Chronic graft-versus-host disease following umbilical cord blood transplantation: retrospective survey involving 1072 patients in Japan.
We have little information on chronic graft-versus-host disease (GVHD) after cord blood transplantation (CBT). We investigated its clinical features in 1072 Japanese patients with hematologic malignancies who received a transplant through the Japan Cord Blood Bank Network. The primary end point was to investigate the incidence of any chronic GVHD. Median age of the patients was 33 years (range, 0-79 years). The cumulative incidence of chronic GVHD 2 years after transplantation was 28%. Chronic GVHD was fatal in 29 patients. Multivariate analysis demonstrated that development of chronic GVHD was favorably associated with both overall survival and event-free survival. Multivariate analysis identified risk factors of chronic GVHD: higher patient body weight, higher number of mismatched antigens for GVHD direction, myeloablative preparative regimen, use of mycophenolate mofetil in GVHD prophylaxis, and development of grades II to IV acute GVHD. Although chronic GVHD is a significant problem after CBT, it is associated with improved survival, perhaps due to graft-versus-malignancy effects.


The prevalence of atopy and hypersensitivity to latex in medical laboratory technologists.
Members of the Alberta Society of Medical Laboratory Technologists were invited to take part in a study of sensitivity to latex gloves. A total of 230 persons volunteered; 108 (47%) had no problems with gloves, and 122 (53%) reacted to latex gloves. A history was obtained regarding atopy, smoking, years in laboratory medicine, and the nature of the problem with latex gloves. Serum was assayed for the total IgE level and the presence of IgE with specificity to common inhalant allergens and to latex. The affected group had an increased population of subjects with an atopic history and a higher incidence of a raised IgE level and a positive screen for inhalant allergens. In the affected group, there was no relationship between the total IgE level and severity of skin reaction. However, smoking was related to severity of reaction and was more common in the groups with a more severe reaction. Three subjects were positive for IgE specific for latex; there were no other data distinguishing them from latex-negative subjects.


Extracellular Vesicle-Associated RNA as a Carrier of Epigenetic Information.
Post-transcriptional regulation of messenger RNA (mRNA) metabolism and subcellular localization is of the utmost importance both during development and in cell differentiation. Besides carrying genetic information, mRNAs contain cis-acting signals (zip codes), usually present in their 5'- and 3'-untranslated regions (UTRs). By binding to these signals, trans-acting factors, such as RNA-binding proteins (RBPs), and/or non-coding RNAs (ncRNAs), control mRNA localization, translation and stability. RBPs can also form complexes with non-coding RNAs of different sizes. The release of extracellular vesicles (EVs) is a conserved process that allows both normal and cancer cells to horizontally transfer molecules, and hence properties, to neighboring cells. By interacting with proteins that are specifically sorted to EVs, mRNAs as well as ncRNAs can be transferred from cell to cell. In this review, we discuss the mechanisms underlying the sorting to EVs of different classes of molecules, as well as the role of extracellular RNAs and the associated proteins in altering gene expression in the recipient cells. Importantly, if, on the one hand, RBPs play a critical role in transferring RNAs through EVs, RNA itself could, on the other hand, function as a carrier to transfer proteins (i.e., chromatin modifiers, and transcription factors) that, once transferred, can alter the cell's epigenome.


Close relationships as a contributor to chronic pain pathogenesis: Predicting pain etiology and persistence.
Chronic stress contributes to the pathogenesis of chronic pain. Yet, the role of close relationship stress in these pathways to pain is not fully understood. To delineate specific psychosocial pathways associated with chronic pain, specifically emphasizing close relationships for midlife adults. We tested whether relationship strain, relationship support, social integration, depression, anxiety, and pain severity predict chronic pain etiology and persistence over 10 years, highlighting specific associations for acute versus chronic pain. Using data from the National Survey of Midlife in the U.S. (MIDUS 2 and 3, collected in 2004-2006 and 2013-2014, respectively), we used logistic regression to test the etiology of new chronic pain (n = 1591) and persistence of pain for adults with acute (n = 352) and chronic pain (n = 367) conditions at baseline. Of participants who reported they did not have chronic pain at baseline, the development of chronic pain 10 years later was significantly associated with baseline family strain (OR = 1.38, p < .01). For participants with acute pain at baseline, the transition of this pain to chronic a decade later was significantly associated with initial reports of pain interference (OR = 1.24, p < .001), family support (OR = 0.60, p < .05), and depression (OR = 1.20, p < .05). Persistent chronic pain was solely associated with baseline pain interference (OR = 1.21, p < .01). Family strain is an important part of the chronic stress profile associated with chronic pain etiology, whereas family support is associated with a reduced risk of acute pain transitioning to chronic pain over time. Prioritizing family relationships in treatment approaches to pain may be an indicated, innovative approach to preventing pain development and escalation and requires systems training in healthcare.


Microgenomic analysis in skeletal muscle: expression signatures of individual fast and slow myofibers.
Skeletal muscle is a complex, versatile tissue composed of a variety of functionally diverse fiber types. Although the biochemical, structural and functional properties of myofibers have been the subject of intense investigation for the last decades, understanding molecular processes regulating fiber type diversity is still complicated by the heterogeneity of cell types present in the whole muscle organ. We have produced a first catalogue of genes expressed in mouse slow-oxidative (type 1) and fast-glycolytic (type 2B) fibers through transcriptome analysis at the single fiber level (microgenomics). Individual fibers were obtained from murine soleus and EDL muscles and initially classified by myosin heavy chain isoform content. Gene expression profiling on high density DNA oligonucleotide microarrays showed that both qualitative and quantitative improvements were achieved, compared to results with standard muscle homogenate. First, myofiber profiles were virtually free from non-muscle transcriptional activity. Second, thousands of muscle-specific genes were identified, leading to a better definition of gene signatures in the two fiber types as well as the detection of metabolic and signaling pathways that are differentially activated in specific fiber types. Several regulatory proteins showed preferential expression in slow myofibers. Discriminant analysis revealed novel genes that could be useful for fiber type functional classification. As gene expression analyses at the single fiber level significantly increased the resolution power, this innovative approach would allow a better understanding of the adaptive transcriptomic transitions occurring in myofibers under physiological and pathological conditions.


Antigenic analysis of the major outer membrane protein of Chlamydia trachomatis with murine monoclonal antibodies.
We prepared monoclonal antibodies against prototype strains of the 15 serovars of Chlamydia trachomatis and identified a subset of reagents that reacted with the major outer membrane protein(s) (MOMPs) of one or more serovars. We then determined the specificities of these anti-MOMP monoclonal antibodies by radioimmunoassay and immunoblot assays against the 15 serovars of C. trachomatis and a C. psittaci strain. We identified 14 different anti-MOMP antibody specificities, including serovar-, several orders of subspecies-, and species-specific determinants. In addition, one antibody reacted with all C. trachomatis serovars and a C. psittaci strain, indicating the presence of a genus-specific epitope on MOMP. Many of the cross-reactions of the subspecies-specific antibodies were similar to those previously reported by use of the microimmunofluorescence technique. We also observed a number of cross-reactions that were unexpected but consistent with data derived by the microimmunofluorescence test. All antibodies, except the genus-specific antibodies, reacted with whole elementary bodies in a radioimmunoassay, suggesting surface exposure of the epitopes. These data confirm and extend previous observations that MOMPs among C. trachomatis serovars are antigenically complex and diverse. In addition, these data indicate that the cross-reaction patterns of some monoclonal antibodies directed against MOMP are similar to those detected by the microimmunofluorescence test and are consistent with the hypothesis that such determinants are contained within MOMPs.


Epidemiology and bioethics: a plea for reconnecting with the public.
The author takes the position that both epidemiology and bioethics, as practiced within academic establishments, have largely although not entirely abstracted the public context of health and well-being from their respective disciplines. It is argued that by and large both disciplines have been highly successful at what they do. However, this success can in part be attributed to each limiting its ability to look beyond its respective academic niche and thus embrace challenges which are socially challenging, politically charged, and academically messy. This narrow focus has become self-serving and ultimately detracts from fundamental remits of both disciplines in protecting the public from harm. Furthermore, it may re-enforce the inequalities of research into health overall, whereby the greatest concentration of effort remains firmly focused upon those who already have the most. Currently marginalized approaches to each of these disciplines - such as social epidemiology, global bioethics, and critical bioethics - provide us with platforms that challenge mainstream academic epidemiologists and bioethicists to seek out and reconnect their expertise with questions that are more relevant to real-world situations.


Nitric oxide synthase 3 and endothelin 1 immunoreactivity in pulmonary hypertension.
Pulmonary hypertension (PH) is a serious and sometimes life-threatening event that occurs as a complication of various cardiopulmonary disorders, of which rheumatic heart disease (RHD) is an important example in our country. The pathogenesis of PH is a complex, multistep process in which "pulmonary endothelial dysfunction" (PED) is widely regarded as the central pathogenetic event. PED is, in turn, influenced by several local and systemic factors, of which nitric oxide synthase 3 (NOS3) and endothelin 1 (ET1) are 2 prime candidates, and are the subject of our study. Our aim was to study the immunoreactivity of NOS3 and ET1 in the pulmonary vasculature of PH patients of various etiologies, with emphasis on RHD cases. A retrospective, autopsy-based study. A total of 49 autopsy cases (39 patients and 10 controls) were chosen for our study. Of the 39 patients, 20 had PH secondary to RHD, whereas the remaining 19 patients had non-RHD etiologies as the basis of their PH. Lung sections taken from all the 49 cases were subjected to routine H and E, elastic van Gieson, and immunohistochemical staining (with NOS3 and ET1 separately). The intensity of immunostaining in all the cases and controls were then graded as focal/diffuse and weak/strong. Controls showed positivity for both NOS3 (bronchiolar epithelium) and ET1 (endothelium of pulmonary arteries). Characteristic changes of PH on H and E were seen in 14 out of 19 non-RHD cases, which matched with the number of ET1 positivity cases. Similarly, for the RHD cases, 14 out of 20 cases showed changes of PH on H and E, but only 2 cases showed mild, focal positivity for ET1. Surprisingly, NOS3 positivity was largely absent in both the non-RHD and RHD cases. Our study showed NOS3 negativity and ET1 positivity in the lung vasculature of patients with PH, a conclusion more or less in line with the predominant view of the other investigators in this field. But at the same time, our study could not conclude an unequivocal role of NOS3 in PH, whereas it could, in the case of ET1.


