Menopause alters temperature sensitivity of muscle force in humans.
Isometric maximum voluntary force (MVF) of the adductor pollicis and first dorsal interosseous muscles was measured in 11 pre- and 11 post-menopausal (Pre-M and Post-M) human subjects. The temperature of the hand varied in the range 18°-38°C by water immersion and skin temperature was recorded. MVF at each temperature was expressed relative to the value at skin temperature above 35°C to give MVF(REL). The form of the relation between MVF(REL) and temperature was different in the Pre-M and Post-M groups (p < 0.01). In the Pre-M group the maximum value of MVF(REL) occurred near 30°C and force fell at both higher and lower temperatures. In the Post-M group MVF(REL) showed an approximately linear decline with cooling across the whole temperature range. The maximum value of MVF(REL) for the Post-M group was near 35°C. The values of MVF(REL) for the Post-M group were significantly lower than for the Pre-M group at temperatures between 18° and 30°C.


A qualitative exploration of the lived experiences of Body Dysmorphic Disorder.
Body Dysmorphic Disorder (BDD) is characterized by an intense preoccupation with one or more perceived "defects" in physical appearance. Despite the distress and impairment associated with BDD, the disorder remains understudied and poorly understood. In particular, there are limited studies available which give voice to those with firsthand experiences of the disorder. A qualitative approach was employed to study lived experience of BDD. In-depth semi-structured interviews were conducted with 12 participants with BDD, aiming to understand their subjective experiences of the disorder. Data was analyzed using Interpretative Phenomenological Analysis (IPA). The results identified three superordinate themes; (1) consumed by the disorder, (2) the flawed self, and (3) intolerance of uncertainty about appearance. The qualitative findings of this study are discussed in relation to current conceptual understandings of BDD, including the cognitive behavioral model.


New potential agents in treating diabetic kidney disease: the fourth act.
Despite the worldwide epidemic of chronic kidney disease complicating diabetes mellitus, current therapies directed against nephroprogression are limited to angiotensin conversion or receptor blockade. Nonetheless, additional therapeutic possibilities are slowly emerging. The diversity of therapies currently in development reflects the pathogenic complexity of diabetic nephropathy. The three most important candidate drugs currently in development include a glycosaminoglycan, a protein kinase C (PKC) inhibitor and an inhibitor of advanced glycation. In targeting primary mechanisms by which hyperglycaemia contributes to diabetic complications, these drugs could provide risk reduction complementary to the partial reduction proven for ACE inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers). Glycosaminoglycans act to restore glycoproteins present in reduced amounts in the glomerular basement membrane and mesangium of diabetic animal models. Components of the drug sulodexide prevent pathological changes and proteinuria in diabetic rats. Reductions in albuminuria, a hallmark of early diabetic kidney disease, have been reported in initial human trials. In the US, a multicentre phase II study has been completed, with an interim analysis indicating reduction in urinary albumin losses. Pivotal phase II trials have begun in patients with type 2 diabetes. A second metabolic pathway of diabetic complications is overexpression of PKC. Several activators of this family of intracellular kinases have been identified and PKC activation may result in tissue damage through a variety of mechanisms. In animal models, the inhibitor ruboxistaurin reduces albuminuria, diabetic histological changes and kidney injury. Like sulodexide, drug development of ruboxistaurin has reached completion of a phase II evaluation with mixed results. The third metabolic target is the nonenzymatic formulation of advanced glycation end-products (AGEs) through well described biochemical pathways. Multiple pathways lead to AGE accumulation in tissues in diabetes and diverse AGE products are formed. AGE deposition has been implicated in animal models of diabetic nephropathy. The leading AGE inhibitor currently in development is pyridoxamine, which has multiple actions that inhibit glycation. Pyridoxamine is an efficient AGE inhibitor in experimental diabetes. A phase II study in diabetic patients with nephropathy reported mixed efficacy results and a favourable safety profile. Phase III evaluation of pyridoxamine has not begun. These three classes of potential therapies, if successfully developed, will confirm that diabetic kidney disease has entered the era of biochemical treatments.


Cross-sectional Versus Longitudinal Change in a Prospective HR-pQCT Study.
Longitudinal studies assessing age-related changes using high-resolution peripheral quantitative computed tomography (HR-pQCT) provide novel insight compared with cross-sectional analyses. The purpose of this cohort study was 1) to determine individuals' change in HR-pQCT parameters over 5 years relative to least significant change (LSC), and 2) to evaluate if predicted rate of change from cross-sectional data is comparable to actual change from longitudinal investigation. A cohort of 466 (162 male, 304 female) participants completed two HR-pQCT scans with 5 years between assessments. After image registration, standard and cortical morphological analyses were conducted. Rate of bone microarchitectural change was compared between cross-sectional models and actual change calculated from longitudinal analyses. At the young end of the life span, we observed gains in total bone density of +0.2% to +2.9% per year, whereas the older participants (aged >50 years) lost total bone density at a rate of -0.3% to -1.3% per year. Declines in total bone density begin at age 40 years in females and 60 years in males, and significant adaptation was found at both ends of the age spectrum with respect to the LSC. Models predicting rate of change from cross-sectional data were similar to the actual change reported in this longitudinal study for total density and cortical thickness at the radius and cortical density at the tibia, but we found that changes in comparison to our 5-year longitudinal results were often overestimated from cross-sectional data. Studies aimed at observing age-related changes in a normative cohort, especially in a follow-up period of less than 5 years, are better to focus on the tibia rather than the radius because of the increased sensitivity to change at the tibia. © 2017 American Society for Bone and Mineral Research.


A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis.
This systematic meta-analysis on randomized controlled trials with diacerein was performed to provide an evidence-based assessment of its symptomatic efficacy in the treatment of osteoarthritis. Electronic databases were searched for randomized controlled trials with diacerein. A manual review of the literature, abstracts, and posters was also conducted. Unpublished final reports were obtained from the manufacturer. Only studies performed in knee and/or hip osteoarthritis were chosen for review. Study inclusion, quality scoring, and data extraction were performed by 2 reviewers independently. Objectives for analysis comprised pain, function, escape medication use, global efficacy, and safety ratings by patients and investigators. Specific study periods, such as the active treatment period and the treatment-free follow-up period (when present), were analyzed. Statistical analyses were based on the intention-to-treat principle as far as possible, and acknowledged tests were used for data analysis. A total of 23 studies were identified, 19 of which were included. Diacerein was significantly superior to placebo during the active treatment phase (Glass score, 1.50 [95% confidence interval, 0.80-2.20]). Both diacerein and nonsteroidal anti-inflammatory drugs (NSAIDs) were similarly efficacious during the treatment period; however, diacerein, but not NSAIDs, showed a carryover effect, persisting up to 3 months after treatment, with a significant analgesic-sparing effect during the follow-up period (Glass score, 2.06 [95% confidence interval, 0.66-3.46]). Tolerability assessment revealed no differences between diacerein and NSAIDs, although the latter showed more severe events. This systematic meta-analysis provides evidence for the symptomatic efficacy of diacerein in the treatment of knee and hip osteoarthritis, with reasonable tolerability.


Effects of fatty acids, ketone bodies, lactate and pyruvate on glucose utilization by guinea-pig cerebral cortex slices.
1. Starvation did not affect the rates of glucose utilization or lactate formation by guinea-pig cerebral cortex slices. 2. Palmitate (1mm), butyrate (5mm) or acetoacetate (5mm) did not affect glucose utilization or lactate formation by cerebral cortex slices from guinea pigs starved for 48hr. 3. dl-beta-Hydroxybutyrate (10mm) increased the formation of lactate without affecting glucose utilization by cerebral cortex slices from guinea pigs starved for 48hr. This implies that beta-hydroxybutyrate decreased the rate of glucose oxidation. 4. Metabolism of added ketone bodies can account for 20-40% of observed rates of oxygen consumption. 5. Lactate or pyruvate (5mm) decreased the rates of glucose utilization by guinea-pig cerebral cortex slices.


Targeting Glycine Reuptake in Alcohol Seeking and Relapse.
It has recently been demonstrated that pharmacological blockade of the glycine transporter 1 (GlyT1) reduced alcohol intake and relapse in rats. The aim of the present study was to further explore the role of GlyT1 in alcohol relapse-like behavior. For this purpose we used three different GlyT1 blockers-SSR504734, A-1246399, and RO4993850-and tested their effect on alcohol-seeking and relapse-like consumption. Two behavioral models, the alcohol deprivation effect model and the cue-induced reinstatement model, were used. Our data show that all three GlyT1 blockers reduce relapse-like alcohol consumption and cause either minimal or no side effects, measured as changes in home-cage activity, water intake, and body weight. In the reinstatement test, GlyT1 blockers completely abolished alcohol-seeking responses. Furthermore, we tested other drug/cue associations and found that cocaine-seeking responses were also abolished by GlyT1 blockade. Our data confirm that GlyT1 can be used as a target to develop novel anticraving and antirelapse drugs.


Glycerol as Precursor of Organoselanyl and Organotellanyl Alkynes.
Herein we describe the synthesis of organoselanyl and organotellanyl alkynes by the addition of lithium alkynylchalcogenolate (Se and Te) to tosyl solketal, easily obtained from glycerol. The alkynylchalcogenolate anions were generated in situ and added to tosyl solketal in short reaction times, furnishing in all cases the respective products of substitution in good yields. Some of the prepared compounds were deprotected using an acidic resin to afford new water-soluble 3-organotellanylpropane-1,2-diols. The synthetic versatility of the new chalcogenyl alkynes was demonstrated in the iodocyclization of 2,2-dimethyl-1,3-dioxolanylmethyl(2-methoxyphenylethynyl)selane 3f, which afforded 3-iodo-2-(2,2-dimethyl-1,3-dioxolanylmethyl) selenanylbenzo[b]furan in 85% yield, opening a new way to access water-soluble Se-functionalized benzo[b]furanes.


Antiproliferative triterpene saponins from Entada africana.
Nine new ester saponins (1-9) were isolated from the roots of Entada africana. Their structures were elucidated by 1D and 2D NMR experiments including 1D and 2D TOCSY, DQF-COSY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis, and chemical methods. The aglycon moieties were found to be echinocystic acid for compounds 1, 2, 4-6, 8, and 9 and acacic acid for 3 and 7. All isolated compounds were tested for their antiproliferative activity against the J774.A1, HEK-293, and WEHI-164 cell lines. Moderate to high cytotoxic potency was found for almost all compounds tested.


