Activation of mitochondrial oxidation by PDK2 inhibition reverses cisplatin resistance in head and neck cancer.
Dichloroacetate (DCA), an orphan drug that promotes a shift from glycolysis to oxidative phosphorylation, has been repurposed for cancer therapy. The present study investigated whether DCA may overcome cisplatin resistance in head and neck cancer (HNC). Two cisplatin-resistant HNC cell lines (AMC-HN4R and -HN9R), their parental lines, and other human HNC lines were used. The effect of DCA, alone and in combination with cisplatin, was assessed by measuring cell cycle, viability, death, reactive oxygen species (ROS) production, mitochondrial membrane potential (ΔΨm), and protein expression in preclinical mouse tumor xenograft models. Increased glycolysis correlated with decreased sensitivity to cisplatin and was reduced by DCA. Cisplatin-resistant cells overexpressed pyruvate dehydrogenase kinase 2 (PDK2). DCA induced HNC cell death by decreasing ΔΨm and promoting mitochondrial ROS production. This effect was decreased by the antioxidant N-acetyl-l-cysteine or by inhibition of caspase-mediated apoptosis. Activation of mitochondrial glucose oxidation by DCA eventually activated downstream mitochondrial apoptotic signaling, leading to the death of chemoresistant cancer cells. Therefore, DCA significantly sensitized resistant HNC cells to cisplatin in vitro and in vivo. High glycolysis and PDK2 overexpression are closely linked to cisplatin resistance in HNC cells; the latter can be overcome by DCA.


Migrating esophageal foreign bodies.
Ingested foreign bodies which migrate extraluminally, although rare in occurrence, are fraught with the potential to cause life-threatening complications. To discuss the management of this pathology. A series of four patients with such occurrences is presented. A discussion on the safe management of such seemingly innocuous foreign bodies allows the authors to propose a therapeutical algorythm.


Amphetamine-induced sensitization has little effect on multiple learning paradigms and fails to rescue mice with a striatal learning defect.
Behavioral sensitization to psychostimulants such as amphetamine (AMPH) is associated with synaptic modifications that are thought to underlie learning and memory. Because AMPH enhances extracellular dopamine in the striatum where dopamine and glutamate signaling are essential for learning, one might expect that the molecular and morphological changes that occur in the striatum in response to AMPH, including changes in synaptic plasticity, would affect learning. To ascertain whether AMPH sensitization affects learning, we tested wild-type mice and mice lacking NMDA receptor signaling in striatal medium spiny neurons in several different learning tests (motor learning, Pavlovian association, U-maze escape test with strategy shifting) with or without prior sensitization to AMPH. Prior sensitization had minimal effect on learning in any of these paradigms in wild-type mice and failed to restore learning in mutant mice, despite the fact that the mutant mice became sensitized by the AMPH treatment. We conclude that the changes in synaptic plasticity and many other signaling events that occur in response to AMPH sensitization are dissociable from those involved in learning the tasks used in our experiments.


Salivary secretion during selective beta-adrenoreceptor stimulation and blockade in the parotid gland of red kangaroos, Macropus rufus.
Intracarotid infusions of noradrenaline (0.3 nmol.kg(-1) x min(-1)) stimulated salivary fluid secretion and caused increases in salivary concentrations of protein, potassium. magnesium. chloride and phosphate, and decreases in bicarbonate. These effects of intracarotid noradrenaline were not reduced by simultaneous intracarotid infusion of phentolamine (3.0 nmol.kg(-1) x min(-1)) but were significantly greater than the responses accompanying intravenous noradrenaline infusion. Concomitant administration of the beta-antagonist, CGP20712A, were much more effective in blocking the noradrenaline-induced changes in salivary composition than equimolar infusions of the beta2-antagonist, ICI118551, thereby confirming the presence of beta1-adrenoreceptors. Intracarotid infusion of salbutamol at 0.6 nmol x kg(-1) x min(-1) and 6.0 nmol x kg(-1) x min(-1) caused increasing but qualitatively similar changes in salivary composition to intracarotid noradrenaline but was less effective than noradrenaline in augmenting salivary protein release. Equimolar intravenous infusions of salbutamol and noradrenaline were equally potent in altering salivary electrolyte concentrations but salbutamol by this route had less effect on protein release and fluid secretion. Concurrent intravenous and intracarotid infusions of beta1-(CGP) and beta2-(ICI) antagonists with intracarotid salbutamol showed that the beta2-antagonist was more potent than the beta1-antagonist by the intracarotid route thereby demonstrating the presence of glandular beta2-receptors and eliminating the possibility that the response to salbutamol was due totally by reflex increases in general sympathetic tone triggered by lowered blood pressure. It was concluded that the kangaroo parotid has functional beta1- and beta2-adrenoreceptor subtypes in endpieces whereas the data provide little support for either adrenoreceptor subtype being present in the excurrent duct system.


Coherent amplification of X-ray scattering from meso-structures.
Small-angle X-ray scattering (SAXS) often includes an unwanted background, which increases the required measurement time to resolve the sample structure. This is undesirable in all experiments, and may make measurement of dynamic or radiation-sensitive samples impossible. Here, we demonstrate a new technique, applicable when the scattering signal is background-dominated, which reduces the requisite exposure time. Our method consists of exploiting coherent interference between a sample with a designed strongly scattering 'amplifier'. A modified angular correlation function is used to extract the symmetry of the interference term; that is, the scattering arising from the interference between the amplifier and the sample. This enables reconstruction of the sample's symmetry, despite the sample scattering itself being well below the intensity of background scattering. Thus, coherent amplification is used to generate a strong scattering term (well above background), from which sample scattering is inferred. We validate this method using lithographically defined test samples.


Solitary metastasis of gastric cancer to fibula: a case report.
Gastric cancer is one of the most common and most fatal neoplasms in human. Its skeletal metastasis is less frequent, particularly when solitary. The objective of this article is to represent a case of solitary fibular metastasis from this cancer not reported before based on Medline search.


Prevalence and prognostic significance of IKZF1 deletion in paediatric acute lymphoblastic leukemia: A systematic review and meta-analysis.
IKZF1 (IKAROS family Zinc Finger 1) alteration is an essential regulator of both T- and B-cell lineage specification with leukemogenic potential. IKZF1 deletion have been described in childhood acute lymphoblastic leukemia (ALL) with varying prevalence often influenced by underlying cytogenetics and also shown to have diverse prognostic significance. We aimed to evaluate the prevalence and prognostic significance of IKZF1 deletion among childhood ALL. Electronic databases of MEDLINE, EMBASE and SCOPUS were searched and 32 studies found eligible. Estimated prevalence of IKZF1 deletion among BCR::ABL1 negative and BCR::ABL1 positive ALL patients was 14% (95%CI:13-16%, I2 = 79%; 26 studies) and 63% (95%CI:59-68% I2 = 42%; 10 studies) respectively. Most common site of IKZF1 deletion was whole chromosome (exon1-8) deletion in 32.3% (95%CI: 23.8-40.7%) followed by exon 4-7 deletion in 28.6% (95%CI: 19.7-37.5%). A positive minimal residual disease at the end of induction was more common among patients with IKZF1 deletion, odds ratio: 3.09 (95%CI:2.3-4.16, I2 = 54%; 15 studies). Event-free survival and overall survival were significantly worse for IKZF1 deletion, hazard ratio (HR): 2.10 (95%CI:1.90-2.32, I2 = 28%; 31 studies) and HR: 2.38 (95%CI:1.93-2.93, I2 = 40; 15 studies) respectively. In summary, the current meta-analysis highlights the frequency of IKZF1 deletion and its negative impact on survival in childhood ALL. Further studies exploring the influence of IKZF1 deletion in the presence of classical cytogenetic and other copy number alterations would further help in characterising its prognostic role.


Keratoacanthoma.
Keratoacanthoma is a benign epithelial tumor with a close resemblance to squamous-cell carcinoma both clinically and histologically. Both the pathologic status and treatment of keratoacanthoma are controversial.


No relationship between gastric pH, small bowel bacterial colonisation, and diarrhoea in HIV-1 infected patients.
Conclusive studies of small bowel bacterial overgrowth in patients with HIV-1 infection are limited. The relation was therefore determined between the quantity and species of bacteria in the proximal small intestine of HIV-1 infected patients and the presence of diarrhoea, gastric acidity, severity of immune deficiency, and clinical outcome. Bacteria in the duodenal fluids obtained endoscopically from 32 HIV-1 infected patients, 21 of whom had diarrhoea, and seven control subjects without HIV-1 risk factors were quantified and speciated. Gastric pH was determined at the time of endoscopy. Clinical follow up was performed to assess outcome. Oropharyngeal Gram positive cocci were present in fluids from 28 patients (88%). Gram negative aerobic or facultatively anaerobic bacteria were present in fluids from 12 patients (38%), and strict anaerobes were detected in six patients (19%), but for both groups colony counts infrequently exceeded 10(4) colony forming units/ml. The number and species of bacteria did not correlate with the presence of diarrhoea, gastric pH, or CD4 lymphocyte count. Small bowel bacterial overgrowth is not common in HIV-1 infected patients, regardless of the presence of diarrhoea, and is not associated with hypochlorhydria


Monoamine oxidase activity in blood platelets from autistic children.
In order to evaluate the possible abnormality in monoamine oxidase (MAO) activity in early infantile autism, blood platelet samples were obtained from 20 autistic children, aged 2--12 years. MAO activity, measured fluorometrically using serotonin as substrate, was 5.24 +/- 1.65 (Mean +/- Standard Deviation) nM/MG protein/hour in these autistic children. This value was not significantly different from either that in 30 age-matched normal children or that in 39 nonautistic children with various psychiatric and neurological disorders, although autistic children had higher platelet serotonin concentration than these nonautistic individuals.


Clinical and Radiographic Predictors of Progression and Survival in Relapsed/Refractory Lymphoma Patients Receiving Anti-CD19 CAR T-cell Therapy.
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of relapsed/refractory (R/R) B-cell lymphomas, though certain patients do not respond to treatment or relapse afterwards. The purpose of this study is to determine patient variables that are predictive of response to CAR-T therapy. We conducted a retrospective review of 59 R/R B-cell non-Hodgkin lymphoma patients who received anti-CD19 CAR T-cell therapy. Risk factors for progression free survival (PFS) and overall survival (OS) were identified and multivariate logistic regression models for PFS and OS at 1 year were created using stepwise selection. The final multivariate logistic regression models were used to estimate the area under the receiver operating curve (AUROC). At median follow up of 25.6 months, median overall survival was not reached, and median progression free survival was 5.7 months. Stage IV disease (odds ratio (OR) 9.335, P = .025) was identified as a predictive variable for progression at day 365 with an AUC of 0.7922 (P < .001). IPI (OR 2.828, P = .014), ALC ≥ 0.50 at collection (OR 0.183, P = .043), CRP ≥ 11 (OR 6.177, P = .019), and tocilizumab administration (OR 0.062, P = .005) as predictors for death at day 365 with an AUC 0.8626 (P < .001). Clinical variables identify R/R lymphoma patients who are at risk for progression and poor overall survival after CAR T-cell therapy. IPI, CRP, ALC, and tocilizumab administration may be predictors of survival.


