Neural Wiskott-Aldrich syndrome protein is recruited to rafts and associates with endophilin A in response to epidermal growth factor.
Neural Wiskott-Aldrich syndrome protein (N-WASP) has been implicated in endocytosis; however, little is known about how it interacts functionally with the endocytic machinery. Sucrose gradient fractionation experiments and immunofluorescence studies with anti-N-WASP antibody revealed that N-WASP is recruited together with clathrin and dynamin, which play essential roles in clathrin-mediated endocytosis, to lipid rafts in an epidermal growth factor (EGF)-dependent manner. Endophilin A (EA) binds to dynamin and plays an essential role in the fission step of clathrin-mediated endocytosis. In the present study, we show that the Src homology 3 (SH3) domain of EA associates with the proline-rich domain of N-WASP and dynamin in vitro. Co-immunoprecipitation assays with anti-N-WASP antibody revealed that EGF induces association of N-WASP with EA. In addition, EA enhances N-WASP-induced actin-related protein 2/3 (Arp2/3) complex activation in vitro. Immunofluorescence studies revealed that actin accumulates at sites where N-WASP and EA are co-localized after EGF stimulation. Furthermore, studies of overexpression of the SH3 domain of EA indicate that EA may regulate EGF-induced recruitment of N-WASP to lipid rafts. These results suggest that, upon EGF stimulation, N-WASP interacts with EA through its proline-rich domain to induce the fission step of clathrin-mediated endocytosis.


Unmasking of Myasthenia Gravis After Introduction of Oral Risperidone in a Schizophrenic Saudi Male: A Case Report.
Myasthenia gravis is an autoimmune disease that affects the neuromuscular junction. It causes generalized muscle weakness that may include the respiratory muscles, potentially leading to a medical emergency known as a myasthenic crisis. This is a case report of a rare incident of a myasthenia gravis exacerbation after administration of the oral antipsychotic risperidone to a schizophrenic patient. Few similar cases have been reported. Although rare, such incidents are dangerous as physicians could easily confuse myasthenia gravis symptoms with extrapyramidal side effects of antipsychotics. This concern should be addressed not just with risperidone but rather with any other antipsychotics that exhibit anticholinergic side effects.


Audit of a program to increase the use of vacuum extraction in Mulago Hospital, Uganda.
Prolonged second stage of labour is a major cause of perinatal and maternal morbidity and mortality in low-income countries. Vacuum extraction is a proven effective intervention, hardly used in Africa. Many authors and organisations recommend (re)introduction of vacuum extraction, but successful implementation has not been reported. In 2012, a program to increase the use of vacuum extraction was implemented in Mulago Hospital, Uganda. The program consisted of development of a vacuum extraction guideline, supply of equipment and training of staff. The objective of this study was to investigate the impact of the program. Audit of a quality improvement intervention with before and after measurement of outcome parameters. Mulago Hospital, the national referral hospital for Uganda with approximately 33 000 deliveries per year. It is the university teaching hospital for Makerere University and most of the countries doctors and midwives are trained here. Data was collected from hospital registers and medical files for a period of two years. Main outcome measures were vacuum extraction rate, intrapartum stillbirth, neonatal death, uterine rupture, maternal death and decision to delivery interval. Mode of delivery and outcome of 12 143 deliveries before and 34 894 deliveries after implementation of the program were analysed. The vacuum extraction rate increased from 0.6 - 2.4 % of deliveries (p < 0.01) and was still rising after 18 months. There was a decline in intrapartum stillbirths from 34 to 26 per 1000 births (-23.6 %, p < 0.01) and women with uterine rupture from 1.1 - 0.8 per 100 births (-25.5 %, p < 0.01). Decision to delivery interval for vacuum extraction was four hours shorter than for caesarean section. A program to increase the use of vacuum extraction was successful in a high-volume university hospital in sub-Saharan Africa. The use of vacuum extraction increased. An association with improved maternal and perinatal outcome is strongly suggested. We recommend broad implementation of vacuum extraction, whereby university hospitals like Mulago Hospital can play an important role.To support implementation, we recommend further research into outcome of vacuum extraction and into vacuum extraction devices for low-income countries. Such studies are now in progress at Mulago Hospital.


Does long sleep duration increase risk of metabolic syndrome in Azar cohort study population?
Background: We decided to assess the correlation between metabolic syndrome (MetS) risks,sleep and napping duration in Azar cohort population according to the increasing incidence of MetS in the world and inconsistence results about sleep duration and MetS. Methods: In this cross-sectional study, MetS and sleep habits of 14916 subjects (35-70 years old) who inhabited in Shabestar city were determined by ATPIII and Pittsburg questionnaire respectively. Inclusion criteria were subjects with 35-70 years old and living in Shabestar for at least 9 months of the year. Results: According to the results, age, living place, body mass index, hypnotic drug use, sleep and napping duration and TV time were the risk factors of MetS. In this regard, long sleep duration (>9 h/24 h), napping (0.25-2 h/day), hypnotic drug use and watching TV (2 h/day)increased the risk of MetS by 1.18 (1.05-1.33), 1.16(1.07-1.26), 1.35(1.13-1.60), and 1.13(1.04-1.23) respectively. Conclusion: According to these results, it appears that proper education for improvement of sleep habit is necessary to reduce incidence of MetS and its consequences. However, there is need for more longitudinal researches and using objective method of sleep habits evaluation for more precise results.


HLA alleles may serve as a tool to discriminate atypical type 2 diabetic patients.
To investigate whether the presence of human leukocyte antigen (HLA) marker could add new information to discriminated atypical diabetic type 2 patients. We analyzed 199 patients initially diagnosed as type 2 diabetes who are treated in special care diabetes clinics (3(rd) level). This population was classified in "atypical" (sample A) and "classic" (sample B) according to HLA typing. We consider "classic patient" when has absence of type 1 diabetes associated HLA alleles and no difficulties in their diagnosis and treatments. By the other hand, we considered "atypical patient" when show type 1 diabetes associated HLA alleles and difficulties in their diagnosis and treatments. The standard protocol Asociacion Latinoamericana de Diabetes 2006 was used for patients follow up. To analyze differences between both populations in paraclinical parameters we used unpaired t tests and contingence tables. Bivariate and multivariate analyses were carried out using the SPSS software program. In all studies we assume differences statistically significant, with a P-value < 0.05 corrected and 95%CI. The typing HLA in the "atypical" populations show that 92.47% patients presented at list one type 1 diabetes associated HLA alleles (DQB1*0201-0302 and DR 3-4) and 7.53% had two of its. The results showed for categorical variables (family history, presence or absence of hypertension and/or dyslipidemia, reason for initial consultation) the only difference found was at dyslipidemia (OR = 0.45, 0.243 < OD < 0.822 (P < 0.001). In relation to continuous variables we found significant differences between atypical vs classic only in cholesterol (5.07 ± 1.1 vs 5.56 ± 1.5, P < 0.05), high density lipoproteins (1.23 ± 0.3 vs 1.33 ± 0.3, P < 0.05) and low density lipoproteins (2.86 ± 0.9 vs 3.38 ± 1.7, P < 0.01). None of the variables had discriminating power when logistic regression was done. We propose an algorithm including HLA genotyping as a tool to discriminate atypical patients, complementing international treatment guidelines for complex patients.


VCAM-1-positive microglia target oligodendrocytes at the border of multiple sclerosis lesions.
The distribution and lineage of vascular cell adhesion molecule-1 (VCAM-1)-positive cells was investigated in 43 lesions from the brain tissue of patients with multiple sclerosis (MS). Numerous VCAM-1-positive macrophages/microglia were detected at the edges of MS lesions. Quantitative analysis of 6 active, 7 chronic active, and 4 chronic inactive MS lesions identified most VCAM-1-positive cells at the actively demyelinating borders of active (102/mm3) and chronic active (29/mm3) lesions, but rarely in chronic inactive lesions (4/mm3). Further, approximately 17% of the VCAM-1-positive cells closely apposed or surrounded oligodendrocyte perikarya at the edges of active and chronic active lesions that were sites of ongoing demyelination. Endothelial cells were VCAM-1-negative in both lesion and non-lesion MS brain tissue. This report is the first to document direct microglial interaction with oligodendrocytes in MS.


Effect of Materialism on Pro-environmental Behavior Among Youth in China: The Role of Nature Connectedness.
We designed three studies to explore the effect of materialistic values on pro-environmental behavior among youth and the mediated role of nature connectedness between materialistic values and pro-environmental behavior. Through a self-report questionnaire survey (Study 1) and an experimental manipulation of materialistic values (Study 2), we found that materialistic values negatively predicted pro-environmental behavior, and that nature connectedness played a mediating role. Further, we used natural contact strategies to control the level of nature connectedness, and found that the negative impact of high materialistic values on pro-environment behavior decreased with the increase of nature connectedness, further supporting the mediating role of nature connectedness (Study 3). These results may contribute to the design of strategies that effectively mitigate the negative effects of materialistic values on pro-environmental behavior.


Incentives and disincentives for treating of depression and anxiety in Ontario Family Health Teams: protocol for a grounded theory study.
There is strong consensus that prevention and management of common mental disorders (CMDs) should occur in primary care and evidence suggests that treatment of CMDs in these settings can be effective. New interprofessional team-based models of primary care have emerged that are intended to address problems of quality and access to mental health services, yet many people continue to struggle to access care for CMDs in these settings. Insufficient attention directed towards the incentives and disincentives that influence care for CMDs in primary care, and especially in interprofessional team-based settings, may have resulted in missed opportunities to improve care quality and control healthcare costs. Our research is driven by the hypothesis that a stronger understanding of the full range of incentives and disincentives at play and their relationships with performance and other contextual factors will help stakeholders identify the critical levers of change needed to enhance prevention and management of CMDs in interprofessional primary care contexts. Participant recruitment began in May 2016. An explanatory qualitative design, based on a constructivist grounded theory methodology, will be used. Our study will be conducted in the Canadian province of Ontario, a province that features a widely implemented interprofessional team-based model of primary care. Semistructured interviews will be conducted with a diverse range of healthcare professionals and stakeholders that can help us understand how various incentives and disincentives influence the provision of evidence-based collaborative care for CMDs. A final sample size of 100 is anticipated. The protocol was peer reviewed by experts who were nominated by the funding organisation. The model we generate will shed light on the incentives and disincentives that are and should be in place to support high-quality CMD care and help stimulate more targeted, coordinated stakeholder responses to improving primary mental healthcare quality.