Two kinds of lithotrophs missing in nature.
Two groups of lithotrophic bacteria, the existence of which may be expected on evolutionary and thermodynamical grounds, have not yet been detected: (A) photosynthetic, anaerobic, ammonia bacteria, analogous to coloured sulphur bacteria, and (B) chemosynthetic bacteria that oxidize ammonia to nitrogen with O2 or nitrate as oxidant.


Feeding patterns of mosquitoes collected in the Senegal River basin.
Mosquitoes were collected with light traps baited with dry ice at 16 locations in Senegal during the rainy season of 1988. Of 62,055 mosquitoes identified, 1,384 (2.2%), representing 25 species in 4 genera, were bloodfed. Mosquito bloodmeals were screened by enzyme-linked immunosorbent assay against antisera to humans, bovines, goats, sheep and chickens. Overall, 88% of the bloodmeals tested were identified. Bloodmeals from 5 species of Culex mosquitoes comprised 82% of the number tested. Culex antennatus (36.6%) and Cx. tritaeniorhyncus (33.5%) were the most abundant. All Culex except those of the Cx. univittatus group fed most often on humans. Aedes species fed almost equally on all mammals tested, while species of Anopheles preferred cattle over humans, goats and sheep.


Selective arterial clamping does not improve outcomes in robot-assisted partial nephrectomy: a propensity-score analysis of patients without impaired renal function.
To assess the benefit of selective arterial clamping (SAC) as an alternative to main renal artery clamping (MAC) during robot-assisted partial nephrectomy (RAPN) in patients without underlying chronic kidney disease (CKD). Our study cohort comprised 665 patients without impaired renal function undergoing MAC (n = 589) or SAC (n = 76) during RAPN from four medical institutions in the period 2008-2015. We compared complication rates, positive surgical margin (PSM) rates, and peri-operative and intermediate-term renal functional outcome between 132 patients undergoing MAC and 66 undergoing SAC after 2-to-1 nearest-neighbour propensity-score matching for age, sex, body mass index, RENAL nephrometry score, tumour size, baseline estimated glomerular filtration rate (eGFR), American Society of Anesthesiologists (ASA) score, Charlson comorbidity index (CCI) and warm ischaemia time (WIT). In propensity-score-matched patients, PSM (5.7 vs 3.0%; P = 0.407) and complication rates (13.8 vs 10.6%; P = 0.727) did not differ between the MAC and SAC groups. The incidence of acute kidney injury for MAC vs SAC (25.0 vs 32.0%; P = 0.315) within the first 30 days was similar. At a median follow-up of 7.5 months, the percentage reduction in eGFR (-9.3 vs -10.4%; P = 0.518) and progression to CKD ≥ stage 3 (7.2 vs 8.5%; P = 0.792) showed no difference. Our study findings show no difference in PSM rates, complication rates or intermediate-term renal functional outcomes between patients with unimpaired renal function who underwent SAC vs those who underwent MAC. When expected WIT is low, the routine use of SAC may not be necessary. Further studies will need to determine the role of SAC in patients with a solitary kidney or with significantly impaired renal function.


Graft Modification of Starch Nanoparticles Using Nitroxide-Mediated Polymerization and the "Grafting to" Approach.
Starch nanoparticles (SNP) were modified with synthetic polymers using the "grafting to" approach and nitroxide-mediated polymerization. SG1-capped poly(methyl methacrylate-co-styrene) (P(MMA-co-S)) copolymers with low dispersity and high degree of livingness were first synthesized in bulk. These macroalkoxyamines were then grafted to vinyl benzyl-functionalized SNP to obtain biosynthetic hybrids. The grafted materials, SNP-g-P(MMA-co-S), were characterized by 1H NMR, FTIR, TGA, and elemental analysis. The total amount of grafted polymer and the grafting efficiency were evaluated for different molecular weights (5870-12150 g·mol-1) of the grafted polymer, the polymer addition approach (batch or semibatch) and the initial polymer loading (2.5, 5, or 10 g polymer/g SNP). The proposed approach presented in this work to graft modify SNP allows for a precise surface modification of the nanoparticles, while permitting that the final properties of the resulting biohybrid to be tunable according to the choice of polymer grafted.


Continuous extraction of alpha- and beta-amylases from Zea mays malt in a PEG4000/CaCl2 ATPS.
In the present work, alpha- and beta-amylase enzymes from Zea mays malt were recovered by continuous extraction in a PEG/CaCl2 aqueous two-phase system (ATPS). The influences of the flux rate (RQ), free area of vane (A(free)) and vane rotation (RV) on enzyme recovery were studied by optimization using response surface methodology (RSM). The protein content and enzyme activity were measured from time to time in the extract and refined fluxes. RSM curves showed a squared dependence of recovery index with the RQ, A(free) and RV. The best system for recovering the maize malt enzymes was with low vane rotation and flux rate and high free area of vane. Alpha- and beta-amylases were purified 130-fold in the salt-rich phase.


STRENGTH EXERCISES COMBINED WITH DRY NEEDLING WITH ELECTRICAL STIMULATION IMPROVE PAIN AND FUNCTION IN PATIENTS WITH CHRONIC ROTATOR CUFF TENDINOPATHY: A RETROSPECTIVE CASE SERIES.
Rotator cuff tendinopathy (RTCT) is regularly treated by the physical therapist. Multiple etiologies for RTCT exist, leading an individual to seek treatment from their provider of choice. Strengthening exercises (SE) have been reported to be effective in the treatment of RTCT, but there is limited evidence on the effectiveness of dry needing (DN) for this condition. The purpose of this retrospective case series was to investigate DN to various non-trigger point-based anatomical locations coupled with strengthening exercises (SE) as a treatment strategy to decrease pain and increase function in healthy patients with chronic RTC pathology. Eight patients with RTCT were treated 1-2 times per week for up to eight weeks, and no more than sixteen total treatment sessions of SE and DN. Outcomes were tested at baseline and upon completion of therapy. A long-term outcome measure follow up averaging 8.75 months (range 3 to 20 months) was also performed. The outcome measures included the Visual Analog Scale (VAS) and the Quick Dash (QD). Clinically meaningful improvements in disability and pain in the short term and upon long-term follow up were demonstrated for each patient. The mean VAS was broken down into best (VAS(B)), current (VAS(C)), and worst (VAS(W)) rated pain levels and the mean was calculated for the eight patients. The mean VAS(B) improved from 22.5 mm at the initial assessment to 2.36 mm upon completion of the intervention duration. The mean VASC improved from 28.36 mm to 5.0 mm, and the mean VAS(W) improved from 68.88 mm to 13.25 mm. At the long-term follow up (average 8.75 months), The mean VAS(B), VAS(C), and VAS(W) scores were 0.36 mm, 4.88 mm, and 17.88 mm respectively. The QD(mean) for the eight patients improved from 43.09 at baseline to 16.04 at the completion of treatment. At long-term follow-up, the QD(mean) was 6.59. Clinically meaningful improvements in pain and disability were noted with the intervention protocol. All subjects responded positively to the intervention and reported quality of life was improved for each subject. The results of this case series show promising outcomes for the combination of SE and DN in the treatment of chronic RTCT. Level 4.


Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells.
Hypoxia is an important and common characteristic of many human tumors. It is a challenge clinically due to the correlation with poor prognosis and resistance to radiation and chemotherapy. Understanding the biochemical response to hypoxia would facilitate the development of novel therapeutics for cancer treatment. Here, we investigate alterations in gene expression in response to hypoxia by quantitative proteome analysis using stable isotope labeling with amino acids in cell culture (SILAC) in conjunction with LCMS/MS. Human HeLa cells were kept either in a hypoxic environment or under normoxic conditions. 125 proteins were found to be regulated, with maximum alteration of 18-fold. In particular, three clusters of differentially regulated proteins were identified, showing significant upregulation of glycolysis and downregulation of mitochondrial ribosomal proteins and translocases. This interaction is likely orchestrated by HIF-1. We also investigated the effect of hypoxia on the cell cycle, which shows accumulation in G1 and a prolonged S phase under these conditions. Implications. This work not only improves our understanding of the response to hypoxia, but also reveals proteins important for malignant progression, which may be targeted in future therapies.


Carrageenans as Sustainable Water-Processable Binders for High-Voltage NMC811 Cathodes.
Poly(vinylidene fluoride) (PVDF) is the most common binder for cathode electrodes in lithium-ion batteries. However, PVDF is a fluorinated compound and requires toxic N-methyl-2-pyrrolidone (NMP) as a solvent during the slurry preparation, making the electrode fabrication process environmentally unfriendly. In this study, we propose the use of carrageenan biopolymers as a sustainable source of water-processable binders for high-voltage NMC811 cathodes. Three types of carrageenan (Carr) biopolymers were investigated, with one, two, or three sulfonate groups (SO3-), namely, kappa, iota, and lambda carrageenans, respectively. In addition to the nature of carrageenans, this article also reports the optimization of the cathode formulations, which were prepared by using between 5 wt % of the binder to a lower amount of 2 wt %. Processing of the aqueous slurries and the nature of the binder, in terms of the morphology and electrochemical performance of the electrodes, were also investigated. The Carr binder with 3SO3- groups (3SO3-Carr) exhibited the highest discharge capacities, delivering 133.1 mAh g-1 at 3C and 105.0 mAh g-1 at 5C, which was similar to the organic-based PVDF electrode (136.1 and 108.7 mAh g-1, respectively). Furthermore, 3SO3-Carr reached an outstanding capacity retention of 91% after 90 cycles at 0.5C, which was attributed to a homogeneous NMC811 and a conductive carbon particle dispersion, superior adhesion strength to the current collector (17.3 ± 0.7 N m-1 vs 0.3 ± 0.1 N m-1 for PVDF), and reduced charge-transfer resistance. Postmortem analysis unveiled good preservation of the NMC811 particles, while the 1SO3-Carr and 2SO3-Carr electrodes showed damaged morphologies.


