Ingestion of acidic foods mimics gastroesophageal reflux during pH monitoring.
Ingestion of acidic foods may produce artifactual drops in pH to < 4 that may be difficult to differentiate from a true acid reflux event. We aimed to evaluate intraesophageal pH changes during the ingestion of acidic food and describe the frequency and implications of acidic food ingestion on ambulatory pH monitoring. Ten normal volunteers (six females; mean age, 34) underwent combined impedance-pH testing with a pH electrode placed 5 cm above the lower esophageal sphincter. Each volunteer received 50 ml each of acidic foods in random order. Nadir and mean pH for 30 sec after ingestion of each substance were recorded. Subsequently 100 randomly selected reflux monitor diaries were reviewed, searching for ingestion of acidic foods, and 100 pH tracings were reviewed to evaluate the impact of including/excluding meal periods on percentage time pH < 4 and DeMeester scores. All foods produced abrupt drops to pH < 4, in 80% of cases exceeding 30 sec. During ambulatory pH monitoring 78% of patients recorded ingestion of at least 1 of the 10 tested substances during meals, the majority admitting ingesting carbonated beverages. Not excluding meal periods would have led to the misinterpretation of 6-16% of tracings, depending on the criteria used to identify abnormal acid exposure. We conclude that ingestion of acidic foods is frequent and carries the risk of overdiagnosing GERD. Current findings support the recommendations to carefully instruct patients to record all oral intake and to exclude meal periods from the analysis.


Salivary cortisol and psychopathy dimensions in detained antisocial adolescents.
Previous research revealed hypothalamic-pituitary-adrenal (HPA) axis abnormalities in relation to antisocial and aggressive behavior. Some evidence suggests that low cortisol levels may serve as a biological marker for a severe antisocial subgroup with pronounced callous-unemotional (CU) traits. Children displaying the combination of severe antisocial behavior and CU traits appear to be particularly at risk of developing adult psychopathy. Given the lack of studies on the relationship between cortisol levels and CU traits in antisocial adolescents, the current study investigates whether cortisol levels are uniquely associated with CU traits as compared to other psychopathy dimensions (i.e., narcissism and impulsivity). Detained antisocial adolescents (n=63) and a community comparison group (n=62) completed diaries and collected three saliva samples daily on two days, with compliance monitored electronically. Psychopathy dimensions were assessed through self-report questionnaires. Externalizing symptoms were assessed by structured clinical interview. Multilevel regression analyses indicated no differences in cortisol levels or diurnal slopes between the two groups. Overall, cortisol levels were not significantly related to psychopathy dimensions. However, greater impulsivity was associated with lower cortisol levels in the community sample, but not in the antisocial group. Results cast doubt on the notion of low cortisol levels as a biological marker for CU traits. Low basal cortisol levels appear to be more closely related to a general deficit in behavioral regulation. Implications for future research are discussed.


A new species of the genus Alienates Barber (Hemiptera: Heteroptera: Enicocephalidae: Alienatinae) from Venezuela.
New species Alienates thomasi sp. nov. Baňař & Štys is described from Venezuela based on a single female. It is the first species recorded from South America, and is illustrated and compared with other Caribbean and Central American Alienates species.


Di (2-ethylhexyl) phthalate impairs primordial follicle assembly by increasing PDE3A expression in oocytes.
It is known that Di (2-ethylhexyl) phthalate (DEHP) may impact mammalian reproduction and that in females one target of the drug's action is follicle assembly. Here we revisited the phthalate's action on the ovary and from bioinformatics analyses of the transcriptome performed on newborn mouse ovaries exposed in vitro to DEHP, up-regulation of PDE3A, as one of the most important alterations caused by DEHP on early folliculogenesis, was identified. We obtained some evidence suggesting that the decrease of cAMP level in oocytes and the parallel decrease of PKA expression, consequent on the PDE3A increase, were a major cause of the reduction of follicle assembly in the DEHP-exposed ovaries. In fact, Pde3a RNAi on cultured ovaries reducing cAMP and PKA decrease counteracted the primordial follicle assembly impairment caused by the compound. Moreover, RNAi normalized the level of Kit, Nobox, Figla mRNA and GDF9, BMP15, CX37, γH2AX proteins in oocytes, and KitL transcripts in granulosa cells as well as their proliferation rate altered by DEHP exposure. Taken together, these results identify PDE3A as a new critical target of the deleterious effects of DEHP on early oogenesis in mammals and highlight cAMP-dependent pathways as major regulators of oocyte and granulosa cell activities crucial for follicle assembly. Moreover, we suggest that the level of intracellular cAMP in the oocytes may be an important determinant for their capability to repair DNA lesions caused by DNA damaging compounds including DEHP.


Brainstem Biomarkers of Clinical Variant and Pathology in Progressive Supranuclear Palsy.
Magnetic resonance brainstem measurements are useful structural biomarkers in the Richardson's syndrome variant of progressive supranuclear palsy (PSP). However, it is unclear how these biomarkers differ across the phenotypic spectrum of PSP and how they relate to underlying pathology. The aim of this study was to compare brainstem imaging measures across clinical variants of PSP and determine sensitivity and specificity based on pathologically diagnosed cases. A total of 153 patients with PSP who represented eight clinical variants were recruited at Mayo Clinic (Rochester, MN, USA) and underwent structural magnetic resonance imaging (MRI). Midbrain and pons area and superior and middle cerebellar peduncle width measurements were performed, and midbrain/pons ratio and Magnetic Resonance Parkinsonism Index (MRPI) were calculated. Among the 43 patients who later died, PSP pathology was confirmed in 29, whereas 14 had other pathology. Brainstem measurements varied across PSP clinical variants and were most abnormal in PSP-Richardson's syndrome and frontal variants, followed by PSP-corticobasal, PSP-speech/language, and PSP-parkinsonism variants. All these variants showed abnormalities compared with controls. The PSP-gait freezing variant and patients with prominent corticospinal tract signs showed normal brainstem measures. Among cases with confirmed PSP pathology, the midbrain area, midbrain/pons ratio, and MRPI were all more abnormal compared to those with other pathologies, with best differentiation obtained with the MRPI (sensitivity = 83%; specificity = 85%). MRI brainstem measures show utility as diagnostic biomarkers across PSP clinical variants and have the potential to be useful in predicting underlying pathology. © 2021 International Parkinson and Movement Disorder Society.


Synthetic idiotypes: the third hypervariable region of murine anti-dextran antibodies.
Synthetic peptides with the sequence of the third hypervariable region of either M104 or J558 murine myeloma proteins have been used to immunize rabbits. Most of the resulting antisera distinguished the two proteins in a specific manner corresponding to the sequence of the immunizing peptide. Thus synthetic peptides have been used to elicit antisera specific for particular idiotypes. These studies have significant implications for our understanding of the molecular basis of idiotypy.


A resting-state electroencephalographic microstates study in depressed adolescents with non-suicidal self-injury.
Neuroimaging studies have revealed abnormal brain activities in depressed teenagers who engage in non-suicidal self-injury (NSSI). We used resting-state electroencephalography (EEG) microstate analysis, which indicates the brief overlap of brain network activation for exploring the characteristics of large-scale cortical activities in depressed adolescents engaged with NSSI to clarify the underlying temporal mechanism. A modified k-means cluster algorithm was used to segment 64-channel resting-state EEG data into microstates. Data from 27 healthy adolescents, 37 adolescents with major depressive disorder (MDD), and 53 adolescents with both MDD and NSSI were examined in this study. The resting-state microstate parameters were compared among groups using the one-way ANOVA and Spearman correlation. Then the associations between significantly different microstate parameters and the depressive severity and self-harming data in the patient groups were further analyzed. The MDD group had higher contribution (p < 0.01), occurrence (p < 0.01) of microstate A, and higher microstate E→A transition (p < 0.05) than the HC and the NSSI group. The MDD group showed a distinctly longer duration (p < 0.05) of microstate A and microstate A→C transition than the HC. The transition probability from B to C was increased in the NSSI group compared to the HC. In the MDD group, the HAMD correlated with the duration of microstate A (Spearman's rho = 0.34, p = 0.044), as the PHQ-9 correlated with its occurrence (Spearman's rho = 0.37, p = 0.028). This research revealed that whereas depressive adolescents with NSSI and MDD displayed similar patterns with healthy controls in EEG microstate, the MDD group did not. Additionally, the non-random transition from microstate E→A may protect against recent self-harm in adolescents with MDD.


An exploratory study of women's experiences and key stakeholders views of moxibustion for cephalic version in breech presentation.
A phenomenological research approach was taken to explore women's feelings and experiences of using moxibustion for cephalic version in breech presentation. Eight women with an uncomplicated breech presentation at term were offered moxibustion. Qualitative interviews were carried out before and after the treatment and women completed daily logs of their experiences. Women experienced anxieties about the implications of breech presentation and the options offered to them. All women carried out the treatment successfully and overall experiences were positive. Compliance was excellent and women reported few negative effects. The partner's co-operation was important to ensure that the procedure was carried out effectively and safely. Key stakeholders were also interviewed to determine their views on the requirements of implementing moxibustion into the maternity services. The need for research evidence of effectiveness was a priority. In addition, a number of practical issues are suggested for consideration in the implementation of a service or in future research designs.


The effects of light therapy on sleep problems: A systematic review and meta-analysis.
Although bright light therapy seems a promising treatment for sleep problems, research shows inconclusive results. This meta-analysis is the first to systematically review the effect of light therapy on sleep problems in general and on specific types of sleep problems in particular (circadian rhythm sleep disorders, insomnia, sleep problems related to Alzheimer's disease and dementia). Fifty-three studies with a total of 1154 participants were included. Overall effects and effects on separate circadian and sleep outcomes were examined. We calculated Hedges' g effect sizes and we investigated the effects of twelve moderators (design-related, treatment-related, participant-related). Light therapy was found effective in the treatment of sleep problems in general (g = 0.39), and for circadian rhythm sleep disorders (g = 0.41), insomnia (g = 0.47), and sleep problems related to Alzheimer's disease/dementia (g = 0.30) specifically. For circadian rhythm sleep disorders, effects were smaller for randomised controlled trials. For insomnia, we found larger effects for studies using a higher light intensity, and for sleep problems related to Alzheimer's disease/dementia larger effects were found for studies with more female participants. There was indication of publication bias. To conclude, light therapy is effective for sleep problems in general, particularly for circadian outcomes and insomnia symptoms. However, most effect sizes are small to medium.


