Actions of prostacyclin (PGI2) on adrenergic neuroeffector transmission in the rabbit kidney.
In the Tyrode's perfused rabbit kidney PGI2 (1.3 x 10(-8)-3.3 x 10(-7)M) dose-dependently inhibited vasoconstrictor responses to sympathetic nerve stimulation, as did PGE2. The dose-effect curve of the two compounds differed, making PGI2 the less potent in the low concentration and the more potent in the high. PGI2 also inhibited the vasoconstrictor response to exogenous noradrenaline, but it had no effect on transmitter release. The main metabolite of PGI2, 6-keto-PGF1 alpha, was ineffective both on noradrenaline release and on vascular responses to nerve stimulation or exogenous noradrenaline. It is suggested that PGI2, if a significant renal prostaglandin, may modulate renal neuroeffector transmission post-junctionally, thereby forming a complement to the prejunctional action of PGE2.


Thalamocortical coherence and causality in different sleep stages using deep brain stimulation recordings.
Previous research has shown an interplay between the thalamus and cerebral cortex during NREM sleep in humans, however the directionality of the thalamocortical synchronization is as yet unknown. In this study thalamocortical connectivity during different NREM sleep stages using sleep scalp electroencephalograms and local field potentials from the left and right anterior thalamus was measured in three epilepsy patients implanted with deep brain stimulation electrodes. Connectivity was assessed as debiased weighted phase lag index and granger causality between the thalamus and cortex for the NREM sleep stages N1, N2 and N3. Results showed connectivity was most prominently directed from cortex to thalamus. Moreover, connectivity varied in strength between the different sleep stages, but barely in direction or frequency. These results imply relatively stable thalamocortical connectivity during NREM sleep directed from the cortex to the thalamus.


Better nerve regeneration with distally based fascicular turnover flap than with conventional autologous nerve graft in a rat sciatic nerve defect model.
The authors hypothesize that a fascicular turnover flap will achieve better nerve regeneration in nerve gap repair than a conventional nerve graft in a rat sciatic nerve defect model. Seven-millimeter-long sciatic nerve defects were repaired with an autologous nerve graft, a proximal fascicular turnover flap, or a distal fascicular turnover flap. Following walking footprint analysis 8 weeks after the surgery, the gastrocnemius-soleus muscles of the hind limbs, nerve graft, and flaps were harvested for wet muscle weight assessment, immunohistochemistry, and transmission electron microscopy. The distal fascicular turnover flap exhibited improvement in the sciatic function index similar as that observed for the autologous nerve graft. Histologically, cross sections showed a higher staining intensity for S-100 in the distal fascicular turnover flap group than for S-100 in the nerve graft group (p = 0.01). In the longitudinal sections, the staining intensity for NF-200 was higher in the distal fascicular turnover flap group than in the nerve graft (p = 0.009) and proximal fascicular turnover flap (p = 0.004) groups. More mature capillaries were observed in the proximal (p < 0.001) and distal (p = 0.029) fascicular turnover flap groups than in the nerve graft group. Transmission electron microscopy results showed a compact, regular myelin sheath around the myelinated nerve fibers in the distal fascicular turnover flap group, unlike observations in the nerve graft and proximal fascicular turnover flap groups. This study demonstrates better nerve regeneration in nerve gap repair with the distal fascicular turnover flap than with the conventional nerve graft.


Correlation exploration among CT imaging, pathology and genotype of pulmonary ground-glass opacity.
To analyse the clinical features, imaging manifestation, pathological typing and genetic testing results of patients undergoing surgery for ground-glass opacity (GGO) nodules, and explore the reasonable diagnosis and treatment program for GGO patients as to provide the basis for the establishment of GGO treatment process. This study is an exploratory study. 465 cases with GGO confirmed by HRCT, undergoing surgery and approved by pathologic diagnosis in Shanghai pulmonary hospital were enrolled in this study. All the patients with GGO were cases with single lesion. The relationship between the clinical, imaging, pathological and molecular biological data of single GGO were statistically studied. (1) Among 465 cases, the median age was 58 years and females were 315 (67.7%); there were 397 (85.4%) non-smoking, and 354 cases (76.1%) had no clinical symptoms. There were 33 cases of benign and 432 cases of malignant GGO. Significant differences were observed on the size, vacuole sign, pleural indentation and blood vessel sign of GGO between two groups (p < 0.05). Of 230 mGGO, there were no AAH, 13 cases of AIS, 25 cases of MIA and 173 cases of invasive adenocarcinoma. The probability of solid nodules in invasive adenocarcinoma was higher than that in micro invasive carcinoma, and the difference was statistically significant (p < 0.05). 360 cases were followed up with the average follow-up time of 6.05 months, and GGO of 34 cases (9.4%) increased. (2) In 428 adenocarcinoma samples approved by pathologic diagnosis, there were 262 (61.2%) lesions of EGFR mutation, 14 (3.3%) lesions of KRAS mutation, 1 (0.2%) lesion of Braf mutation, 9 (2.1%) lesions of EML4-ALK gene fusion and 2 (0.5%) lesions of ROS1 fusion. The detection rate of gene mutation in mGGO was higher than that of pGGO. During the follow-up period, genetic testing results of 32 GGO showed that EGFR mutation rate was 53.1%, ALK positive rate of 6.3%, KRAS mutation rate of 3.1% and no ros1 and BRAF gene mutation. No statistically significant difference was observed in comparison with unchanged GGO. (3) EGFR mutation rate of invasive adenocarcinoma was the highest (168/228, 73.7%), mainly in the 19Del and L858R point mutations. No KRAS mutation was found in atypical adenoma hyperplasia. No significant difference was observed on the mutation rate of KRAS between different types of GGO (p = 0.811). EML4-ALK fusion gene was mainly detected in invasive adenocarcinoma (7/9). GGO tends to occur in young, non-smoking women. The size of GGO is related to the degree of malignancy. Pleural depression sign, vacuole sign and vascular cluster sign are all characteristic images of malignant GGO. pGGO and mGGO reflect the pathological development of GGO. During the follow-up, it is found that GGO increases and solid components appear, which is the indication of surgical resection. The detection rate of EGFR mutations in mGGO and invasive adenocarcinoma is high. pGGO has heterogeneity in imaging, pathology and molecular biology. Heterogeneity research helps to formulate correct individualized diagnosis and treatment plans.


Microparticles in atrial fibrillation: a link between cell activation or apoptosis, tissue remodelling and thrombogenicity.
Microparticles (MPs) are small membrane vesicles that are shed from virtually all cells in response to stress. Widely described in atherothrombotic diseases, recent data suggest a role for circulating MPs in the hypercoagulable state associated with supraventricular tachyarrhythmia. During atrial fibrillation, several mechanisms, such as high ventricular heart rate, low or oscillatory shear stress, stretch, hypoxia, inflammation and oxidative stress, are potent inducers of apoptotic cell death, which leads to the shedding of procoagulant MPs within the vasculature. As key regulators of cell-cell cross-talk and important mediators of inflammatory, thrombogenic and proteolytic pathways, MPs directly or indirectly contribute to the amplification loops involved in atrial fibrillation. Because high levels of platelets and endothelial-derived MPs are identified during stroke and are associated with infarct size and clinical outcome, they are proposed to be a potent marker of ischaemic risk. During pulmonary vein isolation, the additional increases of platelet and leukocyte MP levels suggest the extent of tissue damage and reflect a transient activation of the coagulation cascade that could favour ischaemic stroke. Conversely, the observed decreases of several apoptotic markers some months after the restoration of sinus rhythm suggest that the extent of apoptotic processes is reversible and might enable restoration of haemostasis. In this review, we will summarise the current evidence supporting the roles of apoptosis and cell activation in the development of the prothrombotic state observed in atrial fibrillation, with a particular focus on procoagulant MPs.


Sensitive label-free monitoring of protein kinase activity and inhibition using ferric ions coordinated to phosphorylated sites as electrocatalysts.
Ferric ions show high affinity to the kinase-generated phosphorylated sites of peptides. Thus, the high electrocatalytic activity of the coordinated ferric ions toward the reduction of hydrogen peroxide can be used for sensitive label-free monitoring of protein kinase activity and inhibition.


Function of lymphocytes and macrophages after cryopreservation by procedures for pancreatic islets: potential for reducing tissue immunogenicity.
The survival of tissue allografts can be extended by pretreating the tissue to remove the stimulatory leucocytes that populate the graft; with this in mind, we have recently begun to explore a cryobiological approach to modulating tissue immunogenicity by using the differential susceptibility of different cells to freezing injury. The sensitivity of leucocytes to fast cooling rates, which were used in procedures that have been reported to yield viable pancreatic islets of Langerhans, was examined. The loss of both cell numbers and the ability of peripheral blood lymphocytes to undergo blastogenic transformation in response to the mitogen concanavalin A after freezing and thawing was determined over a range of cell concentrations using the "curve-shift" method. Lymphocytes frozen at 1 degree C/min by a control procedure that was designed to yield maximum survival of lymphocytes showed that although there was a decrease in the number of responding cells, there was no reduction in the ability of the recovered cells to undergo blastogenesis when compared with the response of nonfrozen cells. However, cooling at 1 degree C/min in the experimental procedures resulted in both the loss of cells as well as a marked reduction in the ability of recovered cells to incorporate 125I-deoxyuridine into nucleic acid. Cells cooled at either 20 or 75 degrees C/min by any of the procedures showed total inability to respond to stimulation. Lysozyme is produced continuously by all types of macrophages in culture. The large net increase in total lysozyme content of macrophage cultures is therefore a useful measure of the viability of these accessory cells. Cooling at 1 degree C/min by a control, optimized procedure yielded 91% survival of viable peritoneal exudate cells. Cooling at either 1 or 20 degrees C/min in the experimental procedures resulted in 72-75% survival of cells frozen by one method and 33% survival when frozen by an alternative procedure. Negligible recovery of viable cells was obtained after cooling at 75 degree C/min. The preservation protocols employed in this study differ significantly in the variables known to influence the survival of the cells; these include the concentration of cryoprotectant (CPA), the length and temperature of exposure to CPA, the dilution regimen, and the optimum cooling rate for survival of pancreatic islets. This study therefore defines clearly those conditions most likely to effect a depletion of "passenger" lymphoid cells by freezing during the cryopreservation of islets of Langerhans.