Short-term Effects of Ethanol Intoxication on Ascorbic Acid and Lipid Metabolism and on Drug-metabolizing Enzymes in Liver of Rats.
The effects of one-time ethanol intoxication on ascorbic acid and lipid metabolism and on drug-metabolizing enzymes in liver of rats were investigated. Male Donryu rats that had been fed semi-purified feed were given 5 g/kg ethanol solution (25%, w/v) via a stomach tube and killed 16 h after intubation. The amount of ascorbic acid excreted in the urine after ethanol administration increased, but renal and adrenal concentrations of ascorbic acid decreased. The serum levels of total cholesterol, high-density-lipoprotein cholesterol, triglycerides, phospholipids, and non-esterified fatty acids were elevated in rats given ethanol, but hepatic level of total lipids, cholesterol, triglycerides, phospholipids were not. The hepatic concentrations of cytochrome P-450 and cytochrome b5 did not increase, but this large dose of ethanol increased the activities of aminopyrine N-demethylase and cytochrome c reductase. These results indicated that the single dose of ethanol affected the ascorbic acid and lipid metabolism of rats, and induced drug-metabolizing enzymes in their liver.


Meta-coupler arrays linking propagating waves and photonic topological modes on a chip.
Photonic topological modes (PTMs) have attracted increasing attention due to their robust optical performance, which provides a defect-tolerant strategy for chip-integrated photonic systems. The current coupling schemes rely on bulky structures that severely limit their potential applications in high-density optical integration. Here, plasmonic metasurfaces loaded on topological waveguide arrays are explored to generate PTMs. The normally incident circularly polarized beam can be coupled into the topological interface or edge modes after carefully optimizing the metasurfaces. The result provides a compact and flexible method for PTMs generation on a chip, suggesting a promising avenue toward the application of topological photonic devices.


d-Xylose consumption by nonrecombinant Saccharomyces cerevisiae: A review.
Xylose is the second most abundant sugar in nature. Its efficient fermentation has been considered as a critical factor for a feasible conversion of renewable biomass resources into biofuels and other chemicals. The yeast Saccharomyces cerevisiae is of exceptional industrial importance due to its excellent capability to ferment sugars. However, although S. cerevisiae is able to ferment xylulose, it is considered unable to metabolize xylose, and thus, a lot of research has been directed to engineer this yeast with heterologous genes to allow xylose consumption and fermentation. The analysis of the natural genetic diversity of this yeast has also revealed some nonrecombinant S. cerevisiae strains that consume or even grow (modestly) on xylose. The genome of this yeast has all the genes required for xylose transport and metabolism through the xylose reductase, xylitol dehydrogenase, and xylulokinase pathway, but there seems to be problems in their kinetic properties and/or required expression. Self-cloning industrial S. cerevisiae strains overexpressing some of the endogenous genes have shown interesting results, and new strategies and approaches designed to improve these S. cerevisiae strains for ethanol production from xylose will also be presented in this review.


Differential control of dopamine ascending pathways by serotonin2B receptor antagonists: New opportunities for the treatment of schizophrenia.
Recent studies suggest that the central serotonin2B receptor (5-HT2BR) could be an interesting pharmacological target for treating neuropsychiatric disorders related to dopamine (DA) dysfunction, such as schizophrenia. Thus, the present study was aimed at characterizing the role of 5-HT2BRs in the control of ascending DA pathway activity. Using neurochemical, electrophysiological and behavioral approaches, we assessed the effects of two selective 5-HT2BR antagonists, RS 127445 and LY 266097, on in vivo DA outflow in DA-innervated regions, on mesencephalic DA neuronal firing, as well as in behavioral tests predictive of antipsychotic efficacy and tolerability, such as phencyclidine (PCP)-induced deficit in novel object recognition (NOR) test, PCP-induced hyperlocomotion and catalepsy. Both RS 127445 (0.16 mg/kg, i.p.) and LY 266097 (0.63 mg/kg, i.p.) increased DA outflow in the medial prefrontal cortex (mPFC). RS 127445, devoid of effect in the striatum, decreased DA outflow in the nucleus accumbens, and potentiated haloperidol (0.1 mg/kg, s.c.)-induced increase in mPFC DA outflow. Also, RS 127445 decreased the firing rate of DA neurons in the ventral tegmental area, but had no effect in the substantia nigra pars compacta. Finally, both RS 127445 and LY 266097 reversed PCP-induced deficit in NOR test, and reduced PCP-induced hyperlocomotion, without inducing catalepsy. These results demonstrate that 5-HT2BRs exert a differential control on DA pathway activity, and suggest that 5-HT2BR antagonists could represent a new class of drugs for improved treatment of schizophrenia, with an ideal profile of effects expected to alleviate cognitive and positive symptoms, without eliciting extrapyramidal symptoms.


Violence and trauma response.
This chapter is intended to assist managers and occupational physicians in assessing the impact of violence-induced trauma in the workplace, and in determining the most appropriate responses for both employee and corporate welfare. Among the topics covered are the dimensions of violence in the workplace, the phases of the trauma experience, the objective and subjective experience of employee-victims, and the dynamic interplay and organizational trauma.


The role of c-jun in PDTC-sensitive flow-dependent restenosis after angioplasty and stenting.
Restenosis after balloon angioplasty and stenting is exacerbated by low flow. Flow-dependent restenosis after angioplasty but not stenting is prevented by the antioxidant pyrrolidine dithiocarbamate (PDTC). c-jun may play a role in these events as AP-1 activity is both flow and redox sensitive. Carotid arteries of cholesterol fed rabbits underwent stenting or balloon injury in the presence of low or normal flow. c-jun mRNA expression was enhanced by low flow and injury (stent>balloon) and inhibited by the antioxidant PDTC irrespective of the injury type. The effect of locally delivered DZ13 (a DNAzyme specific for c-jun) or scrambled DZ13 (inactive DNAzyme) was assessed by histomorphometry at 28 days. Low flow significantly increased intimal hyperplasia in B and S relative to normal flow (P<0.05). The active DNAzyme DZ13 markedly reduced intimal hyperplasia (P<0.001) and increased lumen size (P<0.05) in balloon-injured but not in stented segments, and abrogated the effect of low flow on restenosis after angioplasty, similar to the morphological effects of PDTC. We conclude that c-jun expression is enhanced by low flow and by injury (stent>balloon) and markedly attenuated by PDTC, and that c-jun is an important mediator of flow-dependent restenosis in balloon-injured but not stented vessels.


Evaluation of the conformational propensities of peptide isosteres as a basis for selecting bioactive pseudopeptides.
Our aim was to compare the repertoires of conformers formed by the model zwitterionic peptides AA and AAA in aqueous solution with the conformational profiles of a range of their peptide isosteres, so as to facilitate selection of isosteres for synthesis and testing as biologically stable surrogates of bioactive di- and tripeptides. Comparisons were based upon the results of conformational analysis using a random search approach implemented within the SYBYL molecular modelling package, using zwitterionic molecules, simulated aqueous solvation using a dielectric constant of 80 and allowing all torsions to vary. For each compound, individual conformers were grouped on the basis of specific combinations of psi, phi and omega torsions and, using their energies, the aggregated percentage for each group was calculated using a Boltzmann distribution and displayed using a 3D pseudo Ramachandran plot relating percentage conformer to psi and phi torsions. Retroamide, N-methylamide and thioamide isosteres showed the best match to natural peptides and to the molecular recognition parameters defined for substrates of peptide transporters. The results should aid rational design of therapeutic agents in various areas, e.g. oral delivery of drugs by peptide transporters and of peptidase inhibitors. This approach may usefully be applied to various biochemical and pharmaceutical topics.


Lymphocytes of BRCA1 and BRCA2 germ-line mutation carriers, with or without breast cancer, are not abnormally sensitive to the chromosome damaging effect of moderate folate deficiency.
Mutations in BRCA1 and BRCA2 genes may cause defective DNA repair and increase the risk for breast cancer. Folate deficiency is associated with increased breast cancer risk and induces chromosome abnormalities. We hypothesized that BRCA1 and BRCA2 germline mutation carriers are more sensitive to the genome damaging effect of folate deficiency compared with healthy non-carrier controls and that this sensitivity is further increased in those carriers who develop breast cancer. We tested these hypotheses in lymphocytes cultured in a medium containing 12 or 120 nM folic acid (FA) for 9 days and measured proliferative capacity and chromosomal instability using the cytokinesis-block micronucleus assay. BRCA1 and BRCA2 mutation carriers with or without breast cancer were not abnormally sensitive to FA deficiency-induced chromosome instability; however, BRCA2 mutation carriers had significantly reduced cell proliferation. FA deficiency reduced cell proliferation and increased micronucleus formation significantly, accounting for 45-59% and 70-75% of the variance in these parameters compared with 0.3-8.5% and 0.2-0.3% contributed by BRCA1 or BRCA2 mutation carrier status, respectively. The results of this study suggest that moderate folate deficiency has a stronger effect on chromosomal instability than BRCA1 or BRCA2 mutations found in breast cancer families.


A Case Report of the First Nonburn-related Military Trauma Victim Treated with Spray Skin Regenerative Therapy in Combination with a Dermal Regenerate Template.
Massive soft tissue and skin loss secondary to war-related traumas are among the most frequently encountered challenges in the care of wounded warriors. This case report outlines the first military nonburn-related trauma patient treated by a combination of regenerative modalities. Our case employs spray skin technology to an established dermal regenerate matrix. Our patient, a 29-year-old active duty male, suffered a combat blast trauma in 2010 while deployed. The patient's treatment course was complicated by a severe necrotizing fasciitis infection requiring over 100 surgical procedures for disease control and reconstruction. In secondary delayed reconstruction procedures, this triple-limb amputee underwent successful staged ventral hernia repair via a component separation technique with biologic mesh underlay although this resulted in a skin deficit of more than 600 cm2. A dermal regenerate template was applied to the abdominal wound to aid in establishing a "neodermis." Three weeks after dermal regenerate application, spray skin was applied to the defect in conjunction with a 6:1 meshed split thickness skin graft. The dermal regenerate template allowed for optimization of the wound bed for skin grafting. The use of spray skin allowed for a 6:1 mesh ratio, thus minimizing the donor-site size and morbidity. Together, this approach resulted in complete healing of a large full-thickness wound. The patient is now able to perform activities of daily living, walk without a cane, and engage in various physical activities. Overall, our case highlights the potential that combining regenerative therapies can achieve in treating severe war-related and civilian traumatic injuries.


