The single cell gel electrophoresis: a potential tool for DNA analysis of the patients with hematological malignancies.
Single cell gel electrophoresis (SCGE) was used to evaluate the level of DNA damage in peripheral blood (PB), bone marrow (BM), and lymphatic node (LN) cells of patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML) and non-Hodgkin's lymphoma (NHL). The level of DNA damage was compared with the level of basal DNA damage in control group, represented by healthy donors. Statistically significant increase of basal DNA damage was found in leukemia/lymphoma cells of patients suffered from AML, CML, ALL of T-cell subtype (T-ALL), and NHL, however, no difference in basal DNA damage was found in patients with ALL of early B-cell subtype (B-ALL) and CLL in comparison to control group. The mean basal DNA damage increased in the order CLL<early B-ALL<T-ALL<AML<CML<NHL (5.6, 7.2, 10.7, 11.9, 16.9, and 23.4% of tail DNA, respectively) what correlated with survival prediction of patients with particular hematological disease. A large heterogeneity was found in the level of basal DNA damage among patients with AML. By sorting this group according to the immunophenotypic markers and cell maturity a good correlation was found between the level of basal DNA damage and French-American-British (FAB) classification for AML (M1-M2 vs. M4-M5). Though T-ALL group manifested larger homogeneity in comparison with AML, the value of basal DNA damage was also dependent on T-cells maturity and coexpression of surface marker CD10. Chemotherapy resulted in a significant but variable increase of DNA damage in leukemia/lymphoma cells. No increase of DNA damage was repeatedly observed in leukemia/lymphoma cells of patient who did not respond to therapy. The level of DNA damage in cells of patients in remission decreased more or less to the basal level in control cells.


Quality of care for patients hospitalized with heart failure: assessing the impact of hospitalists.
The quality of care provided to patients hospitalized for heart failure has been shown to vary by physician, hospital, and region. Hospitalists appear to reduce costs and length of stay, yet their impact on quality of care is less certain. To compare quality of care and resource utilization among patients with heart failure treated by hospitalists and nonhospitalist general internists. We reviewed the medical records of patients with a principal diagnosis of heart failure between April 1, 1999, and March 30, 2000, at a 550-bed community-based teaching hospital in Massachusetts. We evaluated quality of care by measuring adherence to a set of commonly used process measures and compared resource utilization using severity-adjusted length of stay and costs. The analysis included 280 patients, accounting for 326 heart failure admissions: 20 hospitalists cared for 137 (42%) cases, while 65 nonhospitalists cared for 189 (58%). Of 137 hospitalist cases, 129 (94%) had new or prior left ventricular ejection fraction testing results documented during the hospitalization compared with 165 (87%) of 189 nonhospitalist cases (P =.04). In cohorts of ideal candidates, performance rates for hospitalist and nonhospitalist cases were similar for prescriptions of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for patients with ejection fractions lower than 40% (97% vs 96%; P>.99) and warfarin for patients with atrial fibrillation (60% vs 55%; P =.64). Rates of comprehensive discharge counseling was similar in the 2 groups. Multivariable modeling did not substantially alter these findings. After adjusting for differences in severity, patients treated by hospitalists had a shorter length of stay but similar overall costs when compared with those treated by nonhospitalists. Compared with nonhospitalists, hospitalists were more likely to document assessment of left ventricular function and their patients had a shorter length of stay.


RaScaL: A Pilot Study to Assess the Efficacy, Durability, and Safety of a Single Intervention with Ranibizumab plus Peripheral Laser for Diabetic Macular Edema Associated with Peripheral Nonperfusion on Ultrawide-Field Fluorescein Angiography.
Background and Objectives: To determine the efficacy, durability, and safety of a single treatment with intravitreal ranibizumab plus peripheral scatter laser (RaScaL) in patients with diabetic macular edema associated with peripheral retinal nonperfusion on ultrawide-field fluorescein angiography (UWFA). Study Design: A 6-month, randomized, controlled, prospective phase I/II study of 30 treatment-naïve eyes of 22 patients (8 bilateral patients) with visual impairment secondary to diabetic macular edema associated with peripheral nonperfusion on UWFA. Patients were randomized to receive ranibizumab plus UWFA-guided peripheral scatter laser (n = 15) or triamcinolone acetonide plus macular laser (n = 15). Results: At 6 months, the RaScaL group patients had fewer recurrences warranting retreatment (33% vs. 80%, p < 0.003). Mean change in final visual acuity and central foveal thickness were not statistically significant between groups. Conclusion: This pilot study suggests the efficacy, safety and durability of the RaScaL treatment regimen in patients with diabetic macular edema associated with peripheral nonperfusion on UWFA. © 2014 S. Karger AG, Basel.


Regulating strain states by using the recovery potential of lunch breaks.
The aim of the worksite study is to elucidate the strain reducing impact of different forms of spending lunch breaks. With the help of the so-called silent room cabin concept, it was possible to induce a lunch-break relaxation opportunity that provided visual and territorial privacy. To evaluate the proposed effects, 14 call center agents were assigned to either 20 min progressive muscle relaxation (PMR) or small-talk (ST) break groups. We analyzed the data in a controlled trial for a period of 6 months (every 2 months four measurements a day at 12:00, 13:00, 16:00, 20:00) using independent observer and self-report ratings of emotional, mental, motivational, and physical strain. Results indicated that only the PMR break reduced postlunchtime and afternoon strain. Although further intervention research is required, our results suggest that PMR lunch break may sustainable reduce strain states in real worksite settings.


Role of lactadherin in intestinal barrier integrity in experimental neonatal necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) is one of the most widespread and devastating gastrointestinal diseases in neonates. Destruction of the intestinal barrier is the main underlying cause of NEC. The aim of this study was to determine the role of lactadherin in preventing NEC in a neonatal rat model and investigate the molecular mechanism of lactadherin-mediated protection of the intestinal barrier. Neonatal rats were divided into three groups: dam feeding (DF), NEC (NEC), and NEC supplemented with 10 μg/(g·day) recombinant human lactadherin (NEC+L). Intestinal permeability, tissue damage, and cell junction protein expression and localization were evaluated. We found that lactadherin reduced weight loss caused by NEC, reduced the incidence of NEC from 100% to 46.7%, and reduced the mean histological score for tissue damage to 1.40 compared with 2.53 in the NEC group. Intestinal permeability of lactadherin-treated rats was significantly reduced when compared with that of the NEC group. In addition, the expression levels of JAM-A, claudin 3, and E-calcium in the ileum of NEC group animals increased compared with those in the ileum of DF group animals, and these levels decreased in the NEC+L group. Lactadherin changed the localization of claudin 3, occludin, and E-cadherin in epithelial cells. The mechanism underlying lactadherin-mediated protection of the intestinal barrier might be restoring the correct expression levels and localization of tight junction and adherent junction proteins. These findings suggest a new candidate agent for the prevention of NEC in newborns.


Fluid pinch-off dynamics at nanometer length scales.
The breakup of a drop of inviscid fluid into two smaller drops is determined by a competition between surface and inertial forces. This process forms a thin filament of fluid with a connecting neck that shrinks to zero diameter at a finite time singularity. We present measurements of the electrical resistance of a liquid bridge of mercury as it undergoes pinch off. The electrical measurements allow us to probe the region of the singularity down to nanosecond times and nanometer lengths. Near pinch off, the resistance of the liquid bridge diverges as t(-2/3), as expected for inviscid flow.


What makes a successful volunteer Expert Patients Programme tutor? Factors predicting satisfaction, productivity and intention to continue tutoring of a new public health workforce in the United Kingdom.
Better management of chronic conditions is a challenge for public health policy. The Expert Patients Programme was introduced into the United Kingdom to improve self-care in people with long-term conditions. To deliver self-care courses, the programme relies on the recruitment and continued commitment to delivering the courses of volunteer lay tutors who have long-term conditions. Ensuring the tutor workforce is productive, satisfied in their role and retained long-term is central to the viability of the programme. This exploratory study aimed to determine what factors predict productivity, intention to continue tutoring, and satisfaction in a sample of volunteer tutors from the Expert Patients Programme. A cross-sectional survey of 895 tutors was carried out and 518 (58%) responded. The questionnaire was designed to describe the characteristics, productivity, intention to continue tutoring, and satisfaction of tutors. Multiple linear regression analyses were used to examine the determinants of productivity, intention to continue tutoring, and satisfaction, such as patient demographics, attitudes, physical and mental health, mastery and self-esteem. Attitudes relating to personal goals, and better health were significant predictors of satisfaction with the tutor role. Only a small proportion of the variance in productivity was accounted for, and tutors were more likely to be productive when they were single, homeowners, car owners, and had lower scores on the depression scale. Overall satisfaction and personal goals were predictors of intention to continue tutoring. Demographic factors, health measures and attitudes each predicted different aspects of the experience of work conducted by the volunteer tutors. The results should prove useful for planning interventions to enhance the success of this new workforce initiative. Attempts to increase participation in courses by people from deprived backgrounds are likely to be enhanced if tutors come from similar backgrounds. This study demonstrated that material advantage and attitudes that value personal goals were predictors of satisfaction and productivity in the tutor role. Specific incentives and strategies may be required to recruit and support tutors from more marginalised groups in order to ensure equitable access to effective self-care support for all.


Pre-pubertal diet restriction reduces reactive oxygen species and restores fertility in male WNIN/Obese rat.
Obesity is a multifactorial disorder associated with increased body adiposity, chronic oxidative stress which contributes to impaired fertility in males. Diet restriction and anti-oxidant supplementations are known to protect obese subjects from oxidative stress and improves fertility. However, the role of oxidative stress and the age of intervention in restoring male fertility are poorly understood. This study was aimed to assess the effect of diet restriction on fertility with respect to the age of intervention, body composition and oxidative stress using WNIN/Ob obese mutant rat strain. Unlike lean and carrier phenotypes, obese rats are hyperphagic, hyperlipaemic and infertile. Male obese rats aged for 35, 60 and 90 days were fed either ad libitum or diet restricted for 6 weeks. Upon diet restriction mean body weight, total body fat percentage, circulatory lipids and oxidative stress markers were significantly reduced and it follows the order as 35 < 60 < 90 days. Diet-restricted males of the three age groups were allowed to mate with female carrier rats, and fertility was restored only in 35-day group. Diet restriction in male obese WNIN/Ob rats lowered the rate of body weight gain, with reduced oxidative stress overall and fertility restoration in groups intervened at pre-pubertal stages.


