Risk Factors and Clinical Correlates of Pediatric Serotonin Syndrome in Hospitalized Suicide Attempters.
To evaluate the risk factors and clinical correlates of pediatric serotonin syndrome (SS) given that research on SS in adults exists, there is a dearth of literature on pediatric SS. We conducted a retrospective chart review of 183 pediatric patients who were medically hospitalized after a suicide attempt. We investigated associations between SS and several of its risk factors and clinical correlates. We also assessed the sensitivity/specificity of Hunter's criteria and criterion symptoms in predicting SS. SS occurred in 21.7% of patients with a serotonergic overdose. Recent marijuana use and overdose on a selective serotonin reuptake inhibitor were significantly associated with SS. Individuals with SS required a greater number of days to be medically stabilized and had a greater likelihood of being placed on a ventilator during treatment. Hunter's criteria had 66.7% sensitivity and 92.3% specificity in diagnosing SS. Our study reveals both novel risk factors associated with SS (eg, recent marijuana use) and clinical correlates for patients with pediatric SS. In children, Hunter's criteria appeared to have good specificity but poor sensitivity in identifying SS. Our results set the stage for future work aimed at enhancing clinicians' ability to more rapidly identify and treat pediatric SS.


Duplex TaqMan real-time PCR assay for simultaneous detection and quantification of Anaplasma capra and Anaplasma phagocytophilum infection.
Anaplasma capra and A. phagocytophilum, two species of the family Anaplasmataceae, are zoonotic tick-borne obligate intracellular bacteria affecting wild and domestic ruminants, dogs, cats, horses and humans. A. capra and A. phagocytophilum infections have been steadily increasing in both number and geographic distribution, and the accurate diagnosis of these infections is challenging. This study aimed to develop a rapid, sensitive and reliable duplex real-time PCR assay for the specific detection and differentiation of these Anaplasma species. We designed primers and probes against the conserved regions of A. capra groEL and A. phagocytophilum 16S rRNA genes. A range of PCR-related parameters were evaluated such as the dosage of primers and probes, and annealing temperature. The specificity, sensitivity and repeatability of this assay were evaluated. Assay performance was further evaluated using samples collected from 124 goats in four regions of Henan, China. This set of samples was also tested using conventional PCR under conditions previously described. The developed duplex real-time PCR assay allowed the simultaneous detection of A. capra and A. phagocytophilum in a reasonably short time at levels as small as 102 copies/μL, respectively, with optimal specificity and reproducibility. In addition, this duplex real-time PCR assay is the first DNA-based method designed to detect A. capra and A. phagocytophilum, and will be valuable for timely diagnosis and treatment of these infections.


Replicative helicase loaders: ring breakers and ring makers.
Helicase loaders transfer the ring-shaped replicative helicases onto DNA. They assort into two classes: ring breakers, which place stabile hexameric rings on DNA via transient gaps at subunit interfaces; and helicase makers, which assemble hexameric rings around DNA from monomeric helicase units.


Irradiation with low-dose gamma ray enhances tolerance to heat stress in Arabidopsis seedlings.
Gamma irradiation at low doses can stimulate the tolerance to environmental stress in plants. However, the knowledge regarding the mechanisms underlying the enhanced tolerance induced by low-dose gamma irradiation is far from fully understood. In this study, to investigate the physiological and molecular mechanisms of heat stress alleviated by low-dose gamma irradiation, the Arabidopsis seeds were exposed to a range of doses before subjected to heat treatment. Our results showed that 50-Gy gamma irradiation maximally promoted seedling growth in response to heat stress. The production rate of superoxide radical and contents of hydrogen peroxide and malondialdehyde in the seedlings irradiated with 50-Gy dose under heat stress were significantly lower than those of controls. The activities of antioxidant enzymes, glutathione (GSH) content and proline level in the gamma-irradiated seedlings were significantly increased compared with the controls. Furthermore, transcriptional expression analysis of selected genes revealed that some components related to heat tolerance were stimulated by low-dose gamma irradiation under heat shock. Our results suggest that low-dose gamma irradiation can modulate the physiological responses as well as gene expression related to heat tolerance, thus alleviating the stress damage in Arabidopsis seedlings.


Do the PHQ-8 and the PHQ-2 accurately screen for depressive disorders in a sample of pregnant women?
The aim of this study was to assess the psychometric properties of the Patient Health Questionnaire (PHQ)-8, and the PHQ-2, a two-item version of the PHQ, respectively, in pregnancy. These screeners were compared to a structured diagnostic interview in a cohort of pregnant women attending prenatal care. Based upon studies documenting high sensitivity and specificity on the PHQ-8 and PHQ-2 in the general adult population, we hypothesized that both instruments would be effective in this population. Two hundred eighteen women, 13 of them depressed, were given the Composite International Diagnostic Interview and the PHQ-8 before 17 weeks of pregnancy. Receiver Operating Characteristic curves determined optimal thresholds and sensitivity and specificity were calculated using both dimensional and categorical approaches. Agreement between the PHQ-2 and PHQ-8 was measured using Cohen's kappa. Optimal cutoffs for the PHQ-8 and PHQ-2 were 11 and 4, respectively. Using these cutoffs, the PHQ-8 had a sensitivity of 77% and a specificity of 62% while the PHQ-2 had a sensitivity of 62% and a specificity of 79%. The categorical method of scoring the PHQ-8 yielded a sensitivity of 54% and a specificity of 84%. In our sample, the PHQ-8 and PHQ-2 performed almost equally in detecting probable major depressive disorder in a sample of pregnant women. The categorical scoring method for the PHQ-8 had lower sensitivity but slightly higher specificity than the dimensional version. We found the PHQ-8 and PHQ-2 to have lower sensitivity and specificity in our pregnant population as compared to findings in nonpregnant populations; however, characteristics of our sample and choice of diagnostics instrument could explain these discrepant findings.


Focus on neonatal resuscitation--NOW.
The paper by Saugstad et al. in this issue of Acta Paediatrica presents new and provocative data on the development of the child's physiological status during the first minutes of life. The data were extracted from the database of the Resair 2 study designed to investigate the outcome of resuscitation with air or 100% oxygen. The potential of these variables to predict the outcome of asphyxiated infants was evaluated. The data--in spite of some technical limitations and lack of representative reference measurements--point out the potential value of sequential physiological observations in the early identification of newborn infants at risk of poor outcome, challenge the routine habit of giving ample oxygen to depressed neonates, and call for further studies.


Comparative analysis of dioecious Amaranthus plastomes and phylogenomic implications within Amaranthaceae s.s.
The genus Amaranthus L. consists of 70-80 species distributed across temperate and tropical regions of the world. Nine species are dioecious and native to North America; two of which are agronomically important weeds of row crops. The genus has been described as taxonomically challenging and relationships among species including the dioecious ones are poorly understood. In this study, we investigated the phylogenetic relationships among the dioecious amaranths and sought to gain insights into plastid tree incongruence. A total of 19 Amaranthus species' complete plastomes were analyzed. Among these, seven dioecious Amaranthus plastomes were newly sequenced and assembled, an additional two were assembled from previously published short reads sequences and 10 other plastomes were obtained from a public repository (GenBank). Comparative analysis of the dioecious Amaranthus species' plastomes revealed sizes ranged from 150,011 to 150,735 bp and consisted of 112 unique genes (78 protein-coding genes, 30 transfer RNAs and 4 ribosomal RNAs). Maximum likelihood trees, Bayesian inference trees and splits graphs support the monophyly of subgenera Acnida (7 dioecious species) and Amaranthus; however, the relationship of A. australis and A. cannabinus to the other dioecious species in Acnida could not be established, as it appears a chloroplast capture occurred from the lineage leading to the Acnida + Amaranthus clades. Our results also revealed intraplastome conflict at some tree branches that were in some cases alleviated with the use of whole chloroplast genome alignment, indicating non-coding regions contribute valuable phylogenetic signals toward shallow relationship resolution. Furthermore, we report a very low evolutionary distance between A. palmeri and A. watsonii, indicating that these two species are more genetically related than previously reported. Our study provides valuable plastome resources as well as a framework for further evolutionary analyses of the entire Amaranthus genus as more species are sequenced.


Intramedullary headless compression screw fixation for midshaft fractures of the clavicle: A case report study.
Historically, displaced midshaft clavicle fractures have been managed conservatively. However, recent literature has supported operative management of displaced and shortened clavicle fractures. Several options exist for surgical fixation, including plating and intramedullary (IM) fixation. IM fixation has the potential advantages of a smaller incision and decreased dissection and soft-tissue exposure and less prominent hardware. Rockwood and Hagie pins represented the most popular form of IM fixation during the last two decades,but concerns exist regarding stability and complications. The use of alternative IM implants, such as Kirschner wires, titanium elastic nails, and cannulated screws, also has been described in limited case series. However, concerns persist regarding the complications associated with the use of these implants, including implant failure, migration, skin complications, prominent screw head and construct stability. Our technique describes intramedullary fixation of midshaft clavicle fractures using a single headless compression screw (HCS) 4.5-6.5-mm. which is simple, affordable, and allows intramedullary compression, stability, load sharing, little periosteal stripping, very limited skin incision and rapid recovery after surgery.


Research progress on the application of single-cell sequencing in autoimmune diseases.
Autoimmune diseases (AIDs) are caused by immune tolerance deficiency or abnormal immune regulation, leading to damage to host organs. The complicated pathogenesis and varied clinical symptoms of AIDs pose great challenges in diagnosing and monitoring this disease. Regrettably, the etiological factors and pathogenesis of AIDs are still not completely understood. It is noteworthy that the development of single-cell RNA sequencing (scRNA-seq) technology provides a new tool for analyzing the transcriptome of AIDs. In this essay, we have summarized the development of scRNA-seq technology, and made a relatively systematic review of the current research progress of scRNA-seq technology in the field of AIDs, providing a reference to preferably understand the pathogenesis, diagnosis, and treatment of AIDs.