[Effect of heat shock response on the cleavage of nucleolin induced by oxidative stress].
To observe the cleavage of nucleolin (C23) during apoptosis induced by oxidative stress and to clarify the effect of heat shock response (HSR) on the cleavage of nucleolin and its possible molecular mechanism. We added 0.5 mmol/L peroxide hydrogen (H2O2 ) into cultured cells to mimic oxidative stress. Apoptosis and cleavage of C23 were detected using caspase-3 colorimetric assay and Western blotting respectively. HSR was performed to observe the effect of HSR on cleavage of C23 induced by oxidative stress, and over-expressions of HSP70 and HSP25 were detected by Western blotting. Activity of caspase-3 increased significantly after 2 hours of 0.5 mmol/L H2O2 treatment, and reached the peak after 12 hours. The cleavage of C23 appeared 30 minutes to 1 hour after the treatment of H2O2 as indicated by a cleaved fragmentation of 80 kD, which was significantly inhibited by HSR. Moreover, HSR could induce HSP70 and HSP25 over-expressions. Oxidative stress can induce the activation of caspase-3, cleavage of C23, and apoptosis. HSR can significantly inhibit the cleavage of C23 induced by oxidative stress, which is related to the over-expressions of HSP70, HSP25, and other stress proteins.


Mononucleotide precedes dinucleotide repeat instability during colorectal tumour development in Lynch syndrome patients.
A progressive accumulation of genetic alterations underlies the adenoma-carcinoma sequence of colorectal cancer. This accumulation of mutations is driven by genetic instability, of which there are different types. Microsatellite instability (MSI) is the predominant type present in the tumours of Lynch syndrome patients and in a subset of sporadic tumours. It is generally accepted that MSI can be found in the early stages of tumour progression, such as adenomas; however, the frequencies reported vary widely among studies. Moreover, data on the qualitative differences between adenomas and carcinomas, or between tumours of hereditary and sporadic origin, are scarce. We compared MSI in samples of colorectal adenoma and colorectal carcinoma in order to identify possible differences along the adenoma-carcinoma sequence. We compared germline mismatch repair (MMR) gene mutation carriers and non-carriers, to address possible differences of instability patterns between Lynch syndrome patients and patients with sporadic tumours. We found a comparable relative frequency of mono- and dinucleotide instability in sporadic colorectal adenomas and carcinomas, dinucleotide instability being observed most frequently in these sporadic tumours. In MMR gene truncating mutation carriers, the profile was different: colorectal adenomas showed predominantly mononucleotide instability and in colorectal carcinomas, also more mononucleotide than dinucleotide instability was detected. We conclude that MSI profiles differ between sporadic and Lynch syndrome tumours, and that mononucleotide marker instability precedes dinucleotide marker instability during colorectal tumour development in Lynch syndrome patients. As mononucleotide MSI proves to be highly sensitive for detecting mutation carriers, we propose the use of mononucleotide markers for the identification of possible Lynch syndrome patients.


Atopy and neural damage.
The occurrence of myelitis with atopic diathesis (atopic myelitis) affecting young adults has recently been noted in Japan. The disease preferentially affects the posterior column of the cervical spinal cord, as shown clinically and by MRI. It is characterized by hyperIgEaemia and the presence of mite antigen-specific IgE. The spinal cord lesions have been shown to be eosinophilic inflammation on biopsy and thus an allergic mechanism is thought to be operative in this condition. In addition, we also found that Hirayama disease, juvenile muscular atrophy of the distal upper extremity, is also associated with airway allergy such as allergic rhinitis and atopic asthma. In children, poliomyelitislike illness after acute asthma attacks is well known as Hopkins syndrome. Moreover, by the prospective study of the history of allergic disorders in common neurologic diseases, an association between spinal progressive muscular atrophy (SPMA) and asthma as well as between myelitis and atopic dermatitis has been demonstrated. These observations strongly suggest a link between atopic diathesis and spinal cord damage. Central nervous system damage associated with atopic diathesis may be classified into two types; eosinophilic myelitis preferentially affecting the cervical spinal cord and lower motor neuron damage, such as Hopkins syndrome, Hirayama disease and SPMA. The former is typically associated with atopic dermatitis while the latter, with airway allergy.


Problematic protocols: An overview of medical research protocols not approved by the LUMC medical ethics review committee.
The Committee for Medical Ethics (CME) of Leiden University Medical Center (LUMC) was established as the first medical ethics reviewing committee (MREC) in the Netherlands. In the period 2000-2010 the CME received 2,162 protocols for review. Some of these protocols were never approved. Until now, there has existed neither an overview of these failed protocols nor an overview of the reasons for their failure. This report draws on data from the digital database, the physical archives, and the minutes of the meetings of the CME. Additional information has been obtained from the Central Committee on Research involving Human Subjects (CCRH) and survey-based research. Protocols were itemized based on characteristic features and their reviewing procedures were analyzed. In total, 1,952 out of 2,162 research protocols submitted during 2000-2010 (90.3%) were approved by the CME; 210 of 2,162 protocols (9.7%) were not approved. Of these 210 protocols, 177 failed due to reasons not related to CME reviewing. In 15 cases CME reviewing led to protocol failure, while another 10 protocols were rejected outright. Eight of the 210 submitted protocols without approval had been conducted prior to submission. In the aforementioned period, little protocol failure occurred. For the most part, protocol failure was caused by problems that are not CME related. This type of failure has several identifiable factors, none of which have anything to do with the ethical reviewing procedure by the CME. A mere 1.2% of protocols failed due to ethical review. Unacceptable burden and risks to the subject and an inadequate methodology are the most common reasons for this CME-related protocol failure.


Auto-SCT in refractory celiac disease type II patients unresponsive to cladribine therapy.
Autologous hematopoietic SCT (auto-SCT) has been effective therapy for refractory disease, in both malignancies and severe autoimmune diseases. It seems feasible and safe for refractory celiac disease (RCD) type II, although long-term results have not been evaluated yet. With current therapies, progression into enteropathy-associated T-cell lymphoma (EATL) occurs in 60-80% patients, with a high mortality rate. Therefore, it is important to evaluate new treatment strategies. Between March 2004 and February 2010, 18 RCD II patients were evaluated for auto-SCT preceded by conditioning with fludarabine and melphalan, as a consequence of unresponsiveness to cladribine therapy. Adverse events, survival rate, EATL development and change in clinical, histological and immunological course were monitored. Thirteen patients were transplanted successfully and followed up for >2 years, 4-year survival rate was 66%. Only one patient died because of transplant-related complications. The majority of patients showed an impressive clinical improvement and five a complete histological remission. In five patients, auto-SCT could not be performed; they all died with a median survival of 5.5 months. EATL was observed in one transplanted patient, only after 4 years of follow-up. Auto-SCT after conditioning with high-dose chemotherapy in RCD II patients unresponsive to cladribine therapy is feasible and seems promising.


Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt.
Topical therapy is usually of limited benefit in the treatment of severe atopic dermatitis (AD), and the need for a safe and effective systemic treatment may be required in certain cases especially in children. We evaluated the efficacy and safety of methotrexate and cyclosporine in the treatment of 40 children with severe AD. Patients were divided into two groups (each consisting of 20 patients); group A was treated with methotrexate (7.5 mg/week) while group B was treated with cyclosporine (2.5 mg/kg/day). The severity scoring for atopic dermatitis (SCORAD) was used to indicate efficacy of treatment. In group A, the mean SCORAD score at the beginning of the study was 57.90 ± 3.21 that was reduced at the end of the treatment period to reach 29.35 ± 6.32 with a mean absolute reduction of 26.25 ± 7.03. In group B, the mean SCORAD score was 56.54 ± 4.82 at the start of treatment and was 31.35 ± 8.89 at the end of 12 weeks of treatment. The mean absolute reduction was 25.02 ± 8.21. There was no statistically significant difference in the reduction of SCORAD score between both groups (P ± 0.93). Mild and temporary adverse effects were reported in some patients in both groups. Methotrexate or cyclosporine in low doses can be considered as effective, relatively safe, and well-tolerated treatments for severe AD in children.


LncRNA AK036396 Inhibits Maturation and Accelerates Immunosuppression of Polymorphonuclear Myeloid-Derived Suppressor Cells by Enhancing the Stability of Ficolin B.
Long noncoding RNAs (lncRNA) are emerging as crucial regulators of cell biology. However, the role of lncRNAs in the development and function of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) remains unclear. Here, we identified that the lncRNA F730016J06Rik (AK036396) was highly expressed in PMN-MDSCs and that lncRNA AK036396 knockdown promoted the maturation and decreased the suppressive function of PMN-MDSCs. Ficolin B (Fcnb), the expression of which could be assessed as a surrogate for PMN-MDSC development, was the predicted target gene of lncRNA AK036396 based on microarray results. LncRNA AK036396 knockdown attenuated Fcnb protein stability in a manner dependent on the ubiquitin-proteasome system. Moreover, Fcnb inhibition downregulated the suppressive function of PMN-MDSCs. In addition, the expression of human M-ficolin, which is an ortholog of mouse Fcnb, was increased and positively correlated with arginase1 (ARG1) expression. This suppressive molecule is released by MDSCs, and its production is commonly used to represent the suppressive activity of MDSCs in patients with lung cancer, suggesting clinical relevance for these findings. These results indicate that lncRNA AK036396 can inhibit maturation and accelerate immunosuppression of PMN-MDSCs by enhancing Fcnb protein stability.