Strengths and weaknesses in methods for identifying the causative agent(s) of acquired immunodeficiency syndrome (AIDS).
Human immunodeficiency virus (HIV) is a cytoplasmic retrovirus which is transmitted via body fluids, especially through blood products and sexual contact, and is the causative agent of the acquired immunodeficiency syndrome (AIDS). Only about 5 to 10% of the patients infected with HIV contract AIDS; the great majority of infected people either develop a less aggressive condition (AIDS-related complex) or appear healthy. All persons infected with HIV may transmit the virus. In order to protect the national blood supply and to help in diagnosis, tests have been developed to identify infected persons. These include viral isolation techniques, enzyme-linked immunosorbent assay (ELISA), immunofluorescent assay (IFA), radioimmune precipitation (RIP) assay, Western blot, and, most recently, antigen identification and gene probes. Although the sensitivity and specificity among these methods varies, all are susceptible to false-positive and/or false-negative results. In order to understand the reasons for fragility in methodologies, it is necessary to appreciate several basic concepts related to the biochemistry, biology, pathophysiology, and genetic characteristics of HIV and related viruses. The purpose of this review is to present the strengths and weaknesses of each method, with emphasis on peculiar viral characteristics that lead to methodological defects or efficacies.


Efficacy of benzalkonium chloride against bioluminescent P. aeruginosa ATCC9027 constructs.
Whole cell biosensors have been seldom used in the pharmaceutical and cosmetics industries for preservative efficacy testing (PET). According to several pharmacopoeias, preservatives should be tested for microbial activity using traditional viable count techniques; the use of whole cell microbial biosensors potentially provides an alternative, fast, and efficient method. The aim of the study was to assess the applicability of Pseudomonas aeruginosa ATCC9027 and its validated bioluminescent strains for preservative efficacy tests using benzalkonium chloride (BKC). Applicability of five constitutively-expressed bioluminescent strains was evaluated for preservative efficacy tests (PET) using bacterial replication, bioluminescence and fluorescence in a three-way study. PET using BKC showed no significant difference between bioluminescence and enumeration. Good correlations between bioluminescence, colony-forming units (CFU) count and fluorescence were obtained for BKC concentrations (R>0.9) between 0.0003-0.0025% against strains containing the constructs lys-pMElux, lpp-pMElux and tat-pMElux. Furthermore, two-way ANOVA analysis showed that the bioluminescent method and traditional plate counting method were equivalent for concentrations of BKC (0.0003-0.01%) during preservative efficacy tests. PET testing with BKC showed that tat-pMElux (R>0.9) had consistently high correlation coefficients between CFU and relative bioluminescence; P. aeruginosa ATCC9027 tatH5-pMElux is the best construct for testing various antimicrobial agents.


Clinical Implications of Genetic Mutations in Myelodysplastic Syndrome.
Myelodysplastic syndrome (MDS) is clonal disorder characterized by ineffective hematopoiesis and a tendency to evolve into acute myeloid leukemia (AML). Genetic studies have enabled the identification of a set of recurrently mutated genes central to the pathogenesis of MDS, which can be organized into a limited number of cellular processes, including RNA splicing, epigenetic and traditional transcriptional regulation, and signal transduction. The sequential accumulation of mutations drives disease evolution from asymptomatic clonal hematopoiesis to frank MDS, and, ultimately, to secondary AML. This detailed understanding of the molecular landscape of MDS, coupled with the emergence of cost- and time-effective methodologies for DNA sequencing has led to the introduction of genetic studies into the clinical realm. Here, we review recent advances in our genetic understanding of MDS, with a particular focus on the emerging role for mutational data in clinical management as a potential tool to assist in diagnosis, risk stratification, and therapeutic decision-making.


Asymmetrical dental caries and Streptococcus mutans infection.
A 27-year-old woman chewed unilaterally and had restorations and caries only on the right side of the dentition. The left side had a greater amount of soft and hard deposits and more severe periodontal disease. Plaque samples from occlusal and interproximal tooth surfaces were collected and cultured. The proportion of Streptococcus mutans of the total anaerobic count in the plaque samples from the right side was 1,000 to 10,000 times as high as from the left side. The proportion of S mutans of the total streptococcus was 6% to 20% on the right and less than 1% on the left side.


omb and circumstance.
Since its isolation in a behavioral screen in 1971, work on the gene, optomotor-blind (omb, FlyBase: bifid, bi), has proceeded in many laboratories. The Drosophila T-box transcription factor, Omb, is active in several developmental processes, in particular in those of wing, eye, and abdominal tergites and optic lobes. The orthologous genes, TBX2 and TBX3, are found overexpressed or amplified in an increasing number of human cancers, emphasizing the importance of Tbx genes also in postdevelopmental processes. This review summarizes recent findings pertaining to omb and orthologous genes.


[Cost-effectiveness analysis of immunosuppressive drugs in post-renal transplantation maintenance therapy in adult patients in Brazil].
The aim of the study was to perform cost-effectiveness analysis of immunosuppressive drugs in post-renal transplantation maintenance therapy. A hypothetical cohort of transplanted adults was followed for 20 years, using the Markov model. The 10 evaluated therapeutic regimens contained prednisone (P). Average cost of the medicines was obtained from CMED (Câmara de Regulação do Mercado de Medicamentos). Other patient care costs were included in each disease stage. Costs were expressed in Brazilian reais, effectiveness was measured as years of life gained, and the study adopted a public health system perspective. At the end of follow-up, the analysis with discount showed that all the regimens were dominated by cyclosporine (CSA)+azathioprine (AZA)+P. In the remaining analyses, tacrolimus+AZA+P was not dominated, but the incremental cost-effectiveness ratio between these two regimens was R$ 156,732.07/ years of life gained, a value that exceeds the threshold of three times the Brazilian per capita GDP. In the sensitivity analysis, no qualitative change was observed and the probability of CSA+AZA+P being the most cost-effective regimen was greater than 85%.


Ectopic eruption of the first permanent molars: prevalence and etiologic factors.
The purpose of this research was to study the prevalence of ectopic eruption of the first permanent molars and possible etiologic factors. A group of 4,232 Thai students, from 6 to 9 years old, was examined. The prevalence of ectopic eruption of the first permanent molars in the subjects was 0.75%. Both the severity of the ectopic eruption and the amount of root resorption on the second primary molars were more pronounced in the maxilla than in the mandible. The important etiologic factors were the eruption path of the first permanent molars relative to reference lines and the size of the mandibular second primary molars. The amount of proximal caries did not seem to affect the prevalence of ectopic eruption.


Relative roles of CD90 and c-kit to the regenerative efficacy of cardiosphere-derived cells in humans and in a mouse model of myocardial infarction.
The regenerative potential of cardiosphere-derived cells (CDCs) for ischemic heart disease has been demonstrated in mice, rats, pigs, and a recently completed clinical trial (CADUCEUS). CDCs are CD105(+) stromal cells of intrinsic cardiac origin, but the antigenic characteristics of the active fraction remain to be defined. CDCs contain a small minority of c-kit(+) cells, which have been argued to be cardiac progenitors, and a variable fraction of CD90(+) cells whose bioactivity is unclear. We performed a retrospective analysis of data from the CADUCEUS trial and a prospective mouse study to elucidate the roles of c-kit(+) and CD90(+) cells in human CDCs. Here, we show, surprisingly, that c-kit expression has no relationship to CDCs' therapeutic efficacy in humans, and depletion of c-kit(+) cells does not undermine the structural and functional benefits of CDCs in a mouse model of myocardial infarction (MI). In contrast, CD90 expression negatively correlates with the therapeutic benefit of CDCs in humans (ie, higher CD90 expression associated with lower efficacy). Depletion of CD90(+) cells augments the functional potency of CDCs in murine MI. CD90(-) CDCs secrete lower levels of inflammatory cytokines and can differentiate into cardiomyocytes in vitro and in vivo. The majority population of CDCs (CD105(+)/CD90(-)/c-kit(-)) constitutes the active fraction, both in terms of therapeutic efficacy and in the ability to undergo cardiomyogenic differentiation. The c-kit(+) fraction is neither necessary for, nor contributory to, the regenerative efficacy of CDCs.


The quantity and quality of scientific evidence about the health of working women in occupational health of Japan: A scoping review.
We aim to investigate the quantity and quality of scientific evidence dealing with comprehensive health issues of working women in occupational health. This scoping review of original articles that investigated comprehensive health issues of working women aged 19-64 years in Japan was published in PubMed (1967-2022) and Igaku Chuo Zasshi (or Ichu-shi, 1982-2022). Using identical broad search terms, we first identified 17 122 English and 6154 Japanese articles. We excluded those with clinically relevant topics, or ethnicity other than Japanese and included 853 English and 855 Japanese articles for review and classified them into nine research areas considered to be critical factors for women in the workforce and five study design groups to investigate the quality of the evidence accumulated. Among 853 English-language articles in PubMed, "Mental health" was the most frequent area studied, followed by "Work-related disease" and "Lifestyle-related disease." Among 855 Japanese-language articles from Ichu-shi, "Mental health" was the most frequently studied area followed by "Work and balance," and "Work-related disease." "Infertility, pregnancy, and childbirth" and "Menstruation, menopause, and genital disease" were well studied in Ichu-shi but scarcely published in PubMed. "Harassment and discrimination" were sparsely reported in both databases. As for research designs, many articles in both PubMed and Ichu-shi employed descriptive or cross-sectional study designs. However, a few studies employed cohort/longitudinal or interventional studies. The results underscored the need for higher-quality study designs with more scientific evidence on working women's health in the field of occupational health.


Observation of a new phosphorus-containing reactive intermediate: electronic spectroscopy and excited-state dynamics of the HPBr free radical.
The A (2)A(')-X (2)A(") electronic spectra of jet-cooled HPBr and DPBr have been obtained for the first time using the pulsed electric discharge technique with a precursor mixture of PBr(3) and H(2)/D(2). Laser-induced fluorescence and single vibronic level emission spectra gave the bending and P-Br stretching frequencies in the ground and excited states of both isotopomers. Rotational analyses of the HPBr and DPBr 0(0) (0) bands showed small spin splittings characteristic of a doublet-doublet transition of an asymmetric-top molecule. From the ground- and excited-state rotational constants, effective (r(0)) structures were derived with r(")(PH)=1.4307(86) A, r(")(PBr)=2.2021(9) A, and theta(")=95.2(8) degrees, and r(')(PH)=1.434(31) A, r(')(PBr)=2.1669(26) A, and theta(')=115.5(16) degrees . In a few favorable cases, further hyperfine splitting of the spin-rotation energy levels has been observed, due to the excited-state Fermi contact interaction of the unpaired electron with the spin magnetic moment of the (31)P nucleus, with a(F) (')=0.064(9) cm(-1) for HPBr. Fluorescence depletion spectroscopy and lifetime measurements indicate that higher vibrational levels of the A (2)A(') state are predissociated by a X (2)A(") dissociative continuum. CCSD(T)/aug-cc-pVTZ calculations predict that the most likely dissociation process is HPBr (X (2)A("))-->PH((3)Sigma(-))+Br((2)P(u)).


