[Perception of illness and dispositional optimism in a sample of patients with chronic heart failure].
INTRODUCTION. Psychological research on Chronic Heart Failure has mainly focused on the patient's emotional status, particularly on anxiety and depression. To describe the psychological characteristics of a sample of hospitalized CHF inpatients and to assess their illness perception and their dispositional optimism and pessimism, and the mutual relations among these variables. 77 CHF inpatients of a Department of Cardiovascular Rehabilitation (aged 57.4 +/- 10.0) were consecutively enrolled. The following psychological constructs were assessed: anxiety (HADS-A), depression (BDI-II: total score, Cognitive and Affective Factors), illness perception (Brief IPQ) and dispositional optimism and pessimism (LOT-R). Correlations between Brief IPQ and LOT-R data were calculated and subsequently ANOVAs were performed on Brief IPQ and LOT-R data divided by sex, anxiety and depression. RESULTS. As to anxiety, 57 (74.0%) patients resulted not anxious, whereas 10 (13.0%) reported light anxious symptomatology, 8 (10.4%) moderate and 2 (2.6%) severe. Thirty nine patients (50.7%) resulted not depressed, whereas 19 (24.7%) resulted severely depressed. Significant correlations emerged among dispositional pessimism (LOT-R) and the following Brief IPQ variables: Treatment Control (r = - 0.40 p < 0.0001) and Coherence (r = -0.35 p = 0.002). Anxiety and depression differentiated the sample considering illness perception but not dispositional optimism and pessimism. CONCLUSIONS. As to anxiety and depression our data enlighten the presence of emotional disorders in CHF patients. Moreover illness perception differentiates the sample when analysed considering the emotional status. Interesting are the relationships among illness representations and dispositional pessimism, which deserve further studies. In our sample pessimism seems not to be opposed, in a bipolar construct, to optimism and results not related to depression; besides pessimism might have a predictive role in patient's disease management in a not yet explored direction. Finally our data confirm what usually qualitatively observed in clinical practice during the psychological intervention in rehabilitation cardiology. They also provide scientific information on the utility of an accurate psychological screening and a consequent specific intervention aimed at both providing psychological support and cognitive restructuring.


Potential communicative acts in children with autism spectrum disorders.
To describe potential communicative acts in a sample of 17 children with autism spectrum disorders who produced few to no intelligible words (mean age = 32.82 months). Parents reported on children's potential communicative acts for 10 different communicative functions. A potential communicative act was defined as any behavior produced by an individual that may be interpreted by others to serve a communicative purpose. Significant associations were found between higher number of gesture types and increased scores on language comprehension, language expression, and non-verbal thinking measures. Relative to other types of potential communicative acts, parents reported that children used higher proportions of body movement. Number of body movement types was not related to child ability, while number of gesture types was related to receptive and expressive language. Findings underscore the link between language and gesture, and offer support for an ecological systems perspective of language learning.


Purification and characterization of windmill palm tree (Trachycarpus fortunei) peroxidase.
High peroxidase activity was demonstrated to be present in the leaf of several species of cold-resistant palms. Histochemical studies of the leaf of windmill palm tree (Trachycarpus fortunei) showed the peroxidase activity to be localized in hypoderma, epidermis, cell walls, and conducting bundles. However, chlorophyll-containing mesophyll cells had no peroxidase at all. The leaf windmill palm tree peroxidase (WPTP) was purified to homogeneity and had a specific activity of 6230 units/mg, RZ = 3.0, a molecular mass of 50 kDa, and an isoelectric point of pI 3.5. The electronic spectrum of WPTP with a Soret band at 403 nm was typical of plant peroxidases. The N-terminal amino acid sequence of WPTP was determined. The substrate specificity of WPTP was distinct from that of other palm peroxidases, and the best substrate for WPTP was 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid). The palm peroxidase showed an unusually high stability at elevated temperatures and high concentrations of guanidine.


Hyperspectral Image Super-Resolution via Knowledge-Driven Deep Unrolling and Transformer Embedded Convolutional Recurrent Neural Network.
Hyperspectral (HS) imaging has been widely used in various real application problems. However, due to the hardware limitations, the obtained HS images usually have low spatial resolution, which could obviously degrade their performance. Through fusing a low spatial resolution HS image with a high spatial resolution auxiliary image (e.g., multispectral, RGB or panchromatic image), the so-called HS image fusion has underpinned much of recent progress in enhancing the spatial resolution of HS image. Nonetheless, a corresponding well registered auxiliary image cannot always be available in some real situations. To remedy this issue, we propose in this paper a newly single HS image super-resolution method based on a novel knowledge-driven deep unrolling technique. Precisely, we first propose a maximum a posterior based energy model with implicit priors, which can be solved by alternating optimization to determine an elementary iteration mechanism. We then unroll such iteration mechanism with an ingenious Transformer embedded convolutional recurrent neural network in which two structural designs are integrated. That is, the vision Transformer and 3D convolution learn the implicit spatial-spectral priors, and the recurrent hidden connections over iterations model the recurrence of the iterative reconstruction stages. Thus, an effective knowledge-driven, end-to-end and data-dependent HS image super-resolution framework can be successfully attained. Extensive experiments on three HS image datasets demonstrate the superiority of the proposed method over several state-of-the-art HS image super-resolution methods.


Intestinal inflammation modulates expression of the synaptic vesicle protein neuronal calcium sensor-1.
The calcium-binding protein neuronal calcium sensor 1 (NCS-1) is involved in modulation of neurotransmitter release in the peripheral and central nervous systems. Since intestinal inflammation impairs neurotransmitter release, we evaluated the expression of NCS-1 in the normal rat colon and in dinitrobenzene sulfonic acid (DNBS)-induced colitis. Immunocytochemistry and Western blots showed high levels of NCS-1 in the myenteric plexus and in axons in the smooth muscle layers; 23 +/- 2% of myenteric neurons were NCS-1 positive, with staining restricted to the largest neurons. NCS-1-positive axons decreased to 13.3 +/- 0.4% of total axons by day 2 and dropped further to 7.0 +/- 0.1% by day 4, returning to control levels by day 16. Dual-label Western blot analysis showed that the expression of NCS-1 relative to PGP 9.5 decreased by 50% on day 4 but returned to control by day 16. The selective loss of NCS-1 during colitis may underlie the altered neural function seen in the inflamed intestine.


Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas.
This study analyzed gene expression patterns and global genomic alterations in hepatocellular carcinomas (HCC), hepatoblastomas (HPBL), tissue adjacent to HCC and normal liver tissue derived from normal livers and hepatic resections. We found that HCC and adjacent non-neoplastic cirrhotic tissue have considerable overlap in gene expression patterns compared to normal liver. Several genes including Glypican 3, spondin-2, PEG10, EDIL3 and Osteopontin are over-expressed in HCC vs. adjacent tissue whereas Ficolin 3 is the most consistently under-expressed gene. HCC can be subdivided into three clusters based on gene expression patterns. HCC and HPBL have clearly different patterns of gene expression, with genes IGF2, Fibronectin, DLK1, TGFb1, MALAT1 and MIG6 being over-expressed in HPBL versus HCC. In addition, specific areas of the genome appear unstable in HCC, with the same regions undergoing either deletion or increased gene dosage in all HCC. In conclusion, a set of specific genes and areas of genomic instability are found across the board in liver neoplasia.


Perspectives on a US-Mexico Border Community's Diabetes and "Health-Care" Access Mobilization Efforts and Comparative Analysis of Community Health Needs over 12 Years.
This paper describes a community coalition-university partnership to address health needs in an underserved US-Mexico border, community. For approximately 15 years, this coalition engaged in community-based participatory research with community organizations, state/local health departments, and the state's only accredited college of public health. Notable efforts include the systematic collection of health-relevant data 12 years apart and data that spawned numerous health promotion activities. The latter includes specific evidence-based chronic disease-preventive interventions, including one that is now disseminated and replicated in Latino communities in the US and Mexico, and policy-level changes. Survey data to evaluate changes in a range of health problems and needs, with a specific focus on those related to diabetes and access to health-care issues-identified early on in the coalition as critical health problems affecting the community-are presented. Next steps for this community and lessons learned that may be applicable to other communities are discussed.


Acquisition of cell adhesion and induction of focal adhesion kinase of human colon cancer Colo 201 cells by retinoic acid-induced differentiation.
The human colon adenocarcinoma cell lines Colo 201 and Colo 205 lose adhevise capacity to the extracellular matrix (ECM) and take on a round and floating cell shape. Treatment of these cells with all-trans-retinoic acid (RA) results in inhibition of growth and in a marked increase in the production of carcinoembryonic antigen, thereby indicating that the cells undergo differentiation. This RA-induced differentiation was accompanied by a large increase in the degree of cell adhesion with localization of E-cadherin molecules at cell-cell contact sites. We examined several adhesion molecules involved in cell-cell and cell-ECM interaction by immunoblotting, but no change in E-cadherin, intercellular adhesion molecule-1, or CD44 was observed in RA-treated Colo 201 cells. Although the adhesion of Colo 201 cells to ECM depends on the Arg-Gly-Asp sequence, levels of integrins, alpha 2, alpha 3, alpha 5, alpha V, and beta 1 in differentiated adherent cells were similar to those in untreated cells. In contrast to equivalent amounts of cell surface adhesion molecules before and after differentiation, intracellular focal adhesion kinase (FAK) was markedly induced during RA treatment, and the increase in FAK resulted in elevation of tyrosine-phosphorylated FAK. These findings suggest a role for FAK in activation of cell adhesion of RA-induced differentiation of these colon cancer cells. This may serve as an appropriate model to examine the mode of activation of the adhesive capacity of cancer cells.


Sensitivity of Nutrition Indicators to Measure the Impact of a Multi-Sectoral Intervention: Cross-Sectional, Household, and Individual Level Analysis.
Interventions tackling multiple drivers of child malnutrition have potential, yet the evidence is limited and draws on different analysis and nutrition outcomes, reducing comparability. To better understand the advantages and disadvantages of three different analytical approaches on seven common nutrition indicators, we use panel data (2012, 2014, 2015) on 1420 households from a randomized control study of a multi-sectoral intervention in Chad. We compare program impact using three types of analysis: a cross-sectional analysis of non-matched children; a panel analysis on longitudinal outcomes following the worst-off child in the household; and a panel analysis on longitudinal outcomes of matched children. We find that the sensitivity of the nutrition outcomes to program impact increases with each subsequent analytical approach, despite the reduction in sample size, as the analysis is able to control for more non-measured child and household characteristics. In the matched child panel analysis, the odds of a child being severely wasted were 76% lower (CI: 0.59-0.86, p = 0.001), the odds of being underweight were 33% lower (CI: 0.15-0.48, p = 0.012), and weight-for-height z-score was 0.19 standard deviations higher (CI: 0.09-0.28, p = 0.022) in the treatment versus control group. The study provides evidence for multi-sectoral interventions to tackle acute malnutrition and recommends the best practice analytical approach.