Efficacy of sulfasalazine for the prevention of Pneumocystis pneumonia in patients with rheumatoid arthritis: A multicentric self-controlled case series study.
Pneumocystis pneumonia (PCP) is an opportunistic lung infection and has been reported among patients with rheumatoid arthritis (RA). An animal study revealed that sulfasalazine enhances Pneumocystis clearance from the lung by accelerating macrophage activity. The self-controlled case series (SCCS) method was used to investigate the association between sulfasalazine use and PCP development in patients with RA without the effect of time-invariant, interpatient confounders. PCP episodes which developed in patients with RA at five hospitals between 2003 and 2019 were identified. PCP was defined by the following criteria: 1) detection of Pneumocystis jirovecii in respiratory specimens by polymerase chain reaction; 2) clinical symptoms (pyrexia, dry cough, dyspnea or hypoxia); 3) diffuse interstitial infiltrate on chest imaging; and 4) absence of PCP prophylaxis. The PCP incidence rate ratio (IRR) was compared between periods with and without sulfasalazine use by conditional Poisson regression. Fifty episodes of PCP were identified in 49 patients. Thirty patients received sulfasalazine at some point during their observation. While 49 episodes of PCP developed in 170.3 person-years without sulfasalazine use, only one episode of PCP developed in 103.7 person-years with sulfasalazine use. Sulfasalazine use was associated with a decreased PCP risk (adjusted IRR <0.01; 95% confidence interval <0.01-0.03) after adjusting for age and glucocorticoid, methotrexate, and tumor necrosis factor inhibitor administration. Our study demonstrated a preventive effect of sulfasalazine against PCP in patients with RA.


Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.
Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.


The expression of GABA(A) receptor subunits in the substantia nigra is developmentally regulated and region-specific.
The substantia nigra pars reticulata (SNR) controls the spread of seizures. GABA(A)ergic drug (agonist or antagonist) infusions into the SNR have age-specific and site-specific effects on flurothyl-induced seizures. Developmental and cell-specific regulation of GABA(A) receptor subunit expression may be responsible for these specific effects. To test this hypothesis, in situ hybridization was used to examine regional expression of alpha1 and gamma2L GABA(A) receptor subunit mRNAs in the SNR during development. Distinct temporal and spatial patterns of expression were observed. In rats at postnatal days (PN) 21-60, fewer neurons were labeled with probes directed to alpha1 and gamma2L subunits in SNRanterior compared with SNRposterior. In addition, neurons in SNRanterior contained higher amounts of hybridization grains than in SNRposterior. In PN 15 rats, the labeling of neurons was relatively diffuse throughout the anterior and posterior SNR regions with moderate amounts of hybridization grains for both subunits. The finding of age-related differential distribution of alpha1 and gamma2L subunit mRNAs in the SNR suggests that GABA(A) receptor heterogeneity may play a role in the age-specific and site-specific effects of GABA(A)ergic agents on seizures in the SNR.


A case of struma ovarii in a 92-year-old woman.
A case of struma ovarii in a 92-year-old patient with altered thyroid function is reported.


Pterin transport and metabolism in Leishmania and related trypanosomatid parasites.
The folate metabolic pathway has been exploited successfully for the development of antimicrobial and antineoplasic agents. Inhibitors of this pathway, however, are not useful against Leishmania and other trypanosomatids. Work on the mechanism of methotrexate resistance in Leishmania has dramatically increased our understanding of folate and pterin metabolism in this organism. The metabolic and cellular functions of the reduced form of folates and pterins are beginning to be established and this work has led to several unexpected findings. Moreover, the currently ongoing sequencing efforts on trypanosomatid genomes are suggesting the presence of several gene products that are likely to require folates and pterins. A number of the properties of folate and pterin metabolism are unique suggesting that these pathways are valid and worthwhile targets for drug development.


Axon collaterals of pontine taste area neurons project to the posterior ventromedial thalamic nucleus and to the gustatory neocortex.
Retrograde axonal transport of fluorescent dyes was used to demonstrate collateral projections from neurons of the pontine taste area (PTA) to gustatory-responsive areas of the posterior ventromedial thalamic nucleus (VPM), and to the gustatory neocortex (GN) of the rat. Dual-labeled PTA neurons were reliably observed following application of two different fluorescent dyes to the GN and to VPM thalamus. Dye injections into the GN and into thalamic regions surrounding the VPM nucleus, the bed nucleus of stria terminalis or the infralimbic neocortex, did not result in dual-labeled cells within the PTA. This finding suggests that gustatory information may be relayed simultaneously and specifically to VPM thalamus and to the GN via collateral axons of PTA neurons.


Usability evaluation of mobile medical treatment carts: another explanation by information engineers.
Healthcare services integration is a critical task as it attempts to reform the user practices. In response to the request of facilities upgrade, we perform a usability evaluation of the mobile medical treatment carts (MMTC) installed in the Emergency Medicine Department of our healthcare enterprise. A survey conducted in August 2006 identified that our experimental area needs some improvements to support the MMTC adoption. For example, the MMTC can accompany with several popular nursing care items. Follow-up several undertaken investigations indicated that our expectation of the MMTC solution had been reached. Given the evident heterogeneity of viewpoints, it is imperative for a healthcare enterprise to broadly ascertain the requirements of end users before investing in any information technologies.


Association between aggressive and non-fatal suicidal behaviors among U.S. high school students.
This study quantified the association between aggressive and non-fatal suicidal behaviors (NFSB) among U.S. high school students and examined whether the association could be explained by substance use, bullying and sexual/dating violence victimization, and other potential risk factors. Data were based on self-reports from 14,765 students who responded to the 2017 National Youth Risk Behavior Survey. Confirmatory latent class analysis (LCA) identified two distinct, dichotomous latent class variables manifested by indicators of past-year NFSB (i.e., ideation, plan, and attempt) and aggressive behavior (i.e., physical fighting in general and on school property). The structural model estimated the odds ratios between NFSB, aggressive behavior, and their potential risk factors. Without adjusting for covariates, the confirmatory LCA estimated an odds ratio (OR) of 2.55 (95% confidence interval [CI]: 1.93, 3.37) between two latent class variables for violence against self (NFSB) and others (physical fighting). The net association, however, was rendered nonsignificant (OR = 1.08 [95% CI: 0.88, 1.31]) when adjusted for covariates. Significant common risk factors included exposure to physical dating violence, being bullied on school property and/or electronically, being threatened or injured by someone with a weapon on school property, and lifetime illegal drug use and prescription opioid misuse. Cross-sectional data do not allow assessment of causal relationships. Findings elucidated the association between NFSB and aggressive behavior, with serious implications for prevention and intervention. Targeting substance use, bullying, and sexual and dating violence will protect students from engaging in both types of violent behaviors.


Catheter ablation of atrial fibrillation in the young: insights from the German Ablation Registry.
Catheter ablation of paroxysmal atrial fibrillation (PAF) has been suggested as first-line treatment for selected patients (pts). However, patient characteristics, procedural data, and complication rate in the group of young patients remain undetermined. The German Ablation Registry has been designed as a multi-center prospective registry. AF ablation data were collected from 51 German centers between March 2007 to September 2012 and 2 groups were defined (group A: ≤45 years, group B: >45 years). Data were analyzed according to patient characteristics, procedural data, and complications. To calculate differences between both groups CHI2 or Mann-Whitney-Wilcoxon tests was utilized. A total of 7243 patients undergoing AF ablation were included (group A: 593, 8.2 %; group B: 6650, 91.8 %). Male gender and PAF were significantly more often present in group A. Patient characteristic revealed decreased co-morbidities in the young. In both groups circumferential pulmonary vein isolation represented the procedural cornerstone, whereas substrate modification was significantly more often performed in group B. Procedure-, and fluoroscopy-time was similar but there was a shorter hospital stay and a favorable complication profile in the young. After 12 months AF recurrence and use of antiarrhythmic drugs were less common in group A. The young AF ablation patient has typically paroxysmal AF and less comorbidities. In this group, catheter ablation of AF is associated with a lower major complication rate, shorter hospitalization, and a favorable clinical outcome.


Bifactor structure and model reliability of the Test of Gross Motor Development - 3rd edition.
This study investigated the structure of the Test of Gross Motor Development - 3rd edition (TGMD-3). Specifically, we examine bifactor structure, which simultaneously models a fundamental motor skills (FMS) general factor and specific factors for locomotor skills and ball skills, compared to other models. Cross-sectional design using the TGMD-3 normative sample. The sample (N = 862) of children (Mage = 6.51, SD = 2.23) was matched based on United States census data, ensuring appropriate percentages of demographic representation and disability status. Confirmatory factor analyses, exploratory structural equation modeling, model-based reliability estimates including coefficient omega hierarchical, and coefficient omega hierarchical subscale, explained common variance estimates, and relative parameter bias were examined. Findings revealed bifactor structure produced a better model fit compared to both one-factor and two-factor models. Furthermore, model reliability estimates that parceled true score variance for the general FMS factor, locomotor skills factor, and ball skills factor yielded high internal consistency for FMS (.797) but not locomotor skills (.168) and ball skills (.216). Finally, explained common variance (.852-.879) and relative parameter bias (.018-.072) estimates identified the strength of the run, skip, slide, and dribble skills tests to represent the FMS general factor. Our findings demonstrate the advantages of using bifactor structure to examine the TGMD-3 compared to one-factor and two-factor models. Additionally, these results provide further evidence that using the TGMD-3 to examine an overall FMS general factor may explain more variance in performance and provide a better picture for evaluating children's current FMS levels compared to subscales independently.


The physiological basis for the sensation of gloom: quantitative and qualitative aspects.
As our ambient lighting is gradually reduced from a high level, subjects use the following words - bright, gloomy, dim and dark. On six subjects the light level at which these decisions are given has been measured. It has been found that the word gloomy is used when the rods begin to take over from the colour-sensitive daylight cones.


Hv-CBF2A overexpression in barley accelerates COR gene transcript accumulation and acquisition of freezing tolerance during cold acclimation.
C-Repeat Binding Factors (CBFs) are DNA-binding transcriptional activators of gene pathways imparting freezing tolerance. Poaceae contain three CBF subfamilies, two of which, HvCBF3/CBFIII and HvCBF4/CBFIV, are unique to this taxon. To gain mechanistic insight into HvCBF4/CBFIV CBFs we overexpressed Hv-CBF2A in spring barley (Hordeum vulgare) cultivar 'Golden Promise'. The Hv-CBF2A overexpressing lines exhibited stunted growth, poor yield, and greater freezing tolerance compared to non-transformed 'Golden Promise'. Differences in freezing tolerance were apparent only upon cold acclimation. During cold acclimation freezing tolerance of the Hv-CBF2A overexpressing lines increased more rapidly than that of 'Golden Promise' and paralleled the freezing tolerance of the winter hardy barley 'Dicktoo'. Transcript levels of candidate CBF target genes, COR14B and DHN5 were increased in the overexpressor lines at warm temperatures, and at cold temperatures they accumulated to much higher levels in the Hv-CBF2A overexpressors than in 'Golden Promise'. Hv-CBF2A overexpression also increased transcript levels of other CBF genes at FROST RESISTANCE-H2-H2 (FR-H2) possessing CRT/DRE sites in their upstream regions, the most notable of which was CBF12. CBF12 transcript levels exhibited a relatively constant incremental increase above levels in 'Golden Promise' both at warm and cold. These data indicate that Hv-CBF2A activates target genes at warm temperatures and that transcript accumulation for some of these targets is greatly enhanced by cold temperatures.