Folic acid and homocysteine in age-related disease.
It has been known for decades that babies born to women that have a dietary deficiency in folic acid (folate) are at increased risk for birth defects, and that the nervous system is particularly susceptible to such defects. Folate deficiency in adults can increase risk of coronary artery disease, stroke, several types of cancer, and possibly Alzheimer's and Parkinson's diseases. Recent findings have begun to reveal the cellular and molecular mechanisms whereby folate counteracts age-related disease. An increase in homocysteine levels is a major consequence of folate deficiency that may have adverse effects on multiple organ systems during aging. Humans with inherited defects in enzymes involved in homocysteine metabolism, including cystathionine beta-synthase and 5,10-methylenetetrahydrofolate reductase, exhibit features of accelerated aging and a marked propensity for several age-related diseases. Homocysteine enhances accumulation of DNA damage by inducing a methyl donor deficiency state and impairing DNA repair. In mitotic cells such DNA damage can lead to cancer, while in postmitotic cells such as neurons it promotes cell death. The emerging data strongly suggest that elevated homocysteine levels increase the risk of multiple age-related diseases, and point to dietary supplementation with folate as a primary means of normalizing homocysteine levels and increasing healthspan.


Is democracy good for health?
Studies of health have recognized the influence of socioeconomic position on health outcomes. People with higher socioeconomic ranking, in general, tend to be healthier than those with lower socioeconomic rankings. The effect of political environment on population health has not been adequately researched, however. This study investigates the effect of democracy (or lack thereof) along with socioeconomic factors on population health. It is maintained that democracy may have an impact on health independent of the effects of socioeconomic factors. Such impact is considered as the direct effect of democracy on health. Democracy may also affect population health indirectly by affecting socioeconomic position. To investigate these theoretical links, some broad measures of population health (e.g., mortality rates and life expectancies) are empirically examined across a spectrum of countries categorized as autocratic, incoherent, and democratic polities. The regression findings support the positive influence of democracy on population health. Incoherent polities, however, do not seem to have any significant health advantage over autocratic polities as the reference category. More rigorous tests of the links between democracy and health should await data from multi-country population health surveys that include specific measures of mental and physical morbidity.


Irradiated endothelial cells modulate the malignancy of liver cancer cells.
The tumor microenvironment is closely associated with tumor malignancy, and includes tumor relapse and metastasis trigged by epithelial-mesenchymal transition (EMT), which leads to the expansion of cancer stem-like cells. Radiotherapy is known to acutely and persistently affect changes in this tumor microenvironment by altering the vascular functions of tumor endothelial cells. However, the precise role of endothelial cells in tumor malignancy following treatment with irradiation has not been completely elucidated. The present study investigated the differences in malignant behavior of liver cancer cells in response to irradiated endothelial cells. To achieve this, a co-cultivation system was established to identify the potential role of endothelial cells in malignant liver cancer cells using medium conditioned with endothelial cells. It was observed that the medium conditioned by endothelial cells when irradiated with a single dose (2 Gy), greatly increased the migratory and invasive properties of liver cancer cells, as well as inducing mesenchymal markers, and enhancing the sphere-forming ability of liver cancer cells, The mRNA levels of genes regulating the self-renewal of cancer stem cells were increased in liver cancer cells by treatment with medium conditioned with endothelial cells. However, neither the medium conditioned by endothelial cells irradiated with fractionated doses (2 Gy × 3; 2 Gy/day for 3 days) or with a single dose (6 Gy) greatly influenced the malignancy of liver cancer cells. In conclusion, the data obtained by the present study indicated that 2 Gy irradiation of endothelial cells influenced the increase in tumor malignancy in liver cancer cells. Furthermore, the distinct differences in the indirect effects of ionizing radiation on tumor malignancy may provide valuable information for the improvement in the efficacy of radiotherapy.


Current trends and investigative developments in celiac disease.
Celiac disease has become extensively studied. What could be the cause? Increasing the accuracy of diagnostic tests for celiac disease has led to more discovered cases. Serological diagnosis of celiac disease has undergone important changes in recent years. Application of serological tests has reflected the diagnostic performance of tissue transglutaminase antibody and endomysial antibody as screening tests for celiac disease but also the progress of new serological tests as the antibodies against synthetic deamidated gliadin peptides. Serological tests are largely responsible for the recognition that celiac disease is not a rare disease. The Consensus in celiac disease from 2008 conducted under the aegis of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition jointly with North American Society of Pediatric Gastroenterology, Hepatology and Nutrition which agreed that "Celiac disease is an immune-mediated enteropathy that can affect any system or organ and that can present itself with a wide range of clinical manifestations of variable severity" was confirmed. But increasing prevalence of this disease has led to the need for new methods of treatment among patients with celiac disease. Studies on quality of life of patients with celiac disease have questioned the gluten-free diet. As such new therapies, like TG2 inhibitors, the copolymer P (HEMA-co-SS) and other new experimental therapies, have emerged in celiac disease. The new therapies in celiac disease are based on new investigations in gluten toxicity screening, like K562(S)-cell agglutination, A1 and G12 monoclonal antibodies and proteomics. In this paper we want to present the investigative developments in celiac disease. We also want to find whether a new treatment in celiac disease is necessary.


Metabolic control in insulin-dependent diabetes mellitus, as reflected in the in vitro effects of platelets on endothelial cell proliferation and prostacyclin production.
We tested the hypothesis that the degree of metabolic control in diabetes mellitus may be a determinant of the ability of platelets to stimulate proliferation of endothelial cells (ECs) and smooth muscle cells (SMCs). Platelets were obtained from 24 patients (two groups of 12 patients each) with insulin-dependent diabetes mellitus (IDDM) and increased blood glucose concentrations (HbA1c > 10% Hb), duration of disease 2-45 years, on no other medication than insulin at the time of blood sampling or during the preceding 6 months, and with no signs of coronary artery disease, nephropathy, hypertension or retinopathy. The patients served as their own controls, platelets being obtained from them again 2-4 months later when their mean glucose values were lower (HbA1c < 6.5% Hb). EC proliferation was significantly reduced after exposure to platelets obtained from the patients when their metabolic control had improved, whereas no significant differences were seen in either SMC proliferation or prostacyclin production. There was no correlation between changes in insulin dosage and either cell proliferation or prostacyclin production, or between changes in lipid values and cell proliferative capacity. It is concluded that, EC proliferation will be greater, owing to the platelet effects found in vitro, when metabolic control in diabetics is poor than when it is good, which may be of importance regarding the repair of endothelial lesions.


Grip strength ratio: a grip strength measurement that correlates well with DASH score in different hand/wrist conditions.
Grip strength correlates with personal factors such as gender, age and nutritional status and has a good inter-rater reliability. It reflects fairly well how much people can use their hands.The Disabilities of the Arm, Shoulder and Hand (DASH) Outcome Measure 3 is a 30-item, self-report, questionnaire that reflects the patients' opinion on their disability due to upper-limb disorders. We assessed if grip strength and grip strength ratio correlate with DASH score. In 3 groups (20 healthy volunteers, 17 patients after distal radius fractures, 12 patients with different hand/wrist conditions) grip strength and DASH scores (items 1-21, 22-30 and total) were assessed. To exclude personal factors grip strengths in the injured or non-dominant hand and grip strength ratios (grip strength in the injured or non-dominant hand divided by grip strength in the non-injured or dominant hand) were assessed too. Results were analyzed groups using Pearson Correlation Coefficients and with a multivariate ANOVA. Grip strength ratio was 0.97 in healthy volunteers, 0.52 in patients after distal radius fracture and 0.74 in patients with various other hand/wrist disorders.Significant correlations were found between the grip strength ratio and DASH as well as DASH subsections in all groups and between DASH scores and grip strength in some. The correlations between the ratio of the grip strength (GSR) and DASH were much stronger than the correlation between grip strength and DASH. This emphasizes the value of the GSR. Age showed no correlation with grip strength ratio using a multivariate ANOVA. Grip strength ratio correlates well with the DASH score in different hand and wrist conditions. It is a valuable tool to assess patients that speak a different language and have problems with the non-dominant hand and probably easier to follow over time than the DASH score, which is time consuming to fill in and process.


Repigmentation of extensive inflammatory vitiligo with raised borders using early and aggressive treatment.
Inflammatory vitiligo with raised borders (IVRB) is a rare subtype of vitiligo described as having a rim of raised erythema at the periphery of the depigmented patches. The etiology is poorly understood, and there are few reports of successful treatment of the condition in the literature. We report a 38-year-old South Asian male who presented with diffuse depigmented macules and patches surrounded by blue-gray rims involving a large body surface area. Light microscopy revealed inflammatory vitiligo. He was treated with 2 courses of oral prednisone and whole-body narrow-band ultraviolet B (NB-UVB) therapy, which resulted in cessation of disease spread as well as substantial repigmentation. Our observation suggests that early and aggressive treatment can lead to significant and rapid improvement in patients with IVRB.


Episodic Memory Dysfunction in Behavioral Variant Frontotemporal Dementia: A Clinical And FDG-PET Study.
Episodic memory disturbance is still considered as an exclusion criterion for behavioral variant frontotemporal dementia (bvFTD), but growing evidence suggests that memory can be impaired. Our main purposes were to assess episodic memory in a group of bvFTD patients comparatively with Alzheimer's disease (AD) patients, and analyze the relationship between episodic memory and brain metabolism measured using positron emission tomography imaging with 18F-fluorodeoxyglucose (FDG-PET). Twenty-six bvFTD, 29 AD, and 24 healthy controls were included. Episodic memory was assessed by the Free and Cued Selective Reminding Test (FCSRT), which controls for effective encoding and measures memory consolidation processing. All participants underwent FDG-PET brain scans to provide data for voxel-based brain mapping analysis. Half of bvFTD patients had a deficit of total, free delayed, and total free delayed recall as severe as AD patients (amnestic-FTD). The other half had FCSRT scores similar to controls (non-amnestic-FTD). Imaging analyses revealed that amnestic-FTD showed bilateral lower metabolism than non-amnestic-FTD in anterior parahippocampal and inferior temporal gyri. Additionally, FCSRT total and total delayed scores were inversely correlated with parahippocampal metabolism in both bvFTD and AD. Besides, bvFTD showed an inverse association among FCSRT and inferior temporal metabolism. Our findings support that bvFTD could present a genuine amnesia affecting storage and consolidation abilities, which involves structures implicated in the Papez circuit, as occurs in AD, and also inferior temporal regions. These results contribute to understanding the mechanisms underpinning memory dysfunction in bvFTD, and may be relevant to further revisions of the current diagnostic criteria.


