Clostridium difficile recurrent infection: possible implication of TA systems.
Clostridium difficile is an important nosocomial pathogen associated with antibiotic treatments. C. difficile's ability to survive antimicrobial therapy and transition from inert colonization to active infection is one of the most perplexing aspects of C. difficile infections and suggests that additional mechanisms are involved in persistence. In this regard, novel mechanisms linked with pathogenesis and persistence of C. difficile such as toxin-antitoxin systems might significantly contribute to biofilm formation and persistent infection. This review will focus on advances of toxin-antitoxin systems in C. difficile and their putative roles will be discussed.


Sublingual sugar for hypoglycaemia in children with severe malaria: a pilot clinical study.
Hypoglycaemia is a poor prognostic indicator in severe malaria. Intravenous infusions are rarely feasible in rural areas. The efficacy of sublingual sugar (SLS) was assessed in a pilot randomized controlled trial among hypoglycaemic children with severe malaria in Mali. Of 151 patients with presumed severe malaria, 23 children with blood glucose concentrations < 60 mg/dl (< 3.3 mmol/l) were assigned randomly to receive either intravenous 10% glucose (IVG; n = 9) or sublingual sugar (SLS; n = 14). In SLS, a teaspoon of sugar, moistened with a few drops of water, was gently placed under the tongue every 20 minutes. The child was put in the recovery position. Blood glucose concentration (BGC) was measured every 5-10 minutes for the first hour. All children were treated for malaria with intramuscular artemether. The primary outcome measure was treatment response, defined as reaching a BGC of >or= 3.3 mmol/l (60 mg/dl) within 40 minutes after admission. Secondary outcome measures were early treatment response at 20 minutes, relapse (early and late), maximal BGC gain (CGmax), and treatment delay. There was no significant difference between the groups in the primary outcome measure. Treatment response occurred in 71% and 67% for SLS and IVG, respectively. Among the responders, relapses occurred in 30% on SLS at 40 minutes and in 17% on IVG at 20 minutes. There was one fatality in each group. Treatment failures in the SLS group were related to children with clenched teeth or swallowing the sugar, whereas in the IVG group, they were due to unavoidable delays in beginning an infusion (median time 17.5 min (range 3-40).Among SLS, the BGC increase was rapid among the nine patients who really kept the sugar sublingually. All but one increased their BGC by 10 minutes with a mean gain of 44 mg/dl (95%CI: 20.5-63.4). Sublingual sugar appears to be a child-friendly, well-tolerated and effective promising method of raising blood glucose in severely ill children. More frequent repeated doses are needed to prevent relapse. Children should be monitored for early swallowing which leads to delayed absorption, and in this case another dose of sugar should be given. Sublingual sugar could be proposed as an immediate "first aid" measure while awaiting intravenous glucose. In many cases it may avert the need for intravenous glucose.


Mice Lacking GABAA Receptor δ Subunit Have Altered Pharmaco-EEG Responses to Multiple Drugs.
In the brain, extrasynaptically expressed ionotropic, δ subunit-containing γ-aminobutyric acid A-type receptors (δ-GABAARs) have been implicated in drug effects at both neuronal and behavioral levels. These alterations are supposed to be caused via drug-induced modulation of receptor ionophores affecting chloride ion-mediated inhibitory tonic currents. Often, a transgenic mouse model genetically lacking the δ-GABAARs (δ-KO) has been used to study the roles of δ-GABAARs in brain functions, because a specific antagonist of the δ-GABAARs is still lacking. We have previously observed with these δ-KO mice that activation of δ-GABAARs is needed for morphine-induced conditioning of place preference, and others have suggested that δ-GABAARs act as targets selectively for low doses of ethanol. Furthermore, activation of these receptors via drug-mediated agonism induces a robust increase in the slow-wave frequency bands of electroencephalography (EEG). Here, we tested δ-KO mice (compared to littermate wild-type controls) for the pharmaco-EEG responses of a broad spectrum of pharmacologically different drug classes, including alcohol, opioids, stimulants, and psychedelics. Gaboxadol (THIP), a known superagonist of δ-GABAARs, was included as the positive control, and as expected, δ-KO mice produced a blunted pharmaco-EEG response to 6 mg/kg THIP. Pharmaco-EEGs showed notable differences between treatments but also differences between δ-KO mice and their wild-type littermates. Interestingly mephedrone (4-MMC, 5 mg/kg), an amphetamine-like stimulant, had reduced effects in the δ-KO mice. The responses to ethanol (1 g/kg), LSD (0.2 mg/kg), and morphine (20 mg/kg) were similar in δ-KO and wild-type mice. Since stimulants are not known to act on δ-GABAARs, our findings on pharmaco-EEG effects of 4-MMC suggest that δ-GABAARs are involved in the secondary indirect regulation of the brain rhythms after 4-MMC.


Jejunal intussusception caused by an inflammatory fibroid polyp.
The case of a 56-year old male with a jejunal intussusception due to the inflammatory fibroid polyp is presented. In the literature, eleven cases with jejunojejunal intussusception due to IFP were reported. This rare entitiy was reviewed with different perspectives in this report.


High entropy of edge orientations characterizes visual artworks from diverse cultural backgrounds.
We asked whether "good composition" or "visual rightness" of artworks manifest themselves in a particular arrangement of basic image features, such as oriented luminance edges. Specifically, we analysed the layout of edge orientations in images from a collection of >1600 paintings of Western provenance by comparing pairwise the orientation of each edge in an image with the orientations of all other edges in the same image. From the resulting orientation histograms, we calculated Shannon entropy and parallelism (i.e., the degree to which lines are parallel in the image). For comparison, we analysed the same second-order image properties in photographs of diverse natural patterns and man-made objects and scenes. Results showed that Shannon entropy of relative orientations of edge pairs was high and parallelism was low for the paintings and some of the natural patterns, but differed from other sets of photographs, including other man-made stimuli. The differences were also observed when images were matched for image content. Moreover, high entropy of edge orientations was found in traditional artworks produced by different techniques, in artworks that represented different content matter and art genres, as well as in artworks from other cultural backgrounds (East Asian and Islamic). In conclusion, we found that high entropy of edge orientations characterizes diverse sets of traditional artworks from various cultural backgrounds.


Anomalous Papillary Muscle Insertion Causing Dynamic Left Ventricular Outflow Tract Obstruction without Hypertrophic Obstructive Cardiomyopathy.
Anomalous papillary muscle insertion directly into the surface of the mitral valve leaflet is rare, especially in a subject without apparent evidence of hypertrophic cardiomyopathy. We present a case of this isolated congenital malformation producing two hemodynamic sequelae of dynamic left ventricular outflow tract obstruction and severe mitral regurgitation.


Observer variation, dysplasia grading, and HPV typing: a review.
Squamous dysplasia of the cervix is a morphologic continuum that is divided into a number of categories. When the severity of a morphologic abnormality is assessed, whether in a biopsy sample or in an exfoliative smear, there can be significant observer variation. The statistical quantification of this variation, with particular reference to the kappa statistic and the influence of the number of categories utilized on the kappa statistic, is discussed. The contribution of information theory to the understanding of the reasons for observer variation is explored. The use of a binary (Bethesda) system of classification of squamous dysplasia and its validation by comparing consensus diagnoses with human papilloma virus type both in biopsy samples and in smears is reviewed.


A glimpse of tissue engineering in China.
Tissue engineering activities in China have expanded and advanced to the extent that it is not possible to acknowledge all of the work in one review. Substantial progress has been made in the development of novel biomaterial scaffolds and in the genetic manipulation of cells in vitro. Moreover, certain aspects of tissue engineering strategies have begun to undergo clinical trial. A glimpse of tissue engineering in China was afforded at the First International Conference on Biomaterials (China) held in Beijing, July 24-26, 2001. Several papers presented at the meeting, which was conducted in English only, reflected many of the tissue engineering activities in the country. A brief summary of some of the papers may begin to suggest possibilities for collaboration between tissue engineers inside and outside of China, as well as to facilitate dissemination of important findings.


Degradation of alkanes and highly chlorinated benzenes, and production of biosurfactants, by a psychrophilic Rhodococcus sp. and genetic characterization of its chlorobenzene dioxygenase.
Rhodococcus sp. strain MS11 was isolated from a mixed culture. It displays a diverse range of metabolic capabilities. During growth on 1,2,4-trichlorobenzene, 1,2,4,5-tetrachlorobenzene (1,2,4,5-TeCB) and 3-chlorobenzoate stoichiometric amounts of chloride were released. It also utilized all three isomeric dichlorobenzenes and 1,2,3-trichlorobenzene as the sole carbon and energy source. Furthermore, the bacterium grew well on a great number of n-alkanes ranging from n-heptane to n-triacontane and on the branched alkane 2,6,10,14-tetramethylpentadecane (pristane) and slowly on n-hexane and n-pentatriacontane. It was able to grow at temperatures from 5 to 30 degrees C, with optimal growth at 20 degrees C, and could tolerate 6 % NaCl in mineral salts medium. Genes encoding the initial chlorobenzene dioxygenase were detected by using a primer pair that was designed against the alpha-subunit (TecA1) of the chlorobenzene dioxygenase of Ralstonia (formerly Burkholderia) sp. strain PS12. The amino acid sequence of the amplified part of the alpha-subunit of the chlorobenzene dioxygenase of Rhodococcus sp. strain MS11 showed >99 % identity to the alpha-subunit of the chlorobenzene dioxygenase from Ralstonia sp. strain PS12 and the parts of both alpha-subunits responsible for substrate specificity were identical. The subsequent enzymes dihydrodiol dehydrogenase and chlorocatechol 1,2-dioxygenase were induced in cells grown on 1,2,4,5-TeCB. During cultivation on medium-chain-length n-alkanes ranging from n-decane to n-heptadecane, including 1-hexadecene, and on the branched alkane pristane, strain MS11 produced biosurfactants lowering the surface tension of the cultures from 72 to </=29 mN m(-1). Glycolipids were extracted from the supernatant of a culture grown on n-hexadecane and characterized by (1)H- and (13)C-NMR-spectroscopy and mass spectrometry. The two major components consisted of alpha,alpha-trehalose esterified at C-2 or C-4 with a succinic acid and at C-2' with a decanoic acid. They differed from one another in that one 2,3,4,2'-trehalosetetraester, found in higher concentration, was esterified at C-2, C-3 or C-4 with one octanoic and one decanoic acid and the other one, of lower concentration, with two octanoic acids. The results demonstrate that Rhodococcus sp. strain MS11 may be well suited for bioremediation of soils and sediments contaminated for a long time with di-, tri- and tetrachlorobenzenes as well as alkanes.


