Immunolocalization of anti-agglutinin for spermatozoa in boars.
A boar "anti-agglutinin," which inhibits head-to-head agglutination of spermatozoa, has been identified as a 25-kDa sialoprotein contained in epididymal and seminal plasma. This study was conducted to determine the location of the anti-agglutinin on spermatozoa and in various organs, including epididymides, by indirect immunofluorescence and Western blotting techniques. Ejaculated boar spermatozoa were washed and subjected to immunocytochemical observation. Epididymal plasma was recovered from three different regions of epididymides and subjected to sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) and Western blotting. Twelve kinds of organs (testis, epididymis, seminal vesicle, prostate, heart, liver, kidney, spleen, stomach, small intestine, lung, and muscle) were recovered from boars. The unilateral epididymides were fixed, cut into 10-microm frozen sections, and subjected to immunohistochemical observation. The other organs were homogenized and used for SDS-PAGE and Western blotting. Immunocytochemical observations revealed that the antiserum strongly recognized the acrosomal region and equatorial segment on unfixed and methanol-fixed spermatozoa. Immunohistochemical observations revealed that the epithelia of the epididymal ducts were recognized by the antiserum mainly in the corpus epididymides. Moreover, the antiserum reacted with the luminal contents of the corpus and cauda epididymides. However, no specific reaction was detected in the caput epididymides. Western blotting showed that the antiserum selectively recognized a band of the anti-agglutinin in the corpus and cauda epididymal plasma, although no band was detected in the caput epididymal plasma. In the extracts from various organs, the single band was detected in the corpus and cauda epididymides at the same mobility as the anti-agglutinin, but not in the other organs. Based on these results, the following matters concerning the anti-agglutinin are discussed: (1) the importance of its association with the acrosome of spermatozoa in inhibiting sperm head-to-head agglutination; (2) its origin in the epididymis; and (3) its tissue specificity.


The gene ontology categorizer.
The Gene Ontology Categorizer, developed jointly by the Los Alamos National Laboratory and Procter & Gamble Corp., provides a capability for the categorization task in the Gene Ontology (GO): given a list of genes of interest, what are the best nodes of the GO to summarize or categorize that list? The motivating question is from a drug discovery process, where after some gene expression analysis experiment, we wish to understand the overall effect of some cell treatment or condition by identifying 'where' in the GO the differentially expressed genes fall: 'clustered' together in one place? in two places? uniformly spread throughout the GO? 'high', or 'low'? In order to address this need, we view bio-ontologies more as combinatorially structured databases than facilities for logical inference, and draw on the discrete mathematics of finite partially ordered sets (posets) to develop data representation and algorithms appropriate for the GO. In doing so, we have laid the foundations for a general set of methods to address not just the categorization task, but also other tasks (e.g. distances in ontologies and ontology merger and exchange) in both the GO and other bio-ontologies (such as the Enzyme Commission database or the MEdical Subject Headings) cast as hierarchically structured taxonomic knowledge systems.


Submicron trenches reduce the Pseudomonas fluorescens colonization rate on solid surfaces.
Bacterial adhesion and spreading on biomaterials are considered key features of pathogenicity. Roughness and topography of the substrate have been reported to affect bacterial adhesion, but little is known about their effect on spreading. Submicron row and channel tuning with bacterial diameter (S2) were designed to test bacterial motility on these surfaces. Random nanometer-sized structures (S1) were used as controls. Optical microscopy and AFM were employed to detect biological and surface pattern details in the micro- and nanoscale, respectively. Results showed that motility strategies (flagella orientation, elongation, aggregation in rafts, formation of network structures, and development of a bacterial frontier) were affected by the presence of submicropatterns. Importantly, the rate of bacterial spreading on S2 was significantly reduced and influenced by the orientation of the submicropatterns. Consequently, submicroengineered substrates could be employed as a tool to downgrade bacterial colonization. Such patterns could impact on the design of proper engineered structures to control biofilm spreading on solid surfaces.


Elevational patterns of plant richness in the Taibai Mountain, China.
The elevational distribution of plant diversity is a popular issue in ecology and biogeography, and several studies have examined the determinants behind plant diversity patterns. In this study, using published data of the local flora of Taibai Mountain, we explored the effects of spatial and climatic factors on plant species richness. We also evaluated Rapoport's elevational rule by examining the relationship between elevational range size and midpoint. Species richness patterns were regressed against area, middle domain effect (MDE), mean annual temperature (MAT), and mean annual precipitation (MAP). The results showed that richness of overall plants, seed plants, bryophytes, and ferns all showed hump-shaped patterns along the elevational gradient, although the absolute elevation of richness peaks differed in different plant groups. Species richness of each plant group was all associated strongly with MAT and MAP. In addition to climatic factors, overall plants and seed plants were more related to area in linear regression models, while MDE was a powerful explanatory variable for bryophytes. Rapoport's elevational rule on species richness was not supported. Our study suggests that a combined interaction of spatial and climatic factors influences the elevational patterns of plant species richness on Taibai Mountain, China.


Accurate frequency noise measurement of free-running lasers.
We present a simple method to accurately measure the frequency noise power spectrum of lasers. It relies on creating the beat note between two lasers, capturing the corresponding signal in the time domain, and appropriately postprocessing the data to derive the frequency noise power spectrum. In contrast to methods already established, it does not require stabilization of the laser to an optical reference, i.e., a second laser, to an optical cavity or to an atomic transition. It further omits a frequency discriminator and hence avoids bandwidth limitation and nonlinearity effects common to high-resolution frequency discriminators.


The whisking rhythm generator: a novel mammalian network for the generation of movement.
Using the rat vibrissa system, we provide evidence for a novel mechanism for the generation of movement. Like other central pattern generators (CPGs) that underlie many movements, the rhythm generator for whisking can operate without cortical inputs or sensory feedback. However, unlike conventional mammalian CPGs, vibrissa motoneurons (vMNs) actively participate in the rhythmogenesis by converting tonic serotonergic inputs into the patterned motor output responsible for movement of the vibrissae. We find that, in vitro, a serotonin receptor agonist, alpha-Me-5HT, facilitates a persistent inward current (PIC) and evokes rhythmic firing in vMNs. Within each motoneuron, increasing the concentration of alpha-Me-5HT significantly increases the both the magnitude of the PIC and the motoneuron's firing rate. Riluzole, which selectively suppresses the Na(+) component of PICs at low concentrations, causes a reduction in both of these phenomena. The magnitude of this reduction is directly correlated with the concentration of riluzole. The joint effects of riluzole on PIC magnitude and firing rate in vMNs suggest that the two are causally related. In vivo we find that the tonic activity of putative serotonergic premotoneurons is positively correlated with the frequency of whisking evoked by cortical stimulation. Taken together, these results support the hypothesized novel mammalian mechanism for movement generation in the vibrissa motor system where vMNs actively participate in the rhythmogenesis in response to tonic drive from serotonergic premotoneurons.


Mechanisms of the cochlear nucleus octopus cell's onset response: synaptic effectiveness and threshold.
Octopus cells are one of the principal cell types in the mammalian posteroventral cochlear nucleus. These cells respond to the onset of a toneburst with a precisely timed spike followed by little, if any, sustained activity. While experimental studies have partially characterized the cell, the mechanisms of this onset response are not well understood. The present study involved a model-based investigation that analyzed the responses of a compartmental model of the octopus cell in terms of synaptic effectiveness and dynamic spike threshold. The simulations demonstrate that properties of the onset response (first-spike latency, temporal precision of the first spike, and sustained firing rate) can be predicted from the values of these cell properties for a wide range of model configurations. These relationships were further analyzed through the development of mathematical expressions for synaptic effectiveness and dynamic spike threshold. This computational analysis resulted in a relatively simple explanation of the onset response, as well as predictions of the responses of octopus cells to nontonal, complex stimuli.


Mechanism of entomotoxicity of the Concanavalin A in Rhopalosiphum padi (Hemiptera: Aphididae).
The toxicity effect of Concanavalin A (Canavalia ensiformis lectin, ConA) to bird cherry-oat aphid, Rhopalosiphum padi L. (Hemiptera: Aphididae), was investigated in the laboratory by using artificial diets containing ConA concentrations. Bird cherry-oat aphid performance was affected by the presence of Con A in artificial diets. The lectin added into the liquid diet increased the prereproductive period, mortality, and the average time of generation development (T) and decreased fecundity and the intrinsic rate of natural increase (rm). In attempt to unravel the mode of action of ConA, the interaction of the lectin with insect gut and the effect of ConA on feeding behavior were investigated. Extract of gut of treated grain aphid demonstrated DNA fragmentation, and this was accompanied with an increase in caspase 3 activity. Moreover, addition of ConA to the sucrose-agarose gels reduced salivation and passive ingestion of fluids from the gel. The results indicate that the insecticidal activity of ConA on R. padi may involve effects on death of the gut epithelial cells and effects on feeding behavior. This can be employed to create plants that are resistant to aphids.


The value of the political action committee: dollars and influence for nurse leaders.
Nurse leaders play an important role in the shaping of healthcare policy and the care delivery models of the future. It is vital for nurse leaders to understand the role of money in politics and how donations to a candidate's campaigns can be beneficial in getting one's concerns addressed by Congress. The political action committee (PAC) is a major vehicle for campaign contributions for candidates from any party. This article will detail the following related to PACs: history and background information, government regulations, and why PACs are an important vehicle for nurse leaders to gain access and influence in Congress.


Surfactant protein-A concentration in sera from dogs with pulmonary parenchymal diseases.
Pulmonary surfactant protein A (SP-A) is used as a biomarker to understand the clinical features of pulmonary diseases and associated prognostic indices in human medicine. This study was conducted to investigate whether or not serum SP-A concentration can be used as a biomarker for identifying pulmonary parenchymal diseases in dogs. Thirty-two dogs with pulmonary parenchymal diseases, 34 with nonrespiratory diseases and 57 healthy dogs were included. Serum SP-A concentration was measured in all dogs using sandwich enzyme linked immunosorbent assay with an anti-dog SP-A polyclonal antibody. Median serum SP-A concentration in healthy dogs was <2.0 ng/ml, whereas that in dogs with aspiration pneumonia (n=11), primary lung tumors (n=9) and blunt traumatic lung injury (BTLI; n=12) was 3.1, 7.2 and 2.6 ng/ml, respectively; these values were significantly higher than those in healthy dogs. The serum SP-A concentration in dogs with nonrespiratory diseases was comparable with that in healthy dogs. No correlation was observed between the serum SP-A and plasma C-reactive protein concentrations in dogs with aspiration pneumonia and BTLI. There was a significant correlation between the serum SP-A concentration and thoracic radiographic changes in dogs with BTLI. These findings suggest that the serum SP-A concentration may be a useful clinical biomarker of alveolar damage that can be used for differential diagnosis of pulmonary parenchymal diseases and nonrespiratory diseases in dogs.


