Peroxiredoxin System of Aspergillus nidulans Resists Inactivation by High Concentration of Hydrogen Peroxide-Mediated Oxidative Stress.
Most eukaryotic peroxiredoxins (Prxs) are readily inactivated by a high concentration of hydrogen peroxide (H₂O₂) during catalysis owing to their "GGLG" and "YF" motifs. However, such oxidative stress sensitive motifs were not found in the previously identified filamentous fungal Prxs. Additionally, the information on filamentous fungal Prxs is limited and fragmentary. Herein, we cloned and gained insight into Aspergillus nidulans Prx (An.PrxA) in the aspects of protein properties, catalysis characteristics, and especially H₂O₂ tolerability. Our results indicated that An.PrxA belongs to the newly defined family of typical 2-Cys Prxs with a marked characteristic that the "resolving" cysteine (CR) is invertedly located preceding the "peroxidatic" cysteine (CP) in amino acid sequences. The inverted arrangement of CR and CP can only be found among some yeast, bacterial, and filamentous fungal deduced Prxs. The most surprising characteristic of An.PrxA is its extraordinary ability to resist inactivation by extremely high concentrations of H₂O₂, even that approaching 600 mM. By screening the H₂O₂-inactivation effects on the components of Prx systems, including Trx, Trx reductase (TrxR), and Prx, we ultimately determined that it is the robust filamentous fungal TrxR rather than Trx and Prx that is responsible for the extreme H₂O₂ tolerence of the An.PrxA system. This is the first investigation on the effect of the electron donor partner in the H₂O₂ tolerability of the Prx system.


Malarial hepatitis.
To study the clinical, biochemical and histopathological changes in the liver of patients of Plasmodium falciparum malaria with jaundice. This study was conducted on 50 PBF confirmed cases of Plasmodium falciparum malaria with jaundice. Detailed history, clinical examination, biochemical parameters for liver function test and blood for hepatitis B and C was done in all patients. Liver biopsy was done for detailed histopathological examination in all the 20 patients having serum bilirubin between 3 to 10 mg%. All patients were treated by IV/oral quinine using standard regimen. Age of the patient was ranging from 15-45 years. All patients had jaundice, 70% had pallor, 56% had splenomegaly, 48% had hepatomegaly and 24% of cases had coma. Based on serum bilirubin level, the patients were categorized in group A (18 patients, serum bilirubin < 3 mg%), in group B (20 patients, serum bilirubin 3-10 mg%) and in group C (12 patients, serum bilirubin >10 mg%). Histopathological examination done in all the 20 patients of group B, showed evidence of swollen hepatocytes (100%), malarial pigment deposition (75%), inflammatory infiltrates (60%), congestion of hepatocyte (50%) alongwith centrizonal necrosis in 25% of cases. The evidence of predominant conjugated hyperbilirubinemia, increased levels of AST and ALT along with evidence of hepatocellular necrosis in histopathological examination are strong evidence of gross hepatocytic dysfunction in patients of Plasmodium falciparum malaria with jaundice. Therefore the term malarial hepatitis should not be taken as a misnomer.


TUNEL as a tumor marker of tongue cancer.
Squamous cell carcinoma (SCC) of the tongue has an increasing incidence, a high morbidity rate and a 50% 5-year mortality rate. We analyzed the rate of apoptosis using TDT-mediated dUTP-biotin nick end-labeling (TUNEL), p53 and heparanase in 73 patients with tongue cancer by immonohistochemistry, and tested data for correlation with survival, tumor size, grade and metastasis. TUNEL staining was strong in 54% of the tumors; the remainder lacked staining, as did all healthy control tissues. Significant correlations were found between TUNEL staining level and p53 expression rates (p=0.016) and between TUNEL and heparanase (p=0.039). Moreover, while the cumulative 5-year survival probability for tumors not stained for TUNEL and p53 was 63%, but dropped to 34% with TUNEL staining; for lack of TUNEL and heparanase (=0), 5-year survival rate was 50%, while staining presence (>0) reduced survival to 34%. TUNEL joins other biomarkers in indicating prognosis of understanding pathogenesis of tongue cancer.


Altered coupling of cerebral blood flow and functional connectivity strength in visual and higher order cognitive cortices in primary open angle glaucoma.
Primary open-angle glaucoma (POAG) has been suggested to be a neurodegenerative disease associated with altered cerebral vascular hemodynamics and widespread disruption of neuronal activity within the visual, working memory, attention and executive networks. We hypothesized that disturbed neurovascular coupling in visual and higher order cognitive cortices exists in POAG patients and correlates with glaucoma stage and visual field defects. Through multimodal magnetic resonance imaging, we evaluated the cerebral blood flow (CBF)-functional connectivity strength (FCS) correlations of the whole gray matter and CBF/FCS ratio per voxel for all subjects. Compared with normal controls, POAG patients showed reduced global CBF-FCS coupling and altered CBF/FCS ratios, predominantly in regions in the visual cortex, salience network, default mode network, and dorsal attentional network. The CBF/FCS ratio was negatively correlated with glaucoma stage, and positively correlated with visual field defects in the lingual gyrus in POAG patients. Moreover, early brain changes were detected in early POAG. These findings indicate neurovascular coupling dysfunction might exist in the visual and higher order cognitive cortices in POAG patients and its clinical relevance. The results may contribute to the monitoring of POAG progression and provide insight into the pathophysiology of the neurodegenerative process in POAG.


One-pot synthesis of phthalazines and pyridazino-aromatics: a novel strategy for substituted naphthalenes.
A new one-pot strategy for the synthesis of phthalazines and pyridazino-aromatics starting from aromatic aldehydes has been developed. A variety of substituents ranging from electron withdrawing to donating is tolerated furnishing the desired 1,2-diazine in good to excellent yields. The products have been applied to the bidentate Lewis acid catalyzed inverse electron-demand Diels-Alder (IEDDA) reaction opening a novel two-step entry into substituted naphthalenes, such as Naproxen.


Stance foot alignment and hand positioning alter star excursion balance test scores in those with chronic ankle instability: What are we really assessing?
The literature has consistently shown that the Star Excursion Balance Test (SEBT) is a reliable and valid tool to anticipate the risk of lower extremity injury, assess dynamic postural control differences among groups, and assess the effectiveness of balance training programs in both healthy individuals and people with lower extremity injuries. However, there is no standard administration technique for the SEBT in research, clinical practice, or performance settings. Therefore, the purpose of this investigation was to compare six different combinations (3 different foot alignments × 2 hand positions) on the SEBT performance in those with chronic ankle instability (CAI). Repeated Measures Design. University Research Laboratory. Twenty-five university students with CAI (12 males, 13 females; age: 20.3 ± 2.4 years, height: 172.7 ± 7.4 cm, weight: 77.5 ± 15.3 kg. 25.9 ± 4.0 kg/m2) voluntarily participated in the study. Six different SEBT positions were used to assess dynamic postural control. Three foot positions: 1) Foot centered; 2) Toe fixed; and 3) Toe-heel changing and two hand placements: 1) Hands free and 2) Hands on the hips were used in this study. After 6familiarization trials for each condition, three Star Excursion Balance Test scores were recorded. Normalized reach distance (% of leg length) in the anterior, posteromedial, and posterolateral directions as well as a composite reach score quantified dynamic postural control. Both foot alignment and hand position significantly altered normalized SEBT reach distance in the anterior (p < 0.003), posteromedial (p < 0.001), posterolateral (p < 0.001), and composite reach scores (p < 0.001). Different foot alignments and hand constraints significantly altered normalized reach distances and the composite score in individuals with CAI. These results do not suggest that any combination of foot alignments and/or hand constraints is superior. However, changing the toe/heel position, while maintaining hands on the hips, may provide the best standardization for clinicians and researchers.


Relationship between type of surgical clerkship, order of completion, and achievement on patient management problems.
Complex cognitive skills, such as interpretation of information and problem solving, are essential for the practice of medicine. Patient management problems (PMPs) are used by both medical school faculty and certifying boards to measure higher-order cognitive skills. This study investigates two questions that relate to PMPs. Whether there is a difference among students in their achievement on PMPs that may be attributed to their clinical experience is examined. In addition, the effect of the order in which PMPs are taken is evaluated. For the purpose of this study, three PMPs were developed measuring three different areas of surgical problem solving. One hundred four third-year medical students who took their surgery clerkship during a 9-month period in 1982 were examined. Students were randomly assigned to one of three rotations for an 8-week period. At the end of the rotation, they each took three PMPs in random order. The multivariate analysis of variance procedure was used to examine the hypothesis of no relationship between clinical rotation and order of completion. The proficiency score for each PMP was considered the dependent variable. There was no difference in performance between groups rotating in different clinical surgical settings (multivariate F (6186) = 0.67; p = 0.67.) This suggests that generalization occurs with patient management and problem-solving skills. Statistically significant differences were found between groups on the basis of the order in which they took the PMPs (multivariate F (6186) = 4.07; p less than 0.001.) There are several plausible explanations for this finding. One explanation is that all three problems were difficult. As a result, students' perceptions about their performance on each problem may have influenced their performance on subsequent problems. Another explanation is that motivation to achieve may have diminished with time. These data suggest that there are basic management skills that may be taught in a variety of surgical experiences. Care must be taken in the use of the PMP as a tool for evaluation so that noneducational factors such as order do not play a role in the results.


[The epidermoid tumor of the lateral cerebral ventricle; report of a case (author's transl)].
The authors report a case of epidermoid tumor of the lateral ventricle. Epidermoid tumors are relatively uncommon intracranial lesions and the one situated in the lateral ventricle has not been reported in this country. A 42 year old house wife was admitted to Asahi Central Hospital on February 14, 1973, complaining of progressive right hemiparesis for 2 years. The patient had no headache and no other symptoms of increased intracranial pressure. Neurological examination revealed disorientation, dyscalculia, amnestic aphasia, morter dysphasia, right facial paresis (central type) and right hemiparesis. The laboratory findings, which included complete blood count, serum electrolytes, urinalysis, electrocardiogram and blood Wassermann, were normal. Initial pressure of the spinal tap was 410 mmH2O and crystal clear CSF was obtained. tplain craniogram showed no calcification and was normal. The left CAG showed clearly the signs of the temporal lobe tumor (Fig. 1, 2, 3, 4.), but showed no early veins and no tumor stains. The brain scintigram was normal. A left temporo-parietooccipital craniotomy was performed. The epidural Echogram (horizontal section-Fig. 5, coronall section-Fig. 6) revealed the clear demarcated, multicystic round tumor in the inferior horn of the left lateral ventricle. After the whitesoap like tumor was totaly removed, the all interior surface of the left inferior horn of the lateral ventricle was seen (Fig. 8). Tumor was 5.5 cm in diameter and 50 g in weight. Histological findings of the tumor showed typical epidermoid (Fig. 9, 10). The origin of the intravetricular epidermoids and the usefulness of echo-encephalorgaphy were briefly discussed.