The family narnaviridae: simplest of RNA viruses.
Members of the virus family Narnaviridae contain the simplest genomes of any RNA virus, ranging from 2.3 to 3.6 kb and encoding only a single polypeptide that has an RNA-dependent RNA polymerase domain. The family is subdivided into two genera based on subcellular location: members of the genus Narnavirus have been found in the yeast Saccharomyces cerevisiae and in the oomycete Phytophthora infestans and are confined to the cytosol, while members of the genus Mitovirus have been found only in filamentous fungi and are found in mitochondria. None identified thus far encodes a capsid protein; like several other RNA viruses of lower eukaryotes, their genomes are confined within lipid vesicles. As more family members are discovered, their importance as genetic elements is becoming evident. The unique association of the genus Mitovirus with mitochondria renders them potentially valuable tools to study biology of lower eukaryotes.


Whole exome sequencing identifies both nuclear and mitochondrial variations in an Iranian family with non-syndromic hearing loss.
Genetic contributing factors to non-syndromic hearing loss (NSHL) are remarkably diverse spanning over autosomal to X-linked to mitochondrial inheritance patterns. Facing a quite unconventional pedigree, here we report implementation of whole exome sequencing (WES) to uncover mitochondrial pathogenic variant in a six-generation Iranian family with four cases affected with hereditary NSHL of variable severity. As a result, heteroplasmic transition of A to G at position 1555 of MT-RNR1 gene was identified in all affected individuals co-existing with nuclear c.28G > T (p.A10S) variant in the TRMU gene, only in some patients. The reliability of WES to infer nuclear as well as mitochondrial variants in hearing loss were discussed.


Association Between Distance to an Abortion Facility and Abortion or Pregnancy Outcome Among a Prospective Cohort of People Seeking Abortion Online.
Many people face barriers to abortion care, including long distances to an abortion facility. To investigate the association of distance to the nearest abortion facility with abortion or pregnancy outcome. This cohort study was conducted using data from the Google Ads Abortion Access study, a prospective cohort study of individuals considering abortion recruited between August 2017 and May 2018. Individuals from 50 states and Washington, District of Columbia, who were pregnant and considering abortion based on self-report were recruited online using a stratified sampling technique. Participants completed online baseline and 4-week follow-up surveys. Data were analyzed between May and August 2021. Driving distance to an abortion facility calculated from participant zip code and grouped into 4 categories (<5 miles, 5-24 miles, 25-49 miles, and ≥50 miles). Abortion or pregnancy outcome reported at 4-week follow-up, categorized as had an abortion, still seeking an abortion, or planning to continue pregnancy. Other measures included reported experience of 8 distance-related barriers to abortion, such as having to gather money for travel expenses and having to keep the abortion a secret. Among 1485 pregnant individuals considering abortion who completed the baseline survey and provided contact information, 1005 individuals completed follow-up (follow-up rate, 67.7%) and 856 participants were included in the analytic sample (443 individuals ages 25-34 years [51.8%]; 208 Black individuals [24.3%]; 101 Hispanic or Latinx individuals [11.8%], and 468 White individuals [54.8%]). Most participants had at least some college education (474 individuals [55.5%]). Distance to an abortion facility was less than 5 miles for 233 individuals (27.2%), 5 to 24 miles for 373 individuals (43.6%), 25 to 49 miles for 85 individuals (9.9%), and 50 or more miles for 165 individuals (19.3%) (mean [SD] distance = 28.3 [43.8] miles). Most participants reported at least 1 distance-related barrier (763 individuals [89.1%]), with a mean of 3.3 barriers (95% CI, 3.2-3.5 barriers) reported. For 7 of 8 distance-related barriers, an increased percentage of participants living farther from an abortion facility reported the barrier compared with participants living less than 5 miles from a facility; for example, 61.8% (95% CI, 53.5%-69.4%) of individuals living less than 5 miles reported having to gather money for travel expenses, while 81.2% (95% CI, 70.8%-88.5%; P = .002) of those living 25 to 49 miles and 75.8% (95% CI, 69.9%-81.0%; P = .02) of those living 50 or more miles from a facility reported this barrier. At follow-up, participants living 50 or more miles from a facility had higher odds of still being pregnant and seeking abortion (adjusted odds ratio [aOR] = 2.07; 95% CI, 1.35-3.17; P = .001) or planning to continue pregnancy (aOR = 1.96; 95% CI, 1.06-3.63; P = .03) compared with participants living within 5 miles. This study found that greater distance from an abortion facility was associated with delays in obtaining abortion care and inability to receive abortion care. These findings suggest that innovative approaches to abortion provision may be needed to mitigate outcomes associated with long distances to abortion facilities.


Childhood sexual abuse in relation to neurobiological challenge tests in patients with borderline personality disorder and normal controls.
This study examined whether abnormal responses to neurobiological challenge tests in borderline personality disorder (BPD) are related to a history of childhood sexual abuse (CSA). We compared patients meeting BPD criteria (n=24), with and without histories of CSA, with normal controls (n=12) on the results of challenges with meta-chlorphenylpiperazine (m-CPP), pyridostigmine and clonidine. No differences were found between abused and non-abused patients with BPD. These results do not support the hypothesis that CSA is directly related to neurobiological abnormalities in BPD.


Complications following conversion of a hip hemiarthroplasty to a total hip arthroplasty.
Conversion of hip hemiarthroplasty to total hip arthroplasty (CTHA) is a complication-prone procedure with high dislocation rates and early component loosening. The purpose of this study was to evaluate the complications of CTHA performed using contemporary implants. Forty-six patients who had CTHA were retrospectively matched to a control group of 46 patients who had a first-time THA revision. The mean follow-up was 47 (range 6-149) and 23 (range 6-139) months for CTHA and control groups, respectively. Radiographs taken at the last follow-up visit were evaluated for signs of loosening or other modes of failure. Clinical outcome was evaluated with the Harris Hip Score (HHS). Complications occurred in five patients (10.9 %) in the CTHA group, and all required repeat revision. Two patients (4.3 %) were revised due to recurrent dislocation. The other re-revisions were done for acetabular or femoral component loosening and deep infection. In the control group, complications occurred in six patients (13.0 %), and three (6.5 %) were revised with a constrained liner due to recurrent dislocations. Dislocation rates and re-revision for CTHA were not significantly different than those of first-time THA revision when using contemporary revision implants.


Prognostic significance of splenic follicle size in splenectomized idiopathic thrombocytopenic purpura patients.
The prognostic significance of splenic follicle (B-lymphocyte compartment) size was studied in 62 patients splenectomized for idiopathic thrombocytopenic purpura (ITP). Patients with hyperplasia of splenic follicles (mean follicle diameter greater than 500 micron) were more likely to relapse or to develop additional autoimmune disorders than patients without hyperplastic splenic follicles (mean follicle diameter less than 500 micron) (p less than 0.01). The enlargement of splenic follicles had a positive predictive value of 27% and a negative predictive value of 100% for a poor outcome of splenectomy. Thus, the histological examination of spleens surgically removed for ITP seems to be an appropriate method to obtain the first indication of the possible long-term effect of splenectomy almost immediately after the operation.


Unilateral-dominant reduction in muscle volume in female knee osteoarthritis patients: computed tomography-based analysis of bilateral sides.
Muscle weakness is associated with osteoarthritis pathology. A recent study demonstrated that measuring muscle volume using computed tomography (CT)-based analysis and comparing bilateral muscles in the same patient allowed for accurate evaluation of muscle volume in unilateral hip osteoarthritis (OA) patients. Here, we evaluated muscle volume using CT-based analysis and compared bilateral muscles in knee OA (KOA) patients. CT images were obtained from 35 female radiographic KOA patients the day prior to total knee replacement surgery. Muscle volume (MV) was semi-automatically analyzed. Knee extension muscle strength (MS) was determined using a hand-held dynamometer. The severity of KOA patients' clinical symptoms was examined using four domains of the Japanese Orthopedic Association (JOA) score. We compared the difference in MS (ΔMS) and MV (ΔMV) between the operated side (OS), which exhibited severe radiographic OA or severe pain, and the contralateral side (CS). JOA score was significantly lower in the OS than CS. MV and MS were also significantly lower in the OS than CS. There was no correlation between MV and MS or between MV and MS as a percentage of body weight on either side. However, ΔMV was positively correlated with ΔMS and pain on walking in the JOA. We evaluated MV and MS using bilateral CT images of the legs of KOA patients. A reduction in MV was observed on the OS, and was correlated with a reduction in MS and pain on walking. Bilateral CT image analysis may be useful for evaluating the relationship between OA pathology and muscle atrophy.


Halomonas populi sp. nov. isolated from Populus euphratica.
Three yellow-pigmented, Gram-stain-negative, aerobic, motile by flagella and rod-shaped strains, designated as MCT, PC and RC, were isolated from stems of Populus euphratica. Growth of those three strains occurs at 4-40 °C, pH 6.0-10.0 and with 0.5-18.0% (w/v) NaCl. Respiratory quinones contained ubiquinone-9 and ubiquione-8 as major and minor components, respectively. Major fatty acids (> 10%) were summed feature 8 (C18:1ω6c and/or C18:1ω7c), summed feature 3 (C16:1ω6c and/or C16:1ω7c) and C16:0. Polar lipids included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unidentified phospholipids, one unidentified aminolipid, one unidentified glycolipid and four unidentified lipids. Strains MCT, PC and RC shared pairwise 16S rRNA gene sequence similarities of 99.9-100.0%, and showed higher similarities of 98.4-98.5% with Halomonas songnenensis NEAU-ST10-39T and 98.3-98.4% with Halomonas nanhaiensis YIM M 13059T than to other Halomonas type strains. Genomic comparisons revealed that those three strains had the pan-genome consisting of 4446 orthologous clusters, among which 676 orthologous clusters were absent in other Halomonas type strains. Phylogenomic tree indicated that strains MCT, PC and RC formed an independently stable clade with Halomonas nanhaiensis YIM M 13059T and Halomonas songnenensis NEAU-ST10-39T. The average nucleotide identity and digital DNA-DNA hybridization values between those three strains and other Halomonas type strains were < 89.9% and < 39.3%, respectively. Based upon phenotypic, chemotaxonomic, phylogenetic and genomic results, strains MCT, PC and RC represent a novel species in the genus Halomonas, for which the name Halomonas populi sp. nov. is proposed. The type strain is MCT (= JCM 33545T = MCCC 1K03942T).