The effects of low-pressure hyperbaric oxygen treatment before and after maximal exercise on lactate concentration, heart rate recovery, and antioxidant capacity.
The purpose of this study was to investigate the effects of low-pressure hyperbaric oxygen (HBO) treatment before and after maximal exercise on lactate concentration and heart rate and antioxidant capacity. Ten healthy male college students were recruited from amateur soccer players. Subjects were performed a maximal exercise 3 times at intervals of at least 7 days according to the treatment method (control, pretreatment, posttreatment). Lactate concentration, heart rate, and antioxidant capacity were measured before, post, and after recovery 30 min of maximal exercise. The lactate concentration and heart rate of recovery 30 min was significantly lower in the low-pressure HBO treated group after the maximal exercise compared with the control group and the low-pressure HBO treated group before maximal exercise, and it could affect the removal of the fatigue substance caused by the maximal exercise. These results suggest that the low-pressure HBO treatment which is a new possibility for recovery of peripheral fatigue.


Neurophysiological markers of vulnerability to schizophrenia: sensitivity and specificity of specific quantitative eye movement measures.
Eye-tracking deficits in schizophrenic patients and relatives have generated interest in using eye movements to mark schizophrenia liability. Efforts to develop specific quantitative measures have provided insight into the nature of the deficit and suggested what underlying neurophysiological mechanisms are involved. This study used receiver operating characteristic curve analyses to evaluate and compare the sensitivity, specificity, and overall accuracy of predicting disease liability using single and combined specific and global quantitative measures. Results indicate that measures of predictive pursuit and leading saccades significantly increased predictive accuracy compared with traditional global measures. Combining specific measures provided greater predictive accuracy compared with single measures. Implications for the use of specific eye movement measures to define schizophrenia-related phenotypes in genetic studies are discussed.


Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, in Aspergillus fumigatus.
The functionality of many microsome-associated proteins which exhibit altered abundance in response to iron limitation in Aspergillus fumigatus is unknown. Here, we generate and characterize eight gene deletion strains, and of most significance reveal that MirC (AFUA_2G05730) contributes to the maintenance of intracellular siderophore [ferricrocin (FC)] levels, augments conidiation, confers protection against oxidative stress, exhibits an intracellular localization and contributes to fungal virulence in the Galleria mellonella animal model system. FC levels were unaffected following deletion of all other genes encoding microsome-associated proteins. MirC does not appear to play a role in either siderophore export from, or uptake into, A. fumigatus. Label-free quantitative proteomic analysis unexpectedly revealed increased abundance of siderophore biosynthetic enzymes. In addition, increased expression of hapX (7.2 and 13.8-fold at 48 and 72 h, respectively; p < 0.001) was observed in ΔmirC compared to wild-type under iron-replete conditions by qRT-PCR. This was complemented by significantly elevated extracellular triacetylfusarinine C (TAFC; p < 0.01) and fusarinine C (FSC; p < 0.05) siderophore secretion. We conclude that MirC plays an important role in FC biosynthesis and contributes to the maintenance of iron homeostasis in A. fumigatus.


Effects in the liver of methylene chloride inhaled alone and with ethyl alcohol.
When high concentrations of methylene chloride in combination with high concentrations of ethanol were inhaled for one day by guinea pigs, the extent of the hepatic damage induced suggested an antagonism between the effects of the two agents. However, exposure for five days to approximately 500 ppm of methylene chloride plus high concentrations of ethanol suggested ethanol may potentiate the effects of methylene chloride.


The relationships between temporal lobe and diencephalic structures implicated in anterograde amnesia.
The relationship between the anterograde amnesic syndromes associated with diencephalic and temporal lobe pathology is examined in the light of recent findings. It is proposed that a common feature of anterograde amnesia is damage to part of an "extended hippocampal system" comprising the hippocampus, the fornix, the mammillary bodies, and the anterior thalamic nuclei. Damage to this system results in deficits in the recall of episodic information, the core symptom of anterograde amnesia. In contrast, lesions in this system need not disrupt tests of recognition memory when they primarily tax familiarity judgements. It is assumed that familiarity judgements depend on other regions (e.g. the rhinal cortex in the case of temporal lobe amnesia) and that the extended hippocampal system is principally involved in those aspects of recognition that are retrieval-based rather than familiarity-based. These proposals arise from new evidence on the performance of delayed nonmatching-to-sample by animals, from a meta-analysis of the performance of amnesic subjects on a test of recognition memory, and from new research into the pattern of connections between the medial temporal lobe and the medial diencephalon in primates.


Adherence of Clostridium perfringens spores to human intestinal epithelial Caco-2 cells.
Clostridium perfringens is a gram-positive, spore-forming bacillus, and is a causative agent of foodborne infection, antibiotic-associated diarrhoea and sporadic diarrhoea in humans. In cases of antibiotic-associated and sporadic diarrhoea, C. perfringens colonises the intestine, proliferates and causes disease. However, bacterial colonisation of the intestine is not considered necessary in the pathogenesis of foodborne illness, because such pathogenesis can be explained by anchorage-independent production of diarrhoeic toxin by the bacterium in the intestine. In this study, we used an in vitro adherence assay to examine the adherence of C. perfringens spores to human intestinal Caco-2 cells. Adherence of spores from isolates of foodborne illness and nosocomial infection was observed within 15 min, and plateaued 60 min after inoculation. Electron microscopy revealed a tight association of spores with the surface of Caco-2 cells. The adherence of vegetative cells could not be confirmed by the same method, however. These results suggest that C. perfringens spores may adhere to intestinal epithelial cells in vivo, although its biological significance remains to be determined.


Stereopsis and disparity vergence in monkeys with subnormal binocular vision.
The surgical treatment for strabismus in infants generally results in microtropia or subnormal binocular vision. Although the clinical characteristics of these conditions are well established, there are important questions about the mechanisms of binocular vision in these patients that can best be investigated in an appropriate animal model. In the present psychophysical investigations, spatial frequency response functions for disparity-induced fusional vergence and for local stereopsis were studied in macaque monkeys, who demonstrated many of the major visual characteristics of patients whose eyes were surgically aligned during infancy. In six rhesus monkeys, unilateral esotropia was surgically induced at various ages (30-184 days of age). However, over the next 12 months, all of the monkeys recovered normal eye alignment. Behavioral measurements at 4-6 years of age showed that the monkeys' prism-induced fusional vergence responses were indistinguishable from those of control monkeys or humans with normal binocular vision. Investigations of stereo-depth discrimination demonstrated that each of the experimental monkeys also had stereoscopic vision, but their stereoacuities varied from being essentially normal to severely stereo-deficient. The degree of stereo-deficiency was not related to the age at which surgical esotropia was induced, or to the presence or absence of amblyopia, and was not dependent on the spatial frequency of the test stimulus. Altogether, these experiments demonstrate that a temporary, early esotropia can affect the binocular disparity responses of motor and sensory components of binocular vision differently, probably because of different sensitive periods of development for the two components.


In-vitro study of the influence of octocrylene on a selected metastatic melanoma cell line.
Octocrylene (OCT) is one of the most widespread chemical UV filters used in sunscreens and cosmetic products. Despite the use of sunscreens and personal care products over decades, melanoma as the most serious and aggressive form of skin cancer is still a cause of concern. Hence the aim of this study was to investigate any potential influence of OCT on metabolic activity, cytotoxicity and ABCB5 mRNA expression in melanoma cells. The ABCB5 transmembrane protein was tested due to its well-known role in the initiation, invasion and metastatic spread of various cancers, including melanoma. Metastatic melanoma cell line WM-266-4 (ATCC) was incubated with selected concentrations of OCT and for different time intervals. The MTT and LDH assays to measure the cells' metabolic activity and cytotoxicity were used respectively. Target gene (ABCB5) expression was detected by quantitative real-time PCR (qRT-PCR), using TaqMan® chemistry. Our results suggest decreased metastatic melanoma cells' metabolic activity, increased cytotoxicity and increased ABCB5 mRNA expression (P<0.05) with longer time of exposure to OCT as compared to control cells. Accordingly, we suspect that the surviving cells are more invasive and aggressive, which might explain their microscopically observed cannibalistic activity. With this study, we elucidate a new promising field for further research to contribute to etiology and prevention of melanoma.


Me2AlCH2PMe2: a new, bifunctional cocatalyst for the Ni(II)-catalyzed oligomerization of PhSiH3.
The role of methylaluminoxane (MAO) in the Ni-catalyzed dehydrogenative homologation of PhSiH3 has been investigated with a view to designing new cocatalysts possessing well-defined chemical compositions and structures. These studies show that species such as the bifunctional reagent (Me2PCH2AlMe2)2, 3, should act as co-catalyst for the Si-Si bond formation reactions. Thus, it was found that the combination of (1-Me-indenyl)Ni(PPh3)Me, 2a, and 3 (Ni/Al ratio of 1:1) converts PhSiH3 to cyclic oligomers (PhSiH)n with a turnover frequency (TOF) of >500 h(-1), 50 times faster than with 2a alone. Detailed NMR studies have indicated that this acceleration is due to the formation of the intermediate (1-Me-indenyl)Ni(Me)(Me2PCH2AlMe2), 4. Coordination of the PMe2 moiety in this complex to the Ni center allows the tethered AlMe2 moiety to interact with the Ni-Me moiety in such a way that promotes fairly slow Al-Me/Ni-CD3 exchange (t(1/2) ca. 12 h) but accelerates the Si-H bond activation and Si-Si bond formation reactions. The catalysis promoted by 2a/3 proceeds even faster in the presence of NEt3 or THF (TOF > 1600 h(-1)), because these Lewis bases favor the monomeric form of 3, which in turn favors the formation of 4. On the other hand, the much more nucleophilic base quinuclidine suppresses the catalysis (TOF < 300 h(-1)) by hindering the Ni.R.Al interactions. These observations point to an emerging strategy for using bifunctional reagents such as 3 to place geometrically constrained Lewis acid moieties adjacent to metal centers, thereby activating certain metal-ligand bonds.