Systemic Inflammatory Response Syndrome After Contentious-Flow Left Ventricular Assist Device Implantation and Change in Platelet Mitochondrial Membrane Potential.
The objective of this study was to investigate the change of platelet function and platelet mitochondrial membrane potential in contentious-flow left ventricular assist device (CF-LVAD)-implanted heart failure (HF) patients with or without systemic inflammatory response syndrome (SIRS). We recruited 31 CF-LVAD patients (16 SIRS and 15 non-SIRS) and 11 healthy volunteers as control. Pre- and post-implantation blood samples were collected. We used PFA-100 to test platelet functionality. Mitochondrial potential-sensitive dye was used to detect platelet dysfunction (mitochondrial membrane potential; ΔΨm) via flow cytometry. The percentage of depolarized-ΔΨm platelets was found to be a preexisting condition in all HF patients before CF-LVAD implantation compared with control subjects (10.3 ± 6.3% vs 2.8 ± 2.2%; P < .001). As evident from the PFA-100 test, the HF patients who developed SIRS after CF-LVAD implantation had significantly more qualitative platelet defects and thrombocytopathies compared with baseline. After implantation, the depolarized platelets in the SIRS patients increased by 2-fold compared with baseline (18.2 ± 8.4% vs 9.0 ± 6.6%; P < .01); whereas no change was noticed in the non-SIRS patients (10.9 ± 6.2% vs 11.7 ± 5.8%; P = .75). We identified that platelet function and mitochondrial damage were enhanced in CF-LVAD patients with SIRS. Our findings suggest that depolarization of mitochondrial membrane potential is associated with SIRS after CF-LVAD implantation surgery.


[Retrotendinous ureter. An exceptional cause of obstruction in the upper urinary tract].
Retrotendineus ureter is an exceptional anomaly presenting, in our experience, without clinical signs of urinary infection and obstruction. The radiological diagnosis was retrocaval ureter. The Authors report a case of a 9 years old boy who was successfully treated by ureteral section, excision of the obstructed ureteral segment and uretero-ureteral anastomosis. It seems that the case is the first reported in the medical literature of this anomaly.


The influence of omeprazole on the protective effects of secretagogues against ethanol-induced gastric ulceration in rats.
The influence of omeprazole on the antiulcer effects of histamine, methacholine and pentagastrin on ethanol-induced gastric ulceration was studied. Histamine 5 mg/kg, methacholine 500 micrograms/kg or pentagastrin 100 micrograms/kg pretreatment s.c. markedly reduced ethanol (50%, 10 ml/kg p.o.)-induced gastric ulceration in pylorus-ligated conscious rats, but significantly elevated the gastric secretory volume and acid output. Omeprazole pretreatment 50 mg/kg s.c. reduced gastric secretion and abolished the ulcer-protecting effects of the three secretagogues. The same doses of histamine, methacholine or pentagastrin did not significantly alter the gastric secretory volume but increased the total acid output of ex-vivo stomach chamber preparations in anaesthetised animals. Histamine worsened ethanol-evoked ulceration whereas methacholine and pentagastrin had no effect on the lesions. Omeprazole pretreatment did not prevent ulcer aggravation by histamine. It is concluded that the antiulcer effects of the three secretagogues in conscious animals are probably due to the increased secretory volume which lessens the ulcerogenic action of ethanol by its dilution. Omeprazole reduces the secretory volume and thus prevents the antiulcer effect of these secretagogues. The findings with histamine and omeprazole in the ex-vivo stomach experiments support the suggestion that it is unlikely that increased gastric acid secretion affects the ulcerogenicity of ethanol in rat stomach.


CpG oligodeoxinucleotides functions as an effective adjuvant in aged BALB/c mice.
During aging, there is an increased rise in susceptibility to infectious diseases. However, it is still unresolved whether standard vaccine adjuvants are efficient in the elderly. We report that immunization with OVA plus synthetic oligodeoxinucleotides containing immunostimulatory CpG motifs (CpG-ODN) stimulates specific Th1 response in aged mice. The immunization with OVA/CpG-ODN induced an increase in CD19+ cells. These cells from aged mice in vivo captured OVA-FITC as efficiently as those from young mice. Interestingly, naïve aged mice, which showed Th2 polarization and up-regulation of the expression of GATA-3, with immunization with OVA/CpG-ODN inducing Th1-specific response but maintaining a Th2 pattern in response to a non-specific stimulator of T cells. Our data suggest that the response elicited by CpG-ODN in aged mice have similar properties to the response developed in young mice, emphasizing the importance of the use of this adjuvant during aging.


Vagal nerve stimulator-associated sleep disordered breathing secondary to vagal-induced laryngospasm in pediatric populations: Case presentation and systematic review.
Sleep disordered breathing (SDB) is a well-documented complication of vagus nerve stimulation (VNS) in the literature. Yet, a formal consensus on its management has not been established, particularly in the pediatric population. This study aims to evaluate the current literature on VNS-associated SDB in order to further characterize its presentation, pathogenesis, diagnosis, and treatment. A literature review from 2001 to November 8, 2021 was conducted to search for studies on SDB during vagal nerve stimulation in pediatric populations. Of 277 studies screened, seven studies reported on pediatric patients with VNS-associated SDB. Several investigators found on polysomnogram that periods of apnea/hypopnea correlated with VNS activity. When VNS settings were lowered or turned off, symptoms would either improve or completely resolve. VNS-associated SDB is a well described complication of VNS implantation, occurring due to an obstructive process from vagal stimulation and laryngeal contraction. Diagnosis can be made via polysomnogram. Recommended treatment is through adjustment of VNS settings. However, those who are unable to tolerate this, or who have had pre-existing obstructive issues prior to VNS, should pursue other treatment options such as non-invasive positive pressure or surgery directed by DISE findings.


Design, synthesis and evaluation of novel 2,5,6-trisubstituted benzimidazoles targeting FtsZ as antitubercular agents.
Filamenting temperature-sensitive protein Z (FtsZ), an essential cell division protein, is a promising target for the drug discovery of new-generation antibacterial agents against various bacterial pathogens. As a part of SAR studies on benzimidazoles, we have synthesized a library of 376 novel 2,5,6-trisubstituted benzimidazoles, bearing ether or thioether linkage at the 6-position. In a preliminary HTP screening against Mtb H37Rv, 108 compounds were identified as hits at a cut off concentration of 5 μg/mL. Among those hits, 10 compounds exhibited MIC values in the range of 0.63-12.5 μg/mL. Light scattering assay and TEM analysis with the most potent compound 5a clearly indicate that its molecular target is Mtb-FtsZ. Also, the Kd of 5a with Mtb-FtsZ was determined to be 1.32 μM.


Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats.
To verify if an experimental model of alloxan-diabetic rats promotes oxidative stress, reduces nitric oxide bioavailability and causes vascular dysfunction, and to evaluate the effect of N-acetylcysteine (NAC) on these parameters. Alloxan-diabetic rats were treated or not with NAC for four weeks. Plasmatic levels of malondialdehyde (MDA) and nitrite/nitrate (NOx), the endothelial and inducible nitric oxide synthase (eNOS and iNOS) immunostaining and the vascular reactivity of aorta were compared among diabetic (D), treated diabetic (TD) and control (C) rats. MDA levels increased in D and TD. NOx levels did not differ among groups. Endothelial eNOS immunostaining reduced and adventitial iNOS increased in D and TD. The responsiveness of rings to acetylcholine, sodium nitroprusside, and phenylephrine did not differ among groups. NAC had no effect on the evaluated parameters and this experimental model did not promote vascular dysfunction despite the development of oxidative stress.


In-office balloon dilation of the Eustachian tube under local anesthesia: A retrospective review.
To study the effectiveness and feasibility of in office balloon dilation of the Eustachian tube (BDET) utilizing a novel anesthetic protocol. Study design: retrospective review. Retrospective chart review looking at the tolerability and effectiveness of stand-alone BDET in an office setting utilizing a novel topical anesthesia protocol in 33 patients with Eustachian tube dysfunction as defined by an ETDQ-7 score greater than 2.2 and type B or C tympanograms for greater than 3 months despite maximal medical management, including at least 4 weeks of nasal steroids. BDET in the office was well tolerated with 94% (31/33) of patients completing the procedure as planned. No adverse effects or complications were reported; however, the planned dilation time was cut short in one case due to significant discomfort and aborted prior to dilation in another due significant coughing. Tympanograms normalized at six weeks in 87.1% (27/31) of patients who underwent dilation. This study demonstrates that performing BDET in an office setting utilizing a local anesthesia protocol is feasible and effective when the unique barometric considerations of BDET are addressed.


Comet-assay parameters as rapid biomarkers of exposure to dietary/environmental compounds -- an in vitro feasibility study on spermatozoa and lymphocytes.
Twelve chemical compounds have been selected for the European NewGeneris study on the basis of their potential to damage DNA, in order to establish adequate and reliable biomarkers of exposure. These genotoxic chemicals include heterocyclic amines, organochlorines, polycyclic aromatic hydrocarbons, mycotoxins, lipid peroxidation products and alcohol. Damage in somatic cells such as lymphocytes could give rise to cancer, while damage in germ cells could not only give rise to cancer but also to heritable defects. The alkaline Comet assay, with and without metabolic activation, as well as the neutral Comet assay were used to assess DNA integrity in spermatozoa and lymphocytes after in vitro treatment with low, middle and high doses of each chemical. DNA-reactive aldehydes generated by lipid peroxidation, food mutagens such as heterocyclic amines, nitrosamine and benzo[a]pyrene produced the highest amounts of DNA damage, even without metabolic activation. Damage seen with the neutral Comet assay - detecting primarily double-strand breaks - was lower than with the alkaline assay. In general, there was increased damage in the spermatozoa by comparison with the lymphocytes, with altered slopes in the dose-response curves. The Comet assay with sperm was generally very sensitive in assessing genotoxic damage, with the Comet parameters being good biomarkers of induced DNA damage. Establishing reliable biomarkers of exposure for the evaluation of dietary/environmental carcinogens is of utmost importance to protect our health and the health of our offspring.


Communication skills training for paraprofessional helpers.
The purpose of the present study was to develop and evaluate a training program for paraprofessional helpers. Twenty dormitory counselor candidates were given 20 hours of communication training while 15 other candidates were given no training. The results indicated that the trained subjects demonstrated significantly higher levels of empathy than the untrained subjects and that they maintained their level of empathy after 6 months. Results are discussed in terms of the lasting effects of the training program and the advantages of being able to use trainers with only limited experience.