ACE2/Ang 1-7 axis: A critical regulator of epicardial adipose tissue inflammation and cardiac dysfunction in obesity.
Obesity is characterized by an excessive fat accumulation in adipose tissues leading to weight gain and is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; activated RAS and angiotensin (Ang) II production results in worsening of cardiovascular diseases and angiotensin converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. ACE2 is expressed in the adipocytes and its expression is upregulated in response to high fat diet induced obesity in mice. Loss of ACE2 results in heart failure with preserved ejection fraction which is mediated in part by epicardial adipose tissue inflammation. Angiotensin 1-7 reduces the obesity associated cardiac dysfunction predominantly via its role in adiponectin expression and attenuation of epicardial adipose tissue inflammation. Human heart disease is also linked with inflammed epicardial adipose tissue. Here, we discuss the important interpretation of the novel of ACE2/Ang 1-7 pathway in obesity associated cardiac dysfunction.


Non-human primates in outdoor enclosures: risk for infection with rodent-borne hantaviruses.
Different species of non-human primates have been exploited as animal disease models for human hantavirus infections. To study the potential risk of natural hantavirus infection of non-human primates, we investigated serum samples from non-human primates of three species living in outdoor enclosures of the German Primate Center (GPC), Göttingen, located in a hantavirus endemic region of central Germany. For that purpose we used serological assays based on recombinant antigens of the bank vole (Myodes glareolus) transmitted Puumala virus (PUUV) and the common and field vole (Microtus arvalis, Microtus agrestis) associated Tula virus (TULV) which are both broadly geographically distributed in Germany. In 24 out of 251 (9.6%) monkey sera collected in 2006 PUUV- and/or TULV-reactive immunoglobulin G (IgG) antibodies were detected. Investigation of follow-up sera from 13 animals confirmed for two animals a seroconversion due to hantavirus exposure at the GPC. To prove the origin of the infection, wild rodents from the surrounding regions were analyzed by hantavirus-specific reverse transcriptase-PCR analysis. In 6 of the 73 investigated bank voles and 3 of the 19 investigated Microtus spp. PUUV- and TULV-specific nucleic acid sequences, respectively, were detected. In conclusion, our investigations demonstrate for the first time natural infections of non-human primates in outdoor enclosures in Germany. These findings highlight the importance of hantavirus surveillance in those primate housings and corresponding preventive measures against wild rodents, particularly in hantavirus endemic regions.


Large pleural nodules secondary to Mycobacterium tuberculosis.
Mycobacterium tuberculosis disease is a common disease worldwide. Pleural visualization, however, is usually not required as the diagnosis can typically be made by less invasive methods. Thoracoscopic visualization typically reveals pleural erythema and studding with numerous small pleural tubercules and adhesions. We present images from a patient with less commonly seen large pleural nodules and plaques resulting from tuberculous pleuritis.


Modeling Normal and Pathological Ear Cartilage in vitro Using Somatic Stem Cells in Three-Dimensional Culture.
Microtia (underdeveloped ear) is a rare congenital dysmorphology affecting the development of the outer ear. Although human microtic cartilage has not been fully characterized, chondrogenic cells derived from this tissue have been proposed as a suitable source for autologous auricular reconstruction. The aim of this study was to further characterize native microtic cartilage and investigate the properties of cartilage stem/progenitor cells (CSPCs) derived from it. Two-dimensional (2D) systems are most commonly used to assess the chondrogenic potential of somatic stem cells in vitro, but limit cell interactions and differentiation. Hence here we investigated the behavior of microtic CSPCs in three-dimensional spheroid cultures. Remarkable similarities between human microtic cartilages from five patients, as compared to normal cartilage, were observed notwithstanding possibly different etiologies of the disease. Native microtic cartilage displayed poorly defined perichondrium and hyper-cellularity, an immature phenotype that resembled that of the normal developing human auricular cartilage we studied in parallel. Crucially, our analysis of microtic ears revealed for the first time that, unlike normal cartilage, microtic cartilages are vascularized. Importantly, CSPCs isolated from human microtic and normal ear cartilages were found to recapitulate many characteristics of pathological and healthy tissues, respectively, when allowed to differentiate as spheroids, but not in monolayer cultures. Noteworthily, starting from initially homogeneous cell pellets, CSPC spheroids spontaneously underwent a maturation process in culture, and formed two regions (inner and outer region) separated by a boundary, with distinct cell types that differed in chondrogenic commitment as indicated by expression of chondrogenic markers. Compared to normal ear-derived spheroids, microtic spheroids were asymmetric, hyper-cellularized and the inner and outer regions did not develop properly. Hence, their organization resembled that of native microtic cartilage. Together, our results identify novel features of microtic ears and highlight the importance of 3D self-organizing in vitro systems for better understanding somatic stem cell behavior and disease modeling. Our observations of ear-derived chondrogenic stem cell behavior have implications for choice of cells for tissue engineered reconstructive purposes and for modeling the etiopathogenesis of microtia.


Acquired factor VII inhibitor associated with primary central nervous system Lymphoma: A case report.
Paraneoplastic coagulopathies are uncommon in patients with lymphoma. We report the first case of an acquired coagulopathy in a patient with isolated primary central nervous system lymphoma (PCNSL) demonstrating large-cell histology. In our patient, a paraneoplastic factor VII inhibitor significantly delayed a diagnostic lumbar puncture despite fresh frozen plasma and inactivated prothrombin complex concentrate. While her coagulopathy was effectively overcome with recombinant activated factor VIIa and subsequently with lymphoma-directed therapy, her delayed diagnosis likely contributed to a poor outcome. Our case highlights the importance of rapidly identifying and correcting paraneoplastic coagulopathies when PCNSL is suspected.


Proteomic analysis of the excretory-secretory products from Strongyloides venezuelensis infective larvae: new insights for the immunodiagnosis of human strongyloidiasis.
Serodiagnosis of human strongyloidiasis is a practical alternative to parasitological methods due to its high sensitivity. However, cross-reactivity with other helminth infections limits its utility, and this problem is due to the use of homologous or heterologous somatic extracts of the parasite as an antigen source. Excretory-secretory (E/S) products from Strongyloides infective larvae can be used to improve the serodiagnosis. The combined use of western blot and proteomics became an interesting strategy to identify immunological markers for the serodiagnosis of strongyloidiasis. The present study describes the proteomic analysis of the antigenic components from E/S products of S. venezuelensis infective larvae that were recognized by IgG antibodies from patients with strongyloidiasis. Our results showed that IgG antibodies from patients with strongyloidiasis recognized between 15 and 16 antigenic bands in the E/S products from S. venezuelensis that were incubated in PBS or in RPMI culture medium, respectively. Overall, antigenic bands of low and high molecular weight were more specific than those of intermediate molecular weight, which were cross-reactive. A 36-kDa antigenic band was 93% sensitive and 100% specific (a probably arginine kinase of 37 kDa), while other antigenic bands were highly sensitive but low specific. Proteomic analysis revealed differences between the protein profiles from E/S-RPMI and E/S-PBS since only one-third of all proteins identified were common in both types of E/S products. Bioinformatic analysis showed that more than 50% of the proteins from E/S products are secreted within extracellular vesicles and only a small percentage of them are actually released by the classical secretory pathway. Several components from the E/S products were identified as plasminogen-binding proteins, probably used as an immune evasion mechanism. The data provided here provide valuable information to increase understanding of E/S products from S. venezuelensis infective larvae. This may help us to find new targets for the immunodiagnosis of human strongyloidiasis.


Variations in longitudinal sleep duration trajectories from infancy to early childhood.
This study investigates variations in night, day, and total sleep trajectories across infancy and childhood in Asian children. Participants consisted of a subset of 901 children, within the Growing Up in Singapore Towards healthy Outcomes cohort, which recruited 1247 pregnant women between June 2009 and September 2010. We used a novel conditional probabilistic trajectory model: a probabilistic model for mixture distribution, allowing different trajectory curves and model variances among groups to cluster longitudinal observations. Longitudinal sleep duration data for the trajectory analyses were collected from caregiver-reported questionnaires at 3, 6, 9, 12, 18, 24, and 54 months. We found 3 patterns of night sleep trajectories (n = 356): long consistent (31%), moderate consistent (41%), and short variable (28%); and 4 patterns of day sleep trajectories (n = 347): long variable (21%), long consistent (20%), moderate consistent (34%), and short consistent (25%). We also identified 4 patterns of total sleep trajectories (n = 345): long variable (19%), long consistent (26%), moderate consistent (28%), and short variable (27%). Short, moderate, and long trajectories differed significantly in duration. Children with consistent trajectories also displayed sleep patterns that were significantly more representative of typical developmental sleep patterns than children with variable trajectories. This is the first study to describe multiple sleep trajectories in Singaporean children and identify between-individual variability within the trajectory groups. Compared to predominantly Caucasian samples, night/total sleep trajectories were generally shorter, while day sleep trajectories were longer. Future studies should investigate how these variations are linked to different developmental outcomes.


[New progress in noninvasive method of blood glucose measurement using FT-mid-IR spectroscopy].
The blood glucose concentrations of volunteers from diabetes patients and healthy adults (all patients and volunteers who joined this experiment gave their consents) were measured by using a modified WQF-200 FTIR spectrometer with a newly designed ATR accessory from the Beijing Rayleigh Analytical Instrument Corp. The determination basis for this technique from the physiological point of view is also discussed based on the experimental results, which indicated that the glucose measured by the FT-Mid-IR ATR instrument is from the secretions on the skin and glucose components within the body. The secreted glucose components will increase with the time increasing. The authors' previous study demonstrated 1 120 cm(-1) band as an index to characterize the blood glucose. During the experiments, the authors used the band of 1 455 cm(-1) as internal standard because of its stability, and because the relative intensity of I1 120/I1 455 band possesses the higher sensitivity. Meanwhile, from the spectra, the relative intensity of I1 120/I1 455 band of the glucose in both sources exhibits a linear relationship with blood glucose concentration within the body. The dried blood has the similar spectra as fingers'. The fingers' spectra will exhibit higher sensitivity if the time of measurement is longer after washing hand, and the results showed that when measured 10 minutes after washing hand, the sensitivity will be higher than that when measured 4 minutes after washing hand. All the results can be used in promoting a convenient, rapid and noninvasive way to monitor the continuous variation of blood glucose concentration of diabetes patients in real time.