Nuclear medicine applications in the clinical setting. Imaging studies aid disease staging and management.
Over the last decade, advances in instrumentation have improved the accuracy and quality of conventional nuclear medicine studies. In addition, the approval of many new radiopharmaceuticals has helped integrate cutting-edge imaging techniques into the clinical setting. In this article, Drs Middleton and Shell discuss the latest applications of positron emission tomography (PET), radiolabeled antibody imaging, radioisotope lymphatic mapping, and radiolabeled receptor imaging.


Participant experiences of Talking Circles on type 2 diabetes in two Northern Plains American Indian Tribes.
The Talking Circle, a culturally appropriate, 12-week educational intervention, was employed on two Northern Plains American Indian reservations to provide information on type 2 diabetes. In a phenomenological study, funded as a minority supplement to the Talking Circle intervention, the authors asked 8 American Indian participants of the Talking Circle to describe their experience of being an American Indian Talking Circle participant. Seven common themes describe the phenomenon of participating in a Talking Circle diabetic intervention. The Talking Circle technique was effective in providing information on type 2 diabetes through culturally appropriate community sharing. Type 2 diabetes is viewed by both outsiders and those involved as a chronic disease of the utmost concern in American Indian communities.


The impact of COVID-19 lockdown on the clinical and radiological outcomes of both-bone forearm fractures treated by compression plating at a tertiary care centre in India: a retrospective study.
The COVID-19 pandemic has affected everyone's life. In India, the nationwide lockdown was enforced from March 25, 2020. It has significantly affected the healthcare delivery system. Both-bone forearm (BBFA) fractures are commonly encountered as an emergency. Surgical management with plate fixation is often the primary mode of management in adults and adolescents. During the first wave of the COVID-19 pandemic, follow-up of patients with BBFA fractures who had undergone surgery before the lockdown was severely affected. To understand the effect of lack of regular follow-up on the outcome of BBFA fracture patients, in this study, we assessed their radiological, functional, and clinical outcomes at least 12 months after surgery. This study examined if a lack of routine follow-ups in surgically treated BBFA fracture patients has any impact on their short-term outcomes. We included 30 patients with BBFA fractures who were operated prior to the COVID-19 lockdown and assessed their radiological, functional, and clinical outcomes 12 months after surgery. Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, Patient-Rated Wrist Evaluation (PRWE) score, Grace and Eversmann's score, and Mayo Elbow Performance Index (MEPI) score were assessed subjectively. Fracture site tenderness, and wrist, forearm, elbow, and grip strength range of motion (ROM) were objectively evaluated. Radiological union was recorded using standard forearm anteroposterior and lateral radiography. At follow-up, 28 patients had union at the fracture site, and two patients had a nonunion. A significant reduction was observed in the mean ROM of the injured forearm compared with the uninjured forearm in supination (17.76% less), pronation (31.4% less), dorsiflexion (32% less), palmar-flexion (24.6% less), elbow flexion-extension arc (2.5% less), and grip strength (18% less). The percentage reduction in pronation and dorsiflexion was higher than that in supination and palmar-flexion, respectively. Grace and Eversmann's score was excellent in 16 patients, good in 4, acceptable in 7, and poor in 3 patients. The mean QuickDASH score was 6 ± 6.6. The mean PRWE and MEPI scores were 7 ± 4.5 and 87.16, respectively. The MEPI score was excellent in 21 patients, good in 6, fair in 2, and poor in 1 patient. The clinical, functional, and radiological outcomes of adult patients with BBFA fractures who were treated with compression plating were satisfactory. Inadequate follow-up during the COVID-19 first wave in India had minimal to no effect on their short-term outcomes.


Pneumococcal Carriage, Serotype Distribution, and Risk Factors in Children With Community-Acquired Pneumonia, 5 Years After Introduction of the 10-Valent Pneumococcal Conjugate Vaccine in Ethiopia.
There is a scarcity of data on pneumococcal serotypes carried by children in Ethiopia. We studied pneumococcal nasopharyngeal carriage rate, serotypes, and risk factors among children with community acquired pneumonia (CAP). A prospective observational cohort study was performed in children with CAP, aged 0-15 years, in 2 pediatric emergency departments in Addis Ababa, Ethiopia. Nasopharyngeal swabs were cultured, and serotypes of Streptococcus pneumoniae were determined by sequencing the cpsB gene and by the Quellung reaction. Risk factors were analyzed by using binary logistic regression. Nasopharyngeal swabs were collected from 362 children with CAP. Pneumococcal carriage rate was 21.5% (78 of 362). The most common serotypes were 19A (27%), 16F (8.5%), and 6A (4.9%). In addition, 8.5% of the pneumococcal isolates were nontypeable. In bivariate analysis, children with a parent that smokes were more likely to carry pneumococci (crude odds ratio, 3.9; 95% confidence interval [CI], 1.2-12.3; P = .023) than those with parents that do not smoke. In multivariable analysis, living in a house with ≥2 rooms (adjusted odds ratio [AOR], 0.48; 95% CI, 0.28-0.82; P = .007) and vaccination with ≥2 doses of 10-valent pneumococcal conjugate vaccine (PCV10) (AOR, 0.37; 95% CI, 0.15-0.92; P = .033) were protective of pneumococcal carriage. Five years after introduction of PCV10 in Ethiopia, the vaccine-related serotype 19A was predominant in the nasopharynx of children with CAP. Continued evaluation of the direct and indirect impact of PCV10 on pneumococcal serotype distribution in Ethiopia is warranted.


A single set of exhaustive exercise before local muscular endurance training improves quadriceps strength and endurance in young men.
The purpose of this study was to examine the effects of an additional set of exhaustive exercise before local muscular endurance (LME) training on maximal dynamic strength and endurance of quadriceps muscle in young men. Twenty-seven healthy men (age: 20.9±1.8 years) performed one repetition maximum (1RM), muscular endurance, and magnetic resonance imaging (MRI) tests on two separate occasions (before and after an 8-wk LME training program using a bilateral knee extensor machine). After baseline testing, the subjects were divided into three groups: untrained control (CO, N.=9), traditional training (TR, N.=9), and prior exhaustive training (PE, N.=9). Both the TR and PE groups trained using the same LME training protocol (2 d∙wk-1; 3 sets of 15-20 repetitions at 50% of 1RM) throughout the 8-wk experimental period; the only difference was that the PE group performed an additional set of exhaustive exercise at 80% of 1RM immediately before each training session. After 8 wk, the PE group experienced a greater (P<0.05) increase in 1RM, endurance, and work efficiency than the TR group. Additionally, no changes (P>0.05) in cross-sectional area (CSA), body mass and daily dietary intake were observed from pre- to post-test in either group. These results suggest that the inclusion of a single set of exhaustive exercise at 80% of 1RM immediately before LME training can be a suitable strategy for inducing additional beneficial effects on quadriceps strength and endurance in young men.


The EARN-Health Trial: protocol for a randomised controlled trial to identify health effects of a financial savings programme among low-income US adults.
A theory within the social epidemiology field is that financial stress related to having inadequate financial savings may contribute to psychological stress, poor mental health and poor health-related behaviours among low-income US adults. Our objective is to test whether an intervention that encourages financial savings among low-income US adults improves health behaviours and mental health. A parallel group two-arm controlled superiority trial will be performed in which 700 participants will be randomised to the intervention or a wait list. The intervention arm will be provided an online Individual Development Account (IDA) for 6 months, during which participants receive a $5 incentive (£3.2, €4.5) for every month they save $20 in their account (£12.8, €18), and an additional $5 if they save $20 for two consecutive months. Both groups will be provided links to standard online financial counselling materials. Online surveys in months 0 (prior to randomisation), 6 and 12 (6 months postintervention) will assess self-reported health behaviours and mental health among participants in both arms. The surveys items were tested previously in the US Centers for Disease Control and Prevention national health interviews and related health studies, including self-reported overall health, health-related quality of life, alcohol and tobacco use, depression symptoms, financial stress, optimism and locus of control, and spending and savings behaviours. Trial data will be analysed on an intent-to-treat basis. This protocol was approved by the Institutional Review Board of Stanford University (Protocol ID: 30641). The findings of the trial will be disseminated through peer-reviewed publication. Identifier NCT02185612; Pre-results.


The effect of changes in dialysate volume on glucose and urea equilibration.
To determine the effect of changing dialysate volume on urea and glucose equilibration curves and to determine, if dialysate volume is prescribed on the basis of body surface area, whether equilibrium curves will be consistent in patients of different sizes and ages. A prospective study wherein children with acute or chronic renal failure had peritoneal equilibrium studies done with dwell volumes of 30 mL/kg, 40 mL/kg, and 1200 mL/m2. Twenty-two children: 7 under 3 years of age; 8 between 3 and 10 years of age; 7 older than 10 years of age. Student's t-test. Urea and glucose equilibrated rapidly at dwell volumes of 30 mL/kg, slower at dwell volumes of 40 mL/kg, and slowest at dwell volumes of 1200 mL/m2. Equilibration curves were similar in children of different ages when dialysate volumes of 1200 mL/m2 were infused. Dialysate volumes of 1200 mL/m2 should be used when equilibration studies are being done to compare individuals of different ages and sizes.


The influence of freezer storage of urine samples on the BONN-Risk-Index for calcium oxalate crystallization.
This study was performed to quantify the effect of a 1-week freezer storage of urine on its calcium oxalate crystallization risk. Calcium oxalate is the most common urinary stone material observed in urolithiasis patients in western and affluent countries. The BONN-Risk-Index of calcium oxalate crystallization risk in human urine is determined from a crystallization experiment performed on untreated native urine samples. We tested the influence of a 1-week freezing on the BONN-Risk-Index value as well as the effect of the sample freezing on the urinary osmolality. In vitro crystallization experiments in 49 native urine samples from stone-forming and non-stone forming individuals were performed in order to determine their calcium oxalate crystallization risk according to the BONN-Risk-Index approach. Comparison of the results derived from original sample investigations with those obtained from the thawed aliquots by statistical evaluation shows that i) no significant deviation from linearity between both results exists and ii) both results are identical by statistical means. This is valid for both, the BONN-Risk-Index and the osmolality data. The differences in the BONN-Risk-Index results of both procedures of BONN-Risk-Index determination, however, exceed the clinically acceptable difference. Thus, determination of the urinary calcium oxalate crystallization risk from thawed urine samples cannot be recommended.