Place, Time and Experience: Barriers to Universalization Of Institutional Child Delivery in Rural Mozambique.
Although institutional coverage of childbirth is increasing in the developing world, a substantial minority of births in rural Mozambique still occur outside of health facilities. Identifying the remaining barriers to safe professional delivery services can aid in achieving universal coverage. Survey data collected in 2009 from 1,373 women in Gaza, Mozambique, were used in combination with spatial, meteorological and health facility data to examine patterns in place of delivery. Geographic information system-based visualization and mapping and exploratory spatial data analysis were used to outline the spatial distribution of home deliveries. Multilevel logistic regression models were constructed to identify associations between individual, spatial and other characteristics and whether women's most recent delivery took place at home. Spatial analysis revealed high- and low-prevalence clusters of home births. In multivariate analyses, women with a higher number of clinics within 10 kilometers of their home had a reduced likelihood of home delivery, but those living closer to urban centers had an increased likelihood. Giving birth during the rainy, high agricultural season was positively associated with home delivery, while household wealth was negatively associated with home birth. No associations were evident for measures of exposure to and experience with health institutions. The results suggest the need for a comprehensive approach to expansion of professional delivery services. Such an approach should complement measures facilitating physical access to health institutions for residents of harder-to-reach areas with community-based interventions aimed at improving rural women's living conditions and opportunities, while also taking into account seasonal and other variables.


Nutrition labels decrease energy intake in adults consuming lunch in the laboratory.
Increased visibility of food labels is a potential method to reduce the rate of obesity. However, few empirical studies have investigated the impact of nutrition labeling on food selection or energy intake. This study tested the hypothesis that nutrition labeling in combination with nutrition label education would promote reductions in energy intake using a laboratory-based paradigm. Forty-seven male (n=24) and female (n=23) participants visited the Nutrition and Health Research Laboratory for a single lunch session during the months of May through August 2009. Participants were randomly assigned to one of two video groups (Nutrition Labeling Education or Organic Food Movement) and one of two labeling conditions (Nutrition Labels or No Labels). Participants watched a short educational video and then consumed a buffet lunch. Data were analyzed using a three-way analysis of covariance with sex, video condition, and labeling group as the between-subject factors and age and race as covariates. There were main effects of sex and nutrition label condition on lunch energy intake with females consuming less than males and people with nutrition labels consuming less energy than those without, regardless of sex or video condition. Examination of energy intake from low-energy-density and high-energy-density foods showed that the nutrition labeling group consumed less energy from both low-energy-density and high-energy-density food sources. These data support the use of nutrition labels as a way to reduce energy intake.


Prevalence and characterization of uremic pruritus in patients undergoing hemodialysis: uremic pruritus is still a major problem for patients with end-stage renal disease.
Pruritus is a common disabling problem in patients with advanced end-stage renal disease. Few studies have evaluated the clinical characteristics of uremic itch. The aim of this multicenter study was to provide a comprehensive description of the prevalence and clinical characteristics of pruritus affecting patients with end-stage renal disease who are undergoing hemodialysis. A detailed questionnaire recently developed was used to evaluate pruritus in 219 patients undergoing hemodialysis treatment in 3 dialysis units. We examined the relationship of the quality of dialysis and various factors and medical parameters to itch. Pruritus was a common symptom in the study population. Approximately 66% of the patients had pruritus at some point, and 48% were affected by it at the time of the study. There was no correlation between the occurrence of pruritus and demographic or medical parameters (type of kidney disease, medical management, dialysis efficacy as expressed by Kt/V) of the patient. The data suggest that uremic pruritus tends to be prolonged, frequent, and intense, and it can impair the patient's quality of life including a negative effect on sleep and mood. Major factors found to exacerbate pruritus include rest, heat, dry skin, and sweat. Major factors found to reduce pruritus include activity, sleep, hot and cold shower, and cold. Treatment with angiotensin inhibitors seemed to be more common among those with uremia who had itch (P =.02) whereas furosemide was more commonly used among those who never itched (P =.002). This study provides a detailed description of uremic pruritus with new data on its characteristics including affective and sensory dimensions and associated symptoms.


Central monoamine deficiency in depressions: causative of secondary phenomenon?
There are indications for a functional deficiency of 5-HT and DA in certain kinds of depression. The question arises if these biochemical disturbances are primary or secondary, whether they contribute to the pathogenesis of the depression or whether they result from it. From research with MA precursors we drew the tentative conclusion that they are presumabely primary and interrelated with the depression in a causal and/or predisposing way.


Dropped gallstones during laparoscopic cholecystectomy: the consequences.
During laparoscopic cholecystectomy, gallbladder perforation has been reported, leading to bile leak and spillage of gallstones into the peritoneum. Because the consequences can be dangerous, conversion to laparotomy as an instant management for gallstone spillage is one of the topics of current discussion in laparoscopic cholesystectomy. In this article, we discussed the option of not converting to laparotomy after intraperitoneal gallstone spillage as an acceptable approach to management or not.A prospectively maintained database of 1528 consecutive laparoscopic cholecystectomies performed during a 10-year period at the 4th Surgical Clinic of The Ankara Numune Education and Research Hospital was analyzed. Perforations resulting in gallstone spillage into the abdominal cavity were documented in 58 (3.8%) patients. Among those 58 patients seven (12%) experienced complications from retained stones. To maintain acceptable management of such patients, surgeons should inform each patient preoperatively that stones may be spilled. In the event of spillage, the patient should be informed postoperatively, and followed closely for complications. Follow-up should not waste time and money with unnecessary examinations, and it should avoid psychological trauma to the patient with a wrong diagnosis of cancer as a stone may mimic cancer radiologically. Thus the surgeon should not hesitate to record the events and inform the patient about the spillage of the stones and possible consequences.


Ethical and representational issues in qualitative secondary analysis.
Although secondary analysis holds considerable promise for optimizing the health knowledge that can be constructed in relation to existing qualitative databases, methodological developments to guide design and evaluation of this research have not been fully explored in the qualitative research literature. This article extends preliminary methodological explorations to address two specific concerns arising from secondary analysis: ethics and representation. Because secondary research creates the potential for exaggerating certain errors in both ethics and representation, the risks associated with such analyses must be considered in the light of the opportunities. Preliminary strategies for helping secondary qualitative researchers to articulate and resolve the representational and ethical problems that may arise from their work are offered.


[Features of brain mechanisms of regulation of the level of wakefulness, organization of cognitive functions and adaptive reactions in children with attention deficit with hyperactivity syndrome and healthy children].
In work results of research of features of infringement superslow cortical-truncal, limbic-reticular and upsegmentary mechanisms of regulation of a level of wakefulness at children of 6-7 years with a syndrome of deficiency of attention and hyperactivity and healthy children, pupils of 1 class of a comprehensive school with different type of psychological adaptation are generalized. At use system-integrativity psychophysiology the approach features are established: a) organization emotional-motivational and cognitive spheres; b) psychophysiology mechanisms of formation of adaptive reactions at tactile interaction about earlier unknown alive object--a dolphin at the surveyed contingent of healthy and ill children.


Combining the nuclear-electronic orbital approach with vibronic coupling theory: calculation of the tunneling splitting for malonaldehyde.
The nuclear-electronic orbital (NEO) method is combined with vibronic coupling theory to calculate hydrogen tunneling splittings in polyatomic molecules. In this NEO-vibronic coupling approach, the transferring proton and all electrons are treated quantum mechanically at the NEO level, and the other nuclei are treated quantum mechanically using vibronic coupling theory. The dynamics of the molecule are described by a vibronic Hamiltonian in a diabatic basis of two localized nuclear-electronic states for the electrons and transferring proton. This ab initio approach is computationally practical and efficient for relatively large molecules, and the accuracy can be improved systematically. The NEO-vibronic coupling approach is used to calculate the hydrogen tunneling splitting for malonaldehyde. The calculated tunneling splitting of 24.5 cm(-1) is in excellent agreement with the experimental value of 21.6 cm(-1). This approach also enables the identification of the dominant modes coupled to the transferring hydrogen motion and provides insight into their roles in the hydrogen tunneling process.


Safety and efficacy of a drug regimen to control heart rate during 64-slice ECG-gated coronary CTA in children.
The adult practice for ECG-gated single-source 64-slice coronary CTA (CCTA) includes administering beta-blockers to reduce heart rate. There are limited data on this process in children. To evaluate the safety and efficacy of a drug regimen to decrease heart rate before performing CCTA in children. IV remifentanil and esmolol infusion were chosen to decrease heart rate in 41 children (mean age 6.5 years) while they were under general anesthesia (GA) for CCTA. Drug doses, changes in heart rate and procedural complications were recorded. CCTA image quality was graded on a scale of 1 to 5. The relationships between image quality and heart rate and image quality and age were evaluated. Patient effective radiation doses were calculated. Heart rates were lowered utilizing esmolol (4 children), remifentanil (2 children) or both (35 children); 26 children received nitroglycerin for coronary vasodilation. The mean decrease in heart rate was 26%. There were no major complications. The average image-quality score was 4.4. Higher heart rates were associated with worse image quality (r = 0.67, P < 0.0001). Older age was associated with better image quality (r = 0.66, P < 0.0001). Effective radiation doses were 0.7 to 7.0 mSv. Heart rate reduction for pediatric CCTA can be safely and effectively achieved while yielding high-quality images.


