Autophagy modulation for Alzheimer's disease therapy.
Autophagy is an essential and conserved lysosomal degradation pathway that controls the quality of cytoplasm by eliminating the intracellular aggregated proteins and damaged organelles. Autophagy works in mammalian target of rapamycin (mTOR)-dependent pathway or mTOR-independent pathway to keep the neuronal homeostasis. Mounting evidence has implicated the importance of defective autophagy in the pathogenesis of aging and neurodegenerative diseases, especially in Alzheimer's disease (AD). It has also demonstrated a neuroprotective role of autophagy in mediating the degradation of amyloid beta and tau which are major factors of AD. Amounts of molecules function in either mTOR-dependent pathway or mTOR-independent pathway to induce autophagy, which maybe a potential treatment for AD. In this review, we summarize the latest studies concerning the role of autophagy in AD and explore autophagy modulation as a potential therapeutic strategy for AD. However, to date, little of the researches on autophagy have been performed to investigate the modulation in AD; more investigations need to be confirmed in the future.


Identification of highly concentrated dextrose solution (50% dextrose) extravasation and treatment--a clinical report.
Treatment for significant hypoglycemia includes administration of dextrose containing agents, including 50% dextrose (D50%W) intravenously. Significant extravasation of D50%W can lead to complications, including skin and soft tissue injury, loss of limb, or death. The aim of this case report, using an interdisciplinary team approach, explores extravasation protocols as well as literature review, is to provide information about the proper use of hyaluronidase in patients with D50%W extravasations. A 46-year-old African American man presented to the emergency department (ED) after blood glucose level was initially 13 mg/dL. Emergency medical service established a large bore intravenous (IV) line in the right antecubital vein and administered a total of 50 g of D50%W. Upon arrival to the ED, the patient's level of consciousness had significantly improved. After arrival to the ED, the patient started complaining of pain in his right arm, near the site of the IV line insertion. On inspection, the IV site was grossly infiltrated. Hospital protocols for hyperosmolar infiltration were used. Extravasation is a common medical complication of infused medications and needs to be properly identified and treated. The multitude of skills from nursing, medicine, and pharmacy ensures that extravasation is managed appropriately and effectively to ensure safety to patients. Recognition, communication, and awareness of the institutional guidelines on how to treat infiltration and extravasation should be encouraged in all ED and intensive care unit medical personnel who deal with a variety of infusions and IV medications that have serious implications if not treated correctly.


Solitary toxic adenoma of the thyroid gland.
The incidence of solitary toxic adenoma of the thyroid in a general surgical unit with an interest in thyroid disease has been reviewed over a 15-year period. Six hundred and thirty thyrotoxic cases were treated surgically, 35 (5.6 per cent) having a solitary toxic adenoma. Thyroid enlargement or toxicity had been present for more than 5 years in 7 patients (20.0 per cent). Cardiovascular complications were present in 6 cases (17.1 per cent). Thyroid lobectomy resulted in 30 (85.7 per cent) euthyroid and 5 (143.3 per cent) hypothyroid patients. One toxic adenoma contained a focus of carcinoma. The clinical features, diagnosis and management of solitary toxic adenoma, and the management of symptomatic nodules which are 'hot' but not biochemically toxic, are discussed.


Midtrimester amniocentesis. An analysis of 923 cases with neonatal follow-up.
Maternal, fetal, and neonatal results and complications were analyzed after 923 genetic amniocenteses. Maternal age of 35 years and beyond was associated with a 2.0% risk of fetal trisomy 21 and a 3.0% risk of all major chromosome abnormalities. Comparable rates for women aged 40 and beyond were 4.8% and 7.2%. Neural tube defects were detected in 0.15% of procedures done for maternal age and 3.4% of those done for a previous involved child. The risk of spontaneous abortion as a result of amniocentesis was 0.2% to 1.4%. Mahogany or green fluid was associated with a 29% rate of fetal loss. Unexplained midtrimester elevations of maternal serum alpha-fetoprotein were associated with a 38% risk of a subsequent low-birth weight infant. The only neonatal complication associated with amniocentesis was an apparent marked increase in the incidence of lower-extremity orthopedic abnormalities.


Possible roles for frequent salivary antiepileptic drug monitoring in the management of epilepsy.
Salivary levels of phenytoin, phenobarbitone, carbamazepine and carbamazepine-epoxide correlate with the simultaneous plasma water levels of these substances, after correcting for the effects of pH differences between saliva and plasma in the case of phenobarbitone. Saliva is easy and painless to collect, and salivary levels of the drugs are conveniently measured. Frequent (often daily) monitoring of pre-dose morning anticonvulsant drug concentrations in saliva over periods of weeks or months in 3 groups of epileptic subjects showed that (i) in some but not all poorly controlled epileptic patients seizures tended to occur on days when salivary anticonvulsant levels were lower than on non-seizure days, (ii) in such subjects it was possible to estimate an anticipated optimal drug concentration and dose to minimize seizure activity from the plot of seizure frequency against drug concentrations, (iii) in women with 'catamenial' epilepsy, salivary anticonvulsant levels were lower on perimenstrual days than at mid-cycle in half of the subjects studied, and (iv) in pregnant epileptic women the time course of the change in drug levels relative to dose could be followed more closely throughout pregnancy and the post-natal period than was practicable when using blood level measurements. Frequent measurement of salivary anticonvulsant concentrations appears a promising and inexpensive adjunct to the investigation and management of certain problem areas in epilepsy.


Detection of vibration-mode scattering in electronic shot noise.
We present shot noise measurements on Au nanowires showing very pronounced vibration-mode features. In accordance to recent theoretical predictions the sign of the inelastic signal, i.e., the signal due to vibration excitations, depends on the transmission probability becoming negative below a certain transmission value. We argue that the negative contribution to noise arises from coherent two-electron processes mediated by electron-phonon scattering and the Pauli exclusion principle. These signals can provide unique information on the local phonon population and lattice temperature of the nanoscale system.


Tailoring the Solvation Sheath of Cations by Constructing Electrode Front-Faces for Rechargeable Batteries.
Solvent molecules within the solvation sheath of cations (e.g., Li+ , Na+ , Zn2+ ) are easily to be dehydrogenated especially when coupled with high-voltage cathodes, and lead to detrimental electrolytes decompositions which finally accelerate capacity decays of rechargeable batteries. Tremendous efforts are devoted to tackle with this long-lasting issue. Among them, salt-concentrated strategies are frequently employed to tailor the solvation sheath of cations and improve the stabilities of electrolytes. However, the cost challenges caused by adding extra dose of expensive salts, additives/cosolvents in preparing highly concentrated electrolytes, hinder their further utilizations to some extent. Introducing porous materials-based electrode front-faces on the surface of electrodes even within dilute electrolytes can transfer the high-energy-state desolvated solvents from the reactive electrodes to the nonconductive porous material surfaces, thus eliminate the contact chances between desolvated solvents and electrode materials, and greatly reduce solvents-related decomposition issues. Herein, recent advances in using electrode front-faces to tailor the solvation sheath of metal ions for rechargeable batteries are discussed. Finally, perspectives to the future challenges and opportunities of constructing electrode front-faces to tailor the solvation sheath of cations by constructing electrode front-face for rechargeable batteries are provided.


Cytodifferentiation of quail tectal primordium transplanted homotopically into the chick embryo.
The development of the retinotectal system in the quail embryo starts earlier and evolves faster than in the chick embryo. In order to establish whether the mesencephalic alar plate (i.e., the primordium of the optic tectum) of a quail embryo maintains its own rate of cytodifferentiation after transplantation into a chick embryo or whether this rate could be influenced by the host, we performed homotopic transplantations of the tectal primordium between the two species on day 2 of incubation (E2) by removing the mesencephalic alar plate in the chick and replacing it with that of the quail embryo. Graft extension was evaluated by means of the well-known quail nucleolar marker, and cytodifferentiation of both operated and unoperated tecta was analyzed from E3 to E12. It was found that: in most cases, the operated tectum is a chimera formed by a large dorsal territory consisting solely of grafted quail cells and a smaller ventral territory almost entirely made up of host chick cells. A clear boundary exists at the interface between these two territories. In the host, the temporal sequence of appearance of the various laminae, following a well-established rostroventral-caudodorsal developmental gradient, is comparable in both the operated tectum and the host territory of the chimeric tectum to that of a control chick tectum. In the graft, the migration of postmitotic cells starts earlier than in the host. However, in the former there is about a 12-h delay with respect to a control quail tectum. Proliferation and migration of cells take place in the graft much faster than in the host. Thus, the formation of the 8 deepest layers occurs according to the normal quail schedule, indicating that the early delay is quickly recuperated. This process of lamination follows the normal quail rostroventral-caudodorsal developmental gradient. The post-mitotic neurons originating in the grafted neuroepithelium follow a normal radial migration. Nevertheless, a few grafted cells occupy the host tectal territory far from the host/graft interface. These cells have been observed in both the stratum griseum centralis and the uppermost tectal layers, indicating that some tectal neurons are able to displace themselves tangentially. Contrary to what happens in the 8 deepest layers, which in the graft follow the normal quail cytodifferentiation schedule independently of the host, cytodifferentiation in the upper tectal layers is partially influenced by the host.(ABSTRACT TRUNCATED AT 400 WORDS)


Extraction and isolation of diphenylheptanes and flavonoids from Alpinia officinarum Hance using supercritical fluid extraction followed by supercritical fluid chromatography.
In this paper, an off-line combination method of supercritical fluid extraction and supercritical fluid chromatography was developed for the selective extraction and isolation of diphenylheptanes and flavonoids from Alpinia officinarum Hance. The enrichment of target components was successfully achieved using supercritical fluid extraction with the following conditions (8% ethanol as co-solvent at 45°C and 30 MPa for 30 min). Taking full advantage of the complementarity of supercritical fluid chromatography stationary phases, a two-step preparative supercritical fluid chromatography strategy was constructed. The extract was firstly divided into seven fractions on a Diol column (250 × 20 mm internal diameter, 10 μm) within 8 min by gradient elution increasing from 5% to 20% modifier (methanol) at 55 ml/min and 15 MPa. Then the seven fractions were separated by using a 1-AA or a DEA column (250 × 19 mm internal diameter, 5 μm) at 50 ml/min and 13.5 MPa. This two-step strategy showed superior separation ability for structural analogs. As a result, seven compounds, including four diphenylheptanes and three flavonoids with high purity, were successfully obtained. The developed method is also helpful for the extraction and isolation of other structural analogs of traditional Chinese medicines.


