[Molteno/von Denffer drainage implants in therapy-refractory glaucomas].
In glaucoma eyes in which the pressure regulation was not possible with drugs and surgery or which were blind already, we treated the patients with a Molteno implant by von Denffer. In 10 years (1995 to 2004) we treated 19 eyes with a glaucoma drainage device -- the Molteno implant developed by von Denffer. The average age of the patients was 64 (range: 15 to 77) years. On average 3,1 operations were realised before the implant. The average eye pressure was 44 mm Hg preoperatively. Our patients suffered from different glaucomatous diseases: 7 primary glaucomas (congenital, open and narrow angle glaucoma) and secondary: neovascular glaucoma (4), PEX glaucoma (2), traumatic glaucoma (3) and postoperative glaucoma (3). The intraocular pressure had a successful outcome of under 20 mm Hg in 13 eyes, 5 patients out of these were treated with 1 to 3 drugs. Early complications (flat anterior chamber, hyphaema, hypotonia) were reversible. Late complications were phthisis bulbi (3), explantation of the implant (2) and one evisceration bulbi. We found an improvement of the visual acuity in 4 cases in traumatic and postoperative glaucoma. The stabilisation of visual acuity was possible in primary glaucoma. The implantation of the Molteno implant by von Denffer is an ultimate ratio in eyes with persistent high intraocular pressure. A durable reduction of the pressure is possible in two-thirds and the conservation of the bulbus was achieved in three-fourths of the patients.


A conserved MYB transcription factor is involved in regulating lipid metabolic pathways for oil biosynthesis in green algae.
Green algae can accumulate high levels of triacylglycerol (TAG), yet knowledge remains fragmented on the regulation of lipid metabolic pathways by transcription factors (TFs). Here, via bioinformatics and in vitro and in vivo analyses, we revealed the roles of a myeloblastosis (MYB) TF in regulating TAG accumulation in green algae. CzMYB1, an R2R3-MYB from Chromochloris zofingiensis, was transcriptionally upregulated upon TAG-inducing conditions and correlated well with many genes involved in the de novo fatty acid synthesis, fatty acid activation and desaturation, membrane lipid turnover, and TAG assembly. Most promoters of these genes were transactivated by CzMYB1 in the yeast one-hybrid assay and contained the binding elements CNGTTA that were recognized by CzMYB1 through the electrophoretic mobility shift assay. CrMYB1, a close homologue of CzMYB1 from Chlamydomonas reinhardtii that recognized similar elements for binding, also transcriptionally correlated with many lipid metabolic genes. Insertional disruption of CrMYB1 severely suppressed the transcriptional expression of CrMYB1, as well as of key lipogenic genes, and impaired TAG level considerably under stress conditions. Our results reveal that this MYB, conserved in green algae, is involved in regulating global lipid metabolic pathways for TAG biosynthesis and accumulation.


Liposomal versus plain bupivacaine for pain control following vaginal reconstruction.
Liposomal bupivacaine (LB) is a depot formulation of bupivacaine, which releases the drug over 72 hours to prolong local pain control. This retrospective study compares the effect of using LB versus plain bupivacaine on postoperative pain control, length of hospital stay and cost among patients undergoing vaginal reconstructive surgery. Patients who underwent vaginal reconstructive surgery with levatorplasty and received an injection of 20 cc of either plain bupivacaine or LB for pudendal nerve block were included. The primary outcomes included postoperative narcotic use and subjective pain score. The secondary outcome was postoperative length of stay. Comparisons between groups were performed using the T test, Mann Whitney U and Chi-square tests with p < 0.05 considered significant. Between June 2016 and December 2021, 25 patients had received LB as a pudendal nerve block and 25 had received plain bupivacaine. Demographics between groups were similar. There was no difference between postoperative morphine equivalent dose (MED) for plain bupivacaine versus LB (25.3 ± 65.8 vs. 24.9 ± 31.7 MED; p = 0.159) or length of hospital stay (15.8 ± 12.0 hours vs. 23.8 ± 20.0; p = 0.094). Furthermore, subjective pain was also similar between groups (0 vs. 1.6 ± 2.6, p = 0.68), (4.6 ± 2.3 vs. 4.9 ± 2.0 average POD 1 pain, p = 0.534) and (4.3 ± 2.1 for vs. 4.9 ± 2.1 average POD 2 pain, p = 0.373). LB is not superior to plain bupivacaine for controlling pain following vaginal reconstructive surgery, and justification for the exponentially greater cost of LB is not supported. Prospective investigations with larger sample sizes are needed to determine the optimal pain management for levatorplasty in vaginal reconstructive surgery.


Dantrolene sodium and dystrophia myotonica.
A patient with dystrophia myotonica was given dantrolene sodium to try to provide muscle relaxation during a cholecystectomy. Dantrolene was used as it is accepted that the drug has a place in the control of spasticity and also causes muscle relaxation, whereas conventional muscle relaxants are unable to control myotonia of muscle origin. Dantrolene alone did not provide good enough intubating and operating conditions in this subject. Later studies showed that, after dantrolene, EMG recordings from the patient were not significantly altered, although an impression of a slight increase in the myotonic potentials was gained.


Gender Differences in Predictors of Self-Reported Physical Aggression: Exploring Theoretically Relevant Dimensions among Adolescents from Santiago, Chile.
Research findings remain unclear on whether different factors predict aggression for adolescent men and women. Given that aggression research is rarely conducted with Latin American populations, the current study used multiple imputation and linear regression to assess gender differences in levels and predictors of self-reported physical aggression among a community sample of young (ages 11 through 17) men (n=504) and women (n = 471) from Santiago, Chile. Results revealed that adolescent women reported engaging in higher levels of physical aggression than men. The variables found to be significantly associated with higher levels of reported aggression-younger age, less family involvement, less parental control, less positive relationships with caregivers, having more friends who act out and use substances, having fewer friends committed to learning, presence of dating violence, and more exposure to neighborhood crime-were not moderated by gender, implying that similar factors are related to aggression in adolescent men and women from Chile. Implications for prevention and intervention efforts to address high-risk adolescents and reduce aggression among Chilean youth are discussed.


RNA Interference (RNAi) as a Potential Tool for Control of Mycotoxin Contamination in Crop Plants: Concepts and Considerations.
Mycotoxin contamination in food and feed crops is a major concern worldwide. Fungal pathogens of the genera Aspergillus. Fusarium, and Penicillium are a major threat to food and feed crops due to production of mycotoxins such as aflatoxins, 4-deoxynivalenol, patulin, and numerous other toxic secondary metabolites that substantially reduce the value of the crop. While host resistance genes are frequently used to introgress disease resistance into elite germplasm, either through traditional breeding or transgenic approaches, such resistance is often compromised by the evolving pathogen over time. RNAi-based host-induced gene silencing of key genes required by the pathogen for optimal growth, virulence and/or toxin production, can serve as an alternative, pre-harvest approach for disease control. RNAi represents a robust and efficient tool that can be used in a highly targeted, tissue specific manner to combat mycotoxigenic fungi infecting crop plants. Successful transgenic RNAi implementation depends on several factors including (1) designing vectors to produce double-stranded RNAs (dsRNAs) that will generate small interfering RNA (siRNA) species for optimal gene silencing and reduced potential for off-target effects; (2) availability of ample target siRNAs at the infection site; (3) efficient uptake of siRNAs by the fungus; (4) siRNA half-life and (5) amplification of the silencing effect. This review provides a critical and comprehensive evaluation of the published literature on the use of RNAi-based approaches to control mycotoxin contamination in crop plants. It also examines experimental strategies used to better understand the mode of action of RNAi with the aim of eliminating mycotoxin contamination, thereby improving food and feed safety.


Associations Between CYP2B6 rs707265, rs1042389, rs2054675, and Hirschsprung Disease in a Chinese Population.
Previous studies suggested that cytochrome P450 participated in the tumor metastasis and migration. CYP2B6 also acts as an important enzyme which metabolize partially or primarily metabolism of drugs, environmental contaminants, and mutagens. The objective of this study was to investigate the influence of CYP2B6 polymorphism on susceptibility of Hirschsprung disease. TaqMan assay was performed to determine the genotypes of CYP2B6 rs707265, rs1042389, rs2054675 in 262 cases and 290 control subjects. Logistic regression was used to assess the associations between these polymorphisms and HSCR. We observed a significant association of CYP2B6 rs707265 (G>A) polymorphism and HSCR susceptibility (p < 0.001). Besides, rs707265 A presented a significant risk of HSCR (p < 0.001). Our result suggested that CYP2B6 rs707265 modified the risk of HSCR.


Automated SEM/EDS analysis of airbag residue. I: Particle identification.
Deployed airbags can be a valuable source of probative forensic materials. During an accident, trace evidence can be deposited on the airbag cover and in addition, the residue produced by the gas generation system is released into the passenger compartment of the vehicle as the airbag deflates. This residue can be used to associate a suspect with the vehicle at the time of the accident. This study identifies particles containing zirconium, strontium, and/or copper-cobalt along with other elements from the gas generation systems and aluminum silicon microfibers from airbag filters as the probative material which may be produced and deposited on a suspect's hands and/or clothing. Scanning electron microscopy can be used to identify this metallic residue. Modification of the search criterion used for gunshot residue analysis allows for automated analysis of the samples. Proper collection of the airbag standard is essential to identify which materials were produced. Prompt collection of suspect samples allows the analysts the ability to make the proper identifications and associations. This analytical technique can be a probative tool in criminal investigations.


MiR-122 modification enhances the therapeutic efficacy of adipose tissue-derived mesenchymal stem cells against liver fibrosis.
Mesenchymal stem cell (MSC) transplantation alone may be insufficient for treatment of liver fibrosis because of complicated histopathological changes in the liver. Given that miR-122 plays an essential role in liver fibrosis by negatively regulating the proliferation and transactivation of hepatic stellate cells (HSCs), this study investigated whether miR-122 modification can improve the therapeutic efficacy of adipose tissue-derived MSCs in treating liver fibrosis. MiR-122-modified AMSCs (AMSC-122) were constructed through lentivirus-mediated transfer of pre-miR-122. MiR-122-modified AMSCs expressed high level of miR-122, while they retained their phenotype and differentiation potential as naïve AMSCs. AMSC-122 more effectively suppressed the proliferation of and collagen maturation in HSCs than scramble miRNA-modified AMSCs. In addition, AMSC-derived exosomes mediated the miR-122 communication between AMSCs and HSCs, further affecting the expression levels of miR-122 target genes, such as insulin-like growth factor receptor 1 (IGF1R), Cyclin G(1) (CCNG1) and prolyl-4-hydroxylase α1 (P4HA1), which are involved in proliferation of and collagen maturation in HSCs. Moreover, miR-122 modification enhanced the therapeutic efficacy of AMSCs in the treatment of carbon tetrachloride (CCl4 )-induced liver fibrosis by suppressing the activation of HSCs and alleviating collagen deposition. Results demonstrate that miR-122 modification improves the therapeutic efficacy of AMSCs through exosome-mediated miR-122 communication; thus, miR-122 modification is a new potential strategy for treatment of liver fibrosis.