Hardiness, spirituality, and suicidal ideation among individuals with substance abuse: the moderating role of gender and marital status.
Substance abuse is a serious and major public health problem in Iran and potentially increases the risk of suicidal behavior; therefore, it is essential to increase our knowledge concerning the etiology of suicide among individuals with substance use disorders. The present study sought to examine the associations among hardiness, spirituality, and suicidal ideation in Iranian individuals with substance abuse. This cross-sectional study was conducted in 2012, and participants comprised 450 individuals seeking substance abuse treatment at 10 addiction treatment centers in Tehran, Iran. All data were collected via self-report questionnaires. Sixty-seven percent of participants were male, 47% were married, and 59% were working. Structural equation modeling (SEM) suggested that, as expected, spirituality and hardiness were positively associated with each other. Findings also showed that spirituality and hardiness were negatively associated with suicidal ideation among this group of individuals with substance abuse, explaining 46% of the variance in suicidal ideation. That is, those with low levels of spirituality and low levels of hardiness were more likely to report suicidal ideation. There was a moderating effect of gender, such that greater hardiness predicted a lower likelihood of suicidal ideation for males but not for females. These findings reinforce the importance of spirituality and hardiness as protective factors against suicidal ideation in individuals with substance abuse, as well as the particular role of hardiness for men.


Frequent inactivation of the transforming growth factor beta type II receptor in small-cell lung carcinoma cells.
Small-cell lung cancer (SCLC) has a significantly worse prognosis than other forms of bronchogenic carcinoma. Because transforming growth factor beta (TGF-beta) appears to play an important role in the pathogenesis of SCLC, we examined the status of the TGF-beta receptor system in a series of 11 human small-cell carcinoma cell lines. None of these cell lines expressed more than one-tenth the level of TGF-beta type II receptor (T beta R-II) gene mRNA produced by TGF-beta-sensitive normal epithelial cells. In addition, one of the cell lines expressed a second truncated T beta R-II transcript, which is predicted to encode a protein that lacks the terminal two-thirds of the serine-threonine kinase domain. No other structural alterations in the promoter or coding sequences of the T beta R-II gene were found in any of the cell lines, nor could the loss of T beta R-II mRNA expression be ascribed to de novo hypermethylation of promoter/enhancer sequences. These findings indicate that inactivation of the TGF-beta signaling pathway caused by the loss of T beta R-II gene expression is a common and, therefore, probably pathogenetically important feature of small-cell lung carcinoma.


Sarcoplasmic reticular Ca2+-pump adaptation in cardiac hypertrophy due to pressure overload in pigs.
Ca2+-transport activities of the sarcoplasmic reticulum isolated from the non-failing hypertrophied left ventricle due to supravalvular banding of aorta for 4 and 8 weeks in pigs were compared with those from the sham operated controls. The rate of Ca2+-uptake, but not the capacity, in 4 weeks hypertrophied heart preparations was increased. On the other hand, both the rate and capacity of sarcoplasmic reticulum to accumulate Ca2+ were decreased at 8 weeks of heart hypertrophy. The Ca2+-binding and Ca2+-stimulated Mg2+ dependent ATPase activities of the reticular fractions from 4 and 8 weeks hypertrophied hearts were not significantly different from the control values. No changes in the sarcoplasmic reticular phospholipid contents were evident except that sphingomyelin was significantly decreased in 4 weeks and diphosphatidylglycerol was increased in both 4 and 8 weeks hypertrophied preparations. These results suggest that adaptation of the sarcoplasmic reticulum function in physiologic and pathologic hypertrophied hearts may occur by changing the efficiency of Ca2+-pump system during the development of cardiac hypertrophy.


Monomers of condensed tannins affect the larval exsheathment of parasitic nematodes of ruminants.
The current control of parasitic nematodes in small ruminants relies on the use of chemical anthelmintics, but the development of resistance requires research in alternatives. Bioactive plants represent one of those solutions. Previous results suggest that plants rich in condensed tannins (CTs) might have direct anthelmintic effects. However, the relationships between the biochemistry of active compounds and the mechanisms of action remain to be elucidated. Therefore, this study examined in vitro the effects of different CT monomers on the exsheathment of infective larvae for two nematode species. Monomers of prodelphinidins were more potent inhibitors of exsheathment than those of procyanidins. More severe inhibition was also found with galloyl derivatives. These results suggest that the number of free hydroxy groups of CT monomers is a key factor in interactions with parasite larvae. Comparison of effects between the two nematodes suggests different susceptibility to monomers depending on species, which might be related to the protein composition of sheaths.


Predicting persistent posttraumatic stress disorder (PTSD) in UK military personnel who served in Iraq: a longitudinal study.
In a longitudinal study we assessed which baseline risk factors are associated with persistent and partially remitted PTSD in comparison to fully remitted PTSD. 6427 (68%) of a randomly selected sample of UK service personnel completed the PTSD checklist (PCL) between 2004 and 2006 (Phase 1) and between 2007 and 2009 (Phase 2). 230 (3.9%) had possible PTSD at baseline. 66% of those with possible PTSD at baseline remitted (PCL score <30) or partially remitted (PCL score 30-49) by phase 2 of the study. Associations of persistent PTSD with the fully remitted group for risk factors at phase 1 adjusted for confounders were having discharged from service (OR 2.97, 95% CI 1.26-6.99), higher educational qualification (OR 2.74, 95% 1.23-6.08), feeling unsupported on return from deployment (OR 10.97, 95% CI 3.13-38.45), deployed not with parent unit (OR 5.63, 95% CI 1.45-21.85), multiple physical symptoms (OR 3.36, 95% CI 1.44-7.82), perception of poor or fair health (OR 2.84, 95% CI 1.28-6.27), older age and perception of risk to self (increasing with the number of events reported, p = 0.04). Deploying but not with a parent unit and psychological distress were associated in the partially remitted PTSD when compared to the fully remitted group. The positive and negative likelihood ratios for the factors most highly associated with persistent PTSD indicated they were of marginal value to identify those whose presumed PTSD would be persistent. Many factors contribute to the persistence of PTSD but none alone is useful for clinical prediction.


The relationship of parental drug use and parents' attitude concerning adolescent drug use to adolescent drug use.
The purpose of this study was to examine the relationship of two variables, parental drug use and parental attitude toward adolescent drug use, both as perceived by the adolescent respondent to his or her own use or nonuse of drugs. A sample of 106 drug-using and 96 nondrug-using adolescents was obtained through the use of the anthropological " snowball " technique. All respondents were administered a drug use history profile and a personal data questionnaire. In order to be classed as drug users, respondents had to have been using two or more recreational substances on a regular basis. Nondrug users were those who used no recreational drugs, although individuals who had tried alcohol or tobacco experimentally were included in this group. On the personal data form, respondents were asked to describe their parents' use of alcohol, tobacco, or other substances, and to indicate their parents' attitudes concerning adolescent use of drugs. Parental attitudes were classed as permissive if the respondent indicated that parents were indifferent about drug use, if they accepted a certain range of drugs, or if the decision were left up to the youth. A nonpermissive attitude was defined as one which would not accept drug use by the adolescent. Four 2 x 2 Chi-square analyses were used to determine significance of the relationship between adolescent drug use and parents' use or nonuse of drugs, parents' attitudes about adolescent use or nonuse and actual adolescent use or non-use, and this same attitudinal relationship looking at parent users and nonusers separately.(ABSTRACT TRUNCATED AT 250 WORDS)


[Intervention effect of tongfei mixture on nocturnal hypoxia in patients with chronic obstructive pulmonary disease].
To study the effect of tongfei mixture (TFM, a Chinese recipe mainly consisted of angelica and rehmannia root) on nocturnal hypoxia in patients with chronic obstructive pulmonary disease (COPD). Sixty patients with COPD of remission phase were randomly divided into 3 groups, 20 in each group. Group A was the control group; Group B, the group simply treated with oxygen; Group C, treated with oxygen and TFM. Changes of pulmonary function, diaphragm muscle mobility (DMM), 6 min walk distance (6MWD), morning arterial blood gas, nocturnal lowest oxygen saturation (LSaO2), mean blood oxygen saturation (MSaO2), the percentage of saturation lower than 90% time account for total sleeping time (SLT90%) and ultrasonocardiogram before and after treatment were observed. Levels of LSaO2, MSaO2 and SLT90% in Groups B and C were significantly higher than those in Group A (P<0.05, P<0.01). The lowering of PaCO2 in Group C was more significant than that in Group B (P<0.05). The mPAP level in Group C was lower, FEV1, 6MWD and DMM were improved than those in Group A and B, showing significant difference (P<0.05). Combined use of oxygen therapy and TFM could not only improve the nocturnal hypoxia, but also lower PaCO2. TFM is an important supplement of oxygen therapy.


Germline BRCA mutation does not prevent response to taxane-based therapy for the treatment of castration-resistant prostate cancer.
• To investigate the relationship between BRCA mutation status and response to taxane-based chemotherapy, since BRCA mutation carriers with prostate cancer appear to have worse survival than non-carriers and docetaxel improves survival in patients with castration-resistant prostate cancer. • We determined BRCA mutation prevalence in 158 Ashkenazi Jewish (AJ) men with castration-resistant prostate cancer. Clinical data were collected as part of an institutional prostate cancer research database and through additional medical record review. • Clinical records and DNA samples were linked through a unique identifier, anonymizing the samples before genetic testing for the AJ BRCA1/2 founder mutations. • Response to taxane-based therapy was defined by the prostate-specific antigen nadir within 12 weeks of therapy. • In all, 88 men received taxane-based treatment, seven of whom were BRCA carriers (three BRCA1, four BRCA2; 8%). Initial response to taxane was available for all seven BRCA carriers and for 69 non-carriers. • Overall, 71% (54/76) of patients responded to treatment, with no significant difference between carriers (57%) and non-carriers (72%) (absolute difference 15%; 95% confidence interval -23% to 53%; P= 0.4). • Among patients with an initial response, the median change in prostate-specific antigen was similar for BRCA carriers (-63%, interquartile range -71% to -57%) and non-carriers (-60%, interquartile range -78% to -35%) (P= 0.6). • At last follow-up, all seven BRCA carriers and 49 non-carriers had died from prostate cancer. One BRCA2 carrier treated with docetaxel plus platinum survived 37 months. • In this small, hypothesis-generating study approximately half of BRCA carriers had a prostate-specific antigen response to taxane-based chemotherapy, suggesting that it is an active therapy in these individuals.