A spiraling journey into the small bowel: a case series of novel motorized power spiral enteroscopies.
The small bowel has, to date, remained a difficult area to access via endoscopy. The novel motorized power spiral enteroscopy, recently introduced, has more depth of insertion and is of shorter duration. Presented here is a case series of motorized spiral enteroscopies. Motorized spiral enteroscopy is indicated for patients requiring deep enteroscopy (eg, for a diagnosis of obscure GI bleeding, suspected inflammatory bowel disorder) and for therapeutic interventions, such as polypectomy, hemostasis, or stricture dilatation. It is contraindicated in patients who are not eligible for general anesthesia, with perforation, or with coagulopathy and in the pediatric population. The contraindications for the anterograde route are gastroesophageal varices, foregut stenosis, eosinophilic esophagitis, and so on. The retrograde approach is contraindicated in active colitis, anal stenosis, or colonic stricture. Informed consent was sought from all the patients. The procedure was successful in 13 of 14 (92.8%) in that the target site was reached or panenteroscopy was confirmed. The diagnoses were stricture and ulcers of the jejunum or ileum. The procedures performed were argon plasma coagulation and stricture dilation. The average duration of anterograde enteroscopy was 61.1 minutes and retrograde enteroscopy was 90 minutes. The major adverse events were hypothermia (3 of 14) and pancreatitis (1 of 14), from which the patients recovered fully. Novel motorized power spiral enteroscopy is a great tool in small-bowel diagnostics and therapeutics. Speed and ease add to the attractiveness of the procedure.


Quantitative determination of human protein C. Evaluation of a "fast" functional assay in comparison to a "traditional" functional and an immunological assay.
A fast functional assay for protein C was evaluated and compared with a traditional functional and an enzyme linked immunosorbent assay in parallel for the same plasma samples derived from 43 healthy subjects, 12 patients with severe hepatic dysfunction, and 23 patients under stable oral anticoagulation. By all three test systems significantly lower levels of protein C were obtained in both groups of patients compared with normal subjects (p less than 0.0001). No significant between - assay differences were found in normal subjects and in patients with hepatic dysfunction; by correlation analysis coefficients higher than 0.8 were calculated between the measurements of the three tests. In patients under stable oral anticoagulation, however, the immunologic test yielded higher values than the traditional (p less than 0.05) and, more pronounced, the fast functional assay (p less than 0.0001); no or only borderline significant correlations between the results were found. In these patients protein C levels measured with the traditional functional assay were in the same range as the activity levels of factors II, VII, IX, and X, whereas the fast functional test yielded significantly lower levels. The presented results indicate that very similar protein C levels were obtained with both functional and the immunologic assay except in patients under oral anticoagulation.


A novel method for the transport and analysis of genetic material from polyps and zooxanthellae of scleractinian corals.
We have developed a new simple method for transport, storage, and analysis of genetic material from the corals Agaricia agaricites, Dendrogyra cylindrica, Eusmilia ancora, Meandrina meandrites, Montastrea annularis, Porites astreoides, Porites furcata, Porites porites, and Siderastrea siderea at room temperature. All species yielded sufficient DNA from a single FTA card (19 microg-43 ng) for subsequent PCR amplification of both coral and zooxanthellar DNA. The D1 and D2 variable region of the large subunit rRNA gene (LSUrDNA) was amplified from the DNA of P. furcata and S. siderea by PCR. Electrophoresis yielded two major DNA bands: an 800-base pair (bp) DNA, which represented the coral ribosomal RNA (rRNA) gene, and a 600-bp DNA, which represented the zooxanthellar srRNA gene. Extraction of DNA from the bands yielded between 290 microg total DNA (S. siderea coral DNA) and 9 microg total DNA (P. furcata zooxanthellar DNA). The ability to transport and store genetic material from scleractinian corals without resort to laboratory facilities in the field allows for the molecular study of a far wider range and variety of coral sites than have been studied to date.


Isolation and characterisation of lymphoblastoid cells from cattle and deer affected with 'sheep-associated' malignant catarrhal fever.
Cells with the histological and ultrastructural characteristics of large granular lymphocytes (LGL) have been obtained in culture from both cattle and red deer (Cervus elaphus) reacting with 'sheep-associated' malignant catarrhal fever (MCF). Such cells have been derived from thymus, lymph node and spleen suspensions as well as from cerebrospinal fluid cells and cultured cornea. On most occasions their presence was observed only transitorily but by providing the cells with feeder monolayers and, or, interleukin-2, several lines were maintained indefinitely, and some became independent of these factors after prolonged culture. A similar cell line was also derived from a Père David's deer affected with MCF at Whipsnade zoological park. Functionally, cultured LGL were cytotoxic to both primary cell cultures and cell lines and their cytotoxicity was not restricted to histocompatible target cells. These findings suggest that the cultured cells have natural killer cell-like activity and that they are important targets for the agent of MCF in cattle and deer. One cell line derived from a red deer transmitted the disease but none of the cells generated from cattle did.


The accuracy of autotitrating CPAP-determined residual apnea-hypopnea index.
Autotitrating continuous positive airway pressure (auto-CPAP) devices not only titrate CPAP pressures but also measure residual respiratory events. The aim of the present study was to determine the accuracy of auto-CPAP-derived residual apnea-hypopnea index (AHI). We studied 137 consecutive patients (72.3% men) with obstructive sleep apnea from January 2008 to December 2010 who underwent in-laboratory overnight polysomnography (PSG) using auto-CPAP. We excluded patients with comorbidities like congestive heart disease, chronic obstructive pulmonary disease, or hypoventilation syndromes and patients with central sleep apnea. Residual AHI obtained from the auto-CPAP device by smart card (CPAP-AHI) was compared simultaneously with AHI from an overnight PSG on auto-CPAP (PSG-AHI) using Bland-Altman analysis and Wilcoxon signed-rank test. The mean AHI on the diagnostic study was 45.08 ± 1.8. During the titration, auto-CPAP markedly suppressed the respiratory events (PSG-AHI, 3.40 ± 0.20). On the other hand, CPAP-AHI was 3.35 ± 0.17. Bland-Altman analysis showed good agreement between auto-CPAP-AHI and PSG-AHI (AHI mean difference of 0.05, and the limits of agreement for the AHI were from +4.9 to -4.8). Two methods have also been compared with paired samples t test and no statistically significant difference was found (p > 0.05). Auto-CPAP can identify residual respiratory events equivalent to the use of PSG in a selected population.


Association of alcohol consumption with allergic disease and asthma: a multi-centre Mendelian randomization analysis.
To use the rs1229984 variant associated with alcohol consumption as an instrument for alcohol consumption to test the causality of the association of alcohol consumption with hay fever, asthma, allergic sensitization and serum total immunoglobulin (Ig)E. Observational and Mendelian randomization analyses using genetic variants as unbiased markers of exposure to estimate causal effects, subject to certain assumptions. Europe. We included a total of 466 434 people aged 15-82 years from 17 population-based studies conducted from 1997 to 2015. The rs1229984 (ADH1B) was genotyped; alcohol consumption, hay fever and asthma were self-reported. Specific and total IgE were measured from serum samples. Observational analyses showed that ever-drinking versus non-drinking, but not amount of alcohol intake, was positively associated with hay fever and inversely associated with asthma but not with allergic sensitization or serum total immunoglobulin (Ig)E. However, Mendelian randomization analyses did not suggest that the observational associations are causal. The causal odds ratio (OR) per genetically assessed unit of alcohol/week was an OR = 0.907 [95% confidence interval (CI) = 0.806, 1.019; P = 0.101] for hay fever, an OR = 0.897 (95% CI = 0.790, 1.019; P = 0.095) for asthma, an OR = 0.971 (95% CI = 0.804, 1.174; P = 0.763) for allergic sensitization and a 4.7% change (95% CI = -5.5%, 14.9%; P = 0.366) for total IgE. In observational analyses, ever-drinking versus not drinking was positively associated with hay fever and negatively associated with asthma. However, the Mendelian randomization results were not consistent with these associations being causal.


Progress of acute appendicitis: a study in children.
The results of six simple investigations are compared with the duration of the disease in 100 children with acute appendicitis. The results indicate that during the first day on which the appendix becomes inflamed the local defence mechanisms of the appendix are impaired sufficiently to allow invasion by the bacterial organisms in its lumen. This initially inflamed and subsequently infected appendix may develop in the manner indicated. Local and/or generalized complications may follow, i.e. acute appendicitis in its successive stages of development, which may be regarded as (a) inflamed, (b) infected and (c) complicated, and these changes take place at intervals of 1 day. Bacterial and faeoliths are present in the lumen of the appendix, whether inflamed or not, and it is suggested that they complicate the disease rather than being responsible for causing it.


Spatio-temporal progression of the AEP P300 component using the cortical imaging technique.
The cortical imaging technique (CIT), a mathematical method for simulating the potential fields on the surface of the brain, was used to analyze the spatio-temporal progression of the AEP P300 component (as well as the preceding and subsequent N2a and N3 components) from thirty normal adult subjects recorded in a standard "oddball" paradigm. Comparisons were made between the progressions of the endogenous event-related cognitive potentials and the exogenous stimulus-dependent potentials (N1 component). Cortical imaging results suggest that different and multiple generator sites are involved in the production of exogenous and endogenous evoked responses. We particularly note the asymmetric development of the P300 component and the apparent anterior generator sites for the N2a component. This last result is interesting because the N2a precedes the P300 component and supports an earlier frontal contribution.


Animal Welfare and Parasite Infections in Organic and Conventional Dairy Farms: A Comparative Pilot Study in Central Italy.
The study investigated and compared welfare conditions and gastrointestinal (GI) parasites distribution among organic (ORG) and conventional (CONV) farms in central Italy. Five ORG and five CONV farms were assessed for animal welfare with an adapted version of the AssureWel protocol. Faecal samples collected from the rectum of the animals both in ORG (n = 150) and CONV (n = 150) were analysed using conventional copromiscroscopy. The presence of skin damages in the rear legs was significantly predominant (p < 0.001) in CONV (26.7%) compared with ORG farms (10.0%). No differences were found for lameness, cleanliness, Body Condition Score, hair loss, body lesions and swelling prevalence. Data concerning the productive performances, e.g., total milk, fat and protein yields standardised in mature equivalent (ME) were collected. ME milk yield (ORG: 9656.9 ± 1620.7 kg; CONV: 12,047.2 ± 2635.3) and ME fat yield (ORG: 396.6 ± 66.8; CONV: 450.3 ± 102.8) were significantly lower in ORG farms (p < 0.001). Anthelmintics were used regularly in 4/5 CONV and 0/5 ORG farms. In 2 CONV farms (40%) and 4 ORGs (80%) at least one animal tested positive for GI parasites. No significant differences in parasites prevalence emerged (ORG = 10.7%; CONV = 8%). These data indicate that ORG farming does not influence parasite prevalence and animal welfare status.