Atom loss resonances in a Bose-Einstein condensate.
Atom loss resonances in ultracold trapped atoms have been observed at scattering lengths near atom-dimer resonances, at which Efimov trimers cross the atom-dimer threshold, and near two-dimer resonances, at which universal tetramers cross the dimer-dimer threshold. We propose a new mechanism for these loss resonances in a Bose-Einstein condensate of atoms. As the scattering length is ramped to the large final value at which the atom loss rate is measured, the time-dependent scattering length generates a small condensate of shallow dimers coherently from the atom condensate. The coexisting atom and dimer condensates can be described by a low-energy effective field theory with universal coefficients that are determined by matching exact results from few-body physics. The classical field equations for the atom and dimer condensates predict narrow enhancements in the atom loss rate near atom-dimer resonances and near two-dimer resonances due to inelastic dimer collisions.


Foot Length Growth as a Novel Marker of Early Puberty.
Foot growth is part of overall pubertal growth but its relation to other anthropometric and hormonal changes is unclear. Our objective was to determine how foot length changes relate to changes in other growth parameters (height and weight), Tanner stage, and serum hormones. Adolescents (n = 342) were recruited to a 3-year longitudinal cohort study, underwent annual anthropometric assessments (height, weight, and foot length), and provided self-rated Tanner staging. They also provided blood samples that were analyzed using liquid chromatography-tandem mass spectrometry for serum testosterone and estradiol and classified as pre-pubertal or pubertal based on circulating hormone levels. Average annual percent increase in foot length was greater for pre-pubertal adolescents compared with pubertal. Increased foot length was associated with increases in height, weight, Tanner stage, and serum hormones in males and pre-menarcheal females but not post-menarcheal females. Foot length offers a novel, noninvasive, cost-effective, and easily demonstrable marker of early pubertal changes.


Immunological memory for HIV-1 induced in rabbits by immune poly(A)+ RNA.
New Zealand rabbits were used to demonstrate the in vitro and in vivo transfer of reactivity, including immunological memory, to a synthetic peptide corresponding to residues 586-606 of the gp-160 protein of human immunodeficiency virus (HIV-1). The transfer were mediated by immune poly (A)+ RNA from lymphoid organs (spleen and mesenteric nodules) harvested after immunization of a sheep with the peptide (8 subcutaneous injections plus glucan and complete Freund's adjuvant using a total of 1750 micrograms peptide). Immunological reactivity was detected by the leukocyte adherence inhibition (LAI) test for cellular immunity. A dose of 150 micrograms poly(A)- RNA ml-1 10(7) leukocytes-1 or 2.0 micrograms poly(A)+ RNA ml-1 10(7) leukocytes-1 was used for in vitro transfer. For in vivo transfer the recipient rabbits received 3,000 micrograms poly(A)- RNA or 20 micrograms poly(A)+ RNA. The mean non-adherence index (NAI) obtained in vitro was 10 +/- 7 for leukocytes treated with poly(A)-RNA and 60 +/- 10 leukocytes treated with poly(A)+ RNA. The poly(A)+ RNA fraction induced a primary-like response and memory cells in vivo. The poly(A)-RNA fraction had no effect. Since sheep are refractory to, and rabbits are sensitive to HIV-1, we suggest the use of this animal model for testing the immunomodulating effect of anti-HIV-1 immune poly(A)+ RNA.


Stevens-Johnson syndrome in two patients treated with cranial irradiation and phenytoin.
Stevens-Johnson syndrome (SJS) is a severe cutaneous eruption that most often appears as an adverse reaction to medication. In this report, we present two patients diagnosed with SJS, which developed in patients with brain tumour, after receiving cranial irradiation and phenytoin. Concomitant application of these two therapies may play an important role in the occurrence of the disease.


First Description of a New Disease in Rainbow Trout (Oncorhynchus mykiss (Walbaum)) Similar to Heart and Skeletal Muscle Inflammation (HSMI) and Detection of a Gene Sequence Related to Piscine Orthoreovirus (PRV).
In fall 2013, anorexia, lethargy and mortalities up to 10-12,000 dead fish per week were observed in rainbow trout Oncorhynchus mykiss in three fresh water hatcheries (salinity 0-1 ‰) on the west coast of Norway. The fish (25-100 g) showed signs of circulatory failure with haemorrhages, ascites and anaemia. The histopathological findings comprised inflammation of the heart and red muscle and liver necrosis. The affected fish had a common origin. Disease and mortalities were also observed up to four months after sea water transfer. Microbiological examination did not reveal presence of any known pathogens. Based on histopathological similarities to heart and skeletal inflammation (HSMI) in Atlantic salmon, associated with piscine orthoreovirus (PRV), extended investigations to detect a virus within the family Reoviridae were conducted. By the use of primer sets targeting the PRV genome, a sequence with 85% identity to a part of segment S1 of PRV was obtained. Further analysis showed that the virus sequence could only be aligned with PRV and no other reoviruses both on amino acid and nucleotide level. Two PCR assays were developed for specific detection of the virus. High amounts of the virus were detected in diseased fish at all affected farms and low amounts were detected in low prevalence at the broodfish farms. Further investigations are needed to determine if the virus is associated with the new disease in rainbow trout and to further characterize the virus with respect to classification, relationship with PRV, virulence, pathology and epidemiology.


Traumatic rupture of thoracic epidural capillary hemangioma resulting in acute neurologic deficit: illustrative case.
Thoracic epidural capillary hemangioma is exceedingly rare, with only a few reported cases. The typical presentation usually includes chronic, progressive symptoms of spinal cord compression in middle-aged adults. To the authors' knowledge, this case is the first report in the literature of acute traumatic capillary hemangioma rupture. A 22-year-old male presented with worsening lower extremity weakness and paresthesias after a fall onto his spine. Imaging showed no evidence of spinal fracture but revealed an expanding hematoma over 24 hours. Removal of the lesion demonstrated a ruptured capillary hemangioma. This unique case highlights a rare occurrence of traumatic rupture of a previously unknown asymptomatic thoracic capillary hemangioma in a young adult.


Shrimp-shape domains in a dissipative kicked rotator.
Some dynamical properties for a dissipative kicked rotator are studied. Our results show that when dissipation is taken into account a drastic change happens in the structure of the phase space in the sense that the mixed structure is modified and attracting fixed points and chaotic attractors are observed. A detailed numerical investigation in a two-dimensional parameter space based on the behavior of the Lyapunov exponent is considered. Our results show the existence of infinite self-similar shrimp-shaped structures corresponding to periodic attractors, embedded in a large region corresponding to the chaotic regime.


Physical activity and energy balance.
Energy expenditure rises above resting energy expenditure when physical activity is performed. The activity-induced energy expenditure varies with the muscle mass involved and the intensity at which the activity is performed: it ranges between 2 and 18 METs approximately. Differences in duration, frequency and intensity of physical activities may create considerable variations in total energy expenditure. The Physical Activity Level (= total energy expenditure divided by resting energy expenditure) varies between 1.2 and 2.2-2.5 in healthy adults. Increases in activity-induced energy expenditure have been shown to result in increases in total energy expenditure, which are usually greater than the increase in activity-induced energy expenditure itself. No evidence for increased spontaneous physical activity, measured by diary, interview or accelerometer, was found. However, this does not exclude increased physical activity that can not be measured by these methods. Part of the difference may also be explained by the post-exercise elevation of metabolic rate. If changes in the level of physical activity affect energy balance, this should result in changes in body mass or body composition. Modest decreases of body mass and fat mass are found in response to increases in physical activity, induced by exercise training, which are usually smaller than predicted from the increase in energy expenditure. This indicates that the training-induced increase in total energy expenditure is at least partly compensated for by an increase in energy intake. There is some evidence that the coupling between energy expenditure and energy intake is less at low levels of physical activity. Increasing the level of physical activity for weight loss may therefore be most effective in the most sedentary individuals.


Role of CD44 as cancer stem cell marker in triple-negative breast cancer and its association with histological grade and angiogenesis.
Cancer stem cells (CSC) within the tumors play a central role in tumorigenesis. It is, thus, of utmost importance to identify these cells to develop effective cancer therapy. Triple-Negative Breast Cancer (TNBC) is an aggressive molecular subtype of breast cancer associated with poor patient outcomes. The role of CD44 immunohistochemistry (IHC) as a putative CSC in breast carcinomas, particularly of the TNBC-subtype is ambiguous, with equivocal results. The present study aims to assess the role of CSC in breast carcinoma by immunohistochemical analysis of CD44 expression in TNBC. The association of TNBC expressing CSC with histological grade as well as with angiogenesis (using CD34 IHC) has been studied. Biopsy samples from 58 patients with infiltrating ductal carcinoma, NST were studied. The histology of the tumor was sub-classified into grades 1-3. Based on immunohistochemical analysis (ER, PR, HER2/Neu), the cases were divided into TNBC and NTNBC groups. The tissue sections were also subjected to analysis for CD44 to identify the CSC-phenotype and CD34 to evaluate angiogenesis, to determine the microvascular density (MVD). Out of the 58 cases in the study, 28 were TNBC and 30 were NTNBC. CSC phenotype (CD44 positive) was expressed significantly higher in the TNBC (78%) versus the NTNBC (53%) (p-value 0.043). The MVD estimated using CD34 IHC was lower in the TNBC group in our study, though the difference was not statistically significant. A larger proportion of cases in TNBC showed a higher histological grade (35%) in comparison to NTNBC (27%). However, statistically, it was not significant. Our study demonstrated that CD44 as a CSC marker is seen significantly more in the TNBC category of invasive ductal carcinomas. Further large-scale studies, to confirm these findings, will be of potential therapeutic and prognostic value.