Use of (CA)n polymorphisms to determine the origin of blood cells after allogeneic canine marrow grafting.
We have used a polymerase chain reaction-based assay measuring polymorphic (CA)n repeats, a class of simple sequence repeats, to assess the success of allogeneic canine marrow transplants. Results were compared with those obtained with karyotype analysis of dividing cells in recipients that were sex mismatched with their marrow donors. Twenty recipients were conditioned for transplantation of genotypically DLA-identical littermate marrow by 450 cGy of total-body irradiation. In 2 recipients, results could not be compared, since either only cytogenetic or dinucleotide (CA)n marker data existed. Both dogs had autologous marrow recovery. In 15 of the remaining 18 recipients, complete agreement was found between the results obtained with dinucleotide (CA)n markers, cytogenetic studies, and granulocyte changes after transplantation. Seven of the 15 showed eventual autologous recovery, 6 displayed mixtures of host and donor cells, and 2 showed donor-type hematopoiesis. Two of the 18 dogs showed mixed chimerism with (CA)n markers and autologous recovery by cytogenetics, findings that may be related to differences in cells analyzed by the two techniques--i.e., all nucleated cells by (CA)n markers versus dividing cells by cytogenetics. In one additional recipient, results of marrow cytogenetics, granulocyte changes, and (CA)n markers were consistent with a successful allograft, while peripheral blood cytogenetics suggested autologous recovery, possibly the result of erroneous blood sampling. Polymerase chain reaction-based testing for dinucleotide repeat (CA)n polymorphisms, originally developed for genetic mapping in the dog, is useful and reliable when compared with cytogenetic studies, in assessing the success of allogeneic marrow transplants in dogs.


Feasibility and safety of granulocyte colony-stimulating factor treatment in patients with acute myocardial infarction.
This study examined feasibility and safety of granulocyte colony-stimulating factor (G-CSF) treatment for patients with acute myocardial infarction (AMI). Forty patients with AMI related with the left anterior descending coronary artery, who underwent successful percutaneous coronary intervention (PCI), were randomized into G-CSF group (n=18) or Control group (n=22). G-CSF treatment was started within 24 h after PCI. 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) was performed at 4 days and 6 months after AMI. SPECT data was analyzed for LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF) and myocardial perfusion. LVEF at 6 months was significantly better than that at 4 days in G-CSF group (p=0.013), but not changed in Control group (p=0.245). Although no significant difference was observed for LVEDV between the two groups, LVESV tended to be decreased only in G-CSF group. In G-CSF group, defect score (DS) was significantly decreased from 4 days to 6 months after AMI. Restenosis rate at 6 months after AMI was not significantly different between the two groups. G-CSF treatment for patients with AMI was effective and did not have any clinical and angiographic adverse effects.


High-force NdFeB-based magnetic tweezers device optimized for microrheology experiments.
We present the design, calibration, and testing of a magnetic tweezers device that employs two pairs of permanent neodymium iron boron magnets surrounded by low-carbon steel focusing tips to apply large forces to soft materials for microrheology experiments. Our design enables the application of forces in the range of 1-1800 pN to ∼4.5 μm paramagnetic beads using magnet-bead separations in the range of 0.3-20 mm. This allows the use of standard coverslips and sample geometries. A high speed camera, custom LED-based illumination scheme, and mechanically stabilized measurement platform are employed to enable the measurement of materials with viscoelastic moduli as high as ∼1 kPa.


Conflicting requirements of Plasmodium falciparum dihydrofolate reductase mutations conferring resistance to pyrimethamine-WR99210 combination.
Plasmodium falciparum strains bearing quadruple mutations of dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) at codons 51, 59, 108, and 164 are highly resistant to pyrimethamine (PYR), a diaminopyrimidine, but sensitive to WR99210 (WR), a cycloguanil analog, suggesting different enzyme-inhibitor binding interactions. A combination of these inhibitors to delay the onset of antifolate resistance is proposed. Using error-prone PCR, libraries of random mutants of wild-type PfDHFR and PfDHFR-TS were generated and used to transform Escherichia coli, and transformants were then selected for PYR or WR resistance. Mutants highly resistant to either PYR or WR were also generated from libraries obtained from further random mutagenesis of quadruple mutants (QM) with mutations in PfDHFR or PfDHFR-TS. For reversion mutants carrying altered residues I51N, N108S, and L164I, a further mutation of D54N was required to achieve resistance against WR, but these mutants regained sensitivity to PYR. When a combination of PYR and WR was used, fewer resistant mutants were generated from both mutant libraries using the QM gene templates. The effectiveness of the drug combination in reducing the appearance of resistance mutations is likely due to conflicting requirements for mutations conferring resistance to the two drugs. Thus, a combination of inhibitors from these two drug classes should be effective in impeding the emergence of P. falciparum resistance to antifolates.


The predictive utility of a significantly lower WAIS PIQ with psychiatric inpatients.
Contrasted five aspects of psychiatric inpatient care in two psychometrically distinct inpatient samples. The experimental (N = 35) and control groups (N = 35) differed in that the former Ss all scored higher WAIS VIQs than their respective PIQs by at least 15 units. The controls had WAIS VIQs that were within 5 points of their PIQs . Despite this, the two groups were not differentiated according to two other measures of cognitive integrity (Benton, 1963, and Wechsler Memory Scale, Wechsler, 1958); final diagnosis; severity of the S's presentation; capacity to resume self-attorney on discharge, and, finally, prediction of EEG and CT scan result. It was concluded that the poor predictive utility of this form of WAIS analysis did not justify the high cost of WAIS administration in inpatient psychiatric settings.


Human cervical and foreskin epithelial cells immortalized by human papillomavirus DNAs exhibit dysplastic differentiation in vivo.
Human papillomavirus (HPV) DNAs are detected in approximately 90% of anogenital carcinomas. To assess directly the effect of HPV on squamous differentiation, normal human cervical and foreskin epithelial cells and cells immortalized by recombinant HPV DNAs were transplanted beneath a skin-muscle flap in athymic mice. Xenografts containing normal cells formed well-differentiated stratified squamous epithelia 2 to 3 weeks after transplantation, but cell lines immortalized by four HPV types (HPV16, HPV18, HPV31, and HPV33) detected in anogenital cancer exhibited dysplastic morphology and molecular alterations in gene expression characteristic of intraepithelial neoplasia. Morphological alterations were accompanied by delayed commitment to terminal differentiation, alterations in the pattern of involucrin expression, and reductions in levels of involucrin and keratin 1 RNAs. HPV18-immortalized cells developed dysplastic changes more rapidly than cells immortalized by HPV16 DNA. These results show that human genital epithelial cells immortalized by HPV DNAs detected in genital cancers undergo dysplastic differentiation in vivo.


Congenital leukemia: successful treatment of a newborn with t(5;11)(q31;q23).
A male neonate presented with a high white cell count, an 11q23 translocation, and M5b leukemia. He was treated at 3 days of age with intensive combination chemotherapy after progressing despite exchange transfusions. The patient achieved complete remission at 28 days of age. Therapy was completed at the age of 6 months. At the time of this report, the patient is 17 months old and remains in remission. Twenty-nine patients with congenital acute myeloid leukemia were also reviewed. Twenty of these patients received varying therapies. Ten of the treated patients achieved complete remission; two died of toxicity; and eight died of progressive disease. Two patients had a translocation affecting 11q23. Congenital leukemia is a rare and usually fatal condition in patients without Down syndrome. The patient reported here shows that survival may be achieved with very intensive chemotherapy plus supportive care, despite extremely high white blood cell counts and unfavorable translocation.


Visible-Light-Enabled Trifluoromethylative Pyridylation of Alkenes from Pyridines and Triflic Anhydride.
A general strategy for visible-light-enabled site-selective trifluoromethylative pyridylation of unactivated alkenes has been developed using pyridines and triflic anhydride (Tf2 O). Intriguingly, the N-triflylpyridinium salts, generated in situ from pyridines and Tf2 O, serve as effective modular bifunctional reagents to install both CF3 and pyridyl groups to various olefins while controlling C4-selectivity in radical addition to the pyridine core. This synthetic route exhibited broad substrate scope under metal-free and mild photocatalytic conditions, granting efficient access to valuable C4-alkylated pyridines and quinolines without requiring prefunctionalization of the reaction site.


Cigarette smoking, alcohol consumption, and serum lipid profile among medical students in Greece.
The lack of data regarding health habits of medical students in Greece prompted a cross-sectional study to assess tobacco use, alcohol consumption and serum lipoprotein levels among students in the University of Crete School of Medicine. A self-administered questionnaire on smoking and alcohol consumption was distributed to third-year medical students for twelve consecutive years (1989-2000). A total of 849 students (462 males, 387 females) participated in the survey. Biochemical measurements were taken and multi-variant analysis of the data was performed. The prevalence of smoking among males and females was 33.2% (N = 150) and 28.4% (N = 108), respectively (mean cigarette consumption 13/day). As many as 349 males (77.2%) and 220 females (58.0%) reported consuming alcohol on a regular basis. The prevalence of low HDL-cholesterol (< 0.9 mmol/l) was 14.5% in males and 5.1% in females, and of high LDL-cholesterol levels (> 4.1 mmol/l) in 11.1% of male and 5.5% of female participants. Smoking was related to higher triglyceride (p = 0.032), and lower HDL-cholesterol (p = 0.037) serum levels. Total cholesterol, LDL-cholesterol, and the TC/HDL-cholesterol ratio were strongly related with the level of smoking (p = 0.006, p = 0.008, and p = 0.006 respectively). The results document a high prevalence of smoking among physicians-to-be in Greece. Tobacco use was strongly associated with a lipid profile predisposing to increased risk for cardiovascular disease. Health promotion programmes should therefore be instituted not only during the first years of medical studies, but rather at a much earlier stage in life.


Effect of short-term use of different non-steroidal anti-inflammatory drugs on renal function during fasting in ramadan.
This study was conducted to determine the combined effect of Ramadan fasting and short-term use of different non-steroidal anti-inflammatory drugs (NSAIDs) on renal function in healthy volunteers. The study subjects were assigned to six different groups, five of whom took different NSAIDs (namely nabumetone, indomethacin, diclofenac, sulindac, tenoxicam) and the sixth was a control group. Data were collected on serum sodium, chloride, potassium, urea, creatinine, bicarbonate and uric acid as well as urinary osmolarity, sodium, potassium, chloride and urea. These measurements were taken before fasting, 10 days into fasting while using NSAIDs, and five days after stopping the use of NSAIDs. The results showed slight changes in serum and urine measurements during fasting while using NSAIDs. These changes, although were significant in some cases, were within the normal range and were noted in all the study groups including the control group. We conclude that short-term use of NSAIDs in healthy subjects during fasting is not associated with any major adverse effects on the renal function.