Characterisation of a SAT-1 outbreak of foot-and-mouth disease in captive African buffalo (Syncerus caffer): clinical symptoms, genetic characterisation and phylogenetic comparison of outbreak isolates.
African buffalo (Syncerus caffer) play an important role in the maintenance of the SAT types of foot-and-mouth disease (FMD) in southern Africa. These long-term carriers mostly become sub-clinically infected, maintaining the disease and posing a threat to other susceptible wildlife and domestic species. During an unrelated bovine tuberculosis experiment using captive buffalo in the Kruger National Park (KNP), an outbreak of SAT-1 occurred and was further investigated. The clinical signs were recorded and all animals demonstrated significant weight loss and lymphopenia that lasted 100 days. In addition, the mean cell volume and mean cell haemoglobin values were significantly higher than before the outbreak started. Virus was isolated from several buffalo over a period of 167 days post infection and the molecular clock estimated to be 3 x 10(-5) nucleotide substitutions per site per day. Seven amino acid changes occurred of which four occurred in hypervariable regions previously described for SAT-1. The genetic relationship of the outbreak virus was compared to buffalo viruses previously obtained from the KNP but the phylogeny was largely unresolved, therefore the relationship of this outbreak strain to others isolated from the KNP remains unclear.


The retinal tyrosine kinome of diabetic Akimba mice highlights potential for specific Src family kinase inhibition in retinal vascular disease.
Although anti-VEGF therapies have radically changed clinical practice, there is still an urgent demand for novel, integrative approaches for sight-threatening retinal vascular diseases. As we hypothesize that protein tyrosine kinases are key signaling mediators in retinal vascular disease, we performed a comprehensive activity-based tyrosine kinome profiling on retinal tissue of 12-week-old Akimba mice, a translational model displaying hallmarks of early and advanced diabetic retinopathy. Western blotting was used to confirm retinal tyrosine kinase activity in Akimba mice. HUVEC tube formation and murine organotypic choroidal sprouting assays were applied to compare tyrosine kinase inhibitors with different specificity profiles. HUVEC toxicity and proliferation were evaluated using the CellTox™ Green Cytotoxicity and PrestoBlue™ Assays. Our results indicate a shift of the Akimba retinal tyrosine kinome towards a hyperactive state. Functional network analysis of significantly hyperphosphorylated peptides and upstream kinase prediction revealed a central role for Src-FAK family kinases. Western blotting confirmed hyperactivity of this signaling node in the retina of Akimba mice. We demonstrated that not only Src but also FAK family kinase inhibitors with different selectivity profiles were able to suppress angiogenesis in vitro and ex vivo. In the latter model, the novel selective Src family kinase inhibitor eCF506 was able to achieve potent reduction of angiogenesis, comparable to the less specific inhibitor Dasatinib. None of the tested compounds demonstrated acute endothelial cell toxicity. Overall, the collected findings provide the first comprehensive overview of retinal tyrosine kinome changes in the Akimba model of diabetic retinopathy and for the first time highlight Src family kinase inhibition using highly specific inhibitors as an attractive therapeutic intervention for retinal vascular pathology.


HIV proteins absent from placentas of 75 HIV-1-positive women studied by immunohistochemistry.
Recent epidemiological and virological data suggest that the incidence of maternofetal transmission of HIV-1 infection is between 20 and 30%. The available evidence points to a possible role of peri- and postnatal contamination, but the isolation of HIV from fetuses shows that transplacental transmission also occurs. We attempted to detect, by means of an immunohistochemical method, HIV proteins in frozen placentas from 75 HIV-1-positive women (30 at term, 45 induced abortions). In addition, in situ hybridization using HIV-specific probes was performed in three cases. Neither HIV proteins nor nucleic acid sequences were detected, but CD4+ mononuclear cells were present in the chorion and villi, regardless of the clinical and biological status of the mother (particularly in the nine cases in which the infants were infected). There are several possible mechanisms involving the placenta in the maternofetal transmission of HIV, including active transport of the HIV-immunoglobulin G complex via Fc receptors on trophoblastic cells, passive transplacental passage of HIV during a viraemic episode, the passage of infected maternal cells, and infection of the placenta itself. The methods we used could not rule out the presence of HIV DNA provirus within the genome of placental cells. In any event, immunohistochemical detection of HIV proteins in the placenta is not a technique suitable for the prenatal diagnosis of HIV infection or for identifying newborns likely to develop HIV infection.


Behavior of a supercooled chalcogenide liquid in the non-Newtonian regime under steady vs. oscillatory shear.
The steady and oscillatory shear rate dependence of viscosity of a supercooled chalcogenide liquid of composition As10Se90 is measured at Newtonian viscosities ranging between 103 and 107 Pa s using capillary and parallel plate rheometry. The liquid displays strong violation of the Cox-Merz rule in the non-Newtonian regime where the viscosity under steady shear is nearly an order of magnitude lower than that under oscillatory shear. This behavior is argued to be related to the emergence of unusually large (6-8 nm) cooperatively rearranging regions with long relaxation times in the liquid that result from significant structural rearrangements under steady shear.


[Estimation and allocation of water environmental capacity in nonpoint source polluted river].
Based on the investigation of the application and emission quantities (QAE) of total nitrogen (TN) and total phosphorus (TP) for nonpoint sources in river catchment' s area, included fertilizer applications, livestock and living pollutants emissions, the quantities of TN and TP entered the river were computed by means of export coefficient model in Changle River, southeast China. Self-purification capacities of TN and TP in the reach were also estimated in terms of input-output balance analysis method. According to the provisions of water function planning in the river, the water environment residual capacity (WERC) or the demand for reducing the application and emission (DRAE) of nitrogen and phosphorus in the corresponding catchment were monthly estimated, and WERC and DRAE were respectively allocated among the pollution sources. Results indicated that about 28.8% of TN loads and 51.2% of TP loads could be self-purified respectively in the reach, i. e., purification of 775.9 t a(-1) for TN and 30.9 t a(-1) for TP. Seasonal variations of the self-purification for the pollutants not only resulted from riverine hydrological and ecological conditions, but also affected by the pollution loading. According to the demand of the water quality protection in the reach, about 1581.0 t a(-1) QAE of TN had to reduce in Changle catchment. The maximum demand for the reducing QAE of TN was the fertilizer application (1047.4 t a(-1)), and the highest ratio for the reducing QAE of TN was livestock-poultry breeding (32.4%). There was about 2335.7 t a(-1) WERC for TP in the reach. The largest DRAE of nitrogen was during mid-water season and the least WERC of TP was during higher-water season.


Identification of RISC-associated adenoviral microRNAs, a subset of their direct targets, and global changes in the targetome upon lytic adenovirus 5 infection.
Adenoviruses encode a set of highly abundant microRNAs (mivaRNAs), which are generated by Dicer-mediated cleavage of the larger noncoding virus-associated RNAs (VA RNAs) I and II. We performed deep RNA sequencing to thoroughly investigate the relative abundance of individual single strands of mivaRNA isoforms in human A549 cells lytically infected with human adenovirus 5 (Ad5) at physiologically relevant multiplicities of infection (MOIs). In addition, we investigated their relative abundance in the endogenous RNA-induced silencing complexes (RISCs). The occupation of endogenous RISCs by mivaRNAs turned out to be pronounced but not as dominant as previously inferred from experiments with AGO2-overexpressing cells infected at high MOIs. In parallel, levels of RISC-incorporated mRNAs were investigated as well. Analysis of mRNAs enriched in RISCs in Ad5-infected cells revealed that only mRNAs with complementarity to the seed sequences of mivaRNAs derived from VA RNAI but not VA RNAII were overrepresented among them, indicating that only mivaRNAs derived from VA RNAI are likely to contribute substantially to the posttranscriptional downregulation of host gene expression. Furthermore, to generate a comprehensive picture of the entire transcriptome/targetome in lytically infected cells, we determined changes in cellular miRNA levels in both total RNA and RISC RNA as well, and bioinformatical analysis of mRNAs of total RNA/RISC fractions revealed a general, genome-wide trend toward detargeting of cellular mRNAs upon infection. Lastly, we identified the direct targets of both single strands of a VA RNAI-derived mivaRNA that constituted one of the two most abundant isoforms in RISCs of lytically infected A549 cells. Viral and cellular miRNAs have been recognized as important players in virus-host interactions. This work provides the currently most comprehensive picture of the entire mRNA/miRNA transcriptome and of the complete RISC targetome during lytic adenovirus infection and thus represents the basis for a deeper understanding of the interplay between the virus and the cellular RNA interference machinery. Our data suggest that, at least in the model system that was employed, lytic infection by Ad5 is accompanied by a measurable global net detargeting effect on cellular mRNAs, and analysis of RISC-associated viral small RNAs revealed that the VA RNAs are the only source of virus-encoded miRNAs. Moreover, this work allows to assess the power of individual viral miRNAs to regulate cellular gene expression and provides a list of proven and putative direct targets of these miRNAs, which is of importance, given the fact that information about validated targets of adenovirus-encoded miRNAs is scarce.


Thiamine-deficient infant formula: what happened and what have we learned?
In 2003, a thiamine-deficient soy infant formula was produced in Germany and marketed exclusively in Israel. Between October and November 2003, infants with encephalopathy were admitted to several intensive care units in Israel and were later diagnosed as suffering from thiamine deficiency. The soy formula consumed by these children was found to be the cause of these admissions. A Medline search using the terms 'thiamine deficiency' and 'formula' or 'feeding' without year limit identified relevant published data on that event. Newspapers from Israel were screened from November 2003 until April 2011. On November 2003, 2-6% of infants in Israel consumed this formula. The consumption of this thiamine-deficient formula was associated with the death of 3 infants and with more than 20 infants manifesting neurologic damage. In this report, we summarize the chain of events, the neurologic outcome, and discuss the lessons needed to be learned from this sad event. Based on difficulties in diagnosis of subtle deficiencies, we suggest that apparent history of safe use is not a reliable source for establishing adequate intake. Infant formulae can be produced or imported only under stringent criteria with the manufacturer/importer having total responsibility for the product.