Splinting Strategies to Overcome Confounding Wound Contraction in Experimental Animal Models.
Clinical healing by secondary intention frequently occurs in skin that is firmly anchored to underlying (human) connective tissue. Small animals (rodents) are extensively utilized to model human cutaneous wound healing, but they heal by wound contraction, a process that is limited in the human and confounds quantitative and qualitative evaluation of experimental wound repair. To alleviate wound contraction in loose-skinned species, practical solutions include choosing anatomical sites with firmly attached dermis and subcutis (e.g., rabbit ear) or performing mechanical fixation of the skin by using one of a number of devices or splints. In each case, the wound volume remains relatively constant, allowing the histomorphometric or biomolecular quantification of the cellular response under well-controlled, experimental conditions. In addition, the defined aperture of the splinted wound allows the placement of a variety of materials, including scaffolds, cells, and biologically active formulations into the wound site in an effort to potentiate the healing response and abrogate scarring. In contrast, production of larger experimental wounds or the deliberate distraction of wound margins can be used to model a hypertrophic response. Device design parameters should consider ease of application, durability, and lack of interference with the normal influx of local and circulating cells to the wound site. Improved methods of securing flexible splints would provide a more efficient experimental platform. These devices could also incorporate optical or electronic sensors that report both the mechanical and physiological status of the healing.


Outcomes of children with intermediate-risk neuroblastoma after treatment stratified by MYCN status and tumor cell ploidy.
The goal of Pediatric Oncology Group 9243 was to improve outcomes for children with intermediate-risk neuroblastoma (NB). Patients were assigned to treatments on the basis of age, tumor MYCN status, and tumor cell ploidy. Children in the less intensive arm A received cyclophosphamide/doxorubicin and surgery. Patients not in complete remission postoperatively were treated with cisplatin/etoposide, cyclophosphamide/doxorubicin, and additional surgery. Patients with less favorable features were assigned to arm B, which consisted of carboplatin, etoposide, ifosfamide, and surgery. Survival rates were determined using an intent-to-treat approach. For arm-A patients, the 6-year event-free survival (EFS) was 86% with an SE of 3%. For arm-B patients, the 6-year EFS was 46% with an SE of 7%. MYCN status was the only statistically significant prognostic variable. Among patients whose tumors were MYCN nonamplified, a trend toward improved EFS was seen in children with hyperdiploid versus diploid tumors. However, many of these children responded well to salvage therapy, and overall survival rates did not differ on the basis of ploidy. Six-year EFS rates for arm B were patients with MYCN nonamplified, hyperdiploid tumors, 86% with an SE of 3%; patients with MYCN nonamplified, diploid tumors, 74% with an SE of 10%; patients with MYCN-amplified, hyperdiploid tumors, 46% with an SE of 15%; and patients with MYCN-amplified, diploid tumors, 22% with an SE of 10%. Outcomes for patients with MYCN-nonamplified, hyperdiploid tumors were excellent. Therapy reductions for these patients merit study. A trend toward less favorable outcomes for patients with MYCN-nonamplified, diploid tumors was observed; more children may need to be evaluated before therapy is reduced for this subgroup. For patients with MYCN-amplified tumors, new strategies are needed.


The prevalence of temporomandibular disorders in patients with late whiplash syndrome who experience orofacial pain: a case-control series study.
The authors conducted a study to compare the frequency of specific temporomandibular disorder (TMD) diagnoses in patients who had late whiplash syndrome (LWS) with that in a control group. The authors recruited 65 patients who had orofacial pain and a previous diagnosis of LWS and 65 age- and sex-matched control patients who had chronic orofacial pain without a history of whiplash injury (WI) for a case-control series study. All patients completed a questionnaire pertaining to the Research Diagnostic Criteria for Temporomandibular Disorders and underwent a clinical examination. The authors compared the frequency of TMD diagnoses in case patients with that in control patients by using a χ(2) test; they set the α level a priori at .05. The number of patients diagnosed with myofascial pain (MP) and disk displacement with reduction (DDWR) was significantly higher in the case group than in the control group (P = .002 and P = .001, respectively). The results of this study show a higher frequency of MP and DDWR in patients with LWS than in patients with chronic orofacial pain and no history of WI. Practical Implications. Clinicians should be knowledgeable about the correlation between WI and TMD so they can inform and treat patients accurately.


Adaptive Dynamic Event-Triggered Fault-Tolerant Consensus for Nonlinear Multiagent Systems With Directed/Undirected Networks.
The fault-tolerant consensus of nonlinear multiagent systems (MASs) is studied by using the dynamic event-triggered control and the adaptive control techniques. First, a general dynamic adaptive event-triggered mechanism (DAETM) is proposed, which promotes and improves many existing dynamic event-triggered mechanism and static event-triggered mechanism. On this basis, a new distributed dynamic adaptive event-triggered fault-tolerant controller (DDAETFTC) is designed. Then, two simple and clear criteria are derived, respectively, to ensure consensus can be reached asymptotically for nonlinear MASs with directed networks and with undirected networks under the new DDAETFTC. The obtained results also can apply to linear MASs. Furthermore, it is proven that there is no agent to show the Zeno behavior in MASs under the new DAETM. Finally, an example is given to simulate the obtained results.


Functional and autoradiographic studies of endothelin-1 and endothelin-2 in human bronchi, pulmonary arteries, and airway parasympathetic ganglia.
We compared the contractile potency and efficacy of two of the forms of endothelin (endothelin-1 and endothelin-2) on human bronchi and pulmonary arteries in vitro and examined the effects of sarafotoxin on the bronchial preparations. In addition, we used autoradiographic methods to investigate the location of binding sites for both forms of endothelin within human lung. Endothelin-1 (ET-1) was 2.5 times more potent than endothelin-2 (ET-2) in both the airway and vascular tissues, and both forms of the peptide were 5 times more potent in the isolated pulmonary artery than in the bronchial tissue. There were no differences in the magnitude of the contractions generated by ET-1 and ET-2 in either tissue type. Sarafotoxin also produced a contractile response in the bronchi that was equipotent to ET-1 but of a greater magnitude. Specific binding on the smooth muscle of bronchus, pulmonary artery, and alveolar walls to both ET-1 and ET-2 was detected in autoradiographic studies. In addition, binding sites for both forms of the peptide were localized to parasympathetic ganglia within the airways, where the presence of muscarinic receptors was also confirmed with [3H]QNB. There appeared to be no difference between the endothelins in the location or the density of binding sites. These results indicate that endothelin may have a neuromodulatory role in the airways as well as a direct contractile action on the bronchial and arterial smooth muscle.


Self-Assembly of Chiral Gold Clusters into Crystalline Nanocubes of Exceptional Optical Activity.
Self-assembly of inorganic nanoparticles into ordered structures is of interest in both science and technology because it is expected to generate new properties through collective behavior; however, such nanoparticle assemblies with characteristics distinct from those of individual building blocks are rare. Herein we use atomically precise Au clusters to make ordered assemblies with emerging optical activity. Chiral Au clusters with strong circular dichroism (CD) but free of circularly polarized luminescence (CPL) are synthesized and organized into uniform body-centered cubic (BCC) packing nanocubes. Once the ordered structure is formed, the CD intensity is significantly enhanced and a remarkable CPL response appears. Both experiment and theory calculation disclose that the CPL originates from restricted intramolecular rotation and the ordered stacking of the chiral stabilizers, which are fastened in the crystalline lattices.


Issues in the meta-analysis of cluster randomized trials.
Meta-analyses involving the synthesis of evidence from cluster randomization trials are being increasingly reported. These analyses raise challenging methodologic issues beyond those raised by meta-analyses which include only individually randomized trials. In this paper we review and comment on a selected number of these issues, including problems of study heterogeneity, difficulties in estimating design effects from individual trials and the choice of statistical methods.


Comparison of efficacy of stereotactic body radiotherapy and thoracoscopic surgery in the treatment of early-stage non-small cell lung cancer.
To observe and compare the efficacy and safety between stereotactic body radiotherapy and thoracoscopic surgery in the treatment of early-stage non-small cell lung cancer (NSCLC). The clinical data of 106 early-stage NSCLC patients admitted to the Thoracic Surgery Department of the hospital from February 2014 to February 2016 were retrospectively analyzed. Among these patients, 53 received stereotactic body radiotherapy (SBRT group), and 53 underwent video-assisted thoracoscopic surgery (VATS group). The clinical data of all patients were collected. The short-term response rate, Karnofsky performance status (KPS) score, changes in serum tumor marker levels before and after surgery and adverse reactions were compared between the two groups. Besides, all patients were followed up, and the overall survival (OS) and progression-free survival (PFS) were recorded. The levels of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1) and neurone specific enolase (NSE) were decreased in both groups after treatment, and the differences were not statistically significant between the two groups. The patients tolerated well with SBRT, without evident myelosuppression or adverse hematological effects. In SBRT group, there were 7 cases of radioactive skin reaction, 2 cases of grade I radiation esophagitis and 4 cases of radiation pneumonitis (including 3 cases of grade I radiation pneumonitis and 1 case of grade II radiation pneumonitis). In VATS group, there were 3 cases of incision infection, 2 cases of pulmonary infection, 5 cases of pulmonary atelectasis, 1 case of pulmonary leakage and 1 case of deep vein thrombosis of lower extremity. The 3- year OS and PFS were 79.2% (42/53) and 67.9% (36/53) and 83.0% (44/53) and 77.4% (41/53) in SBRT group and VATS group, respectively. Kaplan-Meier survival showed no statistically significant differences in the OS and PFS between the two groups (log-rank). SBRT achieves better RR and DCR, similar OS and PFS to those of typical thoracoscopic surgery, and good patient tolerance in the treatment of early- stage NSCLC, which is a safe and effective treatment means.


Efficient process technologies for the preparation of oligonucleotides.
Efficient process technologies for the preparation of 2'-substituted nucleoside monomers, as well as for oligonucleotide preparation, are introduced. A novel method for efficient preparation of 2'-substituted uridines is presented. This method employs the 3'-hydroxyl group of 2,2'-anhydrouridine as a tether for the facile intramolecular introduction of nucleophiles to the 2'-position. It allows access to 2'-alkoxy substituents from their alcohol precursors and to substituted 2'-amino substituents, such as the novel O-substituted 2'-hydroxylaminouridines. A novel process for large-scale oligonucleotide synthesis is discussed, which allows solution phase coupling of the monomer to the growing oligonucleotide chain. This is followed by selective isolation of productive coupling product by anchoring to a resin. Release from this resin completes a coupling cycle.