[Combined anti-androgen treatment in adenocarcinoma of the prostate: first use of a new therapeutically efficacious principle in hormone-dependent cancer].
Since the first observation reported by Huggins et al. in 1941, hormonal treatment of advanced prostatic cancer has been directed primarily at neutralizing testicular androgens by orchiectomy or estrogen therapy. These two approaches yielded a 60 to 80% positive response rate in the many studies carried out over the last forty years. However, responses were short-lived and the disease recurred rapidly in nearly every case. A possible reason for these limited results may well be related to the fact that a unique characteristic of man as compared to other species is a high level of secretion of adrenal steroids that act as precursors and are converted into androgens within the prostatic tissue itself. Complete neutralization of both testicular and adrenal androgens is therefore mandatory to achieve total suppression of the influence of androgens on the carcinoma. To accomplish this goal, we have used a combination of an LHRH agonist (or orchiectomy) and a pure antiandrogen in fifty-two previously untreated patients with prostatic carcinoma and bone metastases (stage D2). Average duration of treatment was eighteen months (six to thirty-two months). An objective positive response assessed according to the criteria set forward by the National Prostatic Cancer Project (NPCP) was recorded during the first treatment months in every case, a significant improvement over the 60 to 80% positive response rate following previous treatments confined to neutralization of testicular androgens by orchiectomy or estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)


Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene.
Allele T at promoter region of the eNOS gene has been associated with an increase in coronary disease mortality, suggesting that this allele increases susceptibility for endothelial dysfunction. In contrast, exercise training improves endothelial function. Thus, we hypothesized that: 1) Muscle vasodilatation during exercise is attenuated in individuals homozygous for allele T, and 2) Exercise training improves muscle vasodilatation in response to exercise for TT genotype individuals. From 133 preselected healthy individuals genotyped for the T786C polymorphism, 72 participated in the study: TT (n = 37; age 27 ± 1 yr) and CT+CC (n = 35; age 26 ± 1 yr). Forearm blood flow (venous occlusion plethysmography) and blood pressure (oscillometric automatic cuff) were evaluated at rest and during 30% handgrip exercise. Exercise training consisted of three sessions per week for 18 wk, with intensity between anaerobic threshold and respiratory compensation point. Resting forearm vascular conductance (FVC, P = 0.17) and mean blood pressure (P = 0.70) were similar between groups. However, FVC responses during handgrip exercise were significantly lower in TT individuals compared with CT+CC individuals (0.39 ± 0.12 vs. 1.08 ± 0.27 units, P = 0.01). Exercise training significantly increased peak VO(2) in both groups, but resting FVC remained unchanged. This intervention significantly increased FVC response to handgrip exercise in TT individuals (P = 0.03), but not in CT+CC individuals (P = 0.49), leading to an equivalent FVC response between TT and CT+CC individuals (1.05 ± 0.18 vs. 1.59 ± 0.27 units, P = 0.27). In conclusion, exercise training improves muscle vasodilatation in response to exercise in TT genotype individuals, demonstrating that genetic variants influence the effects of interventions such as exercise training.


[Cholera epidemic in Senegal in 1995-1996: an example of geographic approach to health].
There have been many cholera outbreaks in Senegal since 1971. The last outbreak began in the Dakar region in August 1995. It spread to the Diourbel, Fatick, Saint-Louis and Thies regions. In January 1996, the outbreak hit the Niakhar study area in the Fatick region. A team from ORSTOM (the French Institute of Scientific Research for Development in Cooperation) has been recording demographic events in this area for almost 15 years. The geographic approach is based on the automated mapping of cholera in hamlets and villages. Such studies investigate the factors determining the spread of diseases, within the context of land use. Three sets of data were used: demographic data that had been routinely collected and were available from a database, digitized maps and epidemiological data from a surveillance system set up to monitor the outbreak. A series of incidence maps, over time and on various scales, were generated using specialized software. The maps were analyzed and the outbreak was found to be heterogeneous over time. There were two waves of the outbreak and differences according to age and gender. The degree of heterogeneity depended on the place of residence. Heterogeneity was probably determined by village size, roads and the concentration of inhabitants within hamlets, which is roughly equivalent to the number of people per bore hole. These preliminary results suggest that further research is necessary, looking at different geographical scales (e.g. households, districts and regions). Qualitative studies of water use and the organization of the water supply are also required.


Two colonisation stages generate two different patterns of genetic diversity within native and invasive ranges of Ulex europaeus.
Genetic diversity and the way a species is introduced influence the capacity of populations of invasive species to persist in, and adapt to, their new environment. The diversity of introduced populations affects their evolutionary potential, which is particularly important for species that have invaded a wide range of habitats and climates, such as European gorse, Ulex europaeus. This species originated in the Iberian peninsula and colonised Europe in the Neolithic; over the course of the past two centuries it was introduced to, and has become invasive in, other continents. We characterised neutral genetic diversity and its structure in the native range and in invaded regions. By coupling these results with historical data, we have identified the way in which gorse populations were introduced and the consequences of introduction history on genetic diversity. Our study is based on the genotyping of individuals from 18 populations at six microsatellite loci. As U. europaeus is an allohexaploid species, we used recently developed tools that take into account genotypic ambiguity. Our results show that genetic diversity in gorse is very high and mainly contained within populations. We confirm that colonisation occurred in two stages. During the first stage, gorse spread out naturally from Spain towards northern Europe, losing some genetic diversity. During the second stage, gorse was introduced by humans into different regions of the world, from northern Europe. These introductions resulted in the loss of rare alleles but did not significantly reduce genetic diversity and thus the evolutionary potential of this invasive species.


Rapid prototyping of thermoset polyester microfluidic devices.
This paper presents a simple procedure for the fabrication of thermoset polyester (TPE) microfluidic systems and discusses the properties of the final devices. TPE chips are fabricated in less than 3 h by casting TPE resin directly on a lithographically patterned (SU-8) silicon master. Thorough curing of the devices is obtained through the combined use of ultraviolet light and heat, as both an ultraviolet and a thermal initiator are employed in the resin mixture. Features on the order of micrometers and greater are routinely reproduced using the presented procedure, including complex designs and multilayer features. The surface of TPE was characterized using contact angle measurements and X-ray photoelectron spectroscopy (XPS). Following oxygen plasma treatment, the hydrophilicity of the surface of TPE increases (determined by contact angle measurements) and the proportion of oxygen-containing functional groups also increases (determined by XPS), which indicates a correlated increase in the charge density on the surface. Native TPE microchannels support electroosmotic flow (EOF) toward the cathode, with an average electroosmotic mobility of 1.3 x 10(-4) cm(2) V(-1) s(-1) for a 50-microm square channel (20 mM borate at pH 9); following plasma treatment (5 min at 30 W and 0.3 mbar), EOF is enhanced by a factor of 2. This enhancement of the EOF from plasma treatment is stable for days, with no significant decrease noted during the 5-day period that we monitored. Using plasma-treated TPE microchannels, we demonstrate the separation of a mixture of fluorescein-tagged amino acids (glycine, glutamic acid, aspartic acid). TPE devices are up to 90% transparent (for approximately 2-mm-thick sample) to visible light (400-800 nm). The compatibility of TPE with a wide range of solvents was tested over a 24-h period, and the material performed well with acids, bases, alcohols, cyclohexane, n-heptane, and toluene but not with chlorinated solvents (dichloromethane, chloroform).


Self-aligned nanogaps on multilayer electrodes for fluidic and magnetic assembly of carbon nanotubes.
A self-aligned nanogap between multiple metal layers has been developed using a new controlled undercut and metallization technique (CUMT), and practically applied for self-assembly of individual carbon nanotubes (CNTs) over the developed nanogap. This new method allows conventional optical lithography to fabricate nanogap electrodes and self-aligned patterns with nanoscale precision. The self-aligned nickel (Ni) pattern on the nanogap electrode works as an assembly spot where the residual iron (Fe) catalyst at the end of the CNT is magnetically captured. The captured CNT is forced to be aligned parallel to the flow direction by fluidic shear force. The combined forces of magnetic attraction and fluidic alignment provide massive self-assembly of CNTs at target positions. Both multiwalled nanotubes (MWNTs) and single walled nanotubes (SWNTs) were successfully assembled over the nanogap electrodes, and their electrical characteristics were fully characterized. The CNTs self-assembled on the developed electrodes with a nanogap and showed a very reliable and reproducible current-voltage (I-V) characteristic. The method developed in this work can envisage the mass fabrication of individual CNT-assembled devices which can be applied to nanoelectronic devices or nanobiosensors.


The effects of incorrect pain expectations on acquired fear and pain responses.
Previous experimental research on the effects of incorrect intensity expectations of aversive events can be criticized because intensity expectations were not manipulated independently from changes in objective intensity. The present study aims at investigating the effects of incorrect intensity expectations on the immediate and later responses to a painful stimulus, and on the acquisition of anticipatory responses, with proper experimental control. Subjects (n = 62) received 20 painful stimuli of varying intensity. In the control group intensities were correctly signalled on all trials by an analogue signal. On 3 trials the signal was too large in the overprediction condition, and too small in the underestimation condition. Underpredicted painful experiences were related to subsequent higher pain responses on the physiological level, but not on the subjective level; and to increased anticipatory responses (increased pain expectations, uncertainty, subjective fear, skin conductance responses). Skin conductance level also indicated increased fear after underpredicted experiences. Overpredicted painful experiences were related to a faster decrease in subjective fear compared to the control group, but did not influence other variables. The findings support the notion that underpredictions contribute to the acquisition of fear and disrupt habituation processes. The asymmetrical processing of the two kinds of incorrectly predicted experiences is discussed.


Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring.
A suboptimal in utero environment, for example, as a result of maternal stress, can have detrimental effects on the pregnancy and long-term adverse 'programming' effects on the offspring. This article focuses on the effects of prenatal social stress on the mother, her pregnancy and the offspring, since these issues have ethological relevance in both animals and humans. The consequences of social stress exposure depend on when during pregnancy the stress occurs, and many of the effects on the offspring are sex specific. Social stress during early pregnancy tends to result in pregnancy loss, whereas stress exposure later in pregnancy, when the mother has already invested considerable resources in the foetuses, results in programmed offspring of low birth weight: a risk factor for various adulthood diseases. Neuroendocrine and behavioural responses to stress in the offspring are particularly sensitive to foetal programming by prenatal stress, indicated by enhanced hypothalamo-pituitary-adrenal (HPA) axis responses and increased anxiety behaviour, which result from permanent changes in the offspring's brain. The dysregulation of HPA axis function may also interfere with other systems, for example, the hypothalamic-pituitary-gonadal axis, as there is evidence for alterations in steroidogenesis, reproductive potential and impaired reproductive/social behaviours in prenatally stressed offspring. Prenatal social stress also programmes future maternal behaviour, highlighting the potential for negative phenotypes to be transmitted to future generations. The possible mechanisms through which maternal stress during pregnancy is transmitted to the foetuses and the foetal brain is programmed by prenatal stress and the potential to overwrite programming of the offspring are discussed.