Prolegomena to any future code of ethics for bioethics.
If bioethicists, qua bioethicists, restrict themselves to the humble but honorable task of education and delimit their authority accordingly, they will be on solid ethical ground. Moreover, by adopting and professing this role, bioethicists should ensure that they will continue to be held in high regard by those who, suspicious of partisans and advocates, will turn to them for help, not for certainties and answers, to be sure, and certainly not for moral authority, but rather for a measure of clarity and distinctness in an increasingly complex world. What the bioethicist is rightfully authorized to do or say speaking-as-a-bioethicist is valuable enough and can make a difference.


Estrogen-dependent downregulation of hairy and enhancer of split homolog-1 gene expression in breast cancer cells is mediated via a 3' distal element.
Regulation of hairy and enhancer of split homologue-1 (HES-1) by estradiol and all-trans retinoic acid affects proliferation of human breast cancer cells. Here, we identify and characterize cis-regulatory elements involved in HES-1 regulation. In the distal 5' promoter of the HES-1 gene, we found a retinoic acid response element and in the distal 3' region, an estrogen receptor alpha(ER)alpha binding site. The ERalpha binding site, composed of an estrogen response element (ERE) and an ERE half-site, is important for both ERalpha binding and transcriptional regulation. Chromatin immunoprecipitation assays revealed that ERalpha is recruited to the ERE and associates with the HES-1 promoter. We also show recruitment of nuclear receptor co-regulators to the ERE in response to estradiol, followed by a decrease in histone acetylation and RNA polymerase II docking in the HES-1 promoter region. Our findings are consistent with a novel type of repressive estrogen response element in the distal 3' region of the HES-1 gene.


Taking care of patients--does it matter whether the physician is a woman?
Researchers have recently begun to compare male and female physicians' attitudes toward patients, medical knowledge, and practice styles. Although women start medical school with more "humanistic views," the conservative effect of medical socialization on both male and female students attenuates these differences. While some studies suggested that men are more scientifically knowledgeable, recent studies showed no significant differences in physicians' medical knowledge. Male and female physicians also had comparable diagnostic and therapeutic behavior. In the intimate world of physicians and patients, however, there were notable differences. Women physicians seemed better able to communicate sensitivity and caring to patients, which may account for the common perception that women are more caring and empathic physicians. Medical educators may wish to study more closely female physicians' communication styles to identify these behaviors and inculcate them into all physicians.


The importance of search strategy for finding targets in open terrain.
A number of real-world search tasks (i.e. police search, detection of improvised explosive devices (IEDs)) require searchers to search exhaustively across open ground. In the present study, we simulated this problem by asking individuals (Experiments 1a and 1b) and dyads (Experiment 2) to search for coin targets pseudo-randomly located in a bounded area of open grassland terrain. In Experiment 1a, accuracy, search time, and the route used to search an area were measured. Participants tended to use an 'S'-shaped pattern with a common width of search lane. Increased accuracy was associated with slower, but also variable, search speed, though only when participants moved along the length (as opposed to across the width) of the search area. Experiment 1b varied the number of targets available within the bounded search area and in doing so varied target prevalence and density. The results confirmed that the route taken in Experiment 1a generalizes across variations in target prevalence/density. In Experiment 2, accuracy, search time, and the search strategy used by dyads was measured. While dyads were more accurate than individuals, dyads that opted to conduct two independent searches were more accurate than those who opted to split the search space. The implications of these results for individuals and dyads when searching for targets in open space are discussed.


An emission inventory of marine vessels in Shanghai in 2003.
We developed an air pollutant emission inventory for marine vessels in the Shanghai Port in 2003. We estimated emissions under cruising and maneuvering conditions based on two categories of vessels: (1) vessels in the Outer Port, which enter the area following notification of the Shanghai Maritime Safety Administration, a division of the Ministry of Communications of P.R. China; and (2) vessels in internal waterways, which enter those waters following notification of the local Port Administration Centers. Vessels in the Outer Port consist of three subcategories: (1) international vessels that are engaged in foreign commerce; (2) domestic vessels traveling along the downstream portion of the Huangpu River; and (3) domestic vessels traveling along the coast. We also estimate emissions from vessels over 1000 DWT operating under hotelling conditions in the Outer Port. In 2003, the total number of calls was approximately 1.3 million, of which 57% is attributed to vessels in internal waterways and 43% to vessels in the Outer Port. Total marine emissions for NOx, SO2, PM, HC, and CO2 in 2003 are estimated to be 58,160, 51,180, 6960, 4560, and 3,012,800 tons, respectively. Emissions are allocated to 1 km x 1 km grid cells for the 129 km x 102 km Shanghai Port study domain.


Effect of Contract Compliance Rate to a Fourth-Generation Telehealth Program on the Risk of Hospitalization in Patients With Chronic Kidney Disease: Retrospective Cohort Study.
Chronic kidney disease (CKD) is prevalent in Taiwan and it is associated with high all-cause mortality. We have shown in a previous paper that a fourth-generation telehealth program is associated with lower all-cause mortality compared to usual care with a hazard ratio of 0.866 (95% CI 0.837-0.896). This study aimed to evaluate the effect of renal function status on hospitalization among patients receiving this program and to evaluate the relationship between contract compliance rate to the program and risk of hospitalization in patients with CKD. We retrospectively analyzed 715 patients receiving the telehealth care program. Contract compliance rate was defined as the percentage of days covered by the telehealth service before hospitalization. Patients were stratified into three groups according to renal function status: (1) normal renal function, (2) CKD, or (3) end-stage renal disease (ESRD) and on maintenance dialysis. The outcome measurements were first cardiovascular and all-cause hospitalizations. The association between contract compliance rate, renal function status, and hospitalization risk was analyzed with a Cox proportional hazards model with time-dependent covariates. The median follow-up duration was 694 days (IQR 338-1163). Contract compliance rate had a triphasic relationship with cardiovascular and all-cause hospitalizations. Patients with low or very high contract compliance rates were associated with a higher risk of hospitalization. Patients with CKD or ESRD were also associated with a higher risk of hospitalization. Moreover, we observed a significant interaction between the effects of renal function status and contract compliance rate on the risk of hospitalization: patients with ESRD, who were on dialysis, had an increased risk of hospitalization at a lower contract compliance rate, compared with patients with normal renal function or CKD. Our study showed that there was a triphasic relationship between contract compliance rate to the telehealth program and risk of hospitalization. Renal function status was associated with risk of hospitalization among these patients, and there was a significant interaction with contract compliance rate.


[Genetics of colorectal cancer. Practical value].
The age and family history of colorectal cancer are the main risk factors for colorectal cancer. Taking into account the family history of colorectal cancer, the first degree relatives of a patient have a risk that increases to 2 or 3 as compared to general population. The genetic basis for colorectal cancer was recently investigated by complex segregation analysis. They favoured a dominant gene with a gene frequency of 6 :1000. These analyses represent the first step in order to localize the susceptibility genes that are responsible for the familial aggregation of colorectal cancer.


A simulation based large bus side slip and rollover threshold study in slope-curve section under adverse weathers.
To study the side slip and rollover threshold of large bus in slope-curve section under adverse weather, factors that affect the safety of large buses that run in slope-curve section, such as rain, snow, cross-wind environmental factors, and road geometry, were analyzed to obtain the friction coefficient of the road surface under different rainfall and snowfall intensities through field measurements and to determine the six-component force coefficient of wind that acts on large buses through wind tunnel tests. The force analysis of large bus in slope-curve section was carried out, and the mechanical equations of large bus under the limit conditions of sideslip and rollover in slope-curve section were established. TruckSim simulation test platform was used to establish a three-dimensional road model and large bus mechanical model at a design speed of 100 km/h. Input parameters, such as cross-wind speed and road friction coefficient, simulate the impact of wind-rain/snow coupling. Under the combined action of wind-rain/snow, the operation test of large bus in slope-curve section was carried out, and the key parameters and indicators of the sideslip and rollover of large bus in slope-curve section were outputted and analyzed. The sudden change point of lateral acceleration is the judging condition for sideslip of large bus in slope-curve section under different road friction coefficient (0.2-0.7), changing from 0.15m/s2 and stabilizing to 0.52 m/s2, and a 0N vertical reaction force of the inner tire is the critical judging condition for rollover under road friction coefficient0.8, and the operating speed thresholds were proposed under different road friction coefficient. This study is expected to provide theoretical support for the speed limit of large bus in slope-curve section under adverse weather.


BMP signaling mediates glioma stem cell quiescence and confers treatment resistance in glioblastoma.
Despite advances in therapy, glioblastoma remains an incurable disease with a dismal prognosis. Recent studies have implicated cancer stem cells within glioblastoma (glioma stem cells, GSCs) as mediators of therapeutic resistance and tumor progression. In this study, we investigated the role of the transforming growth factor-β (TGF-β) superfamily, which has been found to play an integral role in the maintenance of stem cell homeostasis within multiple stem cell systems, as a mediator of stem-like cells in glioblastoma. We find that BMP and TGF-β signaling define divergent molecular and functional identities in glioblastoma, and mark relatively quiescent and proliferative GSCs, respectively. Treatment of GSCs with BMP inhibits cell proliferation, but does not abrogate their stem-ness, as measured by self-renewal and tumorigencity. Further, BMP pathway activation confers relative resistance to radiation and temozolomide chemotherapy. Our findings define a quiescent cancer stem cell population in glioblastoma that may be a cellular reservoir for tumor recurrence following cytotoxic therapy.


Image analysis as a monitoring tool for activated sludge properties in lab-scale installations.
An important step in the battle against filamentous bulking is the development of a monitoring system for activated sludge properties. Therefore, a fully automatic image analysis method for recognizing and characterizing flocs and filaments in activated sludge images has been developed. This procedure has been subsequently used to monitor activated sludge properties in a lab-scale installation. The results of a 100-days experiment indicate that the image information correlates well with the evolution of standard settling properties, in this case the Sludge Volume Index. It is shown that, at the onset of severe filamentous bulking, there is an increase in total filament length on the one hand, and a significant change in floc shape on the other hand.