The use of concomitant medications in psychiatric inpatients treated with either olanzapine or other antipsychotic agents: a naturalistic study at a state psychiatric hospital.
Concomitant medications are frequently used in the treatment of resistant psychiatric conditions to augment the primary psychotropic agent or to ameliorate side effects. The present study evaluated the prescription of concomitant psychiatric medications for psychiatric inpatients that were prescribed either olanzapine at its first commercial availability or another first-line antipsychotic agent. Sixty-nine newly admitted patients (mainly with schizophrenia) who were prescribed either olanzapine (n = 35) or another first-line antipsychotic agent (n = 34) were assessed (for the prescription of other concomitant psychotropic drugs) before (2-4 weeks prior to study) and following 8 weeks of treatment (unless discharged sooner). The results indicate that significantly fewer olanzapine-treated subjects were prescribed anticholinergic agents as compared to those prescribed other first-line antipsychotic agents, and a similar trend was noted in the prescription of mood stabilizers as well. Olanzapine-treated subjects used less as needed (PRN) antipsychotic medication compared to pre-olanzapine treatment period. Olanzapine-treated subjects used more anxiolytic agents compared to the control group in the early stages of treatment, probably due to the greater baseline severity of illness. These data suggest that olanzapine use is associated with less use of anticholinergic and mood-stabilizing agents as compared to older antipsychotic agents. These results also suggest that there is less need for PRN antipsychotic medication following olanzapine treatment. More severely ill subjects may require more anxiolytics during olanzapine initiation. The need for less anticholinergic and mood-stabilizing agent use with olanzapine could lead to greater adherence to long-term treatment and perhaps decreased cost (i.e. use of blood and organ system monitoring with mood stabilizers). At the end of treatment, olanzapine-treated subjects had statistically significantly lesser concomitant medicine usage compared to control subjects.


Oncology care provider perspectives on exercise promotion in people with cancer: an examination of knowledge, practices, barriers, and facilitators.
Despite the reported benefits of physical activity in alleviating the impact of cancer and its treatments, oncology care providers (OCPs) are not routinely discussing exercise with their patients, suggesting a knowledge to action gap. We sought to determine OCP's knowledge, beliefs, barriers, and facilitators to exercise discussion. A survey was administered to OCPs at the cancer center in Hamilton, Ontario. Questions comprised of demographics, knowledge and beliefs regarding exercise guidelines, and barriers and facilitators to exercise discussion. Analysis of survey responses was descriptive. Pearson's chi-squared test was used to examine select associations. There were 120 respondents (61% response rate) representing a diversity of professions. Approximately, 80% of OCPs were not aware of any exercise guidelines in cancer and self-reported poor knowledge on when, how, and which patients to refer to exercise programs. OCPs who reported meeting Canada's Physical Activity guidelines were significantly more likely to identify correct guidelines (p = 0.023) and to report good knowledge on how to provide exercise counseling (p = 0.014). Across OCP groups, barriers to exercise discussion included poor knowledge, lack of time, and safety concerns. Most felt that educational sessions and having an exercise specialist on the clinical team would be beneficial. OCPs have low knowledge regarding exercise counseling, but believe that discussing exercise is a multidisciplinary task and expressed a desire for further training. Interventions will require a multi-pronged approach including education for OCPs and guidance on assessment for exercise safety.


Management of macular edema secondary to central retinal vein occlusion: an evidence-based.
Retinal vein occlusions are common retinal vascular disorders with the potential for significant vision-related morbidity. Retinal vein occlusions are classified as either branch retinal vein occlusion (BRVO), central retinal vein occlusion (CRVO), or hemiretinal vein occlusion (HRVO) based on the specific occlusion site. Decreased vision in patients afflicted with CRVO may result from retinal ischemia and/or the accumulation of fluid within the center of the retina (macular edema). The Central Vein Occlusion Study (CVOS) Group demonstrated that grid laser photocoagulation is not an effective treatment for decreased vision due to CRVO-related macular edema. Since publication of that report, the standard of care for patients with decreased vision due to CRVO-associated macular edema was observation. However, in the past 5 years, several major randomized controlled clinical trials have investigated new therapeutic modalities for the treatment of macular edema secondary to CRVO. This article aims to provide insight into current evidence-based approaches to the management of macular edema secondary to CRVO. A companion article reviews approaches for the management of macular edema secondary to BRVO.


Nanomaterials in diagnostics, imaging and delivery: Applications from COVID-19 to cancer.
In the past two decades, the emergence of nanomaterials for biomedical applications has shown tremendous promise for changing the paradigm of all aspects of disease management. Nanomaterials are particularly attractive for being a modularly tunable system; with the ability to add functionality for early diagnostics, drug delivery, therapy, treatment and monitoring of patient response. In this review, a survey of the landscape of different classes of nanomaterials being developed for applications in diagnostics and imaging, as well as for the delivery of prophylactic vaccines and therapeutics such as small molecules and biologic drugs is undertaken; with a particular focus on COVID-19 diagnostics and vaccination. Work involving bio-templated nanomaterials for high-resolution imaging applications for early cancer detection, as well as for optimal cancer treatment efficacy, is discussed. The main challenges which need to be overcome from the standpoint of effective delivery and mitigating toxicity concerns are investigated. Subsequently, a section is included with resources for researchers and practitioners in nanomedicine, to help tailor their designs and formulations from a clinical perspective. Finally, three key areas for researchers to focus on are highlighted; to accelerate the development and clinical translation of these nanomaterials, thereby unleashing the true potential of nanomedicine in healthcare.


Machine learning approach to dynamic risk modeling of mortality in COVID-19: a UK Biobank study.
The COVID-19 pandemic has created an urgent need for robust, scalable monitoring tools supporting stratification of high-risk patients. This research aims to develop and validate prediction models, using the UK Biobank, to estimate COVID-19 mortality risk in confirmed cases. From the 11,245 participants testing positive for COVID-19, we develop a data-driven random forest classification model with excellent performance (AUC: 0.91), using baseline characteristics, pre-existing conditions, symptoms, and vital signs, such that the score could dynamically assess mortality risk with disease deterioration. We also identify several significant novel predictors of COVID-19 mortality with equivalent or greater predictive value than established high-risk comorbidities, such as detailed anthropometrics and prior acute kidney failure, urinary tract infection, and pneumonias. The model design and feature selection enables utility in outpatient settings. Possible applications include supporting individual-level risk profiling and monitoring disease progression across patients with COVID-19 at-scale, especially in hospital-at-home settings.


A crucial role of hepatocyte nuclear factor-4 expression in the differentiation of human ductular hepatocytes.
Ductular structures are suggested to be bipotential progenitor cells that may differentiate into hepatocytes or biliary epithelial cells (BEC). To better understand the differentiation process, we studied the expression of hepatocyte nuclear factor (HNF) in ductular structures. Matured hepatocytes in normal liver expressed HNF-1, HNF-4alpha, HNF-3beta, and C/EBPalpha in the nucleus. Normal BEC expressed HNF-1 but did not express HNF-4alpha, suggesting an important role of HNF-4alpha in maintaining the phenotype of matured hepatocytes. Ductular structures were classified into ductular cells and ductular hepatocytes. Ductular cells showed glandular or bile duct-like appearance and strongly expressed cytokeratin-7. Ductular hepatocytes showed features between BEC and hepatocytes and heterogeneously expressed cytokeratin-7. Both ductular cells and ductular hepatocytes expressed HNF-4alpha, but the nuclear localization of HNF-4alpha was more prominent in ductular hepatocytes. The expression of HNF-4alpha mRNA in ductular hepatocytes was demonstrated at the single cell level by laser capture microdissection. Regenerative hepatocytes strongly expressed all HNFs in the nucleus, whereas residual hepatocytes in massive necrosis showed low or cytoplasmic expression. These results suggest that HNF-4alpha plays an important role in the differentiation and maintenance of the matured hepatocyte phenotype and that nuclear localization of HNFs is implicated in the accomplishment of their function.


Effects of hippocampal afterdischarges on Purkinje cell activity.
Hippocampal afterdischarges can induce increased Purkinje cell activity that characteristically shows a pronounced acceleration during the period of the afterdischarges. Increased Purkinje cell activity may continue for many seconds after termination of the hippocampal activity. Typical frequency histograms are presented. A short period of hippocampal afterdischarges (under 25 sec) may occur with few if any alterations in cerebral activity and vice versa. However, such afterdischarges can produce changes in cerebellar activity as shown by enhanced Purkinje cell activity. These data support the view that the nucleus tegmenti pontis may be prominently involved in relaying hippocampal afterdischarges to the cerebellum whereas much of the neocortical seizure activity is relayed trough the pons, inferior olive, and lateral reticular nucleus, rather than through nucleus tegmenti pontis. EEG tracings taken from these areas illustrate the findings.


The Effect of the Iridium Alloying and Hydrogen Sorption on the Physicochemical and Electrochemical Properties of Palladium.
Thin layers (up to 1 µm) of Pd-Ir alloys were electrodeposited from aqueous, galvanic baths of PdCl2 and IrCl3 mixtures. The morphology of the electrodeposits was examined by means of scanning electron microscopy. The composition of alloys was determined with the use of energy-dispersive spectroscopy, atomic absorption spectrometry, X-ray photoelectron spectroscopy, and Auger electron spectroscopy. For the studies of the electrochemical properties of alloys, cyclic voltammetry, chronoamperometry, and chronopotentiometry were used. It was found that Pd-Ir alloy electrodes were surface-enriched with Pd. Pd-Ir alloys subjected to different electrochemical treatment involving hydrogen sorption changed their surface state. The continuous hydrogen sorption enhanced the Ir ions' dissolution. The values of thermodynamic functions of hydrogen sorption in strong alkaline electrolytes were comparable with those in acidic electrolytes, whereas the kinetics of the process in alkaline medium was hindered. The miscibility gap in the Pd-Ir-H system vanished for the electrode containing ca. 93.7 at.% Pd.