Cyclic AMP levels in isolated frog skin epithelium: effects of phosphodiesterase inhibitors, oxytocin and catecholamines.
Direct measurements of cyclic AMP were performed in the isolated epithelium of frog skin. Phosphodiesterase inhibitors (methylxanthines, papaverine) and activators of adenylyl cyclase (oxytocin, catecholamines) significantly increased the cyclic AMP content. Propranolol completely blocked the generation of cAMP induced by beta-adrenergic agonists but had little or no effect on that induced by oxytocin. Phentolamine enhanced the cAMP production by adrenalin and noradrenalin. At supramaximal concentrations, oxytocin and isoproterenol produced similar increments in cAMP, while exposure to both agents roughly doubled the increase in cAMP. The results suggest the presence of independent receptors for oxytocin and catecholamines in frog skin, with additive effects on cAMP generation.


Comparative analysis of intracardiac neural structures in the aged rats with essential hypertension.
Persistent arterial hypertension initiates cardiac autonomic imbalance and alters cardiac tissues. Previous studies have shown that neural component contributes to arterial hypertension etiology, maintenance, and progression and leads to brain damage, peripheral neuropathy, and remodeling of intrinsic cardiac neural plexus. Recently, significant structural changes of the intracardiac neural plexus were demonstrated in young prehypertensive and adult hypertensive spontaneously hypertensive rats (SHR), yet structural alterations of intracardiac neural plexus that occur in the aged SHR remain undetermined. Thus, we analyzed the impact of uncontrolled arterial hypertension in old (48-52 weeks) SHR and the age-matched Wistar-Kyoto rats (WKY). Intrinsic cardiac neural plexus was examined using a combination of immunofluorescence confocal microscopy and transmission electron microscopy in cardiac sections and whole-mount preparations. Our findings demonstrate that structural changes of intrinsic cardiac neural plexus caused by arterial hypertension are heterogeneous and may support recent physiological implications about cardiac denervation occurring together with the hyperinnervation of the SHR heart. We conclude that arterial hypertension leads to (i) the decrease of the neuronal body area, the thickness of atrial nerves, the number of myelinated nerve fibers, unmyelinated axon area and cumulative axon area in the nerve, and the density of myocardial nerve fibers, and (ii) the increase in myelinated nerve fiber area and density of neuronal bodies within epicardiac ganglia. Despite neuropathic alterations of myelinated fibers were exposed within intracardiac nerves of both groups, SHR and WKY, we consider that the determined significant changes in structure of intrinsic cardiac neural plexus were predisposed by arterial hypertension.


Development of a microsurgery-assisted robot for high-precision thread traction and tension control, and confirmation of its applicability.
Microsurgery requires high skills for suturing using fragile threads, often within narrow surgical fields. Precise tension is required for good healing and to avoid the risk of thread breakage. To meet the demands, we developed a novel assist robot utilizing high-precision sensorless haptic technology. The robot adopts a cable-driven mechanism to maintain a distance from the surgical area and enhances compatibility with surgical equipment such as microscopes. The robot performance was verified through in vitro and in vivo experiments using a rat model. The realization of precise tension control was confirmed in both experiments. In particular, in the in vivo experiments, the developed robot succeeded to produce a knot with an accurate tension of 0.66% error. The developed robot can realize to control traction force precisely. This technology might open up the window for a full assist robot for microsurgery with haptic feeling.


Symbiont abundance is more important than pre-infection partner choice in a Rhizobium - legume mutualism.
It is known that the genetic diversity of conspecific rhizobia present in root nodules differs greatly among populations of a legume species, which has led to the suggestion that both dispersal limitation and the local environment affect rhizobial genotypic composition. However, it remains unclear whether rhizobial genotypes residing in root nodules are representative of the entire population of compatible symbiotic rhizobia. Since symbiotic preferences differ among legume populations, the genetic composition of rhizobia found within nodules may reflect the preferences of the local hosts, rather than the full diversity of potential nodulating rhizobia present in the soil. Here, we assessed whether Vicia cracca legume hosts of different provenances select different Rhizobium leguminosarum genotypes than sympatric V. cracca hosts, when presented a natural soil rhizobial population. Through combining V. cracca plants and rhizobia from adjacent and more distant populations, we found that V. cracca hosts are relatively randomly associated with rhizobial genotypes. This indicates that pre-infection partner choice is relatively weak in certain legume hosts when faced with a natural population of rhizobia.


Cognitive behavior therapy in patients with chronic fatigue syndrome: the role of illness acceptance and neuroticism.
Increasing the quality of life (QoL) of patients with chronic fatigue is challenging because recovery is seldom achieved. Therefore, it is important to identify processes that improve QoL. This study examined the extent of improvement related to cognitive behavior group therapy (CBT), and whether improvement is affected by initial levels of acceptance and neuroticism. Eighty CFS patients followed CBT, and self-reported (pre-post design) on mental and physical QoL (MQoL and PQoL), fatigue, acceptance, and neuroticism. The extent of improvement was analyzed using t-tests, effect sizes, and clinically significant change criteria. Whether acceptance and neuroticism at baseline predicted changes was analyzed by means of correlation and regression analyses. Significant improvement was found for all variables. The effect size for MQoL and PQoL was small; for acceptance and fatigue, effect size was moderate. About 20% (MQoL) to 40% (fatigue) of the participants clinically improved. Pre-treatment level of acceptance was negatively correlated with changes in MQoL, not with PQoL changes. Neuroticism pre-treatment was positively related with MQoL changes. Regression analysis showed an effect of acceptance on changes in MQoL beyond the effect of neuroticism. Although CBT is an evidence-based treatment, the sizes of the effects are often small regarding QoL. Our study also revealed small effect sizes. Our study showed that patient characteristics at baseline were significantly associated with MQoL outcome; indicating that CFS patients with high neuroticism or with a low acceptance show more improvement in MQoL. We propose to specifically target acceptance and neuroticism before treatment in order to maximize clinical relevance.


Target selected treatment with levamisole to control the development of anthelmintic resistance in a sheep flock.
Levamisole phosphate, chosen based on its 100 % efficacy demonstrated by a previous fecal egg count reduction test (FECRT), was used as the exclusive anthelmintic treatment in the Embrapa Southeast Livestock sheep flock from 2009 to 2014 in a target selected treatment scheme. In the present study, the effectiveness of this nematode control scheme was evaluated after 5 years by FECRT, larval development test (LDT), and a molecular test to assess the development of levamisole resistance in Haemonchus contortus. Animals were submitted to treatments with albendazole, levamisole, closantel, ivermectin, moxidectin, and monepantel. Eggs per gram of feces (EPG) counts and fecal cultures were performed, and anthelmintic efficacy was calculated by the RESO 4.0 program. The helminths of the flock (GIN Embrapa2014) were compared to susceptible (McMaster) and resistant (Embrapa2010) H. contortus isolates in the LDT to estimate the LC50 and LC90 of levamisole and in a molecular test to evaluate the 63-bp indel in the acr8 gene associated with levamisole resistance. In the FECRT, parasites were susceptible to monepantel (99.6 %) and closantel (98.3 %), but resistant to moxidectin (93.8 %), levamisole (70.4 %), ivermectin (48.1 %), and albendazole (0 %). In the coproculture on D14, and the control group presented 80 % H. contortus and 20 % Trichostrongylus sp., while in the monepantel group L1 were observed as well as Oesophagostomum sp. L3. LDT and resistance factors provided good separation between susceptible and resistant parasites. The genotypic frequencies of the 63-bp insertion in the acr8 gene in H. contortus were 11.9, 6.7, and 0 % in GIN Embrapa2014, Embrapa2010, and McMaster isolates, respectively. After 5 years of exclusive use, the nematodes developed resistance to levamisole, detected by FECRT and by increase in LC50 and LC90 for levamisole in the LDT. The 63-bp indel was not confirmed as a molecular marker of levamisole resistance in our isolates. The target selected treatment scheme was effective to control helminths in the sheep flock for 5 years, when levamisole's inefficacy was perceived because of no change in the clinical situation of treated animals. Through this scheme, it was possible to promote reversion towards susceptibility or increase of efficacy for other chemical classes. Thus, this is a valid recommendation to control worms and to delay the development of resistance, preserving other anthelmintic classes for future use.


[Chimeric yeast prions with unstable inheritance].
The Saccharomyces cerevisiae [PSI] factor, a cytoplasmic omnipotent nonsense suppressor, is a conformationally changed (prion) form of translation termination factor eRF3 (Sup35p). Induction and maintenance of the [PSI] factor depend on the prionizing peptide located in the N domain of Sup35p. The N domain of Sup35p was fused with phosphoribosylaminoimidazole carboxylase (Ade2p), a purine biosynthesis enzyme, and the hybrid protein (NM-Sup35p::Ade2p) was tested for induction of the [PSI] factor. Transformation with a centromeric plasmid carrying the gene for NM-Sup35p::Ade2p induced a [PSI]-like factor in yeast cells, which was evident from efficient nonsense suppression. The suppressory effect depended on the presence of the prionizing peptide both in the hybrid protein and in Sup35p synthesized from the chromosomal gene, as well as on the presence of the prion-like [PIN] factor in the cell.


High doses of clethodim-based herbicide GrassOut Max poses reproductive hazard by affecting male reproductive function and early embryogenesis in Swiss albino mice.
Clethodim is a widely used and approved class II herbicide, with little information about its impact on the reproductive system. Herein, we investigated the male reproductive toxicity of clethodim using a mouse model. GrassOut Max (26% clethodim-equivalent) or analytical grade clethodim (≥90%) were given orally to male mice for 10 d in varying doses. All parameters were assessed at 35 d post-treatment. Significant decrease in testicular weight, decreased germ cell population, elevated DNA damage in testicular cells and lower serum testosterone level was observed post clethodim based herbicide exposure. Epididymal spermatozoa were characterized with significant decrease in motility, elevated DNA damage, abnormal morphology, chromatin immaturity and, decreased acetylated-lysine of sperm proteins. In the testicular cells of clethodim-based herbicide treated mice, the expression of Erβ and Gper was significantly higher. Proteomic analysis revealed lower metabolic activity, poor sperm-oocyte binding potential and defective mitochondrial electron transport in spermatozoa of clethodim-based herbicide treated mice. Further, fertilizing ability of spermatozoa was compromised and resulted in defective preimplantation embryo development. Together, our data suggest that clethodim exposure risks male reproductive function and early embryogenesis in Swiss albino mice via endocrine disrupting function.