Emergency management in the early phase.
An overview of response management in the early phase of an emergency at a nuclear installation is provided from a systems approach. This starts with the recognition of response goals, and using detailed analyses of threats, past experience, international law and principles, a response strategy is developed. The process is illustrated for the case of severe accidents at pressurized water reactors (PWRs) and identifies the need for and nature of: emergency classification based on plant conditions, notification, radiological monitoring and assessment strategies, operational criteria for implementing protective action decisions and management of public information. From the strategy detailed, functional and infrastructure requirements can be defined. The paper also presents some reflections on the key differences between response to emergencies arising from accidents and those arising from deliberate acts; on the preparedness and response capabilities of States, highlighting areas where generic improvements are needed and how best to achieve that.


Mitochondrial pathways, permeability transition pore, and redox signaling in cardioprotection: therapeutic implications.
Reperfusion therapy is the indispensable treatment of acute myocardial infarction (AMI) and must be applied as soon as possible to attenuate the ischemic insult. However, reperfusion is responsible for additional myocardial damage likely involving opening of the mitochondrial permeability transition pore (mPTP). A great part of reperfusion injury occurs during the first minute of reperfusion. The prolonged opening of mPTP is considered one of the endpoints of the cascade to myocardial damage, causing loss of cardiomyocyte function and viability. Opening of mPTP and the consequent oxidative stress due to reactive oxygen and nitrogen species (ROS/RNS) are considered among the major mechanisms of mitochondrial and myocardial dysfunction. Kinases and mitochondrial components constitute an intricate network of signaling molecules and mitochondrial proteins, which interact in response to stressors. Cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning (PostC), obtained with brief intermittent ischemia or with pharmacological agents, which drastically reduce the lethal ischemia/reperfusion injury. The protective pathways converging on mitochondria may preserve their function. Protection involves kinases, adenosine triphosphate-dependent potassium channels, ROS signaling, and the mPTP modulation. Some clinical studies using ischemic PostC during angioplasty support its protective effects, and an interesting alternative is pharmacological PostC. In fact, the mPTP desensitizer, cyclosporine A, has been shown to induce appreciable protections in AMI patients. Several factors and comorbidities that might interfere with cardioprotective signaling are considered. Hence, treatments adapted to the characteristics of the patient (i.e., phenotype oriented) might be feasible in the future.


A new immunochemical purity test for clinical dextran. Methodology and studies on clinical dextran preparations.
A simple immunochemical procedure, based on reversed single radial immunodiffusion (RSRI) was developed to detect commonly occurring traces of antigenic contaminants in clinical dextran. High-titred antisera against non-dextran components of Leuconostoc mesenteroides NRRL B512 were produced and served as analytical reagents. Dextran samples were incorporated into a gel layer. Presence of contaminants is revealed by precipitate formation following application of antiserum to a well cut into the gel. Antigenic contaminants can be detected in concentrations exceeding 10 ppm by the Leuconostoc-RSRI test. Screen results on 119 clinical dextran samples from manufactures in different countries disclosed presence of antigen traces in 82% of preparations. Introduction of the new test and improved purification measures at Pharmacia AB resulted in purer clinical dextran with negative RSRI test scores in 99% of batches produced. Only batches passing this test are released for clinical use. Although no direct correlation was found between contaminant levels and incidence of dextran reactions, antigenic contaminants may play a contributory role in elicitation of mild reactions.


Analysis of DNA fragmentation of porcine embryos exposed to cryoprotectants.
The chemical toxicity of cryoprotectants to porcine embryos was examined by the evaluation of survival and DNA damage after exposure to cryoprotectants. Porcine blastocysts were exposed to 10% of ethylene glycol (EG), 1,2-propanediol (PD) or glycerol (GLY) for 1 h at room temperature (23-25 degrees C) and then cultured in vitro for 24 h. The survival rates of blastocysts exposed to PD and GLY were significantly lower than those of control blastocysts in which the embryos were exposed to carrier solution without cryoprotectants. Significantly more DNA-fragmented nuclei occurred in the cryoprotectant-exposed blastocysts, compared with the control blastocysts. Moreover, the indices of DNA-fragmented nuclei in the blastocysts without blastocoele re-formation after culture were significantly higher than those with blastocoele re-formation, irrespective of the exposure treatment. These results indicate that the exposure of porcine blastocysts to cryoprotectant decreases the survival rates and increases the DNA-fragmented nuclei in embryos.


Normal and abnormal embryonic development of the anorectum in human embryos.
In the literature, some controversy still exists about the normal and abnormal development of the human anorectum. Therefore, a three-dimensional and histological study was performed on human embryos. In early anorectal development (< or = 49 days postfertilization), the cloaca plays a crucial role, separated from the amniotic cavity by its cloacal membrane. In the cloaca, the yolk sac/primitive hindgut and allantois/primitive urogenital sinus enter. During the embryonic caudal folding process, incorporation of these structures occurs, including their surrounding extraembryonic mesoderm, which fuses to form the urorectal septum. Consequently, this septum does not grow in the direction of the cloacal membrane, and fusion of these structures is likewise never observed. The cloaca remains as such until the cloacal membrane ruptures by apoptotic cell death. The dorsal part of the cloaca then becomes part of the amniotic cavity, and is by no means involved in the development of the anorectum. The tip of the urorectal septum will become the perineal area. Soon after rupture of the cloacal membrane, during late anorectal development (> or = 49 days postfertilization), a secondary occlusion of the anorectal canal occurs, first due to adhesion, followed by formation of an epithelial "plug" at the level of the anal orifice. Recanalization, by apoptotic cell death, of this secondary occluded anal orifice occurs later during development. Based on these embryological observations, congenital anorectal malformations with an abnormal communication to the exterior are best explained as early embryonic defects. The abnormal communications, usually called fistulae, should be regarded as ectopic anal orifices. Anorectal malformations with the anus in normal position are best explained as late embryonic defects.


[Special characteristics of topical treatment in childhood].
Although the barrier function and thickness of the stratum corneum is fully developed in newborns, the infant shows numerous differences in cutaneous and systemic metabolism of topically applied substances in comparison to adults. This discrepancy between children and adults has been explained by the greater systemic availability due to the greater surface area to weight ratio in children. Several topically applied drugs such as hexachlorophene, phenol, salicylic acid and boric acid in high concentration or on large areas have caused toxic reactions and fatalities in infants. Therapeutic approaches to childhood dermatoses differ from these used in adults. These age-dependent differences concerning the topical application of glucocorticosteroids, urea and dyes are described for the treatment of atopic eczema. The development of innovative topical drugs may extend therapeutic options especially in children as shown by a new topical anesthetic cream improving the treatment of mollusca contagiosa, a common childhood problem. Finally, certain physiological differences should be considered in newborn and infant skin care.


Risk of prostate cancer death after radical radiotherapy with neoadjuvant and adjuvant therapy with bicalutamide or gonadotropin-releasing hormone agonists.
Oncological outcome after radical radiotherapy (RRT) combined with neoadjuvant and adjuvant androgen suppression therapy (AST) may differ according to type of AST. The aim of this nationwide register-based study was to investigate risk of prostate cancer (Pca) death after different neoadjuvant and adjuvant ASTs; (i) bicalutamide, (ii) gonadotropin-releasing hormone agonists (GnRH) or (iii) combined bicalutamide and GnRH (CAB), together with RRT. Data for 6882 men diagnosed with high-risk Pca between 2007 and 2020 and treated with primary RRT was retrieved from Prostate Cancer data Base Sweden (PCBaSe) 5.0. Time to Pca death according to type of neoadjuvant and adjuvant AST was assessed by use of Kaplan-Meier plots and Cox proportional hazard models adjusted for putative confounders. Data were stratified by RRT type since the effect of AST in risk of Pca death differed according to type of RRT. Compared with the reference RRT combined with neoadjuvant CAB/adjuvant GnRH, risk of Pca death for men treated with CAB/bicalutamide and conventionally fractionated external beam radiotherapy (CF-EBRT) was hazard ratio (HR) 0.73 (95% CI: 0.50-1.04), hypofractionated EBRT (HF-EBRT), HR 1.35 (95% CI: 0.65-2.81) and EBRT with high dose rate brachytherapy (EBRT-HDRBT), HR 0.85 (95% CI: 0.37-1.95). Risk of Pca death for men treated with bicalutamide/bicalutamide and: (i) CF-EBRT was HR 2.35 (95% CI: 1.42-3.90), (ii) HF-EBRT, HR 0.70 (95% CI: 0.26-1.85), (iii) HF-EBRT, HR 4.07 (95% CI: 1.88-8.77) vs the reference. In this observational study, risk of Pca death between men receiving different combinations of AST varied according to RRT type. No difference was found in risk of Pca death for men treated with bicalutamide or GnRH as adjuvant therapy to RRT following neoadjuvant CAB. Risk of Pca death was increased for men with monotherapy neo-/adjuvant bicalutamide in combination with CF-EBRT or EBRT-HDRBT.


Livestock metabolomics and the livestock metabolome: A systematic review.
Metabolomics uses advanced analytical chemistry techniques to comprehensively measure large numbers of small molecule metabolites in cells, tissues and biofluids. The ability to rapidly detect and quantify hundreds or even thousands of metabolites within a single sample is helping scientists paint a far more complete picture of system-wide metabolism and biology. Metabolomics is also allowing researchers to focus on measuring the end-products of complex, hard-to-decipher genetic, epigenetic and environmental interactions. As a result, metabolomics has become an increasingly popular "omics" approach to assist with the robust phenotypic characterization of humans, crop plants and model organisms. Indeed, metabolomics is now routinely used in biomedical, nutritional and crop research. It is also being increasingly used in livestock research and livestock monitoring. The purpose of this systematic review is to quantitatively and objectively summarize the current status of livestock metabolomics and to identify emerging trends, preferred technologies and important gaps in the field. In conducting this review we also critically assessed the applications of livestock metabolomics in key areas such as animal health assessment, disease diagnosis, bioproduct characterization and biomarker discovery for highly desirable economic traits (i.e., feed efficiency, growth potential and milk production). A secondary goal of this critical review was to compile data on the known composition of the livestock metabolome (for 5 of the most common livestock species namely cattle, sheep, goats, horses and pigs). These data have been made available through an open access, comprehensive livestock metabolome database (LMDB, available at http://www.lmdb.ca). The LMDB should enable livestock researchers and producers to conduct more targeted metabolomic studies and to identify where further metabolome coverage is needed.