Connection of Protein Transport and Organelle Contact Sites in Mitochondria.
Mitochondrial biogenesis and function depend on the intensive exchange of molecules with other cellular compartments. The mitochondrial outer membrane plays a central role in this communication process. It is equipped with a number of specific protein machineries that enable the transport of proteins and metabolites. Furthermore, the outer membrane forms molecular contact sites with other cell organelles like the endoplasmic reticulum (ER), thus integrating mitochondrial function in cellular physiology. The best-studied mitochondrial organelle contact site, the ER-mitochondria encounter structure (ERMES) has been linked to many vital processes including mitochondrial division, inheritance, mitophagy, and phospholipid transport. Strikingly, ER-mitochondria contact sites are closely connected to outer membrane protein translocases. The translocase of the outer mitochondrial membrane (TOM) represents the general mitochondrial entry gate for precursor proteins that are synthesized on cytosolic ribosomes. The outer membrane also harbors the sorting and assembly machinery (SAM) that mediates membrane insertion of β-barrel proteins. Both of these essential protein translocases are functionally linked to ER-mitochondria contact sites. First, the SAM complex associates with an ERMES core component to promote assembly of the TOM complex. Second, several TOM components have been co-opted as ER-mitochondria tethers. We propose that protein import and organelle contact sites are linked to coordinate processes important for mitochondrial biogenesis.


Adherence of Helicobacter pylori to gastric epithelial cells and mucosal inflammation.
Adherence of Helicobacter pylori to the gastric epithelium is believed to be an important step in the induction of active inflammation of the mucosal layer. However, structural evidence showing a quantitative relationship between the adherence of H. pylori and severity of gastric mucosal inflammation is lacking. We therefore investigated the correlations between severity of gastritis and adherence of morphologically different forms of H. pylori. Fifty-seven biopsy specimens from the gastric bodies of patients with H. pylori-induced gastritis were examined. The severity of gastritis and the adherence and structure of H. pylori were determined with the use of light and scanning electron microscopy. We also investigated the ability of H. pylori organisms with different structural features to induce interleukin-8 secretion by human gastric adenocarcinoma (AGS) cells in vitro because production of interleukin-8 is related to H. pylori-associated gastritis. Furthermore, serum pepsinogen concentrations and cytotoxin-associated protein status in relation to adherence of H. pylori to the epithelial surface were examined. The results indicated that H. pylori organisms, which adhered firmly to the epithelial surface, were consistently long, tightly coiled bacilli. Histologically, those gastric mucosa samples with H. pylori firmly attached showed severe gastritis. H. pylori bacilli of greater length induced higher levels of interleukin-8 secretion. The serum pepsinogen I/II ratio showed a significant negative correlation with the grade of H. pylori adhesion (r = -0.401, P <.01). We also noted a significant correlation between cytotoxin-associated protein status and the adherence of H. pylori (r = 0.344, P <.05). A quantitative correlation was found between adherence of H. pylori and gastric inflammation. Both adherence and the induction of inflammation were found to be related to the structure of H. pylori.


Adsorption of branched-linear polyethyleneimine-ethylene oxide conjugate on hydrophilic silica investigated by ellipsometry and Monte Carlo simulations.
The adsorption of and conformation adopted by a branched-linear polymer conjugate to the hydrophilic silica-aqueous solution interface have been studied by in situ null ellipsometry and Monte Carlo simulations. The conjugate is a highly branched polyethyleneimine structure with ethyleneoxide chains grafted to its primary and secondary amino groups. In situ null ellipsometry demonstrated that the polymer conjugate adsorbs to the silica surface from water and aqueous solution of 1 mM asymmetric divalent salt (calcium and magnesium chloride to emulate hard water) over a large pH range. The adsorbed amount is hardly affected by pH and large charge reversal on the negatively charged silica surface occurred at pH = 4.0, due to the adsorption of the cationic polyelectrolyte. The Monte Carlo simulations using an appropriate coarse-grained model of the polymer in solution predicted a core-shell structure with no sharp boundary between the ethyleneimine and ethyleneoxide moieties. The structure at the interface is similar to that in solution when the polymer degree of protonation is low or moderate while at high degree of protonation the strong electrostatic attraction between the ethyleneimine core and oppositely charged silica surface distorts the ethyleneoxide shell so that an "anemone"-like configuration is adopted. The adsorption of alkyl benzene sulfonic acid (LAS) to a preadsorbed polymer layer was also investigated by null ellipsometry. The adsorption data brought additional support for the existence of a strong polymer adsorption and showed the presence of a binding which was further enhanced by the decreased solvency of the surfactant in the salt solution and confirmed the surface charge reversal by the polymer adsorption at pH = 4.0.


Efficient stochastic simulation of biochemical reactions with noise and delays.
The stochastic simulation algorithm has been used to generate exact trajectories of biochemical reaction networks. For each simulation step, the simulation selects a reaction and its firing time according to a probability that is proportional to the reaction propensity. We investigate in this paper new efficient formulations of the stochastic simulation algorithm to improve its computational efficiency. We examine the selection of the next reaction firing and reduce its computational cost by reusing the computation in the previous step. For biochemical reactions with delays, we present a new method for computing the firing time of the next reaction. The principle for computing the firing time of our approach is based on recycling of random numbers. Our new approach for generating the firing time of the next reaction is not only computationally efficient but also easy to implement. We further analyze and reduce the number of propensity updates when a delayed reaction occurred. We demonstrate the applicability of our improvements by experimenting with concrete biological models.


The protective effects of carnosine in alcohol-induced hepatic injury in rats.
Consumption of alcohol leads to oxidative stress in liver by inducing lipid peroxidation. The aim of this study was to investigate the effects of carnosine (CAR) in alcohol-induced liver injury by biochemical and histomorphological evaluations. The rats were divided into four groups, namely, control group, alcohol (AL) group, CAR group and AL + CAR group. Three doses of ethanol (5 g/kg, 25% (v/v) in distilled water) were given by nasogastric catheter for twice-a-day. CAR (100 mg/kg) was given 1 h before the administration of ethanol using the same method. Levels of alanine aminotransferase, aspartate aminotransferase, myeloperoxidase and malondialdehyde were significantly increased in the AL group compared with control, CAR and AL + CAR groups. Glutathione level was significantly decreased in the AL group, while it was increased in the AL + CAR group. Immunoreactivity of caspase-3 and bax increased in the hepatocytes of AL group when compared with control and AL + CAR groups. Expression of bcl-2 was decreased in AL group than AL + CAR group. Under electron microscopy, dense mitochondria, accumulation of lipid, sinusoidal dilatation, vacuolization and decrease in the number of microvilli were observed in AL group, while these findings were markedly less in the AL + CAR group. In conclusion, pretreatment of CAR is effective for recovering biochemical alterations and morphologic damage in the liver of rats treated with ethanol.


Myosin light chain phosphorylation facilitates in vivo myosin filament reassembly after mechanical perturbation.
Phosphorylation of the 20-kDa regulatory myosin light chain (MLC) of smooth muscle is known to cause monomeric myosins in solution to self-assemble into thick filaments. The role of MLC phosphorylation in thick filament formation in intact muscle, however, is not clear. It is not known whether the phosphorylation is necessary to initiate thick filament assembly in vivo. Here we show, by using a potent inhibitor of MLC kinase (wortmannin), that the MLC phosphorylation and isometric force in trachealis muscle could be abolished without affecting calcium transients. By measuring cross-sectional densities of the thick filaments electron microscopically, we also show that inhibition of MLC phosphorylation alone did not cause disassembly of the filaments. The unphosphorylated thick filaments, however, partially dissolved when the muscle was subjected to oscillatory strains (which caused a 25% decrease in the thick filament density). The postoscillation filament density recovered to the preoscillation level only when wortmannin was removed and the muscle was stimulated. The data suggest that in vivo thick filament reassembly after mechanical perturbation is facilitated by the cyclic MLC phosphorylation associated with repeated stimulation.


Dedifferentiation, transdifferentiation, and reprogramming: future directions in regenerative medicine.
The main goal of regenerative medicine is to replace damaged tissue. To do this it is necessary to understand in detail the whole regeneration process including differentiated cells that can be converted into progenitor cells (dedifferentiation), cells that can switch into another cell type (transdifferentiation), and somatic cells that can be induced to become pluripotent cells (reprogramming). By studying the regenerative processes in both nonmammal and mammal models, natural or artificial processes could underscore the molecular and cellular mechanisms behind these phenomena and be used to create future regenerative strategies for humans.


Diffusion permeability of an isolated rete mirabile.
The rete mirabile of the swimbladder of the eeel is a countercurrent exchange organ composed of alternately disposed and venous capillaries. A countercurrent perfusion of these was set up by isolating arterial input and outflow, and venous input and outflow, and perfusing each set of capillaries with oxygenated albumin-containing Krebs-Ringer bicarbonate buffer. Constant arterial infusions containing tracer albumin, inulin, 3-O-methylglucose, urea, and water were begun and tracer concentrations at the outlets of arterial and venous beds were determined. Capillary permeabilities were determined from the resulting steady state values. The method of calculation of permeability values from the data acquired in the rete involves no approximations and appears to yield unequivocal values. For the solutes, the values appear compatible with transcapillary passage by free diffusion. No evidence of increasing restriction (in comparison to the diffuse coefficients) was found over the range of molecular sizes explored. The permeability for labeled water, in relation to the solutes, was too high, and this augmentation was attributed to the larger surface available for its exchange. Despite this larger value, labeled water did not undergo flow-limited exchange. A significant barrier to its distribution is present in this capillary system.


Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists.
Neonates exhibit an increased risk of sepsis mortality compared with adults. We show that in contrast to adults, survival from polymicrobial sepsis in murine neonates does not depend on an intact adaptive immune system and is not improved by T cell-directed adaptive immunotherapy. Furthermore, neonates manifest an attenuated inflammatory and innate response to sepsis, and have functional defects in their peritoneal CD11b(+) cells. Activation of innate immunity with either a Toll-like receptor 4 (TLR4) or TLR7/8 agonist, but not a TLR3 agonist, increased the magnitude, but abbreviated the early systemic inflammatory response, reduced bacteremia, and improved survival to polymicrobial sepsis. TLR4 agonist pretreatment enhanced peritoneal neutrophil recruitment with increased oxidative burst production, whereas the TLR7/8 agonist also enhanced peritoneal neutrophil recruitment with increased phagocytic ability. These benefits were independent of the adaptive immune system and type I interferon signaling. Improving innate immune function with select TLR agonists may be a useful strategy to prevent neonatal sepsis mortality.