Severe vs moderate energy restriction with and without exercise in the treatment of obesity: efficiency of weight loss.
Thirty obese women were randomly assigned to either 40% [severe energy restriction (SER)] or 70% [moderate energy restriction (MER)] of their maintenance energy requirements and to no exercise, aerobic exercise (walking), or aerobic exercise plus circuit weight training. Body composition by hydrostatic weighing and energy expenditure by indirect calorimetry were measured at 0, 3, and 6 mo. In addition, we developed a deficit-efficiency factor (DEF), calculated as body energy loss/dietary energy deficit, to attempt to quantify the effectiveness of the weight-reduction interventions. Subjects in the SER group lost more weight (mean +/- SE: 15.1 +/- 1.4 vs 10.8 +/- 1.0 kg), fat (11.7 +/- 1.1 vs 8.3 +/- 0.6 kg), and fat-free mass (2.8 +/- 0.3 vs 1.8 +/- 0.3 kg) than the MER group (P < or = 0.05). However, the overall DEF was greatest in the MER group (0.80 +/- 0.07) compared with the SER group (0.52 +/- 0.05; P < or = 0.01). Exercise had no significant effect. This study demonstrates that MER may offer an advantage over SER because it produces a greater energy loss relative to energy deficit.


Point of care strategy for rapid diagnosis of novel A/H1N1 influenza virus.
In late June 2009, we implemented for public hospitals of Marseille Point Of Care strategy for rapid diagnosis of novel A/H1N1 influenza virus. During two months, we have tested more than 900 specimens in both Point Of Care laboratories. We believe that implementation of Point of Care strategy for the largest number of suspects cases may improve quality of patients care and our knowledge of the epidemiology of the pandemic.


Evaluation Using Polar Coordinate of the Representation of Movement in the Drawings of Children Aged 5 to 8 Years.
The progressive complexity of mental representation is the basis for changes in human cognitive development. Evaluation of its external manifestations as graphic representation in drawings could be an instrument to understand changes in cognitive development and representational complexity. The aim of this study is to evaluate the appearance and role of the indicators used by children to represent moving figures in their drawings. This allows us to know the continuum from its non-manifestation to full expression through the vectorial interrelationships of the graphic indicators in each of the ages studied. Participants were n = 240 children from 5 to 8 years old; their drawings of two moving figures were analyzed, applying the polar coordinate technique. Results show a map of interrelations among the graphical movement indicators and changes in the drawing elements in an increasing continuum of complexity and the roles conferred to figures sketched. The conclusion is that changes evaluated in drawings can interactively reflect mental representation, and they could promote its transformation. The applied transfer of the results to education is discussed, in order to optimize the representational complexity and cognitive development.


Review of zonisamide development in Japan.
Zonisamide is a benzisoxazole-based compound first synthesized in the early 1970s by the research laboratories of Dainippon Pharmaceutical Company in Osaka, Japan. Identified as an anticonvulsant during exploratory research, zonisamide has since been characterized as having broad-spectrum antiepilepsy and neuroprotective effects. Early clinical studies in Japan demonstrated that zonisamide has a long elimination half-life and is well tolerated; Phase II and III clinical trials established the drug's efficacy and safety for the treatment of partial and generalized seizures. In 1989, zonisamide was approved and marketed in Japan under the trade name of Excegran. Data from postmarketing surveillance studies and clinical observations over 10 years of use have continued to support zonisamide's efficacy and safety, identified its usefulness as monotherapy, and characterized its effectiveness for various seizure types and epilepsy syndromes.


One-year clinical outcomes after complete arterial coronary revascularization.
Conventional coronary bypass surgery applies single internal mammary arteries and saphenous vein graft conduits for revascularization of occluded coronary arteries. While the use of saphenous vein grafts is limited by early graft occlusion, little data exist on clinical experiences with complete arterial revascularization. From January 2003 to July 2004, 390 patients were transferred from Red Cross Hospital Cardiology Center to the Rotenburg Cardiovascular Center for coronary bypass operation. From these patients, 200 were selected for complete arterial revascularization. Mean age of the patients was 66.7+/- 8.0 years; 80.5% were male; 68.5% had triple-vessel disease, 31% had two-vessel disease, and 0.5% had single-vessel disease; 32% were diabetic; and 6.5% had a previous bypass operation. Left ventricular ejection fraction was >50% in 85.5% and 30-50% in 14.5%. Double internal mammary artery grafts were used in 98% and single internal mammary artery grafts in 2%. In 51%, the right internal mammary artery was connected with the left internal mammary artery as a T-graft and in 17%, it was used as a free aortocoronary graft. Radial artery grafts were used in 4%. The average number of anastomoses per patient was 3.4. During the primary in-hospital stay, 1.5% of the patients had to undergo reoperation, 3.5% had myocardial infarctions, 3.5% had wound healing complications, 1.0% experienced an ischemic stroke, and 1 patient died following an acute myocardial infarction. At 12 months, 1.0% underwent percutaneous reinterventions, 0.5% had to be reoperated, 0.5% had a myocardial infarction, and 1.0% died. The actuarial survival rate at 12 months was 99%. When both the internal mammary arteries are used as the preferred surgical strategy, complete arterial revascularization can be performed with excellent clinical results over 12 months.


Bromocriptine for infertile males with mild hyperprolactinemia: hormonal and spermatogenic effects.
To clarify the influence of hyperprolactinemia on spermatogenesis and steroidogenesis in infertile male patients, the serum prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol concentrations were and the effect of bromocriptine treatment on spermatogenesis was examined. A total of 1234 patients were evaluated and 147 men had hyperprolactinemia. Of these, only 30 had PRL concentrations more than twice the upper limit of normal and most of them had a little excess over the upper limit. For 10 of these 30, serum hormone concentrations were measured and semen was analyzed before and after bromocriptine administration. No relationship between the PRL and other hormone concentrations was found. No changes were noted in the LH, FSH, testosterone, or estradiol concentrations, or in the sperm density and motility after treatment. The mean PRL decreased from 26.5 +/- 4.5 to 1.4 +/- 1.8 ng/mL. In infertile men who are mildly hyperprolactinemic, bromocriptine administration does not improve semen analysis, although it does normalize the PRL.


Cilostazol may suppress restenosis and new contralateral carotid artery stenosis after carotid endarterectomy.
Carotid artery restenosis is a serious complication following carotid endarterectomy (CEA), so preventative management of the risk factors is important. The present study investigated the potential of cilostazol, a mediator of vascular stabilization as well as inhibitor of platelet aggregation, to suppress restenosis on the ipsilateral carotid artery and new plaque development on the contralateral carotid artery. Eighty-two patients treated by CEA were divided into two groups according to the postoperative antiplatelet aggregation drugs into the cilostazol and other groups. Patients were periodically examined for recurrence of the plaque on the ipsilateral side, development of plaque on the contralateral side, and the bilateral intermedia thicknesses measured by ultrasonographic examination for up to 6 years. Restenosis and development of the contralateral plaque were not detected in any patients in the cilostazol group, whereas such changes were found in seven patients in the other group. Cilostazol might be effective to inhibit the growth mechanism of plaque.


Involvement of DNA curvature in intergenic regions of prokaryotes.
It is known that DNA curvature plays a certain role in gene regulation. The distribution of curved DNA in promoter regions is evolutionarily preserved, and it is mainly determined by temperature of habitat. However, very little is known on the distribution of DNA curvature in termination sites. Our main objective was to comprehensively analyze distribution of curved sequences upstream and downstream to the coding genes in prokaryotic genomes. We applied CURVATURE software to 170 complete prokaryotic genomes in a search for possible typical distribution of DNA curvature around starts and ends of genes. Performing cluster analyses and other statistical tests, we obtained novel results regarding various factors influencing curvature distribution in intergenic regions, such as growth temperature, A+T composition and genome size. We also analyzed intergenic regions between converging genes in 15 selected genomes. The results show that six genomes presented peaks of curvature excess larger than 3 SDs. Insufficient statistics did not allow us to draw further conclusion. Our hypothesis is that DNA curvature could affect transcription termination in many prokaryotes either directly, through contacts with RNA polymerase, or indirectly, via contacts with some regulatory proteins.


Pricing air pollution: evidence from short-term exposure to air pollution on hospitalization of acute bronchitis and chronic obstructive pulmonary disease in southwestern China.
Existing evidence suggests that ambient air pollution has serious adverse effects on respiratory diseases, yet there is little direct evidence from China regarding corresponding economic losses. Here we quantified air pollution-related acute health effects and related economic losses of the most common two respiratory diseases in southwestern China, acute bronchitis and chronic obstructive pulmonary disease (COPD). We applied a distributed lag non-linear model to analyse the relationship between ambient air pollutants and hospital admissions of acute bronchitis and COPD, then applied the cost of illness method to explore the attributing economic burden. During the study period, 528 334 and 99 419 hospital admissions of acute bronchitis and COPD, respectively, were recorded. As a result, during the study period the total hospitalization economic losses attributable to air pollution were 486.40 and 254.74 million yuan for acute bronchitis and COPD, respectively, accounting for 0.015% of local gross domestic product. Our research provides intuitive evidence on the health and economic impacts of short-term exposure to air pollution, which is a key basis for the formulation of environmental policies.


A new parametric model for survival data with long-term survivors.
We develop a new parametric model using the three-parameter Burr XII distribution for the analysis of survival data with long-term survivors, which includes the previous Weibull mixture model as a special case. The new model is applied to the analysis of a set of leukaemia data for which previous attempts in the literature using traditional parametric models were unsatisfactory due to lack of fit. It is shown that the new model improves the fit to the leukaemia data significantly and is thus capable of providing more credible answers to a variety of statistical inference problems that are of interest to medical researchers and practitioners.


Screening for congenital hypothyroidism (CH) among Filipino newborn infants. Philippine Newborn Screening Study Group.
From June 1996 to June 1998 a total of 62.841 newborn infants were screened for congenital hypothyroidism with thyroid stimulating hormone assay as a primary test. The method used was an immunofluorescent assay using the DELFIA TSH Kit on dried blood specimens collected by heelprick on filter paper. All infants with TSH values greater than 20 microU/ml were retested. If the results remained abnormally high, confirmatory testing was done by radioimmunoassay. All infants who were confirmed to be hypothyroid were referred to pediatric endocrinologists for initial management. The overall weighted incidence of congenital hypothyroidism obtained in this study was 0.000277 (95% CI; 0.000122 - 0.000432) or 1:3,610 which may be higher than that reported by most screening programs worldwide. The recall rate was 0.16%. The higher recall rate may be explained by early testing in a number of cases and by the possibility of iodine deficiency in some of the mothers. On the basis of the results of this study, we would recommend (1) screening on a greater number of infants to verify the incidence of CH and (2) establishing normal TSH values at different hours of life to improve our recall rate.