Metabolic predictors of inflammation, adhesion, and coagulability in healthy younger-aged adults.
Elevated levels of inflammatory biomarkers are associated with the pathophysiology of cardiovascular diseases and are predictors of cardiovascular events. The objective of this study was to determine the unique contributions of metabolic factors as predictors of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)), adhesion (soluble intercellular adhesion molecule-1 (sICAM-1)), and coagulation (D-dimer) in healthy younger-aged adults. Participants were 83 women and 92 men (mean age 30.04 years, s.d. +/- 4.8, range 22-39) of normal weight to moderate obese weight (mean BMI 24.4 kg/m(2), s.d. +/- 3.35, range 17-32). The primary data analytical approaches included Pearson correlation and multiple linear regression. Circulating levels of CRP, IL-6, sICAM-1, and D-dimer were determined in plasma. Higher levels of CRP were independently associated with higher BMI, a greater waist-to-hip ratio, female gender, and higher triglycerides (P < 0.001). Higher IL-6 levels were independently associated with a greater waist-to-hip ratio (P < 0.01). Higher levels of sICAM-1 were independently associated with higher BMI, higher triglycerides, and lower insulin resistance (P < 0.001). Higher D-dimer levels were independently associated with higher BMI and being female (P < 0.001). Having a higher BMI was most consistently associated with elevated biomarkers of inflammation, adhesion, and coagulation in this sample of healthy younger-aged adults, although female gender, insulin resistance, and lipid levels were also related to the biomarkers. The findings provide insight into the adverse cardiovascular risk associated with elevated body weight in younger adults.


Molecular insights into the biosynthesis of the F420 coenzyme.
Coenzyme F(420), a hydride carrier, is found in Archaea and some bacteria and has crucial roles in methanogenesis, antibiotic biosynthesis, DNA repair, and activation of antitubercular compounds. CofD, 2-phospho-l-lactate transferase, catalyzes the last step in the biosynthesis of F(420)-0 (F(420) without polyglutamate), by transferring the lactyl phosphate moiety of lactyl(2)diphospho-(5')guanosine to 7,8-didemethyl-8-hydroxy-5-deazariboflavin ribitol (Fo). CofD is highly conserved among F(420)-producing organisms, and weak sequence homologs are also found in non-F(420)-producing organisms. This superfamily does not share any recognizable sequence conservation with other proteins. Here we report the first crystal structures of CofD, the free enzyme and two ternary complexes, with Fo and P(i) or with Fo and GDP, from Methanosarcina mazei. The active site is located at the C-terminal end of a Rossmann fold core, and three large insertions make significant contributions to the active site and dimer formation. The observed binding modes of Fo and GDP can explain known biochemical properties of CofD and are also supported by our binding assays. The structures provide significant molecular insights into the biosynthesis of the F(420) coenzyme. Large structural differences in the active site region of the non-F(420)-producing CofD homologs suggest that they catalyze a different biochemical reaction.


The extracellular toll-like receptor 2 domain directly binds peptidoglycan derived from Staphylococcus aureus.
Toll-like receptor 2 (TLR2) has been recognized to mediate cell signaling in response to peptidoglycan (PGN), a major cell wall component of Gram-positive bacteria. The mechanism by which TLR2 recognizes PGN is unknown. It is not even clear whether TLR2 directly binds to PGN. In this study, we generated a soluble form of recombinant TLR2 (sTLR2) possessing only its putative extracellular domain by using the baculovirus expression system to examine the direct interaction between sTLR2 and PGN. sTLR2 bound avidly to insoluble PGN (iPGN) from Staphylococcus aureus coated onto microtiter wells in a concentration-dependent manner. In contrast, sTLR2 exhibited a very weak binding to lipopolysaccharide. iPGN cosedimented sTLR2 after the mixture of iPGN and sTLR2 had been incubated and centrifuged. sTLR2 partially attenuated the iPGN-induced NF-kappaB activation in TLR2-transfected HEK 293 cells and the iPGN-induced IL-8 secretion in U937 cells. One of anti-human TLR2 monoclonal antibodies, which blocked iPGN-induced NF-kappaB activation in TLR2-transfected cells, inhibited the binding of sTLR2 to iPGN. In addition, we found that sCD14 interacted with sTLR2 and increased the binding of sTLR2 to iPGN. From these results, we conclude that the extracellular TLR2 domain directly binds to PGN.


A Micro-GA Embedded PSO Feature Selection Approach to Intelligent Facial Emotion Recognition.
This paper proposes a facial expression recognition system using evolutionary particle swarm optimization (PSO)-based feature optimization. The system first employs modified local binary patterns, which conduct horizontal and vertical neighborhood pixel comparison, to generate a discriminative initial facial representation. Then, a PSO variant embedded with the concept of a micro genetic algorithm (mGA), called mGA-embedded PSO, is proposed to perform feature optimization. It incorporates a nonreplaceable memory, a small-population secondary swarm, a new velocity updating strategy, a subdimension-based in-depth local facial feature search, and a cooperation of local exploitation and global exploration search mechanism to mitigate the premature convergence problem of conventional PSO. Multiple classifiers are used for recognizing seven facial expressions. Based on a comprehensive study using within- and cross-domain images from the extended Cohn Kanade and MMI benchmark databases, respectively, the empirical results indicate that our proposed system outperforms other state-of-the-art PSO variants, conventional PSO, classical GA, and other related facial expression recognition models reported in the literature by a significant margin.


Measuring depressive symptomatology in a general population.
Three hundred twenty respondents in selected geographic areas were interviewed with a structured questionnaire that included the Zung Self-Rating Depression Scale. Dimensional analysis indicates that some items are not pure measures of the constructs they were originally intended to assess. Moreover, some of the dimensions within the scale apparently convey different meanings to different segments in the population. In addition, different dimensions within the scale have varying demographic correlates. The analysis suggests that in order for the scale to be a truly useful device for assessing depressive symptomatology in a general population, additional items need to be added and some questions need to be followed by probes to clarify the exact frame of reference of the respondents.


Results of vancomycin-impregnated cancellous bone grafting for infected tibial nonunion.
Bone grafting plays a critical role in promoting bone healing in infected nonunion, although recurrent infection is of concern. Cancellous bone grafting as an antibiotic delivery system has been reported as an effective method to combat infections. In this study, we report the clinical results of vancomycin-impregnated cancellous bone grafting for the treatment of infected tibial nonunion. Between January 1996 and March 2001, 18 patients with infected tibial nonunion treated with vancomycin-impregnated cancellous bone grafting were available for follow-up. According to the Cierny-Mader classification, all patients belonged to type IVA and IVB osteomyelitis. Adequate debridement, stabilization with external fixation, and staged vancomycin-impregnated cancellous bone grafting were used in all patients. Regular clinical and radiographic follow-ups were conducted. Infection control was obtained in all 18 patients with a 100% infection arrest rate. Bone union was achieved in 13 of 18 patients at an average of 5.8 months. Bone union was obtained subsequently in the remaining five patients after closed nailing in four, and plating and bone grafting in one patient. Radiographs showed good consolidation and hypertrophy of grafted bone at an average follow-up of 48 months. We conclude that vancomycin-impregnated cancellous bone grafting is a safe method for the treatment of infected tibial nonunion.


Hepatic transcriptome perturbations in dairy cows fed different forage resources.
Forage plays critical roles in milk performance of dairy. However, domestic high-quality forage such as alfalfa hay is far from being sufficient in China. Thus, more than 1 million tons of alfalfa hay were imported in China annually in recent years. At the same time, more than 10 million tons of corn stover are generated annually in China. Thus, taking full advantage of corn stover to meet the demand of forage and reduce dependence on imported alfalfa hay has been a strategic policy for the Chinese dairy industry. Changes in liver metabolism under different forage resources are not well known. Thus, the objective of the present study was to investigate the effect of different forage resources on liver metabolism using RNAseq and bioinformatics analyses. The results of this study showed that the cows fed a diet with corn stover (CS) as the main forage had lower milk yield, DMI, milk protein content and yield, milk fat yield, and lactose yield than cows fed a mixed forage (MF) diet (P < 0.01). KEGG analysis for differently expressed genes (DEG) in liver (81 up-regulated and 423 down-DEG, Padj ≤0.05) showed that pathways associated with glycan biosynthesis and metabolism and amino acid metabolism was inhibited by the CS diet. In addition, results from DAVID and ClueGO indicated that biological processes related to cell-cell adhesion, multicellular organism growth, and amino acid and protein metabolism also were downregulated by feeding CS. Co-expression network analysis indicated that FAM210A, SLC26A6, FBXW5, EIF6, ZSCAN10, FPGS, and ARMCX2 played critical roles in the network. Bioinformatics analysis showed that genes within the co-expression network were enriched to "pyruvate metabolic process", "complement activation, classical pathway", and "retrograde transport, endosome to Golgi". Results of the present study indicated that feeding a low-quality forage diet inhibits important biological functions of the liver at least in part due to a reduction in DMI. In addition, the results of the present study provide an insight into the metabolic response in the liver to different-quality forage resources. As such, the data can help develop favorable strategies to improve the utilization of corn stover in China.


