The oral anticoagulants' burden
Oral anticoagulants generate a burden of care that can affect the patient's quality of life. The concept of treatment's burden measures the impact of medical care for the patient's quality of life. Various factors can exacerbate the burden. Several studies have assessed the satisfaction of patients treated with oral anticoagulants. This study has assessed the burden of patients treated with oral anticoagulants. An analytical cross-sectional study of patients recruited from pharmacies in the Loire. A questionnaire was carried out using the anti-clot treatment scale, assessing satisfaction, and the Zarit scale, assessing the burden on carers of demented patients. Anticoagulants were a burden for 41% (n = 158) of the 389 responding patients. Anticoagulants' burden was higher when oral anticoagulant was responsible for side effects, anxiety or lifestyle changes. The patients could be satisfied with the benefit of the treatment, satisfied with its practical modalities, and describe modifications of lifestyle habits contributing to the burden of the treatment.


The molecular basis of chemoradiosensitivity in rectal cancer: implications for personalized therapies.
Preoperative chemoradiotherapy represents the standard treatment for patients with locally advanced rectal cancer. Unfortunately, the response of individual tumors to multimodal treatment is not uniform and ranges from complete response to complete resistance. This poses a particular problem for patients with a priori resistant tumors because they may be exposed to irradiation and chemotherapy, treatment regimens that are both expensive and at times toxic, without benefit. Accordingly, there is a strong need to establish molecular biomarkers that predict the response of an individual patient's tumor to multimodal treatment and that indicate treatment-associated toxicities prior to therapy. Such biomarkers may guide clinicians in choosing the best possible treatment for each individual patient. In addition, these biomarkers could be used to identify novel molecular targets and thereby assist in implementing novel strategies to sensitize a priori resistant tumors to multimodal treatment regimens. The aim of this review is to summarize recent findings about the molecular basis of treatment resistance and treatment toxicity in patients with rectal cancer. Whole-genome, as well as single-biomarker or multibiomarker, analyses and their potential implications will be highlighted. At the end, we will outline a future vision of rectal cancer treatment in the era of personalized medicine.


BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway.
Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.


Factors associated with the development of blepharoptosis after pars plana vitrectomy surgery.
To determine the incidence and risk factors for developing blepharoptosis after vitrectomy surgery. This prospective observational study conducted in patients who had vitrectomy surgery at the University of California, San Francisco. The patients' eyelids were photographed before, surgery and follow-up visits at 1 day, 1 week, 1 month, 3 months, and 6 months after surgery. Levator excursion (LE), palpebral fissure (PF) height and marginal reflex distance 1 (MRD1) changes from baseline were evaluated. Operative parameters associated with lid parameter changes were analyzed. Thirty-eight eyes were enrolled in the study. Multivariate analysis performed for PF changes from pre-operative were -0.47 mm, 0.33 mm, and 0.09 mm at 1 week, 1 month and 6 months after surgery, respectively (p-value 0.1, 0.2, and 0.8). The mean change of LE from preoperative was -0.44 mm, -0.15 mm, and 0.35 mm at 1 week, 1 month and 6 months after surgery, respectively (p-value 0.3, 0.7 and 0.4). The reduction of MRD1 at 1 week, 1 month and 6 months after surgery were -0.08 mm, -0.13 mm and -0.01 mm, respectively (p = .003, p = .6 and 0.9). Triamcinolone usage was associated with reduction of MRD1 and LE. Blepharoptosis presents most during the first week after surgery. The possibility of developing transient changes in eyelid position after vitrectomy surgery should be discussed with patients.


[Compulsory treatment in psychiatry: an ethical analysis of the new legal regulations for clinical practice].
The new legal regulations of compulsory treatment in Germany require a change in clinical psychiatric practice as well as an ethical analysis of the consequences for those involved. The new legal regulations are reported and via ethical analysis new problematic fields, such as consequences of the new law are identified and discussed in the context of psychiatry and law. The main ethical identified problems are care of mentally ill with mental competence who refuse medical treatment, the different normative assessment of compulsory treatment and mechanical fixation, the ambivalent role of the conversation between psychiatrist and patient in order to change the natural will of the patient to avoid compulsory measures, the ethical consequences of questionable financial incentives in the context of compulsory treatment and the contradictive legal regulations in the field. The ethical analysis of the new law on compulsory treatment in Germany shows chances for improvement of clinical psychiatric practice as well as normative problematic regulations and fields of conflicts.


Prevention of amphetamine-induced behavioral hypersensitivity by concomitant treatment with microgram doses of apomorphine.
Behavioral hypersensitivity induced by subchronic administration of amphetamine in mice was inhibited by concomitant administration of apomorphine in microgram doses. Acutely, amphetamine followed in 15 min by apomorphine, produces a normal rise in locomotor activity subsequent to the action of amphetamine and an inhibition of that activity by the modulatory action of apomorphine. We suggest that apomorphine acts at a presynaptic neuronal site to interrupt the process(es) responsible for the development of stimulant-induced sensitization.