Comorbidities, biomarkers and cause specific mortality in patients with irritable bowel syndrome: A phenome-wide association study.
Irritable bowel syndrome (IBS) is one of the most common functional digestive disorders. Our understanding about its comorbidities, biomarkers, or long-term risks is still incomplete. To characterize comorbidities and biomarkers for IBS and establish the effect of IBS on overall- and cause specific mortality. We analyzed data from the population-based cohort of the UK Biobank (UKB) with 493,974 participants, including self-reported physician-diagnosed (n = 20,603) and ICD-10 diagnosed (n = 7656) IBS patients, with a mean follow-up of 11 years. We performed a phenome-wide association study (PheWAS) and competing risk analysis to characterize common clinical features in IBS patients. In PheWAS analyses, 260 PheCodes were significantly overrepresented in self-reported physician-diagnosed IBS patients, 633 in patients with ICD-10 diagnosed IBS (ICD-10-IBS), with 221 (40%) overlapping. In addition to gastrointestinal diseases, psychiatric, musculoskeletal, and endocrine/metabolic disorders represented the most strongly associated PheCodes in IBS patients. Self-reported physician-diagnosed IBS was not associated with increased overall mortality and the risk of death from cancer was decreased (hazard ratio [HR] = 0.78 [95% CI = 0.7-0.9]). Lastly, we evaluated changes in serum metabolites in IBS patients and identified glycoprotein acetyls (GlycA) as a potential biomarker in IBS. One standard deviation increase in GlycA raised the risk of self-reported IBS/ICD-10 coded by 9%-20% (odds ratio [OR] = 1.09 [95% CI = 1.1-1.1]/OR = 1.20 [95% CI = 1.1-1.3]) and the risk of overall mortality in ICD-10-IBS patients by 28% (HR = 1.28 [95% CI = 1.1-1.5]). Our large-scale association study determined IBS patients having an increased risk of several different comorbidities and that GlycA was increased in IBS patients.


Small mammal personalities generate context dependence in the seed dispersal mutualism.
Mutualisms are foundational components of ecosystems with the capacity to generate biodiversity through adaptation and coevolution and give rise to essential services such as pollination and seed dispersal. To understand how mutualistic interactions shape communities and ecosystems, we must identify the mechanisms that underlie their functioning. One mechanism that may drive mutualisms to vary in space and time is the unique behavioral types, or personalities, of the individuals involved. Here, our goal was to examine interindividual variation in the seed dispersal mutualism and identify the role that different personalities play. In a field experiment, we observed individual deer mice (Peromyscus maniculatus) with known personality traits predating and dispersing seeds in a natural environment and classified all observed interactions made by individuals as either positive or negative. We then scored mice on a continuum from antagonistic to mutualistic and found that within a population of scatter hoarders, some individuals are more mutualistic than others and that one factor driving this distinction is animal personality. Through this empirical work, we provide a conceptual advancement to the study of mutualism by integrating it with the study of intraspecific behavioral variation. These findings indicate that animal personality is a previously overlooked mechanism generating context dependence in plant–animal interactions and suggest that behavioral diversity may have important consequences for the functioning of mutualisms.


Arteriosclerosis in East Asians.
Arteriosclerosis is remarkably common in East Asians, both in the greater subcontinent and in their adopted countries after migration. Since arteriosclerosis is an acquired disease, East Asians must possess and preserve a common cultural practice related to the cause of arteriosclerosis and its complications. Therefore, an unusual opportunity is provided to examine East Asian migration and customs, especially diet, searching for a clue to the etiology of this disease. The result of this analysis provides additional support for a new theory proposing arteriosclerosis as an infectious disease caused by Cyanobacteria.


Estrogen regulation of superoxide dismutase in normal rat mammary tissues and mammary tumors.
Multiple electrophoretic molecular variants of superoxide dismutase were demonstrated in normal rat mammary tissues and DMBA-induced rat mammary tumors. The specific activities of Cu/Zu superoxide dismutase in mammary tumors of estrogen-treated rats were not significantly different from those activities seen in normal rat mammary tissues. However, the enzyme activities of mammary tumors from untreated rats (no estrogen) were significantly lower than the activities of normal rat mammary tissues. Exogenous estrogen appeared to raise superoxide dismutase levels in DMBA-induced rat mammary tumors to those levels seen in normal rat mammary tissues.


An alternative approach in regulation of expression of a transgene by endogenous miR-145 in carcinoma and normal breast cell lines.
MicroRNAs are small noncoding RNAs that regulate gene expression by repressing translation of target cellular transcripts. Increasing evidences indicate that miRNAs have different expression profiles and play crucial roles in numerous cellular processes. Delivery and expression of transgenes for cancer therapy must be specific for tumors to avoid killing of healthy tissues. Many investigators have shown that transgene expression can be suppressed in normal cells using vectors that are responsive to microRNA regulation. To overcome this problem, miR-145 that exhibits downregulation in many types of cancer cells was chosen for posttranscriptional regulatory systems mediated by microRNAs. In this study, a psiCHECK-145T vector carrying four tandem copies of target sequences of miR-145 into 3'-UTR of the Renilla luciferase gene was constructed. Renilla luciferase activity from the psiCHECK-145T vector was 57% lower in MCF10A cells with high miR-145 expression as compared to a control condition. Additionally, overexpression of miR-145 in MCF-7 cells with low expression level of miR-145 showed more than 76% reduction in the Renilla luciferase activity from the psiCHECK-145T vector. Inclusion of miR-145 target sequences into the 3'-UTR of the Renilla luciferase gene is a feasible strategy for restricting transgene expression in a breast cancer cell line while sparing a breast normal cell line.


Effect of early cardiac rehabilitation on prognosis in patients with heart failure following acute myocardial infarction.
The purpose of this retrospective study is to evaluate the effectiveness of early cardiac rehabilitation on patients with heart failure following acute myocardial infarction. Two hundred and thirty-two patients who developed heart failure following acute myocardial infarction were enrolled in this study. Patients were divided into heart failure with reduced ejection fraction group (n = 54) and heart failure with mid-range ejection fraction group (n = 178). Seventy-eight patients who accepted a two-week cardiac rehabilitation were further divided into two subgroups based on major adverse cardiovascular events. Key cardio-pulmonary exercise testing indicators that may affect the prognosis were identified among the cardiac rehabilitation patients. Early cardiac rehabilitation significantly reduced cardiac death and re-hospitalization in patients. There was more incidence of diabetes, hyperkalemia and low PETCO2 in the cardiac rehabilitation group who developed re-hospitalization. Low PETCO2 at anaerobic threshold (≤ 33.5 mmHg) was an independent risk factor for re-hospitalization. Early cardiac rehabilitation reduced major cardiac events in patients with heart failure following acute myocardial infarction. The lower PETCO2 at anaerobic threshold is an independent risk factor for re-hospitalization, and could be used as a evaluating hallmark for early cardiac rehabilitation.


New pyrrole derivatives as DNA gyrase and 14α-demethylase inhibitors: Design, synthesis, antimicrobial evaluation, and molecular docking.
An efficient one-pot reaction utilizing readily available chemical reagents was used to prepare novel 2-amino-1,5-diaryl-1H-pyrrole-3-carbonitrile derivatives and the structures of these compounds were validated by spectroscopic data and elemental analyses. All the synthetic compounds were evaluated for their antimicrobial activities (MZI assay). The tested compounds proved high activities on Staphylococcus aureus (Gram-positive bacteria) and Candida albicans (Pathogenic fungi). However, they did not show any activity on Escherichia coli (Gram-negative bacteria). The most effective compounds in MZI assay 7c, 9a, 9b, 11a, and 11b were selected to determine their MIC on S. aureus and C. albicans. Furthermore, DNA gyrase and 14-α demethylase inhibitory assays were performed to study the inhibitory activities of 7c, 9a, 9b, 11a, and 11b. The results illustrated that compound 9b was the most DNA gyrase inhibitor (IC50 of 0.0236 ± 0.45 µM, which was 1.3- fold higher than gentamicin reference IC50 values of 0.0323 ± 0.81 µM). In addition, compound 9b demonstrated the highest 14-α demethylase inhibitory effect with IC50 of 0.0013 ± 0.02 µM, compared to ketoconazole (IC50 of 0.0008 ± 0.03 µM) and fluconazole (IC50 of 0.00073 ± 0.01 µM), as antifungal reference drugs. Lastly, docking studies were performed to rationalize the dual inhibitory activities of the highly active compounds on both DNA gyrase and 14-α demethylase enzymes.


Revealing the polar nature of a ferroelectric nematic by means of circular alignment.
The recent discovery of spontaneously polar nematic liquid crystals-so-called ferroelectric nematics-more than a century after the first discussions about their possible existence-has attracted large interest, both from fundamental scientific and applicational points of view. However, the experimental demonstration of such a phase has, so-far, been non-trivial. Here I present a direct method for the experimental verification of a ferroelectric nematic liquid crystal phase. The method utilizes a single sample cell where the two substrates are linearly and circularly rubbed, respectively, and the ferroelectric nematic phase (NF) is revealed by the orientation of the resulting disclination lines in the cell.