Comparative performance assessment of point-of-care testing devices for measuring glucose and ketones at the patient bedside.
Point-of-care (POC) testing devices for monitoring glucose and ketones can play a key role in the management of dysglycemia in hospitalized diabetes patients. The accuracy of glucose devices can be influenced by biochemical changes that commonly occur in critically ill hospital patients and by the medication prescribed. Little is known about the influence of these factors on ketone POC measurements. The aim of this study was to assess the analytical performance of POC hospital whole-blood glucose and ketone meters and the extent of glucose interference factors on the design and accuracy of ketone results. StatStrip glucose/ketone, Optium FreeStyle glucose/ketone, and Accu-Chek Performa glucose were also assessed and results compared to a central laboratory reference method. The analytical evaluation was performed according to Clinical and Laboratory Standards Institute (CLSI) protocols for precision, linearity, method comparison, and interference. The interferences assessed included acetoacetate, acetaminophen, ascorbic acid, galactose, maltose, uric acid, and sodium. The accuracies of both Optium ketone and glucose measurements were significantly influenced by varying levels of hematocrit and ascorbic acid. StatStrip ketone and glucose measurements were unaffected by the interferences tested with exception of ascorbic acid, which reduced the higher level ketone value. The accuracy of Accu-Chek glucose measurements was affected by hematocrit, by ascorbic acid, and significantly by galactose. The method correlation assessment indicated differences between the meters in compliance to ISO 15197 and CLSI 12-A3 performance criteria. Combined POC glucose/ketone methods are now available. The use of these devices in a hospital setting requires careful consideration with regard to the selection of instruments not sensitive to hematocrit variation and presence of interfering substances.


[Ergospirometry in the evaluation of cardiovascular drugs].
In the evaluation of drugs intended to alleviate symptomatology and to improve exercise capacity in congestive heart failure, various pathophysiologic mechanisms including impairment of cardiac output, oxygenation of blood, muscle blood flow, and muscle metabolism have to be considered. In various forms of acute and chronic heart failure these mechanisms contribute more or less to impaired oxygen uptake. In acute forms of heart failure pulmonary congestion and its effects on airway resistance and lung capacity might be the predominating mechanisms of symptoms, while in chronic heart failure impedement of muscle blood flow and metabolic changes, comparable with deconditioning, are additional pathomechanisms. The increase in cardiac output and in muscle blood flow provided by some positive inotropic agents and by vasodilators after acute administration is often paralleled by a decrease in arteriovenous oxygen difference and does not lead to an improvement of oxygen uptake. However, chronic therapy with some vasodilators can lead to improvement in oxygen uptake, either due to training effects or due to flow dependent or direct effects on muscle metabolism. In pulmonary congestion a decrease of elevated filling pressures can acutely lead to some improvement of exercise capacity. Furthermore, chronic decrease in filling pressures by administration of diuretics, nitrates, ACE-inhibitors or dopaminergic drugs leads to long-term improvement in oxygen uptake. By comparing hemodynamic effects of acute and chronic drug therapy in CHF with their effects on exercise capacity, the chronic decrease of filling pressures seems to be the major hemodynamic variable leading to improvement of exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)


Malignant mesothelioma following radiation therapy.
Studies of the growing population of long-term survivors of cancer have led to increased recognition of the neoplastic complications of therapy. The causes of secondary malignancies are probably multifactorial, but radiation therapy and chemotherapy have certainly been implicated in the development of posttherapy neoplasia. A case of pleural mesothelioma after successful radiation therapy for Hodgkin's disease is described with a review of radiation-associated mesotheliomas reported in the literature. In Hodgkin's disease, patients may receive radiation, chemotherapy, or combined treatment; the most common secondary malignancy is acute nonlymphocytic leukemia while sarcomas are the second most common solid tumors. Although mesothelioma is an uncommon sarcoma, its occurrence has been documented numerous times after exposure to diagnostic or therapeutic radiation.


Regulation of Energy Metabolism by Receptor Tyrosine Kinase Ligands.
Metabolic diseases, such as diabetes, obesity, and fatty liver disease, have now reached epidemic proportions. Receptor tyrosine kinases (RTKs) are a family of cell surface receptors responding to growth factors, hormones, and cytokines to mediate a diverse set of fundamental cellular and metabolic signaling pathways. These ligands signal by endocrine, paracrine, or autocrine means in peripheral organs and in the central nervous system to control cellular and tissue-specific metabolic processes. Interestingly, the expression of many RTKs and their ligands are controlled by changes in metabolic demand, for example, during starvation, feeding, or obesity. In addition, studies of RTKs and their ligands in regulating energy homeostasis have revealed unexpected diversity in the mechanisms of action and their specific metabolic functions. Our current understanding of the molecular, biochemical and genetic control of energy homeostasis by the endocrine RTK ligands insulin, FGF21 and FGF19 are now relatively well understood. In addition to these classical endocrine signals, non-endocrine ligands can govern local energy regulation, and the intriguing crosstalk between the RTK family and the TGFβ receptor family demonstrates a signaling network that diversifies metabolic process between tissues. Thus, there is a need to increase our molecular and mechanistic understanding of signal diversification of RTK actions in metabolic disease. Here we review the known and emerging molecular mechanisms of RTK signaling that regulate systemic glucose and lipid metabolism, as well as highlighting unexpected roles of non-classical RTK ligands that crosstalk with other receptor pathways.


Learning to endure: A qualitative examination of the protective factors of homeless transgender and gender expansive youth engaged in survival sex.
Background: Transgender and gender expansive (TGE) youth face a number of adversities that are associated with deleterious consequences, including mental health problems, substance misuse, suicide, and homelessness. However, there is evidence that TGE youth still demonstrate resilience under extraordinary conditions. Aims: Therefore, this study examined how TGE youth who are homeless and engaging in survival sex describe and understand the protective factors present in their lives. Methods: In-depth qualitative interviews were conducted with 57 TGE youth living in a large U.S. city. Participants were 17-26 years old (M = 19.88, SD = 1.55), and identified as transgender woman (53%), transgender man (16%), and other (32%; gender-queer, gender-fluid, androgynous, or non-binary). Youth identified as Black (40%), multiracial (35%), Latinx (16%), White (5%), and as another race (3%). Researchers conducted a secondary analysis of qualitative data using thematic analysis. Results: We identified three themes to capture youth's understanding of their protective factors: relying on oneself and others to avoid violence, accessing gender-affirming health and mental health care, and proactively maintaining sexual health. Participants described strategies for mitigating risk of harm while attempting to meet their basic needs. Additionally, they discussed the importance of having gender-affirming health and mental health services. Participants also expressed keen awareness of their sexual health risks and making calculated, often proactive decisions about their sexual health. Conclusion: The protective factors described by TGE youth reflect the unique ways in which hyper-marginalized youth must navigate their own survival and well-being, and align with literature suggesting resilience is not mutually exclusive from risk. By focusing on TGE youth, this research privileges the experiences of individuals historically underrepresented in research and encourages future research to incorporate these perspectives into policies and programs.


Mutant Tof11 alleles are highly accumulated in early planting-adaptable Japanese summer type soybeans.
To avoid crop failure because of climate change, soybean (Glycine max (L.) Merrill) cultivars adaptable to early planting are required in western Japan. Because current Japanese cultivars may not be adaptable, genetic resources with high early-planting adaptability, and their genetic information must be developed. In the present study, summer type (ST) soybeans developed for early planting were used as plant materials. We examined their phenological characteristics and short reproductive period as an indicator of early planting adaptability and performed genetic studies. Biparental quantitative trait loci (QTL) analysis of a representative ST cultivar revealed a principal QTL for the reproductive period duration on chromosome 11. The results of resequencing analysis suggested that circadian clock-related Tof11 (soybean orthologue of PRR3) is a candidate QTL. Additionally, all 25 early planting-adaptable germplasms evaluated in this study possessed mutant alleles in Tof11, whereas 15 conventional cultivars only had wild-type alleles. These results suggest that mutant alleles in Tof11 are important genetic factors in the high adaptability to early planting of these soybeans, and thus, these alleles were acquired and accumulated in the ST soybean population.


A never-before opportunity to strengthen investment and action on adolescent contraception, and what we must do to make full use of it.
Increasingly, the health and rights of adolescents are being recognized and prioritized on the global agenda. This presents us with a "never-before" opportunity to address adolescent contraception. This is timely, as there are enormous numbers of adolescents who are currently unable to obtain and use contraceptives. From research evidence and programmatic experience, it is clear that we need to do things differently to meet their needs/fulfil their rights. In this commentary, we call for action in several key areas to address adolescents' persistent inability to obtain and use contraceptives. We must move away from one-size-fits-all approaches, from a 'condoms-only' mind set, from separate services for adolescents, from ignoring the appeal of pharmacies and shops, and from one-off-training to make health workers adolescent friendly. Our efforts to expand access to quality contraceptive services to adolescents must be combined with efforts to build their desire and ability to use them, and to do so consistently. In order for these changes to be made, action must be taken on several levels. This includes the formulation of sound national policies and strategies, robust programme implementation with monitoring, regular programmatic reviews, and implementation research. Further, high-quality collection, analysis, and dissemination of data must underlie all of our efforts. As we move ahead, we must also recognize and draw lessons from positive examples of large scale and sustained programmes in countries that have led the way in increasing contraceptive use by adolescents. This unprecedented moment in history gives us a real opportunity to bring about transformational change, particularly when there is so much at stake.


A study of atrial and brain natriuretic peptides in tuberculous meningitis and acute encephalitis.
To report atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels in patients with tuberculous meningitis (TBM) and acute encephalitis syndrome (AES), and evaluate their relationship with hyponatraemia. Consecutive patients with TBM and AES were included in the study. Hyponatraemia was categorised as cerebral salt wasting (CSW), syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and a miscellaneous group based on clinical and laboratory criteria. Serum ANP and BNP levels were measured upon hospital admission, at the time of diagnosis of hyponatraemia and upon correction of hyponatraemia. Outcome at 3 months was assessed using the modified Rankin scale (mRS) as good (mRS 2) and poor (mRS >2). There were 67 patients with TBM and 77 with AES. Hyponatraemia was more common in TBM than in AES (65.7% vs. 27%, P < 0.01). Forty-one (63.1%) patients had CSW, 6 (9.2%) SIADH and 18 (27.7%) had miscellaneous causes of hyponatraemia. During hyponatraemia, ANP (180 ± 45 vs. 106 ± 32 pg/ml, P < 0.01) and BNP (263 ± 118 vs. 163 ± 91 pg/ml, P  0.01) levels were significantly increased compared with baseline, and remained high even after Na+ correction. ANP and BNP levels were increased during hyponatraemia and remained high even after correction of hyponatraemia in TBM and AES, especially in patients with CSW. However, ANP and BNP levels could not be used to differentiate CSW from SIADH.