[Some problems of creating a geriatric service in the regions.]
The article reflects the current state of geriatric care in the Russian Federation at the stage of formation of a three-level model of geriatric service. The problems in the organization of geriatric services at the regional level, including the problem of training the appropriate profile, the negative attitude of the elderly to geriatric departments and geriatrics in General. Measures to improve the work in this direction are proposed.


Weight and body shape changes in a treatment-naive population after 6 months of nevirapine-based generic highly active antiretroviral therapy in South India.
The nutritional and body shape response after the initiation of highly active antiretroviral therapy (HAART) in resource-limited environments has not been documented. In this environment, nutritional compromise is a common complication of human immunodeficiency virus (HIV) infection. We conducted a prospective study of 190 HIV-infected patients who initiated a nevirapine-based HAART regimen. CD4+ T cell count, body weight, body mass index, anthropometry, and bioelectrical impedance data were collected prior to initiation of therapy and after 6 months of therapy. The mean age of participants was 35 years, 85% of participants were male, and 59% received stavudine as 1 of the nucleosides in their initial HAART regimen. The members of the cohort were malnourished before the initiation of therapy and had a mean body mass index of 20.1 (calculated as weight in kilograms divided by the square of height in meters). Overall, body weight increased a mean of 2.8 kg (range, -12.5 to 22.5 kg), and CD4+ T cell counts increased by a mean of 140 cells/mm3. Patients were stratified into those who lost weight (loss of >1 kg, 22%; n=41), those whose weight remained stable (19%; n=37), and those who gained weight (gain of >1 kg, 59%; n=112). Patients in all groups retained body shape symmetry and experienced no change in waist-to-hip ratio or regional body shape by anthropometry. The group that lost weight and the group whose weight remained stable experienced significant CD4+ T cell count increases at 6 months. Although the majority of HIV-infected patients who received nevirapine-based HAART gained weight, there were participants who lost weight despite initiating their first HAART therapy.


Liver and tumour tissue concentrations of TNF-alpha in cancer patients treated with TNF-alpha and melphalan by isolated liver perfusion.
In this study we determined the level of tumour necrosis factor alpha (TNF-alpha) in liver and tumour tissue samples obtained from patients with colorectal metastases confined to the liver, who were treated with isolated liver perfusion with TNF-alpha and melphalan. We adapted a standard enzyme-linked immunosorbent assay kit for the quantification of TNF-alpha in serum to measure the amount of this cytokine in solid tissue. For this purpose, we developed a buffer that lysed the tissues without affecting the TNF-alpha present. The minimum detection level was about 2 pg of TNF-alpha per mg tissue. Using this technique, we found a significant increase in the TNF-alpha level after perfusion in the liver tissue of all evaluable patients, which may explain the transient liver toxicity we observed in all patients. In tumour tissue, a significant TNF-alpha increase was observed in one out of five patients. The level of TNF-alpha in all liver tissue samples and some of the tumours after treatment by isolated liver perfusion was much higher than the peak serum concentrations obtained after systemic administration of the maximum tolerated dose of TNF-alpha. Furthermore, we demonstrated that the level of TNF-alpha in the liver tissue samples was about seven to eight times higher than in tumour tissue. We concluded that regional liver treatment resulted in a relatively high local level of TNF-alpha, but also that this cytokine did not preferentially accumulate in tumour tissue.


Oxytocin Modulates Neural Individuation/Categorization Processing of Faces in Early Face-Selective Areas.
Oxytocin (OT) is known as a neuropeptide that promotes social adaptation. Individuating racial in-group members and viewing racial out-groups in categories is an adaptive strategy that evolved to aid effective social interaction. Nevertheless, whether OT modulates the neural individuation/categorization processing of racial in-group and out-group faces remain unknown. After intranasal OT or placebo administration, 46 male participants (OT: 24, placebo: 22) were presented with face pairs with the same or different identities or races in rapid succession. The neural repetition suppression (RS) effects to identity and race were measured using functional magnetic resonance imaging (fMRI) as indices of individuation/categorization face-processing. The results showed that while OT increased the RS effect to race, it decreased the RS effect to identity in the right fusiform face area. As for the left occipital face area, OT enlarged the differential RS effects to identities of in-group and out-group faces. Additionally, OT modulated the association of interdependence self-construal and the RS effects on identity and race. These findings bring to light preliminary evidence that OT can regulate neuronal specificity of identity and race in early face-selective regions and benefit adaptive individuation/categorization face-processing.


Normal nasal cavity and paranasal sinuses in brown lemurs Eulemur fulvus: computed tomography and cross-sectional anatomy.
Far less is known about the normal anatomy of the nasal cavity of Eulemur fulvus; no computed tomography (CT) scan has ever been published. Relevant CT scans were taken in the transverse, dorsal and longitudinal planes. These scans were compared with anatomical sections of heads. Computed tomography scans revealed almost all nasal structures, but cannot differentiate between the various layers of the nasal mucosa. Results show a double-scroll arrangement of the ventral nasal concha. The dorsal nasal concha protrudes into the maxillary sinus, but no protrusion into the frontal sinus was observed. The ethmoturbinate I is completely closed back on itself and rostrally voluminous. This work shows that at a clinical level, the integrity of the different turbinates can easily be appreciated from a simple CT scan. It will assist clinicians to evaluate pathological conditions that affect the nasal region.


Membranoproliferative glomerulonephritis in the aged and its possible causal relationship with CD8+CD57+ lymphocytes.
Membranoproliferative glomerulonephritis (MPGN) is a chronic progressive glomerulonephritis that occurs primarily in patients under the age of 30, and is rare in the elderly. We report eight aged patients with MPGN associated with CD8+CD57+ lymphocytosis. All eight patients showed a significant increase in CD8+CD57+ lymphocytes with a significant decrease in the ratio of CD4+ cells to CD8+ cells. Infiltration of CD8+CD57+ lymphocytes was observed within capillary lumens to various degrees according to the severity of endocapillary proliferation in each case. Expression of endothelial-leukocyte adhesion molecule-1 was observed in a focal and segmental manner on glomerular endothelial cells and on the endothelium of arterioles and arteries in kidney tissue in four cases in which a pronounced endocapillary proliferation was simultaneously seen. These findings suggest that cell-mediated cytotoxic mechanisms against glomerular endothelial cells may be involved in the pathogenesis of MPGN in the aged.


Visualization and the Digital Humanities.
For the past two years, researchers from the visualization community and the digital humanities have come together at the IEEE VIS conference to discuss how both disciplines can work together to push research goals in their respective disciplines. In this paper, we present our experiences as a result of this collaboration.


Open data and data sharing in articles about COVID-19 published in preprint servers medRxiv and bioRxiv.
This study aimed to analyze the content of data availability statements (DAS) and the actual sharing of raw data in preprint articles about COVID-19. The study combined a bibliometric analysis and a cross-sectional survey. We analyzed preprint articles on COVID-19 published on medRxiv and bioRxiv from January 1, 2020 to March 30, 2020. We extracted data sharing statements, tried to locate raw data when authors indicated they were available, and surveyed authors. The authors were surveyed in 2020-2021. We surveyed authors whose articles did not include DAS, who indicated that data are available on request, or their manuscript reported that raw data are available in the manuscript, but raw data were not found. Raw data collected in this study are published on Open Science Framework (https://osf.io/6ztec/). We analyzed 897 preprint articles. There were 699 (78%) articles with Data/Code field present on the website of a preprint server. In 234 (26%) preprints, data/code sharing statement was reported within the manuscript. For 283 preprints that reported that data were accessible, we found raw data/code for 133 (47%) of those 283 preprints (15% of all analyzed preprint articles). Most commonly, authors indicated that data were available on GitHub or another clearly specified web location, on (reasonable) request, in the manuscript or its supplementary files. In conclusion, preprint servers should require authors to provide data sharing statements that will be included both on the website and in the manuscript. Education of researchers about the meaning of data sharing is needed. The online version contains supplementary material available at 10.1007/s11192-022-04346-1.


Luciferase-Zinc-Finger System for the Rapid Detection of Pathogenic Bacteria.
Rapid and reliable detection of pathogenic bacteria is crucial for food safety control. Here, we present a novel luciferase-zinc finger system for the detection of pathogens that offers rapid and specific profiling. The system, which uses a zinc-finger protein domain to probe zinc finger recognition sites, was designed to bind the amplified conserved regions of 16S rDNA, and the obtained products were detected using a modified luciferase. The luciferase-zinc finger system not only maintained luciferase activity but also allowed the specific detection of different bacterial species, with a sensitivity as low as 10 copies and a linear range from 10 to 104 copies per microliter of the specific PCR product. Moreover, the system is robust and rapid, enabling the simultaneous detection of 6 species of bacteria in artificially contaminated samples with excellent accuracy. Thus, we envision that our luciferase-zinc finger system will have far-reaching applications.


Unique expression of HRF20 (CD59) in human nervous tissue.
Damage to autologous tissue by complement is limited by several widely distributed membrane-associated glycoproteins which restrict the action of the complement in homologous species. These include decay accelerating factor (DAF), membrane cofactor protein (MCP) and 20 kDa homologous restriction factor (HRF20,CD59). Using immunohistochemical techniques, we examined the localization of these proteins in the central nervous system (CNS) and peripheral nervous system (PNS) using non-neurological human nervous tissue since some complement components have been demonstrated to be synthesized in the CNS. There was no evidence of parenchymal staining by anti-DAF or anti-MCP antibodies in either type of tissue except for the staining of the endothelium in capillaries. On the other hand, anti-HRF20 antibody clearly stained myelinated axons in the CNS as well as Schwann cells in the PNS. In addition, we detected positive staining by anti-DAF antibody in the PNS of a Paroxysmal nocturnal hemoglobinuria (PNH) patient who is genetically deficient in HRF20.