Pharmacokinetics, pharmacodynamics, metabolism, distribution, and excretion of carfilzomib in rats.
Carfilzomib [(2S)-N-[(S)-1-[(S)-4-methyl-1-[(R)-2-methyloxiran-2-yl]-1-oxopentan-2-ylcarbamoyl]-2-phenylethyl]-2-[(S)-2-(2-morpholinoacetamido)-4-phenylbutanamido]-4-methylpentanamide, also known as PR-171] is a selective, irreversible proteasome inhibitor that has shown encouraging results in clinical trials in multiple myeloma. In this study, the pharmacokinetics, pharmacodynamics, metabolism, distribution, and excretion of carfilzomib in Sprague-Dawley rats were characterized. After intravenous administration, the plasma concentration of carfilzomib declined rapidly in a biphasic manner. Carfilzomib displayed high plasma clearance [195-319 ml/(min · kg)], a short-terminal half-life (5-20 min), and rapid and wide tissue distribution in rats. The exposure to carfilzomib (C(max) and area under the curve) increased dose proportionally from 2 to 4 mg/kg but less than dose proportionally from 4 to 8 mg/kg. The high clearance was mediated predominantly by extrahepatic metabolism through peptidase cleavage and epoxide hydrolysis. Carfilzomib was excreted mainly as metabolites resulting from peptidase cleavage. Carfilzomib and its major metabolites in urine and bile accounted for approximately 26 and 31% of the total dose, respectively, for a total of 57% within 24 h postdose. Despite the high systemic clearance, potent proteasome inhibition was observed in blood and a variety of tissues. Together with rapid and irreversible target binding, the high clearance may provide an advantage in that "unnecessary" exposure to the drug is minimized and potential drug-related side effects may be reduced.


Evaluation of ocular pulse amplitude in non-arteritic anterior ischaemic optic neuropathy.
To evaluate the ocular pulse amplitude (OPA) in patients with chronic non-arteritic anterior ischaemic optic neuropathy (NAION). This cross-sectional study comprised a study group of 30 eyes from 30 patients with NAION and a control group of 31 eyes from 31 age and gender-matched healthy subjects. Bilateral OPA was measured with dynamic contour tonometry (DCT) and was compared between the study and control groups. No statistically significant difference was found between the study and control groups in terms of hypertension, diabetes mellitus, ischaemic heart disease and hyperlipidemia. The mean intraocular pressure (IOP) measured with Goldmann Applanation Tonometry and DCT in the study and control groups was not statistically different (p1 = 0.094, p2 = 0.240). The mean OPA in the study group and the control group were 2.01 ± 0.69 mmHg and 1.97 ± 0.68 mmHg (p = 0.839). No significant difference was determined in the OPA levels of eyes with NAION at the chronic stage and eyes in the control group.


Understanding the role of the public transport network in the greater Sydney area in providing access to dental care.
Objective The aim of this study was to examine the spatial accessibility of the aged and older adult population of the greater Sydney region to the bus public transport network, and the proximity of this transportation route to public and private dental services. Methods This study used geographic information systems (GIS) to examine, at a population level, the spatial accessibility of the public transport network and dental provider locations. The prime focus of the present study was on the aging population residing within 50 km of the General Post Office of metropolitan Sydney. Retirees (aged ≥65 years) and older adults (aged ≥85 years) were the two subsets of the aging population. Results Sydney's bus network is currently supplying bus transport to both older and disadvantaged groups, facilitating the needs of more than half a million older people. Regardless of socioeconomic status, 12% of the entire population, 11.5% of retirees and 10.8% of older adults resided 500 m away from accessible medium-frequency bus stops. Approximately 40% of the overall population consisted of people of lower socioeconomic status living within 500 m of a medium-frequency bus stop, whereas 60% of the population were of a high socioeconomic status and lived within 500 m of a medium-frequency bus stop. Conclusion Metropolitan Sydney has a transport system that is substantial and robust, and appears to offer relatively similar spatial accessibility for all socioeconomic groups. This system is an example of great urban planning, where the distribution of bus stops is evenly positioned in both high-density areas and areas of low socioeconomic status. What is known about the topic? Older adults and disadvantaged people suffer from higher levels of dental disease compared with the rest of the population. Older adults and disadvantaged people are more likely to rely on public transport to access healthcare services, including dental care. The Australian population is aging rapidly. What does this paper add? Although a previous study examined the accessibility to services via the train network, this is the first analysis of the spatial accessibility to dental services via the bus network in Sydney. Most older adults and disadvantaged people in Sydney enjoy acceptable spatial access to the public transport network, and thereby to dental practices. Urban planning, in terms of determining healthcare service locations and the public transport network, needs to consider the distribution of older adults and disadvantaged populations. What are the implications for practitioners? Practitioners are more likely to attract older adult patients to their practices or clinics if these are located within easy access to the public transport network.


Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies.
To determine the prevalence of hospital admissions associated with ADRs and examine differences in prevalence rates between population groups and methods of ADR detection. Studies were identified through electronic searches of Cumulative Index to Nursing and Allied Health Literature, EMBASE, and MEDLINE to August 2007. There were no language restrictions. A systematic review was conducted of prospective observational studies that used the World Health Organization ADR definition. Subgroup analysis examined the influence of patient age groups and methods of ADR detection on reported ADR admission rates. All statistical analyses were performed using STATA v 9.0. Twenty-five studies were identified including 106,586 patients who were hospitalized; 2143 of these patients had experienced ADRs. The prevalence rates of ADRs ranged from 0.16% to 15.7%, with an overall median of 5.3% (interquartile range [IQR] 2.7-9.0%). Median ADR prevalence rates varied between age groups; for children, the ADR admission rate was 4.1% (IQR 0.16-5.3%), while the corresponding rates for adults and elderly patients were 6.3% (IQR 3.9-9.0%) and 10.7% (IQR 9.6-13.3%), respectively. ADR rates also varied depending on the methods of ADR detection employed in the different studies. Studies that employed multiple ADR detection methods, such as medical record review and patient interview, reported higher ADR admission rates compared with studies that used medical record review alone. Anti-infective drugs were most often associated with ADR admissions in children; cardiovascular drugs were most often associated with ADR admissions in adults and elderly patients. Approximately 5.3% of hospital admissions were associated with ADRs. Higher rates were found in elderly patients who are likely to be receiving multiple medications for long-term illnesses. The methods used to detect ADRs are also likely to explain much of the variation in the reported ADR prevalence rates between different studies.


High Prevalence and Predominance of the aph(2″)-If Gene Conferring Aminoglycoside Resistance in Campylobacter.
Campylobacter is a major foodborne pathogen, and previous studies revealed that Campylobacter isolates from food-producing animals are increasingly resistant to gentamicin in China. The molecular epidemiology and genetic mechanisms responsible for gentamicin resistance in China have not been well understood. In this study, 607 Campylobacter isolates of chicken and swine origins collected in 2014 were analyzed, revealing that 15.6% (25/160) of the Campylobacter jejuni isolates and 79.9% (357/447) of the Campylobacter coli isolates were resistant to gentamicin. PCR detection of the gentamicin resistance genes indicated that aph(2″)-If was more prevalent than the previously identified aacA/aphD gene and has become the dominant gentamicin resistance determinant in Campylobacter Transformation and whole-genome sequencing as well as long-range PCR discovered that aph(2″)-If was located on a chromosomal segment inserted between two conserved genes, Cj0299 and panB Cloning of aph(2″)-If into gentamicin-susceptible C. jejuni NCTC 11168 confirmed its function in conferring high-level resistance to gentamicin and kanamycin. Molecular typing by pulsed-field gel electrophoresis suggested that both regional expansion of a particular clone and horizontal transmission were involved in the dissemination of the aph(2″)-If gene in Campylobacter To our knowledge, this is the first report describing the high prevalence of a chromosomally encoded aph(2″)-If gene in Campylobacter The high prevalence and predominance of this gene might be driven by the use of aminoglycoside antibiotics in food animal production in China and potentially compromise the usefulness of gentamicin as a therapeutic agent for Campylobacter-associated systemic infection.


The dampening effect of employees' future orientation on cyberloafing behaviors: the mediating role of self-control.
Previous studies on reducing employees' cyberloafing behaviors have primarily examined the external control factors but seldomly taken individual internal subjective factors into consideration. Future orientation, an important individual factor, is defined as the extent to which one plans for future time and considers future consequences of one's current behavior. To explore further whether and how employees' future orientation can dampen their cyberloafing behaviors, two studies were conducted to examine the relationship between employees' future orientation and cyberloafing behaviors. The mediation effect of employees' objective and subjective self-control between them was also examined. In Study 1, a set of questionnaires was completed, and the results revealed that the relationship between employees' future orientation and cyberloafing behaviors was negative, and objective self-control mediated the relationship. Next, we conducted a priming experiment (Study 2) to examine the causal relationship and psychological mechanism between employees' future orientation and cyberloafing behaviors. The results demonstrated that employees' future-orientation dampened their attitudes and intentions to engage in cyberloafing, and subjective self-control mediated this dampening effect. Theoretical and practical implications of these findings are also discussed.


Opposite effects of different strains or batches of same strain of BCG on in vitro generation of syngeneic and allogeneic antitumor cytotoxicity.
Pretreatment of mice with three batches of BCG Phipps strain 10 days before in vitro immunization of their spleen cells with syngeneic or allogeneic tumor cells augmented the levels of antitumor cytotoxicity (compared to the levels exhibited by in vitro immunized spleen cells from normal mice), whereas pretreatment with another batch of BCG Phipps strain or with a batch of BCG Tice strain suppressed antitumor cytotoxicity. The suppressive effects of these BCG vaccines could not be attributed to route of administration, dose of BCG, or percentage of colony-forming units in an inoculum. The effect of the interval between BCG pretreatment and in vitro immunization on the generation of antitumor cytotoxicity was evaluated; one BCG batch was of special interest, inasmuch as augmented cytotoxicity was obtained when the interval was short and suppressed cytotoxicity was obtained when the interval was long.