COVID-19 vaccinations: An overview of the Italian national health system's online communication from a citizen perspective.
COVID-19 vaccine hesitancy is still widespread. During the pandemic, the internet has been the preferred channel for health-related information, especially for less-educated citizens who tend to be the most hesitant about vaccination. A well-structured web communication strategy could help both to overcome vaccine hesitancy and to ensure equity in healthcare service access. This study investigated how the various regional and local health authorities in Italy used their institutional websites to inform users about COVID-19 vaccinations between March and April 2021. We browsed 129 institutional websites, checking the availability, quality and quantity, actionability and readability of information using a literature-based common grid. Descriptive statistics and statistical tests were performed. The online public dissemination of COVID-19 vaccination information in Italy was fragmented, both across and within regions. The side effects of vaccinations, were often not reported on the websites, thus missing an opportunity to enhance vaccination uptake. More focus should also be placed on readability, since readability indexes showed that they were difficult to understand. Our research revealed that several actions could be implemented to enhance online communication on COVID-19 vaccination. For instance, simplifying texts can make them more understandable and the information reported actionable.


Metagenomic marine nitrogen fixation--feast or famine?
Natural populations of bacteria in different environments can be astonishingly diverse, as was revealed graphically by large-scale sequencing of samples of their so-called metagenomes. Among the sequence datasets from four different samples of marine bacterial metagenomes, we noted that nitrogen fixation (nif) genes were conspicuous by their absence from three of them. However, in one sample, more than one-third of the bacteria appeared to have a complement of these genes. Here, some reasons behind this site-to-site variability and their implications for how molecular methods, involving large-scale sequencing and/or functional metagenomics, can best be used to describe bacterial diversity in natural environments are discussed.


Pomegranate (Punica granatum) peel extract provides protection against mercuric chloride-induced oxidative stress in Wistar strain rats.
Pomegranate [Punica granatum L. (Lythraceae)] is rich in antioxidants. The present work was undertaken to evaluate the protective effects of methanol extract of pomegranate peel extract (PPE) against a rat model of oxidative stress generated by treatment with mercuric chloride (HgCl(2)). Rats were injected with HgCl(2) (5 mg/kg body weight in 0.9% NaCl) for developing oxidative stress. The methanol extract of pomegranate peel (PPE) was suspended in 0.5% sodium carboxymethylcellulose and fed to rats at 50 mg/kg body weight/day up to 30 days after HgCl(2) treatment. Biomarkers of oxidative stress including erythrocyte plasma membrane redox system (PMRS), lipid peroxidation, advanced oxidation protein products (AOPP), intracellular glutathione, and plasma antioxidant capacity as FRAP values were measured after PPE supplementation. HgCl(2)-treated rats showed increased oxidative stress as evidenced by increased activity of erythrocyte PMRS 153%, lipid peroxidation 31%, and AOPP 290%. There was a significant (p < 0.01) decrease (25%) in plasma antioxidant capacity and intracellular glutathione (75%). Supplementation with PPE protected rats from HgCl(2) induced oxidative damage. PPE supplementation to control rats increased antioxidant defense. The results clearly demonstrate that PPE treatment augments the antioxidant defense mechanism in mercuric chloride-induced oxidant toxicity. To the best of our knowledge this is the first report of the increase in erythrocyte PMRS activity in rats after supplementation with any kind of antioxidant supplementation. This study emphasizes the need for characterizing PPE for potential unknown antioxidant compounds.


[Prevalence of obesity and cardiovascular risk in the general population of a health area in Extremadura (Spain): the Hermex study].
To estimate the prevalence of obesity and its associated cardiovascular risk in the general population of a health area in Extremadura. A cross-sectional study on a random population sample aged 25-79 years from the Don Benito-Villanueva (Badajoz) health area. Risk factors and cardiovascular disease were examined. Anthropometric and blood pressure measurements were collected, and a blood sample was taken. Obese subjects were categorized into different risk levels as proposed by the Spanish Society for the Study of Obesity, and the influence of obesity on estimation of the risk of ischemic heart disease was studied using the Framingham function, as adapted for Spain. A total of 2833 of the 3521 subjects screened (80.5%) participated in the study. Mean age was 51.2 years (SD 14.7), and 46.5% were males. Male subjects had a greater prevalence of overweight and obesity (46.2% and 37.7% respectively) as compared to females (37.7% and 32.6%) (p<0.005 and p<0.05 respectively). Only 10% of obese subjects had no increased cardiovascular risk. Obesity was associated to an 8-fold increase in the presence of a high risk for ischemic heart disease in females (p<0.001), as compared to a 1.4-fold increase in males (p=0.095). Obesity is highly prevalent and affects, together with overweight, 74.1% of the population in an Extremadura health area. A vast majority of obese subjects have an increased cardiovascular risk, which is very marked for ischemic heart disease in females.


Effects of a moderate-intensity static magnetic field on VEGF-A stimulated endothelial capillary tubule formation in vitro.
Effects of a moderate-intensity static magnetic field (SMF) on the early-stage development of endothelial capillary tubule formation were examined during the initial cell growth periods using co-cultured human umbilical vein endothelial cells and human diploid fibroblasts. The co-cultured cells within a well (16 mm in diameter) were exposed to SMF intensity up to 120 mT (Bmax) with the maximum spatial gradient of 21 mT/mm using a disc-shaped permanent magnet (16 mm in diameter and 2.5 mm in height) for up to 10 days. Control exposure was performed without magnet. Some vascular endothelial cells were treated with vascular endothelial growth factor (VEGF)-A (10 ng/ml) to promote the tubule formation every 2-3 days. Four experimental protocols were performed: (1) non-exposure (control); (2) SMF exposure alone; (3) non-exposure with VEGF-A; (4) SMF exposure with VEGF-A. Photomicrographs of tubule cells immunostained with an anti-platelet-endothelial cell adhesion molecule-1 (PECAM-1 [CD31[) antibody as a pan-endothelial marker, were analyzed after culture at 37 degrees C for 4, 7, and 10 days. The mean values of the area density and the length of tubules (related mainly to arteriogenesis) as well as the number of bifurcations (related mainly to angiogenesis) were determined as parameters of tubule formation and were compared between the groups. After a 10 day incubation, in the peripheral part of the culture wells, SMF alone significantly promoted the tubule formation in terms of the area density and the length of tubules, compared with control group. In the central part of the wells, however, SMF did not cause any significant changes in the parameters of tubule formation. After a 7 day incubation, VEGF-A significantly promoted all the parameters of tubule formation in any part of the wells, compared with control group. With regard to the synergistic effects of SMF and VEGF-A on tubule formation, after a 10 day incubation, SMF significantly promoted the VEGF-A-increased area density and length of tubules in the peripheral part of the wells, compared with the VEGF-A treatment alone. However, SMF did not induce any significant changes in the VEGF-A-increased number of bifurcations in any part of the wells. The tubule cells observed in the wells had elongated, spindle-like shapes, and the direction of cell elongation was random, irrespective of the presence and direction of SMF. These findings suggest that the application of SMF to intact or VEGF-A-stimulated vascular endothelial cells leads mainly to promote or enhance arteriogenesis in the peripheral part of the wells, where the spatial gradient increases relative to the central part. The effects of SMF on the VEGF-A-enhanced tubule formation appear to be synergistic or additive in arteriogenesis but not in angiogenesis.


Regulation of SLC6A14 trafficking in breast cancer cells by heat shock protein HSP90β.
SLC6A14 is a plasma membrane transporter specific for neutral and basic amino acids, upregulated in many tumors. This study focused on breast cancer cell lines, showing the fully glycosylated band, known to be at the cell surface, in estrogen receptor positive lines. Inhibition of heat shock protein 90β (HSP90β) decreased the level of this band, what correlated with a decrease of SLC6A14 transport activity. A direct interaction between SLC6A14 and HSP90β was confirmed in proximity ligation assay, pointing to the role of HSP90 in folding control in endoplasmic reticulum and affecting farther transporter trafficking to the cell surface. Either inhibitor of SLC6A14 (α-methyltryptophan) or of HSP90 (radicicol) had the cytotoxic effect, when added alone, while treatment with both compounds had a synergistic effect. This points to SLC6A14 as a druggable target in breast cancer and a combination therapy being more efficient in killing cancer cells.


Acremonium mycetoma: a case report and discussion.
Acremonium mycetoma is a rare fungal infection of the skin, tissue, and bones. We present a case of a 64-year-old man with mycetoma due to gardening. The clinical presentation, laboratory findings, and treatment options are reviewed.


HMG-CoA reductase regulation: use of structurally diverse first half-reaction squalene synthetase inhibitors to characterize the site of mevalonate-derived nonsterol regulator production in cultured IM-9 cells.
The activity of HMG-CoA reductase (HMGR) is tightly regulated, in part through post-transcriptional mechanisms that are mediated by nonsterol products of mevalonate metabolism. Previous reports have suggested that these mediators are derived from farnesyl pyrophosphate (FPP). Recent studies have implicated FPP hydrolysis products (e.g., farnesol), the squalene synthetase (SQS) reaction products presqualene pyrophosphate (PSQPP) and squalene, or their metabolites. To distinguish among these possible mediators, we evaluated the ability of HMGR and SQS inhibitors to induce compensatory increases in HMGR activity in cultured IM-9 cells. Mevinolin (HMGR inhibitor) produced predicted increases in HMGR activity that were related to the degree of cholesterolgenesis inhibition (e.g., 4-fold, 9-fold, and 17-fold increases relative to 50%, 76%, and 90% inhibition, respectively). By contrast, a variety of structurally distinct reversible, competitive, first half-reaction SQS inhibitors all reduced cholesterolgenesis by up to 90% with no appreciable increases in HMGR activity. These observations strongly suggest that nonsterol-mediated post-transcriptional mechanisms regulating HMGR activity remain intact after SQS first half-reaction inhibition, indicating that nonsterol regulator production is independent of SQS action and ruling out PSQPP, squalene and their metabolites as possible mediators. Unexpectedly, the SQS mechanism-based irreversible inactivator, zaragozic acid A (ZGA) exhibited the greatest degree of HMGR modulation, producing 5-fold, 11-fold, and 40-fold increases in HMGR activity at concentrations that produced 25%, 50%, and 75% cholesterolgenesis inhibition, respectively. The markedly greater magnitude of HMGR stimulation by ZGA versus mevinolin at similar levels of cholesterolgenesis inhibition suggests that ZGA may directly interfere with the production or action of the nonsterol regulator.