Identification of neutralizing epitopes on the VP2 protein of infectious bursal disease virus by phage-displayed heptapeptide library screening and synthetic peptide mapping.
Infectious bursal disease virus (IBDV) is the causative agent of infectious bursal disease, which is one of the most important and widespread infectious diseases in commercial chickens. Conformational epitopes have been reported in the highly variable region of the VP2 protein of IBDV. In the present study, a random heptapeptide library was screened by using monoclonal antibodies (mAbs), YNW17 and YNW29, directed to the VP2 of IBDV and two peptide motifs, D-X-P-R and A-R-G, were identified. The motifs are present on the N and C terminal sequences of the highly variable region of VP2. Synthetic overlapping peptides covering the motifs on VP2 were analyzed by Dot- ELISA with the mAbs and two epitopes 197CDSSDRPRVYTIT209 and 329ARGSLAVTI337 identified. The above epitopes were also recognized by chicken anti-IBDV sera and shown to inhibit the binding of their mAbs to recombinant VP2. Both mAbs and sera from mice immunized with the conjugated epitope-peptides were able to neutralize serotype I IBDV. These results indicated that the epitopes are two neutralizing linear B-cell epitopes and would be useful for the development of peptide-based IBD vaccines.


Core-Shell Nitrogen-Doped Carbon Hollow Spheres/Co3 O4 Nanosheets as Advanced Electrode for High-Performance Supercapacitor.
Co3 O4 /nitrogen-doped carbon hollow spheres (Co3 O4 /NHCSs) with hierarchical structures are synthesized by virtue of a hydrothermal method and subsequent calcination treatment. NHCSs, as a hard template, can aid the generation of Co3 O4 nanosheets on its surface; while SiO2 spheres, as a sacrificed-template, can be dissolved in the process. The prepared Co3 O4 /NHCS composites are investigated as the electrode active material. This composite exhibits an enhanced performance than Co3 O4 itself. A higher specific capacitance of 581 F g-1 at 1 A g-1 and a higher rate performance of 91.6% retention at 20 A g-1 are achieved, better than Co3 O4 nanorods (318 F g-1 at 1 A g-1 and 67.1% retention at 20 A g-1 ). In addition, the composite is employed as a positive electrode to fabricate an asymmetric supercapacitor. The device can deliver a high energy density of 34.5 Wh kg-1 at the power density of 753 W kg-1 and display a desirable cycling stability. All of these attractive results make the unique hierarchical Co3 O4 /NHCS core-shell structure a promising electrode material for high-performance supercapacitors.


Restless Legs Syndrome Due to the Use of Trazodone: A Case Report.
Many case reports have demonstrated that using antidepressants and especially the selective serotonin reuptake inhibitors (SSRIs), and the noradrenergic and specific serotonergic antidepresants mirtazapine and mianserin can lead to restless legs syndrome (RLS). However, there are disagreements in the results of the limited number of investigations on the relationship of RLS with antidepressants. Trazodone is a frequently used antidepressant with complex agonistic/antagonistic effects on the serotonergic system and moderate blockage on the histamine receptor. This report dicusses the case of a 39-year old female patient who developed RLS after using trazodone (100mg/day) prescribed by her pscyhiatrist for treating her insomnia complaints. We have learned from the patient's statement that she felt burning, tingling and restlessness in her legs, that started from the first night of the treatment and caused an urge to move her legs. The effects were attributed to trazodone and the treatment was discontinued. The patient reported at her control examination the disappearance of RLS symptoms one day after discontinuing trazodone use and the complete improvement of her insomnia complaints.


Acceptability of multipurpose human papillomavirus vaccines among providers and mothers of adolescent girls: A mixed-methods study in five countries.
Multipurpose vaccines (MPVs) could be formulated to prevent multiple sexually transmitted infections simultaneously. Little is known about acceptability of MPVs among vaccine health care providers (HCPs) or mothers of adolescent girls. 151 adolescent vaccine providers and 118 mothers of adolescent girls aged 9-14 were recruited from five geographically-diverse countries: Argentina, Malaysia, South Africa, South Korea, and Spain. We assessed providers' preferences for single-purpose human papillomavirus (HPV) vaccine versus MPVs (including HPV+herpes simplex virus (HSV)-2, HPV+HIV, or HPV+HSV-2+HIV) via quantitative surveys. Maternal MPV attitudes were assessed in four focus group discussions (FGDs) in each country. Most providers preferred MPVs over single-purpose HPV vaccination, with preference ranging from 61% in Malaysia to 96% in South Africa. HPV+HSV-2+HIV was the most preferred MPV formulation (56-82%). Overall, 53% of the mothers preferred MPVs over single-purpose HPV vaccines, with strongest support in South Africa (90%) and lowest support in South Korea (29%). Convenience and trust in the health care system were commonly-cited reasons for MPV acceptability. Safety and efficacy concerns were common barriers to accepting MPVs, though specific concerns differed by country. Across FGDs, additional safety and efficacy information on MPVs were requested, particularly from trusted sources like HCPs. Though maternal acceptability of MPVs varied by country, MPV acceptability would be enhanced by having HCPs provide parents with additional MPV vaccine safety and efficacy information. While most providers preferred MPVs, future health behavior research should identify acceptability barriers, and targeted provider interventions should equip providers to improve vaccination discussions with parents.


Item Response Theory to Quantify Longitudinal Placebo and Paliperidone Effects on PANSS Scores in Schizophrenia.
As biomarkers are lacking, multi-item questionnaire-based tools like the Positive and Negative Syndrome Scale (PANSS) are used to quantify disease severity in schizophrenia. Analyzing composite PANSS scores as continuous data discards information and violates the numerical nature of the scale. Here a longitudinal analysis based on Item Response Theory is presented using PANSS data from phase III clinical trials. Latent disease severity variables were derived from item-level data on the positive, negative, and general PANSS subscales each. On all subscales, the time course of placebo responses were best described with Weibull models, and dose-independent functions with exponential models to describe the onset of the full effect were used to describe paliperidone's effect. Placebo and drug effect were most pronounced on the positive subscale. The final model successfully describes the time course of treatment effects on the individual PANSS item-levels, on all PANSS subscale levels, and on the total score level.


Structural modeling identifies Plasmodium vivax 4-diphosphocytidyl-2C-methyl-d-erythritol kinase (IspE) as a plausible new antimalarial drug target.
Malaria parasites utilize Methylerythritol phosphate (MEP) pathway for synthesis of isoprenoid precursors which are essential for maturation and survival of parasites during erythrocytic and gametocytic stages. The absence of MEP pathway in the human host establishes MEP pathway enzymes as a repertoire of essential drug targets. The fourth enzyme, 4-diphosphocytidyl-2C-methyl-d-erythritol kinase (IspE) has been proved essential in pathogenic bacteria, however; it has not yet been studied in any Plasmodium species. This study was undertaken to investigate genetic polymorphism and concomitant structural implications of the Plasmodium vivax IspE (PvIspE) by employing sequencing, modeling and bioinformatics approach. We report that PvIspE gene displayed six non-synonymous mutations which were restricted to non-conserved regions within the gene from seven topographically distinct malaria-endemic regions of India. Phylogenetic studies reflected that PvIspE occupies unique status within Plasmodia genus and reflects that Plasmodium vivax IspE gene has a distant and non-conserved relation with human ortholog Mevalonate Kinase (MAVK). Structural modeling analysis revealed that all PvIspE Indian isolates have critically conserved canonical galacto-homoserine-mevalonate-phosphomevalonate kinase (GHMP) domain within the active site lying in a deep cleft sandwiched between ATP and CDPME-binding domains. The active core region was highly conserved among all clinical isolates, may be due to >60% β-pleated rigid architecture. The mapped structural analysis revealed the critically conserved active site of PvIspE, both sequence, and spacially among all Indian isolates; showing no significant changes in the active site. Our study strengthens the candidature of Plasmodium vivax IspE enzyme as a future target for novel antimalarials.


Friend or foe: can activating mutations in NOTCH1 contribute to a favorable treatment outcome in patients with T-ALL?
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Despite significant improvement in the treatment of T-ALL, approximately 20% of children and most adults succumb to resistant or relapsed disease. Transformation events occur during crucial steps of thymocyte development and have been related to the expression of certain oncogenes such as TAL2, TLX1, LYL1, LMO1, and NOTCH1. Mutations that lead to constitutive activation of NOTCH1 are most commonly found in human patients with T-ALL. Moreover, overexpression of the intracellular portion of NOTCH1 can lead to the initiation of T-ALL in mouse models. These findings suggest that NOTCH1 may promote tumorigenesis through the regulation of differentiation of leukemic cells, and, potentially, of leukemia-initiating cell identity and function. Multiple studies and clinical trials aimed at targeting NOTCH1 in T-ALL or using NOTCH1 mutations as a prognostic tool are currently underway. Recent studies unexpectedly found that activating mutations in NOTCH1 are correlated with better treatment outcome. Here we review these studies and discuss possible explanations for these findings.


Emerging role of PARP-1 and PARthanatos in ischemic stroke.
Cell death is a key feature of neurological diseases, including stroke and neurodegenerative disorders. Studies in a variety of ischemic/hypoxic mouse models demonstrate that poly(ADP-ribose) polymerase 1 (PARP-1)-dependent cell death, also named PARthanatos, plays a pivotal role in ischemic neuronal cell death and disease progress. PARthanatos has its unique triggers, processors, and executors that convey a highly orchestrated and programmed signaling cascade. In addition to its role in gene transcription, DNA damage repair, and energy homeostasis through PARylation of its various targets, PARP-1 activation in neuron and glia attributes to brain damage following ischemia/reperfusion. Pharmacological inhibition or genetic deletion of PARP-1 reduces infarct volume, eliminates inflammation, and improves recovery of neurological functions in stroke. Here, we reviewed the role of PARP-1 and PARthanatos in stroke and their therapeutic potential.