Protein homeostasis, aging and Alzheimer's disease.
Alzheimer's disease (AD) is one key medical challenge of the aging society and despite a great amount of effort and a huge collection of acquired data on molecular mechanisms that are associated with the onset and progression of this devastating disorder, no causal therapy is in sight. The two main hypotheses of AD, the amyloid cascade hypothesis and the Tau hypothesis, are still in the focus of AD research. With aging as the accepted main risk factor of the most important non familial and late onset sporadic forms of AD, it is now mandatory to discuss more intensively aspects of cellular aging and aging biochemistry and its impact on neurodegeneration. Since aging is accompanied by changes in cellular protein homeostasis and an increasing demand for protein degradation, aspects of protein folding, misfolding, refolding and, importantly, protein degradation need to be linked to AD pathogenesis. This is the purpose of this short review.


Early and Mid-Term Outcome of Pediatric Congenital Mitral Valve Surgery.
Congenital lesions of the mitral valve are relatively rare and are associated with a wide spectrum of cardiac malformations. The surgical management of congenital mitral valve malformations has been a great challenge. The aim of this study was to evaluate the early and intermediate-term outcome of congenital mitral valve (MV) surgery in children and to identify the predictors for poor postoperative outcomes and death. In this retrospective study, 100 consecutive patients with congenital MV disease undergoing mitral valve surgery were reviewed in 60-month follow-up (mean, 42.4 ± 16.4 months) during 2008 - 2013. Twenty-six patients (26%) were under one-year old. The mean age and weight of the patients were 41.63 ± 38.18 months and 11.92 ± 6.12 kg, respectively. The predominant lesion of the mitral valve was MV stenosis (MS group) seen in 21% and MR (MR group) seen in 79% of the patients. All patients underwent preoperative two-dimensional echocardiography and then every six months after surgery. Significant improvement in degree of MR was noted in all patients with MR during postoperative and follow-up period in both patients with or without atrioventricular septal defect (AVSD) (P = 0.045 in patients with AVSD and P = 0.008 in patients without AVSD). Decreasing trend of mean gradient (MG) in MS group was statistically significant (P = 0.005). In patients with MR, the mean pulmonary artery pressure (PAP) had improved postoperatively (P < 0.001). Although PAP in patients with MV stenosis was reduced, this reduction was not statistically significant (P = 0.17). In-hospital mortality was 7%. Multivariate analysis demonstrated that age (P < 0.001), weight (P < 0.001), and pulmonary stenosis (P = 0.03) are strong predictors for mortality. Based on the echocardiography report at the day of discharge from hospital, surgical results were optimal (up to moderate degree for MR group and up to mild degree for MS group) in 85.7% of patients with MS and in 76.6% of patients with MR. Age (P = 0.002) and weight (P = 0.003) of patients are strong predictors for surgical success in multivariate analysis. Surgical repair of the congenital MV disease yields acceptable early and intermediate-term satisfactory valve function and good survival at intermediate-term follow-up. Strong predictors for poor surgical outcome and death were age smaller than 1 year, weight smaller or equal than 6 kg, and associated cardiac anomalies such as pulmonary stenosis.


Interactions between tectal radial cells in the red-eared turtle, Pseudemys scripta elegans: an analysis of tectal modules.
The optic tectum is a major subdivision of the visual system in reptiles. Previous studies have characterized the laminar pattern, the neuronal populations, and the afferent and efferent connections of the optic tectum in a variety of reptiles. However, little is known about the interactions that occur between neurons within the tectum. This study describes two kinds of interactions that occur between one major class of neurons, the radial cells, in the optic tectum of Pseudemys using Nissl, Golgi and electron microscopic preparations. Radial cells have somata which bear long, radially oriented apical dendrites from their upper poles and short, basal dendrites from their lower poles. They are divided into two populations on the basis of the distribution of their somata in the tectum. Deep radial cells have somata densely packed in the stratum griseum periventriculare. Their plasma membranes form casual appositions. Middle radial cells have somata scattered throughout the stratum griseum centrale and stratum fibrosum et griseum superficiale and do not contact each other. The apical dendrites of both populations of radial cells participate in vertically oriented, dendritic bundles. The plasma membranes of the dendrites in these bundles form casual appositions in the deeper tectal layers and chemical, dendrodenritic synapses within the stratum fibrosum et griseum superficiale. The synapses have clear, round synaptic vesicles and slightly asymmetric membrane densities. Thus, radial cells interact via both casual appositions and chemical synapses. These interactions suggest that radial cells may form a basic framework in the tectum. Because both populations of radial cells extend into the stratum fibrosum et griseum superficiale and stratum opticum, they may receive input from some of the same tectal afferent systems. Because the deep radial cells alone have somata and dendrites in the deep tectal layers, they may receive additional inputs that the middle radial cells do not. Neurons in the two populations interact via chemical dendrodentritic synapses, thereby forming vertically oriented modules in the tectum.


Introduction of quality indicators in German hospital capacity planning - Do results show an improvement in quality?
In Germany, the use of quality data to support hospital capacity planning was introduced in 2017. On behalf of the Federal Joint Committee, IQTIG suggested 11 quality indicators and developed a program on how to collect, evaluate and report data for the clinical areas gynaecological surgery, obstetrics and breast surgery. By analysing data from 2015 to 2021, effects of the introduction of the program on indicator results, statistical discrepancies and impact on care quality are examined. Effects on capacity planning are discussed. Since the program started, indicator results improved in all clinical areas, and statistical discrepancies and the number of assessments with insufficient quality decreased due to enhanced adherence to quality standards and data validity. Effects on capacity planning or the allocation of hospitals have not occurred. Thus, a change of the legal basis to allow a better link between quality and hospital planning is recommended. The approach to use quality data on hospital regulation in Germany is evolving. The current hospital reform in Germany also addresses other approaches to quality-based regulation. Already now, there have been clear improvements in specific indicators as well as lessons for quality assurance and its link to capacity planning provided by the program, which are also applicable to other countries.


How the informed relations between physical, digital and biological dimensions are changing the design practice, as well as the sustainability paradigm.
In the "century of biotechnology", a new form of "bio-digital industry" is emerging in which, thanks to increasingly sophisticated and digitized technologies that allow engineering and production on a biological quantum scale, it is possible to analyze and reproduce the generative, chemical, physical, and molecular processes underlying natural mechanisms. Inheriting methodologies and technologies from biological fabrication, bio-digital practices foster a new material-based biological paradigm that, bringing biomimicry to a material level, allows designers to observe substances and logic used by nature for assembling and structuring its materials, developing more sustainable and strategic ways for artifice manufacturing, as well as replicating complex, tailored, and emergent biological qualities. The paper aims to describe the new hybrid manufacturing techniques, demonstrating how the transition from form-based to material-based approaches also leads to the change of logic and conceptual frameworks in design practices, allowing greater alignment with the paradigms of biological growth. In particular, the focus is on informed relations between physical, digital, and biological dimensions, allowing interaction, development, and mutual empowerment between entities and disciplines belonging to them. Such a correlative strategy can help design to apply systemic thinking, from the scale of the material to that of the product and the process, paving the way to sustainable scenarios, not simply to reduce the human impact on the ecosystem but to enhance nature through original cooperation and integration forms between humans, biology, and machines.


Interplay of gestational parent exposure to ambient air pollution and diet characteristics on preterm birth.
Despite many efforts, preterm birth (PTB) is poorly understood and remains a major public health problem in the United States. Toxicological work suggests gestational parent (GP) diet may modify the effect of ambient pollutants on birth outcomes. We assessed risk of PTB in humans in relation to fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) and variation by diet. 684 GP-singleton infant pairs in the Newborn Epigenetics Study prospective birth cohort were attributed ambient air pollutant exposures for each trimester based on residence. Total energy intake, percent of energy intake from saturated fat, and percent of energy intake from total fat were dichotomized at the 75th percentile. >We used log binomial regressions to estimate risk ratios (RR (95%CI)) for PTB by pollutant interquartile ranges, adjusting for GP age, pre-pregnancy body mass index, GP race/ethnicity, GP education, season of conception, household income, and each diet factor. We assessed departure from additivity using interaction contrast ratios (ICRs). We addressed missing covariate data with multiple imputation. Point estimates suggest that O3 may be inversely associated with PTB when exposure occurs in trimester 2 (min RR: 0.77, 95% CI: 0.39, 1.49), but may be harmful when exposure occurs in trimester 3 (max RR: 1.51, 95% CI: 0.62, 3.64). Additionally, PM2.5 may be inversely associated with PTB when considered with total fat and saturated fat in trimester 2. Imprecise ICRs suggest departure from additivity (evidence of modification) with some pollutant-diet combinations. While confidence intervals are wide, we observed potential modification of pollutant associations by dietary factors. It is imperative that large cohorts collect the required data to examine this topic, as more power is necessary to investigate the nuances suggested by this work.


Effects of extracellular Ca2+ influx on endothelin-1-induced intracellular mitogenic cascades in C6 glioma cells.
We have recently shown that endothelin-1 activates two types of Ca2+-permeable nonselective cation channels (NSCC-1 and NSCC-2) in C6 glioma cells. These channels can be distinguished by their sensitivity to blockers of the receptor-operated Ca2+ channel, 1-[b-(3-[4-methoxyphenyl]propoxy)-4-methoxyphenethyl]-1H-imidazole hydrochloride (SK&F 96365) and (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908). NSCC-1 is sensitive to LOE 908 and resistant to SK&F 96365, whereas NSCC-2 is sensitive to both LOE 908 and SK&F 96365. Moreover, extracellular Ca2+ influx through these channels plays an essential role in endothelin-1-induced mitogenesis in C6 glioma cells. The purpose of the present study was to investigate the effects of extracellular Ca2+ influx on intracellular pathways of endothelin-1-induced mitogenic responses in C6 glioma cells. We focused on extracellular signal-regulated kinase 1 and 2 (ERK1/2) in this context. An inhibitor of mitogen-activated protein kinase, 2-[2-amino-3-methoxyphenyl]-4H-1-benzopyran-4-one (PD 98059), abolished the endothelin-1-induced increase in ERK1/2 activity, but only partially suppressed the mitogenic response. ERK1/2 activation by endothelin-1 was partially suppressed in the absence of extracellular Ca2+. On the basis of the sensitivity to LOE 908 and SK&F 96365, Ca2+ influx through NSCC-1 and NSCC-2 plays an essential role in the extracellular Ca2+-dependent component of ERK1/2 activity. In contrast, Ca2+ influx through NSCC-2 is involved in the ERK1/2-independent component of endothelin-1-induced mitogenesis. These results indicate that (1) the endothelin-1-induced mitogenic response involves both ERK1/2-dependent and -independent mechanisms, (2) ERK1/2 activation by endothelin-1 involves an extracellular Ca2+ influx-dependent cascade as well as an extracellular Ca2+ influx-independent cascade, (3) because endothelin-1-induced mitogenesis is completely dependent on extracellular Ca2+ influx, extracellular Ca2+ influx also plays an important role in mitogenic pathways downstream of ERK1/2, (4) extracellular Ca2+ influx through NSCC-1 and NSCC-2 has an important role in the extracellular Ca2+ influx-dependent component of ERK1/2-dependent mitogenesis, (5) extracellular Ca2+ influx through NSCC-2 has an important role in ERK1/2-independent mitogenesis, and (6) Ca2+ influx through each Ca2+ channel may play a distinct role in intracellular mitogenic cascades.