Occurrence and clinical characteristics of occult hepatitis C virus infection in hemodialysis units at Ismailia, Egypt.
Occult hepatitis C infection is defined as the presence of hepatitis C virus RNA in peripheral blood mononuclear cells (PBMC) ± hepatocytes in the absence of HCV-RNA in serum. It has been a lot of debate and controversy in recent years and not discussed well. This issue has not been discussed or investigated in Egypt, especially in patients on hemodialysis in Ismailia. This study is the first one to investigate the prevalence of occult HCV infection in large populations of chronic hemodialysis (CHD) patients in Ismailia, Egypt. Our study is cross-sectional analytic and included 204 CHD patients; who are negative for HCV infection. Sensitive commercial real-time assay was used to detect HCV-RNA in PBMC. In our study, the presence of genomic HCV-RNA in PBMCs of all these patients was detected by real-time PCR. On the other hand, 22 patients on hemodialysis with an established diagnosis of chronic hepatitis C virus infection were included as a control group and examined by real-time PCR was used to evaluate HCV infection. Occult HCV infection is defined as the presence of HCV-RNA in PBMNCs in patients on chronic hemodialysis, and it was found in 14/204 (7%) of the patients. Patients who were on CHD for a longer time are susceptible to occult HCV infection, and their mean alanine aminotransferase levels are significantly higher during the last 3 months before study entry. In comparison, chronic HCV patients have elevated bilirubin, aspartate transferase and alanine transferase than occult HCV infection. The prevalence of occult HCV infection was 7% in our CHD patients. No available data are showing the virulence of this form of virus. However, further studies in other geographic populations with high HCV endemicity are needed to clarify the significance of occult HCV infection in these patient groups, in addition to test for the presence of negative antigenomic strand to confirm or disconfirm the reliability of occult HCV.


Level Versus Uphill Economy and Mechanical Responses in Elite Ultra-Trail Runners.
The purpose of this brief report was to examine the net oxygen cost, oxygen kinetics, and kinematics of level and uphill running in elite ultra-trail runners. Twelve top-level ultra-distance trail runners performed two 5-minute stages of treadmill running (level, 0%, men 15 km·h-1, women 13 km·h-1; and uphill, 12%, men 10 km·h-1, women 9 km·h-1). Gas exchanges were measured to obtain the net oxygen cost and assess oxygen kinetics. Additionally, running kinematics were recorded with inertial measurement unit motion sensors on the wrist, head, belt, and foot. Relationships resulted between level and uphill running regarding oxygen uptake, respiratory exchange ratio, net energy and oxygen cost, as well as oxygen kinetics parameters of amplitude and time delay of the primary phase, and time to reach V̇O2 steady state. Of interest, net oxygen cost demonstrated a significant correlation between level and uphill conditions (r=0.826, p<0.01). Kinematics parameters demonstrated relationships between level and uphill running as well (including contact time, aerial time, stride frequency, and stiffness; all p<0.01). This study indicated strong relationships between level and uphill values of net oxygen cost, the time constant of the primary phase of oxygen kinetics, and biomechanical parameters of contact and aerial time, stride frequency, and stiffness in elite mountain ultra-trail runners. These results show that these top-level athletes are specially trained for uphill locomotion at the expense of their level running performance and suggest that uphill running is of utmost importance for success in mountain ultra-trail races.


Identification of the SLAM Adapter Molecule EAT-2 as a Lupus-Susceptibility Gene That Acts through Impaired Negative Regulation of Dendritic Cell Signaling.
We showed previously that C57BL/6 congenic mice with an introgressed homozygous 70 cM (125.6 Mb) to 100 cM (179.8 Mb) interval on c1 from the lupus-prone New Zealand Black (NZB) mouse develop high titers of antinuclear Abs and severe glomerulonephritis. Using subcongenic mice, we found that a genetic locus in the 88-96 cM region was associated with altered dendritic cell (DC) function and synergized with T cell functional defects to promote expansion of pathogenic proinflammatory T cell subsets. In this article, we show that the promoter region of the NZB gene encoding the SLAM signaling pathway adapter molecule EWS-activated transcript 2 (EAT-2) is polymorphic, which results in an ∼ 70% reduction in EAT-2 in DC. Silencing of the EAT-2 gene in DC that lacked this polymorphism led to increased production of IL-12 and enhanced differentiation of T cells to a Th1 phenotype in T cell-DC cocultures, reproducing the phenotype observed for DC from congenic mice with the NZB c1 70-100 cM interval. SLAM signaling was shown to inhibit production of IL-12 by CD40L-activated DCs. Consistent with a role for EAT-2 in this inhibition, knockdown of EAT-2 resulted in increased production of IL-12 by CD40-stimulated DC. Assessment of downstream signaling following CD40 cross-linking in the presence or absence of SLAM cross-linking revealed that SLAM coengagement blocked activation of p38 MAPK and JNK signaling pathways in DC, which was reversed in DC with the NZB EAT-2 allele. We conclude that EAT-2 negatively regulates cytokine production in DC downstream of SLAM engagement and that a genetic polymorphism that disturbs this process promotes the development of lupus.


The Efficacy and Tolerability of the Clonidine Transdermal Patch in the Treatment for Children with Tic Disorders: A Prospective, Open, Single-Group, Self-Controlled Study.
To evaluate the efficacy and tolerability of a clonidine transdermal patch in the treatment of children with tic disorders (TD) and to establish a predictive model for patients. Forty-one patients who met the inclusion criteria entered into 12 weeks of prospective, open, single-group, self-controlled treatment with a clonidine transdermal patch. The Yale Global Tic Severity Scale (YGTSS) was employed before therapy (baseline) and at 4, 8, and 12 weeks after therapy. (1) The total effect rates of treatment with a clonidine transdermal patch were 29.27, 53.66, and 63.41% at 4, 8, and 12 weeks, respectively. Compared with the baseline, the differences were significant at three different observation periods. (2) Compared to the level of 25% reduction, there were significant decreases in the score-reducing rate of motor tic and total tic severities at 12 weeks. (3) If the disease course was ≤24 months and the motor tic score was <16 at the baseline, there was an effective rate of 100% for treatment with the clonidine transdermal patch. If the disease course was ≤24 months and the motor tic score was >16, there was an effective rate of 57.1%. If the disease course was >24 months and the clinical classification was chronic TD, there was an effective rate of 62.5%. If the disease course was >24 months and the clinical classification was Tourette's syndrome, 90% of the patients were invalid. (4) The main adverse events were rash, slight dizziness, and headache. (1) When patients were pretreated with a D2-dopamine receptor antagonist that was ineffective or not tolerated well, switching to a clonidine transdermal patch treatment was effective and safe. (2) A clonidine transdermal patch could be a first-line medication for mild and moderate TD cases that are characterized by motor tics.


Electroacupuncture Reduces Seizure Activity and Enhances GAD 67 and Glutamate Transporter Expression in Kainic Acid Induced Status Epilepticus in Infant Rats.
Status epilepticus (SE) is one of the most significant complications in pediatric neurology. Clinical studies have shown positive effects of electroacupuncture (EA) as a therapeutic alternative in the control of partial seizures and secondary generalized clonic seizures. EA promotes the release of neurotransmitters such as GABA and some opioids. The present study aimed to evaluate the anticonvulsive and neuromodulatory effects of Shui Gou DM26 (SG_DM26) acupuncture point electrostimulation on the expression of the glutamate decarboxylase 67 (GAD67) enzyme and the glutamate transporter EAAC1 in an early SE model. At ten postnatal days (10-PD), male rats weighing 22-26 g were divided into 16 groups, including control and treatment groups: Simple stimulation, electrostimulation, anticonvulsant drug treatment, and combined treatment-electrostimulation and pentobarbital (PB). SE was induced with kainic acid (KA), and the following parameters were measured: Motor behavior, and expression of GAD67 and EAAC1. The results suggest an antiepileptic effect derived from SG DM26 point EA. The possible mechanism is most likely the increased production of the inhibitory neurotransmitter GABA, which is observed as an increase in the expression of both GAD67 and EAAC1, as well as the potential synergy between the neuromodulator effects of EA and PB.


Rectal Carcinoid Tumor With Liver Metastases Treated by Local Excision and Orthotopic Liver Transplant With Long-term Follow-up.
In patients affected by unresectable liver metastases from neuroendocrine tumor, liver transplant represents currently the only realistic chance for cure. The first attempt to establish selection criteria for liver transplant in patients affected by neuroendocrine tumor liver metastases was made by Mazzaferro and associates in 2007. We report the case of a 46-year-old man who came to our institution in 2006 with right upper quadrant abdominal pain. Diagnosis of rectal neuroendocrine tumor with bilobar liver nodules was made; the patient underwent transanal local resection. A liver biopsy confirmed the metastatic nature of the hepatic lesion, showing a low-grade neuroendocrine tumor (G1, proliferation index Ki-67 <2%). The patient underwent 2 sessions of transarterial chemoembolization that resulted in stable disease. Afterward, the patient underwent a liver transplant, using the piggyback technique without a venous-venous bypass. His postoperative course was uneventful. The patient has been disease-free for 3 years. Posttransplant treatment has played a key role in increasing the overall survival of the patient and assuring him a good quality of life. He died 9 years (102 mo) after liver transplant.


Prostate Cancer Detection Rate with Koelis Fusion Biopsies versus Cognitive Biopsies: A Comparative Study.
Targeted fusion biopsies have led to an improved prostate cancer (PCa) detection rate (CDR). Our aim was to assess if device-assisted fusion biopsies are superior to cognitive ones in terms of CDR. The association between multiparametric MRI parameters and PCa was also evaluated. We retrospectively enrolled 50 patients who underwent transrectal biopsy with elastic fusion (Koelis; group KB, n = 25) or cognitive approach (group CB, n = 25). Targeted biopsies were done on targets, while a variable number of random biopsies were performed depending on the clinical case. The groups did not significantly differ in terms of age, prostate-specific antigen, prostate volume and previous biopsies. Mean number of random cores was significantly inferior in KB group (8.4 vs. 12.1) and mean number of targeted biopsies was significantly higher (3.6 vs. 2.6). CDR was higher in fusion biopsies (64 vs. 40%), with the gap becoming significant when considering CDR of MRI targets only (59 vs. 27%). The difference was marked for lesions ≤10 mm, where CDR was 52% in KB against 21% in CB group. According to our study, elastic fusion biopsies performed with Koelis achieve an increased per-patient and per-lesion CDR as compared to cognitive biopsies, especially in the case of lesions ≤10 mm.