Reverse pupillary block after implantation of a scleral-sutured posterior chamber intraocular lens: a retrospective, open study.
To report the clinical features of patients with reverse pupillary block (RPB) after scleral-sutured posterior chamber intraocular lens (PC IOL) implantation and biometric changes after laser peripheral iridotomy (LPI). Eight patients attending our hospital's ophthalmology outpatient clinic, who developed RPB after implantation of a scleral-sutured PC IOL due to subluxation of the crystalline lens or IOL, were investigated in this retrospective, observational study. Preoperative evaluations showed angle pigmentation in all cases and iridodonesis in 2 cases. Two subjects had used an α1A-adrenoceptor antagonist for benign prostatic hyperplasia. Pars plana or anterior partial vitrectomy was performed in all cases. All eyes showed an extremely deep anterior chamber, a concave iris configuration, and contact between the IOL optic and the iris at the pupillary margin. Pupil capture was detected in 2 cases. The mean (± SD) anterior chamber angle (ACA) was 89.91 ± 10.06°, and the anterior chamber depth (ACD) was 4.42 ± 0.16 mm before LPI. After LPI, the iris immediately became flat with a decreased ACA (51.70 ± 2.59°; P = 0.018) and ACD (4.14 ± 0.15 mm; P = 0.012). After LPI, the intraocular pressure decreased from 19.75 ± 3.77 mmHg to 15.63 ± 4.30 mmHg (P = 0.011), and the spherical equivalent decreased from -0.643 ± 0.385 D to - 0.875 ± 0.505 D (P = 0.016). Concomitant vitrectomy, angle pigmentation, and iridodonesis may be risk factors for RPB after scleral-sutured PC IOL implantation. LPI is effective for relieving the RPB.


Amniotic membrane for reducing the formation of adhesions in strabismus surgery: experimental study in rabbits.
To evaluate the effect of amniotic membrane in reducing inflammation, fibrosis, adhesion formation, and ocular motility restrictions following strabismus surgery. In the first stage of this prospective, randomized study, 17 rabbits underwent superior rectus muscle recession in both eyes. Surgery was performed in the same manner, but human amniotic membrane was placed over the muscle without sutures in the right eye after recession. After 15 days, the rabbits were killed and their orbits were exenterated and evaluated histopathologically to quantify tissue inflammation and fibrosis. In the second stage, 5 rabbits underwent the same procedure but were killed after 30 days. A dynamometer was used to measure the force required to displace all eyes. At 15 days postoperatively, eyes with amniotic membrane exhibited an increased inflammatory response and less fibrosis than eyes without amniotic membrane. At 30 days postoperatively, eyes with amniotic membrane continued to exhibit increased inflammation and less fibrosis than eyes without amniotic membrane. In the dynamometer test, more force was needed to displace eyes without amniotic membrane after 15 days, but there was no significant difference between the forces required at 30 days. Human amniotic membrane in rabbits led to an increase in the inflammatory process and a decrease in fibrosis formation following strabismus surgery.


Efficacy and Safety of Vasopressin Alone or in Combination With Catecholamines in the Treatment of Septic Shock: A Systematic Review.
Septic shock is one of the life-threatening emergencies in hospital settings. Patients with septic shock have been treated with various vasopressors alone as a first-line or in combination with other agents to improve blood pressure and increase the chance of survival. Our study focuses particularly on the efficacy and safety of vasopressin (VP) alone and in combination with other vasopressors. Our study used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 2020 to do our systematic review. We searched thoroughly for articles in PubMed, PubMed Central (PMC), Medline, and ScienceDirect. To locate all pertinent papers, we employed the medical subject headings (MeSH) systematic search technique. Twelve papers that were related to the study's issue and passed the quality check were extracted after we applied inclusion/exclusion criteria and reviewed the titles and abstracts. We used a variety of assessment methods for diverse study designs as a quality check. We compared all included studies after reviewing them thoroughly. VP and its synthetic variants (Terlipressin and Selepressin) have always been given as adjuvants to catecholamine, especially with Noradrenaline, in low to moderate doses with continuous infusion in patients with septic shock. Furthermore, VP is a better adjuvant agent than Dopamine and Dobutamine. Though VP has been proven superior to other vasopressors as an adjuvant agent in patients with septic shock, it can cause digital ischemia in high doses.


The nuclear argonaute NRDE-3 contributes to transitive RNAi in Caenorhabditis elegans.
The Caenorhabditis elegans nuclear RNA interference defective (Nrde) mutants were identified by their inability to silence polycistronic transcripts in enhanced RNAi (Eri) mutant backgrounds. Here, we report additional nrde-3-dependent RNAi phenomena that extend the mechanisms, roles, and functions of nuclear RNAi. We show that nrde-3 mutants are broadly RNAi deficient and that overexpressing NRDE-3 enhances RNAi. Consistent with NRDE-3 being a dose-dependent limiting resource for effective RNAi, we find that NRDE-3 is required for eri-dependent enhanced RNAi phenotypes, although only for a subset of target genes. We then identify pgl-1 as an additional limiting RNAi resource important for eri-dependent silencing of a nonoverlapping subset of target genes, so that an nrde-3; pgl-1; eri-1 triple mutant fails to show enhanced RNAi for any tested gene. These results suggest that nrde-3 and pgl-1 define separate and independent limiting RNAi resource pathways. Limiting RNAi resources are proposed to primarily act via endogenous RNA silencing pathways. Consistent with this, we find that nrde-3 mutants misexpress genes regulated by endogenous siRNAs and incompletely silence repetitive transgene arrays. Finally, we find that nrde-3 contributes to transitive RNAi, whereby amplified silencing triggers act in trans to silence sequence-similar genes. Because nrde-dependent silencing is thought to act in cis to limit the production of primary transcripts, this result reveals an unexpected role for nuclear processes in RNAi silencing.


Interactive roles of progesterone, prostaglandins, and collagenase in the ovulatory mechanism of the ewe.
Interrelationships between production of progesterone (P4), prostaglandin (PG) E2 and PGF2 alpha, and collagenase by periovulatory ovine follicles and their possible involvements in the ovulatory process were investigated. Follicles were isolated from ovaries at intervals (0 to 24 h) after the initiation of the preovulatory surge of luteinizing hormone (LH). Progesterone and PGs within follicles were determined by radioimmunoassay. Digestion of radioactive collagen during coincubation with tissue homogenates was used to assess the production of a bioactive follicular collagenase(s). Follicular accumulation of PGs and P4 increased at 12 and 16 h, respectively, after the onset of the surge of LH; PGE2 then decreased at 20 h. Collagenolytic activity of follicular tissue increased at 20 h and was maximal at 24 h (during the time of follicular rupture). An inhibitor of synthesis of P4 (isoxazol) or PGs (indomethacin) was injected into the follicular antrum at 8 h. Isoxazol did not prevent the initial rise in PGs, but inhibited synthesis of PGF2 alpha at 16 h and therafter. Isoxazol negated the decline in PGE2 and increase in collagenolysis. Indomethacin did not influence synthesis of P4; however, it suppressed collagenolytic activity of follicular tissue. Ovaries with treated follicles were left in situ and observed for an ovulation point at 30 h. Isoxazol or indomethacin was a potent inhibitor of ovulation. The blockade of ovulation by isoxazol was reversed by systemic administration of P4 or PGF2 alpha, but not by PGE2. Reversal of the blockade by indomethacin was accomplished with PGE2 or PGF2 alpha. Collagenolytic activity of follicular tissue was likewise restored by such treatments.(ABSTRACT TRUNCATED AT 250 WORDS)


Do preoperative branched-chain amino acids have a beneficial effect on the heart after cardiac surgery?
To verify the hypothesis, formulated on the basis of data emerging from animal experiments, that branched-chain amino acids (BCAA) exert a protective effect on the heart during ischaemia, eight patients immediately before aortocoronary reconstruction were provided 400 ml of a 3% BCAA solution. A control group comprised another eight patients. Per- and postoperative myocardial status and myocardial enzyme levels were assessed. Myocardial biopsy was performed during surgery to determine glycogen levels. Creatine kinase (CK) levels were invariably higher in the BCAA group, with statistically significant differences in samples obtained immediately after surgery (10.6 +/- 3.35 mu kat/l vs. 4.07 +/- 0.59, p < 0.0004), in the evening after surgery (14.2 +/- 5.92 vs. 5.91 +/- 2.21, p < 0.06) and in the morning of the first postoperative day (18.0 +/- 10.1 vs. 7.5 +/- 4.76, p < 0.025) when aspartate aminotransferase (AST) levels were likewise higher (1.35 +/- 0.28 vs. 1.00 +/- 0.26, p < 0.035). There were no differences between the groups in the number of defibrillations after ischaemia, myocardial glycogen content, peroperative ischaemia, incidence of arrhythmia and catecholamine support. We conclude that BCAA at the above indicated doses did not raise myocardial glycogen content or improve myocardial status after cardiac surgery. Their administration resulted in a rise in CK and AST in the postoperative period.


Lipocalin2 Induced by Bacterial Flagellin Protects Mice against Cyclophosphamide Mediated Neutropenic Sepsis.
Neutropenic sepsis is a fatal consequence of chemotherapy, and septic complications are the principal cause of mortality. Chemotherapy-induced neutropenia leads to the formation of microscopic ulcers in the gastrointestinal epithelium that function as a portal of entry for intraluminal bacteria, which translocate across the intestinal mucosal barrier and gain access to systemic sites, causing septicemia. A cyclophosphamide-induced mouse model was developed to mimic the pathophysiologic sequence of events that occurs in patients with neutropenic sepsis. The TLR5 agonist bacterial flagellin derived from Vibrio vulnificus extended the survival of cyclophosphamide-treated mice by reducing the bacterial load in internal organs. The protective effect of flagellin was mediated by the antimicrobial protein lipocalin 2 (Lcn2), which is induced by TLR5-NF-κB activation in hepatocytes. Lcn2 sequestered iron from infecting bacteria, particularly siderophore enterobactin-dependent members of the Enterobacteriaceae family, thereby limiting their proliferation. Lcn2 should be considered for the treatment of neutropenic sepsis and gastrointestinal damage during chemotherapy to prevent or minimize the adverse effects of cancer chemotherapy.