Coregistration of multimodal imaging is associated with favourable two-year seizure outcome after paediatric epilepsy surgery.
Multimodal coregistration uses multiple image datasets coregistered to an anatomical reference (i.e. MRI), allowing multiple studies to be viewed together. Commonly used in intractable epilepsy evaluation and generally accepted to improve localization of the epileptogenic zone, data showing that coregistration improves outcome is lacking. We compared seizure freedom following epilepsy surgery in paediatric patients, evaluated before and after the use of coregistration protocols at our centre, to determine whether this correlated with a change in outcome. We included paediatric epilepsy surgery patients with at least one anatomical and one functional neuroimaging study as part of their presurgical evaluation. Preoperatively designated palliative procedures and repeat surgeries were excluded. Multiple pre-, peri-, and postoperative variables were compared between groups with the primary outcome of seizure freedom. In total, 115 were included with an average age of 10.63 years (0.12-20.7). All evaluations included video-EEG (VEEG) and MRI. Seven (6%) had subtraction single-photon emission CT (SPECT), 46 (40%) had positron emission tomography (PET), and 62 (54%) had both as part of their evaluation. Sixty (52%) had extratemporal epilepsy and 25 (22%) were MRI-negative. Sixty-eight (59%) had coregistration. Coregistered patients were less likely to undergo invasive EEG monitoring (p=0.045) and were more likely to have seizure freedom at one (p=0.034) and two years (p<0.001) post-operatively. A logistic regression accounting for multiple covariates supported an association between the use of coregistration and favourable post-surgical outcome. Coregistered imaging contributes to favourable postoperative seizure reduction compared to visual analysis of individual modalities. Imaging coregistration is associated with improved outcome, independent of other variables after surgery. Coregistered imaging may reduce the need for invasive EEG monitoring, likely due to improved confidence in presurgical localization. These findings support the use of multimodal coregistered imaging as part of the presurgical assessment in patients evaluated for surgical treatment of intractable epilepsy.


Autoimmune paraneoplastic cerebellar degeneration: ultrastructural localization of antibody-binding sites in Purkinje cells.
Sera from three of four patients with paraneoplastic cerebellar degeneration (PCD) associated with gynecologic cancer had antibodies that stained the cytoplasm of Purkinje cells in a characteristic discrete and coarsely granular pattern. No such antibodies were found in PCD patients with small cell cancer of the lung, in patients with cerebellar degeneration without cancer, in nonneurologic patients with small cell carcinoma or gynecologic cancer, or in normal subjects. Immunoelectron microscopy revealed that the antibodies of PCD bound to clusters of ribosomes, granular endoplasmic reticulum, and the trans-face of the vesicles of the Golgi complex in Purkinje cells. Immunostaining was localized in orderly arrays of stacked parallel cisternae of the endoplasmic reticulum in the perikaryon and dendritic processes. This pattern suggested that at least one autoantigen of PCD may be a glycoprotein specific cerebellar tissue that is associated with the endoplasmic reticulum. Some patches of Purkinje plasma membrane also were immunostained.


Wear patterns and dental functioning in an Early Cretaceous stegosaur from Yakutia, Eastern Russia.
Isolated stegosaurian teeth from the Early Cretaceous high-latitude (palaeolatitude estimate of N 62°- 66.5°) Teete locality in Yakutia (Eastern Siberia, Russia) are characterized by a labiolingually compressed, slightly asymmetrical and mesiodistally denticulated (9-14 denticles) crown, a pronounced ring-like cingulum, as well as a "complex network of secondary ridges". The 63 teeth (found during on-site excavation in 2012, 2017-2019 and screen-washing in 2017-2019) most likely belong to one species of a derived (stegosaurine) stegosaur. Most of the teeth exhibit a high degree of wear and up to three wear facets has been observed on a single tooth. The prevalence of worn teeth with up to three wear facets and the presence of different types of facets (including steeply inclined and groove-like) indicate the tooth-tooth contact and precise dental occlusion in the Teete stegosaur. The microwear pattern (mesiodistally or slightly obliquely oriented scratches; differently oriented straight and curved scratches on some wear facets) suggest a complex jaw mechanism with palinal jaw motion. Histological analysis revealed that the Teete stegosaur is characterized by relatively short tooth formation time (95 days) and the presence of a "wavy enamel pattern". Discoveries of a "wavy enamel pattern" in the Teete stegosaur, in a Middle Jurassic stegosaur from Western Siberia, and in the basal ceratopsian Psittacosaurus, suggest that this histological feature is common for different ornithischian clades, including ornithopods, marginocephalians, and thyreophorans. A juvenile tooth in the Teete sample indicates that stegosaurs were year-round residents and reproduced in high latitudes. The combination of high degree of tooth wear with formation of multiple wear facets, complex jaw motions, relatively short tooth formation time and possibly high tooth replacement rates is interpreted as a special adaptation for a life in high-latitude conditions or, alternatively, as a common stegosaurian adaptation making stegosaurs a successful group of herbivorous dinosaurs in the Middle Jurassic-Early Cretaceous and enabeling them to live in both low- and high-latitude ecosystems.


Matrix-assisted laser desorption/ionization mass spectrometry of restriction enzyme-digested plasmid DNA using an active Nafion substrate.
Matrix-assisted laser desorption/ionization using a 3-hydroxypicolinic acid matrix from an active Nafion substrate has been used for detection of restriction enzyme-digested double-stranded plasmid DNA using time-of-flight mass spectrometry. DNA strands of up to 267 base pairs were detected with minimal sample purification, although only as species corresponding to single-stranded DNA.


Circulating microRNA, miR-122 and miR-221 signature in Egyptian patients with chronic hepatitis C related hepatocellular carcinoma.
To explore the potential usefulness of serum miR-122 and miR-221 as non-invasive diagnostic markers of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). This prospective study was conducted on 90 adult patients of both sex with HCV-related chronic liver disease and chronic hepatitis C related HCC. In addition to the 10 healthy control individuals, patients were stratified into; interferon-naïve chronic hepatitis C (CH) (n = 30), post-hepatitis C compensated cirrhosis (LC) (n = 30) and treatment-naïve HCC (n = 30). All patients and controls underwent full clinical assessment and laboratory investigations in addition to the evaluation of the level of serum miRNA expression by RT-PCR. There was a significant fold change in serum miRNA expression in the different patient groups when compared to normal controls; miR-122 showed significant fold increasing in both CH and HCC and significant fold decrease in LC. On the other hand, miR-221 showed significant fold elevation in both CH and LC groups and significant fold decrease in HCC group (P = 0.01). Comparing fold changes in miRNAs in HCC group vs non HCC group (CH and Cirrhosis), there was non-significant fold elevation in miR-122 (P = 0.21) and significant fold decreasing in miR-221 in HCC vs non-HCC (P = 0.03). ROC curve analysis for miR-221 yielded 87% sensitivity and 40% specificity for the differentiation of HCC patients from non-HCC at a cutoff 1.82. Serum miR-221 has a strong potential to serve as one of the novel non-invasive biomarkers of HCC.


A Rare Presentation of Acute Kidney Injury in Diffuse Large B-Cell Lymphoma: A Case Report.
Acute kidney injury from bilateral renal infiltration is rare in diffuse large B-cell lymphoma (DLBCL). We present the case of a 45-year-old woman with a three-month history of night sweats, weight loss, fever, and fatigue. Clinical evaluation revealed anemia, edema, cervical lymphadenopathy, and elevated blood pressure. Initial lab results indicated severe kidney injury, initially suspected to be chronic kidney disease, later ruled out. Radiological assessments confirmed mediastinal lymphadenopathy. A cervical lymph node biopsy led to a diagnosis of DLBCL. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy improved renal function and hematological parameters. Subsequent staging CT confirmed lymphadenopathy. Close monitoring revealed a complete return to normal renal function after one month. Further follow-up was missed. This case emphasizes diagnostic complexities and the value of a multidisciplinary approach in managing complex clinical presentations.


Importance of tumor size and repopulation for radiocurability of skin cancer.
Data on 946 skin cancers treated by radiation were used to estimate the importance of repopulation. Six different treatment regimes were used from a single dose to 74 Gy given in 47 fractions. High local control of the small skin cancers (L 1 cm) was independent of dose fractionation. For large tumors, only 74 Gy in 47 fractions was the optimal treatment. Time factor analysis showed a steep increase in the NTD50 values between day 28 and 65 of treatment. This implies that tumor clonogen repopulation starts around 4 weeks of treatment. The present results showed a three-component dose response curve instead of the two-component curves which were found for head and neck and bladder cancer.


Catalogue of the Order Amphipoda from Brazil (Crustacea, Peracarida): Suborders Amphilochidea, Senticaudata and Order Ingolfiellida.
This catalog documents 303 species within 142 genera and 56 families distributed in the suborders Amphilochidea, Senticaudata and order Ingolfiellida that have been described or reported for the Brazilian coast and continent. Data for these species such as type material, type locality, geographic and bathymetric distribution, ecological notes and remarks, when pertinent, was given. From these, 268 species (~ 90%) are benthonic, marine and/or estuarine occurring from a diverse type of substrates as sediment, algae, sponges, cnidarians, ascideans, mangrove roots, fouling habitats, coral rubble, rodolith banks, etc. In terms of bathymetry, there are 214 species (~ 80%) reported for the Brazilian continental shelf (0-200 m) and 60 (~20%) for the deep sea zone (> 200 m, 50% from the Campos Basin area). There are 35 non-marine amphipods reported from Brazil. Hyalella is the restricted and dominant epigean group and is represented by 22 species, including some hypogean and cave species. Cave dwellers includes 15 species within 6 genera as: Hyalella (5); Megagidiella (1); Potiberaba (1); Spelaeogammarus (7), and Seborgia (1). Among the Bogidiellidae, Bogidiella neotropica Ruffo, 1952 and Marigidiella brasiliensis (Siewing, 1953) are hypogean, but not from caves. The former is the only amphipod species recorded from the Brazilian Amazon Biome, within the Tapajós River, Pará and the latter are found in marine coastal groundwater of Bahia and São Paulo. Considering the landhoppers (truly terrestrial), only two introduced species, Talitroides alluaudi (Chevreux, 1896) and Talitroides topitotum (Burt, 1934) have been found in the Atlantic forest biome, urban parks and sylviculture plantations from the southeast and south of Brazil. Moreover, several amphipod records for Brazil were noticed to be dubious or misidentifications and are listed in a table with pertinent literature.