Biosurfactant production by Azotobacter chroococcum isolated from the marine environment.
Preliminary characterization of a biosurfactant-producing Azotobacter chroococcum isolated from marine environment showed maximum biomass and biosurfactant production at 120 and 132 h, respectively, at pH 8.0, 38 degrees C, and 30 per thousand salinity utilizing a 2% carbon substrate. It grew and produced biosurfactant on crude oil, waste motor lubricant oil, and peanut oil cake. Peanut oil cake gave the highest biosurfactant production (4.6 mg/mL) under fermentation conditions. The biosurfactant product emulsified waste motor lubricant oil, crude oil, diesel, kerosene, naphthalene, anthracene, and xylene. Preliminary characterization of the biosurfactant using biochemical, Fourier transform infrared spectroscopy, and mass spectral analysis indicated that the biosurfactant was a lipopeptide with percentage lipid and protein proportion of 31.3:68.7.


Genetically encoded molecular biosensors to image histone methylation in living animals.
Post-translational addition of methyl groups to the amino terminal tails of histone proteins regulates cellular gene expression at various stages of development and the pathogenesis of cellular diseases, including cancer. Several enzymes that modulate these post-translational modifications of histones are promising targets for development of small molecule drugs. However, there is no promising real-time histone methylation detection tool currently available to screen and validate potential small molecule histone methylation modulators in small animal models. With this in mind, we developed genetically encoded molecular biosensors based on the split-enzyme complementation approach for in vitro and in vivo imaging of lysine 9 (H3-K9 sensor) and lysine 27 (H3-K27 sensor) methylation marks of histone 3. These methylation sensors were validated in vitro in HEK293T, HepG2, and HeLa cells. The efficiency of the histone methylation sensor was assessed by employing methyltransferase inhibitors (Bix01294 and UNC0638), demethylase inhibitor (JIB-04), and siRNA silencing at the endogenous histone K9-methyltransferase enzyme level. Furthermore, noninvasive bioluminescence imaging of histone methylation sensors confirmed the potential of these sensors in monitoring histone methylation status in response to histone methyltransferase inhibitors in living animals. Experimental results confirmed that the developed H3-K9 and H3-K27 sensors are specific and sensitive to image the drug-induced histone methylation changes in living animals. These novel histone methylation sensors can facilitate the in vitro screening and in vivo characterization of new histone methyltransferase inhibitors and accelerate the pace of introduction of epigenetic therapies into the clinic.


Comparative study of norfloxacin and trimethoprim for the treatment of elderly patients with urinary tract infection.
One hundred elderly hospitalised patients, aged 70 to 97 years (mean 81.7 years; SD 7.1 years) with a urinary tract infection were entered into a randomised study to compare the efficacy, safety and tolerance of norfloxacin 400 mg twice daily for three days with trimethoprim 300 mg once daily for three days. Forty-two of 49 patients (86%) were cured with norfloxacin, compared with 35 of 51 (69%) with trimethoprim (p less than 0.05). No patient reported any side effects during treatment. Two patients treated with norfloxacin and three treated with trimethoprim developed a disturbance of liver function. Three deaths occurred within 28 days of treatment with trimethoprim but were unrelated to the treatment. In this study norfloxacin proved superior to trimethoprim for the treatment of uncomplicated urinary tract infections in elderly hospitalised patients.


Treatment of intertrochanteric and subtrochanteric fractures of the hip by the Ender method.
Ender's method of intramedullary fixation of intertrochanteric and subtrochanteric fractures is described. Ender's nail is a pre-bent flexible steel nail with a diameter of 4.5 millimeters. Three to five of these nails are inserted from a small incision proximal to the medial epicondyle of the femur into the medullary canal. They are passed through the femur across the fracture site and into the head of the femur, where they diverage. They are in the lines of force and therefore are not subjected to bending moments. The fracture fixation allows immediate weight-bearing. This method of fixation was used in a series of 203 patients. Their average age was sixty-eight years; the mortality rate was 10.3 per cent. In 3.9 per cent superficial infections occurred, but in no case was there a deep infection involving the bone. Functional return (walking) was achieved in all of the survivors who were able to walk at the time of injury, and there were no nonunions.


Effects of basic fibroblast growth factor on in vivo cerebral tumorigenesis in rats.
In vitro evidence suggests that basic fibroblast growth factor (bFGF) promotes tumor cell proliferation and angiogenesis. In this study, we evaluated the early and delayed effects of recombinant human bFGF on the early and late phases of in vivo, in situ tumorigenesis in rats. Brain tumors were induced by transplacentally exposing fetal rats to N-nitrosoethylurea on Day 17 of pregnancy. On postnatal (PN) Day 60 or 90, N-nitrosoethylurea-exposed rats underwent stereotactic intraventricular implantation of Gelfoam saturated with bFGF (60 micrograms) or vehicle; the rats were killed 4 days (early group) or 30 days (delayed group) later. The early and delayed effects of bFGF on the early phase of tumorigenesis (PN Day 60) were evaluated in 14 and 10 rats, respectively; early and delayed effects on the late phase of tumorigenesis (PN Day 90) were evaluated in 12 rats each. Histological examination 30 days after implantation showed a significantly higher tumor rate in rats that had been treated with bFGF on PN Day 90, compared with vehicle-treated control rats (P < 0.05); furthermore, in the bFGF-treated animals there was significantly greater intratumoral and periventricular glial fibrillary acidic protein expression, as determined immunohistochemically. Increased vascularity in the tumor ipsilateral to the implant was found in 2 of 14 rats that had been treated with bFGF on PN Day 60. These findings support in vitro evidence that bFGF and its receptor complex are implicated in the genesis and progression of N-nitrosoethylurea-induced brain tumors in this animal model.


Association between the ICAM-1 gene polymorphism and coronary heart disease risk: a meta-analysis.
Coronary heart disease (CHD) is a complex polygenic disease in which gene-environment interactions play a critical role in disease onset and progression. The Intercellular adhesion molecule 1 (ICAM-1) gene E469K polymorphism is one of the most commonly studied polymorphisms in this gene because of its association with CHD risks, but results were conflicting. The PubMed, Embase, and China National Knowledge Infrastructure databases were searched for case-control studies published up to November 2018. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the association. Eleven eligible studies, comprising 3435 cases and 3199 controls, were included in the meta-analysis. The pooled result showed that the ICAM-1 gene E469K polymorphism was significantly associated with an increased risk of CHD (OR = 1.20, 95% CI = 1.11-1.29, for the allele K versus allele E; OR = 1.66, 95% CI = 1.43-1.92, for the K allele carriers versus EE). Subgroup analysis supported the results in the Chinese populations and in the Caucasian populations. This meta-analysis suggests that the ICAM-1 gene K469E polymorphism is associated with CHD risk and the K allele is a more significant risk factor for developing CHD amongst Chinese and Caucasians populations.


Air velocity spatial variability in open Compost-Bedded Pack Barn system with positive pressure ventilation.
In Compost-Bedded Pack Barn (CBP) systems, air velocity is linked with the thermal comfort of housed dairy cattle and bedding quality and, therefore, assessing ventilation efficiency is essential. In this context, the objective of this study was to evaluate and characterize dependence and spatial distribution of air velocity at the 1.5 m height (vair,M) and at bedding level (vair,B) in an open CBP system with positive pressure ventilation. The study was conducted in 2021, in a facility located in the Zona da Mata region, Minas Gerais, Brazil. The facility area was divided into a mesh composed of 55 equidistant points, where vair,M and vair,B data were collected in the morning (09:00 a.m.) and afternoon (03:00 p.m.) periods, during three weeks in Brazilian winter. Geostatistics techniques were used to assess dependence and spatial distribution. In both periods evaluated, there were a strong occurrence of spatial dependence and non-uniform vair,M and vair,B distributions. The vair,M and vair,B values were lower than recommended (1.8 m∙s-1) in more than 65.0% of the area. Adequate ventilation levels were observed only in the first 20.0 m of the facility, from Southeast to Northwest, because of the fan lines present.


Translational efficiency is up-regulated by alternative exon in murine IL-15 mRNA.
IL-15 promotes the growth of T cells and shares properties of IL-2. IL-2 is produced exclusively by T cells, while IL-15 message is expressed by a variety of tissues. However, it has been difficult to demonstrate IL-15 in the supernatants of many cells that express message for this cytokine. This suggests that IL-15 production is regulated by post-transcriptional controls. In this study, we cloned three types of murine IL-15 cDNA isoforms generated by alternative splicing and compared the translational efficiency among these isoforms. The translational efficiency of isoforms with alternative exon 5 containing another 3' splice site was significantly higher than that of IL-15 cDNA with originally described exon 5, which is generated by internal splicing of alternative exon 5. The translation product of the isoform containing alternative exon 5 has a shorter open reading frame due to stop codons in additional sequence, followed by a new AUG codon, and displays a shorter leader sequence. The shorter isoform of the IL-15 was detected in peritoneal macrophages stimulated with IFN-gamma and LPS, which expressed an abundant level of alternative exon 5. These results suggest that normal IL-15 production in stimulated macrophages is regulated by splicing of alternative exon 5.


Molecular and physiological bases of the K+ circulation in the mammalian inner ear.
Endolymph, the extracellular solution in cochlea, contains 150 mM K(+) and exhibits a potential of approximately +80 mV relative to neighboring extracellular spaces. This unique situation, essential for hearing, is maintained by K(+) circulation from perilymph to endolymph through the cochlear lateral wall. Recent studies have identified ion-transport molecules involved in the K(+) circulation and their pathophysiological relevance.