Biomarkers of Colorectal Cancer Risk Decrease 6 months After Roux-en-Y Gastric Bypass Surgery.
The impact of weight loss on obesity-related colorectal cancer (CRC) risk is not well defined. Previous studies have suggested that Roux-en-Y gastric bypass (RYGB) surgery may have an unexpected adverse impact on CRC risk. This study aimed to investigate the impact of RYGB on biomarkers of CRC risk. Rectal mucosal biopsies and blood were obtained from patients undergoing RYGB (n = 22) and non-obese control participants (n = 20) at baseline and at a median of 6.5 months after surgery. Markers of systemic inflammation and glucose homeostasis were measured. Expression of pro-inflammatory genes and proto-oncogenes in the rectal mucosa was quantified using qPCR. Crypt cell proliferation state of the rectal mucosa was assessed by counting mitotic figures in whole micro-dissected crypts. At 6.5 months post-surgery, participants had lost 29 kg body mass and showed improvements in markers of glucose homeostasis and in systemic inflammation. Expression of pro-inflammatory genes in the rectal mucosa did not increase and COX-1 expression fell significantly (P = 0.019). The mean number of mitoses per crypt decreased from 6.5 to 4.3 (P = 0.028) after RYGB. RYGB in obese adults led to lower rectal crypt cell proliferation, reduced systemic and mucosal markers of inflammation and improvements in glucose regulation. These consistent findings of reduced markers of tumourigenic potential suggest that surgically induced weight loss may lower CRC risk.


Controlling the rheological properties of wheat starch gels using Lepidium perfoliatum seed gum in steady and dynamic shear.
In the present work, the influence of Lepidium perfoliatum seed gum (LPSG) addition in varied concentrations (0%, 0.25%, 0.5%, 0.75% and 1%, w/w) on dynamic and steady shear rheological properties of wheat starch dispersion (4%, /w) was examined. Comparison of the values of dynamic (G', G″, τy, τf, tan δ), shear-dependent (ηa,50, η0, η∞, τ, m) and time-dependent (ηa,3s, k, η0, η∞) rheological parameters of the WS-LPSG mixtures with WS alone, indicated that the viscoelastic and flow properties of the mixtures were greatly affected by the addition of LPSG. According to the standard method provided by the National Dysphagia Diet (NDD), the WS and WS-LPSG gels were placed in the category of nectar-like (WS), honey-like (WS-0.25%LPSG, WS-0.5%LPSG and WS-0.75%LPSG) and spoon-thick (WS-1%LPSG) viscosity. In the simulated oral condition (SOC), the presence of saliva caused the increase of k value (10-81%), whilst decreased the values of η0 (43-95%) and η∞ (68-96%). As the concentration of LPSG increased, less decrease in value of ηa,3s in the SOC was observed. The results of present study demonstrated the feasibility of manipulating the viscosity of the WS gels by addition of LPSG to be suitable for the individuals with varying degrees of swallowing difficulty.


Multimodality imaging to assess immediate response following irreversible electroporation in patients with malignant hepatic tumors.
To assess the diagnostic accuracy of contrast-enhanced ultrasound (CEUS), contrast-enhanced multiphase CT (CECT), and gadoxetic acid-enhanced MRI (EOB-MRI) in identifying residual tumor in the subacute follow-up of patients with malignant hepatic tumors treated by irreversible electroporation (IRE). We enrolled 16 patients with 21 hepatic lesions treated by IRE and examined by CEUS and CECT at 1 day after IRE and by EOB-MRI at 7 days after IRE. Follow-up examinations by EOB-MRI or CECT and CEUS were performed at 3-month intervals. Two radiologists independently reviewed the images and assessed the probability of residual tumor using a five-point scale with receiver operating characteristic (ROC) curve analysis. The sensitivity and specificity were also evaluated. Verifiable local recurrence was assessed using follow-up imaging as the reference standard. The mean area under the ROC curve was significantly higher for CEUS (0.980) than for CECT (0.742, P < 0.01) and EOB-MRI (0.806, P < 0.01), as were the sensitivity and specificity (mean 85.7 and 85.7% for CEUS, respectively, vs 64.3 and 46.4% for CECT and 78.6 and 64.3% for EOB-MRI). CEUS was found to be superior to CECT and EOB-MRI for the diagnosis of residual tumor in the subacute phase following IRE.


Impact of age over 75 years on outcomes after pancreaticoduodenectomy.
The risks associated with pancreaticoduodenectomy (PD) in elderly patients continue to be debated. The aim of our study was to assess the incidence of death and postoperative complications following PD and identify the risk factors in patients >75 y. All patients who underwent PD between January 2000 and September 2009 were analyzed retrospectively. Patients were divided into two groups according to age (Group 1: patients aged <75 y, and Group 2: patients aged ≥ 75 y). Morbidity and perioperative mortality risk factors were analyzed using univariate and multivariate analyses. Among the 314 patients, 273 were included in Group 1 (sex ratio 1.4) and 41 in Group 2 (sex ratio 1). In multivariate analysis, postoperative hemorrhage (PH) (OR 6.61, IC95% [1.96; 22.31], P = 0.002) and age >75 y proved to be predictive factors for mortality (OR 11.04, IC95% [2.57; 47.49], P = 0.001). When compared with Group 1, Group 2 was associated with increased postoperative deaths (24.4% versus 3.66%, P < 0.001) and pancreatic fistulas (26.8% versus 13.2%, P = 0.041), in particular, Grade C fistulas (14.6% versus 4.4%, P = 0.023). In multivariate analysis, only PH proved to be an independent predictive factor for mortality (OR 12.9, IC95% [1.07; 155.5], P = 0.04). PD in elderly patients aged over 75 y appears to be associated with an increased risk of postoperative death and pancreatic fistula. No single preoperative factor made it possible to predict this risk.


Identification of Major Compounds and α-Amylase and α-Glucosidase Inhibitory Activity of Rhizome of Musa balbisiana Colla: An in-vitro and in-silico Study.
α-Amylase and α-glucosidase inhibitors are widely used to suppress postprandial glycemia in the treatment of type-2 diabetes. To evaluate the metallic content, phytocompounds, and α-amylase and α-glucosidase inhibitory activity of Musa balbisiana rhizome using in-vitro and in-silico methods. Heavy metal content was detected by AAS following standard protocol. Major phytochemicals of the plant were analyzed by GC-MS technique. Enzyme inhibition study was carried out by UV/VIS spectrophotometric methods. The drug-likeness and bio-availability properties of major compounds were carried out using computer-aided tools - SwissADME and ADMElab. Docking and visualization were performed in AutoDock vina and Discovery studio tools. The study found that the fruits of M. balbisiana contain a negligible amount of toxic elements. GC-MS analysis showed five major compounds from the rhizome of M. balbisiana. Invitro enzyme assays revealed strong α-amylase and α-glucosidase inhibitory properties of the plant. All five compounds were predicted to have a drug-likeness property with high cell membrane permeability and bio-availability. The compounds were also predicted to have low to moderate toxicity properties. The Docking study showed strong binding affinities of plant compounds with α-amylase and α-glucosidase. Out of five compounds, C5 showed the best binding affinity with active pockets of α-amylase and α-glucosidase. The in-vitro and in-silico study suggests the antihyperglycemic property of the rhizome of Musa balbisiana and a possible candidate for the therapeutic antidiabetic agent(s).


Changes in liver glycogen of broilers during coccidiosis.
Liver glycogen levels of broilers with Eimeria acervulina, E. Brunetti, or E. tenella fell during the acute phase of the infection with the maximum effect at 5-6 days post-inoculation (DPI). During the early recovery phase (6-8 DPI), liver glycogen levels in the E. acervulina-infected birds increased to levels up to 3 times greater than those found in uninoculated control birds. A lesser increase was occasionally seen in E. tenella-infected birds. Pair feeding studies showed that the decrease in liver glycogen was not related to the amount of feed consumed. The magnitude of the glycogen overshoot at 7 DPI was not related to the depression of weight gain at 5 and 6 DPI. When feed was withheld from birds, liver glycogen levels of uninoculated control birds fell rapidly within 1 h after feed withdrawal. In birds infected with E. acervulina, liver glycogen levels remained high even after 3 h starvation. Injection of glucagon indicated that glycogen could be mobilized in both infected and uninfected birds.


Zinc oxide nanoparticles trigger autophagy-mediated cell death through activating lysosomal TRPML1 in normal kidney cells.
Zinc oxide nanoparticles (ZnO NPs) have been widely used in various materials including sunscreens, cosmetics, over-the-counter topical skin products, and pigments. As traces of the used ZnO NPs have been found in the kidney, it is crucial to uncover their potential risks. The aim of this study is to elucidate detrimental effects of ZnO NPs and the molecular mechanism behind their renal toxicity. Cytotoxic effects were measured by MTT assay after HK2 cells were exposed to ZnO NPs for 24 h and IC50 value was determined. ROS and intracellular Zn2+ levels were detected by flow cytometry, and localization of Zn2+ and lysosome was determined by confocal microscopy. Occurrence of autophagy and detection of autophagic flux were determined by Western blot and confocal microscopy, respectively. We performed unpaired student t test for two groups, and one-way ANOVA with Tukey's post hoc for over three groups. ZnO NPs induced cell death in human renal proximal tubule epithelial cells, HK2. Cytosolic Zn2+ caused autophagy-mediated cell death rather than apoptosis. Cytosolic Zn2+ processed in lysosome was released by TRPML1, and inhibition of TRPML1 significantly decreased autophagic flux and cell death. The findings of this study suggest that ZnO NPs strongly induce autophagy-mediated cell death in human kidney cells. Controlling TRPML1 can be potentially used to prevent the kidney from ZnO NPs-induced toxicity.


Finding of Remarkable Synergistic Effect on the Aroxyl-Radical-Scavenging Rates (ks) under the Coexistence of Vitamin E Homologues (or Vegetable Oils) and Ubiquinol-10: Proposal of A New Mechanism to Explain An Increase of ks Value.
Measurements of aroxyl (ArO · )-radical-scavenging rate constants (ksAOH) of antioxidants (AOHs) (i.e., α-, β-, γ-, δ-Tocopherol (TocH) and ubiquinol-10 (UQ10H2)) were performed in ethanol/chloroform/H2O (50/50/1, v/v) solution, using stopped-flow spectrophotometry. ksAOH values were measured not only for each AOH, but also for the mixtures of two AOHs (i.e., TocH and UQ10H2). ksTocH values for α-, β-, γ-, δ-TocH increased 1.21, 1.28, 1.55, and 1.19 times, respectively, under the coexistence of constant concentrations of UQ10H2. Similar measurements were performed for eight vegetable oils 1 - 8, containing different concentrations of α-, β-, γ-, δ-tocopherol (TocH) and -tocotrienol (Toc-3H). ksOil values of all eight vegetable oils 1 - 8 also increased 1.24 - 1.54 times under the coexistence of constant concentrations of UQ10H2. A new mechanism to explain the notable increase of ksAOH values under the coexistence of two kinds of phenolic AOHs was proposed. UV-vis absorption of α-, β-, γ-Toc · radicals, produced by reaction of α-, β-, γ-TocHs (or vegetable oils 1 - 8) with ArO · , disappeared under the coexistence of TocHs (or oils) and UQ10H2, suggesting that the prooxidant reaction resulting from the presence of Toc · radicals is suppressed in the presence of UQ10H2.


