[Clinical value of endoscopic ultrasound-guided transesophageal fine needle puncture of mediastinal lesions].
As the mediastinum has been a region difficult to access for biopsy, mediastinoscopy has been required in most cases. In a prospective study the value of transoesophageal endoscopic ultrasound (TEUS) guided aspiration biopsy was assessed as an alternative. TEUS-guided fine-needle aspirations were performed between May 1995 and March 1998 in 35 patients with mediastinal space-occupying lesions. In all cases the conventional endoscopic method or percutaneous puncture-sonography had been impossible or had failed. In one patient it had been performed after a negative mediastinoscopy. In 34 patients (97%) the aspirated tissue cylinder could be evaluated histologically. There were no complications. Malignancy was demonstrated in 24 patients, and there were one case each of sarcoidosis, silicoanthracosis and two cases of retrosternal goitre. In four of seven patients the negative preoperative diagnosis was confirmed at operation or by follow-up. There were two false-negative results and in one patient there has been no definitive diagnosis. The accuracy of the method was thus 91.4%, the positive predictive value for malignancy 88.9% and the negative predictive value for malignancy 72.7%. Ultrasound alone was a poor predictor of malignancy in lymph node enlargement. TEUS-guided fine-needle aspiration of space-occupying mediastinal lesions is an effective and low-risk method that can in selected cases shorten the diagnostic process and avoid methods that are expensive or lead to complications such as transpulmonary biopsy guided by computed tomography or mediastinoscopy.


Oral immunization against poliomyelitis.
In the ten years since attenuated poliovirus was first administered to man for immunization against poliomyelitis, a vast body of experience has grown up and an attempt can now be made to assess the potentialities of oral poliovirus vaccine. The author of this paper seeks to answer two main questions: how safe are the strains now under study, and is oral vaccine effective in practice under the different conditions in which it may be used?From the information gained in large-scale trials involving a total of nearly 70 million people, he concludes that where poliomyelitis is predominantly a disease of infancy and early childhood the vaccines now available are safe both for the individual and for the community. The Sabin strains appear also to be safe for use in areas where the disease affects older children and adults; there is still not enough information to permit final conclusions to be drawn as to the safety of the Koprowski and Lederle strains in such areas.The evaluation of data on the efficacy of rural vaccines is beset with many problems, but the evidence of serological conversion rates suggests that, with one exception, there are no striking differences in efficacy between any of the strains when used in monovalent vaccines. However, 100% conversion cannot be expected in all circumstances from any oral vaccine given once only; repeated administration is clearly necessary, although it is still too early to say what the best vaccine schedule may be in any particular set of circumstances.While the problems yet to be solved are legion, great progress has nevertheless been made in the past decade, and the author looks forward to a steady extension of the use of live poliovirus vaccine and even to the eventual possibility of the eradication of poliomyelitis.


[Physical development of Moscow's schoolchildren during the past decade].
Long- and short-term follow-ups of the Moscow schoolchildren of the 1960s to the 1990s show that acceleration of their growth and development has mainly ceased now. Certain changes have been found in the children's morphological status. The age of menarche has become 0.5 year older. The authors consider it necessary to perform follow-ups of physical development in a pediatric population along with sociohygienic monitoring.


Pre-gelatinized high-amylose starch enables easy preparation of flexible and antimicrobial composite films for fresh fruit preservation.
While high-amylose starch (HAS) possesses advantageous properties such as high resistant starch content and favorable mechanical attributes, its gelatinization constraints have limited its applicability. This study enhances its versatility by focusing on pre-gelatinized (PG) HAS with exceptional rehydratability, achieved by disorganizing native HAS granules (with amylose contents of 55 % and 68 %, respectively) using a 33 % CaCl2 solution, followed by water-ethanol precipitation and freeze-drying. The resulting PG-HAS exhibited elevated amylose content (61 % and 75 %) with minimal changes in amylose molecular weight. PG-HAS displayed superior water-absorption index (WAI) and water-soluble index (WSI) compared to native HAS, further improved by 2 % CaCl2 solution incorporation. Furthermore, composite films were prepared by mixing PG-HAS with PVA at a 6:4 (w/w) ratio. The PG-G50 (61 % amylose content)/PVA composite film exhibited remarkable elongation (131.1 ± 5.4 %), nearly three times that of a normal corn starch (NCS, with 27 % amylose)/PVA film, attributed to improved starch dispersity and higher amylose content. Nonetheless, the PG-G70 (75 % amylose content)/PVA film at the same ratio showed lower elongation (54.7 ± 8.0 %), potentially due to strong cohesive forces between amylose chains that impede starch-PVA interactions. Moreover, the PG-HAS/PVA composite films, enriched with antibacterial agents, demonstrated effective antibacterial properties with a gradual and sustained release of active compounds. Notably, the PG-G50/PVA/tannic acid (TA) film effectively preserved fresh apple slices by inhibiting bacteria growth and preventing browning. These findings underscore the excellent rehydration of PG-HAS and its potential as an inner packaging material for irregularly shaped foods, such as sliced fruits or meats, due to its nontoxic nature, softness and flexibility, which allows the film to maintain close contact with food surfaces.


The value of childhood combination vaccines: From beliefs to evidence.
Although vaccination is one of the most cost-effective health care interventions, under-vaccination and variation in coverage rates lower than policy targets is rising in developed countries, partly due to concerns about vaccination value and benefits. By merging various antigens into a single product, combination vaccines represent a valuable tool to mitigate the burden associated with the numerous injections needed to protect against vaccine preventable infectious diseases and increase coverage rate, possibly through various behavioral mechanisms which have yet to be fully explored. Beyond their cost-effectiveness in protecting against more diseases with fewer injections, combination vaccines also have several other benefits, for children, their parents/carers, as well as for the health system and the population as a whole. The objectives of this review are to identify and illustrate the value of combination vaccines for childhood immunization. Evidence was classified into 2 groups: benefits for society and benefits for public health and healthcare systems. This article also highlights the value of innovation and challenges of combination vaccine development as well as the need for an increased number of suppliers to mitigate the impact of any potential vaccine shortage. Increasing public confidence in vaccines and combination vaccines is also critical to fully exploit their benefits.


Pregnancy outcomes among Syrian refugee and Jordanian women: a comparative study.
To compare pregnancy outcomes of Syrian refugee women and Jordanian women. In the past few years, thousands of Syrians fled Syria to neighbouring countries such as Jordan as a result of the continuing conflict in their country. Pregnant refugee women are facing many difficulties that increase the prevalence of antenatal complications. However, there is limited awareness of whether Syrian refugee women have different risks of pregnancy outcomes than Jordanian women. Using a retrospective cohort design, we examined pregnancy outcomes for Syrian refugee (N = 616) and Jordanian women (N = 644) giving birth at two governmental hospital in northern Jordan, between 1 January 2014 and 31 December 2014. A checklist of 13 variables was utilized. The primary outcome measures were delivery by Caesarean section, maternal complications, low birthweight (<2500 g), APGAR score and preterm delivery (<37 weeks' gestational age). Statistical analysis revealed that refugee mothers had a significant increase in the rate of Caesarean section and higher rate of anaemia, a lower neonates' weight and APGAR scores when compared to their Jordanian counterparts. Results were congruent with findings from other studies in the region and worldwide. Minimizing inequalities in pregnancy outcomes between Syrian refugees and Jordan women is a healthcare priority. The findings could guide the planning and development of health policies in Jordan that would help to alleviate the situation regarding refugee populations. Action is required by policy makers, specifically targeting public and primary healthcare services, to address the problem of adequately meeting the needs for antenatal care of this vulnerable population.


[Attention deficit and infantile hyperactivity].
Hyperactivity is a very common disorder in children (specially males) that today is considered as a clinical syndrome by scientific medicine. American Psychiatric Association establishes 10 symptoms to diagnose it, but they can be resumed in three characteristics: Impulsivity, Distraction, and Hyperactivity. There are different ways to treat it, but psychiatric medication has major risks in children. From complementary medicine we can find several aids in changing diet patterns and supplementing with vitamins or minerals. Chocolate, sugar, sweeteners, additives, preservatives, dyes, can enhance the incidence of this syndrome; instead the supplementation with lipids rich in PUFA's can prevent it. B complex vitamins, magnesium, copper, manganese or calcium can be interesting and in herbal medicine, sedative plants like passion flower, valerian or lemon balm are useful aids. Also liquorice, fennel and berries can be used for different physiological actions.


[Chronic renal disease in patients with systemic scleroderma: the prevalence and associated factors].
The aim of this work was to study the incidence of chronic renal disease (CRD) in 100 patients with systemic scleroderma (SS) who underwent general clinical and laboratory examination; glomerular filtration rate (GFR) was calculated. Statistica 8.0 and Excel 2007 programs were used to treat the results. 88% of the patients with SS had CRD, 80% showed lowered GFR and 81% suffered hypostenuria and/or proteinuria. GFR correlated with the presence of cardiac lesions and pulmonary hypertension, Valentini activity index, renal vessel resistance, concomitant renal pathology, arterial hypertension and/or CHD. Also, reduced GFR associated with myocardiofibrosis, atrioventricular valve incompetence, age and concomitant diseases (AH, DM, CRD, renal and urinary tract pathology).


Limitations to survival for infants with hypoplastic left heart syndrome before and after transplant: the Loma Linda experience.
Untreated, hypoplastic left heart syndrome is a lethal cardiac defect. Heart transplant has become an accepted therapeutic option for this condition. However, significant limitations to survival remain for infants with this condition who are referred for heart transplantation. Attention to the prevention, early detection, and management of common problems occurring at each stage of the transplantation process is important for improving survival rates. This study retrospectively reviewed the cases of 195 infants with hypoplastic left heart syndrome registered for heart transplantation at Loma Linda University Medical Center between November 1985 and July 1996 to determine causes of death. During the waiting period, progressive cardiac failure and complications from interventional procedures were the leading causes. In the early postoperative period, technical issues and acute graft failure were most important, whereas late deaths (more than 30 days after transplant) were most often related to rejection and posttransplant coronary artery disease.