Depressant effect of androgens on the cat brain electrical activity and its antagonism by ruthenium red.
Electroencephalographic synchronization and a fall in the multiunit activity was observed in the mesencephalic reticular formation, ventromedial hypothalamus and dorsal hippocampus following intravenous administration of some 5 alpha and 5 beta-reduced testosterone derivatives. The most potent compounds were androsterone and androstanediol which have the 3 alpha-hydroxy-5 alpha ring A configuration. Steroids with 5 beta reduction, i.e. 5 beta-dihydrotestosterone, etiocholanolone and epi-etiocholanolone, at high doses produced the inhibitory effect. Testosterone and its closer 5 alpha metabolites (5 alpha-dihydrotestosterone and 5 alpha-androstanedione) were ineffective. The depressive effect of androsterone on neurones was antagonized by the intraventricular injection of ruthenium red. On the other hand, the convulsant effect of ruthenium red was prevented or diminished by the action of androsterone. These findings support the hypothesis that testosterone metabolites reduced either at 5 alpha or 5 beta position can act in the brain at a membrane level and raise the possibility that testosterone may be a prehormone in the regulation of excitability in some brain functions.


Multivariate statistical analysis of electron probe microanalytical data on cell nuclear constituents.
A multivariate statistical analysis (the principal component analysis) has been used to process electron probe microanalytical data from cell nuclei. Fifty-seven measurements from different areas of chromatin and nucleolus in follicular rat cells have been studied. The variables are the X-ray characteristic signals for P, S, Al, Fe, Cu and Zn. This method demonstrates three groups of individuals - the chromatin area which is associated with a stronger concentration of P and two groups of nucleolar areas, one of them being connected with a higher content in S, Al and Zn. This high degree of correlation between these three elements proves the chemical affinity of the metals with the protein, S being the signature for proteins.


Crystal structure of the major peanut allergen Ara h 1.
Ara h 1, a 7S globulin, is one of the three major peanut allergens. We previously reported the crystallization of the core region of recombinant Ara h 1. Here, we present the crystal structure of the Ara h 1 core at a resolution of 2.43 Å. We also assayed the Ara h 1 core thermal stability and compared its final structure against other 7S globulins. The Ara h 1 core has a thermal denaturation temperature of 88.3°C and a structure that is very similar to other 7S globulins. Previously identified linear IgE epitopes were also mapped on the three-dimensional structure. Most linear epitopes were found in the extended loop domains and the coils between the N- and C-terminal modules, while others were found in the less accessible β-sheets of the C-terminal core β-barrel domain of each monomer. Most of these epitopes become either slightly or significantly buried upon trimer formation, implying that allergen digestion in the gut is required for these epitopes to be accessible to immunoglobulins. Our findings also suggest that both intact and partially degraded allergens should be employed in future diagnostic and immunotherapeutic strategies.


Xenografted human amniotic fluid-derived stem cell as a cell source in therapeutic angiogenesis.
Amniotic fluid-derived stem cells (AFSCs) are pluripotent with high renewal capacity and are not tumorigenic. We tested whether AFSCs can function as a cell source for therapeutic angiogenesis in a mouse hindlimb ischemia model. Using a defined culture medium for endothelial lineage cells (ECs), we differentiated human AFSCs into AFSC-derived ECs (AFSC-ECs) in vitro, as evidenced by expression of EC markers, and capillary-like network formation on Matrigel. We assessed the in vivo therapeutic angiogenesis efficacy of AFSC-ECs in an athymic nude mouse model of hindlimb ischemia. One day after high ligation of the external iliac artery in athymic nude mice, AFSC-ECs were intramuscularly injected into ischemic limbs. The AFSC-ECs demonstrated endothelial cell characteristics in vitro. Four weeks later, AFSC-ECs transplantation significantly increased limb salvage (85%), compared to AFSCs (56%), human umbilical vein endothelial cells (HUVECs; 25%), or medium (0%). Laser Doppler perfusion analysis revealed that the ischemic/normal limb blood perfusion ratio significantly improved in the AFSC-EC group. AFSC-EC transplantation significantly increased capillary and arteriole densities as compared to AFSCs, HUVECs, and medium. Transplanted AFSC-ECs were incorporated into vessels in the ischemic region, as confirmed by immunofluorescent staining for human smooth muscle 22α or von Willebrand factor. Matrix metalloproteinase (MMP)-3 and MMP-9 expressions were significantly higher in AFSC-ECs. MMP-9 might activate angiogenesis by regulation of vascular endothelial growth factor. Our study indicated that AFSC-EC transplantation improved limb salvage and blood perfusion by promoting neovascularization. Therefore, AFSC-ECs possess the potential for therapeutic angiogenesis.


Polyphenols in amaranth (A. manteggazianus) flour and protein isolate: Interaction with other components and effect of the gastrointestinal digestion.
In this work, there were analysed the interaction between phenolics present in amaranth flour (F) and amaranth protein isolate (I) with other components, as well as the effect of the gastrointestinal digestion on them (Fd and Id). Extractions were performed under different conditions (temperature, acid, organic solvent, alkali). Methanol/water extracts (25 °C and 80 °C) from F showed the presence of isoquercetin/rutin, quercetin, kaempferol and two unidentified peaks (II and III). In the presence of acid (much more evident at 80 °C), the extraction of some components increased: catechin, 4-hydroxibenzoic acid, isoquercetin/rutin, II, III. When methanol/acetone/water extraction was performed, p-coumaric acid and a new unidentified peak (IV) were observed. About 15% of the total phenol -namely; p-coumaric, rutin/isoquercetin, and kaempferol- were linked to the protein fraction. After the proteins were isolated (I), the amount of some of the compounds which were originally present in a soluble form (e. g. catechin) and in the protein-bound fraction were decreased. Simulated gastrointestinal digestion of flour released some phenolics (catechin, phenolic acids) that were ligated to proteins, and they significantly incremented the ORAC and ABTS activity of most of the extracts. Isoquercetin/rutin, quercetin and kaempferol remained after digestion. Extracts from the digested protein isolate presented differences in the composition and lower ORAC and/or ABTS activities for some of them. The study of the effect of the simulated gastrointestinal digestion process on bioaccessibility and on antioxidant activity (an aspect that, to our knowledge, has not been previously studied on amaranth polyphenols) yielded promising results, which suggest that amaranth flour is a potential antioxidant functional ingredient.


Classes and mechanisms of calcium waves.
The best known calcium waves move at about 5-30 microns/s (at 20 degrees C) and will be called fast waves to distinguish them from slow (contractile) ones which move at 0.1-1 microns/s as well as electrically propagated, ultrafast ones. Fast waves move deep within cells and seem to underlie most calcium signals. Their velocity and hence mechanism has been remarkably conserved among all or almost all eukaryotic cells. In fully active (but not overstimulated) cells of all sorts, their mean speeds lie between about 15-30 microns/s at 20 degrees C. Their amplitudes usually lie between 3-30 microM and their frequencies from one per 10-300 s. They are propagated by a reaction diffusion mechanism governed by the Luther equation in which Ca2+ ions are the only diffusing propagators, and calcium induced calcium release, or CICR, the only reaction; although this reaction traverses various channels which are generally modulated by IP3 or cADPR. However, they may be generally initiated by a second, lumenal mode of CICR which occurs within the ER. Moreover, they are propagated between cells by a variety of mechanisms. Slow intracellular waves, on the other hand, may be mechanically propagated via stretch sensitive calcium channels.


Posttransplant diabetes mellitus: incidence and risk factors.
Posttransplant diabetes mellitus (PTDM) is common post transplantation and is associated with tacrolimus (TAC) and steroid therapy. The aim of the present study was to analyze the incidences of PTDM and associated risk factors. We selected renal transplant recipients treated with TAC, mycophenolate mofetil (MM), and steroids. Exclusion criteria were recipients <18 years old, history of diabetes, recipients of kidney/pancreas, and/or those receiving cyclosporine or sirolimus. PTDM was defined as glucose >126 mg/dL, with or without drug therapy. Among 67 patients who fulfilled the inclusion criteria, 18 (26.8%) developed PTDM within 2 months of transplantation. Compared with normal glucose patients, the PTDM group was older, male, received a kidney from deceased donors, and showed higher pretransplant glucose levels. No differences were noticed in renal function or daily dose of TAC or steroids. However, TAC trough levels in the first month were higher among the PTDM group, despite the lower dose per kilogram. After 1 year of follow-up, weight gain as well as daily TAC per kilogram dose was less among PTDM patients. Analysis of potential risk factors showed a higher incidence of hepatitis C virus infection in the PTDM group, as well as a higher frequency of HLA DR13. The incidence of PTDM diagnosed in the early posttransplant period in the present series was 26.8%. Risk factors included older age, male gender, recipients of kidneys from deceased donors, hepatitis C virus infection, higher pretransplant glucose levels, and higher TAC trough levels during the first month posttransplant.


Superior mesenteric artery injury following blunt abdominal trauma: case report with successful primary repair.
A case of blunt abdominal trauma causing injury to the superior mesenteric artery with successful management is presented. The role of aortography in diagnosis is discussed. The patient, with multiple chest injuries sustained in an automobile accident, has recovered following surgical repair of a laceration of the SMA, treatment for respiratory distress, and spontaneous cessation of rectal diverticular bleeding.


[Results from the epidemiological study on periodontal diseases of the population from the town of Razgrad by CPITN-index].
The authors present data about the incidence of periodontal diseases among the population of the town of Razgrad obtained by mass prophylactic examinations and making use of CPITN index. The analysis of the results, obtained after the processing of the data, allows the specification of the therapeutic needs of 1151 workers examined as regards the periodontal diseases.


Pterocarpans phaseollin and neorautenol isolated from Erythrina addisoniae induce apoptotic cell death accompanied by inhibition of ERK phosphorylation.
The genus Erythrina (Leguminosae), consisting of over 100 different species, is distributed in tropical regions. In traditional medicine, Erythrina species are used to treat cancer, but little is known about the anticancer mechanisms. From the stem bark of Erythrina addisoniae Hutch. & Dalziel, six prenylated pterocarpans were isolated and analysed for pharmacological activity: While calopocarpin, cristacarpin, orientanol c, and isoneorautenol showed only a weak or moderate toxicity in H4IIE hepatoma cells (EC(50)-value> 25 microM), the toxicity of neorautenol and phaseollin was in the low micromolar range (EC(50)-value: 1 and 1.5 microM, respectively). We further focused on these two substances showing that both increased caspase 3/7 activity and nuclear fragmentation as markers for apoptotic cell death. Neorautenol (10 microM, 2h), but not phaseollin induced the formation of DNA strand breaks (comet assay). Both substances showed no effect on NF-kappaB signalling (SEAP assay: basal activity and stimulation with TNF-alpha), on the other hand both pterocarpans (10 microM, 2 h) decreased the activation of the ERK kinase (p44/p42), an mitogen activated protein kinase which is associated with cell proliferation. We conclude that the pterocarpans phaseollin and neorautenol may be responsible for the anticarcinogenic actions of the plant extract reported in the literature. Further analysis of these substances may lead to new pharmacons to be used in cancer therapy.