Laparoscopic approach as primary treatment of common bile duct stones in children.
Preoperative endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy (ES) are an effective strategy for choledocholithiasis, but complications such as pancreatitis and outcome in children are unknown. The laparoscopic cholecystectomy became the new gold standard in children for cholelithiasis. For the choledocholithiasis in children, the attitude is more controversial. We analyzed our series of laparoscopic approach for the management of choledocholithiasis in children to determine if it is an effective procedure. Between 1996 and 2001, 126 children were treated for cholelithiasis in our institution; 13 children (10.3%) were managed for a choledocholithiasis. We reviewed age at symptom onset results of paraclinical examinations, the type of laparoscopic management, and postoperative outcome. The mean age at clinical signs was 9.9 years (range, 3 months-15.5 years). One child was excluded because he had a preoperative ES. Twelve children had a laparoscopic cholecystectomy and cholangiogram at the same time. A choledocholithiasis was found in 10 cases. A flush of the common bile duct (CBD) was performed in all cases with a 3F or 5F ureteral catheter; the stone was pushed into the duodenum in 3 cases and successfully extracted in 3 with a 4F Dormia or Fogarty catheter. One child needed a conversion to open surgery. Three times, an ES was necessary in postoperative course in each case for clinical and biologic signs of CBD obstruction or pancreatitis (30%). All children are symptom-free with an average follow-up of 28 months. Laparoscopic CBD exploration for choledocholithiasis can be performed safely in children at the time of cholecystectomy and can clear all of the stones in the CBD in two thirds of cases. If there is residual obstruction, a postoperative ES can be performed. We suggest primary treatment of choledocholithiasis by laparoscopic approach in children.


Molecular and clinical characterization of a recurrent cryptic unbalanced t(4q;18q) resulting in an 18q deletion and 4q duplication.
Recurrent constitutional non-Robertsonian translocations are very rare. We present the third instance of cryptic, unbalanced translocation between 4q and 18q. This individual had an apparently normal karyotype; however, after subtelomere fluorescence in situ hybridization (FISH), he was found to have a cryptic unbalanced translocation between 4q and 18q [ish der(18)t(4;18)(q35;q23)(4qtel+,18qtel-)]. Oligonucleotide array comparative genomic hybridization (aCGH) refined the breakpoints in this child and in the previously reported child and indicated that the breakpoints were within 20 kb of each other, suggesting that this translocation is, indeed, recurrent. A comparison of the clinical presentation of these individuals identified features that are characteristic of both 18q- and 4q+ as well as features that are not associated with either condition, such as a prominent metopic ridge, bitemporal narrowing, prominent, and thick eyebrows. Individuals with features suggestive of this 4q;18q translocation but a normal karyotype warrant aCGH or subtelomere studies.


Temporal patterns of childhood cancer survival 1991 to 2016: A nationwide register-study based on data from the German Childhood Cancer Registry.
Childhood cancer is the leading disease-related cause of death among under 15 year olds in Europe. Since primary preventive measures are lacking, improving survival probabilities and long-term well-being remain primary goals. With this report, we provide the first long-term assessment and interpretation of patterns in childhood cancer survival in Germany, covering a period of 30 years. Using data from the German Childhood Cancer Registry, we assessed temporal patterns of cancer survival among children (0-14 years) diagnosed in Germany from 1991 to 2016, by cancer type, age at diagnosis and sex. We calculated overall survival (OS) and average annual percentage changes of the respective 5-year OS estimates. OS improved across all cancer types, age groups as well as for boys and girls over time. Five-year OS for all childhood cancers combined increased from 77.8% in 1991-1995 to 86.5% in 2011-2016, with stronger improvements during the early 1990s. The most pronounced survival improvement was seen for acute myeloid leukaemia, at 2% annually and 5-year OS recently reaching 81.5%. Survival improvements for some diagnoses such as neuroblastoma, renal tumours and bone tumours have flattened out. Tremendous enhancements in diagnostics, treatment and supportive care have affected average survival improvements for most cancer types. Recently, survival improvements have decelerated overall and for some cancer types, it plateaued at an unsatisfactory level. As not all children benefited equally from the survival improvements, personal factors (eg, socioeconomic circumstances, health literacy, access to care) likely affect individual prognosis and warrant further investigation.


A comparative study of combination chemotherapy versus marrow transplant in first remission in adult acute lymphoblastic leukaemia.
The results of conventional chemotherapy in adult acute lymphoblastic leukaemia (ALL) have not improved substantially in recent years. The present study is based on a flexible policy of marrow transplantation (allograft and autograft without marrow purging) in first remission compared with a group treated with standard maintenance therapy after a common induction sequence. The actuarial disease free survival (DFS) and actuarial overall survival (OS) at 3 years for autologous marrow grafted patients was 30% and 65% respectively. The allogeneic transplant group had DFS of 30% and OS at 3 years of 38% compared with DFS (12%) and OS (12%) for patients on 6-mercaptopurine and methotrexate maintenance. The actuarial disease free survival calculations include patients on protocol not entering remission, therefore, giving the worst possible result. We conclude that high dose chemo/radiotherapy with autologous marrow rescue in first remission followed by no maintenance provides better results in terms of overall survival and quality of life than standard ALL maintenance in adult patients. Results for allogeneic transplant in ALL are less good in terms of duration and quality of survival and the majority of deaths are related to causes other than leukaemic relapse.


Interaction of MxiG with the cytosolic complex of the type III secretion system controls Shigella virulence.
Gram-negative bacteria use the type 3 secretion system (T3SS) to colonize host cells. T3SSs are ring-shaped macromolecular complexes specific for the transport of effector molecules into host cells. It was recently suggested that a cytosolic ring-shaped protein complex delivers effector molecules to the T3SS. However, how transport of effector proteins is regulated is not known. Here, we report the high-resolution X-ray crystal structure of the whole cytosolic domain of MxiG (MxiG(1-126)), a major component of the inner T3SS rings in Shigella flexneri. MxiG(1-126) folds as an FHA domain, which specifically binds phosphorylated threonines. Indeed, MxiG(1-126) binds to Spa33, a cytoplasmic-ring component of Shigella, as revealed in pulldown studies. Surface plasmon resonance analysis showed specific interaction of MxiG with a Spa33 peptide only if phosphorylated. In total, 24 copies of the MxiG(1-126) crystal structure were fitted into the cryo-EM map of the Shigella T3SS. The phosphoprotein binding site of each MxiG molecule faces the channel of the T3SS, allowing interaction with cytosolic binding partners. Secretion assays and host cell invasion studies of complemented Shigella knockout cells indicated that the phosphoprotein binding of MxiG is essential for bacterial virulence. Our findings suggest that MxiG is involved in T3SS regulation.


Annexin VI binds S100A1 and S100B and blocks the ability of S100A1 and S100B to inhibit desmin and GFAP assemblies into intermediate filaments.
Annexin VI, a member of a family of Ca(2+)-dependent phospholipid- and membrane-binding proteins, interacts with the Ca(2+)-regulated EF-hand proteins, S100A1 and S100B, and blocks the ability of these two proteins to inhibit the assembly of desmin and glial fibrillary acidic protein (GFAP) into intermediate filaments in a Ca(2+)- and dose-dependent manner. S100A1 and S100B each possess one annexin VI binding site, characterized by an affinity for annexin VI in the submicromolar range. Binding of annexin VI to either S100 protein occurs at a site that appears to differ in some parts from that recognizing desmin and GFAP. As S100A1 and S100B exist in solution as homodimers in which the two monomers are related by a 2-fold symmetry axis, each of the above S100 homodimers likely crosslinks two annexin VI molecules, a situation that appears typical of all the annexin-S100 protein complexes described thus far. However, whereas in the cases of other annexin-S100 complexes the C-terminal extension of the S100 molecule appears indispensable for annexin binding, the annexin VI binding site cannot be restricted to the S100A1 and S100B C-terminal extension. We speculate that the annexin VI site on S100A1/B may only partially overlap to the desmin/GFAP site. In contrast, no effects of annexin V on the ability of S100A1 or S100B to affect the desmin and GFAP assemblies could be documented, although binding of annexin V to S100A1 and S100B could be detected at relatively high Ca2+ concentrations. The present data suggest that annexin VI might regulate S100A1 and S100B activities and vice versa.


Molecular characterization of phenylketonuria in Japanese patients.
We characterized phenylalanine hydroxylase (PAH) genotypes of Japanese patients with phenylketonuria (PKU) and hyperphenylalaninemia (HPA). PKU and HPA mutations in 41 Japanese patients were identified by denaturing gradient gel electrophoresis and direct sequencing, followed by restriction fragment length polymorphism analysis to find a large deletion involving exons 5 and 6. Of 82 mutant alleles, 76 (92%) were genotyped showing 21 mutations. The major mutations were R413P (30.5%), R243Q (7.3%), R241 C (7.3%), IVS4nt-1 (7.3%), T2781 (7.3%), E6nt-96A-->g (6.1%), Y356X (4.9%), R111X (3.7%), and 442-706delE5/6 (2.4%). Eight new mutations (L52 S, delS70, S70P, Y77X, IVS3nt-1, A132 V, W187 C, and C265Y) and a polymorphism of IVS10nt-14 were detected. In vitro PAH activities of mutant PAH cDNA constructs were determined by a COS cell expression system. Six mutations, viz., R408Q, L52 S, R241 C, S70P, V388 M, and R243Q, had 55%, 27%, 25%, 20%, 16% and 10% of the in vitro PAH activity of normal constructs, respectively. The mean pretreatment phenylalanine concentration (0.83+/-0.21 mmol/l) of patients carrying the R408Q, R241 C, or L52 S mutation and a null mutation was significantly lower (P<0.0005) than that (1.99+/-0.65 mmol/l) of patients with both alleles carrying mutations associated with a severe genotype. Simple linear regression analysis showed a correlation between pretreatment phenylalanine concentrations and predicted PAH activity in 29 Japanese PKU patients (y=31.9-1.03x, r=0.59, P<0.0001). Genotype determination is useful in the prediction of biochemical and clinical phenotypes in PKU and can be of particular help in managing patients with this disorder.