[Neuronal correlates of changes in the defensive behavior of Helix lucorum L. during ontogeny].
In experiments on the isolated nervous system, responses of the same command neurones of avoidance behaviour to electrical stimulation of the intestinal nerve were compared in adult snails (Helix pomatia) and in snails 1-20 days old. Dynamics of spike reactions of the command neurones to rhythmic nerve stimulation differed in adult and newborn snails. In the neurones of young snails, no sensitization, common in the adult animals, was observed. Study of excitatory input in the command neurones during rhythmic nerve stimulation suggests independence of habituation of synaptic input amplitude and spike response sensitization, because dynamics of habituation coincided in the young and adult snails while spike response underwent sensitization only in adult animals.


Injecting equipment sharing in Russian drug injecting dyads.
In this study, we investigated how individual attributes, dyad characteristics and social network characteristics may influence engaging in receptive syringe sharing, distributive syringe sharing and sharing cookers in injecting partnerships of IDUs in St Petersburg, Russia. We found that all three levels were associated with injecting equipment sharing, and that dyad characteristics were modified by characteristics of the social network. Self-reported HIV discordance and male gender concordance played a role in the risk of equipment sharing. Dyad interventions may not be sufficient to reduce injecting risk in IDU partnerships, but a combination of dyad and network interventions that target both IDU partnerships and the entire IDU population may be more appropriate to address injecting risk among IDUs.


Role of adhesion and contraction in Rac 1-regulated endothelial barrier function in vivo and in vitro.
We demonstrated previously that inhibition of the small GTPase Rac-1 by Clostridium sordellii lethal toxin (LT) increased the hydraulic conductivity (L(p)) of rat venular microvessels and induced gap formation in cultured myocardial endothelial cells (MyEnd). In MyEnd cells, we also demonstrated that both LT and cytochalasin D reduced cellular adhesion of vascular endothelial (VE)-cadherin-coated beads. Here we further evaluate the contribution of actin depolymerization, myosin-based contraction, and VE-cadherin linkage to the actin cytoskeleton to LT-induced permeability. The actin-depolymerizing agent cytochalasin D increased L(p) in single rat mesenteric microvessels to the same extent as LT over 80 min. However, whereas the actin-stabilizing agent jasplakinolide blunted the L(p) increase due to cytochalasin D by 78%, it had no effect on the LT response. This conforms to the hypothesis that the predominant mechanism whereby Rac-1 stabilizes the endothelial barrier in intact microvessels is separate from actin polymerization and likely at the level of the VE-cadherin linkage to the actin cytoskeleton. In intact vessels, neither inhibition of contraction (butanedione monoxime, an inhibitor of myosin ATPase) nor inhibition of Rho kinase (Y-27632) modified the response to LT, even though both inhibitors lowered resting L(p). In contrast butanedione monoxime and inhibition of myosin light chain kinase completely inhibited LT-induced intercellular gap formation and largely reduced the LT-induced permeability increase in MyEnd monolayers. These results support the hypothesis that the contractile mechanisms that contribute to the formation of large gaps between cultured endothelial cells exposed to inflammatory conditions do not significantly contribute to increased permeability in intact microvessels.


Osteoblast adhesion on novel machinable calcium phosphate/lanthanum phosphate composites for orthopedic applications.
Lanthanum phosphate (LaPO(4), LP) was combined with either hydroxyapatite (HA) or tricalcium phosphate (TCP) to form novel composites for orthopedic applications. In this study, these composites were prepared by wet chemistry synthesis and subsequent powder mixing. These HA/LP and TCP/LP composites were characterized in terms of phase stability and microstructure evolution during sintering using X-ray diffraction (XRD) and scanning electron microscopy (SEM). Their machinability was evaluated using a direct drilling test. For HA/LP composites, LP reacted with HA during sintering and formed a new phase, Ca(8)La(2)(PO(4))(6)O(2), as a reaction by-product. However, TCP/LP composites showed phase stability and the formation of a weak interface between TCP and LP machinability when sintered at 1100 degrees C, which is crucial for achieving desirable properties. Thus, these novel TCP/LP composites fulfilled the requirements for machinability, a key consideration for manufacturing orthopedic implants. Moreover, the biocompatibility of these novel LP composites was studied, for the first time, in this paper. In vitro cell culture tests demonstrated that the LP and its composites supported osteoblast (bone-forming cell) adhesion similar to natural bioceramics (such as HA and TCP). In conclusion, these novel LP composites should be further studied and developed for more effectively treating bone related diseases or injuries.


Effective Tube Weaning and Predictive Clinical Characteristics of NICU Patients With Feeding Dysfunction.
The present study evaluated the effectiveness of a multidisciplinary earlier discharge model for neonates receiving home enteral nutrition (HEN). A retrospective data review and analysis was performed on 183 patients discharged out of the neonatal intensive care unit (NICU) receiving partial oral feeds (PO) and partial HEN from September 2016 to March 2018. These patients were followed in a multidisciplinary clinic led by a pediatric gastroenterologist, a neonatal feeding therapist, and a pediatric dietitian. Demographics and data were recorded for patients at discharge, and then chart reviews were performed for additional data. Of 182 patients, 121 (67%) weaned off HEN with a median time to full PO at 79 days (interquartile range [IQR] 15, 247) and had median PO intake of 20% (0, 43) at time of discharge. When comparing patients who gained 100% PO vs patients who did not wean off HEN, the weaned group consisted of 88% nasogastric tubes, with median time off feeds at 27 days (IQR 8, 79) and median PO intake of 29% (11, 50) at discharge. Only 13% of the cohort had an emergency room or hospital admission, which corresponds to 1.6 and 0.8 events, respectively, per 500 tube days specifically due to HEN complications. Our study supports that NICU patients with feeding dysfunction can effectively and safely discharge home earlier while receiving HEN. Our data suggest that a dedicated outpatient clinic can facilitate effective tube weaning in a majority of neonates with complex medical diseases with low rates of adverse events.


Managed care and the dissemination of robotic prostatectomy.
Robotic prostatectomy has rapidly disseminated over the past decade. How managed care, thought by many to be a barrier to new technology, influences the dissemination of robotics is unknown. We sought to better understand the relationship between a market's managed-care penetration and the dissemination of robotic prostatectomy. We used SEER-Medicare data from 2003 through 2007 to identify men ≥66 years of age treated with radical prostatectomy for prostate cancer. We categorized Health Service Areas (HSAs) according to the degree of managed-care penetration (ie, low vs high). We assessed adoption of robotic prostatectomy and utilization among adopting HSAs using Cox proportional-hazards and Poisson regression models, respectively. Compared with markets with little managed care, highly penetrated markets had more racial diversity (24% vs 15% nonwhite, P < .01), higher population densities (1987 vs 422 people/square mile, P < .01), and higher median incomes ($49 374 vs $36 236, P < .01). Robotic prostatectomy adoption and utilization increased over time in both HSA categories. Compared with low managed-care markets, those with high managed care adopted robotic prostatectomy more rapidly (eg, probability 0.37 [low] vs 0.52 [high] in 2007; P < .01). However, the postadoption utilization of robotic prostatectomy was constrained in these highly penetrated markets (eg, probability 0.66 [low] vs 0.52 [high] in 2007; P < .01). High managed-care penetration was associated with more rapid robotic prostatectomy adoption. However, once adopted, utilization increased more slowly in these markets. Understanding this paradox is important as more technologies are unveiled in an increasingly cost-conscious health care environment.


The effectiveness of group psychotherapy with children.
Review of empirical outcome research on children's activity, behavior modification, play, and verbal therapy groups reveals unconvincing evidence of their effectiveness. An approximately equivalent number of studies yielded generally positive, mixed, and null results. Little evidence of deterioration was found. On a comparative basis, the results tend to favor behavioral as opposed to other approaches. This article includes recommendations for improving the quality of the data base and increasing its potential for influencing practice.


Evaluation of the effect of Q-switched ruby and Q-switched Nd-YAG laser irradiation on melanosomes in dermal melanocytosis.
Q-switched ruby laser (QSRL) and Q-switched Nd-YAG laser (QSNYL) treatment of dermal melanocytosis, especially nevus of Ota, has produced favorable results that are mediated by selective photothermolysis. However, the precise effects of irradiation on melanosomes and cells containing melanosomes remain unclear, and an optimal method of irradiation has not been found. In this study synthetic melanin powder and pigmented dermal tissue obtained from five blue nevus lesions, also classified as dermal melanocytosis, were used as targets to identify the specific effects of these forms of irradiation in vitro. Morphological changes were assessed by microscopy after irradiation with QSRL and QSNYL at a fluence of 5 J/cm2, the fluence ordinarily utilized in clinical applications. Light microscopy revealed that most of the synthetic melanin powder retained in 1% agar was no longer visible after QSRL irradiation. In contrast, melanin powder particles were partly crushed by QSNYL irradiation. Electron microscopic examination of melanosomes in the blue nevus tissue after irradiation showed expansion and various other forms of disruption. Statistical analysis by 2-way analysis of variance (ANOVA) of the length of the major axis of the melanosomes indicated that QSRL irradiation caused significantly greater melanosome expansion than QSNYL irradiation. These findings indicate that QSRL irradiation had a greater photothermal effect on dermal melanosomes than QSNYL irradiation. This suggests that QSRL is more efficacious in the treatment of dermal melanocytosis than QSNYL.