Live-3D-Cell Immunocytochemistry Assays of Pediatric Diffuse Midline Glioma.
Cell migration and invasion are specific hallmarks of Diffuse Midline Glioma (DMG) H3K27M-mutant tumors. We have already modeled these features using three-dimensional (3D) cell-based invasion and migration assays. In this study, we have optimized these 3D assays for live-cell immunocytochemistry. An Antibody Labeling Reagent was used to detect in real-time the expression of the adhesion molecule CD44, on the plasma membrane of migrating and invading cells of a DMG H3K27M primary patient-derived cell line. CD44 is associated with cancer stem cell phenotype and tumor cell migration and invasion and is involved in the direct interactions with the central nervous system (CNS) extracellular matrix. Neurospheres (NS) from the DMG H3K27M cell line were embedded into the basal membrane matrix (BMM) or placed onto a thin coating layer of BMM, in the presence of an anti-CD44 antibody in conjunction with the antibody labeling reagent (ALR). The live-3D-cell immunocytochemistry image analysis was performed on a live-cell analysis instrument to quantitatively measure the overall CD44 expression, specifically on the migrating and invading cells. The method also allows visualizing in real-time the intermittent expression of CD44 on the plasma membrane of migrating and invading cells. Moreover, the assay also provided new insights into the potential role of CD44 in the mesenchymal to amoeboid transition in DMG H3K27M cells.


Toll-Like Receptor 2 Agonist Pam3CSK4 Alleviates the Pathology of Leptospirosis in Hamster.
Leptospirosis, caused by pathogenic spirochetes, is a zoonotic disease of global importance. The detailed pathogenesis of leptospirosis is still unclear, which limits the ideal treatment of leptospirosis. In this study, we analyzed the expression of Toll-like receptor 2 (TLR2) and TLR4 in target organs of both resistant mice and susceptible hamsters after Leptospira interrogans serovar Autumnalis infection. TLR2 but not TLR4 transcripts in mouse organs contrasted with delayed induction and overexpression in hamster organs. Coinjection of leptospires and the TLR2 agonist Pam3CSK4 into hamsters improved their survival rate, alleviated tissue injury, and decreased the abundance of leptospires in target organs. The production of interleukin-10 (IL-10) from tissues was enhanced in hamsters of the group coinjected with leptospires and Pam3CSK4 compared with the leptospira-injected group. Similarly, IL-10 levels in TLR2-deficient mice were lower than those in wild-type mice. A high ratio of IL-10/tumor necrosis factor alpha (TNF-α) levels was found in both infected wild-type mice and hamsters coinjected with leptospires and Pam3CSK4. Moreover, TLR2-dependent IL-10 expression was detected in peritoneal macrophages after leptospira infection. Our data demonstrate that coinjection of leptospires and Pam3CSK4 alleviates the pathology of leptospirosis in hamsters; this effect may result from the enhanced expression of TLR2-dependent IL-10.


TREATMENT OF TRIPLANE FRACTURE ANKLE FRACTURES ASSOCIATED WITH IPSILATERAL TIBIAL FRACTURES USING A NOVEL APPROACH.
The aim of this study is to purpose a novel approach to the concomitant triplanar and tibial shaft fracture. Retrospective study between 2001 and 2019. We collected the patients' general information, clinical and radiographic data, and complications after the following three-step treatment: (1) fixation of the Salter-Harris II fracture of the triplane fracture, (2) fixation of the Salter-Harris II/IV fracture with cannulated screws, and (3) fixation of the tibial fracture with flexible titanium nails. The study included seven patients (six males) with a mean age of 14 years and a mean follow-up of 6.4 years (minimum two years). Five triplane fractures had two fragments and two had three fragments. Five fractures were classified as Salter-Harris II and two as Salter-Harris IV. Three tibial fractures were long oblique, three were spiral, and one had a third fragment. Six fractures affected the middle third and one affected the distal third of the tibia. All triplane and tibial fractures consolidated without significant displacement. No physeal damage was identified. This study described the association of tibial fractures with triplane ankle fractures managed by our proposed treatment, which proved to be effective for this fracture association. Level of Evidence IV, Case Series.


Interleukin-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates interleukin-17A and RORgammat in gammadelta T cells.
Interleukin (IL)-23 is essential for the development of various experimental autoimmune models. However, the role of IL-23 in non-autoimmune experimental arthritis remains unclear. Here, we examined the role of IL-23 in the non-autoimmune antigen-induced arthritis (AIA) model. In addition, the regulatory potential of IL-23 in IL-17A and retinoic acid-related orphan receptor gamma t (RORgammat) expression in CD4+ and TCRgammadelta+ T cells was evaluated systemically as well as at the site of inflammation. Antigen-induced arthritis was induced in wild-type, IL-23p19-deficient and IL-17 Receptor A - knockout mice. At different time points, synovial cytokine and chemokine expression was measured. At days 1 and 7 of AIA, splenocytes and joint-infiltrating cells were isolated and analyzed for intracellular IL-17A and interferon (IFN)-gamma ex-vivo by flow cytometry. In splenic CD4+ and TCRgammadelta+ T cells gene expression was quantified by flow cytometry and quantitative PCR. IL-23 was critical for full-blown AIA. Lack of IL-23 did not prevent the onset of joint inflammation but stopped the progression to a destructive synovitis. IL-23 regulated IL-17A expression in CD4+ T cells in the spleen. Of note, IL-17A and IFN-gamma expression was reduced in CD4+ T cells in the inflamed joints of IL-23p19-deficient mice. Interestingly, IL-23 was also critical for the induction of IL-17A and RORgammat but not IFN-gamma in TCRgammadelta+ T cells in the inflamed joints. The importance of the IL-23/IL-17 axis was further confirmed using IL-17 Receptor A knockout mice showing significantly milder AIA compared to control mice, with a disease course comparable to that of IL-23p19-deficient mice. These data show that IL-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates the proportion of IL-17A and IFN-gamma-positive CD4+ T cells at the site of inflammation. Furthermore, IL-23 regulates IL-17A and RORgammat expression in TCRgammadelta T cells in arthritis. These findings indicate that regulating the IL-23 pathway may have therapeutic potential in non-autoimmune arthritis.


Facile, general and template-free construction of monodisperse yolk-shell metal@carbon nanospheres.
Herein, we report a general and template-free protocol to construct novel yolk-shell metal@carbon nanospheres based on confined interfacial copolymerization, which greatly simplifies the synthetic route, yields uniform nanospheres with controllable diameters, and results in highly porous carbon shells. The yolk-shell Au@carbon shows improved adsorption capacity and high catalytic ability due to the synergistic effect of Au and the porous carbon shell.


[Reflections on health policy evaluation in Brazil].
This article aims to contribute to the debate on public policy evaluation, specifically in the Brazilian health sector. The objective is to analyze some of the key issues in this field through a literature search in the SciELO database. Sixty-six articles were selected using the descriptors "health evaluation" and "evaluation of health programs and projects" in indexed Brazilian public health periodicals from 1994 to 2009. The article explores aspects of academic output according to an established typology and in relation to possibilities for developing the theme of policy evaluation, linked to interventions focused on efficacious, efficient, and effective treatment of the population's health problems.


Comparing continuous and dichotomous scoring of the balanced inventory of desirable responding.
The Balanced Inventory of Desirable Responding (BIDR; Paulhus, 1994) is a widely used instrument to measure the 2 components of social desirability: self-deceptive enhancement and impression management. With respect to scoring of the BIDR, Paulhus (1994) authorized 2 methods, namely continuous scoring (all answers on the continuous answer scale are counted) and dichotomous scoring (only extreme answers are counted). In this article, we report 3 studies with student samples, and continuous and dichotomous scoring of BIDR subscales are compared with respect to reliability, convergent validity, sensitivity to instructional variations, and correlations with personality. Across studies, the scores from continuous scoring (continuous scores) showed higher Cronbach's alphas than those from dichotomous scoring (dichotomous scores). Moreover, continuous scores showed higher convergent correlations with other measures of social desirability and more consistent effects with self-presentation instructions (fake-good vs. fake-bad instructions). Finally, continuous self-deceptive enhancement scores showed higher correlations with those traits of the Five-factor model for which substantial correlations were expected (i.e., Neuroticism, Extraversion, and Conscientiousness). Consequently, these findings indicate that continuous scoring may be preferable to dichotomous scoring when assessing socially desirable responding with the BIDR.


[House dust mites and storage compartment mites as allergy inducers].
Perennial respiratory diseases like chronic rhinopathy or bronchial asthma can often be related to an allergy to indoor allergens. Of these, the most relevant allergens are derived from house dust mites. Epidemiologic data show that 8.9% of the general population exhibit a sensitization to house dust mites. Based on a better knowledge of the biology and the living habits of house dust mites effective allergen avoidance measures can be performed which are, however, quite cumbersome and go beyond just encasing mattresses. Of particular relevance is the reduction of the relative humidity below 50%. Relatives of house dust mites are storage mites which are increasingly realized as an important cause of respiratory allergies. The most important is Lepidoglyphus destructor which is dominant in dust probes from Europe and shows crossreactivity with other storage mites. They are found in barns and grain stores and are thus important causes for occupational respiratory diseases in farmers. The existence of storage mites in house dust is connected with damp housing conditions.


Unusual cerebellar ataxia: "worm wobble" revisited.
We present an unusual case of cerebellar ataxia in a 2 year old girl several days after treatment with piperazine citrate for suspected worm infestation. This is the first reported case of delayed onset neurotoxicity following the therapeutic administration of piperazine in a previously well child.