Immunogenicity of the mutated H-2Kbm1 antigen(s). Test of thyroid graft rejection between B6.C-H-2bm1 and C57BL/6 mice following reciprocal immunization with normal versus malignant cells.
The immunogenic properties of one (or few) selected antigen(s) encoded by the mouse major histocompatibility complex was studied using the C57BL/6(B6) mouse strain and its descendant B6.C-H-2bm1(bm1) mutant. These strains differ in a point mutation in the H-2K region. We compared the immunogenic and antigenic expression of the mutated antigen on different bm1 tissues by testing the vulnerability of these tissues to graft rejection response in B6 recipients. Previous results demonstrated that B6 and bm1 mice do not reject reciprocal thyroid transplants, despite the acute rejection of reciprocal skin grafts. Thyroid grafts were rejected, however, after presensitizing the recipients with skin graft syngeneic with the thyroid, but not after sensitization with spleen cells. In the present work we induced tumors in bm1 mice by treating them with a chemical carcinogen (3-methylcholanthrene). We found that two out of four tumors demonstrated strict strain specificity and were rejected by all mouse strains (including the B6 recipients) except by their strain of origin. All tumors were found to be sensitive to in vitro lysis by B6 anti-bm1 effector cells. HZ1-A and HZ1-B tumor cells were rejected by B6 recipient mice but could not immunize B6 mice against a subsequent bm1 thyroid graft. When testing the immunogenicity of B6 originated EL4 leukemia cells (which are fatal to B6 mice), we found that the tumor cells were rejected by bm1 recipients, but, unlike B6 skin grafts, were incapable of inducing the rejection of a subsequent B6 thyroid transplant. The results demonstrated that an H-2K molecule may exhibit different immunological properties when expressed on cells of different tissues. The different expression of the mutated antigen on different cell types, its ability to trigger T cells but not B cells responses and the potential involvement of the tissue specific differentiation molecules in the graft rejection response are discussed.


The role of serum factors in the suppression of experimental allergic encephalomyelitis: evidence for immunoregulation by antibody to the encephalitogenic peptide.
Lewis rats immunized with myelin basic protein (MBP) in Freund's complete adjuvant (FCA) suffer from a single episode of paralysis from which they recover spontaneously. Subsequent to recovery, further episodes of paralysis cannot normally be induced by reimmunization with MBP in FCA. It is well established that serum, obtained from rats in the refractory state, can suppress the induction of experimental allergic encephalomyelitis (EAE) when given to animals from the time of immunization with MBP in FCA. Here it is shown that treatment with some such sera from Day 7 after immunization also suppressed the disease. However, not all convalescent sera were suppressive, indicating that rats immunized with MBP in FCA could become refractory to EAE without assayable levels of suppressive activity in their sera. In the context of this result it was notable that a correlation was found between the level of antibody specific for the encephalitogenic peptide in sera and the ability to suppress EAE. An inverse relationship was also shown between the amount of anti-encephalitogenic peptide antibody produced after immunization and the severity of EAE induced. Spleen cells from animals treated with Lewis anti-MBP serum after immunization with MBP in FCA could be activated to transfer EAE by in vitro culture with MBP despite the absence of any clinical signs in the donor animals, i.e. the serum inhibited the expansion or differentiation of these cells rather than preventing their priming or bringing about clonal deletion.


Impact of compliance on weight loss and health profile in a very low energy diet program.
Although intuitive, little data links program compliance with weight loss and health profile changes in obese Australians. Obese males (n=308) and females (n=734) from one clinic using a very low energy diet intervention were studied over 26 weeks. Physical and health profiles were assessed. Low compliance completed 1-12 weeks, medium 13-20 weeks and high 21-26 weeks. Overall, 52% achieved high compliance (females: 53%, males: 49%). Greater compliance was associated with greater weight loss and health profile changes in both genders. Mean male weight loss approximated 12 kg, 21 kg and 26 kg with low, medium and high compliance; mean female values were 8 kg, 15 kg and 20 kg. Body mass index, waist-hip ratios, and blood pressure, cholesterol, triglyceride and glucose changes were all more marked with high compliance. Unsuprisingly, high compliance in both genders was consistently associated with more substantial reductions (>15%) of body weight and greater health profile improvements.


Expression and characterization of alpha-(1,4)-glucan branching enzyme Rv1326c of Mycobacterium tuberculosis H37Rv.
Glycogen branching enzyme (GlgB, EC 220.127.116.11) catalyzes the third step of glycogen biosynthesis by the cleavage of an alpha-(1,4)-glucosidic linkage and subsequent transfer of cleaved oligosaccharide to form a new alpha-(1,6)-branch. A single glgB gene Rv1326c is present in Mycobacterium tuberculosis. The predicted amino acid sequence of GlgB of M. tuberculosis has all the conserved regions of alpha-amylase family proteins. The overall amino acid identity to other GlgBs ranges from 48.5 to 99%. The glgB gene of M. tuberculosis was cloned and expressed in Escherichia coli. The recombinant protein was purified to homogeneity using metal affinity and ion exchange chromatography. The recombinant protein is a monomer as evidenced by gel filtration chromatography, is active as an enzyme, and uses amylose as the substrate. Enzyme activity was optimal at pH 7.0, 30 degrees C and divalent cations such as Zn2+ and Cu2+ inhibited activity. CD spectroscopy, proteolytic cleavage and mass spectroscopy analyses revealed that cysteine residues of GlgB form structural disulfide bond(s), which allow the protein to exist in two different redox-dependent conformational states. These conformations have different surface hydrophobicities as evidenced by ANS-fluorescence of oxidized and reduced GlgB. Although the conformational change did not affect the branching enzyme activity, the change in surface hydrophobicity could influence the interaction or dissociation of different cellular proteins with GlgB in response to different physiological states.


[Prostadoz opportunity for prostate cancer prevention?]
Prevention of prostate cancer (PCa) is a vital problem dictated by the obvious benefit of prevention compared to the complexity of treatment. To date, a tremendous amount of research both in vitro, and in vivo assessment of different prophylactic measures has been published. They included consumption of protein, carbohydrate, fat, fiber, vegetable extracts and other solid products, and combinations thereof in the diet, vitamins, minerals, and biologically active substances, medicaments. The optimal preventive agent has not been found, and that prompted us to conduct our own research of dietary supplement ProstaDoz. The study was performed on a group of 58 patients with elevated prostate-specific antigen and the results of the histological study confirming the absence of prostate cancer and the presence of a high degree PIN. After 6 month course of ProstaDoz histological analysis of repeated biopsy samples revealed a significantly lower incidence of prostate cancer and atypical small acinar proliferation in the group receiving ProstaDoz (10.4%) compared to control group (20,7%; p <0,024), and in some cases even regression of PIN (32%) in the study group (p = 0.5). Also, there was a significant reduction in prostate-specific antigen after receiving ProstaDoz. These data show the potential effectiveness of ProstaDoz use as a means of PCa chemoprevention.


Using the PEN&PAD information model to support hospital-based clinical care.
The PEN&PAD model for clinical record systems has been successfully used for medical records in both General Practice and hospital-based care. This paper describes experiences of using the model for developing computer-based nursing records. Results from this work show that there are some problems with directly applying the model to the nursing domain. Whilst the main purpose of the nursing record is to document and communicate a patient's care, it has several other, possibly incompatible, roles. Furthermore, the structure and content of the information contained within the nursing record is heavily influenced by the need for the nursing profession to visibly demonstrate the philosophical frameworks underlying their work. By providing new insights into the professional background of nursing records, this work has highlighted the need for nurses to clarify and make explicit, their uses of information, and also provided them with some tools to assist in this task.


Objective excyclotorsion in age-related distance esotropia.
Age-related distance esotropia (ARDE) is thought to be caused by sagging eye syndrome. Sagging of the lateral rectus derives from the naturally occurring aging process and induces excyclotorsion of the eye. To date, no study has compared the cyclodeviation in ARDE with that in the age-matched individuals without strabismus. This study aimed to measure the objective cyclotorsion on fundus photographs of ARDE patients and compare the findings with those for normal age-matched individuals. Objective cyclotorsion was measured by determining the disc-to-fovea angle (DFA) on fundus photographs, which were obtained from two groups: 38 consecutive patients with ARDE (age, 74.1 ± 7.9 years), 76 normal age-matched controls (age, 73.9 ± 8.1 years). DFA in ARDE patients was not different from that in the control group (Welch's t-test: ARDE vs Control, right eye; 7.7° ± 2.9° vs 6.8° ± 3.9°, p = .18. Left eye; 10.0° ± 4.5° vs 9.4° ± 3.6°, p = .54. Sum of both eyes; 17.6° ± 5.8° vs 16.2° ± 4.7°, p = .21). These findings suggest sagging of the lateral rectus is not the sole cause of ARDE. Another aging-related factor, such as decreased phoria adaptation, might also be responsible for ARDE.


A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis.
NS-018 is a Janus-activated kinase 2 (JAK2)-selective inhibitor, targeting the JAK-signal transducer and activator of transcription (STAT) pathway that is deregulated in myelofibrosis. In this phase I, dose-escalation portion of a phase I/II study, patients with myelofibrosis received oral NS-018 in continuous 28-day cycles. The primary study objective was to evaluate safety, tolerability and clinically active dose of NS-018. Forty-eight patients were treated; 23 (48%) had previously received a JAK inhibitor (JAKi). The most common drug-related adverse events were thrombocytopenia (27%)/anemia (15%) for hematologic events, and dizziness (23%)/nausea (19%) for non-hematologic events. Once daily NS-018 at 300 mg was chosen as the phase II study dose based on improved tolerability compared with higher doses. A ⩾50% reduction in palpable spleen size was achieved in 56% of patients (47% of patients with prior JAKi treatment), and improvements were observed in myelofibrosis-associated symptoms. Bone marrow fibrosis grade (local assessment) improved from baseline in 11/30 evaluable patients (37%) after 3 cycles of NS-018. JAK2 allele burden was largely unchanged. Changes in cytokine/protein levels were noted after 4 weeks of treatment. NS-018 reached peak plasma concentration in 1-2 h and did not accumulate with multiple dosing. NS-018 will be assessed in patients with previous JAKi exposure in the phase II portion.


Evidence for microwave-induced acoustical resonances in biological material.
Pulse bursts of microwave energy were used to stimulate resonant-type acoustical response in a rectangular muscle-equivalent model and in a spherical brain-equivalent model. The rectangular model was irradiated using a military radar transmitter at 5.655 GHz, 200 kW peak, and the spherical model was irradiated using a pulse-type cavity oscillator at 1.10 GHz, 4 kW peak. Hydrophone transducers were implanted in the models to record the microwave-induced mechanical vibrations. Four properly timed radar pulses produced a threefold increase in the acoustical amplitudes in the muscle model. In the spherical model, a pulse train of three properly timed microwave pulses doubled the stress wave amplitudes as recorded by the implanted hydrophone. These results show that certain pulse parameters of microwave irradiation can be adjusted to increase the intensity of induced mechanical vibrations in both rectangular and spherical tissue equivalent models.