Special aspects of diagnostic imaging for radiosurgery of arteriovenous malformations.
Radiosurgery can be considered a well-established option for the treatment of arteriovenous malformations (AVMs). The exact application of the therapeutic dose is based on the availability of imaging data sets with superior image quality that can be superimposed using an image fusion algorithm. For follow-up studies, the quantitative comparison of the respective image data sets also plays an important role. Until now, digital subtraction angiography (DSA) has been a mandatory tool for treatment planning and follow-up procedures. The aim of this study was to investigate whether a suitable computed tomographic (CT) and/or magnetic resonance (MR) angiography procedure can replace DSA and, if so, in which cases. For 34 AVM patients, various MR data sets were used together with the stereotactically localized CT and DSA data sets for treatment planning. To define the AVM nidus precisely, all available MR data sets were fused onto the CT data set by the use of an automatic image fusion algorithm. The nidus was outlined in both localized DSA projections, resulting in the DSA target volume. Subsequently, the DSA target volume was adapted by inclusion of the available CT/MR data sets (localized and/or fused, slice by slice), resulting in the final target volume. Finally, both volumes were compared and analyzed. For precise comparison purposes, all available digital follow-up studies were fused. In all cases, the thin-slice MR data sets (1-mm slice width) that included T1-weighted series and time of flight angiographies have been precisely fused onto the stereotactically localized treatment planning CT. The final target volume was compared with the DSA target volume as follows. In 19 cases, the final target volume was larger than the DSA target volume; in six cases, it was smaller; and in five cases, it was approximately equal. The difference was significant (Wilcoxon test, difference <0.0001; t test, t = 3.01; P > 0.005). In four cases, outlining the AVM was not possible without DSA. In five patients, a two- or three-vessel DSA was needed because there were different AVM compartments. In cases in which a previous partial embolization had been undergone by the patient, the use of superimposed CT sets with and without contrast medium was important to define the completely embolized partial volumes that were not subject to treatment. The inclusion of the DSA images enabled a better identification of those arterialized veins that did not belong to the nidus. In six cases, the follow-up MR studies showed contrast enhancements overlapping the AVM nidus as a result of brain-blood barrier disturbances (T1-weighted series with contrast). In seven cases, perifocal reactions were primarily observed (T2-weighted series) 12 months after treatment with rather low clinical relevance. By integrating all available imaging modalities, the exact three-dimensional definition of the AVM nidus was safely realized for all patients. Stereotactic DSA data acquisition remains a crucial tool for safe nidus definition in radiosurgery treatment planning and cannot, therefore, be discarded at present. It is recommended that a quantitative comparison of all MR follow-up studies be established.


Cloning and characterization of a gene for the stage-specific 82-kDa surface antigen of metacyclic trypomastigotes of Trypanosoma cruzi.
We have cloned and sequenced a cDNA clone coding for a metacyclic trypomastigote-specific surface glycoprotein with a molecular mass of 82 kDa (MTS-gp82). By immunoblotting and immunoprecipitation, antibodies against the recombinant protein recognized an 82-kDa protein of metacyclic trypomastigotes, without any detectable reaction towards amastigotes, epimastigotes or tissue culture-derived trypomastigotes. The insert of the MTS-gp82 cDNA clone strongly hybridized with a single 2.2-kb metacyclic trypomastigote mRNA, suggesting that the steady-state levels of mRNAs for MTS-gp82 are developmentally regulated. MTS-gp82 is encoded by a multigene family whose members are distributed in several chromosomes. Sequence analysis revealed 40-56% identity at amino acid level between MTS-gp82 and members of Trypanosoma cruzi gp85/sialidase family (TSA-1, Tt34c1, SA85-1.1). MTS-gp82 showed several amino acid motifs that are characteristic of gp85/sialidase family, such as the Asp box (SxDxGxTW), the subterminal (VTVxNVFLYNR) motif and the putative GPI-anchor sequence. On the basis of its structural features, the MTS-gp82 gene could be included in the T. cruzi gp85/sialidase family, but constituting a distinct group which is preferentially expressed in metacyclic trypomastigotes.


Intramolecular electron transfer in single-site-mutated azurins.
Single-site mutants of the blue, single-copper protein, azurin, from Pseudomonas aeruginosa were reduced by CO2- radicals in pulse radiolysis experiments. The single disulfide group was reduced directly by CO2- with rates similar to those of the native protein [Farver, O., & Pecht, I. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6968-6972]. The RSSR- radical produced in the above reaction was reoxidized in a slower intramolecular electron-transfer process (30-70 s-1 at 298 K) concomitant with a further reduction of the Cu(II) ion. The temperature dependence of the latter rates was determined and used to derive information on the possible effects of the mutations. The substitution of residue Phe114, situated on the opposite side of Cu relative to the disulfide, by Ala resulted in a rate increase by a factor of almost 2. By assuming that this effect is only due to an increase in driving force, lambda = 135 kJ mol-1 for the reorganization energy was derived. When Trp48, situated midway between the donor and the acceptor, was replaced by Leu or Met, only a small change in the rate of intramolecular electron transfer was observed, indicating that the aromatic residue in this position is apparently only marginally involved in electron transfer in wild-type azurin. Pathway calculations also suggest that a longer, through-backbone path is more efficient than the shorter one involving Trp48. The former pathway yields an exponential decay factor, beta, of 6.6 nm-1. Another mutation, raising the electron-transfer driving force, was produced by changing the Cu ligand Met121 to Leu, which increases the reduction potential by 100 mV.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular ionization energies and ground- and ionic-state properties using a non-Dyson electron propagator approach.
An earlier proposed propagator method for the treatment of molecular ionization is tested in first applications. The method referred to as the non-Dyson third-order algebraic-diagrammatic construction [nD-ADC(3)] approximation for the electron propagator represents a computationally promising alternative to the existing Dyson ADC(3) method. The advantage of the nD-ADC(3) scheme is that the (N+/-1)-electronic parts of the one-particle Green's function are decoupled from each other and the corresponding equations can be solved separately. For a test of the method the nD-ADC(3) results for the vertical ionization transitions in C(2)H(4), CO, CS, F(2), H(2)CO, H(2)O, HF, N(2), and Ne are compared with available experimental and theoretical data including results of full configuration interaction (FCI) and coupled cluster computations. The mean error of the nD-ADC(3) ionization energies relative to the experimental and FCI results is about 0.2 eV. The nD-ADC(3) method, scaling as n(5) with the number of orbitals, requires the solution of a relatively simple Hermitian eigenvalue problem. The method renders access to ground-state properties such as dipole moments. Moreover, also one-electron properties of (N+/-1) electron states can now be studied as a consequence of a specific intermediate-state representation (ISR) formulation of the nD-ADC approach. Corresponding second-order ISR equations are presented.


Theobroxide Treatment Inhibits Wild Fire Disease Occurrence in Nicotiana benthamiana by the Overexpression of Defense-related Genes.
Theobroxide, a novel compound isolated from a fungus Lasiodiplodia theobromae, stimulates potato tuber formation and induces flowering of morning glory by initiating the jasmonic acid synthesis pathway. To elucidate the effect of theobroxide on pathogen resistance in plants, Nicotiana benthamiana plants treated with theobroxide were immediately infiltrated with Pseudomonas syringae pv. tabaci. Exogenous application of theobroxide inhibited development of lesion symptoms, and growth of the bacterial cells was significantly retarded. Semi-quantitative RT-PCRs using the primers of 18 defense-related genes were performed to investigate the molecular mechanisms of resistance. Among the genes, the theobroxide treatment increased the expression of pathogenesis-related protein 1a (PR1a), pathogenesis-related protein 1b (PR1b), glutathione S-transferase (GST), allen oxide cyclase (AOC), and lipoxyganase (LOX). All these data strongly indicate that theobroxide treatment inhibits disease development by faster induction of defense responses, which can be possible by the induction of defense-related genes including PR1a, PR1b, and GST triggered by the elevated jasmonic acid.


Recent developments in tuning the efficacy of different types of sunscreens.
Due to recent global warming threats, the changes in the atmosphere have caused significant ultraviolet (UV) radiation exposure, primarily emitted by the sun, which creates more awareness of photoprotection. Sunscreen development has been a convenient and crucial approach to photoprotection against ultraviolet radiation. Due to high demand, upgrading the quality of sunscreen products and certifying methods are necessary to guarantee the safety of commercial sunscreen products for use. Sunscreen products should have a satisfactory amount of sun protection factor (SPF), ultraviolet A protection factor, as well as the photostability of the sunscreens for them to be considered effective and safe for use. A rigorous study on the effectiveness of the sunscreen components and their safety standards is essential for the productive use and further improvement of the available sunscreen materials. This article summarizes the effects and issues, protective measures of sunscreen usage, and its components, mainly ultraviolet filters.


Performance characteristics of the digital uMI550 PET/CT system according to the NEMA NU2-2018 standard.
The aim of this study is to conduct physical performance evaluation on the uMI550 whole-body PET/CT system according to the NEMA NU2-2018 standard. According to the NEMA NU2-2018, spatial resolution, sensitivity, scatter fraction, count-rate performance, accuracy of count losses and random corrections, image quality, and timing resolution were evaluated. Spatial resolution was measured by using a 22Na point source. System sensitivity was measured by inserting an 18F line-source in six concentric aluminum sleeves with varying diameters. Scatter fraction, count-rate performance, accuracy of count loss, and timing resolution were all calculated by analyzing dynamically acquired data of an 18F line-source inside a polyethylene cylinder in 20 cm diameter and 70 cm length. Image quality was assessed using a NEMA IEC body phantom with a 4:1 ratio of activity concentration of spheres to the warm background. Additionally, three patient studies were performed, with one brain scan and two whole-body scans, separately. The patient images were evaluated to get a visual first impression of uMI550. The tangential, radial, and axial spatial resolutions were measured as 2.91 mm, 2.98 mm, and 2.97 mm FWHM, respectively, at 1 cm radial offset. The total system sensitivity to line source at center was 10.24 cps/kBq. A NECR peak was measured as 124.4 kcps at 18.85 kBq/mL. The scatter fraction at NECR peak was 36.65%, and the maximum count-rate error at and below NEC peak was 1.55%. Contrast recovery coefficients were from 46.5 (10 mm) to 83.9% (37 mm). The timing resolution was measured as 372 ps at low count rate. NEMA NU-2 2018 testing was performed on the new SiPM-based uMI550 PET/CT system. The uMI550 shows a high-spatial resolution of less than 3 mm and a good timing resolution of 372 ps. It shows clinical significances on improving potentially diagnostic ability on small lesions.