Impact of COVID-19 on the Level of Work Engagement of Nurses at a Small, Rural Hospital.
Background There is a severe nursing shortage. Nurses are experiencing pressure, stress, and negative effects on their mental health from the ongoing pandemic. Understanding how their work engagement has been affected is essential. Method A descriptive, cross-sectional design was used. A survey plus the Fear of COVID-19 scale, the Utrecht Work Engagement Scale, and three open-ended questions were used. Results Participants (n = 107) were mostly female, had a bachelor degree or higher, worked full-time, had access to personal protective equipment, and followed Centers for Disease Control and Prevention guidelines. Receiving education about COVID-19 and feeling that the hospital provided adequate education were correlated with engagement scores. The type of education significantly correlated with engagement scores, with in-service education having the highest scores. Conclusion Understanding the needs of nurses during a pandemic is critical to engaging and retaining them. This study provides information that may be beneficial in future health crises. [J Contin Educ Nurs. 2022;53(4):157-164.].


Development and Preliminary Validation of a New Type 1 Diabetes Adjustment Scale (DAS-1).
This study focuses on the development and validation of a new Type 1 Diabetes Adjustment Scale (DAS-1). A total of 204 participants aged 15-65 with type 1 diabetes completed the self-report measures of the DAS-1, which includes clinical and psychological variables. Robust confirmatory factor analysis detected a unidimensional structure of the item scores. The omega coefficient was 0.91 and test-retest reliability was 0.87. Classifying subjects as in a Positive or Negative mood state, ROC analysis yielded an optimal cut-off of 50 for the DAS-1 scores, with a clinical accuracy of AUC = 0.85. The DAS-1 demonstrated evidence of good reliability and acceptable construct validity. The DAS-1 demonstrated good clinical utility, good sensitivity and adequate specificity. Clinical and theoretical implications of these results are discussed.


Nuclear roles for cilia-associated proteins.
Cilia appear to be derived, evolutionarily, from structures present in the ancestral (pre-ciliary) eukaryote, such as microtubule-based vesicle trafficking and chromosome segregation systems. Experimental observations suggest that the ciliary gate, the molecular complex that mediates the selective molecular movement between cytoplasmic and ciliary compartments, shares features with nuclear pores. Our hypothesis is that this shared transport machinery is at least partially responsible for the observation that a number of ciliary and ciliogenesis-associated proteins are found within nuclei where they play roles in the regulation of gene expression, DNA repair, and nuclear import and export. Recognizing the potential for such nuclear roles is critical when considering the phenotypic effects that arise from the mutational modification of ciliary proteins.


Pattern of cardiac surveillance among patients with lymphoma receiving anthracycline-based chemotherapy.
Anthracyclines are potent antineoplastic agents in the treatment of lymphoid malignancies, but their therapeutic benefit is limited by cardiotoxicity. The American Heart Association (AHA) recommends routine surveillance, early diagnosis and treatment of anthracycline-based chemotherapy (AC) induced cardiomyopathy (AC-CMP). We aimed to assess the prevalence of AC-CMP in patients with lymphoma, surveillance patterns of left ventricular ejection fraction (LVEF) in those receiving AC and management of patients with AC-CMP at an academic medical centre prior to the development of a comprehensive cardio-oncology programme. We performed a retrospective cohort study examining 218 patients with aggressive B cell non-Hodgkin's lymphomas (B-NHL) who received AC 1992-2012 and had serial follow-up. AC-CMP was defined as LVEF decrease ≥10% with final LVEF≤50% or LVEF reduction ≥15% regardless of final LVEF. Of 218 patients treated with AC, 73 (34%) had LVEF assessment both prior to and after receiving AC. Of these 73 patients, 24 developed AC-CMP and had higher cumulative all-cause mortality than those without AC-CMP (HR 2.35, p=0.03). Coronary artery disease (CAD) was an independent predictor of AC-CMP (p=0.048). Mean post-AC LVEF was lower in patients with CAD compared with those without CAD when their baseline LVEF was 45% (p=0.0009) or 55% (p=0.001) but was similar at 65% (p=0.33). Less than half of patients with AC-CMP received recommended heart failure medication therapy. Historically, one-third of patients with B-NHL treated with AC underwent surveillance according to AHA guidelines. There is substantial opportunity for collaboration between oncologists and cardiologists to improve the care of patients with lymphoma receiving AC.


Predictive factors of poor outcome in road traffic injures; a retrospective cohort study.
Road traffic injuries (RTI) are among the most important health problems worldwide as they cause more than 1.2 million deaths and 50 million injuries each year. Therefore, the present study aims to evaluate the outcome and aftermath of RTI in those who were injured and hospitalized due to a traffic accident. In the present retrospective cohort study with a one-year follow-up, data were extracted from the profiles of the RTI hospitalized patients. Outcome of the patients was evaluated at the time of discharge and 1-year later including their living state, presence of a disability or complete recovery. 1471 patients were studied (mean age of 32.8±17.0; 80.3% male). 571 (38.8%) had mild disability, 684 (46.5%) moderate disability, and 85 (5.8%) had severe disability at the time of discharge. In the end, 53 (3.6%) died. In the 1-year follow-up, 194 (13.2%) had mild disability, 43 (2.9%) had moderate disability, 9 (0.6%) had severe disability, and 7 (0.5%) were in a vegetative state. Presence of an underlying disease (p=0.03), loss of consciousness for more than 24 hours (p=0.04), spinal injury (p=0.002), presence of multiple trauma (p=0.01), increased ISS (p<0.001), need for ventilator (p<0.001), and organ injuries during hospitalization (p<0.001) are independent factors that increase the risk of poor outcome in RTI patients. Based on the results of the present study, underlying illnesses, loss of consciousness for more than 24 hours, spinal injury, multiple trauma, increased ISS, need for ventilator, and organ injuries during hospitalization were independent factors that increased the probability of poor outcome in RTI injuries.


Optical modulator based on propagating surface plasmon coupled fluorescent thin film: proof-of-concept studies.
We demonstrate that the propagating surface plasmon coupled fluorescent thin film can be utilized as a fluorescence modulator to mimic multiple representative Boolean logic operations. Surface plasmon mediated fluorescence presents characteristic properties including directional and polarized emission, which hold the feasibility in creating a universal optical modulator. In this work, through constructing the thin layer with the specific thickness, surface plasmon mediated fluorescence can be modulated with an ON-OFF ratio by more than 5-fold, under a series of coupling configurations.


Rumbrin, a new cytoprotective substance produced by Auxarthron umbrinum. I. Taxonomy, production, isolation and biological activities.
Rumbrin has been isolated from a fungus, Auxarthron umbrinum, by a screening program designed to find microorganism-produced cytoprotective substances. It was purified by use of column chromatography on silica gel, reversed phase HPLC and then isolated as fine red needles. Rumbrin prevented cell death caused by calcium overload and exhibited a potent inhibitory activity against lipid peroxidation.


Simultaneous occurrence of gallbladder cancer in a laundry couple: association between gallbladder cancer and benzene.
Gallbladder (GB) cancer occurs predominately as a biliary tract malignant tumor. It generally has a very poor prognosis, and early detection is often difficult. A variety of carcinogens have been implicated as an important cause for GB cancer. Benzene is a well-known carcinogen for hematologic malignancy, and its casual relationship with GB cancer has been suggested. We report a case of two patients who had operated a laundry cleaning facility together and later simultaneously got GB cancer after prolonged benzene exposure.


Long-acting progestogens.
Steroids can be administered in at least five different ways: injectables; hormone-releasing intra-uterine devices (IUDs); implants; vaginal rings; and pills. Progestogens which are synthetic steroids, are used as the main bioactive substances. Different progestogens are effective for different periods of time. Progestins in daily oral pills are effective for 24 hours. The effectiveness of a progestogen can be prolonged by incorporating it in a sustained-release system that gradually releases the hormone; therefore they can be effective up to 5 years or more. Two progestogen-only injectables are widely available in the family planning programmes, (DMPA and NET-EN) and two combined injectables, Cyclofem (DMPA + EC), and Mesigyna (NET-EN + EV). The ring is placed by the woman in her vagina, where it gradually releases hormone. Implantable contraceptives are placed just under the skin on the inside of the woman's arm. Implant capsules release the progestogen at a slow, steady rate. There are three implantables available in the market: Implanon; Norplant; and Jadelle. They are effective for 1-5 years, but then must be replaced. Natural and synthetic progestogens were first added to IUDs in the early 1970s. The main problem of long-acting progestogens is the disruption of the menstrual cycle.


Cardiovascular risk factor prevalence in three Chinese communities in 1989.
The cardiovascular risk prevalence of 935 adult Chinese living in Chauzhou, Meizhou, and Xinhui cities of Guangdong Province, China, is reported. The three communities are geographically separated, and represent the three major dialect group in Guangdong Province (Teochew, Hakka and Cantonese respectively) which are also the major donor populations of overseas Chinese to Australia and South East Asia. Taking into account historical data, the conventional cardiovascular risk factor prevalence of these combined communities in China as a whole is on the increase and approaches or even exceeds that in Western Society. However, the three communities are not very alike in their prevalences of individual conventional cardiovascular risk factors, notably for hyperlipidaemia (most prevalent in Chauzhou), hypertension (most prevalent in Chauzhou men at 12.4% and least in Meizhou women 5.0%) and cigarette smoking (most prevalent in Xinhui men at 72.7% and least in Xinhui women, 0%). They are similar in stature, body weight, BMI, and waist-to-hip ratio, with very low prevalences of overweight/obesity, or abdominal obesity. An understanding of the contributors to sub-ethnic difference in cardiovascular risk should emerge with further study of these Chinese populations.