No association of the G1287A polymorphism in the norepinephrine transporter gene and susceptibility to major depressive disorder in a Japanese population.
Norepinephrinergic neurotransmission in the central nervous system have a major impact on the symptomatology in major depressive disorder (MDD), and genetic polymorphisms of norepinephrine transporter (NET) have a possibility to be involved in susceptibility to MDD. We investigated the association of the G1287A (rs5569) polymorphism of the NET gene and susceptibility to MDD by comparing 145 major depressive patients with 164 healthy individuals first in a Japanese population. The genotype frequencies in depressed patients and health volunteers of the NET G1287A polymorphism were 52.4% (G/G), 39.3% (G/A) and 8.3% (A/A) in depressed patients, 61.6% (G/G), 29.9% (G/A allele) and 8.5% (A/A) in healthy volunteers, respectively. The allele frequencies in depressed patients and health volunteers of the NET G1287A polymorphism were 72.1% (G allele) and 27.9% (A allele) in depressed patients, 76.5% (G allele) and 23.5% (A allele) in healthy volunteers, respectively. The genotype distribution and allele frequencies were not significantly different between major depressive patients and healthy volunteers. NET G1287A polymorphism appears not to be an important factor in susceptibility to MDD in a Japanese population.


An open trial of olanzapine in anorexia nervosa.
Recent reports raise the possibility that olanzapine can assist weight gain and improve behavioral symptoms during refeeding in anorexia nervosa. Seventeen DSM-IV anorexia nervosa subjects hospitalized between May 1999 and October 2000 were enrolled in open-label treatment with olanzapine for up to 6 weeks. Baseline weight and symptoms were compared to patients' status at the end of treatment. Olanzapine administration was associated with a significant reduction in depression, anxiety, and core eating disorder symptoms, and a significant increase in weight. A comparison with our historical data suggests that subjects in this study had a significantly greater decrease in depression. These data lend support to the possibility that olanzapine may be useful in treating anorexia nervosa. However, a controlled trial is necessary to demonstrate that olanzapine is efficacious.


Wear resistance of TiAlSiN thin coatings.
In the last decades TiAIN coatings deposited by PVD techniques have been extensively investigated but, nowadays, their potential development for tribological applications is relatively low. However, new coatings are emerging based on them, trying to improve wear behavior. TiAlSiN thin coatings are now investigated, analyzing if Si introduction increases the wear resistance of PVD films. Attending to the application, several wear test configurations has been recently used by some researchers. In this work, TiAISiN thin coatings were produced by PVD Unbalanced Magnetron Sputtering technique and they were conveniently characterized using Scanning Electron Microscopy (SEM) provided with Energy Dispersive Spectroscopy (EDS), Atomic Force Microscopy (AFM), Electron Probe Micro-Analyzer (EPMA), Micro Hardness (MH) and Scratch Test Analysis. Properties as morphology, thickness, roughness, chemical composition and structure, hardness and film adhesion to the substrate were investigated. Concerning to wear characterization, two very different ways were chosen: micro-abrasion with ball-on-flat configuration and industrial non-standardized tests based on samples inserted in a feed channel of a selected plastic injection mould working with 30% (wt.) glass fiber reinforced polypropylene. TiAISiN coatings with a small amount of about 5% (wt.) Si showed a similar wear behavior when compared with TiAIN reported performances, denoting that Si addition does not improve the wear performance of the TiAIN coatings in these wear test conditions.


Impact of endometrioma and bilaterality on IVF / ICSI cycles in patients with endometriosis.
Endometriosis, one of the most common gynecological disorder, is a challenging disease observed in 20 %-40 % of subfertile women. Endometriomas affect 17-44 % of women with endometriosis. Because endometrioma has detrimental effects on fertility, many of these women need Assisted Reproductive Technology (ART) to conceive. In this study, we aimed to investigate the effects of endometrioma presence and impact of bilaterality over In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) outcomes. The study was designed retrospectively. A total of 159 women enrolled in IVF / ICSI cycles were included. Patients were divided into two groups as Endometrioma group (n: 73) and control group (n:86). In Endometrioma group, subgroup analysis was performed according to whether endometrioma was unilateral or bilateral. Demographic characters, clinical and laboratory parameters were recorded. SPSS was used for analysis. In endometrioma group, although basal FSH levels was higher than control group, it was within normal limits, while estradiol levels was lower (p < 0.001, p 0.042, respectively). Antral follicle count (AFC), dominant follicle number, total oocyte count, MII oocyte numbers were found to be significantly lower, whereas numbers of embryos achieved, clinical pregnancy rates (PR) and live birth rates (LBR) were found to be similar.There were no statistically significant differences in terms of Antimullerian Hormon (AMH) levels, oocyte and embryo quality, the numbers of embryos achieved, PR and LBR between unilateral and bilateral endometrioma groups. This study shows that presence of endometrioma negatively effects fertility parameters albeit no significant effect over embryo quality, PR and LBR whereas bilaterality doesn't have any influence over any fertility parameters and PR.


PKCδ signalling regulates SR-A and CD36 expression and foam cell formation.
The formation of foam cells is crucial in the initiation and progression of atherosclerosis. One of the critical steps in foam cell formation is the uptake of low-density lipoprotein (LDL) by macrophages via scavenger receptors (SRs). This study examined the role of protein kinase C (PKC) isoforms on foam cell formation. The effects of short-hairpin RNA (shRNA) and small interfering RNA (siRNA) against classical PKC and novel PKC isoforms were investigated in THP-1-derived macrophages and primary macrophages. The knockdown of PKCδ inhibited oxidized LDL (OxLDL) uptake and intracellular cholesterol accumulation in both cell models. The reduction of PKCδ resulted in decreased expression of SR-A and CD36. Similar conclusions were obtained in examining the effects of a PKCδ inhibitor, rottlerin. Molecular investigation revealed that a decrease in PKCδ inhibited protein kinase B (PKB/Akt) expression and extracellular-signal-regulated kinase (ERK) phosphorylation. Surprisingly, PKCδ-knockdown selectively decreased protein but not the mRNA level of PKCβI and PKCβII. We showed that the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt upstream of ERK decreased SR-A and CD36 expression; however, the inhibition of ERK or PKCβ downstream of ERK attenuated SR-A but not CD36 expression. We further demonstrated that PKCδ could be induced by pro-atherogenic mediators, OxLDL and interferon-γ. Notably, PKCδ, phosphorylated ERK, Akt, and SR-A were highly expressed in human atherosclerotic arteries and CD68-positive macrophages as visualized by immunohistochemical staining. Through regulating PI3K/Akt and ERK activity, PKCδ affects SR-A and CD36 expression and foam cell formation. The results suggest PKCδ as a potential target for atherosclerosis therapeutics.


Women's Knowledge on Cervical Cancer Risk Factors and Symptoms: A Cross Sectional Study from Urban India.
Early-stage cervical cancer diagnoses may be the consequence of timely medical care in the presence of symptoms which can be linked to awareness of the symptoms and risk factors. This study aims to determine the knowledge about risk factors and symptoms of cervical cancer and associated factors among women aged 20-49 years. Data were utilized from the survey under the intervention "Increasing access to cervical cancer screening and care through the community-centric continuum of care initiative in India" (2015). The sample size was 1,020 women in the age group of 20-49 years. Descriptive statistics, along with bivariate analysis, was done to represent the preliminary results. Multivariable regression analysis was used to represent the estimates. About 40.1% [Delhi: 56.9% and Rohtak: 20.4%] and 45.5% [Delhi: 52.2% and Rohtak: 37.7%] of respondents had good knowledge about risk factors and symptoms of cervical cancer, respectively. Respondents with primary educational status had an 86% significantly higher likelihood for good knowledge about identified risk factors of cervical cancer [ adjusted odds ratio (aOR): 1.86; CI: 1.12-3.10]. Respondents who were married or widowed/divorced/separated had significantly higher odds for good knowledge about identified risk factors and symptoms of cervical cancer in reference to respondents who were never married. Respondents from Rohtak had 72% and 35% significantly higher odds for good knowledge about identified risk factors [aOR:0.28; CI: 0.21,0.39] and symptoms [aOR:0.65; CI: 0.48,0.88] of cervical cancer, respectively, in reference to respondents from Delhi. Overall awareness about cervical cancer and Human papillomavirus (HPV) as the causative agent was low, more so in Rohtak. This is extremely worrisome as blocking HPV infection is one of the most effective ways to prevent cervical cancer. Moreover, the knowledge about the risk factors and symptoms of cervical cancer is also inadequate, particularly in women from Rohtak.


Solubilization of α-galactosylceramide in aqueous medium: Impact on Natural Killer T cell activation and antitumor responses.
The potent antitumor effect of α-galactosylceramide (α-GalCer) is based on its recognition by invariant Natural Killer T cells (iNKT) after its capture and presentation by antigen presenting cells including dendritic cells (DCs). Synthetic α-GalCer has already been tested in advanced cancer patients but no or only moderate clinical responses were obtained. To optimize α-GalCer efficacy, we have postulated that alternative formulations impacting its molecular organization in aqueous medium could modify DC uptake and iNKT-based immune responses. To this end, we have developed two strategies: (1) the formulation of α-GalCer in non-cationic liposomes and (2) the synthesis of a water-soluble α-GalCer analogue by anchoring a polyethyleneglycol moiety on its sugar head. The biological activities of these new preparations were compared to that induced by the classically used Polysorbate 20 α-GalCer micelles. Both formulations retained their uptake by DCs and activated iNKT cells both in vitro and in vivo. Despite a lower cytokine production, the formulations induced a potent immune response able to control lung murine carcinoma. In conclusion, it is possible to increase α-GalCer solubility in aqueous solution without limiting its antitumor properties.


Type 1 collagen as an endovascular stent-graft material for small-diameter vessels: a biocompatibility study.
To compare patency rates and degrees of neointimal hyperplasia between bovine type 1 collagen stent-grafts and uncovered control stents in small-diameter vessels (< or =4 mm). Uncovered stainless-steel, balloon-expandable stents (n = 5) and type 1 collagen stent-grafts (n = 6) were implanted via the femoral arteries with use of 4-mm balloon catheters into the abdominal aorta of New Zealand White rabbits. Ten animals were available for follow-up. Subjects were followed for 1 month (three uncovered stents; three collagen stent-grafts) or 4 months (two uncovered stents; two collagen stent-grafts). Angiography was performed before animal sacrifice and luminal compromise was compared between groups. Histologic and immunohistochemical analysis was performed to determine presence of neointima and neointimal thickness and area; these parameters were also compared between groups. All stents and stent-grafts remained patent at both time points. Luminal compromise was not detectable angiographically in any subject. Maximum neointimal thickness was less than 5 mum for all subjects. Neointimal thickness and area were not statistically significantly different between groups. Type 1 collagen stent-grafts demonstrate excellent hemocompatibility and biocompatibility in small-diameter vessels in rabbits.