Ligation of the patent ductus arteriousus in the newborn intensive care unit.
During a two-year period, 21 premature infants (weight at birth, 680 to 2,340 gm) had operative closure of patent ductus arteriosus (PDA). The first 6 infants had ligation performed in the operating room (OR); the subsequent 15 had ligation in the Newborn Intensive Care Unit. There were no immediate postoperative deaths. Two infants died from problems presnet preoperatively within 30 days postoperatively. There were no infections. Technique in the unit utilizes an open warmer with local anesthesia and a paralyzing agent. By eliminating transportation to the OR one avoids problems with thermoregulation, loss of lines, malfunction of monitors, poorly controlled ventilation, and fluid overload. Additional advantages to ligation in the unit are that the infant is already monitored, intubated, and on a respirator, and that venous and usually umbilical arterial lines are in place. At the conclusion of operation, management is returned to the neonatologists for optimal continuity of care.


Macroscopic marital interaction coding systems: are they interchangeable?
The present study sought to determine the convergent validity of two macroscopic marital interaction coding systems: the Marital Interaction Coding System-Global and the Global Couple Interaction Coding System. The sample consisted of 40 couples who completed the Dyadic Adjustment Scale, the Potential Problem Checklist and a 30-min problem solving interactional task. Filmed interactions were coded by separate teams of observers using the Marital Interaction Coding System-Global and the Global Couple Interaction Coding System. Results showed that interobserver agreement, as assessed through intraclass correlations, was satisfactory for both coding systems. Between-system comparisons revealed that convergent validity coefficients were moderate; thus, it seems premature to conclude that macroscopic coding systems are interchangeable. Finally, multiple regression analyses indicated that both systems contained significant non-redundant behavioral predictors of marital adjustment. Implications of these results are discussed.


Regulation of MUC16 by inflammatory mediators in ocular surface epithelial cell lines.
The aim of the present study was to evaluate the regulation of membrane-anchored mucin MUC16 by proinflammatory cytokines and bacterial components at the ocular surface. Expression and distribution of MUC16 in conjunctival (HCjE) and corneal (HCE) epithelial cell lines was monitored by RT-PCR and immunohistochemistry. To determine the regulation of MUC16, cultured HCjEs and HCEs were stimulated with different cytokines, bacterial components and bacterial supernatants, and analyzed by real-time PCR, immunodot blot and immunohistochemistry. The results indicate that MUC16 is differentially regulated between HCjEs and HCEs after challenge with inflammatory mediators and suggest shedding of MUC16 from the ocular surface epithelia into the tear film. This seems to be precisely regulated. MUC16 shedding can be differentially increased and decreased, suggesting a protective function of membrane-anchored MUC16 and supporting the hypothesis that dysregulation of membrane-anchored MUC16 at the ocular surface may be involved in dry eye pathology.


Dimensions of Thyroid Cartilage Window for Medialisation Thyroplasty in Indian Population.
To derive optimal thyroid cartilage window for medialisation thyroplasty in Indian population and comparision of the same with standard parameters including Isshiki's thyroplasty type I. Along with comparision it is also attempted to bring out difference if any, to provide a better guidelines of medialisation thyroplasty in Indian population. A total No of 52 (35 male and 17 female) cadaveric laryngeal samples (formalin fixed) taken into study. Cartilage window over thyroid lamina is created and increased gradually. Endoscopic examination of medialisation by appropriate silastic block of true vocal cord noted at each level. Relevant thyroid anatomy at window corners also taken into consideration. In Indian set up, dimensions of window required for medialisation thyroplasty are slightly lesser than the average size quoted by premier study of Isshiki when compared in male population. The window size of males which produced ideal medialisation was 12-14 mm in length and 5 mm in height. In females it was 10-11 mm in length and 4 mm in height.


The potential role of the educational system in addressing the effect of inadequate knowledge of mosquitoes on use of insecticide-treated nets in Ghana.
Since 2001, there has been a tremendous increase in number of households protected by ITN and IRS in Ghana. However, there has not been evidence of a reduction in malaria cases as expected and reported deaths have rather increased since 2007. As a result, this study was undertaken to get a better understanding of perceptions of malaria, knowledge on mosquitoes and the value attached to ITNs among secondary and tertiary students in Cape Coast. Structured questionnaires were administered randomly to gather data on demographic characteristics of students, knowledge of mosquitoes and ITNs and attitude towards the use of ITN in seven public high schools and four tertiary institutions in Cape Coast metropolis. In addition, curriculums of science courses common to all students from junior high school to the university were carefully examined. A total of 492 students took part in this study and more than 90% of them had high knowledge of malaria transmission and ITN, but little knowledge of mosquito life history. Only 1% in secondary and 2.1% in tertiary institutions had seen or knew about all the development stages of mosquitoes. In high school and tertiary institutions, 24.2% and 10.8% of respondents, respectively, were able to mention other genera of mosquitoes, apart from Anopheles. Though 93.9% in senior high school and 86.7% in the tertiary institutions knew that ITNs are either used to protect oneself from mosquito bites or to prevent malaria, 32.7% of the respondents in secondary and 21.9% in tertiary institutions who owned ITN did not use them. The study reveals that respondents did not have adequate knowledge on the biology and behaviour of mosquitoes. This appears to weaken their knowledge of the link between the use of ITN and malaria control; the effect of this is that a significant number owned ITNs but did not use them. The implication is that if people will really accept and use ITN or other mosquito control interventions, then just creating awareness of those interventions is not enough but people should also be educated on the life history of mosquitoes and on the mechanism of the control strategies. This can be effectively done through the formal education system.


Long-term results of coronary artery bypass grafting in elderly Japanese patients.
This study was undertaken to examine long-term results of coronary artery bypass grafting in elderly Japanese patients. Of 1,425 coronary artery bypass grafting patients over the last 13 years, 137 patients were 70 or more years old and 1,288 were less than 70 years old. Mean number of distal anastomoses was similar in both groups. Postoperative survival and event-free proportion were estimated by the Kaplan-Meier actuarial method and compared among the groups by Cox-Mantel statistical analysis. Operative mortality and the incidence of late cardiac death after coronary artery bypass grafting were equivalent between the elderly and younger groups, although the rates of left main trunk disease, acute myocardial infarction, and emergency operation in the elderly group were significantly higher than those in the younger group. Coronary artery bypass grafting in elderly patients had a relatively high hospital mortality and more late noncardiac deaths, but the incidence of postoperative cardiac intervention in elderly patients was lower than that in younger patients. These results suggest that coronary artery bypass grafting for elderly patients is encouraged as well as is that for younger patients in a representative Japanese population.


Onychoscopy: Dermoscopy of the Nails.
Onychoscopy is the examination of the nail unit using a dermoscope. The dermoscopic criteria for a valid diagnosis have been developed and assessed in numerous papers. However, in all nail alterations that are suspicious or potentially malignant, a surgical intervention with subsequent histopathological evaluation should be performed. A simple visualization may not be helpful in diagnosing many nail conditions nor is a nail biopsy diagnostic in all cases. Onychoscopy is a valuable aid in enhancing visible nail features and in revealing cryptic features of diagnostic value.


Ruthenium-Catalyzed Synthesis of β-Hydroxyamides from β-Ketonitriles in Water.
An unprecedented hydration/transfer hydrogenation tandem process for the catalytic conversion of β-ketonitriles into synthetically useful β-hydroxyamides in water has been developed, making use of the ruthenium(II) complex [RuCl2(η6-p-cymene){P(4-C6H4F)2Cl}] in combination with sodium formate.


Endovascular treatment of a hepatic artery pseudoaneurysm associated with gastrointestinal tract bleeding.
Hemosuccus pancreaticus is a rare cause of gastrointestinal bleeding from the pancreatic duct originating from aneurysms or pseudoaneurysms of peripancreatic arteries. It is a life-threatening cause of gastrointestinal bleeding that should always be considered in patients with prolonged or intermittent obscure gastrointestinal blood loss, or both, especially in patients with pancreatic disorders or prior pancreatic surgery. We demonstrate an endovascular treatment strategy in a patient with a common hepatic pseudoaneurysm and upper gastrointestinal tract bleeding, with preserved flow in the hepatic artery. This treatment consisted of a covered stent placement in the hepatic artery, followed by transcatheter coil embolization of collateral feeding arteries.


Bizarre Parosteal Osteochondromatous Proliferation (Nora's Lesion) of Mandible With Recurrence: Case Report and Review of Literature.
Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign lesion exhibiting radiographic and histologic features that can be mistaken for malignancy. Most cases have been reported in the small tubular bones of the hands and feet, but involvement of the skull and jaws is extremely rare. Here, we present a case of BPOP involving the mandible in a 23-year-old male that, after initial excision, recurred within 18 months. To the best of our knowledge, this is only the third published case of BPOP arising in the mandible.


Alcianblue/PAS or PAS/alcianblue? Remarks on a classical technic used in carbohydrate histochemistry.
The combined alcian blue (AB)/PAS technic is widely used for the detection and characterization of mucosubstances in tissue sections. Mostly the sequence AB/PAS is used, occasionally also the reserved sequence PAS/AB. The present study shows clearly that the sequence of the combined technic, i.e. AB/PAS or PAS/AB is substantially influencing the results. So it could be demonstrated that by using the combination PAS/AB originally PAS-positive and AB-negative reacting mucosubstances become AB-positive. This could be caused by periodic acid oxidation followed by addition of hydrogen sulfite to aldehyde group thus providing secondary basophilic resp. AB positive material.


Sufficient extraction of Cr from chromium ore processing residue (COPR) by selective Mg removal.
Chromium ore processing residue (COPR) is a hazardous waste generated during the production of chromate. Currently, approximately 10% of Cr2O3 cannot be extracted after chromite sodium roasting and remains in COPR, wasting valuable Cr resources. In this study, Mg was selectively removed by using (NH4)2SO4 roasting in combination with H2SO4 leaching. The results showed that the selective removal of 79.55% Mg from COPR could be achieved under the optimum (NH4)2SO4 roasting conditions (80 mmol (NH4)2SO4, 800 °C, 2 h). During the subsequent sodium roasting and acid leaching stages, the Cr extraction rate was 84.63% for the COPR direct roasting and 95.39% for the Mg removal residue roasting. The increased Cr extraction efficiency is attributed to the transformation of Mg-rich spinel and diopside (the Mg & Cr coexisting phases) in COPR converted into easily extractable (Fe,Cr)2O3 and Cr2O3 after the Mg treatment. This study investigated that the phase transformation of the Cr host phases is crucial for the sufficient extraction of Cr and provides inspiration for the development of efficient and practical Cr extraction techniques. Moreover, the method can be extended to the effective extraction of Cr from other Cr-containing wastes.