Matrix metalloproteinases and tumor progression.
The matrix metalloproteinases (MMPs) are a family of more than 20 distinct enzymes that are frequently overexpressed in human tumors. Functional studies have shown that MMPs play an important role in the proteolytic destruction of extracellular matrix and basement membranes, thereby facilitating tumor invasion and metastasis. In addition, these enzymes may also be important in other steps of tumor evolution including neoplastic cell proliferation and angiogenesis stimulation. On the basis of the relevance of MMPs in tumor progression, a number of different strategies aimed to block the unwanted activity of these enzymes in cancer have been developed. Unfortunately, most clinical trials with the first series of MMP inhibitors have failed to show clear benefit in patients with advanced cancer. Explanations for this lack of success include the failure to recognize the role of these enzymes in early stages of the disease as well as inadequacy of either the employed inhibitors or the proteases to be targeted. The introduction of novel concepts such as tumor degradome, and global approaches to protease analysis, may facilitate the identification of the relevant MMPs that must be targeted in each individual cancer patient. On the other hand, the finding that MMPs are enzymes whose effects on biologically active substrates can have profound consequences on cell behaviour, suggests that selective inhibition of a limited set of MMPs at early stages of tumor evolution might be much more effective than using wide-spectrum inhibitors active against most family members, and administered to patients at late stages of the disease. Further studies directed to elucidate these questions will be necessary to clarify whether any of the multiple strategies of MMP inhibition may be part of future therapeutic approaches to control tumor progression.


Prospective assessment of incidence of Tako-Tsubo cardiomyopathy in a very large urban agglomeration.
Tako-Tsubo cardiomyopathy (TTC) is a recently described medical entity and the incidence of TTC in a global population is still uncertain. We sought to prospectively assess the incidence of TTC in a large urban area. We included all consecutive patients referred for coronary angiography in three hospitals located in Paris and its suburbs. We prospectively estimated the percentage of TTC among patients referred for coronary angiography and extrapolated the number of cases of TTC in the greater Paris area (11,598,866 inhabitants) according to the CARDIO-ARHIF registry (government agency). Among 2547 patients (2972 coronary angiographies) including 815 acute coronary syndromes, 20 patients presented with TTC (19 women, mean age 66 ± 13 years). The percentage of TTC among suspected acute coronary syndromes was 2.5% (8.2% in women versus 0.2% in men, p<0.001). In the CARDIO-ARHIF registry, we individualized 51,403 coronary angiographies performed in all catheterization laboratories in one year (13,820 women and 10,246 women ≥ 60 years). In this region, the yearly number of TTC cases is estimated to be 346 (95% CI: 216-520). The annual incidence of TTC is estimated to be 29.8 per 1,000,000 inhabitants (95% CI: 18.6-44.9), 48.2 per 1,000,000 inhabitants (95% CI: 29.7-73.0) among women and 187.4 per 1,000,000 inhabitants (95% CI: 103.3-307.2) among women ≥ 60 years. Within a large urban agglomeration, the incidence of TTC is high in women ≥ 60 years. The current rate of this recently described cardiomyopathy has been underestimated in previous retrospective studies and will probably rise with the increase of life expectancy.


Palliation of biliary and duodenal obstruction in patients with unresectable pancreatic cancer: endoscopy or surgery?
Patients with unresectable pancreatic adenocarcinoma often develop biliary and/or duodenal obstruction during the course of their disease. Jaundice, pruritis, nausea and vomiting impact negatively on the quality of life and chemotherapy must often be withheld until these symptoms are resolved. In the past, an open surgical palliative bypass was proposed, but the development of endoprosthetic stents has changed the management of these patients. The success rate for placement of duodenal and biliary stents is greater than 90% with low morbidity. Classical surgical bypass surgery includes biliary-digestive and gastro-jejunal anastomoses. Many studies have compared endoscopic and surgical treatment, and there is a clear advantage to endoscopic treatment in terms of quality of life and cost.


Third molar consent forms: how comprehensive should they be?
To establish a gold standard for the information given to patients about the risks associated with third molar extractions, we surveyed 79 oral and maxillofacial surgeons (OMFS) to find out what information they gave to patients during the consent process. We also surveyed 62 medicolegal solicitors to find out what information they thought patients should be given before the procedure, and in what form. A total of 20/76 OMFS (26%) used a two-stage process to obtain consent; 13 (17%) included paraesthesia on the consent form and also gave out an information leaflet. All the lawyers agreed that patients should give their consent in writing and thought that the risk of paraesthesia should be included on the form. Three-quarters thought that they should also be given an information leaflet that includes paraesthesia. We encourage surgeons to do this as part of the two-stage consent process.


Perceptions of undergraduate students not participating in HIV/AIDS prevention activities in Botswana.
Botswana is one of the countries hardest hit by HIV/AIDS. Prevalence rates of 22.8% and 38.6% have been reported for age groups 15-19 and 20-24 years respectively. The government has solicited a concerted effort of all individuals and agencies in both the public and private sector in the fight against HIV/AIDS. This report is part of the findings of a study conducted at a university to evaluate students' perceptions of the effectiveness of two HIV/AIDS initiatives put in place and aimed at changing the students' knowledge, attitudes and behaviour. The study utilized the Rapid Assessment Process (RAP). Four teams interviewed: students who had taken the course; students who had used the centre; students who had taken the course and used the centre; and students who have neither taken the course nor used the centre. Initial steps in data analysis involved coding and theme derivation. Findings reported here were from participants who neither participated in the course nor used the centre. Participants reported the following problems, which were hindering the success of the programmes: problems in the ABC message; permissive campus environment; lack of entertainment; and students' perceptions about HIV/AIDS and their own vulnerability. Participants came up with suggestions for improving the initiatives. The authors discuss implications of the study findings for the university's initiatives.


Management of complex orbital fractures.
The treatment of orbital injuries has evolved considerably over the last two decades. We describe strategies involved in the emergency management of orbital injuries, the use of imaging, preformed and customised materials for reconstruction, and endoscopic techniques.


Cellular S-denitrosylases: Potential role and interplay of Thioredoxin, TRP14, and Glutaredoxin systems in thiol-dependent protein denitrosylation.
Nitric Oxide is a very well known gaseous second messenger molecule and vasorelaxant agent involved in a variety of signaling in the body such as neurotransmission, ion channel modulation, and inflammation modulation. However, it's reversible covalent attachment to thiol groups of cysteine residues under nitrosative stress leading to aberrant protein S-nitrosylation (PSNO) has been reported in several pathological conditions in the body stemming from neurodegenerative diseases, cancer, cardiovascular system, and immune system disorders. In the cell, PSNOs are partly unstable and transit to a more stable disulfide state serving as an intermediate step towards disulfide formation thus eliciting the biological response. Scientists have identified several cellular thiol-dependent disulfide reductases that have the intrinsic capability to reverse the modification by reducing the stable disulfides formed in PSNOs and thereby rescue S-nitrosylation-induced altered proteins. The physiological roles of these major cellular ubiquitous S-denitrosylases and their probable implementations have not been fully explored. Gaining knowledge from current research and development this review provides a deeper insight into understanding the interplay and role of the major ubiquitous S-denitrosylases in maintaining cellular redox homeostasis. This review umbrellas the mechanism of Thioredoxin, TRP14, and Glutaredoxin systems and highlights their substrates specificities at different cellular conditions, physiological roles, and importance in diseased conditions that would allow researchers to investigate effective therapeutic interventions for nitrosative stress-related diseases and disorders.


Trial of the calcium antagonist nifedipine in the treatment of primary dysmenorrhoea.
The effect of the calcium antagonist, nifedipine, on menstrual pain was investigated in 40 women with severe, primary dysmenorrhoea and 36 of them were observed over 3 consecutive menstrual cycles. Twenty-six patients experienced good pain relief, 10 moderate relief and 4 reported no benefit. The frequency of symptoms associated with menstrual pain was not reduced. Fifteen women regularly suffering from migraine during the menstrual period reported increased headache after intake of the drug. Due to this side effect four of these patients did not continue treatment for more than one cycle. All patients had transient facial flushing occurring 15--30 min after drug intake; this was well tolerated. An increase in pulse rate was also invariably found. However, only 5 patients complained of palpitations. Twenty-five of the 36 women completing the three-month trial wanted to continue nifedipine therapy regularly. It is concluded that calcium antagonists like nifedipine can be used for treatment of severe primary dysmenorrhoea, and that further evaluations of these drugs are indicated.


The detection of human herpesvirus-8 DNA in plasma and peripheral blood mononuclear cells in adult patients with pityriasis rosea by polymerase chain reaction.
Herpesvirus-like particles have been reported to be detectable by electron microscopy in lesional biopsy of patients with pityriasis rosea (PR). We report a study investigating the association of PR with human herpesvirus-8 (HHV-8) infection. Our setting is a teaching clinic affiliated to a university. We recruited eight patients aged 28-47 years (mean: 34.5 years) diagnosed with PR during a one-year period. We collected acute blood specimens at presentation and convalescent blood specimens three to four weeks later. We also collected skin scrapings from the herald patch where present and from truncal secondary lesions. We detected HHV-8 DNA by a nested PCR (polymerase chain reaction) targeting, respectively, a 233-bp and a 160-bp fragment of ORF 26. PCR for HHV-8 DNA was negative in the peripheral blood mononuclear cells and plasma of acute and convalescent specimens of all patients, and negative in all skin scrapings. We detected anti-HHV-8 IgG and IgM antibodies by the indirect immunofluorescence. Four patients had IgG antibodies against HHV-8, but with no significant rise of titre. None were positive for anti-HHV-8 IgM antibody. We conclude that PR is not associated with HHV-8 infection.