Mothers' parenting stress, depression, marital conflict, and marital satisfaction: The moderating effect of fathers' empathy tendency.
The decreased marriage satisfaction has become one of the main reasons for the rising divorce rate. However, few studies have focused on the relationship between mother's parenting stress, mental health, and marriage satisfaction. This study addressed this research gap by examining the direct influence of mothers' parental stress on their marital satisfaction, and the indirect influence of depression and marital conflict. Additionally, we explored the moderating effect of fathers' empathy tendency. Using a sample of parenting couples in Southwest China (n = 2,979) to conduct a questionnaire survey, a moderated mediation analysis was performed to simultaneously analyze the chain mediation of depression and marital conflict, and the moderating role of fathers'' empathy. The mother's childcare pressure was negatively correlated with marital satisfaction (β = -0.478, p < 0.001). Depression and marital conflict have a chain mediating effect in explaining the relationship between mothers'' parenting stress and marital satisfaction (b = -0.064, 95% CI [-0.075, -0.053]). It is important to note that fathers with cognitive empathy can alleviate depression and marital conflict caused by the mothers' parental stress and a decrease in marital satisfaction, while fathers with high empathy can exacerbate these negative effects. The study's findings identify the serious impact of contemporary female parenting pressure on marital satisfaction and confirm the important role of husbands' empathy. The scope of the survey is single, the parenting period is not staged, and there may be limitations such as overlapping stressors, which can be corrected in future research.


Acute nonlymphocytic leukemia with severe hypodiploidy and one double minute chromosome.
We present a case of acute nonlymphocytic leukemia with severe hypodiploidy (38 chromosomes), complex karyotype, and one double minute chromosome. These unusual chromosome findings could be related to the rapid course of the patient's disease.


Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries.
Schistosomiasis is a neglected tropical disease that affects over 200 million people annually. As the antischistosomal drug pipeline is currently empty, repurposing of compound libraries has become a source for accelerating drug development, which demands the implementation of high-throughput and efficient screening strategies. Here, we present a parallelized impedance-based platform for continuous and automated viability evaluation of Schistosoma mansoni schistosomula in 128 microwells during 72 h to identify antischistosomal hits in vitro. By initially screening 57 repurposed compounds against larvae, five drugs are identified, which reduce parasite viability by more than 70%. The activity profiles of the selected drugs are then investigated via real-time dose-response monitoring, and four compounds reveal high potency and rapid action, which renders them suitable candidates for follow-up tests against adult parasites. The study shows that our device is a reliable tool for real-time drug screening analysis of libraries to identify new promising therapeutics against schistosomiasis.


Risk factors for non-gastric-cancer-related death after gastrectomy in elderly patients.
To identify preoperative factors, especially other diseases that cause death, that are associated with the prognosis of gastrectomy in elderly patients with gastric cancer. This retrospective study included a total of 211 consecutive patients aged ≥75 years who underwent radical gastrectomy due to gastric cancer. Time-dependent receiver operating characteristic curve analysis was performed to determine the optimal cutoff values for various perioperative factors. Risk factors for the overall survival and death from other diseases were analyzed using the Cox proportional hazards model. Among the all perioperative factors, sex, neutrophil-to-lymphocyte ratio, skeletal muscle mass index, and lymph node dissection in accordance with guidelines or not extracted as independent risk factors for death from other diseases. In an analysis restricted to the preoperative factors, sex, neutrophil-to-lymphocyte ratio, and skeletal muscle mass index of the patients were extracted as independent risk factors for death from other diseases and overall survival. We divided the patients into four groups according to the number of preoperative risk factors for death from other diseases and found that the 5-year non-gastric-cancer-related survival was different among the four groups (risk factor 0, 91.7%; risk factor 1, 83.3%; risk factor 2, 56.3%; risk factor 3, 27.2%; P < 0.001). Male sex, low skeletal muscle mass index, and high neutrophil-to-lymphocyte ratio are risk factors for non-gastric-cancer-related death and the overall survival of elderly patients undergoing gastrectomy. Cautious treatment strategies are needed for elderly gastric cancer patients with many risk factors.


Multiple Synchronous Lesions in the Genital Tract of a Female: A Rare Combination with Unrelated Histogenesis.
Presenting a case of endometrioid adenocarcinoma of the endometrium, benign cystic teratoma of one ovary, fibrothecoma in the other ovary and adenomyosis in the uterus. Such a combination of synchronous lesion is very rare and is not reported in the English medical literature.


Evaluation of recombinant Neospora caninum antigens purified from silkworm larvae for the protection of N. caninum infection in mice.
Three antigens (NcSAG1, NcSRS2 and NcMIC3) from Neospora caninum were expressed using the BmNPV bacmid system in silkworm larvae and purified from the hemolymph. From 20 silkworm larvae, 1.5, 1.2 and 1.4 mg of purified recombinant NcSAG1, NcSRS2 and NcMIC3 were obtained, respectively. When each purified recombinant antigen was immunized with Freund's incomplete adjuvant (FIA) to mice, recombinant NcSAG1 induced a Th2 immune response in immunized mice and produced a SAG1-specific antibody. In the experiment where NcSAG1-immunized mice were challenged with N. caninum, the cerebral N. caninum burden was significantly reduced compared with that of either the FIA- or PBS-immunized mice. Recombinant NcSRS2 or NcMIC3 induced both Th1 and Th2 immune responses, but NcMIC3-immunization did not induce significant production of NcMIC3-specific antibodies. These results suggest that the silkworm can produce recombinant antigens of N. caninum, which can be used as a recombinant vaccine against N. caninum.


Immunoregulatory potential of exogenous Schistosoma mansoni soluble egg antigen in a model of experimental schistosomiasis--I. Regulation of granuloma formation in vivo.
This study was undertaken to assess the optimum conditions required to reduce the vigorous host granulomatous reaction around Schistosoma mansoni eggs. Soluble schistosomal egg antigen (SEA) at a concentration of 10 or 100 micrograms protein was administered i.p. or i.v. into unprimed C57BL/6 mice. SEA was injected either alone or in combination with cyclophosphamide (CY) 100 or 50 mg/kg via i.p. route. Seven or 14 days later viable eggs of S. mansoni were injected via the tail vein into treated groups and untreated normal controls. Mice were sacrificed 8, 16 and 24 days after the injection of eggs. The lungs were removed for histopathological study, measurement of granuloma diameter and phenotypic analysis of granuloma intralesional T-cell subsets. Compared to untreated controls, the lower concentration of SEA (10 micrograms) administered by the i.v. route 7 days before egg injection, induced a significant reduction in granuloma diameter 16 days after egg injection than that by the i.p. route or at a higher SEA concentration (100 micrograms). Compared to untreated controls, the higher dose of CY (100 mg/kg), given i.p. alone or in combination with 10 micrograms SEA by the i.v. or i.p. route, induced a significant reduction in granuloma diameter, while 50 mg/kg CY did not cause any reduction. The reduction in granuloma diameter by i.v. administration of low SEA concentration alone or in combination with CY IP, was associated with a decrease in the granuloma intralesional L3T4+/Lyt2+ ratio. The decrease in the ratio was due to an increase in Lyt2+ cells. The results suggest that the use of low dose SEA by the i.v. route alone or combined with an immunosuppressive drug ameliorates pathological changes concurrent with S. mansoni infection.


Regionally Distinct Alterations in Membrane Phospholipid Metabolism in Schizophrenia: A Meta-analysis of Phosphorus Magnetic Resonance Spectroscopy Studies.
Existing data on altered membrane phospholipid metabolism in schizophrenia are diverse. We conducted a meta-analysis of studies of phosphorus magnetic resonance spectroscopy, a noninvasive imaging approach that can assess molecular biochemistry of cortex by measuring phosphomonoester (PME) and phosphodiester (PDE) levels, which can provide evidence of altered biochemical processes involved in neuropil membrane expansion and contraction in schizophrenia. We analyzed PME and PDE data in the frontal and temporal lobes in subjects with schizophrenia from 24 peer-reviewed publications using the MAVIS package in R by building random- and fixed-effects models. Heterogeneity of effect sizes, effects of publication bias, and file drawer analysis were also assessed. Subjects with schizophrenia showed lower PME levels in the frontal regions (p = .008) and elevated PDE levels in the temporal regions (p < .001) with significant heterogeneity. We noted significant publication bias and file drawer effect for frontal PME and PDE and temporal PDE levels, but not for temporal PME levels. Fail-safe analysis estimated that a high number of negative studies were required to provide nonsignificant results. Despite methodological differences, these phosphorus magnetic resonance spectroscopy studies demonstrate regionally specific imbalance in membrane phospholipid metabolism related to neuropil in subjects with schizophrenia compared with control subjects reflecting neuropil contraction. Specifically, decreased PME levels in the frontal regions and elevated PDE levels in the temporal regions provide evidence of decreased synthesis and increased degradation of neuropil membrane, respectively. Notwithstanding significant heterogeneity and publication bias, a large number of negative studies are required to render the results of this meta-analysis nonsignificant. These findings warrant further postmortem and animal studies.


[Neurological complications in Down syndrome].
The aim of this study was to look over the neurological disorders associated with Down syndrome. We reviewed 12 patients with Down syndrome hospitalized from 1997 to 2003, suffering from various neurological complications. Among the 5 patients with epilepsy, 3 presented with West syndrome and 2 with partial epilepsy; after treatment all were seizure-free. Four patients had ischemic lesions; 1 presented with Moya-Moya syndrome. Four patients presented with C1-C2 vertebral dislocation; all underwent surgery. One of the patients with epilepsy had neurological ischemic sequelae. West syndrome is the most frequent type of epilepsy encountered in Down syndrome. Outcome is favourable if appropriate treatment is initiated early. Any suspicion or sign of vascular lesion in patients with Down syndrome should be promptly investigated. The hyperlaxity associated with Down syndrome could lead to C1-C2 dislocation and a systematic screening is mandatory in order to avoid neurological complications.


HTLV-I-associated myelopathy: are ferritin, S100beta protein, or guanine nucleotides CSF markers of disease?
In southern Brazil, there is an endemic high prevalence foci of HTLV-I and HTLV-II infection. HTLV-infected individuals may develop HAM/TSP. Little is known about HAM/TSP pathogenesis and there is a lack of disease progression markers. This study investigated ferritin, S-100beta protein, and guanine nucleotides (GN) concentrations in the CSF of 18 patients with HAM/TSP. In HAM/TSP patients, concentrations of ferritin and S100beta were increased, whereas GMP was reduced. CSF ferritin, S100beta, and GN are potential markers for HAM/TSP.