Impact of male partner's awareness and support for contraceptives on female intent to use contraceptives in southeast Nigeria.
Despite the growing body of evidence on use of modern contraceptives among women in sub-Saharan African countries, little is known about the broader context in which female decision-making concerning contraceptive use occurs, particularly the role of their male partners' awareness and support of modern contraceptives. We conducted a cross-sectional survey of 2468 pregnant women and their male partners enrolled in the Healthy Beginning Initiative (HBI), an intervention to increase HIV testing among pregnant women in Enugu, southeast Nigeria. The aims of this study were to determine: 1) male partners' awareness of, and support for, female contraceptive methods, and 2) influence of male partners' contraceptive awareness and support on pregnant women's expressed desire to use contraception. We used logistic regression models to examine the association between male partners' awareness and support of modern contraceptives on their spouses' desire to use contraceptives. Men's awareness of, and support for, use of modern contraceptives were significantly associated with their female partners' desire to use contraception. A majority of the men who were aware of modern contraceptives (66.5 %) and those who supported their spouses' use of contraception (72.5 %) had partners who expressed a desire to use contraception. Men who were aware of female contraception were 3 times more likely to have spouses who desired to use contraception (AOR = 3.17, 95 % C.I: 2.70-3.75). In addition, men who showed support for their spouses' use of contraception were over 5 times more likely to have spouses who indicated a desire to use contraception (AOR = 5.76, 95 % C.I: 4.82-6.88). Living in a household of 5 or more people (AOR = 1.45, 95 % C.I: 1.23-1.72) and residing in an urban area (AOR = 0.81, 95 % C.I: 0.67-0.97) were also significantly associated with women's expressed desire to use modern contraception. Men's awareness of, and support for, use of modern contraceptives were markedly associated with their spouses' desire to use contraception. This underscores the need for men's involvement in programs that seek to address women's uptake of contraception in low and middle income countries.


Electron microscopic evidence of a viral nature for osteoclast inclusions in Paget's disease of bone.
Circumstantial evidence from electron microscopic and immunological studies support the view that Paget's disease of bone represents a slow virus infection. However, there is only limited information available regarding its electron microscopic, enzyme and immunocytochemical characteristics. Two cases were studied using electron microscopy with particular emphasis on the inclusions in osteoclasts. Detailed ultrastructural and cytochemical studies including immuno-electron microscopy were performed. Some osteoclasts demonstrated specific virus-like structures composed of aggregations of microtubules in the nucleus and cytoplasm. The structures were easily digested by trypsin or protease, and were sensitive to RNase, which provided substantial evidence of a proteinaceous nature and inclusion of ribonucleic acid. Immunocytochemical examination identified binding of anti-respiratory syncytial virus and anti-measles virus antibodies in the tissue obtained from one of the two cases examined. The presence of viral antigens in structures in the cytoplasm of Pagetic osteoclasts supports the theory of paramyxovirus involvement in this disease.


Influence of low molecular weight heparin (certoparin) and unfractionated heparin on the release of cytokines from human leukocytes.
We analyzed the influence of heparins (unfractionated heparin, UFH and low molecular weight heparin certoparin) on the generation of IL-1ra, IL-6, IL-10, and IL-12p40 and from leukocyte fractions in vitro. Polymorphonuclear neutrophil leukocytes (PMN) and peripheral blood mononuclear cells (PBMC) from 16 different healthy donors were isolated and adjusted to 1 x 10(6) cells/ml supplemented RPMI 1640. Leukocyte fractions were differentially stimulated (PMN with 1 microg and 5 microg LPS, PBMC with 10 ng TSST- 1 or 2 microg ConA) in the presence or absence of heparins (1 U/ml, 2 U/ml, and 4 U/ml) for 24 h at 37 degrees C. Cytokine release was analyzed by ELISA. Certoparin but not UFH led to a dose-dependent increase in IL-6 from non-stimulated PBMC. In contrast, the release of IL-1ra, IL-10, and IL-12p40 was not modulated by heparins in a dose-dependent fashion. Increases in these cytokines occurred only as single incidents at intermediate heparin levels. An influence of the heparins on the apoptosis of PMN (measured as DNA-fragmentation in non-stimulated or LPS-stimulated cell-fractions) was not observed.


Plasma free fatty acid level patterns according to cardiovascular risk status in postmenopausal women.
The present study examines changes in the pattern of plasma free polyunsaturated fatty acids (PUFA) according to menopausal status and the existence of diabetes mellitus (DM) or coronary heart disease (CHD) in Korean women. The participants were as follows; premenopausal women (PRE, n=20) and postmenopausal women without any known chronic disease (POST, n=35), with DM (DM, n=35), or with angiographically proven CHD (CHD, n=30). Plasma free fatty acids were measured in all participants. Healthy premenopausal women had a higher ratio of omega-3/omega-6 PUFA than postmenopausal women (p=0.001). As expected, the PRE group had higher docsapentaenoic acid (DPA) and docosahexaenoic acid (DHA) levels (p<0.05) and lower arachidonic acid levels (p<0.05) than the POST group. In turn, the healthy POST group had higher levels of DPA and DHA compared to the DM or CHD groups (p<0.05). There were significant shifts of increased omega-6 and decreased omega-3 among the women, according to each disease. There was a significant relationship between omega-3 and omega-6 PUFA profiles and risk for CHD in women. This metabolic profile of PUFA might be an important surrogate marker in postmenopausal women.


Development of a high-resolution molecular marker for tracking Phaeocystis globosa genetic diversity through comparative analysis of chloroplast genomes.
The phytoplankton Phaeocystis globosa thrives in a wide range of marine regions and plays an important role in climate control. It can also form harmful algal blooms (HABs) that threaten environments and impact important coastal infrastructures. Mechanisms underlying the formation of P. globosa blooms still remain poorly understood. Accumulating evidence suggests that P. globosa has high genetic diversity and different P. globosa strains may have differential contributions to the development of P. globosa blooms. However, due to the lack of molecular markers with adequate resolution for distinguishing P. globosa genetic diversity, such differential contributions by different P. globosa strains could not be accurately ascertained. As such, high-resolution molecular markers need to be developed and applied to distinguish P. globosa genetic diversity. In this study, we undertook to define high-resolution molecular marker by assembling and comparing the whole chloroplast genomes of P. globosa strains isolated from different regions of the world. Through comparative analysis of P. globosa cpDNAs and detection of single nucleotide variations (SNVs), a molecular marker pgcp1 with improved resolution was developed. The pgcp1 demonstrated the highest resolution compared with other regions including 18S rDNA V4 region, 28S rDNA D1-D2 region and rbcL region, through genetic distance and phylogenetic analysis of 13 P. globosa strains. Molecular analysis of environmental samples and strains collected in multiple expeditions from a wide range of ocean regions including multiple regions in China, Vietnam, Thailand and Western Pacific using pgcp1 as the molecular marker displayed high genetic diversity of P. globosa with at least four major P. globosa clades. In conclusion, we have developed pgcp1 as a high-resolution molecular marker for the harmful algal bloom species P. globosa, which can be used to track intra-species genetic diversity and dynamics of P. globosa during bloom development.


Dam-mediated flooding impact on outpatient attendance and diarrhoea cases in northern Ghana: a mixed methods study.
Floods are the most frequently occurring natural disaster and constitute a significant public health risk. Several operational satellite-based flood detection systems quantify flooding extent, but it is unclear how far the choice of satellite-based flood product affects the findings of epidemiological studies of associated public health risks. Few studies of flooding's health impacts have used mixed methods to enrich understanding of these impacts. This study therefore aims to evaluate the relationship between two satellite-derived flood products with outpatient attendance and diarrhoeal disease in northern Ghana, identifying plausible reasons for observed relationships via qualitative interviews. A convergent parallel mixed methods design combined an ecological time series with focus group discussions and key informant interviews. Through an ecological time series component, monthly outpatient attendance and diarrhoea case counts from health facilities in two flood-prone districts for 2016-2020 were integrated with monthly flooding map layers classified via the Moderate Resolution Imaging Spectroradiometer (MODIS) and Landsat satellite sensors. The relationship between reported diarrhoea and outpatient attendance with flooding was examined using Poisson regression, controlling for seasonality and facility catchment population. Four focus group discussions with affected community members and four key informant interviews with health professionals explored flooding's impact on healthcare delivery and access. Flooding detected via Landsat better predicted outpatient attendance and diarrhoea than flooding via MODIS. Outpatient attendance significantly reduced as LandSat-derived flood area per facility catchment increased (adjusted Incidence Rate Ratio = 0.78, 95% CI: 0.61-0.99, p < 0.05), whilst reported diarrhoea significantly increased with flood area per facility catchment (adjusted Incidence Rate Ratio = 4.27, 95% CI: 2.74-6.63, p < 0.001). Key informants noted how flooding affected access to health services as patients and health professionals could not reach the health facility and emergency referrals were unable to travel. The significant reduction in outpatient attendance during flooding suggests that flooding impairs healthcare delivery. The relationship is sensitive to the choice of satellite-derived flood product, so future studies should consider integrating multiple sources of satellite imagery for more robust exposure assessment. Health teams and communities should plan spatially targeted flood mitigation and health system adaptation strategies that explicitly address population and workforce mobility issues.


Securing a safer future as cuts bite.
Government plans for NHS reforms will have a direct impact on the specification of security products within hospitals, surgeries, and care facilities, argues Tina Hughan, head of marketing for ASSA ABLOY, who considers the likely ramifications, and how security products must adapt to accommodate these changes.


Genetics Helps to Find Synergy for Immune Checkpoint and Targeted Combination Therapies.
Checkpoint inhibitors, including anti-PD-L1 therapy, emerged as a treatment option for many cancer types, albeit with limited response rates. Combinations of immune-based and -targeted therapies are needed to achieve synergistic antitumor effects and provide much needed treatment personalization and improved response. Genetic alterations can be used as molecular drug targets and as biomarkers to select patients for specific therapies and their combinations. Fukumoto and colleagues present a promising example of this approach for the treatment of ovarian cancer with inactivating ARID1A mutations using a combination of the checkpoint and histone deacetylase inhibitors.See related article by Fukumoto et al., p. 5482.