Encapsulation of ropivacaine in a combined (donor-acceptor, ionic-gradient) liposomal system promotes extended anesthesia time.
Ropivacaine is a local anesthetic with similar potency but lower systemic toxicity than bupivacaine, the most commonly used spinal anesthetic. The present study concerns the development of a combined drug delivery system for ropivacaine, comprised of two types of liposomes: donor multivesicular vesicles containing 250 mM (NH4)2SO4 plus the anesthetic, and acceptor large unilamellar vesicles with internal pH of 5.5. Both kinds of liposomes were composed of hydrogenated soy-phosphatidylcholine:cholesterol (2:1 mol%) and were prepared at pH 7.4. Dynamic light scattering, transmission electron microscopy and electron paramagnetic resonance techniques were used to characterize the average particle size, polydispersity, zeta potential, morphology and fluidity of the liposomes. In vitro dialysis experiments showed that the combined liposomal system provided significantly longer (72 h) release of ropivacaine, compared to conventional liposomes (~45 h), or plain ropivacaine (~4 h) (p <0.05). The pre-formulations tested were significantly less toxic to 3T3 cells, with toxicity increasing in the order: combined system < ropivacaine in donor or acceptor liposomes < ropivacaine in conventional liposomes < plain ropivacaine. The combined formulation, containing 2% ropivacaine, increased the anesthesia duration up to 9 h after subcutaneous infiltration in mice. In conclusion, a promising drug delivery system for ropivacaine was described, which can be loaded with large amounts of the anesthetic (2%), with reduced in vitro cytotoxicity and extended anesthesia time.


Human tissue-type plasminogen activator. Production in continuous serum-free cell culture and rapid purification.
A simplified procedure for the production and purification of human tissue-type plasminogen activator (t-PA) is described. Bowes-melanoma cells were maintained in continuous serum-free culture. The cell nutrient consisted of Dulbecco's modified Eagle's medium (DMEM) supplemented with insulin (5 mg/litre), transferrin (5 mg/litre), progesterone (1 nM), cortisol (10 nM), aprotinin (2 X 10(4) units/litre) and a mixture of trace elements. t-PA accumulated in the culture medium at a rate of 40 units/day per ml and was harvested every third day. Cell losses during each harvest, leading to a steady decline of enzyme yields, were compensated for by treating the cells with 5% (v/v) fetal-bovine serum in DMEM every 6-8 weeks. t-PA was rapidly purified by a combination of cation-exchange chromatography and gel filtration. The procedure yielded mainly single-chain t-PA of a specific activity of 80 000 to 100 000 units/mg.


[Specific features of neovascularization of dysplastic invasiveness and cancer of the breast].
There are shown the results of study related to angioarchitechtonices of displastic pre-cancer outgrows, fibroadenoma and carcinoma of the breast (non-proliferative and proliferative forms of fibro-cystic disease - 35 cases, fibroadenoma - 32 cases, cancer - 55 cases) using histological (hematoxylin and eosin and picrofuxin staining) and immunohistochemical (angiogenesis marker - CD31 and marker of proliferation - Ki67) methods. It was estimated that the character and intensity of vascularization as well as neoangiogenesis of above-named pathologic conditions and breast cancer could be determined by the differentiation of tissue structures and neoplastic cells. The microangioarxitectonics pre-cancer outgrowths and cancer of the breast is so peculiar and characteristic for each concrete case that it should be considered for morphological diagnosing and determining the tactic of treatment.


Ancillary techniques on direct-smear aspirate slides: a significant evolution for cytopathology techniques.
Numerous cytologic techniques aimed at effectively acquiring patient material for molecular testing have been proposed. Such techniques are becoming ever more important in an age of personalized medicine. In this commentary, the authors explored some more commonly proposed techniques to aid in the molecular testing of cytologic specimens. These techniques include the use of cell blocks, direct cytologic smears, filter paper storage, frozen samples, and enriched cellular techniques such as ThinPrep and cytospin preparations. Direct-smeared slides demonstrate excellent preservation of DNA, are easy to prepare, and are amenable to immediate adequacy at the time of the fine-needle aspiration (FNA) procedure as well as effective subsequent tumor purity estimation. Cell block methods cannot be assessed at the time of FNA and often demonstrate insufficiency, whereas filter paper and frozen techniques do not allow for the direct assessment of the presence and purity of tumor cells in the sample. Direct-smeared slides are emerging as the most effective preparation and storage medium of cytologic material to be used for molecular testing. Their cost-effectiveness, ease of use, and reliability have cemented them as the optimal solution for cytopathologists to fulfill the role of providing advanced molecular testing on patient samples.


Multifactorial, site-specific recurrence models after radical cystectomy for urothelial carcinoma: external validation in a cohort of Korean patients.
The aim of this study was to evaluate the accuracy of site-specific recurrence models after radical cystectomy in the Korean population. We conducted a review of an electronic medical record of 572 patients who underwent radical cystectomy for urothelial carcinoma of the bladder. Primary end point was the site-specific recurrence after radical cystectomy. The median follow-up in the validation cohort was 42.3 months (interquartile range: 23.0-89.3 months). During the follow-up period, there were 165 patients (28.8%), 85 (14.9%), 31 (5.4%), and 78 (13.6%) who recurred in abdomen/pelvis, thoracic region, upper urinary tract, and bone, respectively. The c-indices of abdomen/pelvis, thoracic region, upper urinary tract, and bone models 3 years after radical cystectomy were 0.69 (95% confidence interval [CI], 0.65-0.73), 0.69 (95% CI, 0.64-0.75), 0.61 (95% CI, 0.52-0.69), and 0.65 (95% CI, 0.59-0.71), respectively. Kaplan-Meier curves demonstrated that models discriminated well and log-rank test were all highly significant (all p<0.001), except upper urinary tract model (p = 0.366). Decision curve analysis revealed that the use of prediction models for abdomen/pelvis, thoracic region, and bone recurrence was associated with net benefit gains relative to the treat-all strategy, but not the model for upper urinary tract recurrence. Abdomen/pelvis, thoracic region, and bone models demonstrate moderate discrimination, adequate calibration, and meaningful net benefit gains, whereas upper urinary tract model does not seem applicable to patients from Asia because it has suboptimal accuracy.


[Comparative light and scanning electron microscopy studies of the morphologic structure of ligament insertions into the bone].
The microstructure of the osseous ligament insertion was studied by light microscopy and scanning electron microscopy using the insertion of the membrana interossea antebrachii as an example. The scanning electron microscopical findings of specimens which had been prepared by freeze-fracturing confirm the typical 4-zone-structure of the osseous ligament insertion. The findings emphasize the functional importance of both zones of unmineralized and mineralized fibrous cartilage, which represent an effective shock absorbing system for the collagenous structures of the osseous ligament insertion.


Assessing your CHIN (community health information network) readiness.
Whether your health care organization is considering developing a CHIN, an enterprise network, or an integrated delivery system, the CHIN readiness assessment process is a valuable one. Bringing together the information technology staff, managed care and strategic planners, clinical staff, and executive management in a forum for open exchange of ideas and plans is, in itself, a critical activity. A formal assessment will provide your health care organization with a baseline measure of where you are today, and where you need to focus your efforts over the next months and years to achieve your organization's goals.


Single-fraction Radiation Treatment Dose Response in a Genetically Engineered Mouse Model of Medulloblastoma.
Medulloblastoma is the most common malignant brain tumor of children. Although standard of care radiotherapy for pediatric medulloblastoma (PM) can lead to long-term remission or cure in many patients, it can also cause life-long cognitive impairment and other adverse effects. The pathophysiological mechanisms involved in radiation-induced cerebral damage are incompletely understood, and their elucidation may lead to interventions that mitigate radiation toxicity. To explore the mechanisms of radiation-induced cerebral damage, transgenic mouse models of PM and non-tumor-bearing controls were exposed to radiation doses that ranged from 0 to 30 Gy. Between 0-20 Gy, a significant dose-dependent reduction in tumor-associated hydrocephalus and increase in overall survival were observed. However, at 30 Gy, hydrocephalus incidence increased and median overall survival fell to near-untreated levels. Immunohistochemistry revealed that both tumor-bearing and non-tumor-bearing mice treated with 30 Gy of radiation had significantly more reactive astrocytes and microvascular damage compared to untreated controls. This effect was persistent across mice that were given 1 and 2 weeks of recovery time after irradiation. Our data suggest that radiation therapy promotes neural death by inducing long-term neuroinflammation in PM, suggesting radiation delivery methods that limit inflammation may be effective at widening the therapeutic window of radiation therapy in PM patients.


Performance and Return to Sport After Achilles Tendon Repair in National Football League Players.
Achilles tendon injuries are common in sports, including football. The purpose of this study was to determine (1) return-to-sport rate in National Football League (NFL) players following Achilles tendon repair, (2) postoperative career length and games per season, (3) pre- and postoperative performance, and (4) postoperative performance compared with control players matched by position, age, years of experience, and performance. Publicly available records were used to identify NFL players who underwent Achilles tendon repair and matched controls were identified. Ninety-five players (98 surgeries) were analyzed (mean age 28.2 ± 2.8 years; mean 5.5 ± 2 .8 years in NFL at time of surgery). Demographic and performance data were collected. Comparisons between case and control groups and preoperative and postoperative time points were made using paired-samples Student t tests. Seventy-one (72.4%) players were able to return to sport in the NFL at a mean of 339.8 ± 84.8 days following surgery. Thirty-one (32%) Achilles tendon repairs were performed during training camp or preseason. Controls (3.6 ± 2.1 years) had a significantly longer NFL career ( P < .05) than players who underwent Achilles tendon repair (2.7 ± 2.1 years). There was no significant difference in games per season in subsequent seasons following surgery compared with controls. Postoperative performance scores were significantly worse ( P < .05) for running backs (RBs) (n = 4) and linebackers (LBs) (n = 12) compared to preoperative scores. LBs had significantly worse postoperative performance scores when compared to matched controls ( P < .05). Following Achilles tendon repair, less than 75% of players returned to the NFL. Postoperative career length was 1 season shorter than matched controls. No difference was observed in the number of games per season played compared to matched controls. Postoperative performance scores were significantly worse for RBs and LBs compared to preoperative and LBs had significantly worse postoperative performance when compared to matched controls. Level III, retrospective comparative series.