Actin filament remodeling by actin depolymerization factor/cofilin.
We investigate, using molecular dynamics, how the severing protein, actin depolymerization factor (ADF)/cofilin, modulates the structure, conformational dynamics, and mechanical properties of actin filaments. The actin and cofilactin filament bending stiffness and corresponding persistence lengths obtained from all-atom simulations are comparable to values obtained from analysis of thermal fluctuations in filament shape. Filament flexibility is strongly affected by the nucleotide-linked conformation of the actin subdomain 2 DNase-I binding loop and the filament radial mass density distribution. ADF/cofilin binding between subdomains 1 and 3 of a filament subunit triggers reorganization of subdomain 2 of the neighboring subunit such that the DNase-I binding loop (DB-loop) moves radially away from the filament. Repositioning of the neighboring subunit DB-loop significantly weakens subunit interactions along the long-pitch helix and lowers the filament bending rigidity. Lateral filament contacts between the hydrophobic loop and neighboring short-pitch helix monomers in native filaments are also compromised with cofilin binding. These works provide a molecular interpretation of biochemical solution studies documenting the disruption of filament subunit interactions and also reveal the molecular basis of actin filament allostery and its linkage to ADF/cofilin binding.


Are chemical compounds important for soybean resistance to Anticarsia gemmatalis?
The identification and quantification of flavonoids (rutin and genistin) present in extracts of soybean genotypes, and their effects on the biology and physiology of Anticarsia gemmatalis Hübner (Lep.: Noctuidae) were studied. Analysis of covariance and bicoordinate utilization plots were used to remove the effect of feeding time from pupal weight and consumption as well as to separate pre- and postingestive effects of treatment on A. gemmatalis growth. Genotypes PI 274454, PI 227687, and "IAC-100" extracts in general, caused higher mortality, negatively influenced initial larval and pupal weight, and elongated larval cycle. Larvae fed on the "IAC-100" extract diet ingested larger amounts of food per unit of time, but were less efficient in its conversion to biomass. Leaf extracts of PI 227687 had the largest concentration of rutin (quercitin 3-O-rhamnosylglucoside), followed by PI 274454, and "IAC-100"; PI 74454 also had the highest genistin (genistein 7-O-glucoside) content. The susceptible cultivar "BR-16" showed only a kaempferol-based flavonoid in its chemical profile, indicating that after successive crosses, secondary compounds responsible for plant defenses were eliminated. Genotypes PI 274454, PI 227687, and "IAC-100" showed accentuated resistance characteristics and were considered inadequate sources for the development of A. gemmatalis. Considering rutin and genistin concentration in these genotypes, it is suggested that flavonoids are important factors conferring resistance to A. gemmatalis.


Diisopropylfluorophosphate increases clofibric acid clearance: supporting evidence for a futile cycle.
Clofibric acid has been shown previously to undergo a futile cycle in which its net clearance is dependent upon conjugation to form an acyl (ester) glucuronide and a combination of hydrolysis of the conjugate and its renal clearance. If hydrolysis is mediated by esterases then inhibition of these enzymes should increase clofibric acid clearance. Plasma clofibric acid clearance was measured in a group of six rabbits both while conscious and then while anesthetized and treated with diisopropylfluorophosphate (DFP). Clofibric acid clearance also was determined in a control group of six rabbits both while conscious and subsequently while anesthetized. Plasma clearances of unbound and total clofibric acid (protein bound plus unbound) were similar in both groups while conscious but increased 2-fold in DFP-treated compared with conscious animals (P less than .001) and were 3-fold greater in DFP-treated animals than in control, anesthetized animals (P less than .001). These data support the futile cycle for clofibric and implicate esterases in the in vivo hydrolysis of clofibric acid glucuronide.


Effects of micronized okara dietary fiber on cecal microbiota, serum cholesterol and lipid levels in BALB/c mice.
Micronized by a dry grinding method (D-ODF) or a wet granulating method (W-ODF), okara dietary fiber (ODF), was fed to BALB/c mice for 28 d. The water holding capacity of D-ODF and W-ODF was significantly enhanced after micronization. W-ODF had a larger swell capacity and a higher content of soluble dietary fiber than crude ODF and D-ODF. After feeding for 28 d, the populations of Escherichia coli and Lactobacilli in the cecum were significantly lower and higher in the W-ODF group than other groups, respectively, while the population of Bifidobacterium increased in all groups. The effect of each diet on the population of E. coli. Lactobacilli and Bifidobacterium was all maintained for a short period of time except that the effectiveness of W-ODF diet on the Bifidobacterium population lasted slightly longer than other diets. At the end of the feeding period, serum total cholesterol (TC) and triglyceride in D-ODF and W-ODF diets were significantly lower and HDL-C/TC ratio was significantly higher than those in crude ODF.


Determination of sex from the tibia.
Determination of sex from the tibial shaft as well as the entire bone itself has not been generally investigated by osteologists . This paper is an attempt to fulfill this need. The purpose is to determine sex from both the complete tibia and the shaft at the nutrient foramen level. The sample was obtained from the Terry Collection and included 159 specimens of whites and blacks. The tibial length, and circumference, anteroposterior, and transverse measurements at the nutrient foramen level were analyzed by means of step-wise discriminant function analysis. It was found that the circumference alone could give, on the average, 80% accuracy in determining sex. The addition of other dimensions to the function increased the accuracy by about 4%. Comparisons of this study with those on the femur indicated that sexual dimorphism in the tibia was a result not only of the general growth and musculo-skeletal activity, but also of the genetic structure of the population, i.e., racial variation.


Modified binodal model describes phase separation in aqueous two-phase systems in terms of the effects of phase-forming components on the solvent features of water.
The binodal model pioneered by Guan et al. [Y. Guan, T. H. Lilley, T. E. Treffry, J. Chem. Soc. Faraday Trans., 89 (1993) 4283-4298] remains the most successful in regard to the quantitative description of phase diagrams among various theoretical models proposed to describe phase separation in aqueous mixtures of polymers. This is a semi-empirical model based on the assumption that any point on the binodal line may be viewed as a saturated solution of the phase-forming compound-1 in the solution of the phase-forming compound-2. Although this model is originally based on the excluded volume concept, we suggest that the solubility of the compound-1 in solutions of compound-2 may depend on the solvent properties of water in solutions of compound-2. The binodal model described in these terms was very successfully applied to the phase diagrams of aqueous two-phase systems formed by different pairs of polymers (dextran, Ficoll, poly(ethylene glycol)-8000, and Ucon). Phase diagram of a new aqueous two-phase system formed by trimethylamine N-oxide (TMAO) and polypopylene glycol-400 and previously reported phase diagram for system formed by TMAO and poly(ethylene glycol)-600 were also described by this model quite well. It was found that the modified binodal model is also applicable to single polymer-salt and polymer-ionic liquid aqueous two-phase systems. The most important conclusion of our study is that the effects of different compounds (polymers, salts, ionic liquids) on the solvent features of water in their aqueous solutions cause changes in the water structure, resulting in phase separation in the mixtures of these compounds.


Expression of methylation-modulated tumor-related genes in endoscopically resected early esophageal squamous neoplasia.
Smoking and alcohol consumption are major risk factors for the development of esophageal squamous cell carcinoma (ESCC). Recent studies have demonstrated that smoking and alcohol consumption may be associated with altered DNA methylation in human cancer development. The aim of the present study was to evaluate methylation-modulated protein expression of tumor-related genes (TRGs) in the early stages of esophageal squamous neoplasia (ESN). ESN tissue samples (n=141) comprising 19 cases of low-grade intraepithelial neoplasia (LGIN), 70 of high-grade intraepithelial neoplasia/carcinoma in situ (HGIN/CIS) and 52 of invasive cancer, were endoscopically resected. The methylation-modulated protein expression of 5 TRGs [fragile histidine triad (FHIT), E-cadherin, MutL homolog 1 (MLH1) /MutS homolog 2 (MSH2) and cyclooxygenase-2 (COX-2)] as well as p53 was examined with immunohistochemistry, and their expression was compared with patient clinicopathological characteristics. Reduced or loss of FHIT, E-cadherin, MLH1/MSH2 and COX-2 expression was detected in 26.3 (5/19), 5.3 (1/19), 0 (0/19) and 63.2% (12/19) of LGIN cases, 61.4 (43/70), 18.6 (13/70), 7.1 (5/70) and 65.7% (46/70) of HGIN/CIS cases, and 78.8 (41/52), 50.0 (26/52), 11.5 (6/52) and 59.6% (31/52) of invasive cancer cases, respectively. Reduced or absent expression of FHIT and E-cadherin was significantly associated with neoplastic progression (FHIT, P=0.0007; E-cadherin, P=0.00014). The mean number of TRGs (FHIT, E-cadherin, MLH1/MSH2, and COX-2) that exhibited reduced or absent expression in LGIN, HGIN/CIS and invasive cancer specimens was 1.12±0.61, 1.66±0.93 and 2.09±0.96, respectively, demonstrating a significant stepwise increment from LGIN to HGIN/CIS and then to invasive cancer (P<0.05). p53 overexpression was frequently detected in ESN with head and neck carcinomas. However p53 overexpression was not significantly associated with ESN progression. An increase in the number of the 5 TRG proteins with reduced or loss of expression in the early stages of esophageal tumorigenesis was demonstrated, and their decreased expression was observed to be associated with tumor progression. Therefore, smoking and alcohol drinking may be associated with not only carcinogenesis but also the progression of ESN.


Clustering and mechanics in dense depletion and thermal gels.
We report on the microstructure and mechanical properties (elastic modulus) of concentrated depletion and thermal gels of octadecyl-coated silica particles for different values of the strength of interaction--polymer concentration for depletion gels and temperature for thermal gels. The depletion gels are composed of dense clusters and voids, while the thermal gels are devoid of clusters. Shear breaks up clusters in depletion gels while it induces clustering in the thermal gels. In both of these gels, the microstructure recovers to the presheared state upon cessation of shear. The recovery of the elastic modulus mimics the microstructure in the sense that the elastic modulus recovers to the presheared sheared state after shearing is stopped. Calculations of the gel boundary by modeling the interactions with an effective one-component square-well model reveals that suspensions with similar ranges of attraction gel at the same volume fraction at a fixed strength of attraction. Calculations of the elastic modulus using the naïve mode coupling theory for depletion gels are in good agreement with experimental measurements provided clustering is taken into account and have the same magnitude as the elastic moduli of thermal gels with similar strengths of attraction. These calculations, in addition to the experimental observations reinforce the point that the microscopic parameter determining the elastic modulus of dense gels and its recovery is the localization length which is only a fraction of the particle diameter and not the structure on the length scale of the particle diameter and larger.