K+ conductance activated during regulatory volume decrease. The channels in Ehrlich cells and their possible molecular counterpart.
K+ currents activated by hypotonic cell swelling have been studied in Ehrlich ascites tumour cells by the whole-cell recording mode of the patch-clamp technique. K+ together with Cl- currents developed in the absence of added intracellular Ca2+ and with strong buffering of internal Ca2+ in experiments conducted at 37 degrees C. Manipulation of the extracellular medium with other cations suggests a selectivity sequence of K+ > Rb+ > NH4+ > or = Na+ approximately equals Li+ approximately equals Cs+. The current-voltage relationship of the volume-sensitive K+ current was well fitted with the Goldman-Hodgkin-Katz current equation between -130 and 20 mV at both physiological and high K+ extracellular solutions. The class III antiarrhytmic drug clofilium blocked the volume-sensitive K+ current in a voltage-independent manner. Clofilium was also found to be a strong inhibitor of the regulatory volume decrease (RVD) response of Ehrlich cells. The leukotriene D4 (LTD4) can activate the same current in isotonicity, consistent with a role for this compound in the signalling process of volume regulation. It is suggested that K+ channels activated by cell swelling belong to the so-called background K+ channel group. These are voltage-independent channels which underlie the resting potential of many cells and have recently been identified as belonging to a family of K+ channels with two pore domains in tandem (2P-4TM). Preliminary experiments show the presence of the TASK-2 channel, a member of the 2P-4TM family inhibited by acid extracellular pH, in Ehrlich cells and suggest that it might underlie the swelling-induced K+ current.


Prediction of dielectric constants of ABO3-type perovskites using machine learning and first-principles calculations.
In this study, the machine-learning method, combined with density functional perturbation theory (DFPT) calculations, was implemented to predict and validate the dielectric constants of ABO3-type perovskites. For the construction of the training database, the dielectric constants of 7113 inorganic materials were extracted from the Materials Project. The chemical, structural, and physical descriptors were generated and trained using the gradient-boosting-based regressor after feature engineering. The prediction accuracies were 0.83 and 0.67 (R2) and 0.12 and 0.26 (root mean square error) for the electronic and ionic contributions to the dielectric constant, respectively. The constructed surrogate model was then employed to predict the dielectric constants of the ABO3-type perovskites (216 structures), whose thermodynamic stabilities were satisfactory. The predicted values were validated using DFPT calculations. The constructed database was further used to develop a surrogate model for the prediction of dielectric constants. The final R2 prediction accuracies reached 0.79 (electronic) and 0.67 (ionic).


A 4.8 ps root-mean-square resolution time-to-digital converter implemented in a 20 nm Cyclone-10 GX field-programmable gate array.
It is difficult to improve the resolution and precision of a field-programmable gate array (FPGA)-based time-to-digital converter (TDC) in time interval measurement. In this study, we design a carry-look-ahead delay chain structure and integrate an interleaved sampling method with an online calibration and bin readjustment approach to implement a TDC. We take advantage of the adaptive logic module units applied in a Cyclone-10 GX (10CX220YF780E5G), which is a 20 nm low-power consumption and low-cost FPGA. In this new generation FPGA, we implemented a high-precision time interval measurement, which exceeded all our previous works with a 4.8 ps root-mean-square resolution and a 5.68 ps least-significant-bit resolution.


Development of an ion pairing reversed-phase liquid chromatography-mass spectrometry method for characterization of clustered regularly interspaced short palindromic repeats guide ribonucleic acid.
Guide ribonucleic acid (gRNA) is a critical reagent in clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing. The single stranded guide RNA (sgRNA) is the most commonly used gRNA in application. Evaluation of the impurity profile of synthetic sgRNA is important for any CRISPR genome editing experiments. However, the large molecular size, complex impurity profile and unique secondary structure pose many challenges in the analysis of sgRNA by ion pairing reversed-phase liquid chromatography (IP-RPLC), the commonly used method. In this work, we developed a generic IP-RPLC method for guide RNA analysis. We found that large pore size of stationary phase was the most critical column parameter to achieve high resolution separation of sgRNA while particle structure, particle size and surface chemistry had less impact. Our results indicated that charge interaction was the most critical mechanism for retention and mass transfer had less impact on the performance of separation. An IP-RPLC/mass spectrometry (MS) method was also developed with a specific practice to reduce adducts and enable intact MS analysis of sgRNAs. The generic IP-RPLC method demonstrates its feasibility to serve as a release, stability, characterization and in-process control testing method for synthetic sgRNA products.


Expression of an alfalfa (Medicago sativa L.) ethylene response factor gene MsERF8 in tobacco plants enhances resistance to salinity.
Ethylene response factors (ERF) play crucial roles in plant development and response to stresses. Here, a novel cDNA fragment (MsERF8) encoding an ERF protein with an AP2 domain was isolated and characterized from alfalfa. The MsERF8 cDNA has an open reading frame of 603 bp and encodes a nuclear protein of 201 amino acids. Q-RT-PCR analysis revealed that MsERF8 was strongly enriched in roots and leaves compared with stems, flower buds and flowers of mature alfalfa plants. Bioinformatic analysis of the MsERF8 promoter indicated a number of elements associated with stress-related responses, and MsERF8 transcripts in alfalfa seedlings were induced by NaCl, PEG6000, Al(2)(SO(4))(3) and five different hormones. Expression of MsERF8 in transgenic tobacco plants resulted in higher tolerance to salinity than with non-transgenic plants. This data shows that MsERF8 is a gene which prevents or alleviates salinity damage and has strong potential to impart salt tolerance to other crop plants.


Dual oxidases.
Reactive oxygen species (ROS) have an important role in various physiological processes including host defence, mitogenesis, hormone biosynthesis, apoptosis and fertilization. Currently, the most characterized ROS-producing system operates in phagocytic cells, where ROS generated during phagocytosis act in host defence. Recently, several novel homologues of the phagocytic oxidase have been discovered and this protein family is now designated as the NOX/DUOX family of NADPH oxidases. NOX/DUOX enzymes function in a variety of tissues, including colon, kidney, thyroid gland, testis, salivary glands, airways and lymphoid organs. Importantly, members of the enzyme family are also found in non-mammalian species, including Caenorhabditis elegans and sea urchin. The physiological functions of novel NADPH oxidase enzymes are currently largely unknown. This review focuses on our current knowledge about dual oxidases.


[The surgical treatment of chronic ischemic mitral insufficiency].
Operative correction of chronic ischemic mitral regurgitation (CIMR) is associated with a high-risk approach. The objective of this retrospective study was to evaluate the short- and long-term results of surgical treatment of CIMR. From 1989 to 1997, mitral valve replacement or repair was performed on 46 patients with CIMR. The average age range was 63.7 +/- 6.9; 8 patients were females; 30 patients (65.2%) were in New York Heart Association (NYHA) functional class III or IV; 4 patients (8.6%) were in chronic atrial fibrillation and preoperative myocardial infarction was lower in 23 patients (50%). Preoperative echo-Doppler analysis showed severe mitral insufficiency in 15 patients (32.6%). Preoperative mean pulmonary artery pressure (PAP) was 33.6 +/- 13.6 mmHg, mean ejection fraction (EF) 37.8 +/- 13.5%. Mitral valve replacement was performed in 12 patients (26%). Mitral valve repair was performed in 34 patients (73.9%). Myocardial revascularization was performed in 42 patients (91.3%) (mean graft/patient 2.2 +/- 0.8); aneurysmectomy was performed in 5 patients (10.8%), and in 2 patients (4.3%) tricuspid insufficiency was corrected by performing annuloplasty. The overall operative mortality was 8.6% (4 patients). The operative mortality for repair was 5.8% (2 patients) and for replacement was 16.6% (2 patients). One patient was reoperated three days after first operation due to annuloplasty dehiscence. Postoperative morbidity included low output syndrome in 7 patients (15.2%), bleeding in 2 patients (4.3%), and cerebral embolism in 2 patients (4.3%). The mean length of stay in intensive care was 6.5 +/- 10.5 days. Follow-up (mean 27.6 +/- 3.3 months) was 88% complete and revealed good functional and clinical results: 86.4% of the patients in I-II NYHA class. One patient was reoperated due to mitral insufficiency progression. Two late deaths occurred, one due to acute myocardial infarction and the other to lung cancer. While long-term follow-up is mandatory, our results suggest that: a) surgical treatment of CIMI is feasible with acceptable operative risks; b) mid-term functional and clinical results are favorable; c) the choice of treatment--valve replacement or repair--is still debatable.


Cyclic nucleotide-activated currents in cultured olfactory receptor neurons of the hawkmoth Manduca sexta.
Moth pheromones cause rises in intracellular Ca(2+) concentrations that activate Ca(2+)-dependent cation channels in antennal olfactory receptor neurons. In addition, mechanisms of adaptation and sensitization depend on changes in cyclic nucleotide concentrations. Here, cyclic nucleotide-activated currents in cultured olfactory receptor neurons of the moth Manduca sexta are described, which share properties with currents through vertebrate cyclic nucleotide-gated channels. The cyclic nucleotide-activated currents of M. sexta carried Ca(2+) and monovalent cations. They were directly activated by cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), modulated by Ca(2+)/calmodulin, and inhibited by lanthanum. M. sexta cyclic nucleotide-activated currents developed in an all-or-none manner, which suggests that the underlying channels are coupled and act coordinately. At least one cAMP- and two cGMP-activated nonselective cation currents could be distinguished. Compared with the cAMP-activated current, both cGMP-activated currents appeared to conduct more Ca(2+) and showed a stronger down-regulation by Ca(2+)/calmodulin-dependent negative feedback. Furthermore, both cGMP-activated currents differed in their Ca(2+)-dependent inhibition. Thus M. sexta olfactory receptor neurons, like vertebrate sensory neurons, appear to express nonselective cyclic nucleotide-activated cation channels with different subunit compositions. Besides the nonselective cyclic nucleotide-activated cation currents, olfactory receptor neurons express a cAMP-dependent current. This current resembled a protein kinase-modulated low-voltage-activated Ca(2+) current.


[Combined chemotherapy with cisplatin plus vinorelbine showed efficacy in a case of metastatic primary cutaneous adenoid cystic carcinoma].
We report a case of a 65-year-old man with metastatic primary cutaneous adenoid cystic carcinoma that was effectively treated by combination chemotherapy with cisplatin (CDDP) plus vinorelbine(VNR). He detected a tumor mass on the anterior surface of his left patella in 2003 and underwent a tumorectomy in October 2008. He was given a diagnosis of primary cutaneous adenoid cystic carcinoma with metastatic lesions to multiple lungs and left tibial bone and then given chemotherapy combining CDDP plus VNR as the first treatment in December 2008. By this treatment for six cycles, the lung metastatic tumors gradually reduced on chest CT. We reported the efficacy of combined treatment with CDDP plus VNR for primary cutaneous adenoid cystic carcinoma, because this clinical condition was very rare and the standard treatment has still not been established.