Cloning, expression and purification of the α-carbonic anhydrase from the mantle of the Mediterranean mussel, Mytilus galloprovincialis.
We cloned, expressed, purified, and determined the kinetic constants of the recombinant α-carbonic anhydrase (rec-MgaCA) identified in the mantle tissue of the bivalve Mediterranean mussel, Mytilus galloprovincialis. In metazoans, the α-CA family is largely represented and plays a pivotal role in the deposition of calcium carbonate biominerals. Our results demonstrated that rec-MgaCA was a monomer with an apparent molecular weight of about 32 kDa. Moreover, the determined kinetic parameters for the CO2 hydration reaction were kcat = 4.2 × 105 s-1 and kcat/Km of 3.5 × 107 M-1 ×s-1. Curiously, the rec-MgaCA showed a very similar kinetic and acetazolamide inhibition features when compared to those of the native enzyme (MgaCA), which has a molecular weight of 50 kDa. Analysing the SDS-PAGE, the protonography, and the kinetic analysis performed on the native and recombinant enzyme, we hypothesised that probably the native MgaCA is a multidomain protein with a single CA domain at the N-terminus of the protein. This hypothesis is corroborated by the existence in mollusks of multidomain proteins with a hydratase activity. Among these proteins, nacrein is an example of α-CA multidomain proteins characterised by a single CA domain at the N-terminus part of the entire protein.


Compositional Streamline-Based Modeling of Polymer Flooding Including Rheology, Retention, and Salinity Variation.
The chemical enhanced oil recovery (CEOR) technology that is most used worldwide is polymer flooding due to its proven commercial success at field scale, maturity, and versatility to combine with other technologies. So, there has been an increasing interest in expanding its applicability to more unfavorable mobility ratio conditions and adverse environments (such as high-temperature, high-salinity carbonate reservoirs, pH-sensitive polymers, and formations with active clays). Therefore, a requirement for successful field application is to find the design parameters of the process that balance material requirements and oil recovery benefits in a cost-effective manner, which is usually done through reservoir modeling. Polymer flooding predictive tools normally require detailed information and are based on time-consuming field reservoir simulations. Thus, for effective project management, a quick and sound tool is needed to screen for polymer flooding applications without giving up key physical-chemical phenomena that govern the oil recovery. In this research, we developed a two-dimensional polymer flooding model based on the streamlines approach. This is an alternative to having a multidimensional practical tool thoroughly representing the physical and chemical behavior of polymer flooding by considering key phenomena such as rheology behavior (shear thinning and shear thickening), salinity variations, permeability reduction, and polymer adsorption. Previously published streamline multidimensional models for polymer flooding lack the integrated modeling of the above-mentioned key phenomena. Additionally, the models to represent rheology and retention phenomena in the proposed tool consider a more complete description than the present streamline-based simulators. For the construction of streamlines, we considered a black oil formulation to estimate the pressure and saturation 2D distribution by applying the implicit in pressure and explicit in saturation method, coupled with an explicit formulation for the 2D composition computation. For saturation-composition along the streamlines, the 1D practical tool incorporated represents the polymer flooding key phenomena. The numerical algorithm used by the streamline-based tool is supported by laboratory experiments for waterflooding in homogenous porous media, analytical results for waterflooding in heterogeneous media, polymer flooding field scale simulation cases, and a CMG-STARS model built as a reference for waterflooding in both media (homogenous and heterogeneous) and for polymer flooding. The practical tool developed contributes to simplifying the upscaling from laboratory observations to field applications with better fitted numerical simulation models and to determining favorable scenarios; thus, it could assist in understanding how key parameters affect oil recovery without performing time-consuming CEOR simulations.


New magnifying endoscopic classification for superficial esophageal squamous cell carcinoma.
To assess the accuracy of a new magnifying endoscopy (ME) classification for predicting depth of invasion of superficial esophageal squamous cell carcinoma (SESCC). This study included a total of 70 lesions in 69 patients with SESCC who underwent ME with narrow-band imaging (ME-NBI) before resection from August 2010 to July 2016. Accuracy of ME-NBI for predicting depth of invasion of SESCC was analyzed by using a new ME classification proposed by the Japan Esophageal Society (JES), and interobserver agreement was assessed. Overall accuracy of ME-NBI for estimating depth of invasion of SESCC was 78.6%. Sensitivity and specificity of type B1 for tumors limited to the epithelial layer (m1) or invading into the lamina propria (m2) were 71.4% and 100%, respectively. Sensitivity and specificity of type B2 for tumors invading into the muscularis mucosa (m3) or superficial submucosa (≤ 200 μm, sm1) were 94.4% and 73.1%, respectively, while those of type B3 for tumors invading into the deep submucosa (> 200 μm, sm2) were 75.0% and 97.8%, respectively. Interobserver agreement was excellent (κ = 0.86, 95%CI: 0.76-0.95). The recently developed JES ME classification is useful for predicting depth of invasion of SESCC, with reliable interobserver agreement.


[Intraurethral condyloma acuminatum: report of a case].
A 24-year-old male appeared with complaint of tumors at the urethral meatus. Cystourethroscopy showed multiple papillary lesions along the anterior urethra until 2 cm distance from the urethral meatus. Electrofulguration was performed on these tumors and condyloma acuminatum was verified by histopathological examination.


Impact of cell purification technique of autologous human adult stem cells on inflammatory reaction.
Adult stem cells have shown fantastic regenerative potential as the cellular components of biomaterial mediated tissue engineering. Realising the biomedical potential of human adult stem cells (hASCs) however will require delivery in an ultra- purified format, without competing cells which may mediate inflammation, fibrosis or tumorigenesis. Purifying ASCs involves exhuming cells from primary tissue using immunoaffinity; which isolates pure populations with the complication of retained immunoglobulin (Ig); the clinical impact of which is currently not known. One of the negative outcomes of retained surface Ig is exacerbation of inflammation by leucocyte Fc receptor (FcR) activation, with consequences ranging from inflammatory cytokine and ROS release to chronic inflammation. The balance of ROS within a tissue will impact the efficacy of a stem cell therapy as ROS play an important role in stem cell self renewal and differentiation. In this study we utilised a chemiluminescent monitoring technique based on a ROS excitable photoprotein Pholasin, to quantify leucocyte ROS production in response to xenogeneic and recombinant human Ig of varying class and isotype with applications in stem cell selection. We were able to demonstrate inter-class differences in leucocyte ROS response to Ig which also varied between donors. This study highlighted the potential for utilising this technique for personalisation of autologous ASC therapies. This would allow clinicians to perform a rapid pre-operative screen to maximise the probability for success of an ASC intervention based on cell isolation using an Ig most appropriate for a specific patient.


Effect of synthetic tachykinin analogues on airway microvascular leakage in rats and guinea-pigs: evidence for the involvement of NK-1 receptors.
1. The NK-1 selective agonists [beta-Ala4, Sar9]SP-(4-11) sulphone and [pGlu6, Pro9]SP-(6-11) dose-dependently increased vascular permeability in various segments of rat and guinea-pig tracheo-bronchial region, while the NK-2 ([Nle10]NKA-(4-10) and [beta-Ala8]NKA-(4-10)) or NK-3 ([MePhe7]NKB and [MePhe7]NKB-(4-10)) selective agonists were inactive. These findings provide evidence that the inflammatory response of the airway to intravenous tachykinins is exclusively mediated by the NK-1 receptor subtype. 2. Plasma protein extravasation induced by capsaicin was more intense in the caudal segments of the rat airways and paralleled the tissue concentration of substance P-like and calcitonin gene-related peptide-like immunoreactivity. The response to capsaicin was greatly reduced in rats pretreated with high dose of the toxin (655 mumol kg-1 s.c., 3 weeks before) and was smallest in the airway regions where the depletion of neuropeptides had been more severe. 3. The depletion of transmitters from capsaicin-sensitive nerves did not affect the inflammatory response of the airway to serotonin (500 nmol kg-1 i.v.), while increased responsiveness to a threshold dose (0.37 nmol kg-1 i.v.) of [beta-Ala4, Sar9]SP-(4-11) sulphone was observed. This finding gives preliminary evidence that, after depletion of transmitters from capsaicin-sensitive nerves, upregulation of NK-1 receptors may develop in rat trachea.


Prospective neurometric studies during the beginning of carbamazepine and phenytoin therapy.
We studied 23 epileptic outpatients to assess carbamazepine and phenytoin therapy effects on the peripheral nerve conduction velocity, the electromyogram, and the EEG background activity. Immediately before and 3, 5, 11, 22 months after beginning treatment with 300-800 mg carbamazepine or 200-400 mg phenytoin, the patients were examined with electroneuromyographic and quantified EEG tests. Carbamazepine, phenytoin, folate, and vitamin B12 serum concentration were simultaneously monitored. Clinical signs of intoxication or polyneuropathy were not observed. The mean serum concentrations were 29 mumol/l for carbamazepine and 43 mumol/l for phenytoin. There was little evidence that anticonvulsants' serum concentration at these levels are related to changes in the electroneuromyographic tests or the alpha rhythm.


Co-circulation of a novel phlebovirus and Massilia virus in sandflies, Portugal.
In Portugal, entomological surveys to detect phleboviruses in their natural vectors have not been performed so far. Thus, the aims of the present study were to detect, isolate and characterize phleboviruses in sandfly populations of Portugal. From May to October 2007-2008, 896 female sandflies were trapped in Arrábida region, located on the southwest coast of Portugal. Phlebovirus RNA was detected by using a pan-phlebovirus RT-PCR in 4 out of 34 Phlebotomus perniciosus pools. Direct sequencing of the amplicons showed that 2 samples exhibited 72 % nucleotide identity with Arbia virus, and two showed 96 % nucleotide identity with Massilia virus. The Arbia-like virus (named Alcube virus) was isolated in cell culture and complete genomic sequences of one Alcube and two Massila viruses were determined using next-generation sequencing technology. Phylogenetic analysis demonstrated that Alcube virus clustered with members of the Salehabad virus species complex. Within this clade, Alcube virus forms a monophyletic lineage with the Arbia, Salehabad and Adana viruses sharing a common ancestor. Arbia virus has been identified as the most closely related virus with 20-28 % nucleotide and 10-27 % amino acid divergences depending on the analysed segment. We have provided genetic evidence for the circulation of a novel phlebovirus species named Alcube virus in Ph. perniciosus and co-circulation of Massilia virus, in Arrábida region, southwest of Portugal. Further epidemiological investigations and surveillance for sandfly-borne phleboviruses in Portugal are needed to elucidate their medical importance.