Soluble CD163 is a predictor of fibrosis and hepatocellular carcinoma development in nonalcoholic steatohepatitis.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. The serum level of soluble CD163 (sCD163), a macrophage activation marker, is associated with liver tissue changes; however, its prognostic value is unknown. Here, we determined the utility of sCD163 as a marker for hepatocellular carcinoma (HCC) and prognostic marker for NAFLD. This retrospective study obtained data regarding serum sCD163 levels, liver histology, and background factors associated with NAFLD in 287 patients (men/women, 140/147; average age, 53 ± 14 years) with NAFLD who underwent liver biopsy. Repeated liver biopsies of 287 patients with NAFLD (5.0 ± 2.7 years) were compared regarding serum sCD163 levels and liver tissue changes (stage, grade, steatosis, and NAFLD activity score). Serum sCD163 levels increased with the progression of liver fibrosis and inflammation (both P < 0.05) and were particularly helpful in distinguishing cases of Grade 4 fibrosis (P < 0.001). Levels of sCD163 significantly decreased in patients with NAFLD exhibiting alleviated fibrosis and inflammation (P < 0.05). We could also predict the development of HCC and associated mortality based on serum sCD163 levels at the time of NAFLD diagnosis. Serum sCD163 levels were higher in patients with HCC than in patients without HCC (1074 ± 379 ng/ml vs. 669 ± 261 ng/ml; P < 0.0001), and the same trend was observed for mortality. The serum sCD163 level reflects the progression of fibrosis and inflammation in liver tissues, showing much promise as a noninvasive biomarker for nonalcoholic steatohepatitis and NAFLD as well as a possible predictor of HCC development and patient prognosis.


Semaphorin 3A upregulates FOXO 3a-dependent MelCAM expression leading to attenuation of breast tumor growth and angiogenesis.
Semaphorin 3A (Sema 3A), a member of semaphorin family, serves as a guidance clue during embryonic development and is known as a candidate tumor suppressor that attenuates breast tumor progression by binding with its co-receptor, neuropilin-1 (NRP-1). However, the underlying mechanism by which Sema 3A suppresses breast tumor growth is still unexplored. In this study, we report that Sema 3A regulates phosphorylation and nuclear translocation of phosphatase and tensin homolog (PTEN) and FOXO 3a. Moreover, Sema 3A controls NRP-1-mediated PTEN-dependent FOXO 3a activation. Overexpression of PTEN and FOXO 3a enhances Sema 3A-induced attenuation of breast cancer cell migration. Chromatin immunoprecipitation and electrophoretic mobility shift assay data revealed that FOXO 3a regulates MelCAM at the transcriptional level. Furthermore, Sema 3A induces NRP-1-mediated MelCAM expression through PTEN and FOXO 3a. The data also showed that vascular endothelial growth factor-induced angiogenesis is inhibited by Sema 3A. Loss of or gain in function study revealed that Sema 3A modulates phosphorylation of PTEN and FOXO 3a and expression of MelCAM, leading to suppression of tumor growth and angiogenesis using in vivo mice model. Clinical specimen analysis revealed that reduced expression of Sema 3A and p-PTEN are correlated with enhanced breast cancer progression, further strengthening our in vitro and in vivo findings. Correlation of relapse-free survival of breast cancer patients (n=2878) with expression levels of Sema 3A, NRP-1, FOXO 3a and MelCAM were studied by Kaplan-Meier analysis. Statistical analysis revealed a close association between reduced expression of Sema 3A and MelCAM with that of poor patient's survival. Our study demonstrated a novel mechanism of regulation of tumor suppression by Sema 3A in coordination with a chain of tumor-suppressor genes, which in turn inhibits breast cancer cell migration, tumor growth and angiogenesis.


Ionizing radiation enhances IL-6 and IL-8 production by human endothelial cells.
Irradiation exposure is known to induce an inflammatory reaction. Endothelial cells play a crucial role both in the inflammatory process and in radiation damage. Therefore, supernatants and cell lysates of (60)Co-irradiated human umbilical vein endothelial cells (HUVEC) have been assessed for the presence of pro-inflammatory cytokines. After gamma irradiation, interleukin (IL)-1alpha, IL-1beta and tumor necrosis factor (TNF)-alpha remained undetectable in both cell supernatants and cell lysates. However, a dose-dependent increase in the production of IL-6 and IL-8 has been demonstrated up to 6 days after exposure. These data indicate that the pro-inflammatory cytokines IL-6 and IL-8 may be involved in the inflammatory response of vascular endothelium induced by exposure to ionizing radiation.


Influence of the director field structure on extinction and scattering by a nematic liquid-crystal droplet.
On the basis of calculations under the discrete dipole approximation and a proposed extended model of nested ellipsoids for bipolar droplets, the changes in optical properties of a spherical liquid-crystal droplet, caused by a change in director configuration under the influence of an external field, have been considered.


Role of supplemental foods and habitat structural complexity in persistence and coexistence of generalist predatory mites.
Plant traits can influence the interactions between herbivore arthropods and their natural enemies. In these interactions generalist predators are often present, preying on herbivores and also on other arthropods in the same trophic guild. Variation in the strength of intraguild predation (IGP) may be related to habitat structural complexity and to additional resources outside the narrow predator-prey relationship. In this paper we study the food web interactions on grape, which involves two generalist predatory mites. We evaluated the effects of grape powdery mildew (GPM) as supplemental food, and habitat structural complexity provided by domatia. The inoculation of GPM resulted in higher predatory mite densities and reduced the negative impact of unfavorable leaf structure for one species. Access to domatia was the main factor in promoting population abundance and persistence of predatory mites. Access to domatia and GPM availability favored the coexistence of predatory mites at a low density of the intraguild prey. Our findings suggest that structural and nutritional diversity/complexity promote predatory mite abundance and can help to maintain the beneficial mites - plants association. The effect of these factors on coexistence between predators is influenced by the supplemental food quality and relative differences in body size of interacting species.


Pedicle screws can be 4 times stronger than lateral mass screws for insertion in the midcervical spine: a biomechanical study on strength of fixation.
A biomechanical study. To compare, in cervical vertebrae (C3-C6), the pullout strengths of pedicle screws and lateral mass screws after both types of screw had been subjected to a period of cyclic loading in 2 planes. In posterior subaxial cervical fixation systems, screws are usually inserted into the lateral mass. As an alternative to lateral mass fixation, pedicle screw fixation became popular in the 1990s and was first used for lower cervical spine trauma cases. However, it is controversial as to whether lateral mass screw fixation in the upper-middle cervical spine offers as much biomechanical security as compared with pedicle screw fixation. For each of the 32 vertebrae, 1 side was randomly chosen to receive a pedicle screw and the other side a lateral mass screw. The pedicle or lateral mass screws inserted into the first 16 vertebrae were cyclically loaded to simulate torsion and the remaining 16 vertebrae were cyclically loaded to simulate flexion/extension of the spine. At the end of the cyclic loading each screw was pulled out along its long axis. For the torsion group, the mean pullout strength of the pedicle screws was nearly 4 times greater than the mean pullout strength of the lateral mass screws (cf 762 N with 191 N). In contrast, the mean pullout strength of the pedicle screws in the flexion/extension group was only twice the mean pullout strength of the lateral mass screws (cf 571 N with 289 N). Not forgetting the potential risks of inserting pedicle screws in cervical vertebrae, pedicle screws are a better biomechanical choice than lateral mass screws for cervical fixation at the levels C3 through to C6.


Outreach and support in South-London (OASIS) 2001-2020: Twenty years of early detection, prognosis and preventive care for young people at risk of psychosis.
This study aims to describe twenty years of early detection, prognosis and preventive care in the Outreach and Support In South-London (OASIS) mental health service for individuals at Clinical High risk of psychosis (CHR-P). The study presents a comprehensive analysis of the 2001- 2020 activity of the OASIS team encompassing core domains: (i) service characteristics, (ii) detection, (iii) prognosis, (iv) treatment and (v) clinical research. The analyses employed descriptive statistics, population-level data, the epidemiological incidence of psychosis, Kaplan Meier failure functions and Greenwood 95% CIs and Electronic Health Records. OASIS is part of the South London and Maudsley (SLaM) NHS trust, the largest European mental health provider, serving a total urban population of 1,358,646 individuals (population aged 16-35: 454,525). Incidence of psychosis in OASIS's catchment area ranges from 58.3 to 71.9 cases per 100,000 person-years, and it is higher than the national average of 41.5 cases per 100,000 person-year. OASIS is a standalone, NHS-funded, multidisciplinary (team leader, consultant and junior psychiatrists, clinical psychologists, mental health professionals), transitional (for those aged 14-35 years) community mental health service with a yearly caseload of 140 CHR-P individuals. OASIS regularly delivers a comprehensive service promotion outreach to several local community organisations. Referrals to OASIS (2366) are made by numerous agencies; about one-third of the referrals eventually met CHR-P criteria. Overall, 600 CHR-P individuals (55.33% males, mean age 22.63 years, white ethnicity 46.44%) have been under the care of the OASIS service: 80.43% met attenuated psychotic symptoms, 18.06% brief and limited intermittent psychotic symptoms and 1.51% genetic risk and deterioration CHR-P criteria. All CHR-P individuals were offered cognitive behavioural therapy and psychosocial support; medications were used depending on individual needs. The cumulative risk of psychosis at ten years was 0.365 (95%CI 0.302-0.437). At six years follow-up, across two-third of individuals non-transitioning to psychosis, 79.24% still displayed some mental health problem, and only 20.75% achieved a complete clinical remission. Research conducted at OASIS encompassed clinical, prognostic, neurobiological and interventional studies and leveraged local, national and international infrastructures; over the past ten years, OASIS-related research attracted about £ 50 million of grant income, with 5,922 citations in the international databases. Future developments may include broadening OASIS to prevent other serious mental disorders beyond psychosis and fostering translational risk prediction and interventional research. With a twenty-years activity, OASIS' cutting-edge quality of preventive care, combined with translational research innovations, consolidated the service as a leading reference model for evidence-based prevention of psychosis worldwide.


Hepatocyte growth factor promotes migration of human myeloma cells.
Multiple myeloma is characterized by the accumulation and dissemination of malignant plasma cells in the bone marrow. Cell migration is thought to be important for these events. We studied migration in a Transwell two-chamber assay and tested the motogenic effect of various cytokines. In addition to insulin-like growth factor-1 and stromal cell-derived growth factor-1alpha, previously known as chemoattractants for myeloma cells, we identified hepatocyte growth factor as a potent attractant for myeloma cells. Hepatocyte growth factor-mediated migration was dependent on phosphatidylinositol-3-kinase, involved the MAPK/Erk signaling cascade and VLA-4 integrins, but did not involve Akt, mTOR or G proteins.