Personalization matters: the effect of sex in multivitamin-multimineral-based cancer prevention.
The prevention of non-communicable diseases like cancer contributes to healthy aging. Dietary supplements might support such prevention; their effect likely depends on the personal characteristics of the individuals receiving them. To evaluate the influence of sex on reducing cancer incidence with multivitamin-multimineral (MVM) supplementation, sex-specific results of the efficacy of MVM supplementation for cancer prevention were collected and meta-analyzed (using fixed effect (FE) and random effect (RE) models). Three trials included in the "US Preventive Services Task Force Recommendation Statement Report regarding Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer" were used, namely, COSMOS, SU.VI.MAX, and PHS2. A total of 28,558 men and 20,542 women were included. Multivitamin-multimineral supplementation significantly reduced cancer incidence in the entire population (HR 0.93 [95% CI, 0.88-0.99], FE and RE); sex-specific meta-analysis showed beneficial effects of supplementation in men (HR 0.91 [95% CI, 0.85-0.97] (FE)/0.88 [95% CI, 0.77-1.01] (RE)); however, there was no effect in women (HR 1.00 [95% CI, 0.88-1.14], FR and RE); (Pdifference = 0.17). Sex could influence the effect of MVM supplementation in reducing cancer incidence, with supplementation being effective only in male individuals. These results might be informative for future research and public health policy makers.


Five-year patency rates of renal and visceral bypasses after abdominal debranching for thoraco-abdominal aortic aneurysms.
This article aims to report for the first time the long-term bypass graft patency after visceral hybrid repair of thoraco-abdominal aortic aneurysms (TAAAs). Between July 2004 and September 2012 the visceral hybrid procedure was performed in 46 patients with TAAAs, who did not qualify for an open or total endovascular repair. The inflow sites of visceral revascularisation originated either from the native artery or from aortic prosthetic grafts. All patients were included in the study and were followed up with subsequent computed tomography (CT) (mean follow-up 23.5 months). In 46 patients (67.5 years in median; range 35-88), 164 grafts were performed. The 30-day primary patency of all grafts was 87.9%. The long-term patency remained 87.9 ± 2.7%, 86.1 ± 3.2% and 86.1 ± 3.2% after 1, 3 and 5 years, respectively. The patency of all hepatic grafts was 100%. The patency of grafts to the superior mesenteric artery was 88.8 ± 4.8% after 1, 3 and 5 years. The patency was 87.2 ± 6%, 87.2 ± 6% and 87.2 ± 6% for the left renal artery and 76 ± 7%, 69.6 ± 8.8% and 69.6 ± 8.8% for the right renal artery after 1, 3 and 5 years, respectively. Hybrid repair demonstrates excellent results regarding long-term bypass graft patency of renovisceral arteries except for the right renal artery.


High preoperative neutrophil-lymphocyte ratio predicts biochemical recurrence in patients with localized prostate cancer after radical prostatectomy.
To investigate the association between preoperative neutrophil-lymphocyte ratio (NLR) and oncological outcomes in patients with localized prostate cancer (PCa) after radical prostatectomy (RP). We retrospectively reviewed the records of 1367 patients who underwent RP between November 2003 and April 2012. Patients who underwent a concurrent biopsy/procedure in other organs, had evidence of acute infection, or had systemic inflammatory disease were excluded. We divided the patients by NLR level and analyzed their perioperative outcomes. To determine NLR significance, we performed a multivariate logistic regression analysis of the pathological adverse outcomes and a Cox proportional hazard analysis of the biochemical recurrence (BCR), which was defined as a prostate-specific antigen level ≥0.2 ng/mL on two consecutive tests. Among the 1367 patients, 158 (11.6 %) in the high-NLR (≥2.5) group had a higher biopsy Gleason score (p < 0.001), pathological Gleason score (p < 0.001), and pathological stage (p < 0.001) than patients in the low-NLR (<2.5) group (n = 1209, 88.4 %). Multivariate analysis revealed that high NLR was significantly correlated with adverse pathological outcomes of higher pathological stage (HR 1.688; 95 % CI 1.142-2.497; p = 0.009) and extracapsular extension (HR 1.698; 95 % CI 1.146-2.516; p = 0.008). Kaplan-Meier analysis showed significantly worse BCR-free survival (p < 0.001) in patients with a high NLR. A high NLR was a significant predictor of BCR after RP (HR 1.358; 95 % CI 1.008-1.829; p = 0.044). High NLR was significantly related to unfavorable clinicopathological outcomes and worse BCR-free survival. Further studies are needed to clarify the correlation between NLR and PCa.


Clinical outcomes and patency of self-expanding metal stents in patients with malignant colorectal obstruction: a prospective single center study.
Self-expanding metal stents (SEMS) have been used as a palliative treatment for malignant colorectal obstruction. However, the reports about primary stent patency rate and associated factors have been limited. This study was performed to evaluate clinical outcomes and factors associated with long-term complications and patency of SEMS in patients with malignant colorectal obstruction. Patients who underwent palliative endoscopic placement with uncovered SEMS for a malignant colorectal obstruction were prospectively enrolled at Seoul National University Hospital between April 2005 and August 2007. Forty-nine patients underwent 51 SEMS placements. Obstruction sites were rectum in 15 patients (30.6%), descending or sigmoid colon in 25 (51.0%), and transverse colon in nine (18.4%), respectively. The causes of obstruction were colorectal cancer in 36 patients (73.5%), direct invasion of gastric cancer in seven (14.3%) and others in six (12.2%). Technical success was achieved in 100% and clinical success in 86%, and there was one procedure-related perforation. Re-obstruction and migration occurred in 16% and 6%, respectively, during mean follow-up period of 331 days. Median stent patency duration was 204 days, and patency rates at 30, 90, and 180 days were 91.2%, 81.0%, and 53.3%, respectively, which was not associated with patient demographics, site of obstruction, or palliative chemotherapy. Endoscopic SEMS placement is a safe and effective palliative treatment for malignant colorectal obstruction, and overall long-term complication and patency were favorable irrespective of the palliative chemotherapy.


Endocardial, epicardial, and right atrial approach for catheter ablation of premature ventricular contractions from the inferoseptal process of the left ventricle.
Inferoseptal process of the left ventricle (ISP-LV) might be a source of idiopathic ventricular arrhythmias. In these cases, ectopic foci are accessible from the LV endocardium, epicardially from the middle cardiac vein as well as from the right atrium (RA). This study reports a series of patients with premature ventricular contractions (PVCs) arising from the ISP-LV that were successfully ablated following access from different structures. Five patients (4 males, age 61 ± 12.8 years) with PVCs arising from the ISP-LV were successfully ablated using three different approaches for ablation-endocardial, epicardial (through coronary sinus or its branches), and RA approaches. Endocardial LV mapping, RA, and coronary sinus (CS) mapping were performed in all five cases. PVCs demonstrated RBBB or LBBB-like morphology and left superior axis. The three patients ablated endocardially had a maximum deflection index (MDI) of 0.36, 0.43, and 0.54, whereas in the remaining 2 patients, MDI was 0.57 and both demonstrated QS morphology in the inferior leads. Local activation time at the successful ablation site was 35 ± 8.9 (26-55) msec pre-QRS. Pacemapping at the successful ablation site resulted in a good (11/12) or perfect (12/12) QRS match in all cases. Three of the patients demonstrated frequent monomorphic PVCs of another morphology suggesting a remote exit site. All patients remained arrhythmia-free after a mean follow-up of 21 ± 15 (6-36) months. Successful ablation of PVCs from ISP-LV may require access from the CS or even RA apart from LV endocardial approach. Not infrequently patients demonstrate additional PVC foci.


Hepatic reticuloendothelial function in rats with various portasystemic shunts and total liver arterialization.
Hepatic reticuloendothelial function was measured in 6 experimental groups of rats with various portasystemic shunts or total liver arterialization by computer calculation of the hepatic uptake rate of intravenously injected 99mTc-sulphur colloid. Marked reduction of the hepatic reticuloendothelial system (RES) function was found both 1 and 3 weeks after the construction of a mesentericocaval or conventional end-to-side portacaval shunt. Hepatic RES function was also lowered both 1 and 3 weeks after a modified portacaval shunt, but the reduction was much less pronounced. Total liver arterialization produced a similar mild reduction of hepatic RES function after 1 week; however, there was no longer any significant reduction after 3 weeks. This study concludes that total liver arterialization ameliorates the negative effect that portasystemic shunting has on hepatic RES function.


Characterization of glycosylation and adherent properties of melanoma cell lines.
The repertoire of oligosaccharide components of cellular glycoproteins significantly contributes to cell adhesion and communication. In tumor cells, alteration in cellular glycosylation may play a key role in giving rise to invasive and metastatic potential. Over 100 melanoma cell lines deposited in the ESTDAB Melanoma Cell Bank (Tubingen, Germany) were studied for the characteristic glycan composition related to tumor progression. Analysis of: (1) cell adhesion to extracellular matrix proteins--fibronectin, laminin, and collagen; (2) the expression of selected glycosyltransferases--alpha2,3(Gal beta1,3)- and alpha2,3(Gal beta1,4)-sialyltransferases, alpha1,2- and alpha1,3-fucosyltransferases, and N-acetylglucosaminyltransferase V; (3) characterization of N-glycans was carried out on uveal (4), primary cutaneous (6), and metastatic (96) melanoma cell lines. Results showed that uveal cells did not adhere to any of the substrates and, in general, possessed less glycans containing alpha-2,6- and alpha-2,3-linked sialic acid. The average number of polypeptides bearing beta-1,6-branched tri- and tetra antennary glycans (characteristic of the metastatic phenotype) were similar in uveal, primary cutaneous, and metastatic melanoma cell lines. Characterization of N-glycans may open a new perspective in the search for specific glycoproteins that could become targets for the therapeutic modulation of melanoma.


Two nanocage-based metal-organic frameworks with mixed-cluster SBUs and CO2 sorption selectivity.
Two nanocage-based metal-organic frameworks respectively built on two and three types of clusters with diisophthalate ligand were constructed, displaying unprecedented (3,4,6)-connected nets, unusual nanocages, and new bipaddle-wheel tetranuclear cluster, as well as highly selective CO2 capture.


Stony testicle: case of calcific granulomatous orchitis.
A thirty-three-year-old man presented with a hard testicular mass considered preoperatively to be a malignant testicular tumor. Frozen section revealed calcific granulomatous orchitis, which does not appear to have been previously described in man. Granulomatous orchitis is an important differential diagnosis of testicular lesions. The hard nature of this particular lesion contributed to the preoperative diagnosis of malignancy.