Penetration of parenterally administered gentamicin into the cerebrospinal fluid in experimental meningitis.
The penetration of parenterally administered gentamicin into the CSF was examined in dogs. The experiments were carried out in three stages: (1) in healthy dogs, (2) in dogs with meningitis, and (3) during recovery from the acute inflammation. Gentamicin was found to penetrate poorly into the CSF, reaching mean peak levels of 0.7 mug/ml in healthy dogs. During the height of the meningeal inflammation the mean peak gentamicin level in the CSF was 0.9 mug/ml. The ratio of mean maximum CSF to mean maximum serum levels of gentamicin was 5.8% in healthy dogs, and 11.3% in dogs with meningitis. Thus, inflammation increases the penetration of parenterally administered gentamicin into the CSF, but therapeutically adequate levels for gram-negative bacillary meningitis are not achieved.


Spin Echo Attenuation of Restricted Diffusion as a Discord of Spin Phase Structure
By using the particle probability density we analyze the spin echo attenuation of particles, diffusing in a bounded region. It provides a means to expand a nonuniform spin phase distribution into a series of waves that characterize the geometry and boundary conditions of confinement. Random motion disrupts the initial phase structure created by applied gradients and consequently discords its structure waves. By assuming the spin phase fluctuation and/or the randomness of spin phase distribution in the subensemble as a Gaussian stochastic process, we derive a new analytical expression for the echo attenuation related to the particle velocity correlation. For a diffusion in porous structure we get the expression featuring the same "diffusive diffraction" patterns as those being found and explained by P. T. Callaghan and A. Coy ("Principles of Nuclear Magnetic Resonance Microscopy," Oxford Univ. Press, Oxford (1991); J. Chem. Phys. 101, 4599-4609 (1994)) with the use of propagator theory. With the new approach we cast a new light on the phenomena and derive analitically how the diffusive diffractions appear when the sequence of finite or even modulated gradients are applied. The method takes into account the non-Markovian character of restricted diffusion, and therefore the echo dependence on the diffusion lengths and on the strength of applied gradient differs from the results of authors assuming the Markovian diffusion either by dealing with the diffusion propagators or by the computer simulation of Fick's diffusion. Copyright 1998 Academic Press.


Alpha-fetoprotein in the brain of developing rats and pigs. An immunofluorescent study of cell-and-tissue differentiation.
Alpha-fetoprotein (AFP) and some other serum proteins have been studied in the developing brain of rats and pigs using the indirect immunofluorescence technique. AFP is shown to be present in the ventricular ependyma, meningeal envelopes, the choroid plexus, blood vessel walls and in a wide scale of differentiating parenchymal cells ever since early embryonic ages of both species. In brain parenchyma the content of AFP is low in immature germinative cells; in both species it starts increasing in postmigratory neuroblasts and reaches a peak at the time of accelerated nerve cell differentiation. In rats, the amount of AFP is highest towards the end of the first postnatal week; then it starts decreasing and disappears towards the end of the 3rd week. In both species AFP is localized in the cytoplasm of nerve cell perikarya and their differentiating processes. Higher concentration of this protein has often been observed at the axonal pole of the cytoplasm of differentiating pyramidal neurons. Immunoglobulin G has been found in non-parenchymal structures, and small amounts also in parenchymal cells of embryonic and early postnatal rats following a pattern of cell-and-tissue distribution similar to that of AFP. In pigs, a low amount of albumin has been shown in differentiating leptomeninges. These data suggest uptake of AFP, and some other serum proteins, from the cerebrospinal fluid into cells of the immature rat and pig brain and its increase (or higher binding) in differentiating neurons.


Expression of programmed cell death ligand 1 and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy for advanced high-grade serous ovarian cancer.
To investigate the prognostic value of the expressions of programmed cell death ligand 1 (PD-L1) and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy (NAC) for advanced high-grade serous ovarian cancer (HGSOC). We collected pre- and post-NAC tumor samples from patients with advanced HGSOC between 2006 and 2017. Post-NAC tumor tissue samples were available for immunostaining from 131 patients. The expressions of PD-L1 and immune checkpoint markers were assessed by immunohistochemical staining and the status of tumor-infiltrating lymphocytes (TILs) was also evaluated. We examined whether there are significant associations between protein expression status and patient outcomes and whether significant changes in protein expression levels occurred in response to NAC. PD-L1 expression in the tumor cells was evaluated in 113 patients, 12 (10.6%) of whom had high PD-L1 expression (≥25%) in post-NAC tissues. However, these high levels were not associated with progression-free survival (PFS; P = 0.348) or overall survival (OS; P = 0.699). Similarly, high stromal TILs [≥50%; n = 16 (15.0%)] among the 107 patients evaluated did not show any significant impact on PFS (P = 0.250) or OS (P = 0.800). Moreover, an abundance of TILs (intraepithelial, CD8+, and Foxp3+) and the expression of immune checkpoint markers (PD-1, ICOS, and LAG-3) in residual tumors did not confer any significant survival benefit. The impact of NAC on PD-L1 expression and stromal TILs varied considerably among individual patients. Although the expression of PD-L1 and immune checkpoint markers in residual tumors after NAC had no prognostic impact on survival in patients with HGSOC, post-NAC evaluation of these proteins in chemoresistant tumors may help select patients for immunotherapy trials.


Limited trypsinolysis of native Escherichia coli elongation factor G.
Native elongation factor G possesses three peptide bonds or limited regions of the molecule which are especially sensitive to trypsinolysis. Cleavage at these sites occurs in sequence. Initially, the protein, a single peptide chain of 74,000 daltons, is rapidly split into a fragment of 71,000 daltons and one or more small peptides totaling 3000 daltons. This initial scission does not alter the gross three-dimentional structure of the protein, as the native and trypsin-cleaved protein have the same Kd on Sephadex gel filtration. Although cleaved, the modified elongation factor G retains full activity as measured by its ability to form complexes with the ribosome and guanine nucleotides. A single peptide bond (or region) in the 71,000-dalton fragment is then completely cleaved, yielding fragments of 47,000 and 29,000 daltons. These fragments do not remain associated under native conditions, as they are clearly resolved on gel filtration. Loss of activity is concomitant with the scission of the 71,000-dalton fragment. The third cleavage is complete under the conditions employed here and occurs in the 47,000-dalton peptide generating a fragment of 45,000 daltons and one or more small peptides totaling 2000 daltons. Prolonged treatment with higher levels of trypsin ultimately reduces the protein to small peptides but without generating further discrete fragments visible on sodium dodecyl sulfate gel electrophoresis.


IL-21 restricts T follicular regulatory T cell proliferation through Bcl-6 mediated inhibition of responsiveness to IL-2.
T follicular regulatory (Tfr) cells control the magnitude and specificity of the germinal centre reaction, but how regulation is contained to ensure generation of high-affinity antibody is unknown. Here we show that this balance is maintained by the reciprocal influence of interleukin (IL)-2 and IL-21. The number of IL-2-dependent FoxP3+ regulatory T cells is increased in the peripheral blood of human patients with loss-of-function mutations in the IL-21 receptor (IL-21R). In mice, IL-21:IL-21R interactions influence the phenotype of T follicular cells, reducing the expression of CXCR4 and inhibiting the expansion of Tfr cells after T-cell-dependent immunization. The negative effect of IL-21 on Tfr cells in mice is cell intrinsic and associated with decreased expression of the high affinity IL-2 receptor (CD25). Bcl-6, expressed in abundance in Tfr cells, inhibits CD25 expression and IL-21-mediated inhibition of CD25 is Bcl-6 dependent. These findings identify a mechanism by which IL-21 reinforces humoral immunity by restricting Tfr cell proliferation.


Mortality of Chinese in New South Wales, 1969-1978.
A high proportion of adult Chinese living in New South Wales were born elsewhere, most commonly in China. Mortality among these males from 1969-78 was due mainly to ischaemic heart disease (IHD) cancer and cerbrovascular disease. Females showed a similar general pattern. Chinese males had double the risk of dying from cerebrovascular death, but death rates from IHD were similar to those of the Australian population, although the risk of IHD was significantly lower in Chinese females. Male Chinese had significantly higher rates for cancers of the nasopharynx, lung, intestines and rectum, and stomach and liver, whereas females had a significantly higher risk for cancers of the lung and stomach. Mortality patterns were similar to those for United States Chinese. Apart from cancer, relatively little is known about the causes of death in China. Crude death rates only are available for very broad categories of causes of death. Most of our information on Chinese general mortality comes from studies of migrants, or their descendants overseas, mainly in South-East Asia and the USA. In the latter more detailed studies have been made of cancer mortality and cancer incidence than of other causes. The purpose of our study was to describe mortality in Chinese, born in China, and dying in the state of New South Wales from 1969-78.


A Method of Shoulder Spica Cast Application In Shoulder Muscle Transfer Patients In Supine Position.
Background Children with birth brachial plexus injury (BBPI) often require secondary surgery for the shoulder. The shoulder spica is necessary after shoulder muscle transfer surgery in babies with BBPI. However, its application can be difficult in the supine position under anesthesia. The authors describe a simple and cost-effective method of applying the shoulder spica cast without changing the supine position under anesthesia. Technique While still under anesthesia, the child is placed in a supine position and then elevated on the wooden bar. The POP roll is wrapped around in a cylindrical manner, starting from the level one inch above the anterior superior iliac spine. The contralateral shoulder is also incorporated into the cast. Conclusion The spica application technique described comprises commonly available materials, such as a wooden plank, pair of bolsters, plaster of Paris rolls, and dressing materials overcoming the need for customized apparatus or the operation table. The materials are easy to assemble and thereby applicable just about anywhere. The task also becomes less challenging for the anesthetic in the supine position. This technique is easily reproducible and cost-effective.


Continuous Glucose Monitoring: Impact on Hypoglycemia.
The necessity of strict glycemic control is unquestionable. However, hypoglycemia remains a major limiting factor in achieving satisfactory glucose control, and evidence is mounting to show that hypoglycemia is not benign. Over the past decade, evidence has consistently shown that real-time continuous glucose monitoring improves glycemic control in terms of lowering glycated hemoglobin levels. However, real-time continuous glucose monitoring has not met the expectations of the diabetes community with regard to hypoglycemia prevention. The earlier trials did not demonstrate any effect on either mild or severe hypoglycemia and the effect of real-time continuous glucose monitoring on nocturnal hypoglycemia was often not reported. However, trials specifically designed to reduce hypoglycemia in patients with a high hypoglycemia risk have demonstrated a reduction in hypoglycemia, suggesting that real-time continuous glucose monitoring can prevent hypoglycemia when it is specifically used for that purpose. Moreover, the newest generation of diabetes technology currently available commercially, namely sensor-augmented pump therapy with a (predictive) low glucose suspend feature, has provided more convincing evidence for hypoglycemia prevention. This article provides an overview of the hypoglycemia outcomes of randomized controlled trials that investigate the effect of real-time continuous glucose monitoring alone or sensor-augmented pump therapy with a (predictive) low glucose suspend feature. Furthermore, several possible explanations are provided why trials have not shown a reduction in severe hypoglycemia. In addition, existing evidence is presented of real-time continuous glucose monitoring in patients with impaired awareness of hypoglycemia who have the highest risk of severe hypoglycemia.