Building Archean cratons from Hadean mafic crust.
Geologic processing of Earth's surface has removed most of the evidence concerning the nature of Earth's first crust. One region of ancient crust is the Hudson Bay terrane of northeastern Canada, which is mainly composed of Neoarchean felsic crust and forms the nucleus of the Northeastern Superior Province. New data show these ~2.7-billion-year-old rocks to be the youngest to yield variability in neodymium-142 (142Nd), the decay product of short-lived samarium-146 (146Sm). Combined 146-147Sm-142-143Nd data reveal that this large block of Archean crust formed by reworking of much older (>4.2 billion-year-old) mafic crust over a 1.5-billion-year interval of early Earth history. Thus, unlike on modern Earth, mafic crust apparently could survive for more than 1 billion years to form an important source rock for Archean crustal genesis.


Epidemiology of Helicobacter pylori infection and gastric cancer in Asia.
In Asia, the prevalence of Helicobacter pylori (H. pylori) infection varies markedly in different countries. Higher prevalence rates are found in developing Asian countries while lower rates have been reported in more industrialized and developed countries. Within a country, the seroprevalence rates may vary between distinct geographic regions. H. pylori infection is an important etiological factor for the occurrence of non-cardia gastric adenocarcinoma. The incidence rate of gastric adenocarcinoma in Asia tends to mirror the seroprevalence rate of H. pylori infection; however, there are populations with high seroprevalence rates of H. pylori infection that paradoxically have low incidence rates of gastric adenocarcinoma. These diverse clinical outcomes are related to bacterial virulence factors, concomitant environmental factors, host susceptibility and immune response. This review summarizes the current epidemiology of H. pylori infection in Asia and analyzes these data in the context of gastric cancer epidemiology.


No effect of increased water intake on blood viscosity and cardiovascular risk factors.
Observational data have suggested that increased water intake decreases the risk of CHD. A postulated mechanism is that increased water ingestion reduces blood viscosity. The aim of the present study was to assess the effect of increased fluid intake on blood viscosity. Men (n 67) and postmenopausal women (n 27) with one or more risk factors for CVD who reported intake of < or =0.5 litres water daily were randomised to a control group (n 31), an intervention group (n 32) that increased their daily water intake by 1 litre/d and an intervention group (n 31) that ingested 1 litre blueberry juice/d. All were encouraged to continue their usual diet and lifestyle. Whole-blood viscosity and blood and urine chemistries were measured by standard techniques after 2 and 4 weeks. Urine volume increased (by a median of 872 and 725 ml in the water and blueberry juice groups, respectively, v. 10 ml in the control group; P< or =0.002), confirming the subjects' adherence to the protocol. Urine osmolality and urinary levels of Na, K and creatinine decreased in the water and blueberry juice groups v. the controls (P<0.05). No change was seen in whole-blood viscosity or in levels of fibrinogen, total protein, lipids, glucose, insulin, C-peptide or other chemistry and haematology variables. In conclusion, a postulated protective effect of increased water or fluid intake is not explained by a change in blood viscosity and increased fluid intake does not influence CVD risk factors in the short term.


Developing clinical ethics committees.
Formal clinical ethics review first developed in the USA and most hospitals there have structures in place. This is often a clinical ethics committee. Developments have been slower in the UK, where there has been uncertainty and variability about the role of clinical ethics committees. Even in the USA, their exact role is uncertain. Although we now have a good idea of the mechanisms for ethical review of clinical issues in NHS trusts and health authorities, the desirability, composition and terms of reference for clinical ethics committees should be agreed as part of the clinical governance agenda.


Use of efficacy probability maps for the post-operative programming of deep brain stimulation in essential tremor.
Post-operative programming of deep brain stimulation for movement disorders can be both time consuming and difficult, which can delay the optimal symptom control for the patient. Probabilistic maps of stimulation response could improve programming efficiency and optimization. The clinically selected contacts of patients who had undergone ventral intermediate nucleus deep brain stimulation for the treatment of essential tremor at our institution were compared against contacts selected based on a probability map of symptom reduction built by populating data from a number of patients using non-rigid image registration. A subgroup of patients whose clinical contacts did not match the map-based selections prospectively underwent a tremor rating scale evaluation to compare the symptom relief achieved by the two options. Both the patient and video reviewer were blinded to the selection. 54% of the map-based and clinical contacts were an exact match retrospectively and were within one contact 83% of the time. In 5 of the 8 mismatched leads that were evaluated prospectively in a double blind fashion, the map-based contact showed equivalent or better tremor improvement than the clinically active contact. This study suggests that probability maps of stimulation responses can assist in selecting the clinically optimal contact and increase the efficiency of programming.


Automatic thoughts as a predictor of internalizing and externalizing problems in Chinese adolescents: A test of the cognitive content-specificity hypothesis with age effects.
The main aim of the current study was to test the cognitive content-specificity hypothesis across internalizing and externalizing problems in Chinese adolescents. The participants consisted of 2,158 adolescents aged 11-19 years from three middle schools, and they completed a number of measures assessing a wide range of automatic thoughts and syndromes related to internalizing and externalizing problems. Multivariate regression analyses demonstrated that thoughts about social threats, personal failure and hostility were the strongest predictors of anxiety, depression, and externalizing problems, respectively. Age was a statistically significant, albeit modest, moderator of the relationship between automatic thoughts about social threat and anxiety. The current study provides support for the cognitive content-specificity hypothesis in internalizing and externalizing problems in a Chinese sample.


Evaluation of ultrasound-guided transversalis fascia plane block for postoperative analgesia in cesarean section: A prospective, randomized, controlled clinical trial.
Cesarean Delivery (CD) is a commonly performed obstetric procedure. Adding a regional anesthesia technique to multimodal analgesia in CD, may improve the quality of postoperative analgesia. In this study we evaluated the efficacy of Transversalis Fascia Plane Block (TFPB) for postoperative analgesia management in CD. Blinded, prospective, randomized study. Postoperative recovery room & ward, tertiary university hospital, Istanbul, Turkey, PATIENTS: Seventy-five patients (ASA II-III) scheduled to undergo Cesarean delivery were recruited. Following exclusion, 70 patients were randomized into two equal groups (block and control group). Standard multimodal analgesia (routine paracetamol and tramadol PCA in addition to diclophenac sodium as rescue analgesia) was performed in Group C while TFPB block was also performed in the intervention (TFPB) group. The primary outcome was tramadol consumption within the first 24 h. The secondary outcome was Numeric Rating Scale (NRS) scores during rest and movement/coughing. Tramadol consumption in the first 24 h was 175 ± 72.32 mg in the control and 101.42 ± 51.45 mg in the TFPB group (p < 0.05). NRS was lower in Group TFPB during the first 3 h and at the 12th hour. There was no difference in NRS scores at other hours. Bilateral ultrasound guided TFPB leads to effective analgesia and a decrease in analgesia requirement in first 24 h in patients undergoing CD.


Structural domains in phage Mu transposase: identification of the site-specific DNA-binding domain.
Limited proteolysis of phage Mu transposase with three proteases of differing specificities produced a common pattern of fragmentation. The fragments were mapped by using a combination of immunoblotting and amino acid sequence analysis. Our results suggest that the transposase molecule is organized principally into three domains: an amino-terminal domain of molecular mass 30 kDa, a core region of approximately 35 kDa, and a carboxyl-terminal domain of approximately 10 kDa. The amino-terminal domain has at least two additional sites that are partially accessible to proteases. Filter binding and nuclease protection studies were done to determine the functions of the isolated domains. Site-specific binding to Mu DNA was localized to the amino-terminal domain. The core domain showed nonspecific DNA-binding activity.


Development and Validation of a Prognostic Nomogram in AFP-negative hepatocellular carcinoma.
The aim of this study is to establish and validate an effective prognostic nomogram in patients with AFP-negative hepatocellular carcinoma (HCC). The nomogram was based on a primary cohort that consisted of 419 patients with clinicopathologically diagnosed with HCC, all the data was gathered from 2008 to 2014 in Sun Yat-sen University Cancer Center. All the model factors were determined by univariate and multivariate Cox hazard analysis. The concordance index (C-index) and calibration curve were used to determine the predictive accuracy and discriminative ability of the nomogram, and compared with the TNM staging systems on HCC. Internal validation was assessed. An independent validation cohort contained 150 continuous patients from 2014 to 2015. Independent factors for overall survival (OS) were body mass index (BMI), tumor stage, distant metastases, HBs Ag, lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), and albumin (ALB), which were all contained into the nomogram. The calibration curve for probability of OS showed good agreement between prediction by nomogram and actual observation. The C-index of nomogram was 0.807 (95% CI: 0.770-0.844), which was superior to the C-index of AJCC TNM Stage (0.697). The AUC was 0.809(95%CI: 0.762-0.857). In the validation cohort, the nomogram still gave good discrimination (C-index: 0.866, 95% CI: 00.796-0.936; AUC: 0.832, 95%CI: 0.747-0.917) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram: low risk group, middle risk group and a high risk group, respectively. The proposed nomogram presents more accurate and useful prognostic prediction for patients with AFP-negative HCC.


Participatory intervention with objectively measured physical risk factors for musculoskeletal disorders in the construction industry: study protocol for a cluster randomized controlled trial.
There is high prevalence of back pain and neck-shoulder pain among blue collar workers in Denmark. Excessive physical exposures such as heavy lifting or working with bended or twisted back are risk factors for back pain among workers in the construction industry. Technical evaluation of awkward postures and kinematics of upper/ lower extremities (accelerometry) during work combined with the level of muscular activity (EMG) and video recordings can improve quantification of physical exposure and thereby can facilitate designing preventive strategies. Participatory ergonomics potentially increase the success of interventions aimed at reducing excessive physical exposures. The objectives of this study are to; 1) determine which work-tasks in selected job-groups involve excessive physical load of the back and shoulders during a normal working day (measured with accelerometers, EMG and video recordings). And 2) investigate whether a participatory intervention can reduce the excessive physical workloads, drawing on measurements from phase 1. A two-armed parallel-group, single-blind, cluster randomized controlled trial with allocation concealment will be conducted in the Danish construction industry. Approximately 20 construction gangs (≈ 80 subjects) will be recruited and randomized at the cluster level (gang). We will record in situ physical workload using technical measurements (EMG, accelerometers and video recordings) during a working day before and after the intervention. Based on these measurements a physical load matrix for each worker will be developed. The participatory intervention consist of three workshops: 1) One at baseline, involving presentation of video clips of the work-tasks with excessive physical load customized for each gang, followed by a participatory development of solutions on how to reduce excessive workloads, leading to development of an action plan on how to implement these solutions at the workplace. 2) A second workshop where the implemented solutions will be further developed and qualitatively evaluated during group discussions. 3) A final workshop at follow-up to enhance long-time organizational sustainability of the implemented solutions. The results will provide knowledge about the level of physical exposure of the back and shoulders during specific work tasks in the construction industry, and will provide information on options to implement participatory interventions aiming at reducing excessive physical workload. ClinicalTrials.gov (NCT02498197), registered 29 June 2015.