Deletion of the Cold Thermoreceptor TRPM8 Increases Heat Loss and Food Intake Leading to Reduced Body Temperature and Obesity in Mice.
The coupling of energy homeostasis to thermoregulation is essential to maintain homeothermy in changing external environments. We studied the role of the cold thermoreceptor TRPM8 in this interplay in mice of both sexes. We demonstrate that TRPM8 is required for a precise thermoregulation in response to cold, in fed and fasting. Trpm8-/- mice exhibited a fall of 0.7°C in core body temperature when housed at cold temperatures, and a deep hypothermia (<30°C) during food deprivation. In both situations, TRPM8 deficiency induced an increase in tail heat loss. This, together with the presence of TRPM8-sensory fibers innervating the main tail vessels, unveils a major role of this ion channel in tail vasomotor regulation. Finally, TRPM8 deficiency had a remarkable impact on energy balance. Trpm8-/- mice raised at mild cold temperatures developed late-onset obesity and metabolic dysfunction, with daytime hyperphagia and reduction of fat oxidation as plausible causal factors. In conclusion, TRPM8 fine-tunes eating behavior and fuel utilization during thermoregulatory adjustments to mild cold. Persistent imbalances in these responses result in obesity.SIGNIFICANCE STATEMENT The thermosensitive ion channel TRPM8 is required for a precise thermoregulatory response to cold and fasting, playing an important role in tail vasoconstriction, and therefore heat conservation, as well as in the regulation of ingestive behavior and metabolic fuel selection upon cooling. Indeed, TRPM8-deficient mice, housed in a mild cold environment, displayed an increase in tail heat loss and lower core body temperature, associated with the development of late-onset obesity with glucose and lipid metabolic dysfunction. A persistent diurnal hyperphagia and reduced fat oxidation constitute plausible underlying mechanisms in the background of a deficient thermoregulatory adjustment to mild cold ambient temperatures.


Identification of novel prognostic alternative splicing signature in papillary renal cell carcinoma.
Papillary renal cell carcinoma (pRCC) is a heterogeneous disease containing multifocal or solitary tumors with an aggressive phenotype. Increasing evidence has indicated the involvement of aberrant splicing variants in renal cell cancer, while systematic profiling of aberrant alternative splicing (AS) in pRCC was lacking and largely unknown. In the current study, comprehensive profiling of AS events were performed based on the integration of pRCC cohort from the Cancer Genome Atlas database and SpliceSeq software. With rigorous screening and univariate Cox analysis, a total of 2077 prognoses AS events from 1642 parent genes were identified. Then, stepwise least absolute shrinkage and selection operator method-penalized Cox regression analyses with 10-fold cross-validation followed by multivariate Cox regression were used to construct the prognostic AS signatures within each AS type. And a final 21 AS event-based signature was proposed which showed potent prognostic capability in stratifying patients into low- and high-risk subgroups (P < .0001). Furthermore, time-dependent receiver operating characteristics curves confirmed that the final AS signature was effective and robust in predicting overall survival for pRCC patients with the area under the curve above 0.9 from 1 to 5 years. In addition, splicing correlation network was built to uncover the potential regulatory pattern among prognostic splicing factors and candidate AS events. Besides, gene set enrichment analysis revealed the involvement of these candidates AS events in tumor-related pathways including extracellular matrix organization, oxidative phosphorylation, and P53 signaling pathways. Taken together, our results could contribute to elucidating the underlying mechanism of AS in the oncogenesis process and broaden the novel field of prognostic and clinical application of molecule-targeted approaches in pRCC.


Lay public's understanding of equipoise and randomisation in randomised controlled trials.
To research the lay public's understanding of equipoise and randomisation in randomised controlled trials (RCTs) and to look at why information on this may not be not taken in or remembered, as well as the effects of providing information designed to overcome barriers. Investigations were informed by an update of systematic review on patients' understanding of consent information in clinical trials, and by relevant theory and evidence from experimental psychology. Nine investigations were conducted with nine participants. Access (return to education), leisure and vocational courses at Further Education Colleges in the Midlands, UK. Healthy adults with a wide range of educational backgrounds and ages. Participants read hypothetical scenarios and wrote brief answers to subsequent questions. Sub-samples of participants were interviewed individually to elaborate on their written answers. Participants' background assumptions concerning equipoise and randomisation were examined and ways of helping participants recognise the scientific benefits of randomisation were explored. Judgments on allocation methods; treatment preferences; the acceptability of random allocation; whether or not individual doctors could be completely unsure about the best treatment; whether or not doctors should reveal treatment preferences under conditions of collective equipoise; and how sure experts would be about the best treatment following random allocation vs doctor/patient choice. Assessments of understanding hypothetical trial information. Recent literature continues to report trial participants' failure to understand or remember information about randomisation and equipoise, despite the provision of clear and readable trial information leaflets. In current best practice, written trial information describes what will happen without offering accessible explanations. As a consequence, patients may create their own incorrect interpretations and consent or refusal may be inadequately informed. In six investigations, most participants identified which methods of allocation were random, but judged the random allocation methods to be unacceptable in a trial context; the mere description of a treatment as new was insufficient to engender a preference for it over a standard treatment; around half of the participants denied that a doctor could be completely unsure about the best treatment. A majority of participants judged it unacceptable for a doctor to suggest letting chance decide when uncertain of the best treatment, and, in the absence of a justification for random allocation, participants did not recognise scientific benefits of random allocation over normal treatment allocation methods. The pattern of results across three intervention studies suggests that merely supplementing written trial information with an explanation is unlikely to be helpful. However, when people manage to focus on the trial's aim of increasing knowledge (as opposed to making treatment decisions about individuals), and process an explanation actively, they may be helped to understand the scientific reasons for random allocation. This research was not carried out in real healthcare settings. However, participants who could correctly identify random allocation methods, yet judged random allocation unacceptable, doubted the possibility of individual equipoise and saw no scientific benefits of random allocation over doctor/patient choice, are unlikely to draw upon contrasting views if invited to enter a real clinical trial. This suggests that many potential trial participants may have difficulty understanding and remembering trial information that conforms to current best practice in its descriptions of randomisation and equipoise. Given the extent of the disparity between the assumptions underlying trial design and the assumptions held by the lay public, the solution is unlikely to be simple. Nevertheless, the results suggest that including an accessible explanation of the scientific benefits of randomisation may be beneficial provided potential participants are also enabled to reflect on the trial's aim of advancing knowledge, and to think actively about the information presented. Further areas for consideration include: the identification of effective combinations of written and oral information; helping participants to reflect on the aim of advancing knowledge; and an evidence-based approach to leaflet construction.


Atypical Presentation and Delayed Diagnosis of Gyrate Atrophy: Case Reports of Two Siblings.
Gyrate atrophy (GA) is a hereditary condition characterized by ornithine aminotransferase deficiency-related large areas of retinal pigment epithelium and choriocapillaris lobular-shaped atrophy in the peripheral retina. In this report, we present a case of atypical presentation of GA. The aim of this report is to present two siblings, one of which was associated with a lamellar macular hole and with a history of previous diagnosis of retinitis pigmentosa. The delayed diagnosis of GA was made only after her brother, who was 5 years younger than her was diagnosed with GA. In addition, in this report, we evaluated GA in terms of multimodal imaging findings, differential diagnosis, and treatment of macular complications.


Controlling translation via modulation of tRNA levels.
Transfer RNAs (tRNAs) are critical adaptor molecules that carry amino acids to a messenger RNA (mRNA) template during protein synthesis. Although tRNAs have commonly been viewed as abundant 'house-keeping' RNAs, it is becoming increasingly clear that tRNA expression is tightly regulated. Depending on a cell's proliferative status, the pool of active tRNAs is rapidly changed, enabling distinct translational programs to be expressed in differentiated versus proliferating cells. Here, I highlight several post-transcriptional regulatory mechanisms that allow the expression or functions of tRNAs to be altered. Modulating the modification status or structural stability of individual tRNAs can cause those specific tRNA transcripts to selectively accumulate or be degraded. Decay generally occurs via the rapid tRNA decay pathway or by the nuclear RNA surveillance machinery. In addition, the CCA-adding enzyme plays a critical role in determining the fate of a tRNA. The post-transcriptional addition of CCA to the 3' ends of stable tRNAs generates the amino acid attachment site, whereas addition of CCACCA to unstable tRNAs prevents aminoacylation and marks the tRNA for degradation. In response to various stresses, tRNAs can accumulate in the nucleus or be further cleaved into small RNAs, some of which inhibit translation. By implementing these various post-transcriptional control mechanisms, cells are able to fine-tune tRNA levels to regulate subsets of mRNAs as well as overall translation rates.


[Treatment of adolescents with identity diffusion: a modification of transference focused psychotherapy].
This paper is an introduction to a treatment for adolescents with identity diffusion that has been modified from a therapy that has been found to be effective in the treatment of adults with significant identity diffusion, namely, Transference Focused Psychotherapy. The central role of differentiating normal Identity Crisis from Identity Diffusion in adolescents, essential to accurately identifying those adolescents appropriate for this treatment, is articulated. The primary modifications of TFP for adolescent treatment described involve changes in frequency and duration of some of the specific techniques (e.g. increased clarification ; more work in the extra-transferential relationships before directly addressing the transference), tactics (e.g. inclusion of family during the assessment phase and treatment contract setting phases of treatment; inclusion of supportive interventions in the environment while maintaining the analytic stance in sessions), and strategies (e.g. the goal of removing blockages to the development of normal identity integration, not "forced maturation"). This treatment aims to improve adolescent's relationships with friends, parents, and teachers; help clarify life goals ; acquire positive self-esteem; and be better prepared for entering love relation ships.


Yoga for Children and Adolescents After Completing Cancer Treatment.
Survivors of childhood cancer may experience persistent symptoms, including fatigue, sleep disturbance, and balance impairment. Yoga is a complementary therapy that improves fatigue, sleep, and quality of life in adult cancer survivors. Using a one group, repeated measures design, we evaluated the feasibility of a yoga program and assessed if cancer survivor participants ages 10 to 17 years (n = 13) had significantly less fatigue and anxiety, and better balance and sleep, after a 6-week yoga intervention compared with a 6-week pre-intervention wait period. Study recruitment was challenging with a 32% enrollment rate; yoga attendance was 90%. None of the scores for anxiety, fatigue, sleep, and balance had significant changes during the wait period. After the 6-week yoga program, children (n = 7) had a significant decrease in anxiety score (P = .04) while adolescent scores (n = 7) showed a decreasing trend (P = .10). Scores for fatigue, sleep, and balance remained stable post-intervention. Fatigue and balance scores were below norms for health children/adolescents while sleep and anxiety scores were similar to healthy peers.