Fast-Converging Simulated Annealing for Ising Models Based on Integral Stochastic Computing.
Probabilistic bits (p-bits) have recently been presented as a spin (basic computing element) for the simulated annealing (SA) of Ising models. In this brief, we introduce fast-converging SA based on p-bits designed using integral stochastic computing. The stochastic implementation approximates a p-bit function, which can search for a solution to a combinatorial optimization problem at lower energy than conventional p-bits. Searching around the global minimum energy can increase the probability of finding a solution. The proposed stochastic computing-based SA method is compared with conventional SA and quantum annealing (QA) with a D-Wave Two quantum annealer on the traveling salesman, maximum cut (MAX-CUT), and graph isomorphism (GI) problems. The proposed method achieves a convergence speed a few orders of magnitude faster while dealing with an order of magnitude larger number of spins than the other methods.


Descriptive epidemiology of malignant tumors in Ethiopian Jews immigrating to Israel, 1984-89.
This descriptive epidemiological study analyzes the frequency of cancer after the arrival of Ethiopian immigrants as reported to the Israel Cancer Registry from 1984 to 1989. The study cohort comprised 8,272 individuals (estimated 4,253 males and 4,019 females) with 27,966 and 26,848 person-years observed for males and females, respectively. Overall cancer incidence in this migrant cohort was low for both genders compared to cancer incidence among Jews born in Israel. The standardized incidence ratio (SIR) (in percentage) for cancers at all sites was 39 [95% confidence interval (CI) = 22-64] and 63 (95% CI = 41-92) for males and females, respectively. Male primary liver cancer and female thyroid cancer had high SIRs. All other sites had either average or low SIRs. No cases of neoplasms were reported in the respiratory system. Except for primary liver cancer, digestive neoplasms had an inverse male: female ratio.


Naturally occurring circadian rhythm and sleep duration are related to executive functions in early adulthood.
Experimental sleep deprivation studies suggest that insufficient sleep and circadian misalignment associates with poorer executive function. It is not known whether this association translates to naturally occurring sleep patterns. A total of 512 of full-term-born members of the Arvo Ylppö Longitudinal Study [mean age = 25.3, standard deviation (SD) = 0.65] (44.3% men) wore actigraphs to define sleep duration, its irregularity and circadian rhythm (sleep mid-point) during a 1-week period (mean 6.9 nights, SD = 1.7). Performance-based executive function was assessed with the Trail-Making Test, Conners' Continuous Performance Test and Stroop. The self-rated adult version of Behavior Rating Inventory of Executive Function was used to assess trait-like executive function. We found that performance-based and self-reported trait-like executive function correlated only modestly (all correlations ≤0.17). Shorter sleep duration associated with more commission errors. Later circadian rhythm associated with poorer trait-like executive function, as indicated by the Brief Metacognitive Index and the Behavior Regulation Index. Those belonging to the group with the most irregular sleep duration performed slower than others in the Trail-Making Test Part A. All associations were adjusted for sex, age, socioeconomic status and body mass index. In conclusion, naturally occurring insufficient sleep and later circadian rhythm showed modest associations with poorer executive function. Shorter habitual sleep duration was associated with lower scores of performance-based tests of executive function, and later circadian rhythm was associated mainly with poorer trait-like executive function characteristics. Our findings suggest additionally that sleep duration and circadian rhythm associate with different domains of executive function, and there are no additive effects between the two.


Design and synthesis of novel complexes containing N-phenyl-1H-pyrazole moiety: Ni complex as potential antifungal and antiproliferative compound.
Cu(II) (1), Ni(II) (2), Cr(III) (3) and Fe(III) (4) complexes with 3-acetyl-4-benzoyl-1-phenyl-1H-pyrazole (L1) were prepared and structurally characterized. Usual coordination of L1 was achieved through nitrogen of pyrazole moiety and carbonyl acetyl group. Electronic spectra of the complexes indicate that the geometry of the metal center was six coordinate octahedral. In vitro antimicrobial activity of the ligand and complex compounds was screened in terms of antibacterial effect on Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative) and antifungal effect on the fungi Aspergillus flavus and candida albicans using the modified Kirby-Bauer disc diffusion and minimum inhibitory concentrations (MIC) methods. Ni(II) complex (2) exhibited remarkable antifungal inhibition against Candida albicans equal to the standard antifungal agent. To continue our study some structural modifications are formed by adding 4-fluoro-benzoyl moiety to L1 in different forms to produce different ligands, 3-acetyl-4-(4-flourobenzoyl)-1-phenyl-1H-pyrazole (L2) and 3-[(3-acetyl-1-phenyl-1H-4-pyrazolyl)carbonyl]-1-phenyl-4-(4-flourobenzoyl)-1H-pyrazole (L3), Ni complexes (5 and 6) are prepared and comparable in vitro antimicrobial study is evaluated. In vitro cytotoxicity of the Ni(II) complex (2) is studied using MTT assay. The analysis of the cell test showed that (2) displayed quite small cytotoxic response at the higher concentration level which indeed would further enable us for more opportunities in therapeutic and biomedical challenges. Both of the capability as a potent in vitro antifungal agent and the cell test analysis show Ni(II) complex (2) as a promising material in the translation of observed in vitro biological phenomenon into clinical therapies settings.


Treatment and recurrence management of staphylococcal infections: community-acquired MRSA.
The increasing prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has resulted in a change in the paradigm for the treatment of skin and soft-tissue infections. The CA-MRSA strains are more likely to carry the genes for the Panton-Valentine leukocidin toxin and have increased susceptibility to non-beta-lactam antibiotics. As a result, a wide range of therapies is available for treatment of CA-MRSA infections. Relapses occur frequently and the optimal approach to eliminate colonization is not clear. This article reviews the therapeutic options for patients with presumed and definite MRSA infections, as well as for the prevention of relapses.


The Silk flow-diverter stent for endovascular treatment of intracranial aneurysms.
Flow diverter (FD) stents represent a new endovascular technique developed for the treatment of complex intracranial aneurysms (wide neck, fusiform, large, and giant aneurysms) that are challenging for classic endovascular techniques such as coiling, balloon-assisted coiling and stent-assisted coiling. Low porosity, high metal coverage, and high pore density are the main properties of FD stents. These properties induce hemodynamic changes redirecting the blood flow away from the aneurysm and into the parent artery leading to gradual thrombosis of the aneurysm. FD stents also provide scaffolding for subsequent neoendothelial proliferation, and vessel wall remodeling. This is considered as a paradigm shift compared to prior endovascular methods, which predominantly aimed at providing treatment inside the aneurysmal sac. This paper describes in detail the first released FD stent, the Silk flow-diverter stent (Balt Extrusion, Montmorency, France), its mechanism of action and deployment technique. It reviews the pertinent literature regarding safety, efficacy and potential risks and complications associated with the use of this stent.


Induced Disturbances Cause Monomorium pharaonis (Hymenoptera: Formicidae) Nest Relocation.
Budding and relocation of nests are important characteristics of the Pharaoh ant, Monomorium pharaonis (L.), an important pest of artificial structures. Pharaoh ant colony movements induced by several types of disturbances were evaluated in the laboratory. The percentages of workers and brood in the source and new nest sites were determined at Days 0, 1, 3, and 5 following physical disturbance (temporal removal of nestmates), chemical disturbance (application of pyrethroid insecticide), invasion by heterospecific ants, food depletion, and moisture depletion in the laboratory. All disturbances were performed in the source nest, which was connected to an empty new nest site. Almost all workers moved and carried the entire brood to the new nest site when subjected to physical disturbance, chemical disturbance, and ant invasion on Day 1, whereas only <5% of workers were present in the new nest site in the undisturbed control. After these disturbances, the brood was never relocated back to the original nest site in this 5-d study. When subjected to food depletion, ∼60% of the brood were found in the new nest site and ∼40% of the brood remained in the original nest on Day 5, resulting in a polydomous population. In contrast, moisture depletion did not show any significant effect on colony movement. These results provide useful information about the causes of Pharaoh ant colony budding and guidance about how to develop effective control and prevention strategies.


The Effect of Psychological Capital and Role Conflict on the Academic Entrepreneurial Intents of Chinese Teachers in Higher Education: A Study Based on the Theory of Planned Behavior.
Because academic entrepreneurship is an innovation driving force in China's economy, teachers are key knowledge creators in the process of entrepreneurship. Therefore, it is particularly important to give attention to the individual psychological mechanism factors at play in the process of teachers in higher education academic entrepreneurship. The purpose of this study is to identify individual psychological capital and role conflict issues among university teachers in China. To accomplish this aim, we investigated the emergence of positive academic entrepreneurial intents, continued through the process of academic entrepreneurship, and clarified the impact of psychological capital and role conflict on entrepreneurial intent. Based on the theory of planned behavior, we constructed a research model from the perspective of entrepreneurial intent prior to entrepreneurial action. We established a cohort of teachers in 17 higher education institutions (N = 525) in southern China, with psychological capital and role conflict as the prior independent variables and the teachers' academic entrepreneurial intent as the dependent variable. Using quantitative analysis, SPSS 22.0, and AMOS 23.0, we conducted reliability and validity tests, correlation analysis, and structural equation models on the collected data. We reached the following conclusions: (1) psychological capital has a positive effect on attitudes toward academic entrepreneurship; (2) psychological capital has a positive effect on perceived behavioral control; (3) role conflict has a negative effect on perceived behavioral control; (4) academic entrepreneurial attitudes have a positive effect on academic entrepreneurial intent; (5) perceived behavioral control has a positive effect on academic entrepreneurial intent; (6) subjective norms have a positive effect on academic entrepreneurial intent. We also provide some suggestions about academic entrepreneurship for university administrators.