[Fetal warfarin syndrome in twin pregnancy].
We describe a pair of twins, whose mother was being treated by oral anticoagulant drugs, as a result of having received mitral heart valve implantation in the past. The male twins monochorionic, monoamniotic--but one infant showed the features of fetal warfarin syndrome. In the study we discussed the pharmacogentetics and individual variation in the human metabolism during treatment with warfarin-perinatal growth and prevalence of congenital malformations. We analysed the threats to the fetus and mother, connected with administration of anticoagulant drugs.


[Epithelial migration following surgical obliteration of radical cavities].
We investigated whether the self-cleansing mechanism of the normal ear can be restored in operatively reconstructed open cavities. Dots of Indian ink placed on the drumhead were followed for up to 10 weeks. The epithelium migrates outwards, acting as a self-cleansing mechanism. Partial obliteration of open cavities is recommended in the light of other factors (acoustic phenomena, temperature protection of the inner ear).


The fine structure of "dividers" and "non-dividers" in phase II human glial cell cultures.
A method is described which allows a comparison in the transmission electron microscope (TEM) of cells with different remaining proliferative capacity from one and the same culture. The method takes advantage of a mini-cloning technique employing hapatotactic palladium islands in combination with micro-dissection and preparation for TEM of islands carrying various numbers of cells after 10 days in culture, when all miniclones have become density dependent growth inhibited. By means of this technique non-dividers were compared with miniclones of dividers composed of five to eight cells originating from single cells. Moreover, large, immotile cells without peripheral ruffling activity, known to be non-dividers, were compared with small, ruffling cells, known to be dividers, in the reflection-interference mode in sparse cultures of living cells, and in the TEM mode as whole cell preparations after critical point drying of cells cultured on formvar-coated, gold EM-grids. Non-dividers proved to contain a moderate number of residual bodies, well developed Golgi areas, and often branched or circular mitochondria; they were thinly spread over the substratum with many focal points of contact, and large areas of close apposition between cell and substratum.


Using Time-Driven Activity-Based Costing to Implement Change.
Academic medical libraries have responded to changes in technology, evolving professional roles, reduced budgets, and declining traditional services. Libraries that have taken a proactive role to change have seen their librarians emerge as collaborators and partners with faculty and researchers, while para-professional staff is increasingly overseeing traditional services. This article addresses shifting staff and schedules at a single-service-point information desk by using time-driven activity-based costing to determine the utilization of resources available to provide traditional library services. Opening hours and schedules were changed, allowing librarians to focus on patrons' information needs in their own environment.


[Alcohol-related mortality and premature death in Spain between 1999 and 2004].
To assess alcohol-related mortality and premature death in Spain between 1999 and 2004. The records of deaths according to cause of death were used, grouped by age, sex and 60 diagnostic categories. The number of deaths attributable to alcohol consumption according to sex and age group, the mortality percentages, rates per 100,000 inhabitants adjusted to the European population standard, and potential years of life lost (PYLL) per alcohol-related death up to the age of 70 were calculated. Alcohol-related mortality adjusted to the European population standard was 2.1%, decreasing from 1999 to 2004. Chronic causes, in general, accounted for 60% of alcohol-related mortality. Digestive system disorders, and in par ticular <<Liver cirrhosis, unspecified>>, among chronic disorders, were those conditions with the highest contributing rate. The 9.3% of all PYLL in Spain were attributable to alcohol consumption. Acute disorders (about 70% of the PYLL), were the causes that mainly contributed to premature death related to alcohol consumption, being unintentional accidents the main cause. Alcohol consumption is an important cause of death and premature death in Spain.


The transaortic approach for transcatheter aortic valve implantation: a valid alternative to the transapical access in patients with no peripheral vascular option. A single center experience.
Transcatheter aortic valve implantation (TAVI) in patients with poor peripheral vessels still remains problematic, as the transapical approach is not always feasible and is sometimes associated with myocardial damage, bleeding, post-procedural chest pain and pleural effusion. In order to address these issues, we adopted the recently introduced transaortic (TAo) approach. The purpose of this study was to evaluate the efficacy and safety of the TAo-TAVI approach using both the Sapien XT and the CoreValve according to VARC criteria. Of 492 patients (October 2006 to February 2012), TAo-TAVI was performed in 94 consecutive patients with unfavourable peripheral access between January 2011 and February 2012. Aortic root condition, valve anatomy and annulus size were carefully assessed by multidetector computed tomography (MDCT) for possible TAo-TAVI. The aorta was exposed through an inverted 'T' manubriotomy. After retrograde guidewire crossing of the aortic valve, sheath insertion allowed device positioning and deployment subsequent to balloon valvuloplasty. Mean age was 84.1 ± 5.4 years (67-96) and logistic EuroSCORE 17.6 ± 10.2%. The Sapien XT was used in 88.3% and the CoreValve in 11.7% of patients. Full sternotomy allowed concomitant complete off-pump revascularization (2-4 grafts) in 11 patients. Device success rate was 92.6%. Paravalvular leak ≥2/4 was observed in 7.4%. Conversion to open chest surgery was required in 5.3% (3 aortic dissections, 1 valve migration and 1 left main occlusion). Three cerebrovascular accidents (2 transient ischaemia and 1 delayed stroke) were noted. Transfusion ≥4 units was performed in 12 patients (12.8%). Intensive care unit (ICU) and total hospital stay were 4.9 ± 5.0 and 12.2 ± 6.2 days, respectively. Thirty-day mortality and combined safety endpoint were reported in 7.4 and 16.0%, respectively. The TAo approach for both Sapien XT and CoreValve implantation can be used with satisfactory clinical outcome and an acceptable risk. This access route could prove a valid alternative to the transapical approach.


Urinary sediment ICAM-1 level in lupus nephritis.
Urinary intercellular adhesion molecule-1 (ICAM-1) level is potentially a valuable biomarker of lupus nephritis (LN), but because ICAM-1 is a cell-surface molecule, soluble ICAM-1 level in urinary supernatant measured by ELISA may not be biologically relevant. The ICAM-1 level in urine sediment of 12 LN patients, 10 patients with pauci-immune necrotizing glomerulonephritis (NecGN), and six healthy controls were determined with a polymerase chain reaction (PCR)-based assay. The urinary sediment levels of miR-221, miR-222, miR-339-3P and miR-339-5P, which are involved in the regulation of ICAM-1 production, were also quantified. LN patients had lower urinary sediment ICAM-1 levels than the other two groups (overall p = 0.034). In addition, urinary sediment ICAM-1 level inversely correlated with the estimated glomerular filtration rate (GFR) (r = -0.474, p = 0.026) but not other markers of lupus activity, or urinary sediment levels of miR-221, miR-222, miR-339-3P, or miR-339-5P. However, serum anti-dsDNA level inversely correlated with urinary sediment levels of miR-221 (r = -0.591, p = 0.043) and miR-222 (r = -0.689, p = 0.013), while urinary sediment miR-221 level also correlated with serum C3 level (r = 0.658, p = 0.02). We conclude that urinary sediment ICAM-1 level was significantly reduced in LN, and the level inversely correlated with renal function. Urinary sediment miR-221 and miR-222 levels correlate with lupus disease activity and may serve as biomarkers of LN.


Dissecting the temporal requirements for homeotic gene function.
Homeotic genes confer identity to the different segments of Drosophila. These genes are expressed in many cell types over long periods of time. To determine when the homeotic genes are required for specific developmental events we have expressed the Ultrabithorax, abdominal-A and Abdominal-Bm proteins at different times during development using the GAL4 targeting technique. We find that early transient homeotic gene expression has no lasting effects on the differentiation of the larval epidermis, but it switches the fate of other cell types irreversibly (e.g. the spiracle primordia). We describe one cell type in the peripheral nervous system that makes sequential, independent responses to homeotic gene expression. We also provide evidence that supports the hypothesis of in vivo competition between the bithorax complex proteins for the regulation of their down-stream targets.


Example-based super-resolution for enhancing spatial resolution of medical images.
This paper proposes an effective exampled-based super-resolution (SR) method to improve the spatial resolution of medical image heavily corrupted by noise. Based on the sparsity of patches, the reconstruction of a high-resolution (HR) patch from each low-resolution (LR) input patch can be performed with the help of a database, by solving a non-negative sparse optimization problem. The challenge is to effectively solve this problem in case of a large size database. To cope with this issue, we propose a metric to measure the similarity between image patches based on the Earth Mover's Distance (EMD) in order to select only the most similar candidates that will be used in the optimization problem. Experimental results demonstrate the efficiency of our algorithm over many existing SR methods, especially in case of noise-corrupted LR image.


Discrimination of dynamic interaural intensity differences.
An experiment was conducted to measure observers' ability to detect time-varying interaural intensity differences (IIDs). In a two-interval forced-choice task, observers discriminated a binaural amplitude modulated (AM) noise in which the modulating sinusoid was interaurally in-phase from the same AM noise in which the modulator was interaurally phase-reversed. The latter stimulus produces a sinusoidally varying IID whose rate and peak IID depend on the frequency (fm) and depth (m) of modulation. The carrier was a narrow-band noise, interaurally uncorrelated, centered at 500, 1000, or 4000 Hz. Presentation level was 75 dB SPL; duration was 1.0 s. For a given fm, m was varied in an adaptive procedure to estimate the depth required for 71% discriminability (mthr). Three of the four observers displayed "low-pass" modulation functions: at 500 Hz, as fm increased from 0-50 Hz, mthr increased from 0.08 (IID = 1.3 dB) to 0.50 (peak IID = 9.5 dB). At 1000 and 4000 Hz observers were more sensitive to IID and the functions (mthr vs fm) were flatter than at 500 Hz. Comparison of these data to previously published data indicates that the binaural system can follow fluctuations in IID more efficiently than it can follow fluctuations in interaural time difference, although there are large individual differences in subjects' capacity to process these two types of binaural cues.