Waddle and shuffle: gait alterations associated with domestication in turkeys.
Domestication has altered turkey morphology by artificially selecting for increased muscle mass and breast meat. Artificial selection has resulted in birds that weigh up to 3 times more than their wild counterparts, with relatively little change in the length of their bones and limbs. Considering these structural changes, it seems probable that domestic turkey locomotor kinematics and kinetics would also be altered. To examine the locomotor dynamics of wild and domestic turkeys, we had both strains walk down a runway with a force plate at the center to measure their ground reaction forces and gait parameters. The location of their center of mass was also quantified using a force plate and bi-planar x-ray and found to be further anterior in the domestic strain. The domestic turkeys locomoted across a lower range of speeds (0.25-1.64 ms-1) than the wild turkeys (0.26-3.26 ms-1) and increased their stride frequency at a higher rate. They also displayed large lateral oscillations, i.e. waddling, during walking that translated into relatively high medio-lateral ground reaction forces and lateral kinetic energy (3.5 times higher than that of wild turkeys). The results indicate that domestic turkey locomotion is not simply a slowed down version of wild turkey locomotion. The changes in gait observed are similar to the shuffling gait present in some human populations, such as Parkinson's patients, which serves to increase stability. The domestic turkey's increased body mass and more anterior center of mass position may require these kinematic and kinetic gait differences.


Allopurinol Dose Escalation and Mortality Among Patients With Gout: A National Propensity-Matched Cohort Study.
Observational data suggest that hyperuricemia and gout are associated with increased mortality, while allopurinol use is associated with reduced mortality. In addition, the protective effect of allopurinol may be dose dependent. The aim of the current study was to determine whether allopurinol dose escalation is associated with cause-specific mortality in patients with gout. In this 10-year observational, active-comparator study of US Veterans with gout who initiated treatment with allopurinol, propensity score matching, Cox proportional hazards models, and competing risks regression analyses were used to assess differences in cause-specific mortality between patients whose allopurinol dose was escalated (dose escalators) and those whose allopurinol dose was not escalated or was reduced (non-escalators) over a 2-year period. Among the 6,428 dose escalators and 6,428 matched non-escalators, there were 2,867 deaths during the observation period (40.4 deaths per 1,000 person-years). Dose escalators experienced an increase in all-cause mortality (hazard ratio [HR] 1.08, 95% confidence interval [95% CI] 1.01-1.17), with the effect sizes being similar for incidence of cardiovascular-related deaths (HR 1.08, 95% CI 0.97-1.21) and cancer-related deaths (HR 1.06, 95% CI 0.88-1.27), although neither reached statistical significance. Dose escalation to achieve the goal of lowering the serum urate (SU) level to <6.0 mg/dl was infrequent. At 2 years, 10% of dose escalators were receiving a final daily dose of >300 mg and 31% had achieved the SU goal. In a sensitivity analysis limited to dose escalators achieving the SU goal, there was a nonsignificant reduction of 7% in the hazard of cardiovascular-related mortality (HR 0.93, 95% CI 0.76-1.14). This is the largest study to date to investigate the effects of allopurinol use on mortality and is the first to use a rigorous active-comparator design. Dose escalation was associated with a small (<10%) increase in all-cause mortality, thus showing that a strategy of allopurinol dose escalation, which in current real-life practice is characterized by limited dose increases, is unlikely to improve the survival of patients with gout.


Enhancing adsorption capacity while maintaining specific recognition performance of mesoporous silica: a novel imprinting strategy with amphiphilic ionic liquid as surfactant.
In order to facilitate the broad applications of molecular recognition materials in biomedical areas, it is critical to enhance their adsorption capacity while maintaining their excellent recognition performance. In this work, we designed and synthesized well-defined peptide-imprinted mesoporous silica (PIMS) for specific recognition of an immunostimulating hexapeptide from human casein (IHHC) by using amphiphilic ionic liquid as the surfactant to anchor IHHC via a combination of one-step sol-gel method and docking oriented imprinting approach. Thereinto, theoretical calculation was employed to reveal the multiple binding interactions and dual-template configuration between amphiphilic ionic liquid and IHHC. The fabricated PIMS was characterized and an in-depth analysis of specific recognition mechanism was conducted. Results revealed that both adsorption and recognition capabilities of PIMS far exceeded that of the NIMS's. More significantly, the PIMS exhibited a superior binding capacity (60.5 mg g-1), which could increase 18.9% than the previous work. The corresponding imprinting factor and selectivity coefficient could reach up to 4.51 and 3.30, respectively. The PIMS also possessed lickety-split kinetic binding for IHHC, where the equilibrium time was only 10 min. All of these merits were due to the high surface area and the synergistic effect of multiple interactions (including hydrogen bonding, π-π stacking, ion-ion electrostatic interactions and van der Waals interactions, etc) between PIMS and IHHC in imprinted sites. The present work suggests the potential application of PIMS for large-scale and high-effective separation of IHHC, which may lead to their broad applications in drug/gene deliver, biosensors, catalyst and so on.


Quality indicators for Barrett's endotherapy (QBET): UK consensus statements for patients undergoing endoscopic therapy for Barrett's neoplasia.
Endoscopic therapy for the management of patients with Barrett's oesophagus (BE) neoplasia has significantly developed in the past decade; however, significant variation in clinical practice exists. The aim of this project was to develop expert physician-lead quality indicators (QIs) for Barrett's endoscopic therapy. The RAND/UCLA Appropriateness Method was used to combine the best available scientific evidence with the collective judgement of experts to develop quality indicators for Barrett's endotherapy in four subgroups: pre-endoscopy, intraprocedure (resection and ablation) and postendoscopy. International experts, including gastroenterologists, surgeons, BE pathologist, clinical nurse specialist and patient representative, participated in a three-round process to develop 15 QIs that fulfilled the RAND/UCLA definition of appropriateness. 17 experts participated in round 1 and 20 in round 2. Of the 24 proposed QIs in round 1, 20 were ranked as appropriate (put through to round 2) and 4 as uncertain (discarded). At the end of round 2, a final list of 15 QIs were scored as appropriate. This UK national consensus project has successfully developed QIs for patients undergoing Barrett's endotherapy. These QIs can be used by service providers to ensure that all patients with BE neoplasia receive uniform and high-quality care.


Room temperature growth of ultrathin Au nanowires with high areal density over large areas by in situ functionalization of substrate.
Although ultrathin Au nanowires (∼2 nm diameter) are expected to demonstrate several interesting properties, their extreme fragility has hampered their use in potential applications. One way to improve the stability is to grow them on substrates; however, there is no general method to grow these wires over large areas. The existing methods suffer from poor coverage and associated formation of larger nanoparticles on the substrate. Herein, we demonstrate a room temperature method for growth of these nanowires with high coverage over large areas by in situ functionalization of the substrate. Using control experiments, we demonstrate that an in situ functionalization of the substrate is the key step in controlling the areal density of the wires on the substrate. We show that this strategy works for a variety of substrates ranging like graphene, borosil glass, Kapton, and oxide supports. We present initial results on catalysis using the wires grown on alumina and silica beads and also extend the method to lithography-free device fabrication. This method is general and may be extended to grow ultrathin Au nanowires on a variety of substrates for other applications.


A rare case of occipital encephalocele presenting as the largest congenital head mass in an infant.
The prevalence of encephalocele is estimated to be 0.8-5.0 per 10,000 live births. The most frequent encephalocele is the occipital encephalocele. It is a congenital neural tube defect characterized by the protrusion or herniation of intracranial contents through a cranial defect. The term "giant/massive/large encephalocele" is used to describe an encephalocele that is significantly larger than the size of the head. A 2-month-old male infant presented in the neurosurgery outpatient department with one of the largest head masses over the posterior aspect since birth. The swelling was gradually progressive and developed ulceration over the swelling with intermittent cerebrospinal fluid (CSF) discharge but no associated weakness in limbs. Magnetic Resonance Imaging (MRI) brain showed a large occipital meningoencephalocele containing predominantly cyst with part of the cerebellar and occipital lobe. The surgery was planned. The sac contained CSF with the gliotic occipital lobe. The sac and gliotic brain tissue was excised. He had an uneventful postoperative course. Surgery serves several functions, including reducing the torque and weight of the head to allow for more normal motor development, removal of the thin, leaking scalp and dural closure to prevent CSF leak and subsequent infection, and improving the cosmetic and social issues that the child and family may have to endure.


Rapamycin-conditioned donor dendritic cells differentiate CD4CD25Foxp3 T cells in vitro with TGF-beta1 for islet transplantation.
Dendritic cells (DCs) conditioned with the mammalian target of rapamycin (mTOR) inhibitor rapamycin have been previously shown to expand naturally existing regulatory T cells (nTregs). This work addresses whether rapamycin-conditioned donor DCs could effectively induce CD4(+)CD25(+)Foxp3(+) Tregs (iTregs) in cell cultures with alloantigen specificities, and whether such in vitro-differentiated CD4(+)CD25(+)Foxp3(+) iTregs could effectively control acute rejection in allogeneic islet transplantation. We found that donor BALB/c bone marrow-derived DCs (BMDCs) pharmacologically modified by the mTOR inhibitor rapamycin had significantly enhanced ability to induce CD4(+)CD25(+)Foxp3(+) iTregs of recipient origin (C57BL/6 (B6)) in vitro under Treg driving conditions compared to unmodified BMDCs. These in vitro-induced CD4(+)CD25(+)Foxp3(+) iTregs exerted donor-specific suppression in vitro, and prolonged allogeneic islet graft survival in vivo in RAG(-/-) hosts upon coadoptive transfer with T-effector cells. The CD4(+)CD25(+)Foxp3(+) iTregs expanded and preferentially maintained Foxp3 expression in the graft draining lymph nodes. Finally, the CD4(+)CD25(+)Foxp3(+) iTregs were further able to induce endogenous naïve T cells to convert to CD4(+)CD25(+)Foxp3(+) T cells. We conclude that rapamycin-conditioned donor BMDCs can be exploited for efficient in vitro differentiation of donor antigen-specific CD4(+)CD25(+)Foxp3(+) iTregs. Such in vitro-generated donor-specific CD4(+)CD25(+)Foxp3(+) iTregs are able to effectively control allogeneic islet graft rejection.