Phase I and pharmacokinetic study of COL-3 in patients with recurrent high-grade gliomas.
COL-3 is a chemically modified tetracycline that targets multiple aspects of matrix metalloproteinase regulation. This phase I clinical trial was conducted to determine the maximum tolerated dose (MTD) of COL-3 in adults with recurrent high-grade glioma, to describe the effects of enzyme-inducing antiseizure drugs (EIADs) on its pharmacokinetics, and to obtain preliminary evidence of activity. Adults with recurrent high-grade glioma were stratified by EIAD use. COL-3 was given orally daily without interruption until disease progression or treatment-related dose-limiting toxicity (DLT). Three patients in each EIAD group were evaluated at each dose level beginning with 25 mg/m(2)/day and escalated by 25 mg/m(2)/day. Toxicity, response, and pharmacokinetics were assessed. Thirty-three patients were evaluated. The MTD was 75 mg/m(2)/day in the -EIAD patients while one was not determined in +EIAD patients. The common toxicities observed were anemia, ataxia, diarrhea, hypokalemia, CNS hemorrhage, and myalgia. One partial response was observed. -EIAD patients tended to have a higher steady-state trough concentration that was apparent only at the 100 mg/m(2)/day dose level (P = 0.01). This study suggests that: (a) EIAD use does affect the pharmacokinetics of COL-3 at higher doses; and (b) there was not enough suggestion of single-agent activity to warrant further study in recurrent high-grade gliomas.


Another source of individual differences: strategy adaptivity to changing rates of success.
This article explores an alternative approach to the study of individual differences of cognitive function-- that people may have the same strategies but differential ability to adaptively select among them in response to success and failure feedback from the environment. Three studies involving the complex and dynamic Kanfer-Ackerman Air Traffic Control Task (P. L. Ackerman & R. Kanfer, 1994) demonstrate (a) that individuals do differ systematically along this strategy adaptivity dimension, (b) that those differences have important consequences for overall task performance, and (c) that the differences are primarily associated with reasoning ability and working-memory capacity.


Massive Tibial Bone Regeneration with Autologous Peripheral Blood Stem Cells using Ilizarov Bone Transport: A Case Report.
This is a case report of a Gustilo-Anderson Type IIIB comminuted open right tibial fracture with massive bone loss, complicated by methicillin-resistant Staphylococus aureus (MRSA) infection. Non-viable and contaminated bony fragments were removed and infected bone resected. Soft tissue coverage and antibiotics were effective against the MRSA infection. A unifocal bone transport with the Ilizarov method regenerated 13cm of the missing tibia. Autologous peripheral blood stem cells (PBSC) injections into the osteogenesis site boosted bone regeneration and consolidation with a shortened Bone Healing index (BHI) of 23 days/cm.


Does quilting suture prevent seroma in abdominoplasty?
Seroma is the most frequent complication in abdominoplasty. Some patients are more prone to develop this complication. Ultrasound is a well-known method with which to diagnose seroma in the abdominal wall. The purpose of this study was to verify the efficacy of the use of quilting suture to prevent seroma. Twenty-one female patients who presented with abdominal deformity type III/A according to the authors' classification of abdominal skin and myoaponeurotic deformity had undergone abdominoplasty. The selected patients should have had at least one of the following characteristics: body mass index greater than 25 kg/m; weight loss greater than 10 kg; previous incision in the supraumbilical region; or present thinning of the subcutaneous in the area above the umbilicus. Ultrasound was performed for every patient from 15 to 18 days after the operation to search for fluid collection in the abdominal wall. The average fluid collection found was 8.2 cc per patient. Only two patients underwent aspiration because ultrasound showed greater than 20 cc collected above the fascial layer. These patients did not present with recurrence of seroma after aspiration. The quilting suture seems to be an efficient technique with which to prevent seroma formation.


Exploring Human Antimicrobial Antibody Responses on a Single B Cell Level.
Analysis of monoclonal antibodies (MAbs) derived from single B cell cloning has been highly beneficial for antimicrobial immunotherapy, vaccine design, and advancing our understanding of pathogen-triggered effects on the human immunoglobulin repertoire. Sequencing of variable domains of single B cells, and characterization of binding and functional activities of MAbs derived from those sequences, provides in-depth insight not only into sites of susceptibility for antibody-mediated neutralization or opsonization of the pathogen but also into the dynamics of protective antibody evolution during infection. This information can be utilized to rapidly develop novel immunotherapies of completely human origin and provides a roadmap for structure-based vaccine design that aims to elicit similar protective antibody responses. Here, we summarize recent aspects of the single B cell cloning approach.


ChemTrove: enabling a generic ELN to support chemistry through the use of transferable plug-ins and online data sources.
In designing an Electronic Lab Notebook (ELN), there is a balance to be struck between keeping it as general and multidisciplinary as possible for simplicity of use and maintenance and introducing more domain-specific functionality to increase its appeal to target research areas. Here, we describe the results of a collaboration between the Royal Society of Chemistry (RSC) and the University of Southampton, guided by the aims of the Dial-a-Molecule Grand Challenge, intended to achieve the best of both worlds and augment a discipline-agnostic ELN, LabTrove, with chemistry-specific functionality and using data provided by the ChemSpider platform. This has been done using plug-in technology to ensure maximum transferability with minimal effort of the chemistry functionality to other ELNs and equally other subject-specific functionality to LabTrove. The resulting product, ChemTrove, has undergone a usability trial by selected academics, and the resulting feedback will guide the future development of the underlying ELN technology.


Physicochemical and Biological Characterization of Fucoidan from Fucus vesiculosus Purified by Dye Affinity Chromatography.
A comparative study concerning the physicochemical, monomeric composition and biological characters among different fucoidan fractions is presented. Common purification techniques for fucoidan usually involve many steps. During these steps, the important structural features might be affected and consequently alter its biological activities. Three purified fractions were derived from Fucus vesiculosus water extract which, afterwards, were purified by a recently-developed dye affinity chromatography protocol. This protocol is based on dye-sulfated polysaccharide interactions. The first two fractions were obtained from crude precipitated fucoidan at different pH values of the adsorption phase: pH 1 and 6. This procedure resulted in fucoidan_1 and 6 fractions. The other, third, fraction: fucoidan_M, however, was obtained from a buffered crude extract at pH 1, eliminating the ethanol precipitation step. All of the three fractions were then further evaluated. Results revealed that fucoidan_M showed the highest sulfur content (S%), 12.11%, with the lowest average molecular weight, 48 kDa. Fucose, galactose, and uronic acid/glucose dimers were detected in all fractions, although, xylose was only detected in fucoidan_1 and 6. In a concentration of 10 µg·mL(-1), Fucoidan_6 showed the highest heparin-like anticoagulant activity and could prolong the APTT and TT significantly to 66.03 ± 2.93 and 75.36 ± 1.37 s, respectively. In addition, fucoidan_M demonstrated the highest potency against HSV-1 with an IC50 of 2.41 µg·mL(-1). The technique proved to be a candidate for fucoidan purifaction from its crude extract removing the precipitation step from common purification protocols and produced different fucoidan qualities resulted from the different incubation conditions with the immobilized thiazine toluidine blue O dye.


Climate patterns governing the presence and permanence of salmonellae in coastal areas of Bahia de Todos Santos, Mexico.
Despite the importance of salmonellae as one of the major causes of food-borne infections worldwide, data regarding the presence of these organisms in the environment are limited. We investigated the presence of Salmonella spp. in Bahia de Todos Santos (Baja California, Mexico) and evaluated the environmental factors that affect the occurrence of Salmonella spp. in this arid region. A total of 1,331 samples collected from 21 sites along the coast during a period of 3 years were analyzed for Salmonella spp. Geographical and seasonal distribution of Salmonella spp. was evaluated in association with environmental parameters and with human infections in the area. The incidence of Salmonella bacteria throughout the study was 4.8%, with the highest incidence detected in wastewater (16.2%), followed by stream water (10.6%), mollusks (7.4%), and seawater (2.3%). Twenty different serotypes were identified among the 64 Salmonella isolates. The dominant serotype was Typhimurium (23.4%), followed by Vejle (6.2%). The presence of Salmonella spp. in coastal areas was mostly confined to rainy periods and areas of stream discharges, and runoff was identified as the predominant factor influencing the transport of Salmonella bacteria from source points to the sea via streams. Isolation of Salmonella spp. was negatively and significantly associated with temperature, probably because of the effect of solar radiation in the decline of permanence of Salmonella bacteria. Conversely, human infections prevailed during the warmest months and were negatively correlated with the presence of Salmonella spp. in the marine environment.


Goodness-of-fit in generalized nonlinear mixed-effects models.
In recent years, generalized linear and nonlinear mixed-effects models have proved to be powerful tools for the analysis of unbalanced longitudinal data. To date, much of the work has focused on various methods for estimating and comparing the parameters of mixed-effects models. Very little work has been done in the area of model selection and goodness-of-fit, particularly with respect to the assumed variance-covariance structure. In this paper, we present a goodness-of-fit statistic which can be used in a manner similar to the R2 criterion in linear regression for assessing the adequacy of an assumed mean and variance-covariance structure. In addition, we introduce an approximate pseudo-likelihood ratio test for testing the adequacy of the hypothesized convariance structure. These methods are illustrated and compared to the usual normal theory likelihood methods (Akaike's information criterion and the likelihood ratio test) using three examples. Simulation results indicate the pseudo-likelihood ratio test compares favorably with the standard normal theory likelihood ratio test, but both procedures are sensitive to departures from normality.