Surface-assisted reduction of aniline oligomers, N-phenyl-1,4-phenylenediimine and thionin in atmospheric pressure chemical ionization and atmospheric pressure photoionization.
Reduction of the oligomers formed from on-line electropolymerization of aniline, the compound N-phenyl-1,4-phenylenediimine, and the thiazine dye thionin was observed in both an atmospheric pressure chemical ionization and an atmospheric pressure photoionization source. The reduction, which alters the mass of these analytes by 2 Da, was shown to occur by means of a surface-assisted process which involves reactive species, possibly hydrogen radicals, generated from protic solvents in the ionization plasma. Reduction was minimized by limiting protic solvents, by using a high heated nebulizer temperature, and by using a clean, heated nebulizer probe liner. The expected generality of this reduction process, and the possibility of similar reduction processes in other plasma ionization sources are discussed in relation to the use of these ion sources for on-line electrochemistry/mass spectrometry experiments.


A randomized controlled trial of pelvic floor muscle exercises to treat postnatal urinary incontinence.
A randomized controlled trial was carried out to evaluate the extent to which a program of reinforced pelvic floor muscle exercises (PFME) reduces urinary incontinence 1 year after delivery. Two hundred and thirty women who were incontinent 3 months postpartum were randomized to either a control group doing standard postnatal pelvic floor muscle exercises (n = 117) or to an intervention group (n = 113) who saw a physiotherapist for instruction at approximately 3, 4, 6 and 9 months postpartum. Results collected 12 months after delivery included prevalence and frequency of incontinence and PFME, sexual satisfaction, perineometry measurements and pad tests. Twenty-six (22%) of the control group and 59 (52%) of the intervention group withdrew before the final assessment. The prevalence of incontinence was significantly less in the intervention group than in the control group (50% versus 76%, P=0.0003), and this group also did significantly more PFME. There were no significant differences between the groups as regards sexual satisfaction, perineometry measurements or pad test results.


Radiocesium-bearing microparticles discovered on masks worn during indoor cleaning.
A decade has passed since the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident on March 11, 2011. However, radioactive particles have recently been detected in the indoor air of some residences near the FDNPP. Following the recommendations of previous research, we determined the presence of radiocesium-bearing microparticles (CsMPs) and measured the radioactivity of radiocesium that adhered on non-woven face masks worn by six persons during the indoor cleaning of 59 residences in Namie, Futaba, Okuma, and Tomioka towns in Fukushima Prefecture. Of the 284 masks worn in this study, significant 137Cs radioactivity was detected in 268, and 44 new CsMPs were discovered in 28. The results of this study also suggest the presence of highly concentrated soluble radiocesium particles or soluble radioactive cesium aerosols adhered to house dust. This implies that the CsMPs constituted a large proportion of radioactivity in the indoor air contamination for particles in the 1.0-2.5 µm size range due to the radioactive radiocesium particles. It is desirable to wear masks during cleaning to prevent inhalation of CsMPs.


Characterization of the starch synthase under terminal heat stress and its effect on grain quality of wheat.
Terminal heat stress (HS) is a key barrier for wheat grain yield and quality. Various physiochemical and molecular parameters such as photosynthetic rate, expression analysis and activity of starch synthase (SS), total starch, amylose and amylopectin content, total amylolytic activity, and total antioxidant capacity (TAC) were analysed in wheat cvs.HD3059 (thermotolerant) and BT-Schomburgk (thermosusceptible) at grain-filling stage under HS (32 °C and 40 °C, 1 h). The decrease in photosynthetic rate was observed under HS. Expression analysis of the SS gene at transcript level showed downregulation in both the wheat cvs.HD3059 and BT-Schombugk under HS (32 °C and 40 ºC, 1 h) as compared to the control. Although the downregulation of SS gene transcript expression was less in HD3059 than BT-Schombugk. Both the cultivars showed decrease in starch synthase activity and starch content under HS and the overall content was higher in HD3059, compared to BT-Schomburgk. Higher total amylolytic activity and amylose content were observed in BT-Schomburgk. Scanning electron microscopy (SEM) showed un-structured starch granules under HS. Total antioxidant capacity (TAC) was found higher in HD3059 (14.07 mM FeSO4 gm-1 FW) compared to BT-Schomburgk (8.89 mM FeSO4 gm-1 FW) under HS (40 ºC, 1 h). Findings suggest that HS during grain filling stage had more severe impact on the overall physiochemical properties of the wheat grain. Thus the starch bisynthesis pathway associated gene(s) could be exploit to enhance the yield and quality of wheat under heat stress.


Cilia in the Striatum Mediate Timing-Dependent Functions.
Almost all brain cells contain cilia, antennae-like microtubule-based organelles. Yet, the significance of cilia, once considered vestigial organelles, in the higher-order brain functions is unknown. Cilia act as a hub that senses and transduces environmental sensory stimuli to generate an appropriate cellular response. Similarly, the striatum, a brain structure enriched in cilia, functions as a hub that receives and integrates various types of environmental information to drive appropriate motor response. To understand cilia's role in the striatum functions, we used loxP/Cre technology to ablate cilia from the dorsal striatum of male mice and monitored the behavioral consequences. Our results revealed an essential role for striatal cilia in the acquisition and brief storage of information, including learning new motor skills, but not in long-term consolidation of information or maintaining habitual/learned motor skills. A fundamental aspect of all disrupted functions was the "time perception/judgment deficit." Furthermore, the observed behavioral deficits form a cluster pertaining to clinical manifestations overlapping across psychiatric disorders that involve the striatum functions and are known to exhibit timing deficits. Thus, striatal cilia may act as a calibrator of the timing functions of the basal ganglia-cortical circuit by maintaining proper timing perception. Our findings suggest that dysfunctional cilia may contribute to the pathophysiology of neuro-psychiatric disorders, as related to deficits in timing perception.


Important photosynthetic contribution from the non-foliar green organs in cotton at the late growth stage.
Non-foliar green organs are recognized as important carbon sources after leaves. However, the contribution of each organ to total yield has not been comprehensively studied in relation to the time-course of changes in surface area and photosynthetic activity of different organs at different growth stages. We studied the contribution of leaves, main stem, bracts and capsule wall in cotton by measuring their time-course of surface area development, O(2) evolution capacity and photosynthetic enzyme activity. Because of the early senescence of leaves, non-foliar organs increased their surface area up to 38.2% of total at late growth stage. Bracts and capsule wall showed less ontogenetic decrease in O(2) evolution capacity per area and photosynthetic enzyme activity than leaves at the late growth stage. The total capacity for O(2) evolution of stalks and bolls (bracts plus capsule wall) was 12.7 and 23.7% (total ca. 36.4%), respectively, as estimated by multiplying their surface area by their O(2) evolution capacity per area. We also kept the bolls (from 15 days after anthesis) or main stem (at the early full bolling stage) in darkness for comparison with non-darkened controls. Darkening the bolls and main stem reduced the boll weight by 24.1 and 9%, respectively, and the seed weight by 35.9 and 16.3%, respectively. We conclude that non-foliar organs significantly contribute to the yield at the late growth stage.


Focal neuropathy in children with critical illness.
Four children are described who developed focal lower limb nerve palsies following critical illness. Two had clinical and/or neurophysiological evidence of simultaneous generalised critical illness polyneuropathy. The diagnosis was delayed in three patients due to the presence of central motor abnormalities and slow motor recovery. Follow-up from seven months to three years showed minimal or no recovery. In three, a vasculitic skin infarct, compartment syndrome and focal myositis could have caused nerve compression. We suggest that in critical illness peripheral nerves have an increased susceptibility to damage by local pressure.


Acoustic distortion products in rabbit ear canal. II. Sites of origin revealed by suppression contours and pure-tone exposures.
Previous work on acoustic distortion products (DPs) recorded from the ear canal has not established unequivocally whether emitted DPs principally reflect basilar-membrane nonlinearities at the frequency sites of the primary tones, f1 and f2, or if the DP-frequency place itself makes a significant contribution to the emitted response. Results from some studies on acoustic emissions attribute generation of the emitted DP almost exclusively to the regions of maximum primary-tone interaction, while the findings of other investigations implicate reemission of the response from the DP locus as a significant contributor to response magnitude. Using suppression, interfering tones, and temporary threshold shift (TTS) procedures, the work reported here was designed to establish more definitively the precise contributions of the basilar-membrane regions involved in generating acoustic DPs in rabbits. Suppression tuning curves and interfering-tone experiments indicated that for the DP at 2f1-f2, regions near the f1 or f2 frequencies were the major contributors to the emitted response. However, for the higher-frequency DP at 2f2-f1, the basilar-membrane region just basal to the DP site was implicated as the generator. Following brief episodes of TTS at frequencies related to either the DP or the primary tones, the locus of the exposure stimulus that most effectively reduced the magnitude of the 2f1-f2 response also implicated the region of maximal primary-tone interaction in the generation of the acoustic DP. In contrast, for the DP at 2f2-f1, basilar-membrane sites nearer the DP were identified as the primary contributors to the emitted response. Both sets of results imply that different DPs recorded from the ear canal may originate from unique regions of primary-tone interaction along the basilar membrane.


Insight into the short- and long-term effects of Cu(II) on denitrifying biogranules.
This study aimed to investigate the short- and long-term effects of Cu(2+) on the activity and performance of denitrifying bacteria. The short-term effects of various concentrations of Cu(2+) on the denitrifying bacteria were evaluated using batch assays. The specific denitrifying activity (SDA) decreased from 14.3 ± 2.2 (without Cu(2+)) to 6.1 ± 0.1 mg N h(-1)g(-1) VSS (100 mg Cu(2+)L(-1)) when Cu(2+) increased from 0 to 100 mg L(-1) with an increment of 10 mg Cu(2+)L(-1). A non-competitive inhibition model was used to calculate the 50% inhibition concentration (IC50) of Cu(2+) on denitrifying sludge (30.6 ± 2.5 mg L(-1)). Monod and Luong models were applied to investigate the influence of the initial substrate concentration, and the results suggested that the maximum substrate removal rate would be reduced with Cu(2+) supplementation. Pre-exposure to Cu(2+) could lead to an 18.2-46.2% decrease in the SDA and decreasing percentage of the SDA increased with both exposure time and concentration. In the continuous-flow test, Cu(2+) concentration varied from 1 to 75 mg L(-1); however, no clear deterioration was observed in the reactor, and the reactor was kept stable, with the total nitrogen removal efficiency and total organic carbon efficiency greater than 89.0 and 85.0%, respectively. The results demonstrated the short-term inhibition of Cu(2+) upon denitrification, and no notable adversity was observed during the continuous-flow test after long-term acclimation.