HIV Prevalence Among Central American Migrants in Transit Through Mexico to the USA, 2009-2013.
HIV prevalence was estimated among migrants in transit through Mexico. Data were collected on 9108 Central American migrants during a cross-sectional study performed in seven migrant shelters from 2009 to 2013. Considerations focused on their sociodemographic characteristics, sexual and reproductive health, and experience with violence. Based on a sample of 46.6 % of respondents who agreed to be HIV tested, prevalence of the virus among migrants came to 0.71 %, reflecting the concentrated epidemic in their countries of origin. A descriptive analysis was performed according to gender: the distribution of the epidemic peaked at 3.45 % in the transvestite, transgender and transsexual (TTT) population, but fell to less than 1 % in men and women. This gender differential is characteristic of the epidemic in Central America. Furthermore, 23.5 % of TTTs and 5.8 % of women experienced sexual violence. The predominant impact of sexual violence on TTTs and women will influence the course of the AIDS epidemic.


COVID-19 presented with syndrome of inappropriate ADH secretion(SIADH): A case report from Bangladesh.
Novel corona virus(SARS-CoV-2) which emerged from Wuhan, China, has spread to whole worlds very rapidly causing enormous health effect and death. Current publications worldwide showed that COVID-19 is a disease involving multiple system of the body with many unusual presentations. So physicians face the challenges to manage it in the hospital. The syndrome of inappropriate secretion of anti diuretic hormone (SIADH) is one of the most common causes of hyponatremia accounts for approximately one-third of all cases. In the diagnosis of SIADH it is important to ascertain the euvolemic state of extra cellular fluid volume, both clinically and laboratory measurement. Several infections associated with SIADH have been reported. Howover, Coronavirus disease 2019(COVID-19) associated with SIADH were only few cases reported. We are presenting a case of 70 year old female admitted with unconsciousness later diagnosed as severe hyponatremia along with COVID-19 complicated with severe pneumonia.


Optimizing the science of drug development: opportunities for better candidate selection and accelerated evaluation in humans.
Two international meetings were convened in 1998 to review the current science of drug development and the potential opportunities to optimize the evaluation of new drugs in humans. This report represents a synopsis of these meetings, and focuses on the current state of knowledge pertaining to drug development, future scientific and technical needs, and the relative merits of various strategies intended to accelerate the clinical development of drugs.


Genetic and phenotypic relationships between carbohydrate larval antigen (CarLA) IgA, parasite resistance and productivity in serial samples taken from lambs after weaning.
Genetic selection for enhanced levels of protective antibody to specific nematode antigens may be a more user-friendly means of selecting animals for resistance to gastrointestinal nematodes than obtaining faecal samples and selecting on the basis of faecal egg counts. Saliva IgA antibody levels to the L3-specific surface glycan known as carbohydrate larval antigen were measured on six occasions over a 5 month period in approximately 350 lambs. The carbohydrate larval antigen IgA response increased markedly with time as the lambs grazed on pasture naturally contaminated with nematode parasite larvae. The monthly loge transformed carbohydrate larval antigen IgA levels were moderately heritable at all samplings, with a combined value of 0.28±0.10 and a repeatability of 0.35±0.03. The genetic correlations between all samplings were high (0.86), suggesting that testing for a carbohydrate larval antigen IgA response could be carried out at any time in the 5 months post-weaning. The transformed carbohydrate larval antigen IgA levels were genetically and phenotypically correlated negatively with loge transformed (faecal egg count+50), averaging -0.57±0.20 and -0.12±0.03 (P<0.05), respectively. The correlations between carbohydrate larval antigen IgA and breech-soiling (dag score) never reached significance. However, genetic correlations between carbohydrate larval antigen IgA and live weight were always positive and significantly so, especially at the beginning and end of the trial, indicating that carbohydrate larval antigen IgA production may be an important genetic determinant of growth rate for lambs experiencing a larval challenge. The data suggest that the ideal time to sample for a carbohydrate larval antigen IgA response and maximise selection for lowered faecal egg count and increased live-weight would be in the first 2 months after weaning.


Ruxolitinib: a potent and selective Janus kinase 1 and 2 inhibitor in patients with myelofibrosis. An update for clinicians.
Ruxolitinib became the first US Food and Drug Administration approved therapy for myelofibrosis in 2011 and EU approval is anticipated in summer 2012. Two large phase III trials (known as the COMFORT studies) were the basis for this approval and were published recently. In this review article we discuss the challenges in managing myelofibrosis, the information to date about ruxolitinib and speculate as to the future direction with this and similar agents.


Acetylcholine's inhibitory effect on the calcium-dependent depolarization in the heart cells of a reptile (Lacerta sicula campestris). Preliminary notes.
The results of experiments performed with high - K+ solutions suggest that in the lizard atrial cells Ach normally displays its negative inotropic effects by a double mechanism = an "indirect" inhibition, mediated by the increase of the membrane permeability to K+ ions; and a "direct" inhibition of the Ca- carried slow inward current. In the ventricular fibres there isn't a direct-effect of this drug, under normal conditions.


Distribution of nursing workforce in the world using Gini coefficient.
Unequal Access to human resources for health, reduces access to healthcare services, worsens the quality of services and reduces health outcomes. This study aims to investigate the distribution of the nursing workforce around the world. This is a descriptive-analytical study, which was conducted in 2021. The number of nurses and world populations was gathered from World Health Organization (WHO) and The United Nations (UN) databases. The UN has divided world countries based on the Human Development Index (HDI) into four categories of very high, high, medium and low HDI. To investigate the distribution of the nurses around the world, we used the nurse population ratio (per 10,000 population), Gini coefficient, Lorenz curve and Pareto curve. On average, there were 38.6 nurses for every 10,000 people in the world. Nations with the very high HDI, had the highest nurse/population ratio (95/10,000), while the low HDI nations had the lowest nurse/population ratio (7/10,000). Most nurses around the world were females (76.91%) who were in the age group of 35-44 (29.1%). The Gini coefficient of nations in the each four HDI categories varied from 0.217 to 0.283. The Gini coefficient of the nations between the four HDI categories was 0.467, and the Gini coefficient of the whole world was 0.667. There were inequalities between countries all over the world. Policymakers should focus on the equitable distribution of the nursing workforce across all local, national and regional levels.


The role of dietary fat and hepatic triglyceride secretion in cancer-induced hypertriglyceridemia.
Growth of Ehrlich ascites carcinoma induces hyperlipemia in mice. In the present study using male Swiss-Webster mice, we examined whether the usual elevations of plasma triglyceride levels in cancerous mice would occur in the absence of dietary fat. Hypertiglyceridemia developed at a similar rate and to a comparable degree in tumerous mice eating a fat-free (58% glucose) diet and in those fed Purina chow. Maximal hyperlipidemia was observed on day 6 or day 8 in tumorous mice fed either diet. To determine whether the endogenous cancer-induced hyperlipidemia was due to hypersecretion of triglycerides by the liver, triglyceride secretion rates were studied 0, 2, 4, 6, 8, 10, and 12 days after tumor inoculation using Triton WR-1339. The secretory rates did not increase prior to or during the development of hypertriglyceridemia in tumorous mice and were not significantly different from those of control mice. On days 10 and 12, triglyceride secretion actually decreased in tumorous mice. Other possible causes for hypertriglyceridemia are discussed in light of the present findings of undetectable differences in triglyceride secretion rates accompanying growth of Ehrlich ascites carcinoma in mice.


Effects of urea and molybdate on the chick oviduct progesterone receptor.
The chick oviduct cytosol progesterone receptor, when complexed with ligand, can be exposed to urea concentrations as high as 3 M (at 0 degrees C) without loss of steroid binding capacity. The ligand dissociation rate is increased greater than or equal to 10 fold under these conditions. The "native" 8 S form of the receptor is progressively converted to a 4 S species by urea (greater than 2 M) as seen in ultracentrifugation analysis. This conversion is inhibited by Na2MoO4 (5-50 mM) suggesting that molybdate stabilizes the 8 S molecule by direct interaction. At urea concentrations above 2 M, the ligand-free receptor looses progressively its binding capacity. The "transformed", 4 S receptor was less stable than the 8 S species, and could not be protected by molybdate.


In vitro and in vivo transplantation of fetal rat brain cells following incubation with various anatomic tracing substances.
Implantation of fetal brain regional anlage into host brains ('brain transplantation') holds promise as a plausible treatment for certain human neurodegenerative disorders. Improvements in experimental brain transplantation techniques include: (1) utilization of brain cells in tissue culture as opposed to freshly prepared cell suspensions as a transplantation source, (2) prelabeling of fetal brain cells with inert, non-toxic tracer substances to allow subsequent (a) unequivocal identification of those cells as being fetally derived, and (b) anatomical and immunohistochemical identification of transplanted neurons, and (3) development of in vitro models for transplantation to allow physiological studies of connections formed between fetal neurons and host brain tissue. We examined the ability of brain cell suspensions derived from rat fetuses 15-17 gestational days old to accumulate and retain anatomic tracing substances, including Phaseolus vulgaris leucoagglutinin (PHA-L), rhodamine-labeled latex microspheres (RLM) and fluorogold (FG). All tracers were rapidly accumulated by fetal brain cells, but only PHA-L and RLM were retained following implantation into adult hosts or in tissue culture in vitro. PHA-L-labeled fetal brain cells transplanted in vivo showed morphological characteristics similar to fetal neurons kept in tissue culture in vitro. RLM- or PHA-L-labeled fetal brain cells can be co-cultured with rat brain slices maintained in long-term roller culture. This in vitro system will allow identification and physiological or immunohistochemical study of interactions between fetally derived and host brain neurons.


Steroid hydroxylase induction in cultured human lymphocytes: effects of the menstrual cycle.
Steroid hydroxylases (SAH) are inducible in cultured human lymphocytes following treatment with estradiol-17beta. The enzyme systems induced are carbon monoxide sensitive and convert estradiol-17beta to a metabolite chromatographically indistinguishable from estriol. The level of inducibility of SAH varies drastically over a normal menstrual cycle with maximum induction in the late follicular phase and minimum induction during the luteal phase. The use of an oral contraceptive containing both a synthetic progestogen and ethynyl estradiol reduced SAH induction levels to those typically seen during the luteal phase of the menstrual cycle.