Decreased arousals in infants who sleep with the face covered by bedclothes.
The risk of becoming a victim of sudden infant death syndrome is increased in infants who sleep with their face under bedding items. The present study was designed to evaluate auditory arousal thresholds of infants who sleep with their face covered by bedclothes. Twenty healthy infants with a median age of 11.5 weeks (range: 4-22 weeks) were recorded polygraphically for 1 night. Although they slept in their usual supine position, a bed sheet was placed over their face for 60 minutes. Fifteen of the 20 infants were chosen at random and were exposed to white noises of increasing intensities to determine their auditory arousal thresholds. All infants were challenged with the face covered and with the face free during both rapid eye movement (REM) and non-REM (NREM) sleep. Seven infants were first challenged with the face covered, and 8 were challenged with the face free. The following variables were recorded simultaneously: electroencephalogram, breathing and heart rates, and rectal and pericephalic temperatures. In 5 infants who were not exposed to the auditory challenges, end tidal CO2 was recorded for 30 minutes while sleeping with the face covered. During REM sleep, arousals occurred for significantly more intense auditory stimuli when the infant's face was covered than when free. No significant difference was seen in NREM sleep. Compared with the face-free periods, the face-covered sleep periods were characterized by greater rectal and pericephalic temperatures, a greater density of body movements, and a decrease in NREM sleep. Respiratory frequency was increased during the face-covered periods in both REM and NREM sleep. No differences were seen in the frequency or duration of apnea. There was a tendency for heart rate to increase during both sleep stages when the face was covered, compared with the face-free periods, but the changes were not statistically significant. A positive correlation was found between pericephalic temperatures and arousal thresholds (r = 0.60) during REM sleep. End tidal CO2 values increased when the face was covered, reaching a maximum value during the first 5 minutes of the experiment. No fall in oxygen saturation was seen. Covering the infant's face with a bed sheet was associated with a significant increase in auditory arousal threshold. The finding could be related to an elevation in temperatures within the infant's microenvironment.


Gastric outlet obstruction: an unusual case of primary duodenal tuberculosis.
Tuberculosis is a major health problem worldwide. Gastrointestinal tuberculosis presenting as isolated involvement of the duodenum is a rare case. A 13 year male, presented with features of gastric outlet obstruction. CT enterography scan showed circumferential mural thickening in first and second part of duodenal junction causing luminal narrowing. Upper GI endoscopy confirmed the narrowing of D1-D2 junction. Duodenal biopsy showed duodenitis with negative result for AFB stain, Helicobacter Pylori. Patient underwent roux-en-y gastro-jejunostomy. Histo-pathological findings were consistent with tuberculosis. Patient was started on AKT and discharged. At 3 months follow up; patient asymptomatic. The unusual location of gastrointestinal tuberculosis, lack of specific signs and symptoms, radiological studies and endoscopy findings makes diagnosis a challenge. The treatment of duodenal tuberculosis is still medical and surgery should be reserved for emergency like gastric outlet obstruction causing nutritional compromise.


Leading nurses: emotional intelligence and leadership development effectiveness.
Purpose The purpose of this paper is to examine the effectiveness of an emotional intelligence (EI) and leadership development education program involving 20 nurse leaders at nursing homes. Also, it investigates the relationship between EI and transformational leadership. Design/methodology/approach Three research questions are posed. Correlation analysis and t-tests were conducted to answer the questions posed. Findings The findings of this paper indicate that the EI educational development was effective, while the personal leadership development was not. The data also showed a positive significant relationship between EI and transformational leadership. Research limitations/implications This paper is limited by the small sample size; thus, a causal relationship between EI and leadership could not be investigated. Additionally, the sample was not randomly selected because of the commitment needed from the participants. Furthermore, the paper was focused on nurse leaders in nursing homes, so it may not be generalizable to other populations. Practical implications With the increasing need for nursing home facilities and the limited training generally provided to nurses who move into managerial roles in these facilities, it is critical for organizations to understand the effectiveness of educational programs that exist. Moreover, the findings of this paper may provide information that would be useful to others who wish to develop EI and/or leadership education for nurses. Originality/value While much research exists on EI and transformational leadership, little of this research focuses on nurses in nursing home facilities. Thus, this paper fills a gap in the literature.


Role of monocytes and macrophages in adult angiogenesis: a light at the tunnel's end.
In spite of sustained efforts, there are still gaps in our understanding of angiogenesis as it takes place in vivo. Older observations and a number of recent developments strongly involve the blood mononuclear cell population, collectively known as monocytes (MC), in the normal and pathological adult angiogenesis. An emerging paradigm should eventually incorporate the established biochemical cross talk between MC and their descendents, tissular macrophages (Mph), and the endothelial cells (EC); additionally, it should account for both the intercellular cooperation at the morphological level and the phenotypic overlap between the two cell populations. This focused review puts together the pieces of this puzzle in such a way as to suggest an alternative angiogenic model applicable to adult animals, and particularly to pathological conditions. A working hypothesis is put forward, which is centered on the preformation of capillary lumen as a "tunnel" drilled by penetrating MC/Mph. The tunnels may be colonized in a later stage by sprouts, circulating progenitor endothelial cells (CPEC) or transdifferentiated EC. Thus, MC/Mph are suggested to be included among the targets of therapeutic manipulation of angiogenesis.


Inhibition of dentin demineralization by fluoride in vitro.
Compared with the knowledge accumulated on enamel-fluoride interactions, relatively little data is available regarding fluoride effects on dentin. This applies to both laboratory and clinical studies into the efficacy of fluoride schemes for the prevention of root surface caries. This study aimed to determine the effects of fluoride and pH on the demineralization of dentin, such as to provide information necessary to develop preventive programmes. Bovine dentin blocks were subjected to undersaturated calcium- and phosphate-containing solutions in the pH range 4.0-6.0 with fluoride added at concentrations between 0.5 and 10 ppm. Non-fluoride solutions served as controls. Mineral loss was assessed chemically and by transversal microradiography. Comparisons were made with similar studies on enamel demineralization. The results showed that demineralization of dentin depends on both pH and fluoride concentration in the demineralizing solution. Inhibition of demineralization that could be relevant from a clinical point of view was found at fluoride values 5-10 times the corresponding values for enamel. Also rapid depletion of fluoride from the solutions was observed, indicating the high uptake capacity of dentin for fluoride. Lesion depth depended on pH of the solution while the fluoride levels were associated with the surface layer, both in mineral content and depth. For dentin we propose a demineralization mechanism where acid penetrates rapidly into the tissue, presumably through the tubules, after which the released calcium and phosphate is partly trapped by the inward diffusing fluoride. This leads to the formation of a surface layer, which may even be hypermineralized compared to sound dentin.


Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020.
We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21-28 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age > 65 years, antiviral treatment and for severe disease, lactate dehydrogenase > 300 mg/dL.


Developing multicultural ethical guidelines for psychology.
While psychologists have recognized the importance of cultural differences in many areas, multicultural ethical guidelines for psychology are still lacking. This article will review some of the controversial issues that cultural differences raise and discuss literature published on multicultural ethics. The existing American Psychological Association Ethical Principles will be reviewed with suggestions for specific changes to meet the needs of a multicultural society.


Task-dependent changes of the psychophysical motion-tuning functions in the course of perceptual learning.
In some cases, perceptual learning is task-specific. However, task-dependent effects of perceptual learning on psychophysical motion-tuning functions have yet to be clarified. In the present study, subjects performed motion detection or discrimination of the same stimulus over the course of four sessions held on separate days. Subjects who performed motion detection showed the most highly improved performance on the trained motion directions. However, after discrimination training, the highest improvement was not observed at the trained directions but shifted away from them. These results can be explained by lateral inhibition. Task demands may differentially modulate excitatory and inhibitory signals to directions in the vicinity of the trained directions.


Epigenetics and its role in periodontal diseases: a state-of-the-art review.
The immune response to oral bacteria and the subsequent activation of inflammatory signaling is not only dependent on genetic factors. The importance of so-called epigenetic mechanisms presents additional regulatory pathways of genes involved in maintaining chronic inflammation, including gingivitis and periodontitis. The term epigenetics relates to changes in gene expression that are not encoded in the DNA sequence itself and include chemical alterations of DNA and its associated proteins. These changes lead to remodeling of the chromatin and subsequent activation or inactivation of a gene. Epigenetic mechanisms have been found to contribute to disease, including cancer and autoimmune or inflammatory diseases. In this state-of-the art review, the authors provide the latest findings on the involvement of epigenetic modifications in the development of periodontal disease and present emerging therapeutic strategies aimed at epigenetic targets (epidrugs) associated with the disruption of tissue homeostasis and the development of periodontitis.


The LAILAPS search engine: a feature model for relevance ranking in life science databases.
Efficient and effective information retrieval in life sciences is one of the most pressing challenge in bioinformatics. The incredible growth of life science databases to a vast network of interconnected information systems is to the same extent a big challenge and a great chance for life science research. The knowledge found in the Web, in particular in life-science databases, are a valuable major resource. In order to bring it to the scientist desktop, it is essential to have well performing search engines. Thereby, not the response time nor the number of results is important. The most crucial factor for millions of query results is the relevance ranking. In this paper, we present a feature model for relevance ranking in life science databases and its implementation in the LAILAPS search engine. Motivated by the observation of user behavior during their inspection of search engine result, we condensed a set of 9 relevance discriminating features. These features are intuitively used by scientists, who briefly screen database entries for potential relevance. The features are both sufficient to estimate the potential relevance, and efficiently quantifiable. The derivation of a relevance prediction function that computes the relevance from this features constitutes a regression problem. To solve this problem, we used artificial neural networks that have been trained with a reference set of relevant database entries for 19 protein queries. Supporting a flexible text index and a simple data import format, this concepts are implemented in the LAILAPS search engine. It can easily be used both as search engine for comprehensive integrated life science databases and for small in-house project databases. LAILAPS is publicly available for SWISSPROT data at http://lailaps.ipk-gatersleben.de.


High levels of xenoestrogens in patients with low-grade endometrial stromal sarcoma--report of two cases.
Endometrial stromal sarcomas (ESS) are rare uterine tumors with unknown etiological risk factors, but estrogen-dependent growth promotion. We present two patients with advanced ESS, who had increased levels of p,p-DDE; hexachlorobenzene; PCB 28; PCB 52; PCB 101; PCB 138; PCB 153 and PCB 180 in abdominal adipose tissue. Other xenoestrogens were within expected limits for the non-exposed European population. Increased levels of xenoestrogens in patients with ESS may be involved in the pathogenesis of ESS. Chronic exposure to xenoestrogens may be a risk factor for tumor progression.