Effects of prone position and positive end-expiratory pressure on lung perfusion and ventilation.
Prone positioning is frequently used during acute respiratory distress syndrome. However, mechanisms by which it improves oxygenation are poorly understood, as well as its interaction with positive end-expiratory pressure. This study was conducted to decipher the respective effects of positive end-expiratory pressure and posture during lung injury on regional lung ventilation, perfusion and recruitment assessed by positron emission tomography. Experimental study. Research laboratory of a university hospital. Six female piglets. After oleic acid-induced lung injury, all animals were studied in supine and prone position at both positive end-expiratory pressure 0 and positive end-expiratory pressure 10 cm H2O. In each experimental condition, regional lung perfusion and ventilation were assessed with positron emission tomograph using intravenous 15O-labeled water and inhaled nitrogen-13. Nonaerated lung weight was assessed with positron emission tomograph, and alveolar recruitment was defined as the difference of nonaerated lung weight between conditions. Positive end-expiratory pressure was associated with significant alveolar recruitment (130 +/- 85 and 65 +/- 29 g of lung in supine and prone position, respectively [p < 0.05 vs. 0]), whereas recruitment induced by posture was not statistically significant (77 +/- 97 g with positive end-expiratory pressure 0 and 13 +/- 19 g with positive end-expiratory pressure 10 [p > 0.05 vs. 0]). Regardless the posture, positive end-expiratory pressure redistributed both perfusion and ventilation toward dependent regions. Recruitment by positive end-expiratory pressure was restricted to dorsal regions in supine position, but extended diffusely along the ventral-to-dorsal dimension in prone position. Prone position was associated with recruitment in dorsal regions with concomitant derecruitment in ventral regions, magnitude of this being reduced by positive end-expiratory pressure. Prone position redistributed ventilation toward dorsal and ventral regions at positive end-expiratory pressure 0 and positive end-expiratory pressure, respectively. Finally, prone position redistributed perfusion toward ventral regions, to an extent amplified by positive end-expiratory pressure. Positive end-expiratory pressure and posture act synergistically by redistributing lung regional perfusion toward ventral regions, but have antagonistic effects on regional ventilation.


An assessment of HIV treatment outcomes among utilizers of semi-mobile clinics in rural Kenya.
HIV/AIDS is a major cause of morbidity and mortality in Africa, and rates of retention in treatment are low. Some research has shown that mobile clinics are effective in connecting people in rural areas with health care. We compared HIV outcomes between HIV-positive patients who chose to access treatment from a regional hospital to those who chose care in one of four semi-mobile clinics closer to where they live. The subjects for this analysis were HIV-positive residents in West Pokot accessing care at one of four semi-mobile sites (Kabichbich, Chepareria, Kacheliba, and Sigor) or at the regional hospital in Kapenguria. We examined four outcome variables between the two groups: (1) retention in HIV treatment, (2) change in CD4 count, (3) adherence to ARVs, and (4) deaths. The patients who chose semi-mobile clinic care were less well educated, poorer, and sicker than those who chose to continue care in the regional hospital. There were no statistically significant differences between the groups in any of the four outcome measures. Although the population of patients attending semi-mobile clinics was on average poorer and sicker than those attending the hospital, their outcomes were similar. Care at the semi-mobile clinics did not result in significantly different outcomes from care in the district hospital. This program showed that semi-mobile clinics are a viable alternative to hospital care for very ill, isolated populations, but further measures must be taken to improve retention and adherence in these settings.


Anti-candidal activity of essential oils alone and in combination with amphotericin B or fluconazole against multi-drug resistant isolates of Candida albicans.
Therapy for candidiasis is becoming problematic due to the toxicities of currently available antifungal agents and the increasing prevalence of resistance among the etiologic agents. Therefore, new antifungals and alternative approaches are needed. In this study, 20 fluconazole-resistant strains of Candida albicans were found to have varying levels of resistance to other azoles, i.e., itraconazole (MIC of 4-128 μg/ml) and ketoconazole (2-256 μg/ml). In addition, 13 of these isolates appeared resistant to amphotericin B (32-128 μg/ml). A total of 21 plant essential oils were screened for their antifungal activity against these multi-drug resistant isolates. The oils of Cymbopogon martini, i.e., citral and cinnamaldehyde, exhibited strong inhibitory activity with minimum inhibitory concentrations (MIC(50)) ranging from 90-100 μg/ml. The test oils were more effective than fluconazole and amphotericin B in inhibiting azole- and amphotericin B-resistant, as well as amphotericin B-susceptible isolates. The test oils and especially eugenol, exhibited significant synergy with fluconazole or amphotericin B against the test isolates. These findings suggest the possible effective use of certain oils alone or in combination with fluconazole or amphotericin B, against multi-drug resistant isolates of C. albicans.


Synthesis and reactivity of cationic triruthenium clusters derived from 2-methyl- and 4-methylpyrimidines: from conventional cyclometalated ligands to novel types of N-heterocyclic carbenes.
The methylation of the uncoordinated nitrogen atom of the cyclometalated triruthenium cluster complexes [Ru(3)(μ-H)(μ-κ(2)N(1),C(6)-2-Mepyr)(CO)(10)] (1; 2-MepyrH = 2-methylpyrimidine) and [Ru(3)(μ-H)(μ-κ(2)N(1),C(6)-4-Mepyr)(CO)(10)] (9; 4-MepyrH = 4-methylpyrimidine) gives two similar cationic complexes, [Ru(3)(μ-H)(μ-κ(2)N(1),C(6)-2,3-Me(2)pyr)(CO)(10)](+) (2(+)) and [Ru(3)(μ-H)(μ-κ(2)N(1),C(6)-3,4-Me(2) pyr)(CO)(10)](+) (9(+)), respectively, whose heterocyclic ligands belong to a novel type of N-heterocyclic carbenes (NHCs) that have the C(carbene) atom in 6-position of a pyrimidine framework. The position of the C-methyl group in the ligands of complexes 2(+) (on C(2)) and 9(+) (on C(4)) is of key importance for the outcome of their reactions with K[N(SiMe(3))(2)], K-selectride, and cobaltocene. Although these reagents react with 2(+) to give [Ru(3)(μ-H)(μ-κ(2)N(1),C(6)-2-CH(2)-3-Mepyr)(CO)(10)] (3; deprotonation of the C(2)-Me group), [Ru(3)(μ-H)(μ(3)-κ(3)N(1),C(5),C(6)-4-H-2,3-Me(2)pyr)(CO)(9)] (4; hydride addition at C(4)), and [Ru(6)(μ-H)(2){μ(6)-κ(6) N(1),N(1'),C(5),C(5'),C(6),C(6')-4,4'-bis(2,3-Me(2)pyr)}(CO)(18)] (5; reductive dimerization at C(4)), respectively, similar reactions with 9(+) have only allowed the isolation of [Ru(3)(μ-H)(μ(3)-κ(2)N(1),C(6)-2-H-3,4-Me(2)pyr)(CO)(9)] (11; hydride addition at C(2)). Compounds 3 and 11 also contain novel six-membered ring NHC ligands. Theoretical studies have established that the deprotonation of 2(+) and 9(+) (that have ligand-based LUMOs) are charge-controlled processes and that both the composition of the LUMOs of these cationic complexes and the steric protection of their ligand ring atoms govern the regioselectivity of their nucleophilic addition and reduction reactions.


Fecal impaction: a cause for concern?
Fecal impaction (FI) is a common cause of lower gastrointestinal tract obstruction lagging behind stricture for diverticulitis and colon cancer. It is the result of chronic or severe constipation and most commonly found in the elderly population. Early recognition and diagnosis is accomplished by way of an adequate history and physical examination in conjunction with an acute abdominal series. Prompt identification and treatment minimizes the risks of complications such as bowel obstruction leading to aspiration, stercoral ulcers, perforation, and peritonitis. Treatment options include gentle proximal softening in the absence of complete bowel obstruction, distal washout, and manual extraction. Surgical resection of the involved colon or rectum is reserved for cases of FI complicated by ulceration and perforation leading to peritonitis. Recurrence is common, and can be managed by increasing dietary fiber content to 30 gm/day, increased water intake, and discontinuation of medications that can contribute to colonic hypomotility.


Accuracy and definitive interpretation of preoperative technetium 99m sestamibi imaging based on the discipline of the reader.
Technetium 99m sestamibi scans have become a principal means of localizing parathyroid adenomas. Its accuracy and reliability has allowed for the proliferation of minimal access parathyroidectomy. Localizing interpretation of these scans often drives referral of hyperparathyroid patients for surgery. Interpretation of these scans may differ between nuclear medicine physicians and surgeons. We reviewed patients (N = 65) with digital images from an academic medical center with the diagnosis of primary hyperparathyroidism. We assessed the willingness to define an adenoma's location, the interrater reliability, and the accuracy of technetium (Tc-99m) sestamibi read by a surgeon and a nuclear medicine physician. There was poor correlation between both readers for assessment of quality of images (k = 0.54, 0.07) but very good correlation for adenoma location (k = 0.81). Both readers had good accuracy in predicting the location of the parathyroid adenoma. The surgeon was more likely to call a scan positive.


Regulation of the epidermal growth factor receptor by growth-modulating agents: effects of staurosporine, a protein kinase inhibitor.
Staurosporine is a potent microbial inhibitor of a number of protein kinases, including protein kinase C, cyclic AMP-dependent kinase, and the tyrosine kinase pp60src. We have used staurosporine to investigate the role of phosphorylation in the regulation of the epidermal growth factor (EGF) receptor in both human epidermal carcinoma A431 cells and mouse Swiss 3T3 fibroblasts. We report here that staurosporine treatment causes enhancement in high affinity EGF binding and a decrease in the phosphorylation state of the unstimulated receptor at a number of residues, including threonine 669. Staurosporine also antagonizes the inhibition of high affinity EGF binding and the increase in phosphorylation state of the unstimulated EGF receptor by phorbol esters and the calcium ionophore A23187. Staurosporine is an effective inhibitor of the EGF-stimulated receptor tyrosine kinase in vitro and thus does not enhance EGF stimulation of EGF receptor autophosphorylation in vivo. These results suggest that phosphorylation plays a major role in the regulation of the high affinity binding state of the EGF receptor in both unstimulated and mitogenically activated cells.


Breeding new forms of life: a critical reflection on extreme variances of bareback sex.
Many men who have sex with men (MSM) express feeling marginalized by discourses within public health and sexual health nursing that determine bareback sex is deviant and unsafe. Their resistance to risk-based discourses can be seen within radical sex practices such as deliberately becoming-infected with HIV (bug-chasing) and breeding-infection (gift-giving). The metaphors of bug-chasing and gift-giving, particularly those spread across global online spaces, can influence the sexual experiences and practices of MSM. A metaphor analysis was conducted of Internet forums discussing HIV chasing and gifting metaphors, and showed a variety of discursive meanings, tactics and effects to the radical sex practice. A radical research approach was used to explore the processes of becoming-infected and breeding-infection as determinant steps in the symbolic resistance of risk-based discourses, as well as the creation of new forms of life and community among MSM. Our analyses demonstrate how the gifting/chasing metaphors express MSM's marginalization as well as their lines of flight from having their practices captured within public health discourses. We hope to offer alternative nursing approaches for thinking through and engaging with transgressive and queer sexual practices.