Safety and Efficacy of 980nm Diode Laser for Brain Tumor Microsurgery-A Pioneer Case Series.
Quality of life is essential for oncologic patients. Several tools are available to improve microsurgery and reduce morbidity. Diode laser is a precise and useful technology for microsurgery. The goal of this pioneer case series is to describe the oncologic use of the 980nm diode laser and the qualitative variables analyzed. Besides, review the current literature about lasers in neurosurgery. A longitudinal prospective study described patients with meningioma or glioma submitted to neurosurgical laser-assisted procedures. Also, we performed a review in medical databases using the terms "diode laser" and "neurosurgery." No paper described the use of a diode laser in neurooncology. The 980nm diode laser was used in 15 patients. The device is thin, silent, and easy to handle. Excellent hemostasis was observed, especially in skull base meningiomas. Also, it was easy and fast to delimit tumor from normal brain tissue without damage to surrounding parenchyma. No postoperative complications occurred. The diode laser is a useful tool for brain tumor surgery, particularly concerning hemostasis. Surgical site coagulation is effective without damage to adjacent structures, especially in gliomas near eloquent regions. We consider this technique a suitable adjuvant resource for brain tumor surgeries to provide an excellent hemostasis and help cut and vaporize a lesion.


The Ysa type 3 secretion system of Yersinia enterocolitica biovar 1B.
Yersinia enterocolitica biovar 1B maintains two distinct and independently operating type 3 secretion (T3S) systems with the capacity to translocate toxic effector proteins into mammalian cells. Each of these T3S systems plays a role in the outcome of an infection by influencing different stages of infection. Recent investigations of the Ysa T3S system have revealed it is important for Y. enterocolitica survival during the gastrointestinal phase of infection. This sets this system apart from the Ysc T3S system which is important for systemic infections. Identification of the effector proteins has provided insight on how the Ysa T3S system modulates Y. enterocolitica interactions with the host. In part, the Ysa T3S system targets the innate immune response to suppress the ability of the host to rapidly clear an infection.


Bilateral congenital aplasia of the scaphoid.
A case of bilateral congenital aplasia of the carpal scaphoid bone is presented. In contrast to previously reported cases of congenital hypoplasia of the scaphoid, this case was not associated with hypoplasia or absence of thenar and forearm muscles, absence of the sesamoid bones of the thumb, abnormalities of the skeleton of the thumb ray or hypoplasia of the forearm bones.


Assessment of the feasibility of oral controlled release in an exploratory development setting.
Controlled release (CR) formulations have generally been considered as follow-ons to conventional immediate release formulations to manage the life cycle of a product. Although significant opportunities exist to use CR as an enabling technology for certain exploratory drug candidates, they have not been fully exploited. However, progress made in assessing CR feasibility based on the physicochemical and biopharmaceutical properties of the drug, together with advances made in understanding the various CR technologies and developing formulations in a fast and efficient manner, have increasingly made it possible to consider CR in an exploratory development setting.


Induction of contact hypersensitivity in the mouse model.
Contact hypersensitivity (CHS) in the mouse model is a standard method to assess delayed type hypersensitivity (DTH) responses in the skin induced by low molecular weight chemicals that in humans cause contact dermatitis. These responses are clinically important and present as eczematous skin reactions. Here, this chapter describes the standard protocol for T cell-mediated CHS and a variation thereof, which allows to address more specific questions regarding immunologic pathomechanisms.


Ophthalmic contact lens with internal fixation light for examination of the optic nerve head.
Stereoscopic slitlamp examination of the optic nerve head in one-eyed patients is difficult because there is currently no way to provide the patient with a fixation target. This situation is often aggravated in glaucoma patients by a miotic and fixed pupil. We have developed a funduscopic contact lens which incorporates a fixation target, allowing the patient to view the target with the eye being examined. The device has been successfully tested on normal volunteers.


Technical Note: Design and commissioning of a water phantom for proton dosimetry in magnetic fields.
To design and commission a water phantom suitable for constrained environments and magnetic fields for magnetic resonance (MR)-guided proton therapy. A phantom was designed, to enable precise, remote controlled detector positioning in water within the constrained environment of a magnet for MR-guided proton therapy. The phantom consists of a PMMA enclosure whose outer dimensions of 81 × 40 × 12.5 cm 3 were chosen to optimize space usage inside the 13.5-cm bore gap of the magnet. The moving mechanism is based on a low-height H-shaped non-ferromagnetic belt drive, driven by stepper motors located outside of the magnetic field. The control system and the associated electronics were designed in house, with similar features as available in commercial water phantoms. Reproducibility as well as accuracy of the phantom positioning were tested using a high-precision Leica AT 402 laser tracker. Laterally integrated depth dose curves and lateral beam profiles at three depths were acquired repeatedly for a 148.2 MeV proton beam in water. The phantom was successfully operated with and without applied magnetic fields. For complex movements, a positioning uncertainty within 0.16 mm was found with an absolute accuracy typically below 0.3 mm. Laterally integrated depth dose curves agreed within 0.1 mm with data taken using a commercial water phantom. The lateral beam offset determined from beam profile measurements agreed well with data from Monte Carlo simulations. The phantom is optimally suited for detector positioning and dosimetric experiments within constrained environments in high magnetic fields.


Application of an anterior eye segment analysis system in clinical cataract research.
Clinical application of a newly developed ANTERIOR EYE SEGMENT ANALYSIS SYSTEM was introduced. By this system, a Scheimpflug and a retroillumination image of the anterior eye segment are obtained through a CCD camera, separately. To overcome difficult problems experienced with previous types of lens documentation systems, several kinds of new mechanisms were built into this system. Slit and retroillumination images of some cases with cataracts and some examples of anterior eye segment analysis were described.


Test of infant motor performance: Cross-cultural adaptation, validity and reliability in Persian infants.
The Test of Infant Motor Performance (TIMP) is an appropriate tool used to measure infant motor performance in many countries and due to the importance of the TIMP in the early diagnosis of infants with developmental delay, the production of a reliable translation of the TIMP in Iran is necessary. This study was designed to evaluate the validity and reliability of the Persian version of the TIMP and cross-cultural adaptation of the TIMP to Persian. Twenty- two experts were involved in translation, cross-cultural adaptation, validity and reliability. 170 Persian premature infants with post menstrual age (PMA) 34-42 weeks were tested to evaluate inter-rater and intra-rater reliability, test-retest and discriminative validity of the Persian version of the TIMP. The content validity and face validity of the items of the Persian version of the TIMP were confirmed by a 10-expert panel and 10 therapists. High intra- and inter-rater reliability (ICC = 0.98, Kappa = 0.93), test-retest reliability (ICC = 0.98) and internal consistency (α = 0.82) were detected for the Persian version of the TIMP. Discriminative validity confirmed that the TIMP could distinguish groups of infants born with a low birth weight (p ˂ 0.001) and infants born small for gestational age (p = 0.002). High validity and reliability are reported for the Persian version of the TIMP and this test was demonstrated to be differentiate among groups of infants who are at risk of motor delay.


Communicative disorders at a health-care center.
The purpose of this study was to identify the prevalence of communicative disorders in a Children and Youth Program during the 5-yr period 1973-1977. It appears that the numerous speech and hearing surveys recorded fail to do the following: (a) identify speech, language, and hearing pathologie from a comprehensive health-care center and/or hospital; (b) study types of clientele longitudinally; (c) study prevalence and needs of minority groups specifically; and (d) study prevalence of communicative disorders in preshool children. For the Black community under study, it appears that the prevalence of communicative disorders is greater than reported in other surveys. In addition, the current study identifies a community not receiving services. In reviewing the facilities available to this socieconomic community, one finds inadequacies. These inadequacies may be reflected in manpower and equipment rather than programs and resources. The data indicate a tremendous need to expand available services.


High resolution miniaturized stepper ultrasonic motor using differential composite motion.
Experiments show that there is a limited minimum stepped angle in ultrasonic motors (USM). The research on the minimum angle of stepper USM with 15 mm in diameter and wobbling mode is being carried out. This paper presents a novel way to decrease the minimum stepped angle of USM based on the principle of differential composite motion (DCM), i.e. clockwise and counterclockwise rotation. The prototype was fabricated and experiments proved that this method is useful and also keeps a high torque for a large stepped angle. The stator of the prototype is steel, and rotor is fiberglass, antifriction material or steel. The prototype can operate well over 150 h with a 5 kHz wide frequency band. The minimum stepped angle is 46" using a coventional method while 12" using DCM method proposed in this paper.


Traumatic anterior knee dislocation after total knee arthroplasty.
This article describes a traumatic complete anterior knee dislocation of a previously well-functioning total knee arthroplasty. A thorough physical examination with appropriate radiographic imaging study is required for proper evaluation and treatment of this injury, as it is often associated with neurovascular injury and subsequent global instability of the injured knee is likely.


The development of the septal region in the rat. II. Morphogenesis in normal and x-irradiated embryos.
Morphogenesis of the septal region was examined in normal rat embryos from embryonic day (E) 10 to E22. The greater part of the septal region is postulated to form from two separate anlagen which can be clearly distinguished in the telencephalon by E13 and E14. One lies in the anterior ventromedial wall and presumably forms the nucleus of the diagonal band, medial, lateral, and triangular septal nuclei. The other lies in the posterior ventrolateral ridge and presumably forms the bed nuclei of the stria terminalis and the anterior commissure. On E15, the early differentiating cells in these anlagen fuse in the same region where the anterior commissure will cross on E17. With later embryonic development, differentiating cells of the strial bed nucleus accumulate rostral and caudal to the fused area. The same pattern is found in the medial and triangular septal nuclei and in the nucleus of the diagonal band. The differentiating cells of the lateral septal nucleus accumulate dorsal and lateral to medial and triangular septal nuclei. On E16 and E17, a prominent subependymal zone develops in the anterior septal region and presumably gives rise to the nucleus accumbens. A quantitative analysis was made of three cell zones (neuroepithelium, subependymal zone, differentiating cell zone) at coronal levels through the developing nucleus accumbens and the nucleus of the diagonal band (anterior level) and the medial and lateral septal nuclei (middle and posterior levels). At all levels, the area of the neuroepithelium continually declines, that of the differentiating cell zone continually increases, and that of the subependymal zone shows a rise and decline. On a proportional basis, both the neuroepithelium and subependymal zone occupy significantly more area anteriorly than posteriorly, while the differentiating cell zone shows the reverse gradient. To accurately locate regions of primitive mitotic and migratory cells within the zones at each level, the number of cells surviving a single exposure to 200 R X-rays in embryonic brains (E15-E22) were compared with controls. Each zone responded differently to X-ray insult. The radiosensitivity of the neuroepithelium decreases significantly after E19; the subependymal zone is highly radiosensitive throughout; the differentiating cell zone is radioresistant throughout. The significance of these findings is discussed in the light of the autoradiographic determination of the time of formation of septal neurons (Bayer, '79).