The effect of posterior instrumentation of the spine on canal dimensions and neurological recovery in thoracolumbar and lumbar burst fractures.
A prospective study was designed to determine whether posterior instrumentation of the spine in thoracolumbar and lumbar burst fractures produces indirect decompression of the spinal canal leading to better remodeling and neurological recovery. The study was conducted in Kasturba Medical College Manipal, India. Sixty-eight consecutive cases of thoracolumbar and lumbar burst fractures were treated by posterior instrumentation, and approval from the hospital ethical committee was obtained. The degree of initial spinal canal compromise, indirect decompression, and remodeling were assessed from the computed tomography scans. The neurological status at the time of presentation and at final follow-up was assessed by the American Spinal Injury Association's modified Frankel's grading. The median canal compromise in patients with and without neurological deficit was 47.32 and 39.33%, respectively. The overall mean canal compromise at the time of admission, post-operative, and final follow-up were 47.37, 26.58 and 14.85%, respectively (P = <0.001). The median canal compromise in patients who recovered was 44.5% and in those with no neurological recovery was 55.85%. The median percentage of canal decompression achieved in patients who recovered was 22.15%, whereas it was 22% in those who did not recover. The median remodeling in recovered and non-recovered groups was 64.50 and 80%, respectively. None of these differences was statistically significant. This study shows that posterior instrumentation of the spine produces significant indirect decompression of the spinal canal and better remodeling. However, these factors may not improve the neurological recovery.


Lived Lives: A Pavee Perspective. An arts-science community intervention around suicide in an indigenous ethnic minority.
Background: Suicide is a significant public health concern, which impacts on health outcomes. Few suicide research studies have been interdisciplinary. We combined a psychobiographical autopsy with a visual arts autopsy, in which families donated stories, images and objects associated with the lived life of a loved one lost to suicide. From this interdisciplinary research platform, a mediated exhibition was created (Lived Lives) with artist, scientist and families, co-curated by communities, facilitating dialogue, response and public action around suicide prevention. Indigenous ethnic minorities (IEMs) bear a significant increased risk for suicide. Irish Travellers are an IEM with social and cultural parallels with IEMs internationally, experiencing racism, discrimination, and poor health outcomes including elevated suicide rates (SMR 6.6). Methods: An adjusted Lived Lives exhibition, Lived Lives: A Pavee Perspective manifested in Pavee Point, the national Traveller and Roma Centre. The project was evaluated by the Travelling Community as to how it related to suicide in their community, how it has shaped their understanding of suicide and its impacts, and its relevance to other socio-cultural contexts, nationally and internationally. The project also obtained feedback from all relevant stakeholders. Evaluation was carried out by an international visual arts research advisor and an independent observer from the field of suicide research. Results: Outputs included an arts-science mediated exhibition with reference to elevated Irish Traveller suicide rates. Digital online learning materials about suicide and its aftermath among Irish Travellers were also produced. The project reached its target audience, with a high level of engagement from members of the Travelling Community. Discussion: The Lived Lives methodology navigated the societal barriers of stigma and silence to foster communication and engagement, working with cultural values, consistent with an adapted intervention. Feedback from this project can inform awareness, health promotion, education and interventions around suicide and its aftermath in IEMs.


Expanding the molecular landscape of undifferentiated sarcomas of bone with a novel EWSR1-SSX3 gene fusion.
Undifferentiated sarcomas characterized by a primitive monomorphic round to spindle cell phenotype and often non-specific immunoprofile remain difficult to subclassify outside molecular analysis. The increased application of RNA sequencing in clinical practice led to significant advances and discoveries of novel gene fusions that furthered our understanding and refined classification of otherwise undifferentiated neoplasms. In this study, we report an undifferentiated round to spindle cell sarcoma arising in the femur of a 34-year-old female. The round to spindle tumor cells were arranged in short fascicles, with focal rosette formation, within a hyalinized stroma. The tumor immunoprofile included diffuse reactivity for CD99, SATB2, and TLE1 and patchy positivity for Cyclin D1, Keratin AE1/AE3, synaptophysin, and chromogranin. Other markers, such as EMA, SMA, desmin, S100, ERG, and WT1, were negative. Fluorescence in situ hybridization analysis for EWSR1 gene alterations showed a break-apart signal and targeted RNA sequencing revealed an EWSR1::SSX3 gene fusion. The patient received neoadjuvant chemotherapy followed by surgery and subsequently relapsed in less than a year with lung metastasis. Larger series are needed to determine if this fusion defines a novel subset of undifferentiated tumors or represents a genomic variant of already existing primitive round cell sarcoma categories, such as Ewing sarcoma or synovial sarcoma.


Role for the major outer-membrane protein from Vibrio anguillarum in bile resistance and biofilm formation.
Vibrio anguillarum, a fish pathogen, produces a 38 kDa major outer-membrane porin, which may be involved in environmental adaptation. The gene encoding the 38 kDa porin was cloned and deleted. The deduced protein sequence was 75 % identical to that of the major outer-membrane protein (OMP), OmpU, from Vibrio cholerae. LacZ expression from an ompU : : lacZ transcriptional gene fusion was increased 1.5-fold in the presence of bile salts and was decreased 50- to 100-fold in a toxR mutant compared to that in the wild-type, showing that ompU expression is positively regulated by ToxR and induced by bile salts. Similar to a toxR mutant, an ompU mutant showed a slight decrease in motility, an increased sensitivity to bile salts and a thicker biofilm with better surface area coverage compared to that of the wild-type. When ompU was expressed under a ToxR-independent promoter in the toxR mutant, the phenotypes for bile resistance and biofilm formation, but not motility were complemented to that of the wild-type. In rainbow trout, the ompU mutant showed wild-type virulence via immersion into infected seawater and intraperitoneal injection. The ompU mutant produced two colony morphologies: opaque, which did not grow at 0.2 % bile, and translucent, which grew at 2 % bile. The translucent ompU mutant strain produced a second major OMP that was induced by bile. All ompU mutants showed variations in the amount and length of smooth LPS. In V. anguillarum, OmpU is not required for virulence, possibly due to a second OMP also critical for resistance to bile; however, outside of the fish host, OmpU limits the progression of biofilm formation.


Comparing Five Year Out-Come in Two Cohorts of Patients with Early Rheumatoid Arthritis - A BARFOT Study.
The objective of the study was to compare disease characteristics over the first 5 years of disease in patients with RA, with disease onset in 1990s and 2000s, respectively. All 2235 patients with early RA (disease duration ≤12 months) were recruited from the BARFOT prospective observational study. These patients were divided into group 1 included 1992 to 1999 (N=1084, 66% women) and group 2 included 2000 to 2006 (N=1151, 69% women). Disease Activity Score (DAS28), VAS pain and Health Assessment Questionnaire (HAQ) were assessed during 5 years. Remission was defined as DAS28 <2.6. At inclusion, both women and men in group 2 had higher mean DAS28 (SD) than group 1, 5.42 (1.22) vs 5.26 (1.19), p=0.004 and 5.28 (1.22) vs 5.00 (1.27), p=0.004, respectively, mainly dependant on pain and not on inflammatory related measures. Over time DAS28 decreased and was in both genders, from 6 months to the 5-year follow-up, significantly lower in group 2. At 5-year, both women and men in group 2 had higher rate of remission than women and men in group 1. However, despite reduction of VAS pain and HAQ there were no differences in pain and HAQ between groups at any time point. Patients included in the 2000s achieved higher frequency of remission at the 5 year follow-up compared with those included in the 1990s, suggested to reflect the more active medical treatment. Interestingly, however, improvement in pain and HAQ did not differ between the two patient cohorts.


Rat brain cannabinoid receptor modulates N-type Ca2+ channels in a neuronal expression system.
Modulation of neuronal ion channels by the cloned rat brain CB1 cannabinoid receptor was investigated with the use of a heterologous neuronal expression system. Transient expression of the rat brain CB1 cannabinoid receptor was accomplished through microinjection of in vitro transcribed cRNA into the cytoplasm of enzymatically dissociated adult rat superior cervical ganglion neurons. The cannabimimetic aminoalkylindole WIN 55,212-2 inhibited whole-cell Ca2+ currents in neurons injected 16-25 hr previously with rat brain CB1 cannabinoid receptor cRNA. Inhibition of the Ca2+ current was voltage and concentration dependent, with a maximal inhibition of 73% and an IC50 value of 47 nM. The synthetic cannabinoid analogue CP55,940 also inhibited Ca2+ currents, with a maximal inhibition of 38% and an IC50 value of 7 nM. Ca2+ current inhibition was blocked by inclusion of guanosine-5'-O-(2-thiodiphosphate) in the intracellular patch pipette solution or by pretreatment with pertussis toxin. Pretreatment with the N-type Ca2+ channel antagonist omega-conotoxin GVIA reduced the inhibition by 100 nM WIN 55,212-2 from 44% to 6%, indicating that N-type Ca2+ channels are a target of cannabinoid action. On washout of WIN 55,212-2, the Ca2+ current amplitude "overrecovered" in 47% of the neurons tested. Anandamide, the endogenous cannabimimetic compound, had an inconsistent effect on the voltage-dependent Ca2+ currents in the majority of neurons microinjected with cannabinoid receptor cRNA. Ca2+ channels were a specific effector target of the cannabinoid receptor, as two different K+ currents, the M current and the A current, were not modulated by the cannabimimetic WIN 55,212-2.


The effects of unripe grape extract on systemic blood pressure, nitric oxide production, and response to angiotensin II administration.
Hypertension is the most common disease in the world. In Iranian folk medicine, unripe grape juice has been used as antihypertention remedy, but no data is documented for this popular belief. This study was designed to determine the effect of unripe grape extract (UGE) on blood pressure and the response to angiotensin II in rat. Unripe grape was collected, air dried, and extracted and concentrated. Four groups of Wistar rats received single doses of 125, 250, and 500 mg/kg of UGE or saline, respectively. The direct blood pressure and the serum nitrite level were measured one hour post UGE administration. The animals also were subjected to the infusion of various angiotensin II concentrations (100, 300, and 1000 μg/kg/min), and blood pressure was determined. Mean arterial, systolic, and diastolic pressures (MAP, SP, and DP) in all UGE treated groups were less than the control group, but only at the dose of 125 mg/kg (Group 1) they were significantly different (P < 0.05). The level of nitrite in groups 1-3 were significantly greater than the control group (P < 0.05). No significant differences were detected for the MAP, SP, and DP to different concentrations of angiotensin II among these groups. UGE potentially attenuate MAP, SP, and DP via vasodilatation induced by nitric oxide production.