Cross-validation of the peppermint benchmarking experiment across three analytical platforms.
The Peppermint Experiment is a breath analysis benchmarking initiative that seeks to address the lack of inter-comparability of outcomes across independent breath biomarker studies. In this experiment, the washout profiles of volatile terpene constituents of encapsulated peppermint oil (mainlyα-pinene,β-pinene, limonene and 1,8-cineole) in exhaled breath are characterized through a series of measurements at defined sampling intervals up to 6 h after ingestion of the capsule. In the present work, the Peppermint Experiment was carried out on a cohort of volunteers (n= 11) that provided breath samples in three sittings on different days (i.e. triplicates per volunteer) for concurrent analysis by three different analytical platforms. These platforms were proton transfer reaction-time-of-flight-mass spectrometry (PTR-TOFMS) interfaced with a buffered end-tidal (BET) breath sampler, gas chromatography-ion mobility spectrometry (GC-IMS) in conjunction with a compatible handheld direct breath sampler, and thermal desorption comprehensive two-dimensional gas chromatography-time-of-flight-mass spectrometry (TD-GC×GC-TOFMS) with a Respiration Collection forin-vitroAnalysis (ReCIVA) system for trapping breath volatiles onto adsorbent tubes. Regression analysis yielded mean washout times across the cohort of 448 min (PTR-TOFMS and GC-IMS) and 372 min (TD-GC×GC-TOFMS), which are in good alignment with published benchmark values. Large variations in washout profiles were observed at the individuals level, both between (inter-individual) and within (intra-individual) participants, indicating high variability in the degree of absorption, distribution, metabolism and excretion of volatile terpenes in the body within individuals and across the cohort. The comparably low inter-instrument variability indicates that differences in benchmark values from independent studies reported in the literature are driven by biological variability rather than different performances between sampling methods or analytical platforms.


High molecular weight kininogen as substrate for cathepsin B.
We investigated the influence of pH and divalent cations (Zn2+, Mg2+ and Ca2+) on high molecular weight kininogen processing by cathepsin B. At pH 6.3, high molecular weight kininogen is hydrolyzed by cathepsin B at three sites generating fragments of 80, 60 and 40 kDa. Cathepsin B has kininogenase activity at this pH which is improved in the absence of divalent cations. At pH 7.35, high molecular weight kininogen is slightly cleaved by cathepsin B into fragments of 60 kDa, and cathepsin B kininogenase activity is impaired. Our results suggest that high molecular weight kininogen is a substrate for cathepsin B under pathophysiological conditions.


Children's coping with marital conflict and their adjustment and physical health: vulnerability and protective functions.
Children's strategies for coping with parental marital conflict were examined as predictors, mediators, and moderators of the relations between marital conflict and 8- to 11-year-olds' internalizing, externalizing, and physical health problems. In the context of marital conflict, a higher level of active coping and support coping combined was a protective factor against girls' depression symptoms and self-esteem problems and both boys' and girls' health problems. Further, avoidance coping was a vulnerability factor for externalizing, internalizing, and physical health problems in boys, and distraction coping was protective against children's depression and health problems. These findings extend the literature by delineating coping strategies that either protected children against, or heightened their vulnerability to, adjustment and health problems associated with exposure to parental marital conflict.


High-Resolution Manometry Evaluation of Pressures at the Pharyngo-upper Esophageal Area in Patients with Oropharyngeal Dysphagia Due to Vagal Paralysis.
The motility of the pharynx, upper esophageal sphincter (UES), and proximal esophagus in patients with oropharyngeal dysphagia is still not entirely understood. High-resolution manometry (HRM) was recently added to the armamentarium for the study of this area. This study aims to describe HRM findings in patients with vagal paralysis. Sixteen patients (mean age 54 years, 69% females) with oropharyngeal dysphagia due to unilateral vagal paralysis were prospectively studied. All patients underwent HRM. Motility of the UES and at the topography of the velopharynx and epiglottis were recorded. (1) UES relaxation is compromised in a minority of patients, (2) epiglottis pressure does not follow a specific pattern, (3) vellum is hypotonic in half of the patients, (4) dysphagia is related to a low pharyngeal pressure, not to a flow obstruction at the level of the UES, and (5) aspiration is related to low pressures at the level of the UES and epiglottis and higher pressures at the level of the vellum. Pharyngeal motility is significantly impaired in patients with oropharyngeal dysphagia and unilateral vagal paralysis. In half of the cases, UES resting pressure is preserved due to unilateral innervation and relaxation is normal in most patients. Dysphagia therapy in these patients must be directed toward improvement in the oropharyngeal motility not at the UES.


Reminiscing psychotherapy with aging people.
Reminiscing is the process of remembering one's past, either verbally or internally. Time and the individual's selective processes influence what it remembered and how the memories are evoked. Although reminiscing starts around age 10 and persists throughout life, when aging people reflect on the past the behavior often is regarded as a sign of increasing mental deterioration. Some older people avoid reflecting on the past to prevent being labeled "senile." However, some clinical investigators have found reminiscing beneficial. In 1963 Butler wrote that the elderly psychiatric patients he observed engaged spontaneously in reminiscing and what he termed the "life review." He assumed the life review to be a normal, developmental phenomenon triggered by the person's realization of impending personal death. Potential benefits included resolution of old conflicts, personality reorganization, and restoration of meaning in the individual's life. Studying reminiscenses of aging persons who came from various settings, clinical investigators examined Butler's original ideas and noted other findings. Descriptions of the memories of older people without psychiatric illness demonstrate that some reminiscing is simple story-telling and glorification of the past in addition to life review. However, most investigators believed that remembering the past helped aging people personally and socially. Relationships between the content of memories and present conflicts were explored, and individual and group therapeutic approaches with aging people were designed to encourage reminiscing. Reminiscence provides unique opportunities for clients and therapists to have positive growth experiences.


Disordered metabolism of microfilament proteins, tropomyosin and actin, in mouse mammary epithelial cells expressing the Ha-ras oncogene.
Synthesis of 37- and 41-kD tropomyosins (TM) is suppressed in fibroblasts expressing transforming oncogenes, which may contribute to the deranged microfilament structure seen in such cells (Cooper et al., Mol. Cell. Biol. 5, 972, 1985). To determine whether TM metabolism was also deranged when epithelial cells expressed a transforming oncogene, we studied cultured mouse mammary epithelial cells which express the activated c-Ha-ras oncogene either constitutively or through glucocorticoid activation of the oncogene linked to a mouse mammary tumor virus (MMTV) promoter. The epithelial cells expressed three major TM species, one at 37 kD and two at 35 kD, but lacked expression of a 41 kD TM typically found in fibroblasts. In oncogene-expressing cells synthesis of the 37 kD TM was not suppressed but synthesis of actin was increased 2-fold. Actin entered the cytoskeleton (CSK) normally, but TM accumulated in the CSK with a 50% reduction from normal in TM:actin ratio. Thus, in both epithelial cells and fibroblasts expressing transforming ras oncogenes, the metabolism of TM and actin is disordered so as to produce TM-deficient cytoskeletal structures which may be functionally or structurally defective. However, the result is achieved by different effects on metabolism of these proteins in the two cell types, suggesting that cellular responses to oncogene actions may be conditioned by the state of cell differentiation.


Structural diversity in proline-based lead bromide chiral perovskites.
Lead halide hybrid perovskites incorporating chiral organic cations attract considerable attention due to their promising application in multifarious optoelectronic devices. However, the examples of chiral hybrid perovskites are still limited, which greatly impedes their further studies in various optoelectronic fields. Herein, we report on new low-dimensional lead-halide hybrid perovskites incorporating the enantiopure chiral α-amino acid L-proline. Two hybrid perovskites (L-proH)PbBr3·H2O (Pro-PbBr3) and (L-proH)4Pb3Br10·4H2O (Pro-Pb3Br10) have been synthesized by employing different ratios of organic and inorganic precursors. According to structural analysis, the inorganic sublattice of compound Pro-PbBr3 is built of one-dimensional (1D) [PbX3]∞n- lead halide chains, whereas the inorganic sublattice of compound Pro-Pb3Br10 is built upon a rare two-dimensional (2D) [Pb3Br10]∞4n- honeycomb-type inorganic framework. Hirshfeld surface analysis revealed an important role of various hydrogen bonding interactions in providing the binding between organic and inorganic parts of these hybrid perovskites. The optical band gap values of new hybrid perovskites as estimated using the Tauc plot approach are 4.19 eV (Pro-PbBr3) and 4.13 eV (Pro-Pb3Br10). Also, new compounds display low-temperature broadband photoluminescence which can be attributed to the self-trapped excitons. These results show the potential of α-proline for constructing novel and highly demanded chiral hybrid perovskites, which will hold great promise for further optoelectronic applications.


Treating hearing disorders with cell and gene therapy.
Hearing loss is an increasing problem for a substantial number of people and, with an aging population, the incidence and severity of hearing loss will become more significant over time. There are very few therapies currently available to treat hearing loss, and so the development of new therapeutic strategies for hearing impaired individuals is of paramount importance to address this unmet clinical need. Most forms of hearing loss are progressive in nature and therefore an opportunity exists to develop novel therapeutic approaches to slow or halt hearing loss progression, or even repair or replace lost hearing function. Numerous emerging technologies have potential as therapeutic options. This paper details the potential of cell- and gene-based therapies to provide therapeutic agents to protect sensory and neural cells from various insults known to cause hearing loss; explores the potential of replacing lost sensory and nerve cells using gene and stem cell therapy; and describes the considerations for clinical translation and the challenges that need to be overcome.