Effects of glucocorticoids on the hypothalamic-pituitary-adrenal axis in children and adults.
Inhaled and intranasal corticosteroids are widely used as effective, first-line treatments for asthma and allergic rhinitis. Despite a good safety profile of these formulations, there is increasing concern about their propensity to produce systemic adverse effects. Suppression of the hypothalamic-pituitary-adrenal axis is one of the most important potential complications. This article reviews the effects of inhaled and intranasal corticosteroids on the hypothalamic-pituitary-adrenal axis function in adults and children.


Clinical-grade production and safe delivery of human ESC derived RPE sheets in primates and rodents.
Age-related macular degeneration as well as some forms of Retinitis Pigmentosa (RP) are characterized by a retinal degeneration involving the retinal pigment epithelium (RPE). Various strategies were proposed to cure these disorders including the replacement of RPE cells using human pluripotent stem cells (hPSCs), an unlimited source material to generate in vitro RPE cells. The formulation strategy of the cell therapy (either a reconstructed sheet or a cell suspension) is crucial to achieve an efficient and long lasting therapeutic effect. We previously developed a hPSC-RPE sheet disposed on human amniotic membrane that sustained the vision of rodents with retinal degeneration compared to the same cells injected as a suspension. However, the transplantation strategy was difficult to implement in large animals. Herein we developed two medical devices for the preparation, conservation and implantation of the hPSC-RPE sheet in nonhuman primates. The surgery was safe and well tolerated during the 7-week follow up. The graft integrity was preserved in primates. Moreover, the hPSC-RPE sheet did not induce teratoma or grafted cell dispersion to other organs in rodent models. This work clears the way for the first cell therapy for RP patients carrying RPE gene mutations (LRAT, RPE65 and MERTK).


Paired associate performance in the early detection of DAT.
Subjects underwent longitudinal neuropsychological assessment in order to retrospectively determine which measures of cognitive function best predicted later development of dementia of the Alzheimer type (DAT). Three groups of subjects were studied: normal controls, patients with early DAT, and questionable dementia subjects (QD). All subjects were assessed using a battery of standard neuropsychological measures and two subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB), paired associate learning and delayed matching to sample. A structured interview was also used to elicit a profile of the subject's daily functioning. Subjects were assessed every 6 months for 2 years. At the 6 month assessment, almost half of the QD group exhibited significant deterioration in scores on the computerized paired associate learning subtest, while maintaining their scores on standard measures. At the conclusion of the study, all of this QD subgroup fulfilled the NINCDS-ADRDA criteria for probable DAT pertaining to significant cognitive and functional deterioration. Performance on the C


Structure and function of L-lactate dehydrogenases from thermophilic and mesophilic bacteria, VI. Nucleotide sequences of lactate dehydrogenase genes from the thermophilic bacteria Bacillus stearothermophilus, B. caldolyticus and B. caldotenax.
Based on the previously determined amino-acid sequence of lactate dehydrogenase from B. stearothermophilus, an oligonucleotide probe was synthesized and used to clone the structural genes for lactate dehydrogenase from B. stearothermophilus, B. caldolyticus and B. caldotenax. The nucleotide sequences of the entire LDH genes from these three thermophilic bacilli were determined by the method of Maxam and Gilbert. The nucleotide sequence of the LDH gene from B. stearothermophilus is exactly identical to the one published recently; it agrees with the experimentally determined amino-acid sequence except at three positions. The amino-acid homologies among these thermophilic enzymes are 90% or more. The LDH genes are efficiently expressed in E. coli.


PAH depletion in weathered oil slicks estimated from modeled age-at-sea during the Deepwater Horizon oil spill.
During time-periods oil slicks are in the marine environment (age-at-sea), weathering causes significant changes in composition and mass loss (depletion) of oil spill chemicals including the more toxic polycyclic aromatic hydrocarbons (PAHs). The goal of this study was to estimate the age-at-sea of weathered oil slicks using the oil spill module of the Connectivity Modeling System and to use this age to interpret PAH concentration measurements. Percent depletion (PD) for each measurement was computed as the percentage difference between the original and measured PAH concentration in the crude oil and weathered oil slicks, normalized upon the mass losses relative to hopane. Mean PD increased with estimated age-at-sea for all PAHs. Less PD was observed for alkylated than for parent PAHs, likely due to decreasing vapor pressure with increasing degree of alkylation. We conclude that estimated age-at-sea can be used to explain PAH depletion in weathered oil slicks. We propose PAH vapor pressure can be coupled with the model to expand capacity for predicting concentration distributions of individual parent and alkylated PAHs in weathered oil along the coastline. This new module will advance the science supporting oil spill response by providing more certain estimates of health risks from oil spills.


Comparison of Two Concentration Methods for the Molecular Detection of Enteroviruses in Raw and Treated Sewage.
Human enteric viruses are a major causative agent of emerging waterborne diseases and constitute a serious public health concern. Environmental contamination occurs through discharge of waste materials from infected persons. Methods for viral detection should be developed to detect low infective dose of enteric viruses in environment. In this study, we aimed at comparing two concentration methods for the detection of naturally occurring enteroviruses in raw and treated sewage. In the first method, polyethylene glycol is used to concentrate viral particles from the collected samples. The second method is based on ultracentrifugation of viral particles at high speed (110,000×g). Genomes of enteroviruses were quantified by the quantitative real-time PCR method in raw and treated sewage samples. PEG-based method yielded higher genomic copies of enteric viruses (with an average of 5.9 log10 genomic copies/100 mL) when applied to raw sewage samples. While the ultracentrifugation assay in the second method decreases genomic copies number (with an average of 5.4 log10 genomic copies/100 mL). The recovery differences between the two methods were not significant when applied to clean samples (treated sewage). This could be explained by the presence of inhibitors, which interfere with qRT-PCR, in less quantity comparatively to raw sewage. PEG-based method would be more accurate for samples with high-organic matter load. This report emphasizes the importance of matrices nature on the recovery of enteroviruses from sewage samples. This should be taken into consideration for establishing standardized virological assays to ensure the virological quality control of discharged water in environment.


Quantitative biomarkers to predict response to clozapine treatment using resting EEG data.
Clozapine is an anti-psychotic drug that is known to be effective in the treatment of patients with chronic treatment-resistant schizophrenia (TRS-SCZ), commonly estimated to be around one third of all cases. However, clinicians sometimes delay the initiation of this drug because of its adverse side-effects. Therefore, identification of predictive biomarkers of clozapine response is extremely valuable to aid on-time initiation of clozapine treatment. In this study, we develop a machine learning (ML) algorithm based on the pre-treatment electroencephalogram (EEG) data sets to predict response to clozapine treatment in TRS-SCZs, where the treatment outcome, after at least one-year follow-up is determined using the Positive and Negative Syndrome Scale (PANSS). The ML algorithm has two steps: 1) an effective connectivity named symbolic transfer entropy (STE) is applied to resting state EEG waveforms, 2) the ML algorithm is applied to STE matrix to determine whether a set of features can be found to discriminate most responder (MR) SCZ patients from least responder (LR) ones. The findings of this study revealed that the STE features could achieve an accuracy of 89.90%. This finding implies that analysis of pre-treatment EEG could contribute to our ability to distinguish MR from LR SCZs, and that the STE matrix may prove to be a promising tool for the prediction of the clinical response to clozapine.


Evidence of IQ-modulated association between ZNF804A gene polymorphism and cognitive function in schizophrenia patients.
ZNF804A gene polymorphism rs1344706 has been suggested as the most compelling case of a candidate gene for schizophrenia by a genome-wide association study and several replication studies. The current study of 570 schizophrenia patients and 448 controls again found significantly different genotype frequencies of rs1344706 between patients and controls. More important, we found that this association was modulated by IQ, with a stronger association among individuals with relatively high IQ, which replicated results of Walters et al, 2010. We further examined whether this IQ-modulated association also existed between the SNP and the intermediate phenotypes (working memory and executive functions) of schizophrenia. Data were available from an N-back task (366 patients and 414 controls) and the attention network task (361 patients and 416 controls). We found that the SNP and IQ had significant interaction effects on the intermediate phenotypes for patients, but not for controls. The disease risk allele was associated with poorer cognitive function in patients with high IQ, but better cognitive function in patients with low IQ. Together, these results indicated that IQ may modulate the role of rs1344706 in the etiology of both schizophrenia and its cognitive impairments, and pointed to the necessity of considering general cognitive function as indexed by IQ in the future studies of genetic bases of schizophrenia.


Role of nerves in neurofibromatosis type 1-related nervous system tumors.
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that affects nearly 1 in 3000 infants. Neurofibromin inactivation and NF1 gene mutations are involved in various aspects of neuronal function regulation, including neuronal development induction, electrophysiological activity elevation, growth factor expression, and neurotransmitter release. NF1 patients often exhibit a predisposition to tumor development, especially in the nervous system, resulting in the frequent occurrence of peripheral nerve sheath tumors and gliomas. Recent evidence suggests that nerves play a role in the development of multiple tumor types, prompting researchers to investigate the nerve as a vital component in and regulator of the initiation and progression of NF1-related nervous system tumors. In this review, we summarize existing evidence about the specific effects of NF1 mutation on neurons and emerging research on the role of nerves in neurological tumor development, promising a new set of selective and targeted therapies for NF1-related tumors.


[Menstrual headache: subtypes, clinical phenotypes and treatment].
Up to 60% of women relate their episodes of headache to menstrual cycle. Menstrual migraine has been included in the second edition of the International Classification of Headache disorders. Menstrual tension-type headache has not yet been recognised by the International Headache Society. To evaluate the prevalence of different subtypes of menstrual headache and to analyze their clinical features and the treatment prescribed. We prospectively included women attending several neurology outpatient clinics, from January to November 2008 whose headache appeared during the menstrual period. A total of 108 patients were included during the study period. Mean age was 34.8 ± 8.9 years-old. 29.3% suffered from pure menstrual migraine, 58.7% from menstrual related migraine, 4.5% from pure menstrual tension-type headache and 7.5% from menstrual related tension type headache. Our data suggest that menstrual related tension-type headaches exist with a prevalence found about 12%, in our neurology outpatient clinics.