Unbound Bilirubin and Auditory Neuropathy Spectrum Disorder in Late Preterm and Term Infants with Severe Jaundice.
This study evaluates whether unbound bilirubin is a better predictor of auditory neuropathy spectrum disorder (ANSD) than total serum bilirubin (TSB) or the bilirubin:albumin molar ratio (BAMR) in late preterm and term neonates with severe jaundice (TSB ≥20 mg/dL or TSB that met exchange transfusion criteria). Infants ≥34 weeks' gestation with severe jaundice during the first 2 weeks of life were eligible for the prospective observational study. A comprehensive auditory evaluation was performed within 72 hours of peak TSB. ANSD was defined as absent or abnormal auditory brainstem evoked response waveform morphology at 80-decibel click intensity in the presence of normal outer hair cell function. TSB, serum albumin, and unbound bilirubin were measured using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Five of 44 infants developed ANSD. By logistic regression, peak unbound bilirubin but not peak TSB or peak BAMR was associated with ANSD (OR, 4.6; 95% CI, 1.6-13.5; P = .002). On comparing receiver operating characteristic curves, the area under the curve for unbound bilirubin (0.92) was significantly greater (P = .04) compared with the area under the curve for TSB (0.50) or BAMR (0.62). Unbound bilirubin is a more sensitive and specific predictor of ANSD than TSB or BAMR in late preterm and term infants with severe jaundice.


Appearance of hCG-receptor after conversion of newborn ovarian cells into testicular structures by H-Y antigen in vitro.
In a previous report (Zenzes et al., 1978b) it was shown that dissociated ovarian cells of newborn rats in vitro, if exposed to H-Y antigen, reorganize into testicular structures. The current study was designed to see whether this morphological conversion also results in a functional conversion. The LH/hCG receptor was used as a parameter characteristic for the newborn testis, but not for the newborn ovary. In the converted ovary, the LH/hCG receptor becomes detectable a few hours after onset of the culture and remains continuously present afterward. The appearance of this receptor may be due to a hormone-like action of H-Y antigen.


Evaluation and treatment of an adult quarter horse with an unusual fracture of the humerus and septic arthritis.
Humeral fractures are rare and usually carry a guarded prognosis in adult horses. This paper describes the evaluation and the successful surgical management of a fracture of the lateral supracondyloid crest and part of the epicondyle of the humerus in an adult quarter horse.


pGP-B2E, a Recombinant Compatible TA/TB-Ligation Vector for Rapid and Inexpensive Gene Cloning.
DNA cloning is the basic step for different fields of life science, and many efforts have been made to simplify this procedure. In this study, we report two general purpose plasmids (pGP), pGP-XB2E and pGP-B2E, for rapid and cost-effective construct of basic clones. The BciVI and XcmI cleavage sites are designed in pGP-XB2E to test plasmid linearization efficiency. The plasmid has better linearization efficiency by using BciVI which could almost completely digest 2 μg plasmid in 10 min with only one-tenth the recommended enzyme concentration. In order to further optimize the pGP-XB2E, a new plasmid, pGP-B2E, which removed XcmI cleavage site was designed. This vector is highly efficient for cloning PCR products up to 1812 bp, and the number of colonies was about five times that of pGP-XB2E. In addition to TA cloning, blunt-end PCR products with T ended in the primer could be positively linked to the T-vector pGP-B2E without A-tailing treatment (TB cloning). Moreover, as an entry vector, pGP-B2E was also compatible for gateway recombination reaction without frameshift mutations. In general, this vector provides a universal, quick, and cost-efficient method for basic molecular cloning.


Behavioural indexes of movement imagery ability are associated with the magnitude of corticospinal adaptation following movement imagery training.
Movement imagery (MI) is a cognitive process wherein an individual simulates themselves performing a movement in the absence of physical movement. The current paper reports an examination of the relationship between behavioural indexes of MI ability and the magnitude of corticospinal adaptation following MI training. Behavioural indexes of MI ability included data from a questionnaire (MIQ-3), a mental chronometry task, and a hand laterality judgment task. For the measure of corticospinal adaptation, single-pulse transcranial magnetic stimulation (TMS) was administered to elicit thumb movements to determine the representation of thumb movements before and after MI training. MI training involved participants imagining themselves moving their thumb in the opposite direction to the dominant direction of the TMS-evoked movements prior to training. Pre/post-training changes in the direction and velocity of TMS-evoked thumb movements indicated the magnitude of adaptation following MI training. The two main findings were: 1) a positive relationship was found between the MIQ-3 and the pre/post-training changes in the direction of TMS-evoked thumb movements; and 2) a negative relationship between the mental chronometry measure and both measures of corticospinal adaptation following MI training. These results indicate that both ease of imagery and timing of imagery could predict the magnitude of neuroplastic adaptation following MI training. Thus, both these measures may be considered when assessing imagery ability and determining who might benefit from MI interventions.


Influence of Introduced Substituents on the Anion-selectivity of [14]Tetraazaannulene Complexes.
Nickel(II) complexes of [14]tetraazaannulene derivatives incorporating aromatic rings into their azaannulene framework were synthesized, and the anion-selectivity of the [14]tetraazaannulene nickel complexes 1 - 4 was evaluated by potentiometric measurements with solvent polymeric membrane electrodes. All of the [14]Tetraazaannulene nickel complexes, except 3, were found to exhibit high selectivity for the I(-) ion over the SCN(-) ion, although considerable interference of the ClO4(-) ion was observed in all 1 - 4 complexes. Concerning the anion-selectivities of 1 and 4, the incorporation of naphthalene rings into the azaannulene framework decreased not only the interference of the ClO4(-) ion but also the I(-) ion-selectivity over the SCN(-) ion. Comparison studies between the dibenzotetraaza[14]annulene nickel complexes 1 - 3 indicated that differences in the attached substituents of the [14]tetraazaannulene nickel complexes greatly influenced the ion-selectivity as ionophores. According to our computational results, the ionophoric properties of [14]tetraazaannulene nickel complexes 1 - 4 were influenced by their electrostatic properties rather than their topological properties.


Ocular neovascularization. The Krill memorial lecture.
The various vascular systems of the eye can undergo new vessel formation. In this presentation, I discuss new vessel growth in the cornea, lens, iris, ciliary body, choroid, retina, and optic nerve head. No single factor can explain all cases of ocular neovascularization; instead there are multiple factors which can affect the various susceptible vessels. Among the known vasculognic factors are: inflammation and its products, a hypoxic retina diffusable factor, the "tumor angiogenic factor," and possibly an aging factor. The different ocular beds possess differing sensitivity to the various vasculogenic stimuli; the iris and choroid being most sensitive and the retina and ciliary body least sensitive to such stimuli. Retinal neovascularization requires both a biochemical factor and a diseased retinal vascular bed for its induction. Ocular neovascularization is a dynamic process which requires a persisting stimulus or else the new vessels tend to regress. The normal eye seems to possess at least two antivasculogenic agents.


What should be the Optimal Carotid Stent Opening Rate Without Post-Dilation?
There is not a widely accepted optimal rate of stent opening in patients underwent carotid artery stenting. In this study we evaluated the effect of carotid stent opening rate (CSOR) without performing post-dilation on in-hospital and long-term outcomes. A total of 825 patient patients underwent carotid artery stenting without post-dilation enrolled to the study. The patients divided into two groups according to their final CSOR (50% ≤ Post-stent deployment (SD) <80% and 80% ≤ Post-SD ≤ 100%). In-hospital and 3-year outcomes were compared between the groups. During hospitalization, the rate of ipsilateral stroke, major stroke and transient ischemic attacks were similar between the groups (respectively; 6.2% vs. 4.1, P = 0.190; 1.5% vs. 1.8, P = 0.811; 1.5% vs. 1.9%, P = 0.683). The 3-year Kaplan-Meier overall survival rates for the first and second groups were 87.6% and 84.4%, respectively (log rank test P = 0.426). The 3-year Kaplan-Meier overall cumulative ipsilateral stroke rates for the first and second groups were 88.0% and 88.6%, respectively (log rank test P = 0.409) CONCLUSION: Our study demonstrated that a CSOR higher than 50% without performing a post-dilation might be an effective therapeutic approach since there was not a significant difference regarding outcomes between the patients with a 50% ≤ Post-SD <80% and 80% ≤ Post-SD ≤ 100%. The need for post-stent balloon dilation might have been eliminated due to subsequent stent self-expansion.


Slower clozapine titration than the official Japanese protocol led to fewer inflammatory adverse effects: A retrospective chart review of seven hospitals.
Higher frequencies of inflammatory adverse effects of clozapine have been reported in Japan. As the international titration protocol for Asians has set slower dose titration than the Japanese package insert, we hypothesized that a dose titration speed slower than the recommendation of the guideline would be associated with fewer inflammatory-related adverse events. The medical records of all 272 patients who were first started on clozapine at seven hospitals between 2009 and 2023 were studied retrospectively. Of those, 241 were included in the analysis. The patients were divided into two groups regarding whether the titration speed was faster or slower than the guideline for Asians. The incidence of inflammatory adverse events with clozapine was compared between the groups. The frequency of inflammatory adverse events was 34 % (37/110) in the faster titration group and 13 % (17/131) in the slower titration group, and a significant difference was observed by Fisher exact test (odds ratio 3.38; 95 % confidence interval 1.71-6.91; p < 0.001). Serious adverse effects, fever for more than five days, and clozapine discontinuation were significantly more frequent in the faster titration group. Logistic regression analysis indicated significantly more inflammatory adverse events in the faster titration group (adjusted odds ratio 4.01; 95 % confidence interval 2.02-7.87; p < 0.001) considering age, sex, body mass index, concomitant valproic acid, and smoking as confounding factors. Clozapine-induced inflammatory adverse events were less frequent in Japanese individuals when a titration rate was more gradual than the protocol recommended in the Japanese package insert.


Effect of Fenton pretreatment combined with bacterial inoculation on humification characteristics of dissolved organic matter during rice straw composting.
The main purpose of this study was to explore the effects of Fenton pretreatment combined with bacterial inoculation on humification characteristics of dissolved organic matter (DOM) during rice straw composting. Three treatment groups (Fenton pretreatment: FeW, Fenton pretreatment and bacterial inoculation: FeWI, control: CK) were carried out during composting. The results showed that total organic carbon concentration of DOM and HIX showed an increase trend in all treatments in the composting process. The fungi that affect DOM conversion showed remarkable effects, meanwhile, fungal numbers of influencing DOM conversion were higher for FeWI than CK and FeW. The contribution rate of fungi to DOM was greater than that of environmental factors in FeWI composting, while environmental factors accounted for a large proportion in FeW and CK composting. This study exhibits referential significance for the effective degradation of agricultural wastes.