Exploring the use of the Hinting Task in first-episode psychosis.
The aim of the study was to elucidate the association between performance-related neurocognitive abilities and Theory of Mind (ToM) as measured by the Hinting Task (HT) performance and investigate the psychometric properties of the HT for use in First-Episode Psychosis (FEP). Cross-sectional data of 132 participants with FEP, aged 15-25 years, enrolled in a randomised controlled trial of vocational intervention, were analysed. A comprehensive cognitive battery including social cognitive and neurocognitive measures, a social and occupational functioning measure and psychopathological measures, were used. Psychometric properties were measured through bivariate correlations and associations with neurocognitive domains were assessed through hierarchical regression. Low convergent validity of the HT with other ToM measures, moderate discriminant validity with an emotion recognition task, low predictive validity with social and occupational functioning, and high internal consistency were revealed. HT performance was significantly associated with verbal reasoning and verbal memory. Results provide preliminary evidence of low convergent validity and moderate discriminant validity of the HT in FEP, and the influence of verbal reasoning and verbal memory on HT performance, indicating that caution is warranted when employing the HT as a screening tool in isolation for detection of ToM deficits in FEP.


Canadian quality indicators for percutaneous coronary interventions.
Quantifying adherence to quality indicators can serve as a direct measure of quality of care and provide the foundation for quality improvement. However, quality indicators for percutaneous coronary intervention (PCI) have not been developed in Canada. To develop a set of quality and outcome indicators for PCI that can be used across Canada. A 12-member national expert panel was selected to represent practice in different regions of Canada. Potential quality indicators were identified by a detailed search of published guidelines, randomized trials and outcomes studies. A two-step modified Delphi process was employed with an initial screening round of indicator ratings, followed by a national quality indicator panel meeting, and follow-up discussions to obtain consensus. A total of 26 indicators including six structure indicators, nine process indicators, and 11 outcomes indicators were identified by the national expert panel to be representative of high quality of care for PCI. Pharmacological indicators included prescription of acetylsalicylic acid, clopidogrel and statin therapy as adjunctive therapy for PCI. Nonpharmacological process indicators included minimal procedure volumes, door-to-balloon time in primary PCI, prevention of contrast-induced nephropathy and selected patient education counselling instructions. Outcome indicators included death, myocardial infarction, target vessel revascularization and vascular access complications after PCI. A new set of PCI quality indicators for use in the Canadian health care system was developed. The widespread adoption and implementation of PCI quality indicators in clinical practice will facilitate the identification of practice gaps to enable quality improvement efforts and to optimize the outcomes of patients undergoing PCI throughout Canada.


Statistical optimization of indomethacin pellets coated with pH-dependent methacrylic polymers for possible colonic drug delivery.
The objective of this study was to evaluate the effect of two factors (ratio of Eudragit S100 and Eudragit L100 and the coating level) on indomethacin release from pellets in order to optimize coating formulations for colonic delivery. Coating formulations were designed based on the full factorial design. Two independent variables were the ratio of Eudragit S100:Eudragit L100 (1:4, 1:1 and 1:0) and the level of coating (10%, 15% and 20%, w/w), respectively. The evaluated responses were lag time prior to drug release at pH 6.8 (the time required for drug release up to 2%) and percent of drug release at pH 6.8 in 5h. Polymers were coated onto the pellets containing 20% (w/w) indomethacin, using a fluidized bed coating apparatus. Dissolution test was carried out in media with different pH (1.2, 6.5, 6.8 and 7.2). The dissolution data revealed that the level of coating and the ratio of polymers are very important to achieve optimum formulation. Using responses and resulted statistical equations, optimum formulation consisted of Eudragit S100:L100 in 4:1 ratio and the level of coating (20%) was predicted. Practical results showed that the pellets prepared according to above formulation released no indomethacin at pH 1.2 (simulating stomach pH) and pH 6.5 (simulating proximal part of small intestine pH); drug release was slowly at pH 6.8 (simulating lower part of small intestine pH), but it was fast at pH 7.2 (simulating terminal ileum pH). The results of this study revealed that factorial design is a suitable tool for optimization of coating formulations to achieve colon delivery. It was shown that coating formulation consisted of Eudragit S100:Eudragit L100 in 4:1 ratio at 20% coating level has potential for colonic delivery of indomethacin loaded pellets. The optimized formulation produced dissolution profiles that were close to predicted values.


Effect of on-call-related sleep deprivation on physicians' mood and alertness.
Physicians may experience periods of acute sleep deprivation while on-call, in addition to baseline chronic sleep deprivation which may affect physicians' performance and patients' safety. The purpose of this study was to determine the effect of acute sleep deprivation due to working long on-call shifts on mood and alertness, both of which may impair physicians' performance. Eighty-eight junior physicians working in one university hospital completed a questionnaire, before and after completion of a shift, that collected data regarding socio-demographic factors, patterns of work and sleep, Profile of Mood States (POMS), and Stanford Sleepiness Scale. Based on duration of sleep the physicians had during on-call in comparison to their usual average sleep, the participants were categorized into group 1 (those who slept many fewer hours), group 2 (those who slept fewer hours), or group 3 (those who slept the same number of hours). More than 87% of the participant slept 5 or fewer hours while working an on-call shift. Among all participants, the percentage of physicians who were alert post-on-call was significantly reduced compared to the percentage pre-on-call (P = 0.001). The post-on-call total POMS scores of groups 1 and 2 were significantly worse than their pre-on-call scores (P = 0.001 and 0.038, respectively), while there was no significant difference between the pre- and post-on-call POMS scores of group 3 (P = 0.165). Acute sleep loss due to working long on-call shifts significantly decreases daytime alertness and negatively affects the mood state of junior physicians.


PRKACA Somatic Mutations Are Rare Findings in Aldosterone-Producing Adenomas.
Somatic mutations have been found causative for endocrine autonomy in aldosterone-producing adenomas (APAs). Whereas mutations of PRKACA (catalytic subunit of protein kinase A) have been identified in cortisol-producing adenomas, the presence of PRKACA variants in APAs is unknown, especially in those that display cosecretion of cortisol. The objective of the study was to investigate PRKACA somatic variants identified in APA cases. Identification of PRKACA somatic variants in APAs by whole-exome sequencing followed by in vitro analysis of the enzymatic activity of PRKACA variants and functional characterization by double immunofluorescence of CYP11B2 and CYP11B1 expression in the corresponding tumor tissues. APA tissues were collected from 122 patients who underwent unilateral adrenalectomy for primary aldosteronism between 2005 and 2015 at a single institution. PRKACA somatic mutations were identified in two APA cases (1.6%). One APA carried a newly identified p.His88Asp variant, whereas in a second case, a p.Leu206Arg mutation was found, previously described only in cortisol-producing adenomas with overt Cushing's syndrome. Functional analysis showed that the p.His88Asp variant was not associated with gain of function. Although CYP11B2 was strongly expressed in the p.His88Asp-mutated APA, the p.Leu206Arg carrying APA predominantly expressed CYP11B1. Accordingly, biochemical Cushing's syndrome was present only in the patient with the p.Leu206Arg mutation. After adrenalectomy, both patients improved with a reduced number of antihypertensive medications and normalized serum potassium levels. We describe for the first time PRKACA mutations as rare findings associated with unilateral primary aldosteronism. As cortisol cosecretion occurs in a subgroup of APAs, other molecular mechanisms are likely to exist.


Electro-optical effects of high aspect ratio P3HT nanofibers colloid in polymer micro-fluid cells.
This Letter reports the electro-optical (EO) effect of Poly(3-hexylthiophene-2,5-diyl) (P3HT) nanofibers colloid in a polymer micro-fluidic EO cell. P3HT nanofibers are high aspect ratio semiconducting nanostructures, and can be collectively aligned by an external alternating electric field. Optical transmission modulated by the electric field is a manifestation of the electro-optical effect due to high inner crystallinity of P3HT nanofibers. According to our results, the degree of alignment reaches a maximum at 0.6 V/μm of electric field strength, implying a big polarizability value due to geometry and electrical properties of P3HT nanofibers. We believe that one-dimensional crystalline organic nanostructures have a large potential in EO devices due to their significant anisotropy, wide variety of properties, low actuation voltages, and opportunity to be tailored via adjustment of the fabrication process.


Laparoscopic surgery for female posterior urethral bladder diverticulum with bladder outlet obstruction: A case report.
Bladder diverticula (BD) can be classified into congenital and acquired forms, with the latter accounting for approximately 90% of all cases, primarily among male patients. Although BD-associated anatomical bladder outlet obstruction (BOO) is uncommon, existing literature suggests that congenital BD are more frequently observed in male children and rarely in female children. While around 70% of acquired BD are linked to BOO secondary to benign prostatic hyperplasia in male patients, clinical reports of female BD are less common. Furthermore, cases of female BD located posterior to the urethra, which lead to voiding difficulties, are exceedingly rare. Herein, we present a case of laparoscopic treatment in a 53-year-old female patient diagnosed with congenital bladder diverticulum causing progressively worsening dysuria. Voiding cystourethrography revealed a soft cystic protrusion of the posterior urethral wall during voiding, which reinforced the patient's symptoms. Urodynamic examination showed elevated detrusor muscle contraction during voiding, a reduced urinary flow rate, and P/Q values indicative of significant BOO. Considering the patient's clinical condition, we performed laparoscopic bladder diverticulectomy, partial urethral croppingplasty, and cystoplasty. The laparoscopic bladder diverticulectomy, partial urethral croppingplasty, and cystoplasty procedures were completed thoroughly and with great success. However, complete removal of the diverticular epithelium proved challenging, resulting in an overall operative time of approximately 3 hours and 32 minutes. At the postoperative follow-up, the patient presented with symptoms of a lower urinary tract infection for a week, which were effectively resolved with oral antibiotics. At the 8-month follow-up, the patient reported normal urination and the absence of any discomfort during urination. Female bladder outlet obstruction resulting from posterior urethral BD can be challenging to visualize during transurethral cystoscopy, especially with limited angulation, and may even be overlooked. Furthermore, conventional transvaginal diverticulectomy is often difficult to perform effectively. Therefore, laparoscopic bladder diverticulectomy, partial urethral croppingplasty, and cystoplasty are considered appropriate treatment options for such cases.