Plasma levels of angiopoietin-like protein 4 (ANGPTL4) are significantly lower preoperatively in colorectal cancer patients than in cancer-free patients and are further decreased during the first month after minimally invasive colorectal resection.
Surgery has been associated with proangiogenic plasma protein changes that may promote tumor growth. Angiopoietin-like protein 4 (ANGPTL4) is expressed by endothelial cells and other tissues in response to hypoxia. Both intact ANGPTL4 and its partly degraded C-terminal fragment may promote tumor angiogenesis. This study had two purposes: to measure and compare preoperative plasma ANGPTL4 levels in patients with colorectal cancer (CRC) and benign colorectal disease (BCD) and to determine plasma levels after minimally invasive colorectal resection (MICR) for CRC. Plasma was obtained from an IRB-approved plasma/data bank. Preoperative plasma ANGPTL4 levels were measured for CRC and BCD patients, but postoperative levels were determined only for CRC patients for whom a preoperative, a postoperative day (POD) 3, and at least one late postoperative sample (POD 7-55) were available. Late samples were bundled into four time blocks and considered as single time points. ANGPTL4 levels (mean ± SD) were measured via ELISA and compared (significance, p < 0.01 after Bonferroni correction). Eighty CRC (71 % colon, 29 % rectal) and 60 BCD (62 % diverticulitis, 38 % adenoma) patients were studied. The mean preoperative plasma ANGPTL4 level in CRC patients (247.2 ± 230.7 ng/ml) was lower than the BCD group result (330.8 ± 239.0 ng/ml, p = 0.01). There was an inverse relationship between plasma levels and advanced CRC as judged by three criteria. In regard to the postoperative CRC analysis, the "n" for each time point varied: lower plasma levels (p < 0.001) were noted on POD 3 (161.4 ± 140.4 ng/ml, n = 80), POD 7-13 (144.6 ± 134.5 ng/ml, n = 46), POD 14-20 (139.0 ± 117.8 ng/ml, n = 27), POD 21-27 (138.9 ± 202.4, n = 20), and POD 28-55 (160.1 ± 179.0, n = 42) when compared to preoperative results. CRC is associated with lower preoperative plasma ANGPTL4 levels compared with BCD, and the levels may vary inversely with disease severity. After MICR for CRC, levels are significantly lower for over a month compared with the preoperative level; the cause for this persistent decrease is unclear. The implications of both the lower preoperative level and the persistently decreased postoperative levels are unclear. Further studies are needed.


Pelvic Ectopic Kidney Prevalence and Pressure Changes During Cloacal Exstrophy (Omphalocele-Exstrophy-Imperforate Anus-Spinal Defects Syndrome) Closure.
To assess the prevalence of pelvic ectopic kidneys (PEK) and compare renal parameters of the PEK to the orthotopic kidney following pubic bone approximation. In four Omphalocele-Exstrophy-Imperforate Anus-Spinal Defects Syndrome (OEIS) patients undergoing second-stage repair with known pelvic and orthotopic kidneys, changes in the renal pelvis pressure (RPP), peak systolic velocity (PSV), and resistive index (RI) were measured in the pelvic and orthotopic kidneys following pubic bone approximation. A paired t-test was performed for analysis. Prevalence was tabulated using a multi-institutional retrospective review. Mean rise in RPP was +26.0 mmHg in the PEK and +10.3 mmHg in the orthotopic kidney (P = .55). One patient had immediate increase in RPP of 66 mmHg in the PEK (7 mmHg in the orthotopic kidney) which decreased to +17 mmHg in the PEK upon release of the pubic approximation stitch. Mean change in PSV was +67.7 cm/s in the PEK compared to - 25.7 cm/s in the orthotopic kidney (P = .09). Mean change in renal RI was + 0.06 in PEK compared to - 0.01 in the orthotopic kidney (P = .29). Among 80 OEIS patients, 24 (30%) had a PEK. 3 (4%) had a solitary PEK. During second-stage OEIS closure, we witnessed patterns of higher change in RPP, PSV, and RI of the PEK compared to the orthotopic kidney. Furthermore, PEKs were found in nearly a third of our OEIS patients. Real-time RPP monitoring, especially those with solitary PEK, may aid in the management of OEIS patients during the perioperative period.


Endoscopic-guided versus cotton-tipped applicator methods of nasal anesthesia for transnasal esophagogastroduodenoscopy: a randomized, prospective, controlled study.
Ultrathin transnasal esophagogastroduodenoscopy (UT-EGD) is well tolerated by patients, but the methods of nasal anesthesia are various. To compare patient tolerance, safety, and adverse events between the endoscopic-guided (EGNA) and cotton-tipped applicator (CTNA) methods of nasal anesthesia. Between September 2005 and September 2006, we conducted a prospective, randomized, controlled study in a large tertiary referral hospital in eastern Taiwan. In total, 235 consecutive patients were randomly assigned to the CTNA group or EGNA group before unsedated UT-EGD. We compared demographic data, procedural discomfort using a validated 5-point visual analog scale, optical quality, total procedure time, and adverse events between the two groups. After randomization and exclusion, 101 (43 men and 58 women) and 103 (44 men and 59 women) patients were allocated to the CTNA and EGNA groups, respectively. Baseline characteristics and periprocedural hemodynamics of patients in the two groups were similar. There was no statistical difference in insertion failure rates between the two methods (CTNA 10.9%vs EGNA 7.7%, P= 0.59). Pain scores during both anesthesia (2.3 +/- 0.4 vs 3.5 +/- 0.6, P < 0.001) and insertion (2.8 +/- 1.2 vs 3.8 +/- 1.8, P < 0.001) were significantly lower in the EGNA group; however, the sensation of bad taste was significantly worse in the EGNA group (2.3 +/- 1.3 vs 1.9 +/- 1.4, P= 0.040). Less epistaxis happened in the EGNA group than in the CTNA group. The EGNA method had a significantly better visual capacity and shorter procedure time. More patients in the EGNA group said they would like to receive the same procedure the next time. Compared with the CTNA method, in which the taste of lidocaine gel was more acceptable, EGNA appeared to be more tolerable, caused less epistaxis, improved visualization capacity, and reduced procedure time.


Epidemiology and antimicrobial resistance profile of Neisseria gonorrhoeae in Catalonia, Spain, 2016-2019.
Antimicrobial resistance data for Neisseria gonorrhoeae is globally sparse and resistant strains are emerging in Catalonia. We aim to describe epidemiological and antimicrobial resistance in all patients infected with N. gonorrhoeae during the period from 2016 to 2019, using available antimicrobial susceptibility data. We retrospectively analysed confirmed N. gonorrhoeae cases notified to Catalonia's microbiological reporting system. Antibiotic susceptibility testing (azithromycin, cefixime, ceftriaxone, ciprofloxacin, penicillin, spectinomycin, and tetracycline) was assessed using clinical breakpoints published by the European Committee on Antimicrobial Susceptibility Testing. Incidence rates were calculated and proportions were compared using the χ2 test or Fisher's exact test, and analysed using the Statistical Package for Social Sciences (SPSS 18.0). A total of 14,251 confirmed cases of N. gonorrhoeae were notified. Incidence increased from 30.7 cases/100,000 person-years (p < 0.001) in 2016 to 64.7 in 2019. Culture was available in 6,292 isolates (44.2%), of which 5,377 (85.5%) were resistant to at least one of the antibiotics tested. Azithromycin resistance rose from 6.1% in 2016 to 16% in 2019 (p < 0.001). Only 1.0% (45 cases) were resistant to ceftriaxone. Multidrug-resistant N. gonorrhoeae increased from 0.25% in 2016 to 0.42% in 2019 (p = 0.521). One case presented extensively drug-resistant N. gonorrhoeae. In Catalonia, 10% of the N. gonorrhoeae isolates were resistant to azithromycin in the 2016-2019 period. According to World Health Organization guidelines, resistance above 5% indicates an alert to review treatment guidelines. Antimicrobial susceptibility testing in clinical practice followed by surveillance and interventions are essential to monitor trends and prevent the spread of antimicrobial resistance.


Quantitative structural analysis of twin boundary in alpha-Zn7Sb2O12 using HAADF STEM method.
The structure and composition of the 1/4{110} twin boundary in alpha-Zn7Sb2O12 have been determined by using quantitative high-angle annular dark field scanning transmission electron microscopy (HAADF STEM) analysis. The noise in the experimental HAADF STEM images is reduced by using the maximum entropy method and average processing, and the parameters used in dynamical simulations are experimentally determined. From the analysis, it has been found that octahedral sites in the twin boundary slightly shift parallel to the [110] direction, and a reduction of the Sb concentration at the octahedral sites on the plane adjacent to the twin boundary was detected. The reduction was measured from three regions in the same twin boundary, and the Sb concentrations were 4 +/- 3, 8 +/- 3 and 19 +/-2 at% from 33 at%.


Has the prevalence of health care services use increased over the last decade (2001-2009) in elderly people? A Spanish population-based survey.
(1) To describe the prevalence of general practitioner visits and hospitalization according to sex and age groups; (2) to identify which factors are independently associated with a higher use of health care services among elderly Spanish; and (3) to study the time trends in the prevalence of use of health care services 2001-2009. Observational study. We analyzed data from the Spanish National Health Surveys conducted in 2001 (n=21,058), 2003 (n=21,650), 2006 (n=29,478) and 2009 (n=22,188). We included responses from adults aged 65 years and older. The main variables were the number of general practitioner visits in the last 4 weeks and hospitalization in the past year. We stratified the adjusted models by the main variables. We analyzed socio-demographic characteristics, health related variables, using multivariate logistic regression models. The total number of subjects was 24,349 (15,041 woman, 9309 men). Women were significantly older than men (P<0.001). Women had higher prevalence of general practitioner visits than men in all surveys. Men had significantly higher prevalence of hospitalizations than women in the years 2001, 2006 and 2009. When we adjusted the hospitalization by possible confounders using logistic regressions, men had a higher probability of being hospitalized than women (OR 1.53, 1.39-1.69). The variables that were significantly associated with a higher use of health care services were lower educational level, worse self-rated health, chronic conditions, polypharmacy, and the level of disability. The number of general practitioner visits among women and men significantly increased from 2001 to 2009 (women: OR 1.43, 1.27-1.61; men: OR 1.71, 1.49-1.97). The current study revealed an increase in health care services utilization from 2001 to 2009 in the older Spanish population.