An ascorbate-reducible cytochrome b561 is localized in macrophage lysosomes.
Cytochromes b561 (Cyts b561) are a family of intrinsic membrane proteins involved in ascorbate-mediated transmembrane electron transport. The chromaffin granule Cyt b561 (CGCytb) is believed to transport electrons donated by extravesicular ascorbate (ASC) across the membrane to intravesicular monodehydroascorbate (MDA) supporting catecholamine synthesis in neuroendocrine tissues. Another isoform, the duodenal Cyt b561 (Dcytb), was reported to have ferric reductase activity, possibly facilitating intestinal iron uptake. Herein, a new Cyt b561 homologue, LCytb (for lysosomal Cytb561) was found expressed in the late endosomal-lysosomal membrane. LCytb shared high sequence similarity with CGCytb (45% identity) and Dcytb (42% identity). Moreover, four heme-coordinating His residues, and putative ASC and MDA binding sites were highly conserved. Recombinant LCytb exhibited an ASC-reducible b-type Cyt absorbance spectrum with alpha-band maximum at 561 nm in the spectrum of the reduced protein. Northern blots and Western blots revealed that LCytb was predominantly expressed in lung, spleen, thymus, testis and placenta. In situ hybridization and immunofluorescence studies further demonstrated that the protein was expressed in the alveolar macrophages of the lung, in the white pulp of the spleen, widespread in the thymus, and in the Sertoli cells of the testis. Sequence analysis indicated the presence of a (DE)XXXL(LI)-type signal in the C-terminal of the protein, predicting a late endosomal-lysosomal subcellular localization. This localization was confirmed by double labeling experiments in RAW264.7 and 293 cells, stably transfected with LCytb.


Variability in the size of the retroperitoneal oblique corridor: A magnetic resonance imaging-based analysis.
A minimally invasive approach to the L2-S1 disc spaces through a single, left-sided, retroperitoneal oblique corridor has been previously described. However, the size of this corridor varies, limiting access to the disc space in certain patients. Here, the authors retrospectively reviewed lumbar spine magnetic resonance imaging (MRI) in 300 patients to better define the size and variability of the retroperitoneal oblique corridor. Lumbar spine MRI from 300 patients was reviewed. The size of the retroperitoneal oblique corridor from L2-S1 was measured. It was defined as the (1) distance between the medial aspect of the aorta and the lateral aspect of the psoas muscle from L2-L5 and (2) the distance between the midpoint of the L5-S1 disc and the medial aspect of the nearest major vessel on the left at L5-S1. In addition, the rostral-caudal location of the iliac bifurcation was measured. The size of the retroperitoneal oblique corridor at L2/3, L3/4, L4/5, and L5/S1 was, respectively, 17.3 ± 6.4 mm, 16.2 ± 6.3 mm, 14.8 ± 7.8 cm, and 13.0 ± 8.3 mm. The incidence of corridor size <1 cm at L2/3, L3/4, L4/5, and L5/S1 was 10.3%, 16.0%, 30.0%, and 39.3%, respectively. The iliac bifurcation was most commonly found behind the L4 vertebral body (n = 158, 52.67%) followed by the L4/5 disc space (n = 74, 24.67%). The size of the retroperitoneal oblique corridor diminishes in a rostral-caudal direction, often limiting access to the L4/5 and L5/S1 disc spaces.


Perspectives on the use of microspectrophotometry in the diagnosis of pretumorous processes and malignant tumors.
Comparative microspectrophotometric study of the nuclear Feulgen DNA content in pretumorous processes and cancers (larynx, endometrium, large intestine, and stomach) has made it possible to formulate an exponential law of DNA accumulation in cell populations in proliferating and malignant tissue. The dynamics of changes in the "index of DNA accumulation" can be used as an objective quantitative diagnostic test. A scale of malignant transformation was proposed with which the degree of probability of malignancy in pretumorous processes could be estimated. The data obtained allowed the author to propose a hypothesis of DNA superproduction as the basic cause of progressive neoplastic growth.


Platelet-rich plasma reduces the oxidative damage determined by a skeletal muscle contusion in rats.
Platelet-rich plasma (PRP) has received increasing attention and is widely used in clinical practice in order to stimulate human tissue healing. Contusions are very common injuries observed in sports and affect the function of the musculoskeletal system. This study investigated the effects of PRP on the oxidative damage determined by a contusion induced in gastrocnemius muscle of rats. PRP was injected intramuscularly immediately after injury and every 48 h, and the biochemical analysis was performed 1, 3, 5, or 7 days after the contusion onset in order to evaluate the changes characteristics of the healing process. The contusion increased the levels of oxidative stress markers such as thiobarbituric acid reactive substances and oxidized dichlorofluorescein both in skeletal muscle tissue and erythrocytes preparations, and PRP treatment significantly reduced these oxidative damage markers. Furthermore, the contusion decreased the cellular viability in the site of the lesion and PRP was effective in diminishing this effect. Moreover, PRP increased the levels of enzymatic antioxidants superoxide dismutase and catalase activities in the injured muscle, and also the non-protein thiols (-SH) group levels in erythrocytes. In conclusion PRP, in the form that was used in this study, was able to modulate the oxidative damage determined by a classical skeletal muscle injury possibly by reducing the impairment of myocytes mitochondrial function and improving their endogenous antioxidant defense systems.


[Immunologic reactions following heart transplantation and their detection].
Transplantation antigens of the major histocompatibility complex are able to stimulate the rejection of the graft. Class I and class II antigens presented by dendritic cells to the host macrophages are found on parenchymal cells (class I) or combined on all passenger leucocytes. Humoral factors like interleukin 1 produced by the macrophages activate the helper-lymphocyte subpopulation. The cytotoxic effector cells but also antibody producing B-cells receive their signal (interleukin 2) from the helper cells. Cellular and humoral mechanisms attack the vascular endothelium and the endocard first. Typical perivascular infiltrates or antibodies on the sarcolemm of myocard fibres and the intima herald the two types of rejection. The activated lymphocytes and their blast forms recirculate in various amounts in the peripheral blood, reflecting the severity of the event. Hematological evaluation including differentiation of lymphocyte subsets by monoclonal antibodies according to their phenotype seem to be a tool to recognize these mechanisms at an early stage. It is suggested that the optimal therapy and the necessary biopsy can be adjusted even more precisely using this immunological monitoring.


Ectopic enterogenous cyst.
Enterogenous cyst is a rare congenital lesion presumably of endodermal derivation. It is usually located in the medistinum, the abdominal cavity, skull or within the spinal canal. To our knowledge, it has not been reported in the subcutaneous tissue. We report the first case of ectopic (left scapular region) subcutaneous enterogenous cyst in a 46-year-old man, who presented with a lump over the left scapular region of several years' duration. Clinical diagnosis of lipoma was made. The final histological diagnosis was enterogenous cyst. Enterogenous cysts at ectopic locations should be kept in mind and studied further especially with respect to their development. A better understanding of the embryology, histopathology and genetics of ectopic enterogenous cyst is desired.


Thermocrinis jamiesonii sp. nov., a thiosulfate-oxidizing, autotropic thermophile isolated from a geothermal spring.
An obligately thermophilic, chemolithotrophic, microaerophilic bacterium, designated strain GBS1T, was isolated from the water column of Great Boiling Spring, Nevada, USA. Thiosulfate was required for growth. Although capable of autotrophy, growth of GBS1T was enhanced in the presence of acetate, peptone or Casamino acids. Growth occurred at 70-85 °C with an optimum at 80 °C, at pH 6.50-7.75 with an optimum at pH 7.25, with 0.5-8 % oxygen with an optimum at 1-2 % and with ≤ 200 mM NaCl. The doubling time under optimal growth conditions was 1.3 h, with a final mean cell density of 6.2 ± 0.5 × 107 cells ml- 1. Non-motile, rod-shaped cells 1.4-2.4 × 0.4-0.6 μm in size occurred singly or in pairs. The major cellular fatty acids (>5 % of the total) were C20 : 1ω9c, C18 : 0, C16 : 0 and C20 : 0. Phylogenetic analysis of the GBS1T 16S rRNA gene sequence indicated an affiliation with Thermocrinis ruber and other species of the genus Thermocrinis, but determination of 16S rRNA gene sequence similarity ( ≤ 97.10 %) and in silico estimated DNA-DNA hybridization values ( ≤ 18.4 %) with the type strains of recognized Thermocrinis species indicate that the novel strain is distinct from described species. Based on phenotypic, genotypic and phylogenetic characteristics, a novel species, Thermocrinis jamiesonii sp. nov., is proposed, with GBS1T ( = JCM 19133T = DSM 27162T) as the type strain.


Factors associated with the development of neonatal tolerance after the administration of a plasmid DNA vaccine.
A plasmid DNA vaccine encoding the circumsporozoite protein of malaria (pCSP) induces tolerance rather than immunity when administered to newborn mice. We find that this tolerance persists for >1 yr after neonatal pCSP administration and interferes with the induction of protective immunity in animals challenged with live sporozoites. Susceptibility to tolerance induction wanes rapidly with age, disappearing within 1 wk of birth. Higher doses of plasmid are more tolerogenic, and susceptibility to tolerance is not MHC-restricted. CD8+ T cells from tolerant mice suppress the in vitro Ag-specific immune response of cells from adult mice immunized with pCSP. Similarly, CD8+ T cells from tolerant mice transfer nonresponsiveness to naive syngeneic recipients. These findings clarify the cellular basis and factors contributing to the development of DNA vaccine-induced neonatal tolerance.


Selective and Sensocompatible Electrochemical Nitric Oxide Sensor with a Bilaminar Design.
Macrophages mediate mammalian inflammation in part by the release of the gasotransmitter, nitric oxide (NO). Electrochemical methods represent the best means of direct, continuous measurement of NO, but monitoring continuous release from immunostimulated macrophages remains analytically challenging. Long release durations necessitate consistent sensor performance (i.e., sensitivity and selectivity for NO) in proteinaceous media. Herein, we describe the fabrication of an electrochemical sensor modified by an electropolymerized 5-amino-1-naphthol (poly(5A1N)) film in conjunction with a fluorinated xerogel topcoat. The unique combination of these membranes ensures selective detection of NO that is maintained over extended periods of use (>24 h) in biological media without performance deterioration. The hydrophobic xerogel topcoat protects the underlying NO-selective poly(5A1N) film from hydration-induced desorption. The bilaminar sensor is then readily adapted for measurement of the temporal NO-release profiles from immunostimulated macrophages.