Effect of artificial sweeteners on insulin resistance among type-2 diabetes mellitus patients.
Incidence of diabetes mellitus has increased over the past few years, mainly due to our eating habits and physical inactivity. This also includes the use of artificial sweetening agents which have broadly replaced other forms of sugars and have shown a paradoxical, negative effect on blood glucose. Ingestion of these artificial sweeteners (AS) results in the release of insulin from pancreas which is mistaken for glucose (due to their sweet taste). This increases the levels of insulin in blood eventually leading to decreased receptor activity due to insulin resistance. It is a crosssectional study that was conducted on patients diagnosed with type-2 diabetes mellitus of a tertiary care hospital in Central India. All the diabetics that presented in the OPD were divided into 2 groups based on whether they use AS (group A) or not (group B). Insulin resistance was calculated for each group using HOMA-IR and graphs were plotted. The HOMAIR values for Group A and B ranged from 0.9-24.33 and 0.12-10.83 with mean values 7.39 and 2.6, respectively, showing that the ones who used AS had a higher insulin resistance. The study also showed that the duration of use of artificial sweeteners had a direct impact on insulin resistance.


Commentary: personality disorder and diminished responsibility--the significance of priorities and objectives.
Professor Landy Sparr's paper systematically examines issues and anomalies of courtroom practice in relation to offenders who are considered to have a personality disorder. The in-depth description of a recent case from the International War Crimes Tribunal for the former Yugoslavia forms the basis of the paper. As an international forum, the Tribunal illustrates clearly the different practices and interpretations in various jurisdictions. Sparr provides much detail about the machinations of the Tribunal, leading to speculation about the principles that underlie the complex legislation as it is applied in different countries. Despite the considerable differences in mental health systems among different countries, there are probably shared themes and trends that influence the practice of forensic psychiatry.


Stiffness of Protease Sensitive and Cell Adhesive PEG Hydrogels Promotes Neovascularization In Vivo.
Materials that support the assembly of new vasculature are critical for regenerative medicine. Controlling the scaffold's mechanical properties may help to optimize neovascularization within implanted biomaterials. However, reducing the stiffness of synthetic hydrogels usually requires decreasing polymer densities or increasing chain lengths, both of which accelerate degradation. We synthesized enzymatically-degradable poly(ethylene glycol) hydrogels with compressive moduli from 2 to 18 kPa at constant polymer density, chain length, and proteolytic degradability by inserting an allyloxycarbonyl functionality into the polymer backbone. This group competes with acrylates during photopolymerization to alter the crosslink network structure and reduce the hydrogel's stiffness. Hydrogels that incorporated (soft) or lacked (stiff) this group were implanted subcutaneously in rats to investigate the role of stiffness on host tissue interactions. Changes in tissue integration were quantified after 4 weeks via the hydrogel area replaced by native tissue (tissue area fraction), yielding 0.136 for softer vs. 0.062 for stiffer hydrogels. Including soluble FGF-2 and PDGF-BB improved these responses to 0.164 and 0.089, respectively. Softer gels exhibited greater vascularization with 8.6 microvessels mm-2 compared to stiffer gels at 2.4 microvessels mm-2. Growth factors improved this to 11.2 and 4.9 microvessels mm-2, respectively. Softer hydrogels tended to display more sustained responses, promoting neovascularization and tissue integration in synthetic scaffolds.


The Role of Mentoring in the Development of Successful Orthopaedic Surgeons.
Mentoring plays an integral role in orthopaedic surgeons' career development and personal growth. Effective mentors are committed to their roles, provide skilled instructional support, model continuous learning, and communicate optimism. Numerous obstacles impede productive mentoring relationships in medicine, including reluctance to ask for help, time constraints due to extensive work obligations, lack of institutional support, relational difficulties, and lack of mentoring skills. Effective partnerships require a concerted effort to establish behaviors conducive to mentoring, such as sharing knowledge and providing constructive feedback. Given that women represent only 13% of orthopaedic surgery residents and racial/ethnic minorities account for 3% to 10% of US orthopaedic surgeons, mentoring may help diversify the workforce by providing early exposure and professional support to physicians from underrepresented demographic groups. Orthopaedic leaders must embrace their professional obligation to cultivate and inspire the next generation of orthopaedic surgeons.


An Evaluation of Electroacupuncture at the Weizhong Acupoint (BL-40) as a Means of Relieving Pain Induced by Extracorporeal Shock Wave Lithotripsy.
Background. Extracorporeal shock wave lithotripsy (ESWL) is the preferred option for urolithiasis treatment. However, intensities of pain may be induced and the sedative anesthetic or analgesics were usually needed. The aim of this study was to develop an improved acupuncture-assisted anesthesia approach in pain relief. Methods. We conducted a single-blind, randomized controlled study in China Medical University Hospital. Patients treated by ESWL due to upper urolithiasis were randomly divided into control group, sham-EA group, and 100 Hz EA group. The high frequency electroacupuncture (EA) was applied at the Weizhong acupoint (100 Hz EA group) for 20 minutes prior to the ESWL. In the sham-EA group, the same procedures were performed as those of 100 Hz EA group but no electric current was given to stimulate the acupoints. In the control group, no action was taken before operation. The information including the numbers and dosage of analgesic requirements, pain score, vital signs, and the satisfaction of procedure was collected. Results. A total of 74 subjects were recruited and we found that the interval to the first request analgesic, the number/total dosage of additional analgesic, recovery time from anesthesia, and the satisfaction were all better in both the 100 Hz EA and the sham-EA group. The 100 Hz EA also showed better relief of painful sensations by delaying the onset of pain. Conclusions. The 100 Hz EA and the sham-EA can effectively relieve pain due to ESWL as well as reducing the dosage of opium analgesic used.


A study of two-stage anaerobic digestion of solid potato waste using reactors under mesophilic and thermophilic conditions.
A two-stage anaerobic digestion process operated under mesophilic and thermophilic conditions was investigated for the treatment of solid potato waste to determine optimal methane yield, efficiency of operation and process stability. A solid-bed reactor was used for hydrolysis/acidification stage while an upflow anaerobic sludge blanket (UASB) reactor was used in the second stage, for methanogenesis. Three sets of conditions were investigated: (1) mesophilic + mesophilic, (II) mesophilic + thermophilic and (III) thermophilic + thermophilic in the hydrolysis/acidification and methanogenesis reactors, respectively. The methane yield was higher under mesophilic conditions (0.49 l CH4 g COD(-1)degraded) than thermophilic conditions (0.41 l CH4 g COD(-1)degraded) with reference to the methanogenic reactors. (COD)--chemical oxygen demand. However, the digestion period was shorter in systems II and III than in system I. Also, in system III the UASB reactor (thermophilic conditions) could handle a higher organic loading rate (OLR) (36 g COD 1(-1)d(-1)) than in system I (11 g COD 1(-1)d(-1)) (mesophilic conditions) with stable operation. Higher OLRs in the methanogenic reactors resulted in reactor failure due to increasing total volatile fatty acid levels. In all systems, the concentration of propionate was one of the highest, higher than acetic acid, among the volatile fatty acids in the effluent. The results show the feasibility of using a two-stage system to treat solid potato waste under both mesophilic and thermophilic conditions. If the aim is to treat solid potato waste completely within a short period of time thermophilic conditions are to be preferred, but to obtain higher methane yield mesophilic conditions are preferable and therefore there is a need to balance methane yield and complete digestion period when dealing with large quantities of solid potato waste.


Imbalanced synaptic plasticity induced spatial cognition impairment in male offspring rats treated with chronic prenatal ethanol exposure.
As chronic prenatal ethanol (EtOH) exposure (CPEE) may cause deficiencies in a variety of behavioral and cognitive functions, the aim of present study is to investigate the effects of CPEE on spatial learning and memory and examine the action of CPEE on synaptic plasticity balance in the hippocampus of adolescent male rats. The animal model was produced by EtOH exposure throughout gestational period with 4 g/kg bodyweight, while the male offspring rats were used in the study. Morris water maze (MWM) test was performed, and then, long-term potentiation (LTP) and depotentiation were recorded from Schaffer collaterals to CA1 region in the hippocampus. It was shown that escape latencies in learning period and re-acquisition period were prolonged in CPEE-treated group compared with that in control group. Furthermore, LTP was drastically inhibited, and depotentiation was distinctly enhanced in CPEE-treated group compared with that in control group. It is suggested that the balance between cognitive stability and flexibility was broken by the bidirectional effects of long-term synaptic plasticity. In addition, the spatial cognition was attenuated by the alteration of synaptic plasticity balance in CPEE-treated male adolescent rats.


Heparin Induces the Mobilization of Heart-Derived Multipotent Mesoangioblasts During Cardiac Surgery With Cardiopulmonary Bypass or Cardiac Catheterization.
We previously identified circulating mesoangioblasts (cMABs), a subset of mesenchymal stem cells that express cardiac mesodermal markers, in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). We also found that hepatocyte growth factor (HGF) is upregulated during cardiac surgery with CPB in humans, and induces MAB-like cell mobilization in rodents. These results strongly suggest that heparin induced MAB mobilization via HGF upregulation. Here, we tested this hypothesis in patients undergoing cardiac surgery or cardiac catheterization. We also examined whether human cMABs are derived from the heart.Methods and Results:Plasma HGF levels were determined by ELISA. Mononuclear cells isolated from blood samples were cultured on fibronectin-coated dishes, and outgrowing cMAB colonies were counted. We first confirmed that HGF upregulation and cMAB mobilization were observed before the start of CPB, excluding the possibility that CPB is the primary inducer of cMAB mobilization. We then examined patients undergoing cardiac catheterization and found that heparin significantly increased plasma HGF levels and the number of cMAB colonies in a dose-dependent manner. The results of simultaneous blood sampling from the aortic sinus, coronary sinus, and right atrium were consistent with the notion that human cMABs are derived from the heart. Human cMABs are mobilized by heparin injection during cardiac surgery or cardiac catheterization, presumably via HGF upregulation.