Management of recurrent malignant pleural effusion with chemical pleurodesis.
Malignant pleural effusion is a common complication of primary and metastatic pleural malignancies. It is usually managed by drainage and pleurodesis, but there is no consensus as to the best method of pleurodesis. We compared the effectiveness, side effects, and cost of different chemical pleurodesis agents used in patients with malignant pleural effusion. Between January 1990 and December 2001, 108 patients with malignant pleural effusion underwent chemical pleurodesis in our department. Thoracoscopy was performed in 64 patients (59%), a minithoracotomy in 18 (17%), tube thoracostomy in 11 (10%), and a small-bore catheter was inserted in 15 (14%). Talc was used in 68 (63%) patients, tetracycline in 26 (24%), and bleomycin in 14 (13%). Talc was instilled by insufflation during surgery after drainage, whereas tetracycline and bleomycin were instilled via tube or catheter for pleural analgesia. Talc resulted in significantly earlier tube and catheter removal, after an average 4.1 days versus 5.1 days after tetracyline, and 6.3 days after bleomycin (P = 0.026, P = 0.001, respectively). A significantly lower reaccumulation ratio in 90 days was achieved by the talc group, with nine (13.2%) patients, representing an 86.8% success rate, than in the tetracyline and bleomycin groups, with seven (26.7%) and five (35.7%) patients, respectively, representing 73.8% and 64.3% success rates (P = 0.04). Talc resulted in the earliest expansion, minimal drainage, and the earliest tube and catheter removal.


The avian pecten provides a potent substrate for growth and development of dissociated embryonic neural implants.
A cell suspension of the optic tecta of 3-day-old chick embryos was injected into the vitreal chamber of 2-day-old posthatch chicks. After a 14-21-day survival period, examination of eyeballs showed that all implants survived and, in 50% of cases, were attached to the pecten. The implants had proliferated and showed a laminated pattern of organization, with small cells in the superficial regions and large cells in the deep regions of the implant. The implants also contained a well-developed neuropil with mature synapses. The host retina was not affected by the presence of the implant. We suggest that the avian pecten represents a highly amenable structure for studies involving the response(s) by damaged retinae to neural implants.


Recombinant human parathyroid hormone synthesized in Escherichia coli. Purification and characterization.
Recombinant human parathyroid hormone (hPTH) was expressed in Escherichia coli harboring a plasmid containing a synthetic human parathyroid hormone gene under the control of the E. coli lac promoter. Three major forms of the hormone were isolated by acid extraction and purified to homogeneity by high performance liquid chromatography. By amino acid analysis and NH2-terminal sequencing, these were identified as hPTH-(1-84), formyl-methionyl-hPTH-(1-84), and hPTH-(8-84). The recombinant hPTH-(1-84) was immunologically indistinguishable from a World Health Organization standard of extracted native hPTH-(1-84). Recombinant hPTH-(1-84) was also bioactive in renal and skeletal adenylate cyclase assays. In the skeletal bioassay performed in UMR 108 osteosarcoma cells its activity was identical to that of an hPTH-(1-84) standard. In this bioassay, formyl-methionyl-hPTH-(1-84) had 10% of the activity of hPTH-(1-84) and hPTH-(8-84) was inactive. The results demonstrate the importance of isolating hPTH-(1-84) from other recombinant forms and metabolites to achieve full hormonal bioactivity and indicate that purified recombinant hPTH-(1-84) can thereby be obtained which should be a useful source of hormone for both basic and clinical studies.


Two new phenylethanoid glycosides from Ginkgo biloba leaves and their tyrosinase inhibitory activities.
Two undescribed phenylethanoid glycosides, Ginkgoside C (1) and D (2), together with ten known glycosides (3-12) were isolated from Ginkgo biloba leaves. Their structures were characterized by physical data analyses such as NMR, HRESIMS, as well as chemical hydrolysis. All compounds were tested for their tyrosinase inhibitory activities. At a concentration of 25 μM, compounds 2, 4, 5, 6, and 11 showed obvious mushroom tyrosinase inhibition activities, with %inhibition values of 19.12 ± 2.59%, 25.79 ± 1.83%, 16.07 ± 1.07%, 24.46 ± 1.10%, 18.64 ± 3.62%, respectively, with kojic acid used as the positive control (27.50 ± 2.72%).


Levels of mitochondrial reactive oxygen species increase in rat neuropathic spinal dorsal horn neurons.
Reactive oxygen species (ROS) are toxic agents that may be involved in various neurodegenerative diseases. Recent studies indicate that ROS are also involved in persistent pain through a spinal mechanism. Since the major source of ROS in neurons is mitochondria, mitochondrial ROS generation was examined in dorsal horn neurons of neuropathic rats. Neuropathic rats were produced by L5 spinal nerve ligation and mitochondrial ROS was detected by the mitochondrial marker, Mitotracker Red CM-H(2)XRos (MT-Red). Neurons were identified immunohistochemically for the neuronal marker NeuN. The number of MT-Red positive cells was increased 60-100% in the neuropathic dorsal horn. Approximately 75-85% of MT-Red positive cells were neurons. These data suggest that increased mitochondrial ROS in dorsal horn neurons may contribute to central sensitization in neuropathic rats.


Impact of renal function on treatment options and outcomes in advanced non-small cell lung cancer.
Certain chemotherapeutic agents commonly used for advanced non-small cell lung cancer (NSCLC) require minimum threshold renal function for administration. To determine how such requirements affect treatment options, we evaluated renal function patterns in this population. We performed a single-center retrospective analysis of patients treated for stage IV NSCLC from 2000 to 2007. Associations between patient characteristics, calculated creatinine clearance (CrCl), and clinical outcomes were determined using univariate and multivariate analyses, Cox proportional hazard models, and mixed model analysis. 298 patients (3930 creatinine measurements) were included in the analysis. Patients had a median of 5 (interquartile range [IQR] 4-18) Cr measurements. Median baseline CrCl was 96 mL/min (IQR 74-123 mL/min); median nadir CrCl was 78 mL/min (IQR 56-100mL/min). Renal function was associated with age (P<0.001), race (P=0.009), and gender (P=0.001). 23% of patients had a recorded CrCl<60 mL/min (threshold for cisplatin), with median onset 83 days after diagnosis and median time to recover to ≥60 mL/min of 27 (IQR 3-85) days; 11% of patients had a recorded CrCl<45 mL/min (threshold for pemetrexed), with median onset 122 days after diagnosis and median recovery time of 36 (IQR 3-73) days. For both thresholds, approximately 35% of patients had no documented recovery. In this cohort of patients treated for stage IV NSCLC, renal function falls below commonly used thresholds for cisplatin and for pemetrexed in fewer than a quarter of patients. However, these declines may preclude administration of these drugs for prolonged periods.


The use of milrinone in neonates with persistent pulmonary hypertension of the newborn - a randomised controlled trial pilot study (MINT 1).
To assess the impact of milrinone administration on time spent on nitric oxide (iNO) in infants with acute pulmonary hypertension (aPH). We hypothesized that intravenous milrinone used in conjunction with iNO would reduce the time on iNO therapy and the time spent on invasive ventilation in infants ≥34 weeks gestation with a diagnosis of aPH. We aimed to assess the practicality of instituting the protocol and contributing to a sample size calculation for a definitive multicentre study. This was a multicentre, randomized, double-blind, two arm pilot study, with a balanced (1:1) allocation. Infants with a gestation ≥34 weeks and a birth weight ≥2000 grams aPH, an oxygenation index of ≥10, and commenced on iNO were eligible. Participants on iNO were assigned to either a milrinone infusion (intervention) or a normal saline infusion (placebo) for up to 35 h. The primary outcome was time on iNO and feasibility of conducting the protocol. The trial was terminated early after 4 years of enrollment due to poor recruitment. Four infants were allocated to the intervention arm and 5 to the placebo arm. The groups were well matched for baseline variables. No differences were seen in any of the primary or secondary outcomes. Conducting an interventional trial in the setting of acute pulmonary hypertension in infants is not feasible using our current approach. Future studies in this area require alternative trial design to improve recruitment as this topic remains understudied in the neonatal field. www.isrctn.com ; ISRCTN:12949496; EudraCT Number:2014-002988-16.


Characters of coagulase-negative staphylococci and micrococci from cases of endocarditis.
Strains of coagulase-negative staphylococci and micrococci submitted to a reference laboratory from 137 cases of endocarditis over a 5 year period were reviewed. Staphylococcus epidermidis biotype 1 (SII) was the commonest biotype in all groups of patients but exceeded 80 per cent in the 61 patients who had undergone prosthetic valve surgery and the 16 patients who had undergone other forms of surgery. Biotype 4 (SVI) was recovered from 10 of the 34 patients without surgery. Strains from prosthetic valve endocarditis were frequently resistant to many antibiotics while strains from natural valve endocarditis were frequently sensitive to all, or resistant only to penicillin. The value of bacteriophage typing was confirmed.


High-pressure liquid chromatographic separation of the naturally occurring toxicants myristicin, related aromatic ethers and falcarinol.
The naturally occurring toxicants myristicin, twelve related aromatic ethers and the toxic acetylenic alcohol, falcarinol, were separated from one another by high-pressure liquid chromatography (HPLC). The technique employed a microparticulate nitrile phase column and used heptane and tetrahydrofuran as the eluting solvents. Preparative HPLC with 5-micrometer silica allowed isolation of gram quantities of parsleyapiole and dillapiole from extracts of plain parsley seeds and dill seeds, respectively. Commercially available myristicin as well as other aromatic ethers were also purified in gram quantities with the preparative column.


Controlled release of insect sex pheromones from paraffin wax and emulsions.
Paraffin wax and aqueous paraffin emulsions can be used as controlled release carriers for insect sex pheromones for mating disruption of orchard pests. Paraffin can be applied at ambient temperature as an aqueous emulsion, adheres to tree bark or foliage, releases pheromone for an extended period of time, and will slowly erode from bark and biodegrade in soil. Pheromone emulsions can be applied with simple spray equipment. Pheromone release-rates from paraffin were measured in laboratory flow-cell experiments. Pheromone was trapped from an air stream with an adsorbent, eluted periodically, and quantified by gas chromatography. Pheromone release from paraffin was partition-controlled, providing a constant (zero-order) release rate. A typical paraffin emulsion consisted of 30% paraffin, 4% pheromone, 4% soy oil, 1% vitamin E, 2% emulsifier, and the balance water. Soy oil and vitamin E acted as volatility suppressants. A constant release of oriental fruit moth pheromone from paraffin emulsions was observed in the laboratory for more than 100 days at 27 degreesC, with release-rates ranging from 0.4 to 2 mg/day, depending on the concentration and surface area of the dried emulsion. The use of paraffin emulsions is a viable method for direct application of insect pheromones for mating disruption. Sprayable formulations can be designed to release insect pheromones to the environment at a rate necessary for insect control by mating disruption. At temperatures below 38 degreesC, zero-order release was observed. At 38 degreesC and higher, pheromone oxidation occurred. A partition-controlled release mechanism was supported by a zero-order pheromone release-rate, low air/wax partition coefficients, and pheromone solubility in paraffin.


Case for implant platform unswitching.
Platform switching was introduced to reduce marginal bone loss and therefore maintain the gingival architecture, leading to a more favorable esthetic result. In the patient presented, recession had resulted in the exposure of the implant neck and threads; this was managed with a custom-made additional prosthetic component. The result, although not ideal esthetically, provided an implant abutment interface that was easier for the patient to clean.