Corollary Discharge and Oculomotor Proprioception: Cortical Mechanisms for Spatially Accurate Vision.
A classic problem in psychology is understanding how the brain creates a stable and accurate representation of space for perception and action despite a constantly moving eye. Two mechanisms have been proposed to solve this problem: Herman von Helmholtz's idea that the brain uses a corollary discharge of the motor command that moves the eye to adjust the visual representation, and Sir Charles Sherrington's idea that the brain measures eye position to calculate a spatial representation. Here, we discuss the cognitive, neuropsychological, and physiological mechanisms that support each of these ideas. We propose that both are correct: A rapid corollary discharge signal remaps the visual representation before an impending saccade, computing accurate movement vectors; and an oculomotor proprioceptive signal enables the brain to construct a more accurate craniotopic representation of space that develops slowly after the saccade.


Ultrastructural changes of the peritoneum in a rabbit model of peritoneal dialysis.
The number of patients with end-stage renal diseases treated with chronic dialysis is increasing over the last years. Long-term peritoneal dialysis is associated with progressive development of structural and functional alterations of peritoneal membrane. The aim of the study was to analyze ultrastructural alterations of mesothelial monolayer and submesothelial tissue in a modified nonuremic experimental model of peritoneal dialysis in rabbits. The study was performed on 5 healthy Chinchilla rabbits. Surgical procedures of implantation and removal of peritoneal catheter, prevention of catheter clothing, prevention of infection and dialysate instillation were performed according to previously described protocols. Peritoneal tissue samples were collected upon catheter placement and removal after a 5-week follow-up and processed for transmission electron microscopy (TEM) examination. The rabbits tolerated anesthesia, surgical procedure and the applied regimen of dialysate instillations well. The animals recovered completely and no adverse effects were noted. In the animals treated with peritoneal dialysis instillations, TEM revealed alterations of the mesothelial monolayer and submesothelial tissue. The mesothelial cells in direct contact with dialysis fluid were prone to shrinking. They lost the typical cobblestone morphology and assumed a flattened shape. The mesothelial cells were often detached from the basement membrane. These cells showed euchromatic nuclei, higher number of microvilli in their apical part and very numerous vesicles. A higher quantity of collagen fibers was noticed in the peritoneal lamina propria in close relation to the basement membrane of mesothelium. The nuclei of the fibroblasts were also euchromatic. Numerous mitochondria, granules and vesicles were present in their cytoplasm. The used rabbit model of peritoneal dialysis is simple, practical to perform, reproducible, not expensive and not requiring advanced devices. It is suitable for obtaining peritoneal tissue samples for histological examination and can be used to analyze the effects of dialysis solutions on the rabbit peritoneal membrane.


Natural infection by Paramphistomoidea Stiles and Goldberger, 1910 trematodes in wild Marsh Deer (Blastocerus dichotomus Illiger, 1815) from Sérgio Mottas's hydroelectric power station flooding area.
Studies on helminthfauna of marsh deer Blastocerus dichotomus Illiger, 1815 are rare, although helminthic diseases are an important cause of mortality in these animals. Fifteen male and female adult marsh deer from Sergio Motta's hydroelectric power station flooding area at Paraná River which died during the capture and quarantine procedures, between 1998 and 1999, were necropsied. Three trematodes species, Paramphistomum cervi, Balanorchis anastrofus and Zygocotyle lunatum, all belonging to superfamily Paramphistomoidea, were identified. The obtained trematodes were identified, counted and their respectives descriptors of infection were determined. All necropsied animals were infected by helminths. Paramphistomum cervi was the most prevalent species, while Zygocotyle lunatum was found in only one animal.


P(VDF-TrFE)/BaTiO3 Nanoparticle Composite Films Mediate Piezoelectric Stimulation and Promote Differentiation of SH-SY5Y Neuroblastoma Cells.
Poly(vinylidene fluoride-trifluoroethylene, P(VDF-TrFE)) and P(VDF-TrFE)/barium titanate nanoparticle (BTNP) films are prepared and tested as substrates for neuronal stimulation through direct piezoelectric effect. Films are characterized in terms of surface, mechanical, and piezoelectric features before in vitro testing on SH-SY5Y cells. In particular, BTNPs significantly improve piezoelectric properties of the films (4.5-fold increased d31 ). Both kinds of films support good SH-SY5Y viability and differentiation. Ultrasound (US) stimulation is proven to elicit Ca(2+) transients and to enhance differentiation in cells grown on the piezoelectric substrates. For the first time in the literature, this study demonstrates the suitability of polymer/ceramic composite films and US for neuronal stimulation through direct piezoelectric effect.


A common motif targets huntingtin and the androgen receptor to the proteasome.
Huntington disease derives from a critically expanded polyglutamine tract in the huntingtin (Htt) protein; a similar polyglutamine expansion in the androgen receptor (AR) causes spinobulbar muscular atrophy. AR activity also plays an essential role in prostate cancer. Molecular mechanisms that regulate Htt and AR degradation are not well understood but could have important therapeutic implications. We find that a pentapeptide motif (FQKLL) within the Htt protein regulates its degradation and subcellular localization to cytoplasm puncta. Disruption of the motif by alanine substitution at the hydrophobic residues increases the steady state level of the protein. Pulsechase analyses indicate that the motif regulates degradation. A similar motif (FQNLF) has corresponding activities in the AR protein. Transfer of the Htt motif with five flanking amino acids on either side to YFP reduces the steady state YFP level by rendering it susceptible to proteasome degradation. This work defines a novel proteasome-targeting motif that is necessary and sufficient to regulate the degradation of two disease-associated proteins.


[Midterm Outcomes of Root Replacement Using Homograft for Aortic Valve Infective Endocarditis].
From August 2003 to June 2013, 9 patients with aortic valve endocarditis underwent aortic root replacement using homografts which were harvested and preserved in our institute. The median patient age was 62 years (range 46~84) and 5 patients were men. Four cases were prosthetic valve infections. The in-hospital mortality was 0%. In 8 of 9 cases were evaluated on midterm outcomes. At a median of 52 months (range 19~156), overall survival was 100%, freedom from cardiovascular events was 87.5%. The peak aortic pressure gradient was 9.04 ± 4.2 mmHg. Aortic regurgitation was less than 2 of 4 in all cases.


Spontaneous and experimental malignancies in non-human primates.
Contrary to earlier established opinion that tumors in monkeys are found rarely, now the large material confirms that monkey tumors are frequent phenomenon. Tumor incidence clearly increases with age. Frequencies of benign and malignant tumors of various locations and histogenesis are slightly different. Tumors of hematopoietic system are the most frequent. Sporadic cases and enzootic outbreaks of lymphomas are described for different kinds of monkeys, including apes, and probably are caused by viruses. Two viruses were isolated by us from sick monkeys - the retrovirus C-type STLV-1 and the herpes virus papio HVP. Inoculation of virus cultures into monkeys and rabbits induces neoplasms. Monkey neoplasms can be induced by exposure to various chemical agents, and by oncogenic and non-oncogenic viruses. There is no strict species specificity of tumor viruses. The role of polyoma viruses in neoplasms etiology is discussed.


An open-label trial of olanzapine for corticosteroid-induced mood symptoms.
Prescription corticosteroids are given for a variety of common medical conditions. Psychiatric symptoms including depression, psychosis, and especially mania are common side effects of corticosteroid therapy. However, minimal data are available on the treatment of corticosteroid-induced psychiatric symptoms. In this study, 12 outpatients with manic or mixed symptoms secondary to corticosteroids were enrolled in a 5-week prospective, open-label trial of olanzapine. Psychiatric symptom measures included the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS). Side effects were monitored with the Simpson Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Scale (BAS). Weight and blood glucose were obtained at baseline and exit. Olanzapine dosing was flexible beginning at 2.5 mg/day and titrated upward as necessary to a maximum dose of 20 mg/day. Data were analyzed with Wilcoxon signed rank tests using baseline and exit data on all 12 participants. Participants showed significant reductions in YMRS (primary outcome measure), HRSD, and BPRS scores with no significant change in the SAS, AIMS, BAS, weight, or blood glucose levels. One participant discontinued early due to lack of efficacy. These data suggest that olanzapine is well tolerated and appears to be useful for mood disturbances associated with corticosteroid therapy. Controlled trials seem warranted to confirm these observations.


Delirium in hospitalized elderly patients and post-discharge mortality.
To determine the impact of delirium on post-discharge mortality in hospitalized older patients. Delirium is frequent in hospitalized older patients and correlates with high hospital mortality. There are only a few studies about its impact on post-discharge mortality. This is a prospective study of patients over 60 years old who were hospitalized in the Geriatric Unit at Hospital das Clínicas of São Paulo between May 2006 and March 2007. Upon admission, demographics, comorbidities, number of drugs taken, and serum albumin concentration were evaluated for each patient. Delirium was diagnosed according to the DSM-IV criteria. Patients were divided into group A (with delirium) and group B (without delirium). One year after discharge, the patients or their caregivers were contacted to assess days of survival. The sample included 199 patients, 66 (33%) of whom developed delirium (Group A). After one year, 33 (50%) group A patients had died, and 45 (33.8%) group B patients had died (p = 0.03). There was a significant statistical difference in average age (p = 0.001) and immobility (p <0.001) between groups A and B. There were no statistically significant differences between groups A and B in number of drugs taken greater than four (p = 0.62), sex (p = 0.54) and number of diagnoses greater than four (p = 0.21). According to a multivariate analysis, delirium was not an independent predictor of post-discharge mortality. The predictors of post-discharge mortality were age > or = 80 years (p = 0.029), albumin concentration < 3.5 g/dl (p = 0.001) and immobility (p = 0.007). Delirium is associated with higher post-discharge mortality as a dependent predictor.


Emergency Medical Services Pre-Hospital Care Reports as a Data Source for Logging Injury Surveillance.
Logging workers are at high risk of injury, and although data on fatal injuries exists, less is known about non-fatal injuries. The purpose of this study is to describe initial trends in logging morbidity in Maine and New Hampshire using pre-hospital care reports. Demographics and specifics of the event were recorded for each incident case. Both quantitative and qualitative analyses were employed. Logging injuries (n = 70) were primarily due to trees, heavy equipment, and chainsaws. Interventions focused on heavy equipment safety (particularly slips, trips, and falls), and personal protective equipment use would be warranted based on the findings of this surveillance system. Our methods are able to capture traumatic injury in logging, in sufficient detail to prioritize interventions and to evaluate their outcomes. The system is low-cost and has the potential to be sustained over a long period.