Geometric differences of the mitral valve apparatus in atrial and ventricular functional mitral regurgitation.
Functional mitral regurgitation (FMR) occurs in patients with annular dilation (atrial, aFMR) or patients with left ventricular (LV) disease (ventricular, vFMR). Meticulous understanding of the mechanisms underpinning regurgitation is crucial to optimize therapeutic strategies. Patients with moderate-severe FMR were identified from a registry of patients referred for transcatheter mitral valve intervention. In addition, controls without cardiovascular disease were identified. Differences in the geometry of the LV and mitral valve apparatus (including leaflet and tenting geometry, papillary muscle displacement and movement, annular dimensions, and dynamism) between atrial and ventricular FMR, and control subjects, were assessed using multiphasic cardiac CT. Of 183 FMR patients, 18 patients (10%) were found to have aFMR. The remaining patients had either ischemic or non-ischemic ventricular FMR. In aFMR, both increasing LV end-systolic volume (rho 0.701, p < 0.01) and left atrial volume (rho 0.909, p < 0.01) were associated with larger annular area. By contrast, in vFMR larger annular area was most strongly associated with larger left atrial volume (rho 0.63, p < 0.01). In controls, increased annular area was associated with larger LVEDV (rho 0.78, p < 0.01) and LVESV (rho 0.824, p < 0.01), but not left atrial size (rho 0.16, p = 0.45). Ventricular FMR comprised apicolaterally displaced, akinetic posteromedial papillary muscles, resulting in pronounced leaflet tethering, leaflet elongation compared to controls, and only modest relative LA dilatation. Compared to vFMR, aFMR was characterised by marked relative annular dilation, smaller but discernible mitral valve tenting, shorter leaflet lengths when related to annular size, but normal papillary geometry. FMR is characterised by multiple changes within the mitral valve complex. Atrial and ventricular FMR differ significantly in terms of the drivers of annular size, and geometry and function of the subvalvular apparatus. This highlights the need to consider these as separate disease entities.


Respiratory viruses in nepalese children with and without pneumonia: a case-control study.
The causative role of respiratory viruses detected in upper airway secretions in childhood pneumonia needs further investigation. To measure the association between infection with respiratory RNA viruses and pneumonia in children. From March 2006 to July 2007, we conducted a case-control study of 680 pneumonia cases (WHO criteria) and 680 randomly selected, concurrently sampled age-matched controls among children aged 2-35 months in Bhaktapur, Nepal. A nasopharyngeal aspirate from each child was examined for 7 respiratory viruses using reverse transcription polymerase chain reaction. We calculated the matched odds ratios (MORs) for the detection of the individual viruses from a case compared with a control as measures of pathogenicity using conditional logistic regression. At least 1 virus was recovered in 248 (36.5%) cases and 48 (7.1%) controls. The MOR varied from 2.0 to 13.0; the highest associations were observed for parainfluenza virus type 3 (MOR 13.0; 95% confidence interval [CI] 6.0-28.0), respiratory syncytial virus (MOR 10.7; CI 4.6-24.6), and influenza A (MOR 6.3; CI 1.9-21.4). We observed that the association was lower for children age 2-5 months compared with older children for parainfluenza virus type 3 (P value for interaction 0.002). All of the 7 respiratory viruses were associated with pneumonia, but their pathogenicity varied. Parainfluenza type 3, RSV, and influenza A were most strongly associated with pneumonia.


Ultrasound assessment of the elbow.
Ultrasonography of the elbow is a very helpful and reliable diagnostic procedure for a broad spectrum of rheumatic and orthopedic conditions, representing a possible substitute to magnetic resonance imaging for evaluation of soft tissues of the elbow. Musculoskeletal ultrasound (US) shows many advantages over other imaging modalities, probably the most important being its capability to perform a dynamic assessment of musculoskeletal elements with patient's partnership and observation during examination. In addition, ultrasonography is cost effective, easy available, and has excellent and multiplanar capability to visualize superficial soft tissue structures. Among all imaging procedures, US is highly accepted by patients. US assessment of the elbow requires good operator experience in the assessment of normal anatomy, and suitable high-quality equipment. US of the elbow provides detailed information including joint effusions, medial and lateral epicondylitis, tears of the distal biceps and triceps tendons, radial and ulnar collateral ligament tears, ulnar nerve entrapment, cubital or olecranon bursitis and intra-articular loose bodies. The aim of this paper is to review the screening technique and the basic normal and pathological findings in elbow US.


Total knee arthroplasty following patellectomy.
Patients with prior patellectomy may continue to experience pain and instability following total knee arthroplasty. Seventeen such cases were found, 14 of which were available for study. One knee was fused for deep infection. Of the remaining 13, six were revised for continuing pain. The final results correlated to the intrinsic stability of the prosthesis. All hinges (5 cases) had good results, one of two unlinked hinges had good results, and two of six semiconstrained prostheses had acceptable results. Since the patellar mechanism with the cruciates functions as a four-bar linkage to ensure functional anteroposterior stability, one of these linkage systems must remain intact. If both are destroyed, a prosthesis with inherent anteroposterior stability should be used.


An investigation of stop place of articulation as a function of syllable position: a locus equation perspective.
Locus equations were employed to phonetically describe stop place categories as a function of syllable-initial, -medial, and -final position. Ten speakers, five male and five female, produced a total of 2700 CVC and 4500 VCV utterances that were acoustically analyzed to obtain F2 onset, F2 vowel, and F2 offset frequencies for locus equation regression analyses. In general, degree of coarticulation, as indexed by locus equation slope, was reduced for post-vocalic (VC) stops relative to pre-vocalic stops (pooled data from initial and medial positions), but significant differences were observed as a function of stop consonant. All stops showed significantly reduced R2 values and increased standard errors of estimate for VC relative to CV productions. Separability of stop place categories in a higher-order slope X y-intercept acoustic space also diminished for VC vs CV stop productions. The degradation of classic locus equation form (high correlation and linearity) for VC relative to CV productions was attributed to greater articulatory precision in the production of pre-vocalic compared to post-vocalic stops. This greater articulatory precision was interpreted as reflecting a greater need to normalize vowel context-induced variability of the F2 transition for syllable onset relative to final stops. The decline in acoustic lawfulness of syllable-final stops is discussed in terms of coarticulatory interactions and expected perceptual correlates.


Movienet: Deep space-time-coil reconstruction network without k-space data consistency for fast motion-resolved 4D MRI.
To develop a novel deep learning approach for 4D-MRI reconstruction, named Movienet, which exploits space-time-coil correlations and motion preservation instead of k-space data consistency, to accelerate the acquisition of golden-angle radial data and enable subsecond reconstruction times in dynamic MRI. Movienet uses a U-net architecture with modified residual learning blocks that operate entirely in the image domain to remove aliasing artifacts and reconstruct an unaliased motion-resolved 4D image. Motion preservation is enforced by sorting the input image and reference for training in a linear motion order from expiration to inspiration. The input image was collected with a lower scan time than the reference XD-GRASP image used for training. Movienet is demonstrated for motion-resolved 4D MRI and motion-resistant 3D MRI of abdominal tumors on a therapeutic 1.5T MR-Linac (1.5-fold acquisition acceleration) and diagnostic 3T MRI scanners (2-fold and 2.25-fold acquisition acceleration for 4D and 3D, respectively). Image quality was evaluated quantitatively and qualitatively by expert clinical readers. The reconstruction time of Movienet was 0.69 s (4 motion states) and 0.75 s (10 motion states), which is substantially lower than iterative XD-GRASP and unrolled reconstruction networks. Movienet enables faster acquisition than XD-GRASP with similar overall image quality and improved suppression of streaking artifacts. Movienet accelerates data acquisition with respect to compressed sensing and reconstructs 4D images in less than 1 s, which would enable an efficient implementation of 4D MRI in a clinical setting for fast motion-resistant 3D anatomical imaging or motion-resolved 4D imaging.


Prolonged dual antiplatelet therapy in invasively treated acute coronary syndrome patients with different lipoprotein(a) concentrations.
Lipoprotein(a) [Lp(a)] was positively associated with recurrent ischemic events in patients with acute coronary syndrome (ACS). This study was performed to investigate the effect of Lp(a) levels on outcomes of dual antiplatelet therapy (DAPT) > 1 year versus DAPT ≤ 1 year after percutaneous coronary intervention (PCI) in this population. A total of 4,357 ACS patients who were event-free at 1 year after PCI were selected from the Fuwai PCI Registry, and patients were stratified into four groups according to DAPT duration (≤ 1 year vs. > 1 year) and Lp(a) levels (≤ 30 mg/dL vs. > 30 mg/dL). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of cardiac death, myocardial infarction or stroke. After 2.4-year follow-up, the incidence of MACCE (HRadjusted 0.284, 95% CI 0.115-0.700; HRIPTW 0.351, 95% CI 0.164-0.751) were significantly reduced in DAPT > 1 year group than that in DAPT ≤ 1 year group in individuals with elevated Lp(a) levels. However, in individuals with normal Lp(a) levels, no statistically difference was found between these two groups in terms of MACCE, although the risks of all-cause death and definite/probable stent thrombosis were lower in DAPT > 1 year group. Notably, the risk of clinically relevant bleeding did not statistically differ between these two groups in individuals with different Lp(a) levels. This study firstly demonstrated that extended DAPT (> 1 year) was statistically associated with lower risk of ischemic events in ACS patients with elevated Lp(a) levels after PCI, whereas this association was not found in individuals with normal Lp(a) levels.


Infant Dengue a 10-Year Experience from a Tertiary Center in South India.
Dengue remains a major problem in the tropics. Several Asian countries have reported an increasing trend in the proportion of infants with dengue fever. However, most studies are limited to case reports or small case series from isolated outbreaks. We planned this study to look at clinico-laboratory profile, outcome, and predictors of severity in a large cohort of infants over a decade. Electronic medical records of infants admitted at a tertiary center of South India, with laboratory confirmed dengue infection between 2009 and 2019 were reviewed. Diagnosis was based on detection of NS-1 antigen and/or immunoglobulin M antibody against DENV(dengue virus) or positive DENV RNA polymerase chain reaction in infants presenting with acute febrile illness and clinical features consistent with dengue. Of 395 children with dengue admitted during study period, 99 (25%) were infants. A cyclical incidence pattern was noted, with higher cases in alternate years. Fever (99%) was most common, followed by gastrointestinal symptoms (vomiting, diarrhea-28%) and upper respiratory symptoms (cough, coryza-22%). Fifty-three infants had severe dengue, and 39 had shock. Fourteen children had multiorgan dysfunction syndrome, and 13 died. Infants with severe dengue were older than those with nonsevere disease, had lower serum albumin and greater frequency of severe thrombocytopenia, and had coagulopathy. On multivariable analysis, low serum albumin predicted development of severe dengue [P = 0.003, odds ratio 12.4 (95% confidence interval: 2.42-63.7)]. Dengue in infants may be challenging to recognize because of its undifferentiated presentation, with gastrointestinal and upper respiratory symptoms that are similar to other viral illness. Severe dengue is common in this sample, and lower serum albumin at presentation was predictive of severe disease.