Member characteristics, participation, and interests: Public Health Nutrition Practice Group.
A survey was developed to assess the level of participation and the membership interests of the Public Health Nutrition Practice Group (PHNPG). Forty-six percent (500 members) returned a completed survey. More than 80% of members believe PHNPG to be their main professional practice area "home" within the Council on Practice structure. Members overwhelmingly viewed practice group contributions as a responsibility, with personal career benefits being of secondary importance. Reading the practice group's newsletter and voting in elections were major areas of involvement. However, willingness to contribute time was a positive finding. Areas of interest and issues of greatest concern were identified. Results of the survey can be used to prepare long-range plans for PHNPG. Membership involvement in practice group activities is the key to an increase in re-enrollments and in new memberships.


Rett Syndrome: A Tale of Altered Genetics, Synaptic Plasticity, and Neurodevelopmental Dynamics.
Rett syndrome (RTT) is a neurodevelopmental disorder that is a leading cause of severe cognitive and physical impairment. RTT typically occurs in females, although rare cases of males with the disease exist. Its genetic cause, symptoms, and clinical progression timeline have also become well-documented since its initial discovery. However, a relatively late diagnosis and lack of an available cure signify that our understanding of the disease is incomplete. Innovative research methods and tools are thereby helping to fill gaps in our knowledge of RTT. Specifically, mouse models of RTT, video analysis, and retrospective parental analysis are well-established tools that provide valuable insights into RTT. Moreover, current and anticipated treatment options are improving the quality of life of the RTT patient population. Collectively, these developments are creating optimistic future perspectives for RTT.


NTproBNP-guided drug treatment for chronic heart failure: design and methods in the "BATTLESCARRED" trial.
How best to decide when to introduce drugs and what doses are optimal in individual patients with chronic heart failure (CHF), is unclear. We will determine whether titration of drug treatment according to plasma NTproBNP is superior regarding clinical outcomes to intensive standardised clinical assessment; whether either of the regimens noted above is superior to usual care; and whether age alters the relative efficacy of NTproBNP guided treatment. We will randomise 360 patients, stratified by age, to drug treatment directed by plasma NTproBNP, to intensive standardised clinical assessment, or to usual care. The primary outcome is total mortality, and secondary outcomes include death plus hospital admission for any cardiovascular event plus episodes of outpatient decompensated heart failure. Analyses will be conducted at the end of one and two years. 308 patients have been recruited, the majority being in NYHA functional class II, 60.6% being >75 years. The entry plasma NTproBNP level is 238, 50-1250 pmol/l, median and range, approximately 400-11,000 pg/ml. We describe details of a study to test the potential utility of serial measurements of NTproBNP in adjusting the drug treatment of patients with CHF. Projected completion date is 2007.


Surgical management of intraocular lens dislocations.
To report and compare the surgical, visual, and anatomical outcomes following treatment of dislocated intraocular lenses (IOLs). The medical records of 28 eyes of 28 patients were evaluated. Age, gender, pre-and postoperative best-corrected visual acuity (BCVA), surgical methods, and complications were recorded. Pre-and postoperative BCVA ranged from counting fingers to 20/32 and from counting fingers to 20/25, respectively. Late-onset dislocations were the most frequently observed complication. The most frequent surgical method was IOL repositioning in 15 of 28 patients, followed by IOL exchange in 11 patients, and IOL removal in 2 patients. Only 1 patient required surgical re-intervention with IOL capture. Visual acuity improved following the use of either IOL repositioning or IOL exchange. No superiority of one method over the other was observed. In the present retrospective case series, management of dislocated IOLs with repositioning or exchange of the primary implant conferred comparable surgical and visual outcomes.


Bluetooth-Enabled Implantable Cardiac Monitors and Two-Way Smartphone Communication for Patients With Hypertrophic Cardiomyopathy.
Sudden cardiac death (SCD) risk stratification in hypertrophic cardiomyopathy (HCM) currently relies on arrhythmic burden quantification by 24 or 48-hour Holter monitoring. Whether this approach adequately captures arrhythmic burden, compared with longer-term continuous monitoring, is unclear. We sought to assess the long-term incidence of nonsustained ventricular tachycardia (NSVT) in HCM patients at low or moderate SCD risk, using implantable cardiac monitors (ICMs) paired with a novel Bluetooth-enabled 2-way communication platform. This prospective, single-arm, observational study enrolled 33 HCM patients. Patients were implanted with an Abbott (Chicago, IL) Confirm Rx ICM and monitored using a protocolized care pathway. A total of 20 patients (60.6%) had ≥ 1 episode of NSVT recorded on the ICM, the majority of whom had previous Holter monitors that did not identify NSVT (60%, n = 12). A total of 71 episodes of NSVT were detected. Median time to first NSVT detection was 76.5 days (range: 0-553 days). A total of 19 patients underwent primary prevention implantable cardioverter defibrillator implantation during an average follow-up of 544 days (range: 42-925 days). A total of 172,112 automatic transmissions were received, and 65 (0.04%) required clinical follow-up. A total of 325 manual transmissions were received and managed. A total of 14 manual transmissions (4.3%) required follow-up, whereas 311 (95.7%) were managed solely with a text message. Surveillance and reporting systems utilizing 2-way communication enabled by novel ICMs are feasible and allow remote management of patients with HCM. Prolonged monitoring with ICMs identified more patients with nonsustained arrythmias than did standard Holter monitoring. In many cases, this information impacted both SCD risk stratification and patient management.


Australian Council on Healthcare Standards surveyor recommendations: analysis of compliance in the medical services.
This article reports on an analysis of hospitals surveyed by the Australian Council on Healthcare Standards (ACHS) in 1990. The major areas found to require further attention within the medical services were quality assurance processes, mechanisms for appointments and delineation of clinical privileges and some lines of communication with other hospital staff/departments. Similar results also were found in an earlier ACHS analysis of 216 hospitals surveyed 1987-1989. Despite the highlighted areas of concern, 70% of medical services recommendations made at earlier surveys had been fully implemented and 15% partially implemented by hospitals at the time of their next survey in 1990.


Why Othering should be considered in research on health inequalities: Theoretical perspectives and research needs.
•Othering is relevant to public health as an analytical lens that helps to understand the link between minority status and health inequalities.•To investigate health inequalities caused by Othering, it is necessary to include the semantic-symbolic construction of Others.•Othering operates as a discursive practice and occurs on multiple levels.•Research on Othering requires consideration of intersectionality and power structures derived from socially and historically grown hierarchies.•Interventions against Othering require deconstructive concepts - this means deconstructing the institutionalized and embodied normality of the We.


Lullaby: A Novel Algorithm to Extract Fetal QRS in Real Time Using Periodic Trend Feature.
Fetal heart rate (fHR) is an important indicator for monitoring of fetal cardiac health and development. The widely-used method based on ultrasound, however, is not continuous and often requires an expert to perform; thus, it is mostly used in clinics during checkups. The advances in wearable technology have paved the way for home assessment of fHR via the extraction of the mother's abdominal electrocardiogram (ECG) acquired by novel patches. Several methods have been developed for such; however, the computation is either too slow for real-time monitoring or too heavy to be performed in a wearable. In this work, we develop and validate the Lullaby algorithm - a novel method for fetal QRS extraction from aECG. The results showed that Lullaby is almost 7 times faster than existing methods with a better F1-score of 0.815, holding promise to transform perinatal monitoring.


Evolution of Voice Quality in Type 1-2 Transoral CO2 Laser Cordectomy: A Prospective Comparative Study.
To compare the 12-month evolution of voice quality outcomes in patients who benefited from types 1-2 transoral CO2 laser cordectomy (TLC) for an early-stage vocal fold squamous cell carcinoma (VFSCC). Prospective uncontrolled study. Sixty patients with cT1 VFSCC were consecutively recruited from a single medical center. Thirty patients benefited from type 1 TLC, while type 2 TCL was performed in 30 patients. The following voice quality outcomes were evaluated at baseline, 3-, 6-, and 12-month post-TLC: voice handicap index (VHI), GRBAS, speech rate, maximum phonation time (MPT), and acoustic parameters. Voice quality evolution was compared between type 1 and type 2 TLC. Fifty-seven patients completed the evaluations. Type 1 TLC patients reported significant improvements of VHI, grade of dysphonia, and breathiness at 3-, 6-, and 12-month post-TLC. Speech rate and jitter values improved 6- and 12-month post-TLC. A few voice quality outcomes reported 3- or 6-month post-TLC improvements in type 2 TLC group, while VHI, grade of dysphonia improved at 6- and 12-month post-TLC. MPT significantly decreased at 6- and 12-month post-TLC, while there were no acoustic measurement changes in type 2 TLC. The effect of TLC on voice quality may depend on the type of TLC. Type 1 TLC was associated with faster voice quality improvements compared with type 2 TLC. VHI and dysphonia grade were identified as the most relevant tool of voice changes irrespective to the TLC type. 3 Laryngoscope, 132:1421-1426, 2022.


Low seroprevalence and zero incidence rate of hepatitis E in men who have sex with men during a hepatitis A outbreak.
Hepatitis E virus (HEV) and hepatitis A virus (HAV) are both secreted in feces. Despite HEV transmission in Europe is mainly zoonotic, person-to-person transmission has not been completely excluded. Men who have sex with men (MSM) constitute a high-risk group for HAV mostly due to oral sex. We investigated the potential transmission of HEV during an acute hepatitis A (AHA) outbreak mainly affecting MSM. One hundred and two patients were diagnosed with AHA. Sixty-nine (68%) self-reported to be MSM, 75% of whom had high-risk sexual behaviors and 46% had suffered previous sexually transmitted diseases. We collected serum from 85 (83%) patients during AHA. HEV-IgG seroprevalence was not different among MSM (7%) compared with non-MSM (8%) patients. Two patients had positive anti-HEV-IgM, but all samples tested negative for HEV-RNA. These results suggest that HEV does not spread by sexual contact or person-to-person in our area.


A 2-year study of Candida-associated denture stomatitis treatment in aged care subjects.
To test the efficacy of two methods of treatment for denture stomatitis in aged care institutions. Candida-associated denture stomatitis has been associated with a lack of denture hygiene. Sixty subjects with denture stomatitis were randomly divided into three groups: sodium hypochlorite denture soak, microwaving and control. Both methods of treatment were carried out on a nightly basis for 1 week, excepting the control group. Standardised photographs of the palate and microbial samples of palate, upper and lower dentures were taken before and after treatment. Both hypochlorite and microwave irradiation significantly reduced the numbers of Candida and aerobic bacteria on both dentures and both methods significantly reduced Candida on the palate. However, palatal aerobic bacteria were not significantly reduced by either method and the controls showed insignificant changes at all three sites for both Candida and aerobes. While both methods of denture disinfection were successful, except for the counts of palatal aerobic bacteria, three independent observers of the clinical photographs had difficulty in identifying the controls but were more successful with the treatments. The raters also showed that there was no difference between both methods of disinfection and this agreed with the microbiological analysis.