Influence of various cytokines on adhesion and migration of the colorectal adenocarcinoma cell line HRT-18.
The stroma of colorectal adenocarcinoma contains both abundant extracellular matrix (ECM) and an inflammatory cell infiltrate. The latter is the source of various cytokines, present in different concentrations in the tumor cell microenvironment. The aim of the present study was to investigate whether cytokines act as motility factors for HRT-18 rectal carcinoma cells and if this effect depends on the ECM. The main result of our study is that cytokines affect tumor cell motility in a matrix-dependent manner, and that stimulatory and inhibitory effects may depend on the composition of the ECM. Hepatocyte growth factor/scatter factor was the strongest migration factor for HRT-18 cells independent of the ECM. On the other hand, IL-6 was a strong migration stimulator for cells on Tenascin-C but was inhibitory on collagen type V. Therefore, different degrees of invasiveness at the tumor-host interface are not necessarily related to specific genetic alterations but might be related to different environmental conditions as well.


Early conversion of classic Fontan conversion may decrease term morbidity: single centre outcomes.
The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts. A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion. A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure. Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.


Super enhanced permeability and retention (SUPR) effects in tumors following near infrared photoimmunotherapy.
To date, the delivery of nano-sized therapeutic agents to cancers largely relies on enhanced permeability and retention (EPR) effects that are caused by the leaky nature of cancer vasculature. However, nano-sized agents delivered in this way have demonstrated limited success in oncology due to the relatively small magnitude of the EPR effect. For achieving superior delivery of nano-sized agents, super-enhanced permeability and retention (SUPR) effects are needed. Near infrared photo-immunotherapy (NIR-PIT) is a recently reported therapy that treats tumors with light therapy and subsequently causes an increase in nano-drug delivery up to 24-fold compared with untreated tumors in which only the EPR effect is present. SUPR effects could enhance delivery into tumor beds of a wide variety of nano-sized agents including particles, antibodies, and protein binding small molecular agents. Therefore, taking advantage of the SUPR effects after NIR-PIT may be a promising avenue to utilize a wide variety of nano-drugs in a highly effective manner.


The prognosis of NX stage differentiated thyroid cancer based on propensity score matching and SEER data.
Few studies have evaluated the prognosis or treatment of patients with differentiated thyroid cancer (DTC) according to their NX status. This study investigated this issue to provide a new perspective regarding the treatment guidelines for these patients. Data from 92,447 patients with DTC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2013). Survival outcomes were evaluated using Kaplan-Meier analyses with the log-rank test and Cox proportional hazards regression analysis. The rates of cancer-specific mortality and all-cause mortality (per 1,000 person-years) were significantly higher for patients with NX disease, compared to patients with N0 or N1 disease. Multivariate Cox regression modeling revealed that NX stage was an independent risk factor for cancer-specific mortality compared to N1 stage, but not to N0 stage. Similar results were observed for all-cause mortality. After adjustment using propensity score matching, the cancer-specific and all-cause mortality rates were lower for NX stage compared to N0 stage, whereas no significant difference was observed when comparing the NX stage and N1 stage groups. The unexpectedly poor prognosis of patients with NX stage DTC provides new information that may be relevant for treating these patients.


The Epidemiology of Substance Use Disorders among the Adult Jewish Population in Israel.
Substance use disorders (SUDs) are a leading cause of morbidity and mortality worldwide, having a profound and global impact on health, well-being, safety, and productivity. Although traditionally the prevalence of SUDs in Israel has been estimated to be lower than those in high-income countries, estimates and characteristics of individuals with SUDs in the past decade are lacking. In this work, we explored the prevalence of SUDs among the adult Jewish population in Israel, per different classes of substances across sex, age group, and other sociodemographic factors. Data from an online representative sample of 4,025 respondents were collected, including the alcohol, smoking, and substance involvement screening test (ASSIST) metric and sociodemographic data. We found that the most common SUDs were alcohol (10.5% [9.5-11.4]), cannabis (9.0% [8.2-9.9]), and sedative (3.6% [3.0-4.2]) use disorders. Alcohol-cannabis (3.2% [2.7-3.7]) and alcohol-sedative (1.04% [0.7-1.35]) were the most prevalent co-occurring SUDs. Among those with cannabis use disorder, the prevalence of alcohol use disorder was found to be 35.3% [30.4-40.2]. The estimated risk for alcohol use disorder was found to be inversely proportional to age, cannabis use disorder increased, peaked, and decreased with age, and that of sedative use disorder increased with age, particularly among women. While older individuals (in the 51-60 years of age group) were at lower risk (OR = 0.5 [0.3, 0.8]) compared to those <20 years of age for alcohol use disorder, they were at increased risk for sedative use disorder (OR = 3.1 [1.2, 9.7]). These findings represent substantially higher rates of SUDs in Israel than those previously reported and should affect resources allocated to addiction prevention and treatment. Further research on the role of gender, age, culture, and ethnicity in the propensity to develop SUDs is necessary for the development of more focused preventive and intervention measures. Focusing on non-Jewish populations in Israel and broadening the scope to include behavioral addictions should be addressed in future studies.


Estimating willingness-to-pay for health care: A discrete choice experiment accounting for non-attendance to the cost attribute.
The literature suggests that discrete choice experiments (DCEs) are a preferable method for estimating willingness-to-pay (WTP) values, as they may avoid some biases often observed in contingent valuation surveys, such as protest and strategic behaviour. However, the choice studies have demonstrated that attribute non-attendance may be a serious issue that leads to biased WTP estimates. A DCE was used to estimate patients' WTP for dental care at the dental school clinic. The endogenous attribute attendance (EAA) model was used to estimate WTP for dental care attributes, while accounting for non-attendance to the cost attribute. The EAA model revealed that almost every second respondent had ignored the cost attribute when making choices, indicating that patients were very sensitive to other characteristics of dental care. Dental care providers should pay particular attention to providing a detailed explanation of treatment to their patients, as this was the most valued attribute of dental care. The welfare estimates from the EAA model, which accounted for non-attendance to the cost attribute, were more than two times lower than welfare estimates from a traditional multinomial logit model and mixed logit model estimated in WTP space. The findings raise concerns for derived WTP estimates in DCE studies that did not consider non-attendance to the cost attribute during the estimation process. Non-attendance to the cost attribute overestimates WTP values, even if being motivated by the true preferences of respondents.


An insight into methanol oxidation mechanisms on RuO2(100) under an aqueous environment by DFT calculations.
In this work, we have studied methanol oxidation mechanisms on RuO2(100) by using density functional theory (DFT) calculations and ab initio molecular dynamics (MD) simulations with some explicit interfacial water molecules. The overall mechanisms are identified as: CH3OH* → CH3O* → HCHO* → HCH(OH)2* → HCHOOH* → HCOOH* → mono-HCOO* → CO2*, without CO formation. This study provides a theoretical insight into C1 molecule oxidation mechanisms at atomic levels on metal oxide surfaces under an aqueous environment.


Field-Tunable One-Sided Higher-Order Topological Hinge States in Dirac Semimetals.
Recently, higher-order topological matter and 3D quantum Hall effects have attracted a great amount of attention. The Fermi-arc mechanism of the 3D quantum Hall effect proposed to exist in Weyl semimetals is characterized by the one-sided hinge states, which do not exist in all the previous quantum Hall systems, and more importantly, pose a realistic example of the higher-order topological matter. The experimental effort so far is in the Dirac semimetal Cd_{3}As_{2}, where, however, time-reversal symmetry leads to hinge states on both sides of the top and bottom surfaces, instead of the aspired one-sided hinge states. We propose that under a tilted magnetic field, the hinge states in Cd_{3}As_{2}-like Dirac semimetals can be one sided, highly tunable by field direction and Fermi energy, and robust against weak disorder. Furthermore, we propose a scanning tunneling Hall measurement to detect the one-sided hinge states. Our results will be insightful for exploring not only the quantum Hall effects beyond two dimensions, but also other higher-order topological insulators in the future.


High expression of galectin-7 associates with poor overall survival in patients with non-metastatic clear-cell renal cell carcinoma.
Galectin-7, has a controversial role in tumor progression, can either suppress tumor growth or induce chemoresistance depends on different tumor histology types. The aim was to appraise Galectin-7 expression on the overall survival (OS) of patients with non-metastatic clear cell renal cell carcinoma (ccRCC) following surgery. High galectin-7 expression was specifically correlated with necrosis (P = 0.015). Multivariate analysis confirmed galectin-7 as an independent prognosticator for OS (P = 0.005). High galectin-7 expression suggested poor OS (P < 0.001), particularly with UISS intermediate and high score groups. Notably, the predictive accuracy of the traditional prognostic scores was improved when combined with galectin-7 expression. We retrospectively enrolled 416 patients who underwent nephrectomy at a single institute between 2008 and 2009 and detected their intratumor galectin-7 expression by immunohistochemistry. Kaplan-Meier method was conducted to plot survival curves and multivariate cox regression analysis for potential independent prognostic factors on OS. A nomogram was constructed with concordance index (C-index) and Akaike's Information Criteria (AIC) to appraise prognostic accuracy of different models. High galectin-7 expression is an independent adverse predictor for survival. Evaluation of galectin-7 could help guide postsurgical management for non-metastatic ccRCC patients.


Patient-specific MRI-based 3D FSI RV/LV/patch models for pulmonary valve replacement surgery and patch optimization.
A patient-specific right/left ventricle and patch (RV/LV/patch) combination model with fluid-structure interactions (FSIs) was introduced to evaluate and optimize human pulmonary valve replacement/insertion (PVR) surgical procedure and patch design. Cardiac magnetic resonance (CMR) imaging studies were performed to acquire ventricle geometry, flow velocity, and flow rate for healthy volunteers and patients needing RV remodeling and PVR before and after scheduled surgeries. CMR-based RV/LV/patch FSI models were constructed to perform mechanical analysis and assess RV cardiac functions. Both pre- and postoperation CMR data were used to adjust and validate the model so that predicted RV volumes reached good agreement with CMR measurements (error <3%). Two RV/LV/patch models were made based on preoperation data to evaluate and compare two PVR surgical procedures: (i) conventional patch with little or no scar tissue trimming, and (ii) small patch with aggressive scar trimming and RV volume reduction. Our modeling results indicated that (a) patient-specific CMR-based computational modeling can provide accurate assessment of RV cardiac functions, and (b) PVR with a smaller patch and more aggressive scar removal led to reduced stress/strain conditions in the patch area and may lead to improved recovery of RV functions. More patient studies are needed to validate our findings.