On some mortality rate processes and mortality deceleration with age.
A specific mortality rate process governed by the non-homogeneous Poisson process of point events is considered and its properties are studied. This process can describe the damage accumulation in organisms experiencing external shocks and define its survival characteristics. It is shown that, although the sample paths of the unconditional mortality rate process are monotonically increasing, the population mortality rate can decrease with age and, under certain assumptions, even tend to zero. The corresponding analysis is the main objective of this paper and it is performed using the derived conditional distributions of relevant random parameters. Several meaningful examples are presented and discussed.


Venom alkaloids in Monomorium "rothsteini" Forel repel other ants: is this the secret to success by Monomorium in Australian ant communities?
Species of the cosmopolitan ant genus Monomorium are small, slow-moving and non-aggressive ants that are extremely successful members of diverse Australian ant communities. Unlike other abundant taxa, they have no obvious specializations enabling them to co-exist with the highly aggressive species of Iridomyrmex that dominate these communities. Here we report results which suggest that Monomorium species owe their success to the topical application of venom alkaloids which repel other ants. The venom alkaloids (trans-2-ethyl-5-undecylpyrrolidine and trans-2-ethyl-5-tridecylpyrrolidine) of Monomorium "rothsteini" were identified and synthesized, and the repellency to other ants of the synthetic alkaloids were tested using bioassays involving the attraction to honey baits of three native species of Iridomyrmex, three tropical "tramp" species, and M. "rothsteini" itself. Repellency to all other ant species was total or nearly so, but only partial to M. "rothsteini". Defensive alkaloids produced from a variety of glands are found in other ant genera, and may be a potent yet poorly appreciated force in interference competition between ant species and thereby the structure of ant communities.


Low apparent diffusion coefficient cluster-based analysis of diffusion-weighted MRI for prognostication of out-of-hospital cardiac arrest survivors.
Recent studies suggested quantitative analysis of diffusion-weighted magnetic resonance imaging as a promising tool for early prognostication of cardiac arrest patients. However, most of their methods involve significant manual image handling often subjective and difficult to reproduce. Therefore developing a computerized analysis method using easy-to-define characteristics would be useful. Comatose out-of-hospital cardiac arrest (OHCA) patients who underwent brain MRI between January 2008 and July 2012 were identified from an OHCA registry. Apparent diffusion coefficient (ADC) axial images were analyzed using a program to detect and characterize clusters of low ADC pixels from six brain regions including frontal, occipital, parietal, rolandic and temporal and basal ganglia region. Identified clusters were ranked according to size, mean ADC and minimum ADC to assess the regional maximum cluster size (MCS), lowest mean ADC (LMEAN) and lowest minimum ADC (LMIN). Their power to predict poor outcome, defined as 6-month CPC 3 or higher, was assessed by contingency table analyses. 51 OHCA patients were eligible during the study period. The sensitivities of MCS, LMEAN and LMIN to detect poor outcome varied according to brain region from 62.5 to 90.0%, 50.0 to 72.5% and 42.5 to 82.5% with their specificities set to 100%, respectively. The MCS of occipital region showed most favorable test profile (sensitivity 90%, specificity 100%; AUROC 0.940, 95% confidence interval 0.874-1.000). The cluster-based computerized image analysis might be a simple but useful method for prediction of poor neurologic outcome. Future studies validating its prognostic performance are required.


Developing novel lentiviral vectors into clinical products.
Gene therapy vectors based on murine retroviruses have now been in clinical trials for over 20 years. During that time, a variety of novel vector pseudotypes were developed in an effort to improve gene transfer. Lentiviral vectors are now in clinical trials and a similar evolution of vector technology is anticipated. These modifications present challenges for those producing large-scale clinical materials. This chapter discusses approaches to process development for novel lentiviral vectors, highlight considerations, and methods to be incorporated into the development schema.


Measurement of in vivo tendon function.
Chronic tendon pathologies (eg, rotator cuff tears, Achilles tendon ruptures) are common, painful, debilitating, and a significant source of medical expense. Treatment strategies for managing tendon pathologies vary widely in invasiveness and cost, with little scientific basis on which to base treatment selection. Conventional techniques for assessing the outcomes of physical therapy or surgical repair typically rely on patient-based assessments of pain and function, physical measures (eg, strength, range of motion, or stability), and qualitative assessments using magnetic resonance imaging or ultrasound. Unfortunately, these conventional techniques provide only an indirect assessment of tendon function. The inability to make a direct quantitative assessment of the tendon's mechanical capabilities may help to explain the relatively high rate of failed tendon repairs and has led to an interest in the development of tools for directly assessing in vivo tendon function. The purpose of this article is to review methods for assessing tendon function (ie, mechanical properties and capabilities) during in vivo activities. This review will describe the general principles behind the experimental techniques and provide examples of previous applications of these techniques. In addition, this review will characterize the advantages and limitations of each technique, along with its potential clinical utility. Future efforts should focus on developing broadly translatable technologies for quantitatively assessing in vivo tendon function. The ability to accurately characterize the in vivo mechanical properties of tendons would improve patient care by allowing for the systematic development and assessment of new techniques for treating tendon pathologies.


Asymmetric and Diffuse Uptake of Left Femur in a 3-Year-Old Child Bone Scan: An Unusual Aspect in Acute Lymphoblastic Leukemia.
Acute leukemia is a severe disease frequently encountered in childhood, often diagnosed in later stages because of nonspecific symptoms. It is known to produce uptake in bone scan, and previously described patterns have shown symmetrical abnormalities. However, we report the unusual aspect of the bone scan in a 3-year-old child who was referred to explore an isolated pain of his lower left limb, with hyperthermia and markers of inflammation. A bone scan showed an intense, asymmetrical uptake of the entire left femur. A few days later, his blood count showed circulating blast cells, leading to the diagnosis of leukemia.


Social isolation does not alter brain regional benzodiazepine binding site numbers, affinity and coupling in the rat.
Male Sprague-Dawley rats were differentially housed for 21 days immediately after weaning. Isolated animals showed a selective suppression of exploration of the light side of a two compartment box; spending significantly less time in the light, and making fewer transitions between the light and dark compartments compared to socially reared controls. However, both basal and GABA-stimulated [3H] flunitrazepam binding was unaltered in the frontal cortex, hippocampus, amygdala and cerebellum following social isolation. These results are discussed in relation to other studies on central benzodiazepine receptor changes following a variety of experimental stressors.


A comparison of household food insecurity rates in Newfoundland and Labrador in 2011-2012 and 2017-2018.
The prevalence of household food insecurity in Newfoundland and Labrador (NL) fell sharply between 2007 and 2011, but it appears to have risen since then. Our objective was to compare the prevalence of food insecurity between 2011-2012 and 2017-2018 in relation to population socio-demographic characteristics. Our analytic sample comprised all NL households in the Canadian Community Health Survey (CCHS) cycles 2011-2012 and 2017-2018, n = 6800. We stratified the prevalence of household food insecurity for each cycle by socio-demographic characteristics and applied multivariable logistic regression models to determine food insecurity odds in 2017-2018 compared with 2011-2012 after controlling for socio-demographic covariates. Interactions of covariates with survey cycle were tested and models stratified when warranted. The prevalence of food insecurity rose from 12.0% (95% CI 10.5, 13.6) in 2011-2012 to 14.7% (95% CI 13.1, 16.6) in 2017-2018. After adjusting for household socio-demographic variables, the odds of food insecurity was 1.49 (95% CI 1.27, 1.75) in 2017-2018. The prevalence of food insecurity had increased significantly among unattached individuals, renters, households with low educational attainment, and households with income above the Low Income Measure, with concomitant increases in the contribution of these groups to the total provincial prevalence of food insecurity in 2017-2018 compared with that in 2011-2012. The odds of food insecurity among NL households increased significantly from 2011-2012 to 2017-2018. Given the serious negative health implications of household food insecurity, the province should draw on the lessons from its earlier success in food insecurity reduction to reverse the current trend.


An integrated model for the relationship between socio-cultural factors, Attitudes Toward Suicide, and intensity of suicidal ideation in Korean, Japanese, and American populations.
Although many studies have identified the risk factors for suicide, the absence of a statistical model that integrates several risk areas makes it difficult to understand the abnormally high suicide rate in South Korea. Therefore, we aimed to establish a multidimensional structural equation model of suicide incorporating socio-cultural and psychiatric factors. We performed cross-national comparisons to identify the unique factors influencing South Korea's suicide rate. We conducted a web survey inviting adults aged 20- to 59-years from South Korea, Japan, and the United States to respond to questionnaires. A total of 2,213 subjects were included. We then developed a structural equation model, exhibiting a good fit in all countries. A permissive attitude was the factor that most strongly predicted the intensity of suicidal ideation in all countries. In South Korea, a low income was directly associated with both permissive attitude and the intensity of suicidal ideation. South Korea's highly fatalistic attitude related to more receptive attitudes toward suicide. Individual's resilience to stress provided significant protection against suicidal ideation in the United States and Japan, but not in South Korea. Since our sample excluded adults over 60 years, thus reducing the generalizability of our results. Furthermore, we employed a cross-sectional design; a longitudinal study is needed to draw causal inferences about suicidal death CONCLUSIONS: This study developed the first multidimensional, integrated statistical model of suicidal ideation. Our findings explain the causes of South Korea's high suicide rate and can be used to develop new interventions.


Reduction of Hexavalent Chromium [Cr(VI)] by Heavy Metal Tolerant Bacterium Alkalihalobacillus clausii CRA1 and Its Toxicity Assessment Through Flow Cytometry.
A chromate-resistant bacterial strain was isolated from tannery effluent; based on morphological, biochemical, and 16S rRNA gene sequencing, it was identified as Alkalihalobacillus clausii and designated A. clausii CRA1. It was found to be halophilic, alkaliphilic, and resistant to multiple heavy metals like Cr(VI), Cd(II), As(II), Pb(II), Ni(II), Hg(II), Cu(II), Zn(II), and Fe(II). The strain was found to reduce 72% of chromate in 6 days in Cr(VI) spiked Luria Bertani medium with unaffected bacterial growth at an initial C(VI) concentration of 50 mg L-1. Chromate reductase activity of culture supernatant (cultivated in LB broth) and cell lysate of the bacterium was found to be 23 and 43U, where 1U is µmol of Cr(VI) reduced/min/mg protein. Flow cytometry studies revealed that no significant effect of Cr(VI) on cell viability was observed till 12 h of exposure at 100, 200, 400 mg L-1 concentrations, indicated by non-significant cell death (propidium iodide positive cells). However, at 800 and 1000 mg L-1 Cr(VI) concentration, toxicity (cell death) was observed after 12 h of exposure. FACs studies also indicated that exposure to Cr(VI) increases cell size and cell granularity, which was also confirmed in SEM and TEM images of Cr(VI) treated cells. The presence of Cr(III) species in EDX spectra of Cr(VI) treated cells confirms that reduction of Cr(VI) to Cr(III) is the primary mechanism of Cr(VI) removal by the bacterium. Therefore, the bacterium A. clausii has potential for application in chromate removal from industrial waste effluents.