Need of improvement of diet and life habits among university student regardless of religion professed.
At present, few studies have assessed the possible influence of culture and religion on healthy eating habits among the university population. The aim of this study was to identify differences in healthy and eating habits among university students of different religions. A cross-sectional study was performed with a sample population of 257 students (22.4 ± 4.76 y) at the campus of the University of Granada in Melilla (Spain). The quality of diet was assessed by the Healthy Eating Index (HEI) and the adherence to the Mediterranean diet by a validated score (MDS). There were a higher prevalence of overweight in Christian boys and girls compared to Muslims. Muslim students omit breakfast and dinner more often than Christians. Significant differences in sodium intake (p < 0.001) were observed among boys of Christian and Muslim faith, with significantly higher intakes in Christians. In contrast, a higher cholesterol intake (p = 0.038) was observed in Muslim girls compared to Christians. Regarding alcohol intake, its consumption being much higher among students of Christian faith. Likewise, there were no significant differences in the quality of the diet as assessed by HEI, this being of poor, together with a low adherence to the Mediterranean diet in both groups. Muslim university students have a lower risk of drinking alcohol (OR = 7.88, 95% CI = 4.27, 14.54). Few differences were found between girls and boys in both religions although the Mediterranean Diet Score was lower for girls. In conclusion, Melilla university students eat low quality foods and have little adherence to the Mediterranean diet regardless of the religion professed or gender, although Christians tend to drink more alcohol and to smoke more cigarettes and Muslims skip some meals.


Development of intrinsic electrophysiological properties in neurons from the gustatory region of rat nucleus of solitary tract.
There is no current understanding of the nature or time course of maturation of intrinsic electrophysiological properties for neurons in the gustatory region of the nucleus of the solitary tract (NST). Therefore, we used whole cell recordings in an in vitro slice preparation of the rat brainstem to characterize development of resting membrane, action potential and repetitive discharge properties of cells in gustatory NST at postnatal days 5, 10, 15, 20, and 30, and adult ages. Neurons were filled with Biocytin to verify location and characterize morphology. Membranes from younger neurons demonstrated a steeper current-voltage relation or higher input resistance, and a longer time constant than mature cells. Action potentials in younger cells had a slower rate of rise and were longer in duration. The afterhyperpolarization that typically follows the spike discharge usually had one phase in younger neurons, but was characterized by two or more phases in an increasing proportion of older cells. The repetitive discharge frequency in response to a range of depolarizing current pulses increased during development, and frequency/current plots were steeper in older compared with younger neurons. However, in all age groups there was clear accommodation of the discharge frequency. The greatest changes in resting membrane, action potential, and discharge properties were observed between P5 and P15, and mature values were generally reached by P20. At each postnatal age, neurons could be categorized in four neuron groups, based on the discharge pattern in response to a hyperpolarizing/depolarizing current protocol. Anatomical reconstructions indicated that although cells increased in overall dendritic expanse during development, neurons became less complex as illustrated by decreases in number of dendritic branch points, and in number and density of spines. The timing of major developmental differences in intrinsic electrical characteristics observed here is associated with a period of previously reported maturational changes in extracellular taste responses to number and concentration of chemical stimuli. However, further alterations in extracellular taste responses proceed after apparent maturation of intrinsic neural properties.


Estimating the social cost of respiratory cancer cases attributable to occupational exposures in France.
The objective of this article was to estimate the social cost of respiratory cancer cases attributable to occupational risk factors in France in 2010. According to the attributable fraction method and based on available epidemiological data from the literature, we estimated the number of respiratory cancer cases due to each identified risk factor. We used the cost-of-illness method with a prevalence-based approach. We took into account the direct and indirect costs. We estimated the cost of production losses due to morbidity (absenteeism and presenteeism) and mortality costs (years of production losses) in the market and nonmarket spheres. The social cost of lung, larynx, sinonasal and mesothelioma cancer caused by exposure to asbestos, chromium, diesel engine exhaust, paint, crystalline silica, wood and leather dust in France in 2010 were estimated at between 917 and 2,181 million euros. Between 795 and 2,011 million euros (87-92%) of total costs were due to lung cancer alone. Asbestos was by far the risk factor representing the greatest cost to French society in 2010 at between 531 and 1,538 million euros (58-71%), ahead of diesel engine exhaust, representing an estimated social cost of between 233 and 336 million euros, and crystalline silica (119-229 million euros). Indirect costs represented about 66% of total costs. Our assessment shows the magnitude of the economic impact of occupational respiratory cancers. It allows comparisons between countries and provides valuable information for policy-makers responsible for defining public health priorities.