[Effects of clonidine vs trinitroglycerin on myocardial oxygen balance and on pulmonary gas exchange after myocardial revascularization].
The authors examined the effects of clonidine, a preferential alpha-adrenergic agonist, upon myocardial oxygen balance and pulmonary function during the perioperative period in patients undergoing CABG surgery. Anesthesia was provided by fentanyl infusion reaching the final dose of 100 micrograms.kg.min-1 in 10 minutes before skin incision. Ten patients received clonidine 0.125 mg intravenously after induction of anesthesia; a group of 10 patients was managed identically except for nitroglycerin infusion during the pre-CPB period, in order to keep the aortic pressure in the normal range. Intergroup differences in hemodynamics, respiratory data, rewarming time, post-operative ST-tract pattern and enzyme values were evaluated. Results are suggestive (in the clonidine group) for ameliorating myocardial oxygen balance by reducing oxygen consumption indexes (systolic aortic pressure, cardiac index, rate pressure product) and increasing coronary blood flow [coronary perfusion pressure (p < 0.01)] at the end of the surgery and intensive care. Global oxygen consumption reduction, recorded in the clonidine group patients, the oxygen available being unchanged, ameliorated the total oxygen balance mainly after sternotomy (p < 0.05) and at the end of bypass (p < 0.05). Cardiac index was greater during the awakening and rewarming period in intensive care and the ventilatory/perfusion ratio was improved, allowing a minor minute ventilation required in clonidine group patients, specially during admission to intensive care.


Step-by-step instructions for detecting whirlpool sign in adnexal torsion.
Objective: Adnexal torsion is a common gynecological emergency whose prompt diagnosis is essential because a delay may lead to ovarian dysfunction. Although the whirlpool sign is reliable for diagnosing ovarian cyst torsion, technical difficulties hinder its use by sonographers. Here we developed a systematic approach to visualizing this sign by focusing on the fact that torsion arises from the space between the uterus and the pelvic wall. One must determine the origin of the torsion via transverse imaging of the uterus and follow the twisted ligaments to the ovarian cyst. Patients and Methods: Two women aged 56 (Case 1) and 28 years (Case 2) visited our hospital with lower abdominal pain. Transvaginal ultrasonography showed a 7-cm right ovarian cyst in Case 1 and a 5-cm cyst in the Douglas pouch in Case 2; normal bilateral ovaries and the whirlpool sign were detected in both cases. Under laparoscopic guidance in Cases 1 and 2, an ovarian cyst and a paraovarian cyst were confirmed and removed. Results: Our step-by-step method allowed us to identify the whirlpool sign and confirm adnexal torsion, leading to prompt surgery in both cases. Conclusion: Using a systematic procedure helps less experienced practitioners detect the whirlpool sign.


Patterns of gun deaths across US counties 1999-2013.
We examined the socio-demographic distribution of gun deaths across 3143 counties in 50 United States' states to understand the spatial patterns and correlates of high and low gun deaths. We used aggregate counts of gun deaths and population in all counties from 1999 to 2013 from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (WONDER). We characterized four levels of gun violence, as distinct levels of gun death rates of relatively safe, unsafe, violent, and extremely violent counties, based on quartiles of 15-year county-specific gun death rates per 100,000 and used negative binomial regression models allowing clustering by state to calculate incidence rate ratios and 95% confidence intervals (95% CIs). Most states had at least one violent or extremely violent county. Extremely violent gun counties were mostly rural, poor, predominantly minority, had high unemployment rate and homicide rate. Overall, homicide rate was significantly associated with gun deaths (incidence rate ratios = 1.08, 95% CI = 1.06-1.09). In relatively safe counties, this risk was 1.09 (95% CI = 1.05-1.13) and in extremely violent gun counties was 1.03 (95% CI = 1.03-1.04). There are broad differences in gun death rates across the United States representing different levels of gun death rates in each state with distinct socio-demographic profiles.


Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy.
The incidence of prostate cancer is frequent, occurring in almost one-third of men older than 45 years. Only a fraction of the cases reach the stages displaying clinical significance. Despite the advances in our understanding of prostate carcinogenesis and disease progression, our knowledge of this disease is still fragmented. Identification of the genes and patterns of gene expression will provide a more cohesive picture of prostate cancer biology. In this study, we performed a comprehensive gene expression analysis on 152 human samples including prostate cancer tissues, prostate tissues adjacent to tumor, and organ donor prostate tissues, obtained from men of various ages, using the Affymetrix (Santa Clara, CA) U95a, U95b, and U95c chip sets (37,777 genes and expression sequence tags). Our results confirm an alteration of gene expression in prostate cancer when comparing with nontumor adjacent prostate tissues. However, our study also indicates that the gene expression pattern in tissues adjacent to cancer is so substantially altered that it resembles a cancer field effect. We also found that gene expression patterns can be used to predict the aggressiveness of prostate cancer using a novel model.


Two cases of inferior dislocation of the patella with impaction into the femoral trochlea of osteophytes on the superior pole of the patella.
Traumatic dislocation of the patella is classified as lateral, medial, or intra-articular according to the direction of dislocation. Lateral dislocation is the most common type of patellar dislocation, and intra-articular dislocation is rare. Intra-articular dislocation is classified as superior, inferior, or vertical dislocation. Inferior dislocation is categorized as Type I, which occurs in young people, and Type II, which occurs in the elderly. In Type II, osteophytes on the superior pole of the patellar are believed to become entrapped in the intercondylar notch, dislocating the patella inferiorly. These were two extremely rare cases of inferior dislocation of the patella in elderly people. The mechanism involved was considered to be the exertion of sudden upward traction on the patella due to the muscular force of the quadriceps when the knee was flexed, causing osteophytes on the superior pole of the patella to become impacted into the femoral trochlea. Dislocations were successfully reduced without anesthesia, and osteophyte resection or complete osteophyte fracture during reduction meant that there was no recurrence of the dislocation.


Reply to Correspondence on "Synergy and Antagonism between Allosteric and Active-Site Inhibitors of Abl Tyrosine Kinase".
Manley and co-workers provide data demonstrating that, at super-pharmacological concentrations (300 μM), a ternary complex between Abl, asciminib, and ATP-competitive inhibitors is possible. The work in our manuscript concerns the interplay of asciminib (and GNF-2) with ATP-competitive inhibitors at pharmacologically relevant concentrations (Cmax =1.6-3.7 μM for asciminib). Manley and co-workers do not question any of the studies that we reported, nor do they provide explanations for how our work fits into their preferred model. Herein, we consider the data presented by Manley and co-workers. In addition, we provide new data supporting the findings in our Communication. Asciminib and ATP-competitive inhibitors do not simultaneously bind Abl at pharmacologically relevant concentrations unless the conformation selectivity for both ligands is matched.


Comparison between sevoflurane and isoflurane anesthesia in pig hepatic ischemia-reperfusion injury.
Sevoflurane and isoflurane have been reported to exert protective effects against ischemia-reperfusion injury (IRI) in various organs. To compare the effect of sevoflurane anesthesia on liver IRI with that of isoflurane anesthesia, we performed the present study in pigs. Nineteen pigs were assigned to either the sevoflurane ( n = 9) or the isoflurane group ( n = 10). Hepatic warm ischemia was produced by 30-min hepatic artery and portal vein clamping beginning 90 min after the start of the inhalation anesthesia; this was followed by a 240-min reperfusion. To extend our evaluation, we evaluated the degree of IRI using various parameters (plasma alpha-glutathione-S-transferase [alpha-GST], lipid peroxide, and lactate concentrations), in addition to the conventionally used liver damage markers. The lactate level was significantly higher under isoflurane than under sevoflurane at 120 min after reperfusion (4.0 +/- 0.4 mmol.l(-1) vs 2.5 +/- 0.3 mmol.l(-1); P < 0.05). How-ever, this difference had disappeared after 240 min of reperfusion. No significant differences between the two groups were observed in values for alpha-GST, lipid peroxides, aspartate aminotransferase, alanine aminotransferase, or lactic dehydrogenase. The extent of the hepatic IRI seen under sevoflurane anesthesia in pigs did not differ significantly from that seen under isoflurane, as judged from measurements of a number of parameters over a 240-min reperfusion period.


Pseudomonas fluorescens DR54 Reduces Sclerotia Formation, Biomass Development, and Disease Incidence of Rhizoctonia solani Causing Damping-Off in Sugar Beet.
Effects of the biocontrol strain, Pseudomonas fluorescens DR54, on growth and disease development by Rhizoctonia solani causing damping-off in sugar beet were studied in soil microcosms and in pot experiments with natural, clay-type soil. In pot experiments with P. fluorescens DR54-treated seeds, significantly fewer Rhizoctonia-challenged seedlings showed damping-off symptoms than when not inoculated with the biocontrol agent. In the rhizosphere of P. fluorescens DR54 inoculated seeds, the bacterial inoculant was present in high numbers as shown by dilution plating and immunoblotting. By the ELISA antibody technique and direct microscopy of the fungal pathogen grown in soil microcosms, it was shown that the presence of P. fluorescens DR54 on the inoculated seeds had a strong inhibitory effect on development of both mycelium biomass and sclerotia formation by R. solani. In the field experiment, plant emergence was increased by treatment with P. fluorescens DR54 and the inoculant was found to be the dominating rhizosphere colonizing pseudomonad immediately after seedling emergence.


The reduction potential of nitric oxide (NO) and its importance to NO biochemistry.
A potential of about -0.8 (+/-0.2) V (at 1 M versus normal hydrogen electrode) for the reduction of nitric oxide (NO) to its one-electron reduced species, nitroxyl anion (3NO-) has been determined by a combination of quantum mechanical calculations, cyclic voltammetry measurements, and chemical reduction experiments. This value is in accord with some, but not the most commonly accepted, previous electrochemical measurements involving NO. Reduction of NO to 1NO- is highly unfavorable, with a predicted reduction potential of about -1.7 (+/-0.2) V at 1 M versus normal hydrogen electrode. These results represent a substantial revision of the derived and widely cited values of +0.39 V and -0.35 V for the NO/3NO- and NO/1NO- couples, respectively, and provide support for previous measurements obtained by electrochemical and photoelectrochemical means. With such highly negative reduction potentials, NO is inert to reduction compared with physiological events that reduce molecular oxygen to superoxide. From these reduction potentials, the pKa of 3NO- has been reevaluated as 11.6 (+/-3.4). Thus, nitroxyl exists almost exclusively in its protonated form, HNO, under physiological conditions. The singlet state of nitroxyl anion, 1NO-, is physiologically inaccessible. The significance of these potentials to physiological and pathophysiological processes involving NO and O2 under reductive conditions is discussed.