Parameters controlling the strength of stochastic fibrous materials.
Many materials of everyday use are fibrous and their strength is important in most applications. In this work we study the dependence of the strength of random fiber networks on structural parameters such as the network density, cross-link density, fiber tortuosity, and the strength of the inter-fiber cross-links. Athermal networks of cellular and fibrous type are considered. We conclude that the network strength scales linearly with the cross-link number density and with the cross-link strength for a broad range of network parameters, and for both types of networks considered. Network strength is independent of fiber material properties and of fiber tortuosity. This information can be used to design fiber networks for specified strength and, generally, to understand the mechanical behavior of fibrous materials.


HArtMuT-modeling eye and muscle contributors in neuroelectric imaging.
Objective.Magneto- and electroencephalography (M/EEG) measurements record a mix of signals from the brain, eyes, and muscles. These signals can be disentangled for artifact cleaning e.g. using spatial filtering techniques. However, correctly localizing and identifying these components relies on head models that so far only take brain sources into account.Approach.We thus developed the Head Artifact Model using Tripoles (HArtMuT). This volume conduction head model extends to the neck and includes brain sources as well as sources representing eyes and muscles that can be modeled as single dipoles, symmetrical dipoles, and tripoles. We compared a HArtMuT four-layer boundary element model (BEM) with the EEGLAB standard head model on their localization accuracy and residual variance (RV) using a HArtMuT finite element model (FEM) as ground truth. We also evaluated the RV on real-world data of mobile participants, comparing different HArtMuT BEM types with the EEGLAB standard head model.Main results.We found that HArtMuT improves localization for all sources, especially non-brain, and localization error and RV of non-brain sources were in the same range as those of brain sources. The best results were achieved by using cortical dipoles, muscular tripoles, and ocular symmetric dipoles, but dipolar sources alone can already lead to convincing results.Significance.We conclude that HArtMuT is well suited for modeling eye and muscle contributions to the M/EEG signal. It can be used to localize sources and to identify brain, eye, and muscle components. HArtMuT is freely available and can be integrated into standard software.


INDIVIDUAL ARTICLE: NECOM 3: A Practical Algorithm for the Management of Radiation Therapy-Related Acute Radiation Dermatitis.
In the Nordic European countries in 2020, cancer diagnoses accounted for 175,925 patients. About 50% of cancer patients receive radiation therapy (RT), which may lead to radiation dermatitis (RD). Notably, patients with breast, head, neck, and anal cancers may be prone to developing RD. However, few algorithms exist for the prevention and treatment of RD. The Nordic European Cutaneous Oncodermatology Management (NECOM) project aims to improve cancer patient outcomes by offering tools to prevent and treat cancer therapy-related cutaneous adverse events (cAEs). The first 2 NECOM papers presented various cAEs and skincare regimens involving hygiene, moisturization, sun protection, and camouflage products for preventing and managing cAEs. The NECOM 3 practical algorithm for preventing and managing acute RD (ARD) is intended to promote healthy skin and reduce RT-related ARD, improving cancer patient outcomes.  Results: The NECOM advisors discussed the results of a systematic literature review and obtained consensus on the evidence and opinion-based practical algorithm for ARD to support all stakeholders in the Nordic European healthcare setting. The algorithm starts with skin-preserving therapy, followed by skin condition assessment and patient-specific interventions based on the grade of RD present.  Conclusion: ARD may lead to symptoms of pruritus and pain, decreased QoL and morbidity, and treatment interruptions. Patient education on the prevention of RD and treatment recommendations given in the NECOM 3 algorithm may help prevent and manage RD and improve the overall care of patients receiving RT. J Drugs Dermatol. 2023;22:11(Suppl 2):s3-s10.


Combined stool-based multiplex PCR and microscopy for enhanced pathogen detection in patients with persistent diarrhoea and asymptomatic controls from Côte d'Ivoire.
Infectious diarrhoea ranks among the leading causes of morbidity worldwide. Although most acute diarrhoeal episodes are self-limiting, the diagnosis and treatment of persistent diarrhoea (≥2 weeks) are cumbersome and require laboratory identification of the causative pathogen. Stool-based PCR assays have greatly improved the previously disappointing pathogen detection rates in high-income countries, but there is a paucity of quality data from tropical settings. We performed a case-control study to elucidate the spectrum of intestinal pathogens in patients with persistent diarrhoea and asymptomatic controls in southern Côte d'Ivoire. Stool samples from 68 patients and 68 controls were obtained and subjected to molecular multiplex testing with the Luminex(®) Gastrointestinal Pathogen Panel (GPP), microscopy and rapid antigen detection tests for the diagnosis of diarrhoeagenic pathogens. Overall, 20 different bacteria, parasites and viruses were detected by the suite of diagnostic methods employed. At least one pathogen was observed in 84% of the participants, and co-infections were observed in >50% of the participants. Enterotoxigenic Escherichia coli (32%), Giardia intestinalis (29%) and Shigella species (20%) were the predominant pathogens, and Strongyloides stercoralis (10%) was the most prevalent helminth. Pathogen frequencies and numbers of co-infections were similar in patients and controls. Although the Luminex(®) GPP detects a broad range of pathogens, microscopy for helminths and intestinal protozoa remains necessary to cover the full aetiological spectrum in tropical settings. We conclude that highly sensitive multiplex PCR assays constitute a useful screening tool, but that positive results might need to be confirmed by independent methods to discriminate active infection from asymptomatic faecal shedding of nucleic acids.


Recent advances in thiol and sulfide reactive probes.
Because of the biological relevance of thiols and sulfides such as cysteine, homocysteine, glutathione and hydrogen sulfide, their detection has attracted a great deal of research interest. Fluorescent probes are emerging as a new strategy for thiol and hydrogen sulfide analysis due to their high sensitivity, low cost, and ability to detect and image thiols in biological samples. In this short review, we have summarized recent advances in the development of thiol and hydrogen sulfide reactive fluorescent probes. These probes are compared and contrasted with regard to their designing strategies, mechanisms, photophysical properties, and/or reaction kinetics. Biological applications of these probes are also discussed.


Repetitive common peroneal nerve stimulation increases ankle dorsiflexor motor evoked potentials in incomplete spinal cord lesions.
Plasticity of corticospinal tract (CST) activity likely plays a key role in motor function recovery after central nervous system (CNS) lesions. In non-injured adults, 30 min of repetitive common peroneal nerve stimulation (rCPnS) increases CST excitability by 40-50% and the effect persists for at least 30 min. The present study evaluated with transcranial magnetic stimulation (TMS) the changes in CST excitability after 30 min of rCPnS in people with foot drop due to incomplete SCI. Suprathreshold rCPnS (25 Hz, alternating 1 s on 1 s off stimulation cycle) was given for two 15-min periods, while the subject sat at rest with ankle and knee joints fixed. Before, between, and after the periods of stimulation, the tibialis anterior (TA) motor evoked potentials (MEPs) to TMS were measured at a TMS intensity that originally produced a half-maximum MEP (typically 10-20% above threshold) while the sitting subject provided 25-30% maximum voluntary TA contraction. In 10 subjects with SCI, the peak-to-peak TA MEP increased by 14 ± 3% after rCPnS and the peak increase (+21 ± 7%) occurred 15 min after the cessation of rCPnS. The TA H-reflex, measured in separate experiments in 7 subjects, did not increase after rCPnS. The results indicate that rCPnS can increase CST excitability for the TA in people with incomplete SCI, although its effects appear smaller and shorter lasting than those found in non-injured control subjects. Such short-term plasticity in the CST excitability induced by rCPnS may contribute to long-term therapeutic effects of functional electrical stimulation previously reported in people with CNS lesions.


SREDA: A Rare but Confusing Benign EEG Variant.
Subclinical rhythmic EEG discharges in adults (SREDA) is a very rare benign EEG pattern. The electrophysiological features and atypical variants of SREDA has wide spectrum and they are poorly known. It resembles ictal discharges, and overinterpretation of SREDA may lead to misdiagnosis of epilepsy. Herein, we aimed to report patients with SREDA to identify the frequency and characterized clinical, demographic, electrophysiological features. We reviewed 22,234 EEG reports that are reported by the same experienced clinical neurophysiologists, between 2012 and 2018. The EEGs with SREDA were reevaluated blindly by three clinical neurophysiologists. The demographic, clinical characteristics, and neuroimaging features of the patients were reviewed. Subclinical rhythmic EEG discharges in adults was present in 14 EEG records (0.06%), in nine patients. The mean age of patients was 52.1 ± 17.7 (range, 21-71) years. The patients had been diagnosed with several neurologic diseases, including cerebrovascular disease, epilepsy, psychogenic nonepileptic seizures, mental retardation, Alzheimer disease, and transient global amnesia. One patient had unilateral lesion, in whom SREDA had appeared on contralateral side of the lesion, whereas other patients with normal or nonlateralized lesions had SREDA bilaterally and symmetrical. This variant had been misdiagnosed as an ictal discharge in previous EEGs in three patients. This study indicates that SREDA is difficult to associate with any specific condition. The pathophysiology of SREDA can not be explained by a single mechanism. Even if it is mostly observed in older adults, it is also observed in young adults in this study. It is important to differentiate SREDA from ictal discharge to prevent misdiagnosis of epilepsy especially in nonepileptic paroxysmal events.


