was still independently associated with a higher risk for colon cancer in patients with ulcerative colitis or Crohn's disease (ulcerative colitis: aOR 1.43, CI 1.08-1.89; Crohn's disease: aOR 1.46, CI 1.10-2.00). Conclusions Patients with IBD who have non-cholestatic liver disease might have a higher risk for colon cancer, even at a younger age. These patients may require close colon cancer surveillance.

Human BRCA1-associated breast cancer: no increase in numerical chromosomal instability compared to sporadic tumors.

BRCA1 is a major gatekeeper of genomic stability. Acting in multiple central processes like double-strand break repair, centrosome replication, and checkpoint control, BRCA1 participates in maintaining genomic integrity and protects the cell against genomic instability. Chromosomal instability (CIN) as part of genomic instability is an inherent characteristic of most solid tumors and is also involved in breast cancer development. In this study, we determined the extent of CIN in 32 breast cancer tumors of women with a BRCA1 germline mutation compared to 62 unselected breast cancers. We applied fluorescence in situ hybridization (FISH) with centromere-specific probes for the chromosomes 1, 7, 8, 10, 17, and X and locus-specific probes for 3q27 (BCL6), 5p15.2 (D5S23), 5q31 (EGR1), 10q23.3 (PTEN), and 14q32 (IGH@) on formalin-fixed paraffin-embedded tissue microarray sections. Our hypothesis of an increased level of CIN in BRCA1-associated breast cancer could not be confirmed by this approach. Surprisingly, we detected no significant difference in the extent of CIN in BRCA1-mutated versus sporadic tumors. The only exception was the CIN value for chromosome 1. Here, the extent of CIN was slightly higher in the group of sporadic tumors.

Cost analysis and efficiency of sub-district health facilities in two districts in Ghana.

To establish the full costs borne by sub-district health facilities in providing services, we analysed the costs and revenues of 10 sub-district health facilities located in two districts in Ghana. The full costs were obtained by considering staff costs, cost of utilities, cost of using health facility equipment, cost of non-drug consumables, equipment maintenance expenses, amounts spent on training, community information sessions and other outreach activities as well as all other costs incurred in running the facilities. We found that (i) a large proportion of sub-district health facility costs is made up of staff salaries; (ii) at all facilities, internally generated funds (IGFs) are substantially lower than costs incurred in running the facilities; (iii) average IGF is several times higher in one district than the other; (iv) wide variations exist in efficiency indicators and (v) there is some evidence that sub-district health facilities may not necessarily be financially more efficient than hospitals in using financial resources. We suggest that the study should be replicated in other districts; but in the mean time, the health authorities should take note of the conclusions and recommendations of this study. Efforts should also be made to improve record keeping at these facilities.