Progressive pseudorheumatoid arthritis of childhood (PPAC) and normal adult height.
Two brothers and a sister presented with spondyloepiphyseal dysplasia and progressive arthropathy. Stiffness and restricted mobility of several large joints had been present since childhood. Their adult height was normal, and skeletal radiography showed mild platyspondyly, abnormal epiphyses and severe osteoarthrosis with extensive synovial osteochondromatosis. This autosomal recessive type of spondyloepiphyseal dysplasia tarda must be distinguished from other forms of spondyloepiphyseal dysplasia, rheumatoid arthritis in childhood and osteoarthrosis in adults.


Combined Endodontic Therapy and Intentional Replantation for the Treatment of Palatogingival Groove.
A palatogingival groove is an anatomic malformation that predisposes the involved tooth to a severe periodontal defect. When the condition is complicated by pulpal necrosis, affected teeth often present a dilemma in terms of diagnosis and treatment planning. In this report, we describe the case of a patient with a maxillary lateral incisor with a deep palatogingival groove extending to the root apex and severe periodontal destruction (local pocketing). Suggested treatment modalities included curettage of the affected tissues, elimination of the groove by grinding and/or sealing with a variety of filling materials, and surgical procedures. In this case, a combined treatment approach, involving both endodontic therapy and intentional replantation after restoration with a self-etching flowable composite, resulted in periodontal healing and significant healing of the periradicular radiolucency at 12 months. In short, intentional replantation offers a predictable procedure and should be considered a viable treatment modality for the management of palatogingival grooves, especially for single-rooted teeth.


The efficacy of praziquantel (Droncit R) against Raillietina tetragona (Molin, 1958) in domestic fowl.
The efficacy of different dose rates of Praziquantel (Droncit R) in tablet and liquid (injectable) form against Raillietina tetragona in the domestic fowl was studied. A dose of 10 mg kg-1 of Praziquantel in tablet form and 0.15 ml kg-1 in liquid form was found to be effective against R. tetragona infection irrespective of age, sex and intensity of infestation of the host. Intramuscular (IM) administration of liquid Praziquantel was found to be more effective than subcutaneous (SC) administration. Susceptibility of the parasite to this drug increased with age.


[Staphylococcus spp. in Spain: present situation and evolution of antimicrobial resistance (1986-2006)].
Since 1986 we have carried out five nationwide point-prevalence studies in Spain analyzing Staphylococcus spp. The 2006 data, corresponding to the sixth study, are presented herein. A total of 145 hospitals from all geographic areas of the country participated in the study. We investigated 866 staphylococcal isolates (463 S. aureus). Antimicrobial susceptibility testing was performed against 16 antimicrobials by an automated microdilution method. Susceptibility to tigecycline was determined by the E-test method. Resistance of S. aureus to oxacillin seemed to have stabilized (31.2% in 2002 vs. 29.2% in 2006), and the same was true for resistance to erythromycin, clindamycin and ciprofloxacin. In 2006, isolates were more susceptible to gentamicin (16.9% resistance in 2002 vs. 8.6% in 2006, P < 0.001). None of the isolates presented decreased susceptibility to vancomycin, and the resistance to cotrimoxazole (0.9%) and rifampin (0.6%) was minimal. One isolate showed linezolid resistance. Resistance of coagulase negative staphylococci to oxacillin (61.3% in 2002 vs. 66.7% in 2006) and erythromycin (63.0% in 2002 vs. 66.5% in 2006) remained stable, although resistance to gentamicin (27.8% in 2002 vs. 44.2% in 2006, P < 0.001), ciprofloxacin (44.9% in 2002 vs. 54.3% in 2006, P = 0.010) and clindamycin (33.8% in 2002 vs. 46.2% in 2006, P = 0.001) has increased. Two isolates presented decreased susceptibility to teicoplanin and one was linezolid-resistant. All Staphylococcus spp. were uniformly susceptible to quinupristin-dalfopristin and tigecycline. Resistance of Staphylococcus spp. to oxacillin remains high in Spain, but seems to have stabilized in the last years. Linezolid resistance is emerging.


Photocytotoxicity of heavy-atom-free thiobarbituric acid functionalized pyrene derivatives against MCF-7 cancer cells.
Two thiobarbituric acid-functionalized pyrene derivatives (P1, P2) have been synthesized to explore the photophysical properties and photodynamic activity of dyes of this type. Both compounds exhibit an intense intramolecular charge transfer (ICT) band at ca. 470 nm, which is absent in the spectra of the precursor. P1 and P2 exhibit singlet oxygen generation on irradiation with light with moderate singlet oxygen yields of 0.36 and 0.32, respectively, in DMSO. P1 showed better photodynamic activity against MCF-7 cells with an IC50 value of 18.3 μM under illumination at 455 nm for 60 min with a Thorlabs M455L3 LED (330 mW.cm-2).


An exploration of accident and emergency nurse experiences of triage decision making in Hong Kong.
This study used a descriptive qualitative design to explore emergency nurse experiences of decision making about triage in Hong Kong. Seven experienced nurses who were working in three different accident and emergency departments participated in the study. Unstructured interviews were used to provide the nurses with opportunities to describe their experiences. The findings fall into three main categories, including the experience of triage decision making, the use of information in the triage decision-making process, and the factors that influence triage decision making. Although the experience of triage was generally positive, the nurses felt frustrated and uncertain in some circumstances. In addition, triage decision making was influenced by a series of factors that occur in daily practice. The findings of this study have implications for the development of formal triage training and triage decision-making protocols in accident and emergency nursing. They also provide positive reinforcement and support to triage nurses that will enhance their ability to make decisions about triage. Avenues for further research in the area are recommended.


Peak mitral annular velocity during early diastole and propagation velocity of early diastolic filling flow are not interchangeable as the parameters of left ventricular early diastolic function.
The difference between peak mitral annular velocity during early diastole (Ea) and the propagation velocity of left ventricular (LV) early diastolic filling flow (Vp) obtained using Doppler imaging as LV relaxation parameters was not fully elucidated. Thus, this issue was investigated in 117 patients with suspected coronary artery disease. During cardiac catheterization, LV volumes, the LV relaxation time constant Tp, and inertia force of late systolic aortic flow were obtained. Ea significantly and closely correlated with Tp (r = -0.70, p <0.0001) and significantly but weakly correlated with LV ejection fraction (r = 0.37, p <0.0001) and inertia force (r = 0.34, p = 0.0002). Conversely, Vp significantly and closely correlated with both LV ejection fraction (r = 0.66, p <0.0001) and inertia force (r = 0.72, p <0.0001) and significantly but weakly correlated with Tp (r = - 0.35, p = 0.0001). In conclusion, Ea and Vp reflect different aspects of LV behavior from end-systole to early diastole. Ea can be used to index LV relaxation, whereas Vp might not be a proper parameter of LV intrinsic relaxation because it is significantly dependent on LV systolic function and LV chamber size at end-systole. Both parameters are not interchangeable as those of LV early diastolic function. Vp may be a noninvasive parameter of LV elastic recoil.


Bioprospecting a native silver-resistant Bacillus safensis strain for green synthesis and subsequent antibacterial and anticancer activities of silver nanoparticles.
Green nanomaterials have gained much attention due to their potential use as therapeutic agents. The present study investigated the production of silver nanoparticles (AgNPs) from a silver-resistant Bacillus safensis TEN12 strain, which was isolated from metal contaminated soil and taxonomically identified through 16S rRNA gene sequencing. The formation of AgNPs in bacterial culture was confirmed by using UV-vis spectroscopy with an absorption peak at 426.18 nm. Fourier transform infrared (FTIR) spectroscopy confirmed the involvement of capping proteins and alcohols for stabilization of AgNPs. Moreover, X-ray diffraction analysis (XRD), scanning and transmission electron microscopy (SEM and TEM) confirmed the crystalline nature and spherical shape of AgNPs with particle size ranging from 22.77 to 45.98 nm. The energy dispersive X-ray spectroscopy (EDX) revealed that 93.54% silver content is present in the nano-powder. AgNPs showed maximum antibacterial activity (20.35 mm and 19.69 mm inhibition zones) at 20 µg mL-1 concentration against Staphylococcus aureus and Escherichia coli, respectively and significantly reduced the pathogen density in broth culture. Furthermore, AgNPs demonstrated significant anticancer effects in the human liver cancer cell line (HepG2) in MTT assay, whereas, no cytotoxic effects were demonstrated by AgNPs on normal cell line (HEK293). The present study suggests that the biogenic AgNPs may substitute chemically synthesized drugs with wider applications as antibacterial and anticancer agents.


Evaluation of craft beers through the direct determination of amino acids by capillary electrophoresis and principal component analysis.
The composition of beer wort in terms of amino acid (AA) content affects the final product quality, once it is related to the vitality of yeast during the initial exponential growth phase and throughout fermentation. The objective of this work was the use of a capillary zone electrophoresis method with UV-vis detection in association with Principal Component (Data) Analysis for craft beer classification. Cysteine, histidine, phenylalanine, lysine, tryptophan and arginine were the monitored AAs in wort and finished beer, which were extracted through cation exchange resin. Good differentiation among samples according to their production was obtained, showing a profile of AAs (<LQ-99 µg mL-1) for each wort, which can be used as indicator of the quality of a beer. One of the samples had the mashing step monitored, showing an increasing profile in the concentrations of AAs (6.5-55 µg mL-1), which can be explained by the protein cleavage.


Identification of Bombyx mori 14-3-3 orthologs and the interactor Hsp60.
The 14-3-3 protein family consists of evolutionarily conserved, acidic 30 kDa proteins composed of seven isoforms named beta, gamma, epsilon, zeta, eta, theta, and sigma in mammalian cells. The dimeric complex of 14-3-3 isoforms, acting as a molecular adaptor, plays a central role in regulation of neuronal function. Since aberrant expression of 14-3-3 is identified in the brains of Alzheimer disease and Parkinson disease, a convenient insect model, if it is available, is highly valuable for studying a pathological role of 14-3-3 in neurodegeneration. Here, we identified the silkworm Bombyx mori 14-3-3 orthologs, zeta and epsilon isoforms highly homologous in amino acid sequences to the human 14-3-3zeta and 14-3-3epsilon. By Western blot, the expression of zeta and epsilon isoforms was identified at substantial levels in the first instar larva, markedly upregulated in the second instar larva, and the highest levels were maintained in the late stage of larva, the pupa, and the adult. Furthermore, by protein overlay and immunoprecipitation, we identified Hsp60 as a 14-3-3-binding partner. The 14-3-3 proteins interacted with the N-terminal fragment of Hsp60. The 14-3-3zeta and epsilon isoforms, along with Hsp60, were expressed widely with overlapping distribution in larval and adult tissues, including brain, fat body, silk gland, Malpighian tube, midgut, ovary, testis, antenna, and pheromone gland. These observations suggest that a molecular adaptor 14-3-3 and a molecular chaperone Hsp60 cooperate to achieve a wide range of cellular functions in B. mori.