Flow cytometric method for the measurement of epidermal growth factor receptor and comparison with the radio-ligand binding assay.
A method for the purification, conjugation, and use of EGF-R antibody to quantify EGF receptors on tumour cells by flow cytometry is described. The quantification of both internal and external EGF receptors was determined by treatment with saponin, rendering the cells permeable to the EGF-R antibody. Using QCS bead standards, the number of EGF-R binding sites per cell was assessed. Results were compared with conventional EGF-R quantification using a radio-ligand binding assay. A high degree of correlation was found between the two methods. The flow cytometric method for EGF-R quantification described is simple, rapid, and reproducible. The assay may be of particular value in measuring EGF-R on urgent clinical samples or those that are too small (such as breast aspirates) for measurement by the radio-ligand binding assay. Advantages of this assay over the radio-ligand binding assay include reduction in use of radio-labelled iodine compounds, a decrease in analysis time, and reduced cost and quantity of material needed for assay. In addition, flow cytometry offers the possibility of selecting cell phenotypes by gating as well as live/dead cells by using multi-parameter flow cytometry.


Salt-dependent expression of glucosylglycerol-phosphate synthase, involved in osmolyte synthesis in the cyanobacterium Synechocystis sp. strain PCC 6803.
The cyanobacterium Synechocystis sp. strain PCC 6803 is able to acclimate to levels of salinity ranging from freshwater to twice the seawater concentrations of salt by accumulating the compatible solute glucosylglycerol (GG). Expression of the ggpS gene coding for the key enzyme (glucosylglycerol-phosphate synthase) in GG synthesis was examined in detail. Under control conditions, the GgpS protein is stable, so that weak constitutive transcription of the ggpS gene resulted in a significant protein content. However, the enzyme activity was biochemically switched off, and no GG was detectable. After a salt shock, an immediate increase in mRNA content proportional to the salt content occurred, while the GgpS protein and GG contents rose in a linear manner. Furthermore, the stability of the ggpS mRNA increased transiently. In salt-acclimated cells expression of the ggpS gene, the GgpS protein content, and the amount of accumulated GG depended linearly on the external salt concentration. Mapping of the 5' end of the ggpS transcript revealed a long nontranslated 5' sequence and a putative typical cyanobacterial promoter, which did not show any obvious salt-regulatory element. The alternative sigma factor sigma(F) was found to be involved in salt-dependent regulation of ggpS, since in a sigma(F) mutant induction of this gene was strongly reduced. The present study demonstrated that in addition to biochemical regulation of GgpS activity, alterations of ggpS expression are involved in regulation of GG synthesis in Synechocystis sp. strain PCC 6803. A model showing the interaction of the two regulatory levels is presented.


Endovascular Treatment of a Giant Aneurysm of the Aberrant Right Hepatic Artery in a Patient with Osler-Weber-Rendu Syndrome: A Case Report.
Osler-Weber-Rendu syndrome (OWR) is an autosomal dominant disorder characterized by recurrent epistaxis, mucocutaneous or visceral telangiectasias, and arteriovenous malformations in the lungs, liver, brain, and gastrointestinal tract. Hepatic artery aneurysms (HAAs) can also occur in OWR patients. HAAs are the second most common type of visceral artery aneurysm, and mortality rates are high owing to the lack of a tamponade effect. Anatomical variations of the celiacomesenteric vasculature are common, and the most common variation is that of the right hepatic artery originating from the superior mesenteric artery (SMA). We present the endovascular treatment of a patient with OWR and an aberrant right HAA originating from the SMA, with coil embolization and stent grafting. Giant HAAs can be treated endovascularly. However, stent graft placement should be reconsidered because of the need for antithrombotic medication, which may increase the incidence of epistaxis attacks in that patient group.


Influence of interstitial lung disease on outcome in systemic sclerosis: a population-based historical cohort study.
Interstitial lung disease (ILD) is a frequent complication of systemic sclerosis (SSc) and a major cause of SSc-related deaths. This study aimed to determine the influence of ILD on SSc in a population-based historical cohort study. The hypothesis was that patients with SSc who develop ILD have increased morbidity and mortality when compared with patients with SSc without ILD. Using the record linkage system of the Rochester Epidemiology Project in Olmsted County, Minnesota, this study identified the incidence of SSc between 1980 and 2010 and point prevalence on December 31, 2010 and determined the progression of organ involvement and its influence on outcome. During the 30-year interval, we identified 64 incident cases of SSc: 57 women and seven men, median age 49.1 years (interquartile range [IQR], 39.8-67.6 years). There were 43 prevalent cases. ILD occurred in 19 cases, usually after the diagnosis of SSc (median, 2 years; IQR, 0-10 years), with only three cases occurring 6 to 24 months beforehand. Pulmonary arterial hypertension (PAH) was diagnosed in 14 cases, heart failure in 27 cases, and chronic kidney disease (CKD) in 21 cases. Seventeen patients died during the study period, with a median survival time after diagnosis of 22.9 years. ILD, PAH, and CKD were associated with an increased risk of death. The incidence of ILD associated with SSc was relatively low in this population-based cohort. ILD appeared to be a contributing factor to mortality. Other factors, including age, PAH, and CKD, were also associated with poor outcome.


Discovery of a novel selective kappa-opioid receptor agonist using crystal structure-based virtual screening.
Kappa-opioid (KOP) receptor agonists exhibit analgesic effects without activating reward pathways. In the search for nonaddictive opioid therapeutics and novel chemical tools to study physiological functions regulated by the KOP receptor, we screened in silico its recently released inactive crystal structure. A selective novel KOP receptor agonist emerged as a notable result and is proposed as a new chemotype for the study of the KOP receptor in the etiology of drug addiction, depression, and/or pain.


A new basket trial design based on clustering of homogeneous subpopulations.
As new findings in oncology suggest a focus on individualized and targeted therapies, the demand for adequate clinical trial designs rises, whereby the focus is mainly on early development phases (phase I and II). Phase II oncology trials are often planned and analysed by Simon two-stage design, which corresponds to a one-armed trial design with the option to stop early for futility. Whereas a classical phase II study focuses on one tumour type and location, the relatively new basket trial design allows testing the efficacy of a single drug simultaneously in a number of patient subsets, which correspond to different tumour types. Such trials can be analysed in various ways, including separate analyses of all baskets or by pooling across all baskets. The work presented here tries to find an adequate compromise between these two extremes by implying rules for clustering some baskets, which are reasonably homogeneous. By means of Monte-Carlo simulations, we compare the efficiency of our proposed cluster-based basket trial design with a standard approach proposed recently which only allows for complete pooling or separate analyses. The results suggest that our new design offers a considerable advantage in power, sensitivity and specificity as well as in average sample size compared to the standard approach. The proposed clustering design is an attractive option to conduct basket trials in oncology with higher efficiency and better performance.


Pulmonary metastases: a rare manifestation of the most common cancer.
Basal cell carcinoma (BCC) is the most common human malignancy but rarely metastasises. We report on two patients with symptomatic lung metastases and a past history of recurrent BCC excisions. In our first patient, a heavy smoker with multiple lung lesions, histology of a resected nodule was first reported as non-small cell lung cancer but a repeat nodule biopsy a year later was recognised as a pulmonary metastasis from primary cutaneous BCC. Our second patient, a young never-smoker with two previous BCC, was confirmed as having a pulmonary metastasis from BCC on the lung resection specimen. Pulmonary metastasis from an unidentified primary site is a common clinical situation. These patients emphasise the importance of considering the most common cancer as a potential primary.


A new meningococcal B vaccine for adolescents and adults: characteristics and methods of use.
The invasive disease from Neisseria meningitidis is one of the leading causes of death for meningitis and sepsis at all ages. The highest incidence of cases occurs at paediatric and adolescent age, but no age of life is considered protected from this infection and disease. Prevention against the five main serogroups is possible using the combined conjugated polysaccharide vaccine against the ACWY (anti-MenACWY) serogroups and the meningococcal B (anti-MenB) protein vaccines. Trumenba® vaccine, approved by the EMA (European Medicine Agency) for use in individuals aged ≥ 10 years, protects against serogroup B invasive disease. This bivalent, recombinant vaccine is able, when given with a 0-6 month schedule, to induce a protective response in adolescents and young adults, comparable with a 3-doses schedule. For this reason, the Trumenba® vaccine should be used routinely with the 2-dose schedule (0-6 months). The 3-doses use could be considered in particular situations, like an occurring epidemic or particular individual risk factors such as asplenia or complement deficit, but is not needed for underlying conditions like diabetes or heart diseases.


Comparison of Effort of Breathing for Infants on Nasal Modes of Respiratory Support.
To directly compare effort of breathing between high flow nasal cannula (HFNC), nasal intermittent mechanical ventilation (NIMV), and nasal continuous positive airway pressure (NCPAP). This was a single center prospective cross-over study for patients <6 months in the cardiothoracic or pediatric intensive care unit receiving nasal noninvasive respiratory support after extubation. We measured effort of breathing using esophageal manometry with pressure-rate product (PRP) on all 3 modes. NIMV synchrony was determined by comparing patient efforts (esophageal manometry) with mechanically delivered breaths (spirometry in ventilator circuit). On NIMV, PRP and synchrony was also measured after adding a nasal clip on 26 patients. Forty-two children were included. Median (IQR) age was 2 (0.5, 4) months. There was no difference in median PRP between HFNC 6 liters per minute, 355 (270,550), NIMV 12/5 cm H2O, 341 (235, 472), and NCPAP 5 cm H2O, 340 (245,506) (P?=?.33). Results were similar regardless of HFNC flow rate or NIMV inspiratory pressure. Median PRP on CPAP of 5 cm H2O prior to extubation 255 (176, 375) was significantly lower than all postextubation values (P?<?.002). On NIMV, less than 50% of patient efforts resulted in a ventilator breath, which was not improved with a nasal clip (P?>?.07)). However, as NIMV synchrony improved (>60%), PRP on NIMV was lower than on HFNC. For infants, effort of breathing is similar on HFNC, NIMV, and NCPAP after extubation, regardless of flow rate or inspiratory pressure. We speculate that bi-level NIMV may be superior if high levels of synchrony can be achieved.