An insight into the roles of regulatory ncRNAs in plants: An abiotic stress and developmental perspective.
Different environmental cues lead to changes in physiology, biochemistry and molecular status of plant's growth. Till date, various genes have been accounted for their role in regulating plant development and response to abiotic stress. Excluding genes that code for a functional protein in a cell, a large chunk of the eukaryotic transcriptome consists of non-coding RNAs (ncRNAs) which lack protein coding capacity but are still functional. Recent advancements in Next Generation Sequencing (NGS) technology have led to the unearthing of different types of small and large non-coding RNAs in plants. Non-coding RNAs are broadly categorised into housekeeping ncRNAs and regulatory ncRNAs which work at transcriptional, post-transcriptional and epigenetic levels. Diverse ncRNAs play different regulatory roles in nearly all biological processes including growth, development and response to changing environments. This response can be perceived and counteracted by plants using diverse evolutionarily conserved ncRNAs like miRNAs, siRNAs and lncRNAs to participate in complex molecular regimes by activating gene-ncRNA-mRNA regulatory modules to perform the downstream function. Here, we review the current understanding with a focus on recent advancements in the functional studies of the regulatory ncRNAs at the nexus of abiotic stresses and development. Also, the potential roles of ncRNAs in imparting abiotic stress tolerance and yield improvement in crop plants are also discussed with their future prospects.


Stimuli strategy and learning dynamics promote the wisdom of crowds.
Collective wisdom is the ability of a group to perform more effectively than any individual alone. Through an evolutionary game-theoretic model of collective prediction, we investigate the role that reinforcement learning stimulus may play the role in enhancing collective voting accuracy. And collective voting bias can be dismissed through self-reinforcing global cooperative learning. Numeric simulations suggest that the provided method can increase collective voting accuracy. We conclude that real-world systems might seek reward-based incentive mechanism as an alternative to surmount group decision error.


Low serum progesterone on day of transfer adversely impacts ongoing pregnancy rates in hormonally prepared single blastocyst frozen embryo transfer cycles.
To evaluate if serum progesterone (P) levels on the day of transfer influence ongoing pregnancy rate (OPR) in hormonally prepared single blastocyst frozen embryo transfer (FET) cycles? Single center prospective cohort study conducted between June 2021 and August 2022 analyzed 217 single good quality blastocyst FET cycles hormonally prepared with oral estradiol valerate and micronized vaginal progesterone 400 mg twice daily. Mean serum P on the day of embryo transfer (ET) was 9.76 ± 5.19 ng/ml. Receiver operator curve (ROC) showed a significant predictive value of serum P levels on the day of ET for OPR, with an area under curve (AUC) (95 %CI) = 0.58 (0.49-0.66). Optimal serum P threshold for OPR was 7.7 ng/ml (Sensitivity 76.8%, Specificity 43.7%). 35.9% patients had serum P below this threshold. BMI was significantly higher (26.8 ± 3.7 vs 25.6 ± 4.3; p = 0.048) in patients with serum P < 7.7 ng/ml vs ≥ 7.7 ng/ml. OPR was significantly lower (24.4% vs 45.3%; p = 0.002) and clinical miscarriage rates significantly higher (37.9% vs 19.2%; p = 0.042) if serum P < 7.72 ng/ml vs ≥ 7.7 ng/ml. This study found that serum P level on the day of transfer in hormonally prepared FET cycles was a significant predictor of OPR.


Age-related and individual differences in the performance of a delayed response task (the A-not-B task) in infant twins aged 7-12 months.
The aim of the present work was to analyze the age-related dynamics and nature of interindividual differences in performing the A-not-B task, which addresses working memory in children aged 7-12 months. The cohort consisted of 150 children aged 7-12 months from mono- and dizygotic twin pairs. Working memory was assessed in terms of the maximum delay which the children could tolerate in a delayed response test (the A-not-B task). Performance of the task improved with age, such that a sharp change in the ability to tolerate the delay occurred between nine and ten months of age. Mental development as assessed using the Bayley scale showed a significant correlation with the duration of the delay in the task only after a threshold period (9-10 months of age) in the development of working memory. Analysis of intrapair correlations in mono- and dizygotic twins showed that interindividual differences in the A-not-B task delay at age 7-9 months were completely determined by individual environmental factors (including measurement errors), while at age 10-12 months the leading role in the interindividual variability in this measure was taken by the systematic environment. These results show that the abilities to tolerate delays at the beginning and end of the second six months of life are based on different mechanisms.


Glutathione S-transferase P1 Ile105Val polymorphism modulates allergen-induced airway inflammation in human atopic asthmatics in vivo.
Glutathione S-transferase P1 is a Phase II cytoprotective and detoxifying enzyme that is widely expressed in human airways. The glutathione S-transferase P1 Ile105Val polymorphism has been linked with atopic disorders and asthma. Yet, little remains known about the regulation of allergic inflammation by glutathione S-transferase P1 in human asthmatics. To establish the effect of the glutathione S-transferase P1 Ile105Val polymorphism on allergen-induced airway inflammation and oxidant stress, and non-specific bronchial hyperresponsiveness to methacholine and reactivity to specific allergen in mild human atopic asthmatics in vivo. Five Val(105)/Val(105) , twelve Val(105)/Ile(105) and twenty Ile(105)/Ile(105) mild atopic asthmatics underwent methacholine challenge, inhaled allergen challenge and endobronchial allergen provocation through a bronchoscope. A panel of inflammatory cytokines and chemokines, F2 -isoprostanes and isofuranes, markers of oxidative stress, thromboxane B2 and immunoglobulin E were measured in bronchoalveolar lavage fluid at baseline and 24 h after allergen instillation. Asthmatics with glutathione S-transferase P1 Val(105)/Val(105) compared with asthmatics with the glutathione S-transferase P1 Val(105)/Ile(105) and Ile(105)/Ile(105) had greater generation of acute phase cytokines (TNF-α, IL-6, CXCL8), IL-12, CCL11, thromboxane B2 and immunoglobulin E at 24 h after local allergen challenge. The GSTP1 genotype had no effect on airway hyperresponsiveness to methacholine and the reactivity to specific allergen. The glutathione S-transferase P1 Ile105Val polymorphism markedly modifies allergen-provoked airway inflammation in atopic asthmatics in vivo. Modulation of the biochemical milieu in response to allergen provides a mechanistic explanation for regulatory effects of glutathione S-transferase P1 polymorphism on airway pathophysiology, and may guide improvement of future therapeutic methods in human atopic asthmatics. These findings must me confirmed in a larger study population of asthmatics with various ethnicities.


Two HMOs retrofit buildings in historic and commercial downtown areas.
Renovation of nearby mill and warehouses provides HMOs with convenient locations, additional space at lower costs, and unusual, attractive, and functional facilities.


Nutraceutical functionalities of polysaccharides from marine invertebrates.
Many researchers are seeking functional materials from marine resources. These marine resources can be used as traditional food additives, and specifically, these are based on polysaccharides. To date, there is a big opportunity to develop new high-value added products with indispensable functional characteristics, which can be used in nutraceuticals either as additives or supplements. Also, a crossover in the pharmaceutical market may be established. Some glycosaminoglycans (GAGs) mimetic-type molecules are already being utilized in the field of nutrition as well as in the cosmetics industry. This chemical is used as a dietary supplement to maintain the structure and function of cartilages, for the relief of pain caused by osteoarthritic joints, and can also be used as an anti-inflammatory agent. Recently, in relation to the prevalence of mad cow disease and avian influenza, the production of GAGs from marine invertebrates offers new market opportunities as compared with that obtained from bovine or avian livestock.


Shortcomings of color Doppler sonography in the diagnosis of testicular torsion.
We determined the shortcomings of color Doppler sonography for the diagnosis of testicular torsion. We reviewed 5 cases of testicular torsion in which findings on color Doppler sonography were inconsistent with surgical findings. Color Doppler sonography showed blood flow in 2 patients who had necrotic testes at surgery. In 3 other patients blood flow was also normal by color Doppler sonography of whom 2 were treated for epididymitis with subsequent loss of the testes and 1 underwent salvage by immediate exploration. Testicular torsion is a clinical diagnosis requiring consideration of many variables. Color Doppler sonography is helpful but should not be regarded as the definitive discriminator.


Plasticity of reproductive components at different stages of development in the annual plant Thlaspi arvense L.
This study examines the effect of different densities and the removal of all neighbours at different stages of development on all components of reproduction in the inbreeding annual Thlaspi arvense L. A 64-fold increase in density significantly reduced all repooductive components. The number of flower buds per plant was decreased most strongly; the order of decreasing plasticity among the other components was number of capsules per flower, individual seed weight, ovule number per capsule, flowers per flower bud and seeds per ovule. Removing neighbours at all stages of development increased seed yield of plants in comparison to the control without density reduction, but patterns of plasticity depended strongly on time of treatment. The main effect of the removal of neighbours at the vegetative stage was to increase the number of flowers per plant, but the number of ovules per capsule and seed weight increased also, and abortion of capsules decreased. Removing neighbours at the onset of flowering initially failed to affect flower number per plant, instead it resulted in a strong reduction of capsule abortion and an increase in seed weight. However, several weeks after flowering had initially ceased, fresh lateral inflorescences were produced, resulting in a second flush of reproduction. Removing neighbours at the stage of fruit ripening resulted at first only in an increase in seed witht, but later a second reproductive phase occurred. Fresh lateral branches were produced, but the apical meristem was also reactivated. The overall pattern of plasticity among all reproductive components in response to a removal of neighbours was the same as in response to density. The position of a capsule along the inflorescence influenced its number of ovules, the rate of seed abortion and the mean weight of seeds, with the type of effect depending on the developmental stage at which neighbours were removed. Significant negative correlations were found between the mean weight of seeds and the number of seeds in a capsule under all treatments.


Factors which influence 'healthy' eating patterns: results from the 1993 Health Education Authority health and lifestyle survey in England.
This study explores the factors that influence eating patterns in a nationally representative sample of the English population. Subjects were interviewed in 1993; questions covered basic demographic details, attitudes about nutrition, and they completed a short food frequency questionnaire that had previously been validated. Cluster analysis was used to summarize dietary intake into more or less healthy clusters. A random sample of the English population. A cross-sectional survey of 5553 men and women (response rate 70%) aged between 16 and 74 years. As defined from the cluster analysis about half the sample were currently reporting a more healthy diet; respondents in the better educated middle-aged demographic cluster were more likely to report eating a more healthy diet than respondents in the younger lower-income family cluster. About three-quarters of all respondents believed that they either already ate a healthy diet or had changed to a healthy diet in the last 3 years. For those respondents who said they were eating a healthy diet about half of them were eating a more healthy diet. Respondents who had not changed their diet were more likely than those who had to believe that healthy foods were just another fashion (men 34% v. 13%; women 30% v. 12%), or expensive (men 50% v. 35%; women 53% v. 40%); they were less likely to care about what they ate (men 45% v. 13%; women 27% v. 7%). Nearly three-quarters of all respondents agreed that experts never agree about what foods are good for you. Younger, low-income families, and those who smoked, were the group least likely to be eating a more healthy diet. The results of this study suggest that about half of the population has reported a change to a healthier diet over the last 3 years and that overall about half of the population report eating a healthy diet. Those who had not made any change and were currently reporting a less healthy diet were more likely to smoke and come from the 'worse off group in the survey; they were also more likely to hold negative attitudes about healthy eating. A more focused and integrated approach to promoting healthy lifestyle in general is required, while at the same time ensuring that there is continued support for the majority of the population who have made healthy dietary changes.