The genetic variant C825T of the beta 3 subunit of G protein is associated with hypertension in a Portuguese population.
Hypertension is an important public health problem, affecting about 25% of the adult population worldwide.1 Genetic and environmental factors contribute to its pathogenesis. The T allele of the C825T polymorphism of the beta 3 subunit of G protein (rs5443) leads to the production of a truncated variant that enhances intracellular signaling and may interfere with the regulation of blood pressure. This genetic variant has been described as a risk factor for hypertension, although study results are controversial. The objective of this study was to analyze the association of the C825T polymorphism of the GNB3 gene with the occurrence of hypertension in a Portuguese population from the Madeira archipelago. A case-control study was performed with 1641 Caucasian individuals (mean age 50.6±8.1 years), 848 with hypertension and 793 controls. Blood was collected from all participants for biochemical and genetic analysis, including genotyping of the C825T polymorphism. Logistic regression analysis was performed to determine which variables were significantly associated with the onset of hypertension. Statistical analyses were performed using IBM SPSS version 19.0 and p-values <0.05 were considered statistically significant. In our study, there was a significant association between the C825T polymorphism of the GNB3 gene and the occurrence of hypertension (odds ratio 1.275; 95% confidence interval 1.042-1.559; p=0.018) in the dominant model, after multivariate analysis. We conclude that the C825T polymorphism of the beta 3 subunit of G protein is significantly and independently associated with the occurrence of hypertension in the study population.


Mechanosensitive membrane probes.
This article assembles pertinent insights behind the concept of planarizable push-pull probes. As a response to the planarization of their polarized ground state, a red shift of their excitation maximum is expected to report on either the disorder, the tension, or the potential of biomembranes. The combination of chromophore planarization and polarization contributes to various, usually more complex processes in nature. Examples include the color change of crabs or lobsters during cooking or the chemistry of vision, particularly color vision. The summary of lessons from nature is followed by an overview of mechanosensitive organic materials. Although often twisted and sometimes also polarized, their change of color under pressure usually originates from changes in their crystal packing. Intriguing exceptions include the planarization of several elegantly twisted phenylethynyl oligomers and polymers. Also mechanosensitive probes in plastics usually respond to stretching by disassembly. True ground-state planarization in response to molecular recognition is best exemplified with the binding of thoughtfully twisted cationic polythiophenes to single- and double-stranded oligonucleotides. Molecular rotors, en vogue as viscosity sensors in cells, operate by deplanarization of the first excited state. Pertinent recent examples are described, focusing on λ-ratiometry and intracellular targeting. Complementary to planarization of the ground state with twisted push-pull probes, molecular rotors report on environmental changes with quenching or shifts in emission rather than absorption. The labeling of mechanosensitive channels is discussed as a bioengineering approach to bypass the challenge to create molecular mechanosensitivity and use biological systems instead to sense membrane tension. With planarizable push-pull probes, this challenge is met not with twistome screening, but with "fluorescent flippers," a new concept to insert large and bright monomers into oligomeric probes to really feel the environment and also shine when twisted out of conjugation.


Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females.
The development of robust laboratory procedures for acute stress induction over the last decades has greatly advanced our understanding of stress responses in humans and their underlying neurobiological mechanisms. Nevertheless, attempts to uncover linear relationships among endocrine, neural, and affective responses to stress have generally yielded inconsistent results. Here, 79 healthy females completed a well established laboratory procedure of acute stress induction that was modified to prolong its effect. Endocrinological and subjective affect assessments revealed stress-induced increases in cortisol release and negative affect that persisted 65 and 100 min after stress onset, respectively, confirming a relatively prolonged acute stress induction. Applying latent class linear mixed modeling on individuals' patterns of cortisol responses identified three distinct trajectories of cortisol response: the hyper-response (n = 10), moderate-response (n = 21), and mild-response (n = 48) groups. Notably, whereas all three groups exhibited a significant stress-induced increase in cortisol release and negative affect, the hyper-response and mild-response groups both reported more negative affect relative to the moderate-response group. Structural MRI revealed no group differences in hippocampal and amygdala volumes, yet a continuous measure of cortisol response (area under the curve) showed that high and low levels of stress-induced cortisol release were associated with less hippocampal gray matter volume compared with moderate cortisol release. Together, these results suggest that distinct trajectories of cortisol response to prolonged acute stress among healthy females may not be captured by conventional linear analyses; instead, quadratic relations may better describe links between cortisol response to stress and affective responses, as well as hippocampal structural variability.SIGNIFICANCE STATEMENT Despite substantial research, it is unclear whether and how individual neuroendocrine stress response patterns are linked to affective responses to stress and structural variability in neuroendocrine regulatory brain regions. By applying latent class linear mixed modeling on individuals' patterns of cortisol responses to a prolonged acute stressor, we identified three distinct trajectories of cortisol response. Relative to the group showing a moderate cortisol response, groups characterized by hyper and mild cortisol response were both associated with more negative affect. Moreover, a continuous measure of cortisol response showed that high and low levels of stress-induced cortisol release correlated with reduced hippocampal gray matter volume. Given that neuroendocrine stress responses are conceptualized as biomarkers of stress susceptibility, these insights may have clinical implications.


Six weeks of intensive rehearsals for the Swan Lake ballet shows ultrasound tissue characterization changes of the Achilles tendons in dancers.
The objective was to investigate, first, whether six weeks of intensive ballet dance exposure is associated with structural and clinical changes in the Achilles tendon; second, the importance of demographics, self-reported Achilles pain, and generalized joint hypermobility (GJH). Data were collected at baseline and at six weeks' follow-up, using Achilles tendon ultrasound tissue characteristics (UTC) as primary outcome (percentage distribution of echo-type I-IV: type I = intact and aligned bundles, type II = discontinuous/wavy bundles, type III = fibrillar, and type IV = amorphous cells/fluid). Secondary outcomes included clinical signs of Achilles tendinopathy, Achilles tendon pain during single-leg heel raise, self-reported symptoms (VISA-A questionnaire), and GJH. Sixty-three ballet dancers (aged 18-41) participated. From baseline to follow-up, UTC echo-type I decreased significantly (β = -3.6, p = 0.001; 95% CI: -5.8;-1.4), whereas echo-type II increased significantly (β = 3.2, p < 0.0001, 95% CI: 1.6;4.8). Furthermore, a significant effect of limb (left limb showed decreased echo-type I and increased echo-type III + IV) and sex (women showed decreased echo-type I and increased in type II) was found. No significant changes in the remaining secondary outcomes were found. Ballet dancers showed structural changes in UTC, corresponding to a decreased echo-type I distribution after six weeks of rehearsing for Swan Lake ballet. No changes in self-reported symptoms, clinical signs of Achilles tendinopathy, and single-leg heel raise test were seen from pre- to post-rehearsal. Thus, UTC changes in the Achilles tendon seem to appear earlier than clinical signs of tendinopathy.


CD40 Agonists Alter the Pancreatic Cancer Microenvironment by Shifting the Macrophage Phenotype toward M1 and Suppress Human Pancreatic Cancer in Organotypic Slice Cultures.
CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. CD163+ (predominant in M2 macrophages) and FOXP3+ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163+ expression had shorter overall survival than those with low CD163+ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR+ (predominant in M1 macrophages) and a decrease in CD163+ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR+ and decrease CD163+ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.


Survival and reproduction of the cat flea (Siphonaptera: Pulicidae) fed human blood on an artificial membrane system.
Adult cat fleas, Ctenocephalides felis (Bouché), survive and reproduce when fed human blood through an artificial membrane system. When a dog hair substrate was included in cages with the fleas, mean adult mortality was 2.4 after 12 d of bloodfeeding. Egg production began after 3 d and was continuous for 12 d, ranging from 3 to 4 eggs per female per day. In cages without hair, mean adult mortality was 61.2% after 12 d of bloodfeeding. Egg production began after 2 d, reached a maximum of two eggs per female per day after 7 d, and decreased thereafter. No significant differences in egg hatch were seen in treatment groups sampled from 5 to 7 d after the onset of bloodfeeding. After 7 d, however, egg hatch for fleas maintained in cages without hair was significantly lower than in cages where fleas were maintained on dog hair. Adult emergence from these larvae did not differ significantly between the two groups. Egg hatch and adult emergence in both groups of fleas fed on human blood did not differ significantly from egg hatch and adult emergence in fleas fed on colony cats.


Edge Caching in Fog-Based Sensor Networks through Deep Learning-Associated Quantum Computing Framework.
Fog computing (FC) based sensor networks have emerged as a propitious archetype for next-generation wireless communication technology with caching, communication, and storage capacity services in the edge. Mobile edge computing (MEC) is a new era of digital communication and has a rising demand for intelligent devices and applications. It faces performance deterioration and quality of service (QoS) degradation problems, especially in the Internet of Things (IoT) based scenarios. Therefore, existing caching strategies need to be enhanced to augment the cache hit ratio and manage the limited storage to accelerate content deliveries. Alternatively, quantum computing (QC) appears to be a prospect of more or less every typical computing problem. The framework is basically a merger of a deep learning (DL) agent deployed at the network edge with a quantum memory module (QMM). Firstly, the DL agent prioritizes caching contents via self organizing maps (SOMs) algorithm, and secondly, the prioritized contents are stored in QMM using a Two-Level Spin Quantum Phenomenon (TLSQP). After selecting the most appropriate lattice map (32 × 32) in 750,000 iterations using SOMs, the data points below the dark blue region are mapped onto the data frame to get the videos. These videos are considered a high priority for trending according to the input parameters provided in the dataset. Similarly, the light-blue color region is also mapped to get medium-prioritized content. After the SOMs algorithm's training, the topographic error (TE) value together with quantization error (QE) value (i.e., 0.0000235) plotted the most appropriate map after 750,000 iterations. In addition, the power of QC is due to the inherent quantum parallelism (QP) associated with the superposition and entanglement principles. A quantum computer taking "n" qubits that can be stored and execute 2 n presumable combinations of qubits simultaneously reduces the utilization of resources compared to conventional computing. It can be analyzed that the cache hit ratio will be improved by ranking the content, removing redundant and least important content, storing the content having high and medium prioritization using QP efficiently, and delivering precise results. The experiments for content prioritization are conducted using Google Colab, and IBM's Quantum Experience is considered to simulate the quantum phenomena.