Washing of waste prior to landfilling.
The main impact produced by landfills is represented by the release of leachate emissions. Waste washing treatment has been investigated to evaluate its efficiency in reducing the waste leaching fraction prior to landfilling. The results of laboratory-scale washing tests applied to several significant residues from integrated management of solid waste are presented in this study, specifically: non-recyclable plastics from source separation, mechanical-biological treated municipal solid waste and a special waste, automotive shredded residues. Results obtained demonstrate that washing treatment contributes towards combating the environmental impacts of raw wastes. Accordingly, a leachate production model was applied, leading to the consideration that the concentrations of chemical oxygen demand (COD) and total Kjeldahl nitrogen (TKN), parameters of fundamental importance in the characterization of landfill leachate, from a landfill containing washed wastes, are comparable to those that would only be reached between 90 and 220years later in the presence of raw wastes. The findings obtained demonstrated that washing of waste may represent an effective means of reducing the leachable fraction resulting in a consequent decrease in landfill emissions. Further studies on pilot scale are needed to assess the potential for full-scale application of this treatment.


Atopic dermatitis: current treatment guidelines. Statement of the experts of the Dermatological Section, Polish Society of Allergology, and the Allergology Section, Polish Society of Dermatology.
Atopic dermatitis (AD) is a condition frequently encountered in medical practices across the country. More than 60% of children with AD are at risk to develop allergic rhinitis or asthma (the atopic march). Patients with AD have a unique predisposition to colonization or infection by Staphylococcus aureus. Treatments for AD need to rapidly control symptoms of the disease, improve quality of life and prevent exacerbations. Given the chronic and relapsing nature of the disease, therapies need to encourage good compliance and be well tolerated.


In vitro and in vivo antimicrobial activity of covalently coupled quaternary ammonium silane coatings on silicone rubber.
Biomaterial-centered infection is a dreaded complication associated with the use of biomedical implants. In this paper, the antimicrobial activity of silicone rubber with a covalently coupled 3-(trimethoxysilyl)-propyldimethyloctadecylammonium chloride (QAS) coating was studied in vitro and in vivo. Gram-positive Staphylococcus aureus ATCC 12600, Staphylococcus epidermidis HBH, 102, and Gram-negative Esherichia coli O2K2 and Pseudomonas aeruginos AK1 were seeded on silicone rubber with and without QAS-coating, in the absence or presence of adsorbed human plasma proteins. The viability of the adherent bacteria was determined using a live/dead fluorescent stain and a confocal laser scanning microscope. The coating reduced the viability of adherent staphylococci from 90% to 0%), and of Gram-negative bacteria from 90% to 25% while the presencc of adsorbed plasma proteins had little influence. The biomaterials were also subcutaneously implanted in rats for 3 or 7 days, while pre- or postoperatively seeded with S. aureus ATCC 12600. Preoperative seeding resulted in infection of 7 out of 8 silicone rubber implants against 1 out of 8 QAS-coated silicone rubber implants. Postoperative seeding resulted in similar infection incidences on both implant types, but the numbers of adhering bacteria were 70% lower on QAS-coated silicone rubber. In conclusion, QAS-coated silicone rubber shows antimicrobial properties against adhering bacteria, both in vitro and in vivo.


Effects of the heart-lung machine on melatonin metabolism and mood disturbances.
Cardiothoracic surgery using the heart-lung machine (HLM) provokes a pronounced endocrine-metabolic response leading to circadian rhythm disturbances that affect postoperative morbidity. Focus has been laid on changes in melatonin metabolism. The effects of an extra-corporal artificial circulation have not been adequately addressed. Seventeen patients scheduled for open heart surgery using the HLM were compared with 15 patients undergoing major surgery without cardiopulmonary bypass (non-HLM). Late afternoon and night urinary 6-sulfatoxymelatonin were measured at baseline, immediately after the operation and on return to the normal ward. Mood disturbances were assessed at baseline and final sampling times using a standardized questionnaire (arbitrary units). Vital signs were comparable between groups. The difference (delta) between day and night melatonin levels was similar at baseline (HLM group 1.1 ng/ml, non-HLM group 1.4 ng/ml, p=0.25). Immediately following surgery melatonin day-night deltas were unchanged to baseline (HLM 1.0 ng/ml, p=0.67; non-HLM 0.8 ng/ml, p=0.46) but at final sampling normal circadian melatonin profile was abolished (-0.3 ng/ml, p=0.001 and 0.0 ng/ml, p=0.07). However, this effect was not different between the two studied groups (p=0.17). No mood disorders were detectable at baseline (HLM 8.0 vs non-HLM 7.0, p=0.97) and no changes occurred after surgery (7.0 vs 6.5, p=0.33). Overall, patients with a worsening psychological score had pronounced postoperative washout of afternoon-night melatonin delta (p=0.04). We found no relevant influence of the HLM on perioperative circadian melatonin profiles. Additionally, no alterations in mood assessment before and after surgery were observed. However, worsening of psychological score was associated with a pronounced disruption of the normal circadian melatonin profile.


The effect of exercise and oxidant-antioxidant intervention on the levels of neurotrophins and free radicals in spinal cord of rats.
This study was designed to investigate the effects of oxidant and antioxidant treatment, as well as regular exercise, on neurotrophin levels in the spinal cord of rats. Reactive oxygen species (ROS) play a role in neurodegenerative diseases, but ROS at moderate levels could stimulate biochemical processes through redox-sensitive transcription. Exercised or sedentary animals were injected subcutaneously with hydrogen peroxide (H(2)O(2)), N-tert butyl-alpha-phenyl nitrone (PBN) or saline for the last 2 weeks of a 10-week experimental period to challenge redox balance. Free radical (FR) concentration was evaluated in the spinal cord by electron spin resonance, protein carbonyls, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) levels and the mRNA expression of BDNF receptor and tyrosine kinase receptor B (TrKB). Research Institute of Sport Science, Semmelweis University, Budapest, Hungary. Exercise or PBN decreased the concentration of FR, whereas the carbonyl content did not change. BDNF was significantly decreased in exercised sham and sedentary PBN-treated groups, and its content correlated with the level of FR. GDNF was significantly increased in sedentary H(2)O(2)-treated groups. No differences were observed in TrkB mRNA expression among groups. Results suggest that regular exercise alone and PBN in sedentary animals can successfully decrease FR levels in the spinal cord. Redox alteration seems to affect the levels of GDNF and BDNF, which might have clinical consequences, as neurotrophins play an important role in cellular resistance and regeneration.


Metabolism of 3-phosphoglyceroyl phosphate in phosphoenolpyruvate-enriched human erythrocytes.
The concentration of 3-phosphoglyceroyl phosphate in erythrocytes was increased by more than 100-fold when red cells were incubated with extracellular phosphoenolpyruvate at 37 degrees C. Since these elevated levels were maintained for 60 min, the metabolism of 3-phosphoglyceroyl phosphate and related compounds could be investigated in phosphoenolpyruvate-treated erythrocytes. 2,3-Bisphosphoglycerate synthesis was not affected by intracellular pH when the 3-phosphoglyceroyl phosphate level was constant but did vary with 3-phosphoglyceroyl phosphate concentration. On the other hand, the relationship between the rate of 2,3-bisphosphoglycerate synthesis and 3-phosphoglyceroyl phosphate concentration was not straightforward. At relatively low concentrations of 3-phosphoglyceroyl phosphate, the observed rate of 2,3-bisphosphoglycerate synthesis agreed with a rate calculated from a formula incorporating kinetic parameters of purified 2,3-bisphosphoglycerate synthase (Rose, Z.B. (1973) Arch. Biochem. Biophys. 158, 903-910). However, at high concentrations of 3-phosphoglyceroyl phosphate, the observed rate of 2,3-bisphosphoglycerate synthesis was lower than the calculated value. The concentration of glucose 1,6-bisphosphate did not increase even when 3-phosphoglyceroyl phosphate was elevated to 200 microM. Elevated levels of intracellular 2,3-bisphosphoglycerate did not inhibit glycolytic activity in these erythrocytes. These results suggest that incubation of erythrocytes with phosphoenolpyruvate is a useful technique to investigate the effect of metabolic perturbations at the intermediate stages of glycolysis.


Organization of the mouse cerebral cortex: a histochemical study using glycogen phosphorylase.
The postmortem phosphorylase a activity in cryostat sections taken from the brains of mice killed without any prior period of maintained anaesthesia ('unanaesthetized' mice) was compared histochemically with the activity in sections taken from mice anaesthetized with pentobarbitone prior to decapitation ('anaesthetized' mice). This study provides evidence for the existence of two separate overlapping modular subdivisions of the somatosensory cortex. The modules observed in the 'unanaesthetized' mice were restricted to layer IV and corresponded to the hollows of the whisker barrels where the thalamic afferents terminate. In contrast, the modules observed in the 'anaesthetized' mice extended from layer I to layer V, and formed a mosaic of cylinders that was out of register with the whisker barrels. These cylinders may correspond to the terminal fields of corticocortical afferents. In a few of the 'unanaesthetized' mice bands of high phosphorylase a activity are evident in the visual areas 17 and 18. This suggests that in the mouse, as in higher mammals, the thalamic input to the visual cortex gives rise to a columnar organization. In the 'anaesthetized' mice the mosaic of modules observed in the somatosensory cortex is also present in the auditory and motor areas. The modules in both groups of mice have similar diameters of between 200 and 350 microns.


Identification of a neodeterminant in complexes of human brain Thy-1.
Human Thy-1 glycoprotein was purified from brain cortex membranes. Antibodies were produced in rabbits by immunization with purified Thy-1 and with brain homogenate. Both preparations of antibodies reacted with monomers of 125I-labeled Thy-1. In addition, the antibodies against the purified antigen also recognized a determinant which was absent, or present in very low amounts, in homogenates of human brain. Analysis by gel filtration in Nonidet-P40 or deoxycholate revealed the presence of complexes of purified Thy-1 that were specifically precipitated by antibodies against this determinant. It was also shown that anti-monomer antibodies were unable to react with the complex form of Thy-1. These complexes seemed to be composed of a varying number of Thy-1 molecules. By treatment with sodium dodecyl sulfate, the multimers were completely dissociated into monomers. The tendency to complex formation seems to be unique for human Thy-1, since Thy-1 analogues of other species do not show this property when isolated.