Characterization and in vivo distribution of influenza-virus-specific T-lymphocytes in the murine respiratory tract.
Cloned populations of antigen-specific, murine T-lymphocytes, maintained in long-term continuous culture, have been reported to exhibit functional activity upon adoptive transfer. Few data are currently available on the in vivo distribution of these homogeneous, functional cell populations. Such information is important to understanding the mechanisms by which T-lymphocytes exert their effector activity. We examined 2 cloned populations of influenza virus-specific T-lymphocytes. One clone was a Lyt-2+, L3T4-, class I MHC-restricted, cytolytic T-lymphocyte subset. The other clone was a Lyt-2-, L3T4+, Class II MHC-restricted clone of the helper/amplifier T-cell subset. Both clones promote recovery from lethal pulmonary influenza infection upon adoptive transfer. Using cell populations labeled with [3H]thymidine, we examined the distribution of these cells in tissue sections from various organs. These cloned cell populations were preferentially retained in the lungs of uninfected and influenza-virus-infected animals. This retention is independent of the cell's viral antigenic specificity, but may be dependent on the phenotype of the clone. Once retained in the lungs, these cells migrated across the bronchial lamina propria and entered the epithelium and pulmonary lumen. The significance of these observations for in vivo T-lymphocyte functions is discussed.


Antigenic population changes of Leptospira biflexa strains grown under the selective pressure of factorial antibodies.
Serovars jequitaia and tororò of Leptospira biflexa were cultured in the presence of homologous factor serum containing factorial antibodies (FcAbs) to their major antigens. After 39 serial passages they were then re-tested to determine whether their major antigens had remained unchanged. It was found that each parent strain had been replaced by an antigenic variant. The disappearance of each parent strain and its replacement by an antigenic variant was attributed to the selective conditions imposed by FcAbs. The antigenic variants behaved like true mutants. They lacked the major serovar antigens of the parent strains and had acquired some major antigens similar to those of two different serovars, one of which belonged to the same serogroup as the parent strain and the other to a different serogroup. A comparison of the major antigens of the parent strains with those of their antigenic variants indicated that factorial antibodies may be used selectively to obtain antigenic variants with a predefined pattern of major antigens.


On-Demand Fully Enclosed Superhydrophobic-Optofluidic Devices Enabled by Microstereolithography.
Superhydrophobic surface-based optofluidics have been introduced to biosensors and unconventional optics with unique advantages, such as low light loss and power consumption. However, most of these platforms were made with planar-like microstructures and nanostructures, which may cause bonding issues and result in significant waveguide loss. Here, we introduce a fully enclosed superhydrophobic-based optofluidics system, enabled by a one-step microstereolithography procedure. Various microstructured cladding designs with a feature size down to 100 μm were studied and a "T-type" overhang design exhibits the lowest optical loss, regardless of the excitation wavelength. Surprisingly, the optical loss of superhydrophobic-based optofluidics is not solely decided by the solid area fraction at the solid/water/air interface, but also the cross-section shape and the effective cladding layer composition. We show that this fully enclosed optofluidic system can be used for CRISPR-labeled quantum dot quantification, intended for in vitro and in vivo CRISPR therapeutics.


[Tuberculosis outbreak at a public school].
At school there are special circumstances of living together and a particular susceptibility, which favour the emergence of tuberculosis microepidemics. We report here the microepidemic occurred at a school among 9-year old children. After ruling out a possible familiar source in a child with pulmonary tuberculosis, we detected a case with high bacillar shedding in a female teacher and conducted a tuberculin search among children and teachers, initially outlining the theoretical groups at risk. Tuberculin positive children underwent chest-X-ray and when abnormalities were found, children were derived to the pediatrician for chemotherapy. All converters received secondary chemoprophylaxis and all non-respondents primary chemoprophylaxis. The classroom where the teacher spent most of het time had a higher rate of converters (70%) than other classroom, where the index teacher spent only a partial time (40%; RR: 1.75; CI: 1.06-2.88) or the collective of teachers (45.4%; RR: 1.45; CI: 0.94-2.23). Three additional cases of secondary disease were detected, all of them children. The initial compliance with chemoprophylaxis was greater among (for) children (97.0%) than among teachers (41.6%). Among children there was one case of tuberculin conversion compared with three cases among teachers. No additional cases were detected; also, an abnormal rate of reactors outside the initially studied groups was also not detected. Our results somehow agree with those reported from other school outbreaks. To note the anergy and lack of symptoms in the index case and the suggestion to delineate the degree of spending hours together to identify groups with a higher theoretical risk of being infected. Thus, an unnecessary expense of resources and a social alarm would be avoided.


Dithranol therapy in childhood psoriasis: unjustifiably on the verge of falling into oblivion.
In childhood psoriasis, physicians aim for an effective and safe treatment such as with dithranol. This study presents the largest study of dithranol-treated patients described in the literature. The aim of the study was to determine the position of dithranol in the treatment strategy for psoriasis. All juvenile patients receiving dithranol treatment at our center were evaluated retrospectively. Sixty patients (with 82 treatment episodes in total) were included. The mean age at the start of dithranol treatment was 11.1 years (range: 3.7-17.9 years). The result of the treatment was: excellent (3.7%), good (69.5%), moderate (8.5%), reasonable (13.4%) or disappointing (4.9%). Mild irritation was seen in 39%, and severe irritation in 63% of the patients. Dithranol can be regarded as an efficacious and safe topical therapy for the treatment of childhood psoriasis. It is a valuable alternative topical treatment which should not be disregarded in the treatment regimen for childhood psoriasis and should be commenced before ultraviolet or systemic treatments are initiated.


[Thrombophilia, venous thromboses and their treatment].
Thromboses are leading among causes of death worldwide. Arterial thromboses--the underlying cause of myocardial infarctions, strokes and acute ischemia--develop due to a defect of atherosclerotic plaque. Venous thromboses and associated venous thromboembolism killing one of 1000 world population develop in unaffected vascular wall. Recent data show that 70% cases of venous thromboembolism can be prevented by identification of thrombophilia markers--inheritable conditions associated with thromb formation. Current information on variants and prevalence of thrombophilia is given as well as recommendations on venous thromboembolism prevention.


Perceived parenting style, self-esteem and psychological distress in adolescents with heart disease.
The aim of the study was to assess the relationships between perceived parenting style, depressed mood, anxiety and self-esteem in adolescents with heart disease compared with healthy adolescents. Forty-five adolescents, aged 12-18 with congenital or acquired heart disease and 50 healthy age-matched adolescents answered perceived parental behaviour, self-esteem, depressed mood and anxiety questionnaires. The study group reported higher perceived acceptance and lower perceived parental control than healthy adolescents, but similar levels of depressed mood, anxiety and self-esteem. Fischer's r-to-z transformation and regression analyses showed different associations between perceived parenting style and depressed mood, anxiety and self esteem. In the study group, higher perceived parental acceptance was associated with lower depressed mood and higher self-esteem, whereas these associations were not significant in the control group. In the control, but not the study group, higher perceived parental control was associated with lower depressed mood and lower anxiety. Parenting style proved to exert a differential effect on adolescents with and without heart disease. For the former, perceived parental acceptance had a more substantial effect on psychological well-being than perceived parental control. Professionals caring for these adolescents should be aware of the special importance of parenting style on the well-being of adolescents with heart disease, and address this issue in the clinical setting with the patients and their parents.


The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.
Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions. Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge. We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs.


Risky migrations: Race, Latin eugenics, and Cold War development in the International Labor Organization's Puno-Tambopata project in Peru, 1930-60.
Histories of economic development during the Cold War do not typically consider connections to race science and eugenics. By contrast, this article historicizes the debates sparked by the International Labor Organization's Puno-Tambopata project in Peru and demonstrates how Cold War development practice shared common epistemological terrain with racial and eugenic thought from the Andes. The International Labor Organization project's goal of resettling indigenous groups from the Peruvian highlands to lower-lying tropical climates sparked heated debates about the biological specificity of Andean highlanders' physiques and ability to survive in the tropics. Such concerns betrayed the antitypological consensus expressed in the United Nations Educational, Scientific and Cultural Organization (UNESCO) Race Statements and defended by one of the main proponents of the resettlement project, the Swiss-American anthropologist Alfred Métraux. The concern with Andean racial types was central to the research agenda of the acclaimed Peruvian physiologist Carlos Monge, who endorsed modernization projects that did not entail moving highlanders outside of their traditional climate. The debates sparked by the Puno-Tambopata project demonstrate how Cold War development discourse grappled with racial and eugenic thought from Latin America and the Global South and thereby produced projects of indigenous "improvement."


Communication: minimum in the thermal conductivity of supercooled water: a computer simulation study.
We report the results of a computer simulation study of the thermodynamic properties and the thermal conductivity of supercooled water as a function of pressure and temperature using the TIP4P-2005 water model. The thermodynamic properties can be represented by a two-structure equation of state consistent with the presence of a liquid-liquid critical point in the supercooled region. Our simulations confirm the presence of a minimum in the thermal conductivity, not only at atmospheric pressure, as previously found for the TIP5P water model, but also at elevated pressures. This anomalous behavior of the thermal conductivity of supercooled water appears to be related to the maximum of the isothermal compressibility or the minimum of the speed of sound. However, the magnitudes of the simulated thermal conductivities are sensitive to the water model adopted and appear to be significantly larger than the experimental thermal conductivities of real water at low temperatures.


Uptake of dissolved free amino acids by the scleractinian coral Stylophora pistillata.
This study was designed to assess the importance of dissolved free amino acids (DFAA) as a nitrogen source for the scleractinian coral Stylophora pistillata. For this purpose, experiments were performed using (15)N-enriched DFAAs, and %(15)N enrichment was measured both in animal tissue and zooxanthellae at different DFAA concentrations, incubation time and light levels. As previously observed for urea, which is another source of organic nitrogen, DFAA uptake exhibited a biphasic mode consisting of an active carrier-mediated transport for concentrations below 3 micromol l(-1) and a linear uptake for higher concentrations. The value of the carrier affinity (K(m)=1.23 micromol l(-1) DFAA) indicated good adaptation of the corals to the low levels of DFAA concentrations measured in most oligotrophic waters. DFAA uptake was also correlated with light. The DFAA contribution to the nitrogen requirements for tissue growth was compared to the contribution of ammonia, nitrate and urea, for which uptake was also measured in S. pistillata. Inorganic sources (NH(4)(+) and NO(3)(-)) contributed 75% of the daily nitrogen needs against 24% for organic sources. Taken altogether, dissolved organic and inorganic nitrogen can supply almost 100% of the nitrogen needs for tissue growth.