Identification, characterization, and transcription analysis of xylogen-like arabinogalactan proteins in rice (Oryza sativa L.).
Xylogen, a chimeric arabinogalactan protein containing a non-specific lipid transfer protein domain, can promote xylem cell differentiation. No comprehensive study has been carried out on the XYLP gene family in rice. As a first step in research on this gene family and as a useful strategy in general, a genome-wide analysis of the OsXYLP gene family is thus needed. In this study, we identified 21 XYLP genes from the rice genome and comprehensively analyzed their protein structures, phylogenetic relationships, chromosomal locations, and gene duplication status. Our results indicate that gene duplication has played major roles in the expansion of the OsXYLP gene family. We used expressed sequence tag, microarray, massively parallel signature sequencing, and quantitative real-time PCR data to analyze OsXYLP gene expression during various developmental stages and under abiotic stress conditions. We found that many OsXYLP genes are abundantly expressed in vascular tissues and seeds, with some genes regulated under hormonal or abiotic stresses. In addition, we identified knockout mutants of OsXYLP7 and OsXYLP16 and discovered that the mutant xylp7 has a defect in stem height. We analyzed expression profiles of 21 XYLP genes and characterized the structures and evolutionary relationships of their proteins. Our results demonstrate that the rice XYLP gene family may play roles in plant vascular system development and hormone signaling. Among the 21 detected OsXYLPs, 19 are newly identified genes encoding arabinogalactan proteins. Our results provide comprehensive insights that will assist future research on the biological functions of the rice XYLP gene family.


Nanoparticles Loaded with a New Thiourea Derivative: Development and In vitro Evaluation Against Leishmania amazonensis.
Leishmaniasis is a neglected tropical disease caused by protozoa of the genus Leishmania. Current treatments are restricted to a small number of drugs that display both severe side effects and a potential for parasites to develop resistance. A new N-(3,4-methylenedioxyphenyl)-N'- (2-phenethyl) thiourea compound (thiourea 1) has shown promising in vitro activity against Leishmania amazonensis with an IC50 of 54.14 μM for promastigotes and an IC50 of 70 μM for amastigotes. To develop a formulation of thiourea 1 as an oral treatment for leishmaniasis, it was incorporated into Nanoparticles (NPs), a proven approach to provide long-acting drug delivery systems. Poly (D,L-Lactic-co-Glycolic Acid) (PLGA) polymeric NPs containing thiourea 1 were obtained through a nanoprecipitation methodology associated with solvent evaporation. The NPs containing thiourea 1 were characterized for Encapsulation Efficiency (EE%), reaction yield (% w/w), surface charge, particle size and morphology by Transmission Electron Microscopy (TEM). NPs with thiourea 1 showed an improved in vitro leishmanicidal activity with a reduction in its cytotoxicity against macrophages (CC50>100 μg/mL) while preserving its IC50 against intracellular amastigotes (1.46 ± 0.09 μg/mL). This represents a parasite Selectivity Index (SI) of 68.49, which is a marked advancement from the reference drug pentamidine (SI = 30.14). The results suggest that the incorporation into NPs potentiated the therapeutic effect of thiourea 1, most likely by improving the selective delivery of the drug to the phagocytic cells that are targeted for infection by L. amazonensis. This work reinforces the importance of nanotechnology in the acquisition of new therapeutic alternatives for oral treatments.


A Recombinant Rabies Virus Expressing Fms-like Tyrosine Kinase 3 Ligand (Flt3L) Induces Enhanced Immunogenicity in Mice.
Rabies is a zoonotic disease that still causes 59,000 human deaths each year, and rabies vaccine is the most effective way to control the disease. Our previous studies suggested that the maturation of DC plays an important role in enhancing the immunogenicity of rabies vaccine. Flt3L has been reported to own the ability to accelerate the DC maturation, therefore, in this study, a recombinant rabies virus expressing mouse Flt3L, designated as LBNSE-Flt3L, was constructed, and its immunogenicity was characterized. It was found that LBNSE-Flt3L could enhance the maturation of DC both in vitro and in vivo, and significantly more TFH cells and Germinal Center B (GC B) cells were generated in mice immunized with LBNSE-Flt3L than those immunized with the parent virus LBNSE. Consequently, expressing of Flt3L could elevate the level of virus-neutralizing antibodies (VNA) in immunized mice which provides a better protection from a lethal rabies virus challenge. Taken together, our study extends the potential of Flt3L as a good adjuvant to develop novel rabies vaccine by enhancing the VNA production through activating the DC-TFH-GC B axis in immunized mice.


Dental Treatment Effect on Blood Glucose Level Fluctuation in Type 1 Balanced Diabetic Children.
Pediatric dentists, while treating diabetic patients, have a major concern about the occurrence of hypo- or hyperglycemia complications. So far, no dental care protocol is elaborated to help practitioners in creating a safe environment for their patients. This study aims to evaluate the blood glucose level (BGL) fluctuation in type 1 diabetic children according to the type of the delivered treatment and its duration, to outline guidance for predicting the occurrence of a hypo- or hyperglycemia complication. A cross-sectional approach was conducted on 70 balanced diabetic children aged between 7 years and 12 years old (32 females and 38 males) in the Department of Pediatric Dentistry at the Lebanese University in Beirut. Only the patients having a BGL between 70 mg/dL and 300 mg/dL could undergo dental treatment. The gender, the duration of the dental session (≤30 or >30 minutes), the BGLs at the baseline and the end of the session were noted. The types of the performed dental treatment were classified as simple, and unpleasant acts. For the female group, only eight sessions lasted ≤30 minutes. The results of simple and unpleasant interventions >30 minutes showed that BGLs before and after treatment were almost identical (p > 0.05). In the male group, for the simple acts >30 minutes, the BGL showed a significant fluctuation (p = 0.02). Dentists must be aware of signs of discomfort in balanced type 1 diabetic children to avoid severe complications. This study highlights a new range of BGLs (70-300 mg/dL) that allows safe dental treatment. Nassif N, Noueiri B. Dental Treatment Effect on Blood Glucose Level Fluctuation in Type 1 Balanced Diabetic Children. Int J Clin Pediatr Dent 2021;14(2):212-216.


Antimicrobial Peptides: An Approach to Combat Resilient Infections.
It was apparent by the end of 1980s that the success against the threats of bacterial pathogens on public health was an illusion, with the rapid development of resistant strains more than the discovery of new drugs. As a consequence, the remedial services were in the backfoot position of being on the losing side of this never-ending evolutionary war. The quest for new antibiotics to overcome resistance problems has long been a top research priority for the researchers and the pharmaceutical industry. However, the resistance problems remain unresolved due to the abrupt misuse of antibiotics by common people, which has immensely worsened the scenario by disseminating antibiotic-resistant bacterial strains around the world. Thus, immediate action is needed to measure emerging and re-emerging microbial diseases having new resistance mechanisms and to manage their rapid spread among the common public by means of novel alternative metabolites. Antimicrobial Peptides (AMPs) are short, cationic peptides evolved in a wide range of living organisms and serve as the essential part of the host innate immunity. For humans, these effector molecules either can directly kill the foreign microbes or modulate the host immune systems so that the human body could develop some resistance against the microbial infections. In this review, we discuss their history, structural classifications, modes of action, and explain their biological roles as anti-infective agents. We also scrutinize their clinical potentiality, current limitations in various developmental stages and strategies to overcome for their successful clinical applications.


Prevalence of Mycoplasma genitalium and other sexually-transmitted pathogens among high-risk individuals in Greece.
The aim of the present study was to determine the prevalence of Mycoplasma genitalium (MG) infection among individuals at high risk for sexually-transmitted diseases (STDs) at a major urban STD clinic in Athens, in view of the lack of data pertaining to this infection in Greece. Urethral and cervical samples from 176 individuals consecutively attending the clinic and agreeing to participate were prospectively collected and tested for MG infection using conventional PCR and TaqMan Real-Time PCR. All individuals were also examined for alternative STD pathogens. A total of 161 individuals (91.5%) reported symptoms, while 15 individuals (8.5%) were asymptomatic. MG was detected in 5.7% (10/176) of the total population and in 5.6% (9/161) of those with symptoms, corresponding to 5.7% (5/87) of symptomatic men and 5.4% (4/74) of symptomatic women. Among symptomatic males, 3.4% (3/87) displayed MG mono-infection. The median age of MG infected individuals was 25 years (IQR 21.5-29.5 years). Individuals infected with MG were more likely to be coinfected with Ureaplasma spp. [OR=5.12, 95%CI, 1.27-20.57] (p=0.017). MG infection was also more common among individuals who had received antibiotics in the previous 15 days [OR=6.04, 95%CI, 1.37-26.64] (p=0.035). MG was found to represent an important microbial pathogen among patients presenting with symptoms of urethritis or cervicitis in Greece. Consideration of MG as cause of STD seems crucial in diagnostic algorithms and treatment strategies.


Microcontroller-based servo for two-crystal X-ray monochromators.
Microcontrollers have become increasingly easy to incorporate into instruments as the architectures and support tools have developed. The PIC series is particularly easy to use, and this paper describes a controller used to stabilize the output of a two-crystal X-ray monochromator at a given offset from its peak intensity position, as such monochromators are generally used.


Ferrocen-yl(meth-yl)diphenyl-silane.
In the title mol-ecule, [Fe(C(5)H(5))(C(18)H(17)Si)], the distances of the Fe atom from the centroids of the unsubstituted and substituted cyclo-penta-dienyl (Cp) rings are 1.651 (1) and 1.646 (1) Å, respectively. The dihedral angle between the two Cp rings is 3.20 (17)°. The crystal packing is mainly stabilized by van der Waals forces.


The relative effectiveness of four methods of teaching practical scientific skills to secondary school students.
The investigation compares the effectiveness of four methods of teaching students how to perform two practical scientific skills. The methods commonly used combinations of four different modes of communication. Method W uses written instructions only. Method WG has these written instructions supplemented with graphics. Method WGS adds spoken instructions to the combination used in Method WG, and Method WGSD also includes a video-recorded demonstration of the practical task. After teaching random groups (N = 20) of students aged 14-15 years with one of the methods, their effectiveness was assessed in terms of the students' performance on test exercises which required the students to carry out these tasks. The results showed that the methods involving the use of spoken instructions (i.e. WGS and WGSD) were significantly worse than those that did not use spoken instructions. The use of graphics also had no significant beneficial effect, and the demonstration had a significant positive effect only in one task.


Phenomenology and Prevalence of Neuroleptic-Induced Akathisia in Late Life.
The authors examined 115 patients totaling 127 admissions to an acute care geriatric psychiatry inpatient unit using the Barnes Akathisia Scale. Subjective complaints of akathisia were associated with a diagnosis of major depression and correlated with Hamilton Rating Scale for Depression scores but were not associated with current neuroleptic treatment. Objective evidence of akathisia was strongly associated with current neuroleptic use. Patients from 45 admissions were receiving neuroleptics at the time of assessment. By using the presence of objective akathisia to define the syndrome, the authors identified 8 patients from these 45 (17.8%) as having neurolepticinduced akathisia (NIA). The presence of MA was associated with a lower rate of antiparkinsonian agent use. NIA contributed to the presenting complaints on admission in 7 patients, comprising 5.5% of all 127 admissions.