Cross-cultural differences in somatic awareness and interoceptive accuracy: a review of the literature and directions for future research.
This review examines cross-cultural differences in interoception and the role of culturally bound epistemologies, historical traditions, and contemplative practices to assess four aspects of culture and interoception: (1) the extent to which members from Western and non-Western cultural groups exhibit differential levels of interoceptive accuracy and somatic awareness; (2) the mechanistic origins that can explain these cultural differences, (3) culturally bound behavioral practices that have been empirically shown to affect interoception, and (4) consequences for culturally bound psychopathologies. The following outlines the scope of the scientific review. Part 1 reviews studies on cultural variation in spontaneous somatic word use, linguistic expressions, traditional medical practices, and empirical laboratory studies to assess the evidence for cultural differences in somatic processes. Integration of these findings suggests a startling paradox: on the one hand, non-Western cultures consistently exhibit heightened somatic focus and awareness across a variety of contexts; on the other hand, non-Western cultures also exhibit less interoceptive accuracy in laboratory studies. Part 2 discusses the various mechanistic explanations that have been proposed to explain these cultural differences in somatic awareness and interoceptive accuracy, focusing on cultural schemas and epistemologies. Part 3 addresses the behavioral and contemplative practices that have been proposed as possible "interventions," or methods of cultivating bodily awareness and perceptual accuracy. Finally, Part 4 reviews the consequences of interoception for psychopathology, including somatization, body dysmorphia, eating disorders, and anxiety disorders.


Latent structure of the Children's Category Test after pediatric traumatic head injury.
The performance of 100 9-16-year-old children with traumatic head injury (THI) on the Children's Category Test (CCT-2; Boll, 1993) was examined to determine the underlying factor structure. Exploratory principal factor analysis with oblique rotation identified a two-factor solution. Factor 1 was composed primarily of subtests IV, V, and VI, whereas Factor 2 was defined primarily by subtests III and VI. Age and Full Scale IQ, as measured by the Wechsler Intellectual Scale for Children-Third Edition (WISC-III; Wechsler, 1991), were significantly related to both factors. Factor 1, but not Factor 2, demonstrated clear sensitivity to severity of THI. It is concluded that interpretation of the CCT-2 with children who have sustained a THI should consider the multifactorial nature of the instrument, and that exclusive reliance on the summary total error score may impede diagnostic accuracy.


DNA microarray analysis of Salmonella serotype Typhimurium strains causing different symptoms of disease.
Salmonella enterica subsp. enterica is one of the leading food-borne pathogens in the USA and European countries. Outcome of human Salmonella serotype Typhimurium infections ranges from mild self-limiting diarrhoea to severe diarrhoea that requires hospitalization. Increased knowledge of the mechanisms that are responsible for causing infection and especially the severity of infection is of high interest. Strains were selected from patients with mild infections (n = 9) and patients with severe infections (n = 9) and clinical data allowed us to correct for known underlying diseases. Additionally, outbreak isolates (n = 3) were selected. Strains were analyzed on a DNA-DNA microarray for presence or absence of 281 genes covering marker groups of genes related to pathogenicity, phages, antimicrobial resistance, fimbriae, mobility, serotype and metabolism. Strains showed highly similar profiles when comparing virulence associated genes, but differences between strains were detected in the prophage marker group. The Salmonella virulence plasmid was present in 72% of the strains, but presence or absence of the virulence plasmid did not correspond to disease symptoms. A dendrogram clustered strains into four groups. Clustering confirmed DT104 as being a clonal phagetype. Clustering of the remaining strains was mainly correlated to presence or absence of the virulence plasmid and mobile elements such as transposons. Each of the four clusters in the tree represented an almost equal amount of strains causing severe or mild symptoms of infection. We investigated clinical significance of known virulence factors of Salmonella serotype Typhimurium strains causing different disease symptoms, and conclude that the few detected differences in Salmonella serotype Typhimurium do not affect outcome of human disease.


Antioxidant activity of indigenous edible mushrooms.
The current study was undertaken to measure the antioxidant potential from water and methanolic extracts of fruiting bodies of 23 species of mushrooms naturally grown in different geographic locations of India. The antioxidant ability of each species was analyzed for the total antioxidative status, employing multimechanistic antioxidative assays such as inhibition of lipid peroxidation, determination of reducing power, and free radical scavenging ability, in addition to determination of total phenolics and identification of phenolic acids by HPLC analysis, because the phenolics are known to contribute largely to antioxidant potential. The antioxidant potential of these varieties of mushrooms was determined by summing the antioxidative activity (AOA) of each variety by varied antioxidant assays followed by determining the relative percent of AOA defined as the "antioxidant index" (AI). On the basis of the AI, the mushroom species were graded as very high, high, moderate, and low. Termitomyces heimii was identified as the best variety, which showed 100% AI with 37 mg of phenolics/g of sample, 418 units of reducing power ability (RPA)/g, and an IC50 of approximately 1.1 mg (dry weight)/mL, free radical scavenging activity (FRS) in the water extract followed by 11.2 mg of phenolics/g, 275 units of RPA/g, and an IC50 of approximately 2.7 mg (dry weight)/mL of FRS in the methanolic extract. Following T. heimii, Termitomyces mummiformis exhibited an AI of 86% within the "very high" group. Potent inhibitions of lipid peroxidation of approximately 100 and 69% was also observed in T. heimii and T. mummiformis, respectively. Water extracts ranged from 34 to 49% and methanolic extracts varied from 20 to 32% on dry weight of mushroom fruiting body. Total phenolic compounds were higher in the water extracts (2-37 mg/g) than in methanolic extract (0.7-11.2 mg/g). The AOA measured in the water extract was better than that from the methanolic extract. HPLC analysis of phenolic acids in the two mushroom species, namely, T. heimii and T. mummiformis, displaying maximum AOA potential indicated a preponderance of tannic acid, gallic acid, protocatacheuic acid, and gentisic acid. Studies thus provide the precise antioxidant status of 23 indigenous species of mushrooms, which can serve as a useful database for the selection of mushrooms for the function of preparation of mushroom-based nutraceutics.


Recent Advances in Asymmetric Catalytic Methods for the Formation of Acyclic α,α-Disubstituted α-Amino Acids.
Because of their greater stability and unique conformational properties, unnatural amino acids are highly valued by pharmaceutical, biological, and organic chemists. This synopsis surveys the various catalytic methods used to access enantioenriched, acyclic α,α-disubstituted α-amino acids with a focus on the processes developed since 2007, when the last major reviews in this area were published.


Morphometric analysis of the vestibular complex in the rat.
The characteristics of the four major vestibular nuclei and accessory cell groups in the rat have been studied in serially cut horizontal sections. Camera lucida drawings of the vestibular nuclei and their neurons were made in these sections and subjected to a computerized image analysis. The dimensions (volume and length) and the number of cells of each vestibular nucleus were obtained, as well as morphometric parameters of their neurons (cross-sectional area, maximum and minimum diameter, and shape). These parameters were statistically analyzed by comparing the cell population from different nuclei and different parts of each nucleus. Of the major nuclei, the medial, which is the largest, has the greatest number of cells, its neurons being the smallest of all the nuclei, with the size of cells decreasing in a rostrocaudal direction. In contrast, the lateral nucleus contains the fewest cells but also the largest ones. Neurons of the superior and descending nuclei are of an intermediate size and number, with a rostrocaudal decrease in the size of the descending nucleus cells. In addition, minor nuclei are identified and described in their relationship to the other structures in the brain stem. The relevant aspects of the anatomical information in regard to functional roles are reviewed.


Behavior change and health-related interventions for heterosexual risk reduction among drug users.
Prevention of heterosexual transmission of HIV between and from drug users is important for controlling the local and global HIV heterosexual epidemic. Sex risk reduction interventions and health-related interventions are important for reducing the sex risk behaviors of drug users. Sex risk reduction interventions address individual-level, peer-level, and structural-level determinants of risk reduction. Health-related interventions include HIV counseling and testing, prevention and treatment of sexually transmitted diseases, and delivery of highly active antiretroviral therapy. It is important to adapt effective interventions implemented in resource-rich countries to the realities of the resource-constrained settings and to address relevant contextual factors.


Glyoxylate, a new marker metabolite of type 2 diabetes.
Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs). Reactive aldehydes derived from sugars play an important role in the generation of AGEs. Using metabolite profiling to characterize human plasma from diabetic versus nondiabetic subjects we observed in a recent study that the reactive aldehyde glyoxylate was increased before high levels of plasma glucose, typical for a diabetic condition, could be measured. Following this observation, we explored the relevance of increased glyoxylate in diabetic subjects and in diabetic C57BLKS/J-Lepr (db/db (-/-)) mice in the pathophysiology of diabetes. A retrospective study using samples of long-term blood donors revealed that glyoxylate levels unlike glucose levels became significantly elevated up to 3 years prior to diabetes diagnosis (difference to control P = 0.034). Elevated glyoxylate levels impact on newly identified mechanisms linking hyperglycemia and AGE production with diabetes-associated complications such as diabetic nephropathy. Glyoxylate in its metabolic network may serve as an early marker in diabetes diagnosis with predictive qualities for associated complications and as potential to guide the development of new antidiabetic therapies.


Laparoscopic Pyeloplasty for Ureteropelvic Junctions Obstruction in Adults: 6 Years' Experience in One Center.
Ureteropelvic junction obstruction (UPJO) is a common cause of symptomatic ureteral obstruction. The aim of this study is to assess the outcome of laparoscopic pyeloplasty in patients with UPJO. Medical reports of 47 UPJO patients treated with laparoscopic pyeloplasty were retrospectively analysed. All patients were recruited from our center in the period 2004-2011. We evaluated 47 patients. Mean age was 36 years and mean hospital stay 3.6 days. 42 (79%) of the patients had pain and 46 (98%) were diagnosed with hydronephrosis. 19 patients (40%) had a renal function below 40% of the affected kidney and 49% had impaired renal scan drainage. Postoperative significant improvement in pain score and renal scan drainage was found in 92% and 47% of the patients, respectively. Improvement of renal function > 10% was found in 11 patients (23%); the function remained stable in 31 patients (66%) and deteriorated > 10% in 5 patients (11%). We found no correlation between sex or age and the outcome. Laparoscopic pyeloplasty for UPJO leads to relief of pain and preserved or improved renal function in the majority of the patients. Overall laparoscopic pyeloplasty is an efficient treatment for UPJO.