Triose phosphate isomerase deficiency associated with two novel mutations in TPI gene.
We report the clinical, haematological and molecular characteristics of two triose phosphate isomerase deficient patients affected by haemolytic anaemia and neuromuscular impairment. The sequence of complete TPI gene showed the presence of two previously undescribed mutations: c.722 T>C (Phe240Ser) and c.28 insG; each of the two unrelated patients showed the new mutation in compound heterozygosity with the most common variant Glu104Asp. The association of Glu104Asp with c.28 insG resulted in a very severe clinical pattern.


Association of TP53 Codon 72 Arg>Pro Polymorphism with Breast and Lung Cancer Risk in the South Asian Population: A Meta-Analysis.
A transversion missense polymorphism of the TP53 tumor suppressor gene at the codon 72 codes proline instead of arginine causes an altered p53 protein expression and has been found to be associated with an elevated risk of various cancer; especially breast and lung cancer. As the previous case-control studies on the South Asian population have shown controversial results, we performed a meta-analysis to evaluate a precise estimation of the relationship between the TP53 Arg72Pro polymorphism with breast and lung cancer. A total of 12 related studies on the South Asian population have been included through comprehensive database searching. Six studies were selected for breast cancer meta-analysis involving 950 cases and 882 controls; the other six studies were for lung cancer meta-analysis including 975 cases and 1397 controls. The results have been determined by using the Review Manager (RevMan) 5.3. Additionally, the stability of our analysis was assessed by heterogeneity, publication bias analysis and sensitivity testing. A significantly increased risk of breast cancer was found in Pro allele (Pro vs. Arg), co-dominant model 2 (Pro/Pro vs. Arg/Arg), dominant model (Pro/Pro + Arg/Pro vs. Arg/Arg). In case of lung cancer, significantly increased risk was found in the allele, co-dominant 1, co-dominant 2, co-dominant 3, dominant, and recessive models. No association with other genetic models with breast and lung cancer risk was found in the South Asian population. Our results indicate that TP53 Arg72Pro polymorphism is a risk factor for the development of breast cancer and lung cancer in the South Asian population.


Herbert Pardes, MD.
Though mergers, affiliations, and financial challenges pervade all of academic medicine, New York City exhibits in microcosm the changes taking place throughout the country. At the helm of Columbia University College of Physicians and Surgeons is Herbert Pardes, MD, who came to Columbia in 1984 from the NIH and has served as dean since 1989. Since becoming dean, Pardes has received high marks for re-invigorating the academic strengths of Columbia while skillfully managing the financial issues faced by an inner-city medical center. Interviewed in his office in upper Manhattan, Pardes candidly discussed life and times in the big city and the difficulties of maintaining an emphasis on research in an era when money talks.


Dexmedetomidine alleviates inflammatory response and oxidative stress injury of vascular smooth muscle cell via α2AR/GSK-3β/MKP-1/NRF2 axis in intracranial aneurysm.
Vascular smooth muscle cell (VSMC) phenotypic modulation regulates the initiation and progression of intracranial aneurysm (IA). Dexmedetomidine (DEX) is suggested to play neuroprotective roles in patients with craniocerebral injury. Therefore, we investigated the biological functions of DEX and its mechanisms against IA formation and progression in the current study. The rat primary VSMCs were isolated from Sprague-Dawley rats. IA and superficial temporal artery (STA) tissue samples were obtained from patients with IA. Flow cytometry was conducted to identify the characteristics of isolated VSMCs. Hydrogen peroxide (H2O2) was used to mimic IA-like conditions in vitro. Cell viability was detected using CCK-8 assays. Wound healing and Transwell assays were performed to detect cell motility. ROS production was determined by immunofluorescence using DCFH-DA probes. Western blotting and RT-qPCR were carried out to measure gene expression levels. Inflammation responses were determined by measuring inflammatory cytokines. Immunohistochemistry staining was conducted to measure α2-adrenergic receptor levels in tissue samples. DEX alleviated the H2O2-induced cytotoxicity, attenuated the promoting effects of H2O2 on cell malignancy, and protected VSMCs against H2O2-induced oxidative damage and inflammation response. DEX regulated the GSK-3β/MKP-1/NRF2 pathway via the α2AR. DEX alleviates the inflammatory responses and oxidative damage of VSMCs by regulating the GSK-3β/MKP-1/NRF2 pathway via the α2AR in IA.


The incidence and prevalence of inflammatory bowel disease continues to increase in the Faroe Islands - a cohort study from 1960-2020.
The highest reported incidence rate of inflammatory bowel disease (IBD), and especially of ulcerative colitis (UC), is found in the Faroe Islands. This study aimed to assess the incidence rate and temporal trends in prevalence over six decades.Methods: All incident and prevalent patients diagnosed with IBD between 1960-2020 from the nationwide and population-based Faroese IBD cohort were included in this study. All patients fulfilled the Copenhagen Diagnostic Criteria. Overall, 873 individuals were diagnosed with IBD during the study period, 559 (64%) with UC, 151 (17%) with CD and 163 (19%) with IBDU. A total of 59 patients had paediatric-onset IBD. The incidence of IBD continued to increase throughout the study period, as the age-standardised incidence rate started at 8 per 100,000 person-years (py) (European Standard Population, ESP) in 1960-79 and reached 70 by 2010-20. In 2021, the age-standardised period prevalence was 1,414 per 100,000 persons. The IBD incidence was unevenly distributed among the islands with Sandoy having the highest rate of 106 per 100,000 py in 2010-2020. The incidence of IBD continues to increase in the Faroe Islands, mainly driven by UC. The incidence presents with an uneven geographical distribution, which suggests an adverse interaction between unknown environmental factors and genetic traits. The prevalence in 2021 corresponded to 1.3% of the Faroese population suffering from IBD. Environmental risk factors are suspected to impact this homogenous high-risk population; however, the reason is unclear.


Muscle hypertrophy experimentally induced by administration of denervated muscle extract.
The effects of systemic administration of muscle extract on normal muscle were studied. Male Wistar rats received intraperitoneal injections of normal and denervated muscle extract over 5 consecutive days. Soleus muscles were then submitted to histological, histochemical and quantitative-morphometric analysis. The group receiving denervated muscle extract showed considerable muscle fiber hypertrophy, together with the formation of new fibers suggestive of hyperplasia. The systemic administration of denervated muscle extract was shown to have a considerable myotrophic effect on normal muscle, evident in the hypertrophy and hyperplasia of muscle fibers.


How bees distinguish colors.
Behind each facet of the compound eye, bees have photoreceptors for ultraviolet, green, and blue wavelengths that are excited by sunlight reflected from the surrounding panorama. In experiments that excluded ultraviolet, bees learned to distinguish between black, gray, white, and various colors. To distinguish two targets of differing color, bees detected, learned, and later recognized the strongest preferred inputs, irrespective of which target displayed them. First preference was the position and measure of blue reflected from white or colored areas. They also learned the positions and a measure of the green receptor modulation at vertical edges that displayed the strongest green contrast. Modulation is the receptor response to contrast and was summed over the length of a contrasting vertical edge. This also gave them a measure of angular width between outer vertical edges. Third preference was position and a measure of blue modulation. When they returned for more reward, bees recognized the familiar coincidence of these inputs at that place. They cared nothing for colors, layout of patterns, or direction of contrast, even at black/white edges. The mechanism is a new kind of color vision in which a large-field tonic blue input must coincide in time with small-field phasic modulations caused by scanning vertical edges displaying green or blue contrast. This is the kind of system to expect in medium-lowly vision, as found in insects; the next steps are fresh looks at old observations and quantitative models.


Comparison of intramuscular dexmedetomidine and midazolam premedication for elective abdominal hysterectomy.
The purpose of this study was to compare the perioperative effects of the intramuscular (i.m.) alpha 2 agonist, dexmedetomidine (DEX), and midazolam (MID) premedication. The study comprised 192 women (64 per group) scheduled for abdominal hysterectomy. The doses of the study drugs were chosen to obtain equal sedative effects. The three groups were: 1) i.m. DEX (2.5 micrograms/kg) and intravenous (i.v.) placebo (DexPla group), 2) i.m. DEX and i.v. fentanyl (FENT) (1.5 micrograms/kg) (DexFent group), and 3) i.m. MID (0.08 mg/kg) and i.v. FENT (MidFent group). I.m. drugs were administered 45-90 min before induction of anesthesia. Preoperative sedation and anxiolysis after DEX was comparable to that after MID. The maximum arterial blood pressure response to endotracheal intubation was blunted in the DexFent group, while in the two other groups blood pressure increased 30-34 mm Hg after endotracheal intubation. The mean isoflurane concentration during surgery was 0.14% in the DexFent group, 0.24% in the DexPla group, and 0.34% in the MidFent group (P < 0.001). During surgery, bradycardia (heart rate < 40 bpm) was observed in 6.2% of DEX patients, and no MID patients, whereas postoperatively 14.1% of DEX patients and 1.6% of MID patients had bradycardia. Fewer patients suffered from postoperative shivering after DEX (10%) than after MID (52%). We conclude that DEX has many desirable effects, but side effects such as bradycardia may limit its routine use in ASA physical status I-II patients.


[Performance-related income budget. A means for reorganizing hospital financing].
Performance-related budgets are the result of negotiated performance units per hospital multiplied by state-wide negotiated prices. Such hospital budgets contain profit chances and loss risks. Exceeding the contractual fixed amount leads to price reductions, falling below that amount leads to lower reimbursement. A consistent pricing system for basic and department performance units could solve the present problem of cost separation in Germany. A step in this direction is the definition of hospital department groups and the construction of an average department treatment case, which could be priced on an average cost base. In the long run, more flexibility according to pricing and budgeting can be developed. Competitive insurance companies should be free to find their own budgets so that a hospital can have several independent contractors.


Acid digestion, hydride evolution atomic absorption spectrophotometric method for determining arsenic and selenium in foods: collaborative study. tpart I.
The hydride evolution atomic absorption spectrophotometric (AAS) method for determining As and Se in foods developed and evaluated by the Food and Drug Administration and Agriculture Canada laboratories was subjected to collaborative study, Twenty-four laboratories provided results for As and 23 provided results for Se levels in 13 different samples consisting of tuna, swordfish, flounder, oyster, liver, flour, skim milk poweder, spinach, kale, and apple containing natural levels of As and Se in the ranges 0-15,000 and 0-4000 ng/g, respectively. Reference materials formed a substantial segment of samples, and a number of other laboratories using fluorometry, colorimetry, neutron activation, spark source mass spectrometry, and graphite furnace AAS provided confirmative reference values for the remaining samples. A variety of hydride generation instruments were used, ranging from commercially available devices to semiautomated and fully automated custom-made instruments. Although the accuracy of the method was fairly good, between-laboratory and between-determination (hydride evolution AAS measurement) precisions were not favorable. The main advantage of the hydride AAS method is the rapidity of the determinative step.