Lack of association between DRD3 gene polymorphism and response to clozapine in Turkish schizoprenia patients.
It is hypothesized that molecular components of dopaminergic system, especially the dopamine D3 receptor gene (DRD3), may play a crucial role in the pathophysiology of schizophrenia, because it is abundant in the limbic system of the brain and it binds antipsychotic drugs. Several groups attempted to find an association between a serine-to-glycine polymorphism of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. In this study, we aimed to investigate the relationship of the Serine/Glycine polymorphism of the DRD3 gene with therapeutic response to clozapine treatment between Turkish schizophrenia patients (N = 92) and healthy controls (N = 100). Genotype groups were comparable in BPRS, SAPS, SANS analysis of response to clozapine. Our results suggest that an association between the Ser/Gly polymorphism of DRD3 gene and response to clozapine in Turkish schizophrenia patients is unlikely to exist.


Survival rates of patients hospitalized in French burns units during 1985.
This survey analyses data from 17 French burn units with respect to age, severity of injury and survival of patients admitted to hospital during 1985. Of the 2398 patients treated, more than half were between 15 and 50 years old. About 90 per cent of the patients had burns covering less than 50 per cent of the body surface area. The overall mortality rate was 11.8 per cent. The LD50 for the 2398 patients was a burned surface area of approximately 60 per cent of the total body surface area. The LD50 for patients less than 30 years old was a burn covering just over 80 per cent of the total body surface. The survival rate as a function of the Baux index was also analysed.


Melanocytoma in the orbital apex.
We report a case of a 49-year-old man presenting with a melanocytoma located in the orbital apex. The tumor was subtotally removed and adjuvant chemotherapy was given. The patient has remained under follow-up for the past 12 years without any evidence of recurrence. Although the characteristic neuroradiological images of the lesion prove the presence of melanin, histological examination is crucial to establish the diagnosis of melanocytoma. Besides the clinical and neuroradiological presentation, the histological, immunohistochemical, and ultrastructural findings are described. To our knowledge, this is the second published case of intraorbital melanocytoma initially confined to the orbital apex. Melanocytoma should be included in the differential diagnosis of intraorbital tumors in such a location.


Burden of cardiovascular disease attributable to particulate matter pollution in the eastern Mediterranean region: analysis of the 1990-2019 global burden of disease.
Particulate matter pollution is the most important environmental mediator of global cardiovascular morbidity and mortality. Air pollution evidence from the Eastern Mediterranean Region (EMR) is limited, owing to scarce local studies, and the omission from multinational studies. We sought to investigate trends of particulate matter (PM2.5)-related cardiovascular disease (CVD) burden in the EMR from 1990 to 2019. We used the 1990-2019 global burden of disease methodology to investigate total PM2.5, ambient PM2.5, and household PM2.5-related CVD deaths and disability-adjusted life years (DALYs) and cause-specific CVD mortality in the EMR. The average annual population-weighted PM2.5 exposure in EMR region was 50.3 μg/m3 [95% confidence interval (CI):42.7-59.0] in 2019, which was comparable with 199 048.1 μg/m3 (95% CI: 36.5-65.3). This was despite an 80% reduction in household air pollution (HAP) sources since 1990. In 2019, particulate matter pollution contributed to 25.67% (95% CI: 23.55-27.90%) of total CVD deaths and 28.10% (95% CI: 25.75-30.37%) of DALYs in the region, most of which were due to ischaemic heart disease and stroke. We estimated that 353 071 (95% CI: 304 299-404 591) CVD deaths in EMR were attributable to particulate matter in 2019, including 264 877 (95% CI: 218 472-314 057) and 88 194.07 (95% CI: 60 149-119 949) CVD deaths from ambient PM2.5 pollution and HAP from solid fuels, respectively. DALY's in 2019 from CVD attributable to particulate matter was 28.1% when compared with 26.69% in 1990. The age-standardized death and DALY rates attributable to air pollution was 2122 per 100 000 in EMR in 2019 and was higher in males (2340 per 100 000) than in females (1882 per 100 000). The EMR region experiences high PM2.5 levels with high regional heterogeneity and attributable burden of CVD due to air pollution. Despite significant reductions of overall HAP in the past 3 decades, there is continued HAP exposure in this region with rising trend in CVD mortality and DALYs attributable to ambient sources. Given the substantial contrast in disease burden, exposures, socio-economic and geo-political constraints in the EMR region, our analysis suggests substantial opportunities for PM2.5 attributable CVD burden mitigation.


Active metabolite of the neurotoxic rodenticide bromethalin along with anticoagulant rodenticides detected in birds of prey in the northeastern United States.
Little is known about the ecologic fate of the neurotoxic rodenticide bromethalin, which is currently registered for use in the United States, Canada, and other countries including Australia. There is minimal research on bromethalin's potential to cause secondary toxicosis in nontarget wildlife. The aim of this study was to evaluate adipose tissue in four species of birds of prey presented to a wildlife clinic in Massachusetts, USA, for desmethylbromethalin (DMB), the active metabolite of bromethalin. Birds were also screened for anticoagulant rodenticides (ARs) in liver tissue to present a more complete picture of rodenticide exposures in this geographic area and to evaluate the impact of current mitigation measures in place during the time of sampling, 2021-2022. A total of 44 hawks and owls were included; DMB was found in 29.5% of birds and ARs were present in 95.5%. All birds with DMB detections also had residues of ARs. Among birds positive for ARs, 81% had two or more compounds. To the authors' knowledge the data presented here represent the first published monitoring study to document bromethalin/DMB bioaccumulation in obligate carnivores. As DMB is a more potent neurotoxicant than its parent compound, these results are cause for concern and an indication that further monitoring and study of the potential risk of bromethalin to wildlife species is needed. These findings have global implications as increasing concern regarding exposure to and toxicosis from ARs in nontarget wildlife worldwide leads to a search for alternatives and effective mitigation approaches.


Single-nanoparticle phase transitions visualized by four-dimensional electron microscopy.
The advancement of techniques that can probe the behaviour of individual nanoscopic objects is of paramount importance in various disciplines, including photonics and electronics. As it provides images with a spatiotemporal resolution, four-dimensional electron microscopy, in principle, should enable the visualization of single-nanoparticle structural dynamics in real and reciprocal space. Here, we demonstrate the selectivity and sensitivity of the technique by visualizing the spin crossover dynamics of single, isolated metal-organic framework nanocrystals. By introducing a small aperture in the microscope, it was possible to follow the phase transition and the associated structural dynamics within a single particle. Its behaviour was observed to be distinct from that imaged by averaging over ensembles of heterogeneous nanoparticles. The approach reported here has potential applications in other nanosystems and those that undergo (bio)chemical transformations.


Disease in the Pld4thss/thss Model of Murine Lupus Requires TLR9.
Phospholipase D4 (PLD4) is an endolysosomal exonuclease of ssRNA and ssDNA, rather than a phospholipase as its name suggests. Human polymorphisms in the PLD4 gene have been linked by genome-wide association studies to systemic sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. However, B6.129 Pld4-/- mice develop features of a distinct disease, macrophage activation syndrome, which is reversed in mice mutated in TLR9. In this article, we compare a Pld4 null mutant identified on the BALB/c background, Pld4thss/thss, which has distinct phenotypes: short stature, thin hair, and features of systemic lupus erythematosus. All phenotypes analyzed were largely normalized in Pld4thss/thssTlr9-/- mice. Thus, Pld4thss/thss represents a rare model in which mouse lupus etiology is TLR9 dependent. Compared with PLD4-deficient B6 mice, Pld4thss/thss mice had elevated levels of serum IgG, IgG anti-dsDNA autoantibodies, BAFF, and IFN-γ and elevated B cell numbers. Overall, the data suggest that PLD4 deficiency can lead to a diverse array of rheumatological abnormalities depending upon background-modifying genes, and that these diseases of PLD4 deficiency are largely driven by TLR9 recognition of ssDNA.


Improved MIN6 β-cell function on self-assembled peptide amphiphile nanomatrix inscribed with extracellular matrix-derived cell adhesive ligands.
Understanding the role of the pancreatic extracellular matrix (ECM) in supporting islet survival and function drives the pursuit to create biomaterials that imitate and restore the pancreatic ECM microenvironment. To create an ECM mimic holding bioinductive cues for β-cells, self-assembled peptide amphiphiles (PAs) inscribed with four selected ECM-derived cell adhesive ligands are synthesized. After 7 days, compared to control groups cultured on biologically inert substrates, MIN6 β-cells cultured on PAs functionalized with YIGSR and RGDS cell adhesive ligands exhibit elevated insulin secretion in responses to glucose and also form β-cell clusters. These findings suggest that the self-assembled PA nanomatrix may be utilized to improve pancreatic islet transplantation for treating type 1 diabetes.


Upregulation of HB-EGF, Msx.1, and miRNA Let-7a by administration of calcitonin through mTOR and ERK1/2 pathways during a window of implantation in mice.
Successful implantation of embryos requires endometrial receptivity. Calcitonin is one of the factors influencing the implantation window. This study aimed to evaluate calcitonin effects on endometrial receptivity. To this end, the effects of calcitonin on the implantation window in the ovarian stimulation and the normal ovarian cycle were investigated by the morphological study of the endometrium as well as the expression of MSX.1, HB-EGF, and micro-RNA (miRNA) Let-7a; then the mechanisms of calcitonin effects were studied through the mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways. A total of 64 Bulb/c mice were divided into two groups: Normal ovarian cycle and ovarian stimulation. Each group consisted of four subgroups: Ctrl, CT, PP242, and CT + PP242. Calcitonin and PP242 were injected on the fourth day of pregnancy and 24 hr later all the mice were killed. Uterine tissue samples were used for morphological analysis and the endometrial epithelial and the stromal cells were isolated from myometrium for evaluation of gene and protein expression. Ovarian stimulation increased the phosphorylation levels of mTOR and ERK1/2 and the expression of miRNA Let-7a. Calcitonin injection increased the expression of HB-EGF, Msx.1, and miRNA Let-7a in a normal ovarian cycle and in ovarian-stimulated mice. It also increased eukaryotic initiation factor 4E-binding protein 1 and ERK1/2 phosphorylation in normal ovarian cycles. Calcitonin improved the receptivity of the uterine endometrium by upregulation of the HB-EGF, Msx.1, and miRNA Let-7a likely through mTOR and ERK1/2 signaling pathway.