Electrochemical Detecting Lung Cancer-Associated Antigen Based on Graphene-Gold Nanocomposite.
Using a Au nanoparticle/reduced graphene oxide composite (AuNP-RGO), a signal-enhanced electrochemical immunosensor without label was created to detect neuron-specific enolase (NSE). Furthermore, an environmentally-friendly method was developed to prepare AuNP-RGO by employing chitosan (CS), which served as reducing and stabilizing agent. We showed that the sensitivity of the immunosensor designed in this report was remarkably enhanced because of the numerous active sites in the sensor provided by the AuNP-RGO nanostructure. For the quantification of NSE, the immunosensor exhibited a positive linear relationship with the concentration in the range of 0.1 to 2000 ng/mL, where the limit of the detection was 0.05 ng/mL.


Nasal Glial Heterotopia with Cleft Palate.
Congenital midline nasal masses are rare anomalies of which nasal glial heterotopia represents an even rarer subset. We report a case of a 25-day-old male child with nasal glial heterotopia along with cleft palate suggesting embryonic fusion anomaly which was treated with excision and primary closure for nasal mass followed by palatal repair at later date.


Cognitive vulnerability to auditory hallucination. Impaired perception of meaning.
Forty-four psychiatric patients were separated into four groups on the basis of presence/absence of hallucinations and reactive/process status. Reactive hallucinators were found to be singularly impaired in two aspects of cognitive processing: (1) tolerance of ambiguity; and (2) availability of alternative meanings. The perceptual errors produced by premature judgment and limited consideration of alternative meanings for misperceptions are discussed as factors predisposing to auditory hallucination.


Redescription and molecular characterization of Anoplocephala manubriata, Railliet et al., 1914 (Cestoda: Anoplocephalidae) from a Sri Lankan wild elephant (Elephas maximus).
The present work provides a detailed morphological and molecular description of Anoplocephala manubriata in elephants. Adult worms were recovered during an autopsy of a wild elephant in Elephant Transit Home, Udawalawe, Sri Lanka. Necropsy findings revealed a severe cestode infection in the small intestine. These tapeworms were tightly attached to the intestinal mucosae, resulted in hyperemic thickened intestinal mucosae, variable size irregular well-demarcated multifocal ulcerative regions sometimes covered with necrotic membranes and variable size, diffuse, well-demarcated raised nodular masses were evident in the small intestine. The article provides an account of the biology of A. manubriata and a comparative analysis of the morphology and morphometrics of Anoplocephala species that occur in different hosts. Phylogenetic analysis of the second internal transcribed spacer region (ITS-2), a portion of the 28S region and cytochrome oxidase subunit 1 (COX1) genes revealed that A. manubriata is closely associated with Anoplocephala species in horse in comparison to other Anoplocephalines. This study will enhance the current knowledge in taxonomy of elephant tapeworms and contribute to future phylogenetic studies.


The cushion-star Parvulastra exigua in South Africa: one species or more?
The cushion-star Parvulastra exigua (Lamarck, 1816) is a widely distributed member of the temperate intertidal fauna in the southern hemisphere. In South Africa, it occurs in sympatry with the endemic Parvulastra dyscrita (Clark, 1923), the two species being differentiated predominantly by gonopore placement. Several recent studies have suggested that there may be additional cryptic species within the Parvulastra exigua complex in South Africa, based variously on color morphology, genetic evidence and the differential placement of the gonopores. This paper attempts to resolve whether one or more species are represented within Parvulastra exigua. A total of 346 Parvulastra exigua and 8 Parvulastra dyscrita were collected from sites on the west and south-west coasts of South Africa; morphological, anatomical and genetic analyses were performed to determine whether cryptic species and/or Parvulastra exigua specimens with aboral gonopores were present. Results show that neither cryptic species nor Parvulastra exigua specimens with aboral gonopores occur at these sites. This study thus refutes previous claims of the existence of aboral gonopores in South African Parvulastra exigua, and suggests that a single species is represented. The distinction between Parvulastra exigua and Parvulastra dyscrita is also confirmed, and features separating these two species are clarified and documented.


Dinuclear cobalt(II) complexes with double phosphate ester bridges and tetradentate ligands having anisole or quinoline appendages.
Phosphate esters provide a rigid and stable polymeric backbone in nucleic acids. Metal complexes with phosphate ester groups have been synthesized as structural and spectroscopic models of phosphate-containing enzymes. Dinucleating ligands are used extensively to synthesize model complexes since they provide the support required to stabilize such complexes. The crystal structures of two dinuclear CoII complexes, namely bis(μ-diphenyl phosphato-κ2O:O')bis({2-methoxy-N,N-bis[(pyridin-2-yl)methyl]aniline-κ4N,N',N'',O}cobalt(II)) bis(perchlorate), [Co(C12H10O4P)2(C19H19N3O)2](ClO4)2, and bis(μ-diphenyl phosphato-κ2O:O')bis({N,N-bis[(pyridin-2-yl)methyl]quinolin-8-amine-κ4N,N',N'',O}cobalt(II)) bis(perchlorate), [Co(C12H10O4P)2(C21H18N4)2](ClO4)2, with tetradentate 2-methoxy-N,N-bis[(pyridin-2-yl)methyl]aniline (L1) and N,N-bis[(pyridin-2-yl)methyl]quinolin-8-amine (L2) ligands are reported. The complexes have similar structures, with distorted octahedral geometries around the metal centres. Both are centrosymmetric (Z' = 0.5), with the CoII centres doubly bridged by diphenyl phosphate ester groups. A number of aromatic-aromatic interactions are present and differ between the two complexes as the anisole group in L1 is replaced by a quinoline group in L2. A detailed study of these interactions is presented.


Baicalin increases developmental competence of mouse embryos in vitro by inhibiting cellular apoptosis and modulating HSP70 and DNMT expression.
Scutellaria baicalensis has been effectively used in Chinese traditional medicine to prevent miscarriages. However, little information is available on its mechanism of action. This study is designed specifically to reveal how baicalin, the main effective ingredient of S. baicalensis, improves developmental competence of embryos in vitro, using the mouse as a model. Mouse pronuclear embryos were cultured in KSOM medium supplemented with (0, 2, 4 and 8 μg/ml) baicalin. The results demonstrated that in vitro culture conditions significantly decreased the blastocyst developmental rate and blastocyst quality, possibly due to increased cellular stress and apoptosis. Baicalin (4 µg/ml) significantly increased 2- and 4-cell cleavage rates, morula developmental rate, and blastocyst developmental rate and cell number of in vitro-cultured mouse embryos. Moreover, baicalin increased the expression of Gja1, Cdh1, Bcl-2, and Dnmt3a genes, decreased the expression of Dnmt1 gene, and decreased cellular stress and apoptosis as it decreased the expression of HSP70, CASP3, and BAX and increased BCL-2 expression in blastocysts cultured in vitro. In conclusion, baicalin improves developmental competence of in vitro-cultured mouse embryos through inhibition of cellular apoptosis and HSP70 expression, and improvement of DNA methylation.


Ultrastructural identification of spirochetes and flagellated microbes at the brush border of the large intestinal epithelium of the rhesus monkey.
Spiral-shaped organisms exclusively and intimately populate the brush border of the cecal and colonic epithelium of healthy monkeys (Macaca mulatta). These organisms replace the glycocalyx, destroy most microvilli, and attenuate the terminal web of the brush border. Despite these remarkable alterations, the remaining host cellular structure is unchanged. Two structurally distinct microbes, a spirochete and a flagellate, were recognized by electron microscopy. These spirochetes share the general characteristics of other known spirochetes: they are 3 to 6 mum long and 0.2 to 0.4 mum wide, spiral 2 to 6 times, and have axial fibrils of 6-12-6 and 4-8-4 arrangements. Flagellated microbes are 4 to 6 mum long and 0.2 to 0.4 mum wide, spiral 2 to 4 times, and are characterized by a polar flagellum which originates from the terminal button at each end of the cytoplasmic body. This in vivo ultrastructural study of anaerobic spiral-shaped organisms bypasses the difficulties of in vitro culture techniques and provides a detailed description and identification of these organisms in their host environment.


Unconscious or underpowered? Probabilistic cuing of visual attention.
Recent debate about the reliability of psychological research has raised concerns about the prevalence of false positives in our discipline. However, false negatives can be just as concerning in areas of research that depend on finding support for the absence of an effect. This risk is particularly high in unconscious learning experiments, where researchers commonly seek to demonstrate that people can learn to perform a task in the absence of any explicit knowledge of the information that drives performance. The fact that some unconscious learning effects are typically studied with small samples and unreliable awareness measures makes false negatives especially likely. In the present article we focus on a popular unconscious learning paradigm, probabilistic cuing of visual attention, as a case study. First, we show that, at the meta-analytic level, previous experiments reveal positive signs of participant awareness, although individual studies are severely underpowered to detect this. Second, we report the results of 2 empirical studies in which participants' awareness was tested with alternative and more sensitive dependent measures, both of which manifest positive evidence of awareness. We also show that, based on the predictions of a formal model of probabilistic cuing and given the reliabilities of the dependent measures collected in these experiments, any statistical test aimed at detecting a significant correlation between learning and awareness is doomed to return a nonsignificant result, even if at the latent level both constructs are actually related and participants' knowledge is completely explicit. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Integrated effects of light intensity and fertilization on growth and flavonoid accumulation in Cyclocarya paliurus.
Cyclocarya paliurus has been used for drug formulations and ingredients in functional foods in China. Field studies were conducted to examine the relationships between environmental factors and flavonoid accumulation. A split-plot randomized design was used to establish three shading treatments and three fertilization levels, and growth parameters and flavonoid contents were detected. The greatest biomass production was achieved in intermediate shade and fertilization treatment, and leaf production per seedling increased by 139.5% compared to the treatment without shade and fertilization. Overall, shade and fertilization had a significantly negative effect on contents of total flavonoid, kaempferol, quercetin, and isoquercitrin in leaves of C. paliurus. However, the greatest accumulation of total flavonoid in the leaves was observed in intermediate shade and fertilization treatment, achieving 364.4 g/plant. The results suggest that manipulating the field growing conditions and optimizing the silvicultural system would be important for obtaining the greatest yield of targeted health-promoting substances.