Characterization and classification of adherent cells in monolayer culture using automated tracking and evolutionary algorithms.
This paper presents a novel method for tracking and characterizing adherent cells in monolayer culture. A system of cell tracking employing computer vision techniques was applied to time-lapse videos of replicate normal human uro-epithelial cell cultures exposed to different concentrations of adenosine triphosphate (ATP) and a selective purinergic P2X antagonist (PPADS), acquired over a 24h period. Subsequent analysis following feature extraction demonstrated the ability of the technique to successfully separate the modulated classes of cell using evolutionary algorithms. Specifically, a Cartesian Genetic Program (CGP) network was evolved that identified average migration speed, in-contact angular velocity, cohesivity and average cell clump size as the principal features contributing to the separation. Our approach not only provides non-biased and parsimonious insight into modulated class behaviours, but can be extracted as mathematical formulae for the parameterization of computational models.


Concentration dependent effect of (-)-Epicatechin on Na(+) /K(+) -ATPase and Ca(2+) -ATPase inhibition induced by free radicals in hypertensive patients: comparison with L-ascorbic acid.
Although the antioxidant properties of flavonoids are well documented, it is still unclear whether these effects are dependent on radical scavenging or iron chelating activities. Oxidative stress, a state of excessive reactive oxygen species (ROS) activity, is associated with vascular disease conditions such as hypertension. Both the anti- and pro-oxidant effects of tea catechins have been implicated in the alterations of cellular functions that determine their chemoprotective and therapeutic potentials in health and diseases. The present study examined the concentration dependent (10(-7) to 10(-4) m) effects of (-)-epicatechin and L-ascorbic acid on Na(+) /K(+) -ATPase and Ca(2+) -ATPase activity in hypertensive patients and normal subjects. L-ascorbic acid has been used as a positive control to compare the effect of (-)-epicatechin. A significant (p < 0.0001) decrease in the activities of Na(+) /K(+) -ATPase and Ca(2+) -ATPase was observed in hypertensive patients compared with normal subjects. We report that (-)-epicatechin shows a significant (p < 0.001) dose-dependent protective effect against oxidative stress induced by tert-butyl hydroperoxide (t-BHP), which is manisfested as a decrease in the activity of erythrocyte Na(+) /K(+) -ATPase and Ca(2+) -ATPase, in hypertensive patients as well as normal subjects. The effect of L-ascorbic acid was also significant (p < 0.001) and was comparable with that of (-)-epicatechin.


Sociological evaluation of patients with lung cancer--revision study in hospital patients.
Lung cancer was a rare disease until the middle of the XX century, a time when it became one of the most important causes of morbidity and mortality in the actual world. Nowadays, it is esteemed that one million people all over the world die every year due to lung cancer, which means that a life is lost each 30 seconds. The quality of life of this patients decreases inevitably, being frequent hospital readmission due to the lack of conditions to lead a normal and painless life. The aim of this study was to evaluate physical and cognitive incapacity and the social needs of patients with lung cancer in the outpatient department of Hospital de S. João--Porto. Our study includes 68 patients, predominantly married male, with average age of 63, retired, ex-smokers. Moreover, they had high physical dependence degrees and the most frequent social need was the attribution of the "complemento por dependência". In this type of patients, the family has a very important role on which the treatment is concerned, as well as to the level of the personal adjustment of the patient to his disease. Its social workers job to play a mediating role between the patients and their relatives and the several institutions which can give better responses to the needs of this sort of patients.


Association between COVID-19 and myasthenia gravis (MG): A genetic correlation and Mendelian randomization study.
Observational studies have suggested an association between coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG). Here, we aimed to estimate the genetic correlation and causal relationship between COVID-19 susceptibility, hospitalization, severity, and MG phenotypes using linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) approach. Summary statistics of COVID-19 susceptibility, hospitalization, and severity were used as instrumental variables for exposure traits. Large-scale genome-wide association study (GWAS) data for MG were used as outcome traits. The inverse variance weighted approach was used for the main MR analysis, complemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analysis was implemented using Cochran's Q test, MR-PRESSO method, and MR-Egger intercept test. LDSC analysis did not reveal any genetic correlation among COVID-19 susceptibility, hospitalization, severity, and MG phenotypes, including MG, early-onset MG, and late-onset MG (p > .05). Our MR analysis did not provide evidence supporting a causal effect of COVID-19 susceptibility, hospitalization, or severity on MG phenotypes (p > .05). Extensive sensitivity analysis strengthened the robustness and consistency of the MR estimates. Our study did not find evidence of a genetic correlation or causal relationship among COVID-19 susceptibility, hospitalization, severity, and MG. Future studies with more GWAS data are needed to evaluate the association between COVID-19 phenotypes and MG and its subgroups.


Evidence for an oviposition-deterring pheromone in Tephritis bardanae (Schrank) (Diptera: Tephritidae).
Female Tephritis bardanae (Schrank) exhibit a characteristic ovipositor-dragging behaviour immediately after laying eggs into a flowerbud of Arctium minus (Hill) Bernh. To establish whether this behaviour is associated with an oviposition-deterring pheromone (ODP), female T. bardanae were presented with clean, unattacked flowerbuds and fly activity was monitored using video recording equipment. The distribution of oviposition and fly behaviour were analysed. Avoidance of attacked buds was revealed by the oviposition pattern becoming overdispersed. Spacing out of eggs continued until, on average, each bud contained one egg-batch, after which the distribution became more random or clumped. Analysis of fly behaviour showed that attacked and unattacked buds received similar numbers of visits, but fewer oviposition attempts were made on attacked buds. This behaviour was consistent with use of a contact pheromone deterring repeated oviposition and applied to the bud surface during ovipositor-dragging. Avoidance of attacked buds should increase the efficiency of resource use by T. bardanae populations in the field; however, distributions of egg-batches in flowerhead samples collected from Monks Wood NNR, Cambridgeshire, during 1983-1985, were highly clumped and did not provide supportive evidence. This suggests that the effectiveness of oviposition deterrence in the field is reduced, because the active life of ODP under natural conditions is short, and/or because wild females frequently experience high oviposition drive due to scarcity of suitable flowerbuds.


Parathyroid hormone-stimulated calcium absorption in cTAL from vitamin D-deficient rabbits.
Cortical thick ascending limbs of Henle's loop were dissected from the kidneys of chronically vitamin D-deficient or -replete rabbits and perfused in vitro. Unidirectional transepithelial calcium fluxes from lumen to bath were measured with 45Ca. The tubules were bathed in a solution containing 150 mM sodium and perfused with a solution containing 60 mM sodium to simulate conditions in the cortical thick ascending limb in vivo. Transepithelial voltages were equal across tubules from vitamin D-deficient and -replete rabbits. Likewise, baseline and parathyroid hormone-stimulated calcium fluxes were the same in tubules from the two groups. Because calcidiol and calcitriol were undetectable in the serum of the vitamin D-deficient rabbits, we suggest that neither of these endogenous vitamin D metabolites is essential in the regulation of calcium absorption in this portion of the rabbit nephron.


Performance of quantitative ultrasound measurements of bone for monitoring raloxifene therapy.
Raloxifene increases bone mineral density (BMD) and decreases vertebral fracture risk; the effects on quantitative ultrasound (QUS) variables, however, have been less well studied. We aimed to further evaluate the effectiveness of QUS for monitoring raloxifene treatment and withdrawal effects. Osteopenic, postmenopausal women (age=50-80 yr, n=125), who completed a 96-wk study (phase A) evaluating treatment compliance or monitoring, were invited to participate in a 96-wk raloxifene withdrawal study (phase B). Those originally receiving treatment were then randomized to continue on raloxifene (60 mg/d)+calcium (500 mg/d) (n=23) or to discontinue raloxifene and take placebo+calcium (500 mg/d) (n=23). Previously untreated women remained untreated (n=12). Yearly QUS and BMD measurements were performed. At the end of phase A, lumbar spine BMD (p=0.005), amplitude-dependent speed of sound (Ad-SoS) (p=0.006) and average SoS (p=0.040) decreased in untreated women but remained stable in treated women. Significant changes in Ad-SoS and ultrasonic bone profiler index had occurred in treated women by the end of phase B (p<0.01). All variables, except bone transmission time, were higher for those receiving any raloxifene treatment (p<0.05). Until further knowledge has been acquired, QUS measurement variables should only be used in conjunction with BMD when assessing changes in bone because of raloxifene therapy.


Cyanide-arene Meisenheimer complex generated in electrospray ionization mass spectrometry using acetonitrile as a solvent.
The C - C bond formation activated under negative electrospray ionization of an acetonitrile solution of 1,3,5-trinitrobenzene is reported. The solvent function is to provide a source of cyanide ion, a highly problematic reagent, which is found to attack the electron-deficient aromatic ring to form a covalently bound anionic complex (Meisenheimer complex). The structure of the complex is elucidated by means of collision induced dissociation mass spectrometry and IR multiple photon dissociation spectroscopy in the 'fingerprint' region.