Are there any differences between antagonist administration on days <6 and ≥6 of Controlled Ovarian Hyperstimulation on assisted reproductive technique outcomes?
The aim of this study was to investigate the cost-effectiveness of antagonist administration on stimulation on days <6 and ≥6 of COH on assisted reproductive technique (ART) outcomes. In this retrospective cohort study, 412 patients who were admitted to the ART Department were evaluated. In group 1 (203 patients), antagonist administration was provided on days <6 of COH. For group 2 (209 patients), antagonist administration was provided on days ≥6 of COH. We preferred a flexible antagonist protocol in clinical practice and added an antagonist treatment regimen when dominant follicles were enlarged to 13 mm or the serum blood E2 was >300 pg/mL. There were no differences between antagonist administration on days <6 and days ≥6 of COH in terms of age, BMI, duration and etiology of infertility, AFC, serum FSH, LH, peak E2 levels, the number of MII oocytes, 2PN, FR, the number of transferred embryos, and CPR per woman. However, there were statistically significant differences between the duration of stimulation, the total gonadotropin dose required, and progesterone levels on day hCG [8.26 ± 1.83 vs 9.56 ± 1.51 (p = 0.001); 2173.71 ± 860.00 vs 2749.17 ± 1079.51 (p = 0.001); 0.75 ± 0.44 vs 0.92 ± 0.59 (p = 0.002), respectively]. Our results have demonstrated that there was no effect of antagonist administration on days <6 and ≥6 of COH on ART outcomes. However, taking cost-effectiveness into consideration, we suggest an antagonist administration on days <6 of COH since the necessary gonadotropin dose is lower.


Inhibition of gastric mucosa carbonic anhydrase by pirenzepine in patients with gastroduodenal ulcers.
Pirenzepine (Gastrozepin) is a drug recently introduced in the therapy of gastroduodenal ulcer (GDU). Although its effect of decreasing acid secretion is clinically known, its mechanism of action remains uncertain. The authors present investigations proving by in vitro experiments carried out on pure carbonic anhydrase (CA) and on CA from human gastric mucosa that GZ is a strong inhibitor of CA. In this acceptation, GZ may be considered both an enzymatic inhibitor and an antagonist of histamine H2 receptors.


R 76713, a new specific non-steroidal aromatase inhibitor.
The effects of R 76713, a new triazole derivative, on rat ovarian, testicular and adrenal steroidogenesis were investigated both in vitro and in vivo. In vitro R 76713 is a very potent inhibitor of the aromatase enzyme in rat granulosa cells, showing an IC50-value of 3.0 +/- 0.2 nM. The compound is about 1000 times more active than aminoglutethimide which shows an IC50-value of 3900 +/- 2800 nM in the same system. R 76713 is also a highly selective aromatase inhibitor. In cultures of ovarian, testicular and adrenal cells, formation of progesterone, androgens and glucocorticoids was only affected by drug concentrations higher than 1 microM. In vivo, single oral drug doses of 0.05 mg/kg lowered plasma estradiol levels of PMSG-primed female rats by more than 90%. An ED50-value of 0.005 mg/kg could be calculated. A single oral dose of 1 mg/kg suppressed plasma estradiol levels almost completely for 24 h. A dose of 0.1 mg/kg lowered plasma estradiol by more than 90% for 8 h. In vivo, R 76713 also showed a highly selective profile. In LHRH/ACTH-injected rats, plasma levels of testicular and adrenal steroids remained unchanged after administration of a drug dose of 20 mg/kg. R 76713 at drug concentrations of 10 microM, showed no interaction in vitro with estrogen-, progestin-, androgen- and glucocorticoid-receptors. Given orally at 20 mg/kg for 3 days the compound also showed no estrogen or androgen agonistic or antagonistic effects.


Case Report: Hemolytic Anemia Following Deceased Donor Renal Transplantation Associated With Tranexamic Acid Administration for Disseminated Intravascular Coagulation.
Long-term outcomes of kidney transplantation with organs from donors with disseminated intravascular coagulation (DIC) are comparable with those from other deceased donors. The use of tranexamic acid to impair fibrinolysis in the treatment of DIC is becoming increasingly frequent, particularly in the trauma setting. However, the effects of tranexamic acid on a transplanted kidney allograft are unknown. We report 2 cases of kidney transplantation following administration of tranexamic acid to the donor prior to organ donation. Microthrombi were present in the renal allografts. Both recipients experienced clinically significant hemolytic anemia, which typically occurs at a very low frequency. These cases illustrate a potential concern for the use of tranexamic acid in deceased kidney donors with DIC.


Medicinal chemistry strategies to extend duration of action of inhaled drugs for intracellular targets.
Prolonging duration of action of inhaled drugs is a challenging endeavor and guidance for medicinal chemistry teams is very limited, particularly if the site of action is intracellular. Herein, we identified recent literature reports of newly designed inhaled compounds with intracellular targets and summarized learnings from different approaches and strategies undertaken by medicinal chemistry teams. We highlight key properties that have shown to lead to longer duration of action and provide guidance on the best strategy to follow while designing a new inhaled drug with an intracellular target.


(-)-Epigallocatechin-3-gallate stimulates myogenic differentiation through TAZ activation.
Muscle loss is a typical process of aging. Green tea consumption is known to slow down the progress of aging. Their underlying mechanisms, however, remain largely unknown. In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), a polyphenolic compound of green tea, on myogenic differentiation and found that EGCG significantly increases myogenic differentiation. After EGCG treatment, the expression of myogenic marker genes, such as myosin heavy chain, are increased through activation of TAZ, a transcriptional coactivator with a PDZ-binding motif. TAZ-knockdown does not stimulate EGCG-induced myogenic differentiation. EGCG facilitates the interaction between TAZ and MyoD, which stimulates MyoD-mediated gene transcription. EGCG induces nuclear localization of TAZ through the dephosphorylation of TAZ at its Ser89 residue, which relieves 14-3-3 binding in the cytosol. Interestingly, inactivation of Lats kinase is observed after EGCG treatment, which is responsible for the production of dephosphorylated TAZ. Together, these results suggest that EGCG induces myogenic differentiation through TAZ, suggesting that TAZ plays an important role in EGCG induced muscle regeneration.


Carbon dioxide dynamics in a residential lawn of a tropical city.
Turfgrass is an important component of the urban landscape frequently considered as an alternative land cover to offset anthropogenic CO2 emissions. However, quantitative information of the potential to directly remove CO2 from the atmosphere by turfgrass systems is lacking, especially in the tropics. Most assessments have considered the carbon accumulated by grass shoots and soil, but not the release of CO2 to the atmosphere by soil respiration (i.e., soil CO2 efflux). Here, we measured at high-temporal resolution (30-min) soil CO2 efflux, production, and storage rate for nearly three years in a residential lawn of Singapore. Furthermore, we quantified the carbon capture related to biomass production and CO2 emissions from fossil fuel consumption associated with maintenance activities (e.g., mowing equipment). Warm and humid conditions resulted in relatively constant rates of soil CO2 efflux, CO2 storage in soil, and aboveground biomass production (3370, 652, 1671 Mg CO2 km-2 yr-1; respectively), while the systematic use of mowing machinery emitted 27 Mg CO2 km-2 yr-1. Soil CO2 efflux and CO2 mowing emissions represent carbon losses to the atmosphere, while CO2 storage in soil and biomass productivity represent gains of carbon into the ecosystem. Under a steady state in which soil CO2 losses are only compensated by atmospheric CO2 uptake by photosynthesis, an ideal clipping waste disposal management, in which no CO2 molecule returns to the atmosphere (i.e., clippings are not burnt), and a 3-week mowing regime, this site can act as a sink of 2296 Mg CO2 km-2 yr-1. In the scenario of incinerating all clippings, the lawn acts as an emission source of 1046 Mg CO2 km-2 yr-1. Thus, management practices that reduce mowing frequency together with clipping disposal practices that minimize greenhouse gas emissions are needed to make urban lawns a potential natural solution to mitigate global environmental change.


Powered intraosseous device (EZ-IO) for critically ill patients.
We reviewed the charts of 25 patients who underwent powered intraosseous line insertion between July 1, 2008 and August 31, 2010 to determine its users, indications, procedural details, success rates, and complications. Intraosseous (IO) line was inserted in the anteromedial aspect of the proximal tibia in all patients. The first attempt was successful in 80%, and the median duration for insertion of the IO line was 4 hours. Extravasation was the most common complication. Ninety-six percent of the physicians had undergone prior training in IO insertion. Because of its high success and short procedure time, IO access should be the first alternative to failed vascular access in critically ill children. Training in IO should be extended to all who care for pediatric patients in inpatient as well as in prehospital and emergency department settings.


Mercury levels in total suspended matter and in plankton of the Mediterranean basin.
Mercury levels in total suspended matter (TSM) and in plankton of sea water from some Mediterranean areas have been determined. The mercury concentration in TSM collected with a filter of 0.45 micron pore size ranges from 0.1 to 2.4 ng l-1 and from 0.1 to 4.7 ng mg-1, dry wt. These levels are 3-10 times higher than those observed in plankton (0.08-0.29 ng mg-1 dry wt.) collected with a 200 microns net mesh size. The larger amounts of mercury in TSM than in the matter collected by the plankton nets are probably due to the high abundance of smaller sized particles selected by the filter.


Poor correlation between handgrip strength and isokinetic performance of knee flexor and extensor muscles in community-dwelling elderly women.
To investigate the correlation between handgrip strength and performance of knee flexor and extensor muscles determined using an isokinetic dynamometer in community-dwelling elderly women. This was a cross-sectional study. Sample selection for the study was made by convenience, and 221 (71.07 ± 4.93 years) community-dwelling elderly women were included. Knee flexor and extensor muscle performance was measured using an isokinetic dynamometer Biodex System 3 Pro. The isokinetic variables chosen for analysis were peak torque, peak torque/bodyweight, total work/bodyweight, total work, average power, and agonist/antagonist ratio at the angular velocities of 60°/s and 180°/s. Assessment of handgrip strength was carried out using the Jamar dynamometer. Spearman's correlation coefficient was calculated to identify intervariable correlations. Only knee flexor peak torque (60°/s) and average power (60°/s), and knee extensor peak torque (180°/s) and total work (180°/s) were significantly (P < 0.05), yet poorly, correlated with handgrip strength (r < 0.30). The majority of analyses did not show any correlation between variables assessed by isokinetic dynamometer and handgrip dynamometer. Caution is required when generalizing handgrip strength as a predictor of global muscle strength in community-dwelling elderly women.