Freeze-fracture studies on tardigrade cuticle.
The cuticles of the heterotardigrade Echiniscus testudo and the eutardigrades Macrobiotus hufelandi and Milnesium tardigradum have been studied using freeze-fracture technique. Most of the layers seen in conventional TEM micrographs can be visualized. There is no clear evidence that the trilaminar components of the cuticle such as the outer epicuticle and the tripartite layer separating epi- and intracuticle or procuticle (whose membranous origin has been suggested by previous authors) fracture like a lipid bilayer. Microfibres not resolved or only poorly resolved by TEM can be recognized in the procuticle of all three species. Obviously their visualization depends upon the fracture angle. In Echiniscus testudo and Milnesium tardigradum the intracuticle or at least parts of it show a wavy arrangement of microfibres. Parts of the ventral intracuticle of E. testudo fracture in an obviously non-random pattern revealing distinct sublayers.


Outcomes of Cancer Patients with COVID-19 in a Hospital System in the Chicago Metropolitan Area.
Patients with a history of malignancy have been shown to be at an increased risk of COVID-19-related morbidity and mortality. Poorer clinical outcomes in that patient population are likely due to the underlying systemic illness, comorbidities, and the cytotoxic and immunosuppressive anti-tumor treatments they are subjected to. We identified 416 cancer patients with SARS-CoV-2 infection being managed for their malignancy at Northwestern Medicine in Chicago, Illinois, between March and July of 2020. Seventy-five (18.0%) patients died due to COVID-related complications. Older age (>60), male gender, and current treatment with immunotherapy were associated with shorter overall survival. Laboratory findings showed that higher platelet counts, ALC, and hemoglobin were protective against critical illness and death from COVID-19. Conversely, elevated inflammatory markers such as ferritin, d-dimer, procalcitonin, CRP, and LDH led to worse clinical outcomes. Our findings suggest that a thorough clinical and laboratory assessment of infected patients with cancer might help identify a more vulnerable population and implement more aggressive proactive strategies.


Aetiology and diagnostics of paediatric hydrocephalus across Africa: a systematic review and meta-analysis.
We aimed to identify the aetiological distribution and the diagnostic methods for paediatric hydrocephalus across Africa, for which there is currently scarce evidence. In this systematic review and meta-analysis, we searched MEDLINE (Ovid), the Cochrane Database of Systematic Reviews (Wiley), Embase (Ovid), Global Health (Ovid), Maternity & Infant Care (Ovid), Scopus, African Index Medicus (Global Index Medicus, WHO) and Africa-Wide Information (EBSCO) from inception to Nov 29, 2021. We included studies from any African country reporting on the distribution of hydrocephalus aetiology in children aged 18 years and younger, with no language restrictions. Hydrocephalus was defined as radiological evidence of ventriculomegaly or associated clinical symptoms and signs of the disorder, or surgical treatment for hydrocephalus. Exclusion criteria were studies only reporting on one specific subgroup or one specific cause of hydrocephalus. We also excluded conference and meetings abstracts, grey literature, editorials, commentaries, historical reviews, systematic reviews, case reports and clinical guidelines, as well as studies on non-humans, fetuses, or post-mortem reports. The proportions of postinfectious hydrocephalus, non-postinfectious hydrocephalus, and hydrocephalus related to spinal dysraphism were calculated using a random-effects model. Additionally, we included a category for unclear cases. Diagnostic methods were described qualitatively. To assess methodological study quality, we applied critical appraisal checklists provided by the Joanna Briggs Institute. The study was registered in Prospero (CRD42020219038). Our search yielded 3783 results, of which 1880 (49·7%) were duplicates and were removed. The remaining 1903 abstracts were screened and 122 (6·4%) full articles were sought for retrieval; of these, we included 38 studies from 18 African countries that studied a total of 6565 children. The pooled proportion of postinfectious hydrocephalus was 28% (95% CI 22-36), non-postinfectious hydrocephalus was 21% (95% CI 13-30), and of spinal dysraphism was 16% (95% CI 12-20), with substantial heterogeneity. The pooled proportion of hydrocephalus of unclear aetiology was 20% (95% CI 13-28). Our findings suggest that postinfectious hydrocephalus is the single most common cause of paediatric hydrocephalus in Africa. For targeted investments to be optimal, there is a need for consensus regarding the aetiological classification of hydrocephalus and improved access to diagnostic services. Rikshospitalet, Oslo University Hospital, Oslo, Norway.


Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA.
Very few proteins encoded by the presumed non-coding RNA transcripts have been identified. Their cellular functions remain largely unknown. This study identifies the tumor-suppressor function of a novel microprotein encoded by the precursor of miR-34a. It consists of 133 amino acid residues, thereby named as miPEP133 (pri-microRNA encoded peptide 133). We overexpressed miPEP133 in nasopharyngeal carcinoma (NPC), ovarian cancer and cervical cancer cell lines to determine its effects on cell growth, apoptosis, migration, or invasion. Its impact on tumor growth was evaluated in a xenograft NPC model. Its prognostic value was analyzed using NPC clinical samples. We also conducted western blot, immunoprecipitation, mass spectrometry, confocal microscopy and flow cytometry to determine the underlying mechanisms of miPEP133 function and regulation. miPEP133 was expressed in normal human colon, stomach, ovary, uterus and pharynx. It was downregulated in cancer cell lines and tumors. miPEP133 overexpression induced apoptosis in cancer cells and inhibited their migration and invasion. miPEP133 inhibited tumor growth in vivo. Low miPEP133 expression was an unfavorable prognostic marker associated with advanced metastatic NPC. Wild-type p53 but not mutant p53 induced miPEP133 expression. miPEP133 enhanced p53 transcriptional activation and miR-34a expression. miPEP133 localized in the mitochondria to interact with mitochondrial heat shock protein 70kD (HSPA9) and prevent HSPA9 from interacting with its binding partners, leading to the decrease of mitochondrial membrane potential and mitochondrial mass. miPEP133 is a tumor suppressor localized in the mitochondria. It is a potential prognostic marker and therapeutic target for multiple types of cancers.


Tangential flow filtration of Bordetella pertussis submerse cultures.
A procedure is reported for the large scale separation of Bordetella pertussis microorganisms from liquid culture media by tangential flow filtration (cross flow filtration) using anisotropic membranes with a cut-off limit of 1 x 10(6) daltons, and microporous membranes with a pore size of 0.22 micrometer.


[Ultrasonic size of fetal crump-rump length in first trimester of pregnancy. Accuracy of gestational age assessment (author's transl)].
The fetal crown rump length was measureed by means of pulsed ultrasound. The normal values between 49 and 94 days from the onset of the last menstrual period were determined in 72 patients. Statistical analysis showed a good correlation between gestationnal age and fetal crown rump length. The usefulness of this measure is so demonstrated: assessment of gestational age, within few days.


The functional effects of piperine and piperine plus donepezil on hippocampal synaptic plasticity impairment in rat model of Alzheimer's disease.
The modulatory effects of piperine on drug metabolizing enzymes play an important role in the control of pharmacokinetic and the bioavailability properties of the administered drugs. The present study investigated the effect of piperine and piperine-donepezil co-administration on cognitive functions and synaptic plasticity at hippocampal perforant pathway (PP) to dentate gyrus (DG) synapses in an experimental model of Alzheimer's disease (AD). Intracerebroventricularly (ICV) streptozotocin (STZ) injected rats were treated once daily with piperine, donepezil and piperine combined with donepezil for 4 weeks. Cognitive performance was evaluated using passive avoidance and Morris water maze performance tasks. Analysis of evoked field potentials was done to explore possible effects on input/output response, paired-pulse facilitation and long-term synaptic plasticity (LTP) at PP to DG synapses of hippocampus. Rats subjected to ICV injection of STZ exhibited cognitive deficit associated with a hippocampal oxidative stress, effects that were reversed by chronic treatment with piperine or donepezil and or piperine combined with donepezil. Chronic treatment with piperine or donepezil restored the disruptive effects of STZ on LTP without altering basal synaptic transmission. We found that optimal hippocampal function is dependent on tissue redox homeostasis. Piperine might reduce the synaptotoxic effects of STZ on hippocampal synaptic neurotransmission and correspondently is a good potential for neuroprotection against oxidative damage from ICV injection of STZ. These results suggest that piperine or donepezil significantly ameliorate cognitive deficit and LTP induction by attenuating oxidative status.


Evaluation of Bond Strength and Fracture Load of Teeth With Flared Root Canals Restored With Prefabricated, Anatomical, and Computer-aided Design and Computer-aided Manufacturing Fiber Posts.
This study compared the use of anatomical glass fiber posts using bulk-fill composite resin with computer-aided design and computer-aided manufacturing (CAD/CAM) milled glass fiber post in oversized root canals, through bond strength (BS) and fracture resistance (FR) tests (fracture load). A total of 48 mandibular premolars were selected, half of them had their crowns removed at the cemento-enamel junction (CEJ) and the other half were sectioned 2 mm above the CEJ. Subsequently, teeth were endodontically treated. After 1 week, the standard preparation of the canals was carried out, and the roots were divided into three groups (n=16), according to the use of different restorative techniques (control: prefabricated glass fiber post [PFP], direct anatomical glass fiber post [AFP], and CAD/CAM milled glass fiber post [MFP]). After luting procedures using Single Bond Universal and RelyX Ultimate (3M ESPE), for eight teeth in each group, six specimens were obtained (two slices from each root third: cervical, middle, and apical). For the remaining eight roots of each group, standardized preparations for metal-free crowns, milling of 5 mol% yttria-stabilized tetragonal zirconia polycrystalline, cementation of the crowns, and periodontal ligament simulation were performed. Then, for each group, the BS was evaluated through the push-out test, and the FR was evaluated in compression. The data obtained from BS were submitted to two-way analysis of variance (ANOVA; group vs root region) and Tukey (α=0.05) and from FR to one-way ANOVA (group) and Tukey (α=0.05). For the BS test, the MFP group was statistically superior to the PFP group in all root regions and was statistically superior to the AFP group only in the cervical region, being statistically similar in the middle and apical root regions. For the FR test, the MFP group was statistically superior to the PFP and AFP groups. The milled fiber post technique can be a legitimate alternative in the restoration of weakened roots with flared root canals.