Pediatric Eating Assessment Tool-10 as an indicator to predict aspiration in children with esophageal atresia.
Airway aspiration is a common problem in children with esophageal atresia (EA). Pediatric Eating Assessment Tool-10 (pEAT-10) is a self-administered questionnaire to evaluate dysphagia symptoms in children. A prospective study was performed to evaluate the validity of pEAT-10 to predict aspiration in children with EA. Patients with EA were evaluated for age, sex, type of atresia, presence of associated anomalies, type of esophageal repair, time of definitive treatment, and the beginning of oral feeding. Penetration-aspiration score (PAS) was evaluated with videofluoroscopy (VFS) and parents were surveyed for pEAT-10, dysphagia score (DS) and functional oral intake scale (FOIS). PAS scores greater than 7 were considered as risk of aspiration. EAT-10 values greater than 3 were assessed as abnormal. Higher DS scores shows dysphagia whereas higher FOIS shows better feeding abilities. Forty patients were included. Children with PAS greater than 7 were assessed as PAS+ group, and scores less than 7 were constituted as PAS- group. Demographic features and results of surgical treatments showed no difference between groups (p>0.05). The median values of PAS, pEAT-10 and DS scores were significantly higher in PAS+ group when compared to PAS- group (p<0.05). The sensitivity and specificity of pEAT-10 to predict aspiration were 88% and 77%, and the positive and negative predictive values were 22% and 11%, respectively. Type-C cases had better pEAT-10 and FOIS scores with respect to type-A cases, and both scores were statistically more reliable in primary repair than delayed repair (p<0.05). Among the postoperative complications, only leakage had impact on DS, pEAT-10, PAS and FOIS scores (p<0.05). The pEAT-10 is a valid, simple and reliable tool to predict aspiration in children. Patients with higher pEAT-10 scores should undergo detailed evaluation of deglutitive functions and assessment of risks of aspiration to improve safer feeding strategies. Level II (Development of diagnostic criteria in a consecutive series of patients and a universally applied "gold standard").


Oncologic Phenotype of Peripheral Neuroblastic Tumors Associated With PHOX2B Non-Polyalanine Repeat Expansion Mutations.
Germline non-polyalanine repeat expansion mutations in PHOX2B (PHOX2B NPARM) predispose to peripheral neuroblastic tumors (PNT), frequently in association with other neurocristopathies: Hirschsprung disease (HSCR) or congenital central hypoventilation syndrome (CCHS). Although PHOX2B polyalanine repeat expansions predispose to a low incidence of benign PNTs, the oncologic phenotype associated with PHOX2B NPARM is still not known in detail. We analyzed prognostic factors, treatment toxicity, and outcome of patients with PNT and PHOX2B NPARM. Thirteen patients were identified, six of whom also had CCHS and/or HSCR, one also had late-onset hypoventilation with hypothalamic dysfunction (LO-CHS/HD), and six had no other neurocristopathy. Four tumours were "poorly differentiated," and nine were differentiated, including five ganglioneuromas, three ganglioneuroblastomas, and one differentiating neuroblastoma, hence illustrating that PHOX2B NPARM are predominantly associated with differentiating tumors. Nevertheless, three patients had stage 4 and one patient had stage 3 disease. Segmental chromosomal alterations, correlating with poor prognosis, were found in all the six tumors analyzed by array-comparative genomic hybridization. One patient died of tumor progression, one is on palliative care, one died of hypoventilation, and 10 patients are still alive, with median follow-up of 5 years. Based on histological phenotype, our series suggests that heterozygous PHOX2B NPARM do not fully preclude ganglion cell differentiation in tumors. However, this tumor predisposition syndrome may also be associated with poorly differentiated tumors with unfavorable genomic profiles and clinically aggressive behaviors. The intrafamilial variability and the unpredictable tumor prognosis should be considered in genetic counseling.


Long-term follow-up of platelet-rich plasma injections for refractory lateral epicondylitis.
Lateral epicondylitis (LE)1 affects between 1 and 3% of the population. Recently, platelet-rich plasma (PRP)2 has gained popularity. Assess the long-term outcomes of PRP for patients with refractory LE. We assessed 31 patients who had failed conservative management using the Oxford Elbow Score (OES).3. Mean follow-up: 5.2 years (range 4.2-6.1 years).87.1% exhibited minimum clinically important difference (MCID)4 in pain scores between pre-op and long-term. 90.3% displayed MCID in function and psycho-social domains.Two patients had a repeat injection and six underwent open release. PRP is successful in treating refractory LE in most patients and avoiding surgery.


Structural models of the bovine papillomavirus E5 protein.
The bovine papillomavirus E5 protein is thought to be a type II integral membrane protein that exists as a disulfide-linked homodimer in transformed cells. Polarized-infrared measurements show that the E5 dimer in membrane bilayers is largely alpha-helical and has a transmembrane orientation. Computational searches of helix-helix conformations reveal two possible low-energy dimer structures. Correlation of these results with previous mutagenesis studies on the E5 protein suggests how the E5 dimer may serve as a molecular scaffold for dimerization and ligand-independent activation of the PDGF-beta receptor. We propose that on each face of the E5 dimer a PDGF-beta receptor molecule interacts directly with Gln17 from one E5 monomer and with Asp33 from the other E5 monomer. This model accounts for the requirement of Gln17 and Asp33 for complex formation and explains genetic results that dimerization of the E5 protein is essential for cell transformation.


Treating the right patient at the right time: access to heart failure care.
Heart failure affects over 500,000 Canadians, and 50,000 new patients are diagnosed each year. The mortality remains staggering, with a five-year age-adjusted rate of 45%. Disease management programs for heart failure patients have been associated with improved outcomes, the use of evidence-based therapies, improved quality of care, and reduced costs, mortality and hospitalizations. Currently, national benchmarks and targets for access to care for cardiovascular procedures or office consultations do not exist. The present paper summarizes the currently available data, particularly focusing on the risk of adverse events as a function of waiting time, as well as on the identification of gaps in existing data on heart failure. Using best evidence and expert consensus, the present article also focuses on timely access to care for acute and chronic heart failure, including timely access to heart failure disease management programs and physician care (heart failure specialists, cardiologists, internists and general practitioners).


Metric and non-metric randomization methods, geographic variation, and the single-species hypothesis for Asian and African Homo erectus.
This paper proposes a statistical test of the single-species hypothesis using non-metric characters as a complement to statistical tests using more traditional metric characters. The sample examined is that of Asian and African Homo erectus. The paleoanthropological community is divided on the taxonomic distinction of these fossils, with workers arguing both for and against the species-level distinction between Asian and African populations. Previous arguments have focused on patterns of apparent morphological differentiation between the African and Asian cranial samples. To assess this question, three tests were performed that compared the range of variation in the fossil sample to a single-species group with a similar geographic distribution; this comparative sample was composed of 221 modern humans from Africa and Asia. For the first test, 23 metric characters were analyzed on the fossil and comparative samples. Using resampling procedures, the variation for these characters was examined, recreating 1000 samples from the human analogs and comparing the CV distributions of these samples to the CVs of the fossil group. The second test used the metric data to calculate a Euclidean distance between the African and Asian fossil samples. This distance was compared to a distribution of Euclidean distances calculated between 1000 randomly selected samples of African and Asian modern humans. For the third test, a grading scale was created for ten non-metric characters that encompassed the total morphological variation found in the fossil and modern human samples. The Manhattan distance between the Asian and African fossil samples was calculated and compared to a distribution of distances calculated between 1000 randomly selected samples of African and Asian moderns. The first two tests, using the metric data, failed to falsify the null hypothesis. However, in the third test, using non-metric data, the total Manhattan distance for the fossil sample approached the 100th percentile of the resampled distances calculated from the moderns. The implications of the contrasting results are discussed.


Short-term surgical outcomes and histomorphological evaluation of thermal injury following palatoplasty performed with diode laser or air plasma device in dogs with brachycephalic airway obstructive syndrome.
Brachycephalic obstructive airway syndrome (BOAS) is a common disorder presenting enlarged soft palate, stenotic nares and abnormal turbinate growth. Surgical correction of BOAS abnormalities with caudal palatoplasty is an elective therapy. This prospective study aimed to compare the effect of an air plasma device and diode laser in dogs undergoing palatoplasty. Outcome measures were as follows: (1) intra-operative and immediate post-operative complications; (2) evaluation of thermal injury in histological tissue sections of the excised soft palate. Twenty dogs with enlarged soft palates underwent palatoplasty, using an air plasma device (n=10) and diode laser (n=10). Soft palate specimens underwent masked histopathological analysis to assess post-operative thermal injury. In this pilot study, no differences were observed in surgical times; all dogs were discharged 24h after surgery and had stable respiration. In the air plasma group, post-operative bleeding occurred in two cases and revision surgery was performed. No difference in thermal injury was observed using the two devices (P>0.05). The air-plasma device was a viable surgical option for palatoplasty in dogs with BOAS.


Changes in measures of consciousness during anaesthesia of one hemisphere (Wada test).
In the Wada test, one hemisphere is selectively anaesthetised by unilateral intracarotid injection of a fast-acting anaesthetic agent. This gives a unique opportunity to observe the functions and physiological activity of one hemisphere while anaesthetising the other, allowing direct comparisons between brain states and hemispheres that are not possible in any other setting. To test whether potential measures of consciousness would be affected by selective anaesthesia of one hemisphere, and reliably distinguish the states of the anesthetised and non-anesthetised hemispheres. We analysed EEG data from 7 patients undergoing Wada-tests in preparation for neurosurgery and computed several measures reported to correlate with the state of consciousness: power spectral density, functional connectivity, and measures of signal diversity. These measures were compared between conditions (normal rest vs. unilateral anaesthesia) and hemispheres (injected vs. non-injected), and used with a support vector machine to classify the state and site of injection objectively from individual patient's recordings. Although brain function, assessed behaviourally, appeared to be substantially altered only on the injected side, we found large bilateral changes in power spectral density for all frequency bands tested, and functional connectivity changed significantly both between and within both hemispheres. Surprisingly, we found no statistically significant differences in the measures of signal diversity between hemispheres or states, for the group of 7 patients, although 4 of the individual patients showed a significant decrease in signal diversity on the injected side. Nevertheless, including signal diversity measures improved the classification results, indicating that these measures carry at least some non-redundant information about the condition and injection site. We propose that several of these results may be explained by conduction of activity, via the corpus callosum, from the injected to the contralateral hemisphere and vice versa, without substantially affecting the function of the receiving hemisphere, thus reflecting what we call "cross-state unreceptiveness".


Recent advances in sudden infant death syndrome: possible autonomic dysfunction of the airways in infants at risk.
Epidemiological studies of sudden infant death syndrome (SIDS) reveal a progressive increase in the incidence of cases, suggesting that the in utero environment and postneonatal care were less than optimal. Subtle differences in symptoms could indicate that, since birth, the SIDS infants are different from control infants, some having an autonomic dysfunction of the airway controls. These observations could contribute to a better understanding of some of the causes of sudden death in infants and could eventually lead to new therapeutic approaches.