Long-term patient satisfaction after retropubic and transobturator mid-urethral slings for female stress urinary incontinence.
The aim of this study was to report long-term patient outcomes after retropubic and transobturator mid-urethral slings for female stress urinary incontinence. Women who underwent mid-urethral sling for stress urinary incontinence between 2000 and 2010 were invited to participate in a survey regarding their overall improvement. Patients' outcomes were assessed using the International Consultation on Incontinence Questionnaire - Short Form and the Global Response Assessment Scale. The questionnaires were completed by 330 patients. Their median age at the time of surgery was 54.8 years (±12.9) and the median follow-up period was 11.9 years (±6.4). Retropubic and transobturator approaches were performed in 128 (38.8%) and 202 (61.2%) patients, respectively. The International Consultation on Incontinence Questionnaire - Short Form score dropped from an average of 14 (±4.1) to 6.4 (±6) with no significant difference between the two groups. The Global Response Assessment Scale showed an 9% greater improvement in the retropubic (66.4%) over the transobturator (57.4%) approach. De novo overactive bladder was the commonest long-term reported adverse event, affecting 18/330 patients (5.5%). Voiding dysfunction that required surgical correction following the retropubic approach occurred in three patients (2.3%). Mid-urethral slings for the management of female stress urinary incontinence had good and durable long-term effects. Although the retropubic approach gave better results, they were not significantly different than those of the transobturator approach.


Alveolar Micromechanics in Bleomycin-induced Lung Injury.
Lung injury results in intratidal alveolar recruitment and derecruitment and alveolar collapse, creating stress concentrators that increase strain and aggravate injury. In this work, we sought to describe alveolar micromechanics during mechanical ventilation in bleomycin-induced lung injury and surfactant replacement therapy. Structure and function were assessed in rats 1 day and 3 days after intratracheal bleomycin instillation and after surfactant replacement therapy. Pulmonary system mechanics were measured during ventilation with positive end-expiratory pressures (PEEPs) between 1 and 10 cm H2O, followed by perfusion fixation at end-expiratory pressure at airway opening (Pao) values of 1, 5, 10, and 20 cm H2O for quantitative analyses of lung structure. Lung structure and function were used to parameterize a physiologically based, multicompartment computational model of alveolar micromechanics. In healthy controls, the numbers of open alveoli remained stable in a range of Pao = 1-20 cm H2O, whereas bleomycin-challenged lungs demonstrated progressive alveolar derecruitment with Pao < 10 cm H2O. At Day 3, ∼40% of the alveoli remained closed at high Pao, and alveolar size heterogeneity increased. Simulations of injured lungs predicted that alveolar recruitment pressures were much greater than the derecruitment pressures, so that minimal intratidal recruitment and derecruitment occurred during mechanical ventilation with a tidal volume of 10 ml/kg body weight over a range of PEEPs. However, the simulations also predicted a dramatic increase in alveolar strain with injury that we attribute to alveolar interdependence. These findings suggest that in progressive lung injury, alveolar collapse with increased distension of patent (open) alveoli dominates alveolar micromechanics. PEEP and surfactant substitution reduce alveolar collapse and dynamic strain but increase static strain.


Measles: Why it's still a threat.
A recent outbreak in Minnesota underscores the need to maintain vigilance and adhere to best practices in immunization and containment of known cases.


DNA bending creates favored sites for retroviral integration: an explanation for preferred insertion sites in nucleosomes.
The choice of retroviral integration sites is strongly influenced by chromatin: integration in vitro occurs more efficiently into nucleosomal DNA than into naked DNA, and a characteristic pattern of preferred insertion sites with a 10 bp periodicity is observed at the outer face of the nucleosomal DNA. At least three features of nucleosomal DNA could be responsible for the creation of these favored sites: the presence of histones, attachment of the DNA to a protein surface, and DNA bending. To test each of these possibilities, we studied integration in vitro with human immunodeficiency virus and murine leukemia virus integrases into four model targets that mimic features of nucleosomal DNA: (i) catabolite activator protein-DNA complexes; (ii) lac repressor-operator complexes; (iii) lac repressor-induced loops; and (iv) intrinsically bent A-tract DNA. We found that bending of the target DNA can create favored integration sites at the outer face of the helix, irrespective of whether the bent DNA is attached to a protein surface. Our findings offer an explanation for the preferred usage of nucleosomes as integration targets. In addition, they suggest that bending of the target DNA might be an intrinsic feature of the integration reaction.


Comparative haemodynamic dose-response effects of intravenous propranolol, acebutolol and penbutolol in angina pectoris.
The relevance of the ancillary pharmacological properties of intrinsic sympathomimetic activity (ISA) and cardioselectivity to the haemodynamic profile following intravenous beta-blockade was examined in a randomised study of propranolol (16 mg), acebutolol (160 mg) or penbutolol (4 mg) in 30 patients with stable angina pectoris. Haemodynamic measurements were undertaken at rest and during four minutes steady-state supine bicycle exercise (25 to 50 W), load limited to the angina threshold, before and after each drug. The randomised groups were statistically similar for major haemodynamic and clinical variables. The plasma concentrations achieved for each drug were in the therapeutic range. At rest, propranolol resulted in greater reductions in resting cardiac output and greater increase in pulmonary artery occluded pressure compared with acebutolol and penbutolol. During the sympathetic stimulus of dynamic exercise, penbutolol resulted in less depression of exercise cardiac performance than either acebutolol or propranolol. These observations are compatible with previous studies which suggested that the possession of ISA by a beta-blocking drug offset the depression of cardiac performance following intravenous beta-blockade; the benefits of ISA on haemodynamic profile appeared maximum at rest and were reduced or abolished during dynamic exercise.


Tailored Morphology in Polystyrene/Poly(lactic acid) Blend Particles: Solvent's Effect on Controlled Janus/Core-Shell Structures.
Controlling the morphology of polymeric particles is vital for their diverse applications. In this study, we explored how solvent composition influences the morphology of poly(styrene)/poly(lactic acid) (PS/PLA) particles prepared via the emulsion solvent evaporation method. We used toluene, dichloromethane (DCM), and various mixtures to prepare these particles. We investigated phase separation within the PS/PLA/solvent system using the Flory-Huggins ternary phase diagram and MesoDyn simulation, revealing pronounced immiscibility and phase separation in both PS/PLA/DCM and PS/PLA/toluene systems. We employed scanning electron microscopy (SEM) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) to characterize the resulting morphologies. Our study unveiled the substantial impact of solvent composition on particle structure. Using pure toluene resulted in acorn-shaped Janus particles. However, incorporating DCM into the solvent induced a transition from Janus to core-shell morphology. Remarkably, core-shell particles exhibited a single-core structure in a mixed toluene/DCM solvent, indicating thermodynamic stability. In contrast, pure DCM favored kinetically controlled multicore morphology, leading to lower PLA crystallinity due to increased PS-PLA interfaces. Samples with high Janus balance formed a self-assembled, two-dimensional (2-D) monolayer film, demonstrating the interfacial activity of the Janus particles. This 2-D monolayer film exhibits desirable emulsification properties with potential applications in various fields. Our study combines theoretical and experimental analyses, shedding light on the profound impact of solvent composition on the PS/PLA particle morphology. We observed transitions from Janus to core-shell structures, highlighted the influence of solvent viscosity on particle size, and uncovered the formation of self-assembled 2-D monolayer films. These insights are pivotal for tailoring polymeric particle structures. Furthermore, our findings advance macromolecular science in interface design, offering promising prospects for innovative materials development.


Interleukin-6 (B-cell stimulatory factor 2)-dependent growth of a Lennert's lymphoma-derived T-cell line (KT-3).
A T lymphoma cell line (KT-3) established from a patient with Lennert's lymphoma showed macrophage-dependent growth. Macrophage-derived factors were able to replace the macrophage functions. Experiments using a variety of cytokines demonstrated that KT-3 proliferated in response to recombinant interleukin-2 (rIL-2), rIL-4, or rIL-6 but did not proliferate in response to rIL-1 alpha, rIL-1 beta, rIL-3, recombinant granulocyte colony-stimulating factor (rG-CSF), rGM-CSF, recombinant interferon-alpha (rIFN-alpha), rIFN-gamma, recombinant tumor necrosis factor (rTNF-alpha), or native IFN-beta. Polyclonal rabbit anti-IL-6 antibody almost completely neutralized the activities of macrophage-derived factors or IL-6 but not IL-2 or IL-4. Scatchard plot analysis demonstrated that KT-3 cells indeed express IL-6 receptors. The results indicate that the macrophage-derived factor that supports the growth of KT-3 is IL-6 and suggest that macrophage-derived IL-6 may play an important role in the histopathogenesis of Lennert's lymphoma.


Use of denaturing high-performance liquid chromatography to identify Bacillus anthracis by analysis of the 16S-23S rRNA interspacer region and gyrA gene.
Denaturing high-performance liquid chromatography (DHPLC) was evaluated as a method for identifying Bacillus anthracis by analyzing two chromosomal targets, the 16S-23S intergenic spacer region (ISR) and the gyrA gene. The 16S-23S ISR was analyzed by this method with 42 strains of B. anthracis, 36 strains of Bacillus cereus, and 12 strains of Bacillus thuringiensis; the gyrA gene was analyzed by this method with 33 strains of B. anthracis, 27 strains of B. cereus, and 9 strains of B. thuringiensis. Two blind panels of 45 samples each were analyzed to evaluate the potential diagnostic capability of this method. Our results show that DHPLC is an efficient method for the identification of B. anthracis.


Surgical treatment of ascending aorta and innominate artery trunk aneurysm with displaced brachiocephalic vessels.
The surgical treatment of ascending aortic and arch aneurysms, even though technically complex and requiring care to avoid neurological sequelae, is well established. Nevertheless, the presence of a significant innominate artery trunk aneurysm implies an adaptation of the surgical options available. We report a case of an aortic aneurysm that involved the ascending aorta, the proximal transverse arch and the brachiocephalic trunk with cranial displacement of the right subclavian and common carotid arteries. This pattern, meant that it was mandatory to change the usual surgical approach. We resected the ascending aorta and the proximal aortic arch replacing them with a dacron prosthesis in a usual fashion. Nevertheless, we were compelled to perform the anastomoses of the innominate trunk branches in an extrathoracic fashion. Furthermore, to ensure an uninterrupted cerebral perfusion, the usual surgical steps were personalized. The anatomical findings, computed tomographic images, surgical technique, cerebral protection and postoperative evaluation are described.