A continuous model of physiological prion aggregation suggests a role for Orb2 in gating long-term synaptic information.
The regulation of mRNA translation at the level of the synapse is believed to be fundamental in memory and learning at the cellular level. The family of cytoplasmic polyadenylation element binding (CPEB) proteins emerged as an important RNA-binding protein family during development and in adult neurons. Drosophila Orb2 (homologue of mouse CPEB3 protein and of the neural isoform of Aplysia CPEB) has been found to be involved in the translation of plasticity-dependent mRNAs and has been associated with long-term memory. Orb2 protein presents two main isoforms, Orb2A and Orb2B, which form an activity-induced amyloid-like functional aggregate, thought to be the translation-inducing state of the RNA-binding protein. Here we present a first two-states continuous differential model for Orb2A-Orb2B aggregation. This model provides new working hypotheses for studying the role of prion-like CPEB proteins in long-term synaptic plasticity. Moreover, this model can be used as a first step to integrate translation- and protein aggregation-dependent phenomena in synaptic facilitation rules.


Role of automated measurements in understanding lifestyle effects on blood pressure.
Ambulatory measurements are increasingly used to evaluate the effects of different aspects of lifestyle on blood pressure. Such measurements provide greater statistical power than casual measurements and are particularly useful for assessing diurnal variations, 24-hour load and variability, and both acute and sustained effects of common behaviours. Concomitant heart rate and biochemical and genetic measurements can provide clues as to the mechanisms underlying the effects of lifestyle on blood pressure in different target populations. The information obtained is proving helpful in evaluating actions and interactions of smoking, alcohol, physical activity, caffeine consumption, various types of psychological stress, obesity, and dietary habits.


Behavioral and receptor binding analysis of the alpha 2-adrenergic agonist, 5-bromo-6 [2-imidazoline-2-yl amino] quinoxaline (UK-14304): evidence for cognitive enhancement at an alpha 2-adrenoceptor subtype.
The ability of the alpha 2-agonists clonidine, B-HT920 (6-allyl-2-amino-5,6,7,8-tetrohydro-4H-thiazolo-[4,5-d]-azepine) and guanfacine to improve memory in aged monkeys has been related to their affinity to bind at a proposed rauwolscine-insensitive (Ri) subtype of alpha 2-adrenergic receptor, while their hypotensive and sedating effects have been related to affinity at a rauwolscine-sensitive site (Rs) (Arnsten et al., 1988). The present study examined the alpha 2-agonist UK-14304 (5-bromo-6 [2-imidazoline-2-yl amino] quinoxaline) for its binding characteristics in tissue from the brain of the rat and for its behavioral effects in aged monkeys. The drug UK-14304 was found to have slightly higher affinity for the Ri than the Rs site (Ki values of 138 and 245 nM, respectively), but was not as selective as the alpha 2-agonist guanfacine (Ki values of 23 and 340 nM, respectively). Consistent with this binding profile, very small doses of UK-14304 (0.00017-0.17 micrograms/kg) produced a reliable but modest improvement in memory in the aged monkeys (average improvement of 16.7% +/- 2.6% following an optimal dose). No hypotensive or sedating side effects were observed at these small doses. However, hypotension and sedation emerged rapidly when the dose was raised above 1.7 micrograms/kg and at the largest doses tested (50.0-100.0 micrograms/kg), hypotension was severe (systolic pressure below 70 mm Hg) and the animals were too sedated to complete cognitive testing. The separation between doses that improved memory and those that produced hypotension and sedation was not as great for UK-14304 as it was for guanfacine, consistent with the greater selectivity of guanfacine for the Ri site. These results offer a fourth example whereby the ability of an alpha 2-agonist to improve cognitive function, without side effects, could be related to the relative affinities for the Ri and Rs sites.


The preventive effects of taurine on neural tube defects through the Wnt/PCP-Jnk-dependent pathway.
The aim of this study was to clarify the protective role of taurine in neuronal apoptosis and the role of the Wnt/PCP-Jnk pathway in mediating the preventive effects of taurine on neural tube defects (NTDs). HT-22 cells (a hippocampal neuron cell line) were divided into a control group, a glutamate-induced apoptosis group, and glutamate (4.0 mmol/L) plus low-dose taurine (L; 0.5 mmol/L) and high-dose taurine (H; 2.0 mmol/L) groups. The MTT assay was used to monitor cell proliferation and cell survival. Immunofluorescence and Western blot analyses were used to determine caspase 9 expression. Retinoic acid (RA) induced embryonic NTDs in Kunming mice, thus establishing an NTD model. Pregnant mice were divided into a control group, an RA (30 mg/kg body weight) group, and an RA (30 mg/kg body weight) plus taurine (free drinking of 2 g/L solution) group. Immunohistochemistry and Western blot analyses were used to detect the expression of Dvl, RhoA and phosphorylated (p)-Jnk/Jnk in the embryonic neural tubes. In HT-22 cells, the apoptosis rate was significantly higher and caspase 9 activation was also significantly increased in the glutamate-induced apoptosis group compared to the L and H taurine groups. In the NTD model, the expression levels of Dvl, RhoA, and p-Jnk were significantly higher in the RA group than in the control group, whereas they were significantly reduced in the RA + taurine group. This study suggests that taurine has positive effects on neuronal protection and NTD prevention. Moreover, the Wnt/PCP-Jnk-dependent pathway plays an important role in taurine-mediated prevention of NTDs.


Polymorphic NF-Y dependent regulation of human nicotine C-oxidase (CYP2A6).
In humans, cytochrome P450 2A6 (CYP2A6) constitutes the principal nicotine C-oxidase. Several different polymorphic CYP2A6 gene variants are known which contribute to the highly variable expression of this enzyme among individuals. In this study we report a novel polymorphism located in the 5' flanking region (-745A > G) of the CYP2A6 gene disrupting a CCAAT box. Electrophoretic mobility shift assays (EMSA) indicated that NF-YA is part of this nuclear protein complex. Chromatin immunoprecipitation revealed that NF-Y recognizes a region of the CYP2A6 5' flanking region located between -932 and -606. EMSA showed that out of the three CCAAT boxes in the CYP2A6 promoter, with CCAAT core sequences located between -839/-835, -748/-744, and -689/-685, only the one at -748/-744 was able to compete with the nuclear protein complex binding to the -748/-744 CCAAT box. Cotransfection experiments indicated that NF-Y acts as a positive regulatory element on CYP2A6 gene regulation. EMSA demonstrated that an NF-Y consensus oligonucleotide but not the -745A > G oligonucleotide competed efficiently with binding of the protein complex to the -748/-744 CCAAT box. Promoter activity of the -745A > G variant was significantly reduced to 78% relative to the wild-type allele in HepG2 cells transfected with luciferase reporter plasmids. Finally, haplotype analysis was carried out comprising the -745A > G variant in combination with all known CYP2A6 3' and 5' flanking single nucleotide polymorphisms: -1013A > G, -48T > G, and the CYP2A6/CYP2A7 3' flank conversion. A new haplotype, CYP2A6*1H was identified, with allele frequencies of 3.1% in Swedish and 5.2% in Turkish populations.


Hemangiopericytoma associated with multiple keratocystic odontogenic tumors in an adolescent patient: a case report.
Hemangiopericytoma, initially described by Stout and Murray in 1942 (1), is a rare vascular tumor arising from mesenchymal cells with pericytic differentiation. Hemangiopericytomas usually occur in the 5th decade of life and account for 3-5% of all soft tissue sarcomas and 1% of all vascular tumors (2). The tumor usually occurs in the limbs, pelvis, or head and neck region; 15-30% of all hemangiopericytomas occur in the head and neck (2,3). Here we present a case of hemangiopericytoma of the submandibular region with keratocystic odontogenic tumors in an adolescent patient.


[Malaria vectors: from the field to genetics. Research in Africa].
Only about 60 Anopheline species transmit malaria among more than 3,000 mosquito species recorded in the world. In Africa, the major vectors are Anopheles gambiae,An. arabiensis, An. funestus, An. nili and An. moucheti. They all belong to species complexes or groups of closely related species that are very difficult to set apart on morphological grounds, but which may have highly variable behaviours and vectorial capacities. Understanding this complexity is of major importance in vector control programs or for implementing any public health intervention program such as drugs or vaccine trials. Among the seven species of the complex,Anopheles gambiaes.s. shows a huge chromosomal polymorphism related to adaptation to specific natural or anthropic environments, from equatorial forested Africa to dry sahelian areas. Recent studies conducted in West and Central Africa suggest an incipient speciation into 2 molecular forms provisionally called M and S. A similar evolutionary phenomenon is observed in An. funestus, in which sympatric populations carrying specific chromosomal paracentric inversions showed restricted gene flow. Distribution of species from An. nili group and An. moucheti complex is restricted to more humid regions of Africa. However in some areas these species play the major role in malaria transmission. Comprehensive knowledge of transmission cycles and of behavioural and underlying genetic heterogeneities that exist within and among natural vector populations will thus benefit the whole area of malaria control and epidemiology. Molecular and genetic studies, as well as in depth monitoring of vector biology, have been recently facilitated by advances in functional and comparative genomics, including recent publication of the nearly complete genome sequence of An. gambiae. Challenge for the next years is to answer to the very simple question: why is an insect a vector?


Photoelectrical Stimulation of Neuronal Cells by an Organic Semiconductor-Electrolyte Interface.
As a step toward the realization of neuroprosthetics for vision restoration, we follow an electrophysiological patch-clamp approach to study the fundamental photoelectrical stimulation mechanism of neuronal model cells by an organic semiconductor-electrolyte interface. Our photoactive layer consisting of an anilino-squaraine donor blended with a fullerene acceptor is supporting the growth of the neuronal model cell line (N2A cells) without an adhesion layer on it and is not impairing cell viability. The transient photocurrent signal upon illumination from the semiconductor-electrolyte layer is able to trigger a passive response of the neuronal cells under physiological conditions via a capacitive coupling mechanism. We study the dynamics of the capacitive transmembrane currents by patch-clamp recordings and compare them to the dynamics of the photocurrent signal and its spectral responsivity. Furthermore, we characterize the morphology of the semiconductor-electrolyte interface by atomic force microscopy and study the stability of the interface in dark and under illuminated conditions.