Enantiomeric separation of free L- and D-amino acids in hydrolyzed protein fertilizers by capillary electrophoresis tandem mass spectrometry.
Two capillary electrophoresis-tandem mass spectrometry (CE-MS(2)) methods were optimized in this work using cyclodextrins (CDs) as chiral selectors in order to determine the degree of racemization of the free amino acids contained in different hydrolyzed protein fertilizers used as plant biostimulants. The methodologies developed were characterized by the specificity of MS(2) experiments enabling the identification of all protein amino acids, except for cysteine. The enantiomeric separation of up to 14 amino acids was achieved with resolutions above 1.0 and limits of detection between 0.02 and 0.8 μM. The methods were applied to the analysis of complex samples such as hydrolyzed protein fertilizers to evaluate the presence of d-amino acids after different kinds of hydrolysis treatments. The results corroborated the absence or almost negligible presence of enantiomeric conversions of the L-amino acids into D-amino acids in the case of fertilizers obtained by enzymatic hydrolysis, as well as the high racemization rate for those obtained through a chemical hydrolysis.


Molecular regulators of leucocyte chemotaxis during inflammation.
A fundamental feature of any immune response is the movement of leucocytes from one site in the body to another to provide effector functions. Therefore, elucidating the molecular mechanisms underlying the migration of leucocytes from the blood to tissues is critical to our understanding of immune function during inflammation. The classic steps of leucocyte trafficking involve leucocyte tethering and rolling on vessel walls of the vasculature, followed by firm adhesion to the endothelium. Recent evidence suggests that upon adhering, leucocytes crawl within the vessels before transmigrating across vessel walls and crawling into targeted tissues. The directed nature of the crawling events is orchestrated by a complex array of soluble factors and molecular regulators in combination with the local intravascular and extracellular environment. In fact, this process is known as chemotaxis and orientates cell movement in relation to the ligand gradient. Several signalling pathways have been proposed to be involved in this gradient-sensing and amplification process, but the best studied, discussed in detail here, is the phosphatidylinositol 3-kinase pathway. Substantial progress has been made in understanding how cells roll and adhere in blood vessels; however, how cells crawl in blood vessels, emigrate, and then crawl in tissues has received much less attention. Therefore, the focus of this review is to provide recent insights into molecular mechanisms and cellular processes that mediate leucocyte crawling in blood vessels and tissues during the inflammatory response.


Corticostriatal transformations in the primate somatosensory system. Projections from physiologically mapped body-part representations.
1. The basal ganglia of primates receive somatosensory input carried largely by corticostriatal fibers. To determine whether map-transformations occur in this corticostriatal system, we investigated how electrophysiologically defined regions of the primary somatosensory cortex (SI) project to the striatum in the squirrel monkey (Saimiri sciureus). Receptive fields in the hand, mouth, and foot representations of cortical areas 3a, 3b, and 1 were mapped by multiunit recording; and small volumes of distinguishable anterograde tracers were injected into different body-part representations in single SI areas. 2. Analysis of labeled projections established that at least four types of systematic remapping occur in the primate corticostriatal system. 1) An area of cortex representing a single body part sends fibers that diverge to innervate multiple regions in the putamen, forming branching, patchy fields that are densest in the lateral putamen. The fields do not form elongated cylindrical forms; rather, they are nearly as extended mediolaterally as they are rostrocaudally. 2) Cortical regions representing hand, mouth, and foot send globally somatotopic, nonoverlapping projections to the putamen, but regions with closely related representations (such as those of the thumb and 5th finger in area 3b) send convergent, overlapping corticostriatal projections. The overlap is fairly precise in the caudal putamen, but in the rostral putamen the densest zones of the projections do not overlap. 3) Regions representing homologous body parts in different SI cortical areas send projections that converge in the putamen. This was true of paired projections from areas 3a and 3b, and from areas 3b and 1. Thus corticostriatal inputs representing distinct somatosensory submodalities can project to the same local regions within the striatum. Convergence is not always complete, however: in the rostral putamen of two cases comparing projections from areas 3a and 1, the densest zones of the projections did not overlap. 4) All projections from SI avoid striosomes and innervate discrete zones within the matrix. 3. These experiments demonstrate that the somatosensory representations of the body are reorganized as they are projected from SI to the somatosensory sector of the primate putamen. This remapping suggests that the striatal representation of the body may be functionally distinct from that of each area of SI. The patchy projections may provide a basis for redistribution of somatosensory information to discrete output systems in the basal ganglia. Transformations in the corticostriatal system could thus be designed for modulating different movement-related programs.


The Perils of Buddy Wire Use With a Filterwire.
Embolic protection devices may decrease the risk of distal embolization during percutaneous coronary intervention of saphenous vein graft and highly thrombotic lesions. Use of a buddy wire can facilitate equipment delivery but carries perils when used together with a filter. We present two cases demonstrating potential complications of buddy wire use with a filter. In the first case a saphenous vein graft perforation occurred after stenting. A buddy wire and second balloon were used to maintain hemostasis while removing the Filterwire. The buddy wire, however, was caught in the filter retrieval catheter, interlocking the two guide catheters and was eventually removed after forceful pulling. In the second case a Filterwire was used to prevent distal embolization of a highly thrombotic right coronary artery lesion. A buddy wire was used to assist with equipment delivery. A stent was inadvertedly deployed over the buddy wire, entrapping the Filterwire. The entrapped Filterwire was eventually removed after multiple balloon inflations over the buddy wire.


Nanometer-resolved quantification of mechanical response in nanoparticle-based composites.
Nanocomposites constitute an upcoming class of materials that has enormous potential within a broad range of areas, particularly with regard to mechanical applications. However, the tuning of material properties requires a full understanding of the mechanical response of the nanocomposite across all length scales. While characterization from the micro to macroscale is well established at this point, quantification of mechanical behavior at the nanoscale is still an unresolved challenge. With this background, the current work demonstrates the capabilities of quantitative contact resonance atomic force microscopy (CR-AFM) to localize and reliably characterize Ni nanoparticles that are embedded below the surface of thermally oxidized silicon thin films. Correlating these results with numerical simulations as well as high-resolution transmission electron microscopy measurements provides a comprehensive understanding of the subtle interplay between the structure and nanomechanical response of the composite.


Chronic calcific pancreatitis in a patient with Waldenstrom's macroglobulinemia.
We report on a patient with chronic calcific pancreatitis associated with Waldenstrom's macroglobulinemia, and we have hypothesized a possible relationship between these two entities. The hyperviscosity of serum in Waldenstrom's macroglobulinemia may be associated with a viscous pancreatic juice that leads to stone formation.


[Thoracoscopic repair of esophageal atresia].
We present the first three cases of esophageal atresia with tracheoesophageal fistula treated with a thoracoscopic approach in our Service. The technique was accomplished through three trocar inserted in the right hemithorax. Carbon dioxide insufflation was required for lung retraction Primary correction was carried out in all the cases without major perioperative complications. The mean surgical time was 240 minutes. One patient had an anastomotic leak, resulting in a complicated postoperative course. The leak healed on conservative treatment. The others two patients were fed at the seventh postoperative day. Mean hospital stay in these cases was 12 days. Although thoracoscopic repair of esophageal atresia with fistula is a currently feasible technique that offers different advantages on the conventional open technique, a greater number of cases is needed in order to advance in the learning curve and determine the exact place that this technique can have in the future treatment of esophageal atresia.


Hydrogels for Bioprinting: A Systematic Review of Hydrogels Synthesis, Bioprinting Parameters, and Bioprinted Structures Behavior.
Nowadays, bioprinting is rapidly evolving and hydrogels are a key component for its success. In this sense, synthesis of hydrogels, as well as bioprinting process, and cross-linking of bioinks represent different challenges for the scientific community. A set of unified criteria and a common framework are missing, so multidisciplinary research teams might not efficiently share the advances and limitations of bioprinting. Although multiple combinations of materials and proportions have been used for several applications, it is still unclear the relationship between good printability of hydrogels and better medical/clinical behavior of bioprinted structures. For this reason, a PRISMA methodology was conducted in this review. Thus, 1,774 papers were retrieved from PUBMED, WOS, and SCOPUS databases. After selection, 118 papers were analyzed to extract information about materials, hydrogel synthesis, bioprinting process, and tests performed on bioprinted structures. The aim of this systematic review is to analyze materials used and their influence on the bioprinting parameters that ultimately generate tridimensional structures. Furthermore, a comparison of mechanical and cellular behavior of those bioprinted structures is presented. Finally, some conclusions and recommendations are exposed to improve reproducibility and facilitate a fair comparison of results.


Transplant outcomes in bone marrow failure syndromes and hemoglobinopathies.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potential cure for most bone marrow (BM) failure syndromes and hemoglobinopathies. Over the past decade, umbilical cord blood (UCB) has been used more frequently as a stem cell source in patients who lack a suitable BM donor. Although graft failure remains a significant problem, UCB transplantation (UCBT) using the optimal conditioning regimen can be a salvage treatment for patients without a suitable BM donor and warrants evaluation in further prospective studies.


Low-cost wavemeter with a solid Fizeau interferometer and fiber-optic input.
A wavemeter suitable for measuring the wavelength of pulsed and continuous laser light has been constructed on the basis of a solid Fizeau interferometer (SFI). An accuracy of 1 part in 10(6) has been demonstrated in a range extending from 563 to 613 nm. The use of the SFI and of a combination of a single-mode optical fiber and an achromatic lens as a beam collimating system substantially simplifies the optical layout and reduces cost. The difficulties connected with the dispersion of the SFI have been overcome by an analytical description of the characteristics of the interferometer and accurate temperature stabilization.


Ultrasonic modulation of multiply scattered coherent light: an analytical model for anisotropically scattering media.
In this work, we have calculated analytically the temporal autocorrelation function of the electrical field component of multiply scattered coherent light transmitted through an anisotropically scattering media irradiated with a plane ultrasonic wave. The accuracy of the analytical solution is verified with an independent Monte Carlo simulation for different values of the ultrasonic and optical parameters. The analytical model shows that an approximate similarity relation exists; if the reduced scattering coefficient is unchanged regardless of the mean cosine of the scattering angle, the autocorrelation function remains approximately the same.