Drug transporters as targets for cancer chemotherapy.
Transporter proteins play an important role in taking up nutrients into and effluxing xenobiotics out of cells to sustain cell survival. Transporters that affect drug absorption, distribution and excretion are the so-called drug transporters. In the last decade, a number of studies revealed interactions between drug transporters and clinically important anticancer agents. Utilizing the knowledge of transporter functions offers us the possibility of delivering a drug to the target tissues, avoiding distribution to other tissues and improving oral bioavailability. Many transporters have been reported to be differentially up-regulated in cancer cells compared to normal tissues, suggesting that the differential expression of transporters in cancer cells may provide good targets for enhancing drug delivery as well as diagnostic markers for cancer therapy. This review will focus on the role of drug transporters in the adaptation and growth of tumors and in their potential usefulness as therapeutic targets in cancer.


The toxic effects of glutamate and related compounds in the retina and the brain.
This paper has reviewed information pertaining to an interesting group of amino acids--glutamate, aspartate, and certain of their structural analogs, some of which are neurotransmitter candidates, and all of which have both neuroexcitatory and neurotoxic activities. Evidence for the excitotoxic concept, which holds that an excitatory and possibly synapse-related mechanism underlies the neurotoxicity of these compounds, is presented. Unlike a number of environmental neurotoxicants which induce toxic changes primarily in axons, these agents attack the dendrosomal portions of the neuron, which has led to their use as "axon-sparing" lesioning agents. When administered either systemically or by direct microinjection into the CNS, they delete intrinsic neurons from infiltrated regions without disturbing axons that are passing through or terminating therein. They are potentially useful tools, therefore, for studying anatomical pathways and structure-function relations in the CNS. The basis for their use as systemic investigational tools--that they have access from blood to the retina and specialized regions of brain, the circumventricular organs--is also the basis for considering them potentially hazardous for use as food additives or drugs. Ways in which the consumer may be exposed to these agents are considered and relevant mechanisms of risk are discussed.


Beneficial effects of triple drug combination of pioglitazone with glibenclamide and metformin in type 2 diabetes mellitus patients on insulin therapy.
The thiazolidinediones are a class of antidiabetes medication that enhance the actions of insulin in muscle, liver, and adipose tissue. Data have been lacking on their use in combination with both sulfonylurea and metformin among patients of type 2 diabetes who are on insulin therapy secondary to failure of routine oral hypoglycemic drugs in controlling their diabetes. To determine the effects of pioglitazone in combination with sulphonylurea and metformin on diabetes control in patients being treated with insulin due to secondary failure of oral hypoglycemic agents. One hundred and twenty-four consecutive type 2 diabetes patients (mean age, 57.13 years) attending four centres in Mumbai, who were being treated with insulin were selected. They were switched on to triple drug combination of glibenclamide 5 mg, metformin 500 mg and pioglitazone 15 mg along with insulin. Study participants were required to have type 2 diabetes mellitus for atleast 5 years. Patients were excluded if they had any of the following: serum creatinine concentration greater than 1.5 mg/dl, alanine aminotransferase (ALT) level more than two times the upper limit of normal, symptomatic angina, cardiac insufficiency or history of myocardial infarction. Pioglitazone 15 mg with glibenclamide 5 mg and metformin 500 mg, significantly decreased hemoglobin HbA1c level from 11.5% to 7.32% (P < 0.001), average fasting blood glucose from 194.8 mg/ dl to 124.06 mg/dl (p < 0.01), average post-prandial blood glucose from 256.24 to 162.32 mg/dl (p < 0.01). At 6 months, 43.35% of patients did not need to be continued on insulin. The total insulin requirement in 124 patients reduced by 71.81%. There were no significant side effects, liver enzymes were within acceptable levels, average weight gain was 2.23 kg, significant hypoglycemia was observed in 28 patients with two requiring hospitalisation, these patients were those who did not stick to follow-up schedules. With proper patient selection, pioglitazone with glibenclamide and metformin can be safely used in patients receiving insulin with good results.


Electrorheological Fluids with High Shear Stress Based on Wrinkly Tin Titanyl Oxalate.
Electrorheological (ER) fluids are considered as a type of smart fluids because their rheological characteristics can be altered through an electric field. The discovery of giant ER effect revived the researchers' interest in the ER technological area. However, the poor stability including the insufficient dynamic shear stress, the large leakage current density, and the sedimentation tendency still hinders their practical applications. Herein, we report a facile and scalable coprecipitation method for synthesizing surfactant-free tin titanyl oxalate (TTO) particles with tremella-like wrinkly microstructure (W-TTO). The W-TTO-based ER fluids exhibit enhanced ER activity compared to that of the pristine TTO because of the improved wettability between W-TTO and the silicone oil. In addition, the static yield stress and leakage current of W-TTO ER fluids also show a fine time stability during the 30 day tests. More importantly, the dynamic shear stress of W-TTO ER fluids can remain stable throughout the shear rate range, which is valuable for their use in engineering applications. The results in this work provided a promising strategy to solving the long-standing problem of ER fluid stability. Moreover, this convenient route of synthesis may be considered a green approach for the mass production of giant ER materials.


Atomically Precise Gold Nanoclusters Accelerate Hydrogen Evolution over MoS2 Nanosheets: The Dual Interfacial Effect.
Hydrogen generation via electrocatalytic water splitting holds great promise for future energy revolution. It is desirable to design abundant and efficient catalysts and achieve mechanistic understanding of hydrogen evolution reaction (HER). Here, this paper reports a strategy for improving HER performance of molybdenum disulfide (MoS2 ) via introducing gold nanoclusters as a cocatalyst. Compared to plain MoS2 nanosheets, the Au25 (SR)18 /MoS2 nanocomposite exhibits enhanced HER activity with a small onset potential of -0.20 V (vs reversible hydrogen electrode) and a higher current density of 59.3 mA cm-2 at the potential of -0.4 V. In addition to the interfacial interaction between nanoclusters and MoS2 , the interface between the Au25 core and the surface ligands (thiolate vs selenolate) is also discovered to distinctly affect the catalytic performance. This work highlights the promise of metal nanoclusters in boosting the HER performance via tailoring the interfacial electronic interactions between gold nanoclusters and MoS2 nanosheets, as well as the interface between metal core and surface ligands.


Short report: cysticercosis of the breast, a rare imaging finding.
Parasitic infection of the breast is rare, especially in cases of cysticercosis. This disease is acquired by ingestion of tapeworm eggs in contaminated food and water supplies or from hands improperly washed after a bowel movement. Diagnosis is usually made incidentally. We report a patient with cysticercosis of the breast. The patient was a 63-year-old woman who had no clinical manifestations, but cysticercus was observed to cause calcifications detected by mammography. Computed tomography demonstrated brain lesions. A definitive diagnosis of cysticercosis was made by demonstration of characteristic calcified larvae. The definitive diagnosis was confirmed by excisional surgery.


School Readiness Research in Latin America: Findings and Challenges.
Educational results in Latin America (LA) are well below those of developed countries. One factor that influences how well children do at school is school readiness. In this article, we review studies conducted in LA on the readiness skills of preschool children. We begin by discussing contextual factors that affect what is expected of children upon school entry, and we examine critical aspects of children's developmental contexts in LA. We then review local research on the level and determinants of three readiness skills of preschoolers in LA. Few studies allow comparisons between LA and other regions, but some results suggest that the oral language of children in LA before school entry is lower than in developed countries. These entry-level differences do not seem large enough to explain the poor educational results obtained by children in LA. We conclude regarding research needed to explain educational results and to inform educational policies.


Inhibition of aldose reductase and sorbitol accumulation by astilbin and taxifolin dihydroflavonols in Engelhardtia chrysolepis.
Dihydroflavonol taxifolin and its glycoside, astilbin, from Engelhardtia chrysolepis inhibited rat lens and recombinant human aldose reductase. Taxifolin also inhibited sorbitol accumulation in human red blood cells. Furthermore, this dihydroflavonol aglycone maintained the clarity of rat lens incubated with a high concentration of glucose. These dihydroflavonols may be effective for preventing osmotic stress in hyperglycemia.


Conservative management of lumbar spinal stenosis. Identifying patients likely to do well without surgery.
Lumbar spinal stenosis is a painful condition that often leads to irreversible neurologic damage and functional disability. Thus, early diagnosis and management are important. Conservative therapy, which is appropriate for many patients, minimizes invasive intervention and decreases the risks of morbidity. As more people live to older ages, the incidence of lumbar spinal stenosis will likely increase. If results of a thorough history and physical examination suggest the disorder, a course of appropriate physical therapy should be started promptly; more expensive tests and treatments are reserved for patients whose pain is refractory to early conservative intervention. However, if pain is severe, if the origin is not clear, or if neurologic deficits quickly become worse, immediate neuroradiologic studies should be considered, including timely EMG. Strong guidance by the primary care physician is of paramount importance because the therapeutic program is lengthy. Additional help from a physiatrist, neurologist, or orthopedic surgeon may be indicated as treatment progresses.


Marker-based estimation of heritability in immortal populations.
Heritability is a central parameter in quantitative genetics, from both an evolutionary and a breeding perspective. For plant traits heritability is traditionally estimated by comparing within- and between-genotype variability. This approach estimates broad-sense heritability and does not account for different genetic relatedness. With the availability of high-density markers there is growing interest in marker-based estimates of narrow-sense heritability, using mixed models in which genetic relatedness is estimated from genetic markers. Such estimates have received much attention in human genetics but are rarely reported for plant traits. A major obstacle is that current methodology and software assume a single phenotypic value per genotype, hence requiring genotypic means. An alternative that we propose here is to use mixed models at the individual plant or plot level. Using statistical arguments, simulations, and real data we investigate the feasibility of both approaches and how these affect genomic prediction with the best linear unbiased predictor and genome-wide association studies. Heritability estimates obtained from genotypic means had very large standard errors and were sometimes biologically unrealistic. Mixed models at the individual plant or plot level produced more realistic estimates, and for simulated traits standard errors were up to 13 times smaller. Genomic prediction was also improved by using these mixed models, with up to a 49% increase in accuracy. For genome-wide association studies on simulated traits, the use of individual plant data gave almost no increase in power. The new methodology is applicable to any complex trait where multiple replicates of individual genotypes can be scored. This includes important agronomic crops, as well as bacteria and fungi.