Comparison of recurrence rates after anterior colporrhaphy for cystocele using three different surgical techniques.
To compare the recurrence rates after anterior colporrhaphy for cystocele using three different surgical techniques: standard plicating, purse-string, and rolling anterior colporrhaphy. A retrospective chart review of women undergoing anterior colporrhaphy for cystocele with or without concomitant operations between 1988 and 2000 was conducted. Women were assessed by vaginal examination pre- and postoperatively at 6 weeks and over 2 years. Grades of cystocele were assessed by Baden-Walker halfway grading system. chi(2) tests and ANOVAs were performed for categorical and continuous variables, respectively. Cox regressions were used to calculate recurrent rates. Among the studied 363 women, 296, 33, and 34 underwent standard plicating, purse-string and rolling techniques, respectively. There was no significant difference in age, parity, menopausal status, or mean length of follow-up among the three groups. The purse-string group revealed a significantly higher risk of recurrence than the standard plicating group (hazard ratio: 2.67; 95% CI: 1.05-6.08). The severity of cystocele was another key role of determining the prognosis for recurrences (grades 3 & 4 relative to grade 1, hazard ratio: 3.35; 95% CI: 1.34-8.38). Our study showed that standard plicating and rolling technique provided similar anatomic cure rates. However, the purse-string technique was less effective in restoring vaginal anatomy than standard plicating anterior colporrhaphy.


Nitrosoureas inhibit the stathmin-mediated migration and invasion of malignant glioma cells.
Malignant gliomas are the most common primary intrinsic brain tumors and are highly lethal. The widespread migration and invasion of neoplastic cells from the initial site of tumor formation into the surrounding brain render these lesions refractory to definitive surgical treatment. Stathmin, a microtubule-destabilizing protein that mediates cell cycle progression, can also regulate directed cell movement. Nitrosoureas, traditionally viewed as DNA alkylating agents, can also covalently modify proteins such as stathmin. We therefore sought to establish a role for stathmin in malignant glioma cell motility, migration, and invasion and determine the effects of nitrosoureas on these cell movement-related processes. Scratch wound-healing recovery, Boyden chamber migration, Matrigel invasion, and organotypic slice invasion assays were performed before and after the down-regulation of cellular stathmin levels and in the absence and presence of sublethal nitrosourea ([1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea]; CCNU) concentrations. We show that decreases in stathmin expression lead to significant decreases in malignant glioma cell motility, migration, and invasion. CCNU, at a concentration of 10 micromol/L, causes similar significant decreases, even in the absence of any effects on cell viability. The direct inhibition of stathmin by CCNU is likely a contributing factor. These findings suggest that the inhibition of stathmin expression and function may be useful in limiting the spread of malignant gliomas within the brain, and that nitrosoureas may have therapeutic benefits in addition to their antiproliferative effects.


Stobadine-inhibitor of cyclophosphamide-induced micronuclei in mice.
The potential antimutagenic effect of stobadine dipalmitate (STB) on the frequency of micronuclei in reticulocytes of peripheral blood in female ICR mice was studied. The cyclophosphamide model was used to verify this effect. Stobadine dipalmitate was administered orally in three concentrations: STB I, 7.07; STB II, 23.6; STB III, 70.07 mg/kg body wt 2 h prior to or 4 h after (STB II only) cyclophosphamide administration (intraperitoneally, twice 80 mg/kg body wt with a 24 h interval). The method designed by Hayashi et al. [(1990) Mutat. Res., 245, 245-249] was used to prepare and to stain the slides. The results of the experiment show that pretreatment with stobadine 2 h prior to cyclophosphamide administration significantly decreased its mutagenic effect, as manifested by the reduced frequency of micronucleated reticulocytes. This protective effect of stobadine was concentration-dependent with the highest concentration of stobadine inducing the most pronounced decrease of micronuclei. Analysis and identification of the exact mechanism of the protective effects of stobadine is the aim of our further studies.


Autocrine catecholamine biosynthesis and the beta-adrenoceptor signal promote pigmentation in human epidermal melanocytes.
Earlier it has been shown that human proliferating/undifferentiated basal keratinocytes hold the full capacity for autocrine catecholamine synthesis/degradation and express beta2-adrenoceptors (beta2-AR). In this report, we show that human melanocytes also express all of the mRNA and enzymes for autocrine synthesis of norepinephrine but fail to produce epinephrine. So far, it was established that human melanocytes express alpha1-AR which are induced by norepinephrine yielding the inosine triphosphate diacylglycerol signal. The presence of catecholamine synthesis and the beta2-AR signal escaped definition at that time. Using RT-PCR, immunofluorescence and radioligand binding with the beta2-AR antagonist (-)-[3H]CGP 12177, we show here that human melanocytes express functional beta2-AR (4230 receptors per cell) with a Bmax at 129.3 and a KD of 3.19 nM but lack beta1-AR expression. beta2-AR stimulation with epinephrine 10(-6) M and salbutamol 10(-6)-10(-5) M yielded a strong cyclic adenosine monophospate (cAMP) response in association with upregulated melanin production. Taken together these results indicate that the biosynthesis and release of epinephrine (10(-6) M) by surrounding keratinocytes can provide the cAMP response leading to melanogenesis in melanocytes via the beta2-AR signal. Moreover, the discovery of this catecholaminergic cAMP response in melanocytes adds a new source for this important second messenger in melanogenesis.


Detection of canonical hedgehog signaling in breast cancer by 131-iodine-labeled derivatives of the sonic hedgehog protein.
Activation of hedgehog (HH) pathway signaling is observed in many tumors. Due to a feedback loop, the HH receptor Patched (PTCH-1) is overexpressed in tumors with activated HH signaling. Therefore, we sought to radiolabel the PTCH-1 ligand sonic (SHH) for detection of cancer cells with canonical HH activity. Receptor binding of ¹³¹I-SHH was increased in cell lines with high HH pathway activation. Our findings also show that PTCH-1 receptor expression is decreased upon treatment with HH signaling inhibitors, and receptor binding of ¹³¹I-SHH is significantly decreased following treatment with cyclopamine. In vivo imaging and biodistribution studies revealed significant accumulation of ¹³¹I-SHH within tumor tissue as compared to normal organs. Tumor-to-muscle ratios were approximately 8 : 1 at 5 hours, while tumor to blood and tumor to bone were 2 : 1 and 5 : 1, respectively. Significant uptake was also observed in liver and gastrointestinal tissue. These studies show that ¹³¹I-SHH is capable of in vivo detection of breast tumors with high HH signaling. We further demonstrate that the hedgehog receptor PTCH-1 is downregulated upon treatment with hedgehog inhibitors. Our data suggests that radiolabeled SHH derivatives may provide a method to determine response to SHH-targeted therapies.


Endocrine therapy of advanced breast cancer.
Recent research has resulted in several new options for endocrine treatment of advanced breast cancer. Since one of the most intriguing characteristics of endocrine therapy is that new remissions can be achieved when using subsequent endocrine modalities it is of importance to evaluate their optimal sequence. Tamoxifen has become the most commonly used endocrine therapy of advanced breast cancer due to its few side effects and an overall response rate of 35%, which has been obtained in randomized trials of tamoxifen compared with either ablative, additive or inhibitive treatment approaches. Crossover data from these trials indicate that the highest overall response rate is obtained when tamoxifen is used as first line endocrine therapy. Furthermore, it seems that oophorectomy in premenopausal and aminoglutethimide or progestins in postmenopausal patients are equally effective as second line endocrine therapy. Despite an obvious clinical rationale for combined endocrine therapy most trials exploring this concept have failed to show any benefit. Although data from trials combining tamoxifen with prednisolone or androgens seem exciting, the use of combined endocrine therapy still have to be considered experimental.


In vitro and in silico characterization of fibrous scaffolds comprising alternate colistin sulfate-loaded and heat-treated polyvinyl alcohol nanofibrous sheets.
A multilayer mat for dispensing colistin sulfate through a body surface was prepared by electrospinning. The fabricated system comprised various polyvinyl alcohol fibrous layers prepared with or without the active ingredient. One of the electrospun layers contained water-soluble colistin sulfate and the other was prepared from the same polymer type and composition without the active drug and was finally heat-treated. The heat treatment modified the supramolecular structure and conferred the polymer nanofibre with the rate-controlling function. The microstructure of different layers was tracked by positron annihilation lifetime spectroscopy, and detailed morphological analysis of the fibre mats was performed using a scanning electron microscope. The drug-release profiles of various layer arrangements were studied in relation to their antimicrobial activity. The finite element method was applied to overcome the challenge of diffusion-controlled drug release from multilayer polymer scaffolds. The finite element method was first verified using analytical solutions for a simple arrangement (one drug-loaded swellable fibre and one rate-controlling nonswellable fibre) under perfect sink conditions and in a well-stirred finite volume. The effect of alternate layer arrangements on the drug-release profiles was also investigated to plan for controlled topical drug release from fibrous scaffolds. This design is expected to aid in increasing local effectiveness, thus reducing the systemic loading and the consequent side effects of colistin.


Effects of body mass index on gastric slow wave: a magnetogastrographic study.
We measured gastric slow wave activity simultaneously with magnetogastrogram (MGG), mucosal electromyogram (EMG) and electrogastrogram (EGG) in human subjects with varying body mass index (BMI) before and after a meal. In order to investigate the effect of BMI on gastric slow wave parameters, each subject's BMI was calculated and divided into two groups: subjects with BMI ≤ 27 and BMI > 27. Signals were processed with Fourier spectral analysis and second-order blind identification (SOBI) techniques. Our results showed that increased BMI does not affect signal characteristics such as frequency and amplitude of EMG and MGG. Comparison of the postprandial EGG power, on the other hand, showed a statistically significant reduction in subjects with BMI > 27 compared with BMI ≤ 27. In addition to the frequency and amplitude, the use of SOBI-computed propagation maps from MGG data allowed us to visualize the propagating slow wave and compute the propagation velocity in both BMI groups. No significant change in velocity with increasing BMI or meal was observed in our study. In conclusion, multichannel MGG provides an assessment of frequency, amplitude and propagation velocity of the slow wave in subjects with differing BMI categories and was observed to be independent of BMI.