Surgical treatment of earlobe keloid with CO2 laser radiation: case report and clinical standpoints.
Keloids are considered to be benign hyperproliferative growths of dense fibrous tissue and overabundant deposition of disorganized, thick, hyalinized collagen that result from an abnormal tissue response to cutaneous injury. Keloids do not have a specific cause, although genetic predisposition is heavily implicated. We present a case report of a patient with an earlobe keloid that was treated with carbon dioxide laser radiation (CO(2)) with an 0.8-mm focus, 7 W, a power density of 2.5 W/cm(2), in a continuous mode. The patient was seen for follow-up 6 months later. An intact hole for placement of an earring was observed with a very good esthetic and functional result.


Serous Tubal Intraepithelial Carcinoma or Not? Metastases to Fallopian Tube Mucosa Can Masquerade as In Situ Lesions.
- Nonuterine high-grade serous carcinomas (HGSCs) are believed to arise most often from precursors in the fallopian tube referred to as serous tubal intraepithelial carcinomas (STICs). A designation of tubal origin has been suggested for all cases of nonuterine HGSC if a STIC is identified. - To highlight that many different types of nongynecologic and gynecologic carcinomas, including HGSC, can metastasize to the tubal mucosa and mimic de novo STIC. - A mini-review of several recently published studies that collectively examine STIC-like lesions of the fallopian tube. - The fallopian tube mucosa can be a site of metastasis from carcinomas arising elsewhere, and pathologists should exercise caution in diagnosing STIC without first considering the possibility of metastasis. Routinely used immunohistochemical stains can often be used to determine if a STIC-like lesion is tubal or nongynecologic in origin. In the context of uterine and nonuterine HGSC, STIC may represent a metastasis rather than the site of origin, particularly when widespread disease is present.


Analysis of Arf GTP-binding protein function in cells.
This unit describes techniques and approaches that can be used to study the functions of the ADP-ribosylation factor (Arf) GTP-binding proteins in cells. There are six mammalian Arfs and many more Arf-like proteins (Arls), and these proteins are conserved in eukaryotes from yeast to humans. Like all GTPases, Arfs cycle between GDP-bound, inactive and GTP-bound active conformations, facilitated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that catalyze GTP binding and hydrolysis, respectively. This unit describes approaches that can be taken to examine the localization and function of Arf and Arl proteins in cells. A simple protocol for measuring activation (GTP-binding) of specific Arf proteins in cells using a pull-down assay is also described. Approaches that can be taken to assess function of GEFs and GAPs in cells is described.


A survey of the views of palliative care healthcare professionals towards referring cancer patients to participate in randomized controlled trials in palliative care.
Clinical trials in palliative care (PC), especially randomised controlled trials (RCTs), are notoriously difficult to complete. One perceived challenge is gatekeeping, the reluctance of some healthcare professionals (HCPs) to refer patients for research studies. This study aimed to identify the extent of gatekeeping from palliative RCTs. An anonymous questionnaire was sent to 597 HCPs with an interest in PC in Australia and New Zealand to assess their willingness to refer patients for RCTs. Respondents considered key issues that might affect their decision, documented willingness to refer to RCTs of increasing complexity in a hypothetical pain situation and documented the degree of patient inconvenience considered acceptable. Demographic data were collected. One hundred ninety-eight questionnaires were returned (33%), 122 from doctors and 76 from other HCPs. Very few were willing to refer to complicated studies involving many extra tests and/or hospital visits. Non-medical HCPs were less interested than doctors in studies that involved randomisation, placebo controls or double-blind methodology. The majority would refer patients for non-pharmacological studies, but were less willing to refer for pharmacological studies with possible side effects. Non-medical HCPs were less willing than doctors to refer to trials that involved patient inconvenience. Two factors predicted for greater willingness to refer: previous research experience and male gender. The survey revealed an unwillingness on the part of many HCPs to refer patients for RCTs in PC. It identifies trial-related factors that may encourage or discourage referral. Gatekeeping has the potential block recruitment and introduce a selection bias.


Online control of anticipated postural adjustments in step initiation: evidence from behavioral and computational approaches.
Anticipatory postural adjustments (APAs) prior to step execution are thought to be immutable once released. Here we challenge this assumption by testing whether APAs can be modified online if a body perturbation occurs during execution. Two directions of perturbation (resisting and assisting) relative to the body weight transfer were used during the execution of APAs. We found that APAs are modified online (increase in both ground pressure and muscle activity) to compensate for resisting perturbations. The outcomes of a biomechanical model confirmed that the early changes in the APAs resulted from an active control of the APAs and were not merely mechanical consequences of the perturbation. However, no modification of the initial feedforward command was observed for assisting perturbations. The motor command changes for the resisting perturbation may originate from the mismatch between passively originated forces and those actively specified by the central command when acting in the opposite direction. The absence of a mismatch in the assisting perturbation might explain why the central nervous system was not prompted to modify the APAs in this condition.


CD69 expression on lymphocytes and interleukin-15 levels in synovial fluids from different inflammatory arthropathies.
The aim was to study a possible relationship between CD69 expression on lymphocytes and interleukin-15 (IL-15) levels in synovial fluid (SF) from patients with different inflammatory arthropathies. CD69 expression was assessed by two-color flow cytometry on different subsets of synovial fluid lymphocytes (SFL) obtained from patients with diagnoses of rheumatoid arthritis (RA), seronegative spondyloarthropathy (SSd), and crystal-associated arthritis (CAA). The IL-15 levels in synovial fluid supernatants were measured by enzyme-linked immunoassay (ELISA). No significant differences between the three groups of arthropathies were observed in the distribution of synovial fluid lymphocyte subsets. CD69-positive SFL were mainly CD3-, CD45RO-, and CCR5-positive cells. Although no significant differences in the percentage of CD69-positive lymphocytes were observed between the three groups of patients, the highest level of CD69 expression on lymphocytes was observed in RA patients (mean fluorescence intensity 37.9 +/- 5.2 compared to 17.5 +/- 3.3 in SSd and 12.4 +/- 2.6 in CAA, P = 0.007 and P < 0.001, respectively). In addition, the expression of CD69 on SFL from RA correlated with their respective IL-15 levels measured in SF supernatants. Our data provide in vivo evidence of the putative role that IL-15 can play in the high expression of CD69 on SFL from RA patients.


[Treatment of ischemic heart disease with beta-receptor blockers and isosorbide dinitrate (author's transl)].
The effects of a beta-receptor blocker (Betadrenol), an isosorbide dinitrate preparation (Isoket) and the combination of the two substances (Betaket) were compared with a placebo in a controlled double blind trial in 20 patients with confirmed attacks of angina pectoris and/or ischemic changes in the ECG on ergometer exercise. Important assessment criteria of the efficacy were regression of ischemic ECG changes on standardized ergometer exercise, increase in load resistance and the nitroglycerine requirement. Treatment with the combination of betablocker and isosorbide dinitrate (Betaket) was more effective in comparison to treatment with the individual substances.


Primary vesicoureteral reflux: A 26-year experience in a single centre.
To determine the nature of primary vesicoureteral reflux (VUR) and the association of VUR with hydronephrosis and renal damage. The medical records of children ≤ 15 years diagnosed with VUR, attending the Department of Pediatrics, Prince of Songkla University, Thailand between 1987 and 2013 were reviewed. Renal ultrasound and technetium-99m dimercaptosuccinic acid renal scan (DMSA) results were examined to determine the severity of hydronephrosis and renal damage, respectively. There were 177 boys and 211 girls. 350 (90.2%) were diagnosed following urinary tract infection (UTI). The median (IQR) age at diagnosis of first VUR was 7.6 (4.3-12.2) months in boys and 18.6 (9.0-46.6) months in girls (P < 0.001). Renal ultrasound was performed in 340 patients. Hydronephrosis was found in 105 patients and 135 kidneys and 22.5% VUR kidneys and 11.0% non-VUR kidneys (P = 0.01). The severity of hydronephrosis was associated with VUR grade (44.2% of grades IV and V VUR had hydronephrosis vs 11.9% of grades I-III VUR, P < 0.001). DMSA was performed in 332 patients. Abnormalities were found in 30.1% VUR kidneys and 4.1% non-VUR kidneys (P < 0.001). Abnormal DMSA results were strongly associated with VUR grade (17.8% for VUR grades I-III vs 60.5% for VUR grades IV and V, P < 0.001). Primary VUR in this group was most commonly diagnosed following investigation of UTI and detected during infancy, earlier in boys. Hydronephrosis and renal damage were associated with severity of VUR.


Effect of respiratory syncytial virus infection on regulated on activation, normal T-cells expressed and secreted production in a murine model of asthma.
Synthesis of regulated on activation, normal T-cells expressed and secreted (RANTES) in the airway has previously been shown to be elevated after respiratory syncytial virus (RSV) infection. However, since few studies have examined whether RSV-infected asthma patients express a higher level of RANTES than do normal individuals, we used a murine model of asthma to address this question. We prepared Dermatophagoides farinae-sensitized mice as an asthma model, and then infected them with RSV and analyzed the changes in airway responsiveness and the cell populations and cytokine levels of bronchoalveolar lavage fluid. RANTES synthesis increased in response to RSV infection in both control mice and in asthma model (D. farinae) mice. However, there was no significant difference in the amount of RANTES produced following RSV infection between control and D. farinae mice. RSV infection affected neither interferon-γsynthesis nor airway responsiveness in either control or D. farinae mice. RSV infection did not induce more RANTES in a murine model of asthma than in control mice.


Role of estrogen receptor alpha on vaginal epithelialization of patients with Mayer-Rokitansky-Kuster-Hauser syndrome submitted to neovaginoplasty using oxidized regenerated cellulose.
The purpose of this study was to evaluate the expression of estrogen receptor alpha (ERα) on the neovaginal tissue of patients with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome submitted to modified Abbé-McIndoe neovaginoplasty using oxidized regenerated cellulose. The current study involved eight subjects with MRKH syndrome. Serial samples of the neovagina were obtained after the surgery and immunohistochemical detection of ERα was performed using antibody NCL-L-ER-6F11. The operation was performed successfully in all subjects without complications. A total of 22 samples of neovaginal tissue were analyzed. The expression of ERα was detected only 6 months after the surgery, when the neovagina acquired characteristics of normal vagina. In our study, the expression of ERα occurred when complete epithelialization of vaginal tissue was observed. Other mechanisms may be involved in the formation of vaginal epithelium in patients with MRKH syndrome.