A nonsurgical approach to the management of primary vesicoureteral reflux.
We performed a retrospective review to evaluate the results of a nonsurgical approach to the management of primary vesicoureteral reflux during a 10-year period (1976 to 1986). During that interval patients with reflux were studied initially with a standard voiding cystourethrogram and either an excretory urogram or a renal scan with glomerular filtration rate and/or differential renal function determination. Height, weight, blood pressure, urine cultures and serum creatinine measurements also were obtained. Isotope cystography was used for followup examinations. A single, negative isotope cystogram was the radiological criterion for cessation of reflux. The charts of 545 children (55 per cent had bilateral reflux) with 844 refluxing ureters were reviewed. Based upon the international classification vesicoureteral reflux was grade I in 6.6 per cent of the cases, grade II in 54.2 per cent, grade III in 31.6 per cent, grade IV in 5.7 per cent and grade V in 1.9 per cent. All children were kept on long-term continuous prophylactic antibiotics and they were re-evaluated annually with isotope cystography. The followup rate for the entire group was 88 per cent. During the observation period spontaneous resolution of reflux was noted in 36 per cent of the patients and 39 per cent of the total refluxing ureters. Only 13 per cent of the entire group underwent surgical correction of reflux. Presently, 39 per cent (215) of the patients continue to be followed with reflux. Of the total group 66 patients (12 per cent) were lost to followup. In the 194 patients with spontaneous resolution of reflux the mean duration of reflux was 1.69 years, with 30 to 35 per cent resolving each year. Based on Student's t test there was a significant difference in duration of reflux in patients with grade II compared to grade III reflux (1.56 versus 1.97 years, p less than 0.04). When age at presentation was compared with duration of reflux there was a significantly shorter duration of reflux only in those patients presenting from age 0 to 12 months, compared to those 13 months and older (1.44 versus 1.85 years, p less than 0.02). Renal function was evaluated by serum creatinine, calculated glomerular filtration rate or differential diethylenetriaminepentaacetic acid scan results.(ABSTRACT TRUNCATED AT 400 WORDS)


Brainstem auditory evoked response in HIV-infected patients with and without AIDS.
The purpose of this paper is to determine the type and frequency of brainstem auditory evoked potential abnormalities in HIV-infected patients with and without acquired immune deficiency syndrome (AIDS). Brainstem auditory evoked potentials were performed in 44 HIV-infected patients; 22 of these patients were asymptomatic carriers and 22 presented clinical manifestation of AIDS at the time of the study. Twenty healthy young adults were studied as controls. When brainstem auditory evoked potentials were performed, none of the HIV-infected patients had neurologic clinical findings. The interwave intervals I-V showed significant differences (p <0.05) between both HIV-infected groups and the control group. There were non-significant differences between the two groups including HIV-infected patients with or without clinical features of AIDS. It is concluded that the HIV infection may produce subclinical pathologic changes in the cochlear nerve and brainstem, which can be detected by BAEP test.


Flyash augmented Fe3O4 as a heterogeneous catalyst for degradation of stabilized landfill leachate in Fenton process.
In this study magnetite (Fe3O4) was augmented over coal flyash and analyzed for the effectiveness as a catalyst in heterogeneous Fenton process for the degradation of persistent organic pollutant present in stabilized landfill leachate. Fe3O4 and flyash augmented Fe3O4 was prepared by simple chemical precipitation method and both had magnetic nature. XRD, FTIR and SEM with EDX characterization were consummated for both catalysts. The Fenton experiments were performed in batch mode and to identify the optimal operating condition for effective COD removal the leachate pH, catalysts and H2O2 dosages were varied. The reusability of the catalysts was studied. To understand the degradation mechanism adsorption study, Fenton oxidation of benzoic acid and scavenging experiments with KI and NaF were performed. It was witnessed that flyash augmented Fe3O4 exhibited 84.7% of COD degradation which was 12.3% of higher removal efficiency than Fe3O4 at optimum pH 3, 0.05 M H2O2 and 1000 mg/L of catalyst dosage in 100 min reaction time. This flyash augmented Fe3O4 showed 68% of TOC removal and good increment in biodegradability. Poor NH3-N removal was observed in the Fenton treatment process. Decrease in aromaticity was found based on SUVA254 value and also indicated the removal of organic matter. Similarly, reusability and stability were higher than Fe3O4. The results indicate that flyash augmented Fe3O4 is a competent catalyst in heterogeneous Fenton process for treatment of mature leachate. The usage of waste material flyash with Fe3O4 decreases the co-aggregation of Fe3O4 and improves the catalytic performance.


Effect of riboflavin supplementation on zinc and iron absorption and growth performance in mice.
Diets prevalent in vegetarian populations using rice and other whole grains as staples with little consumption of yellow vegetables are low in riboflavin. These diets have poor bioavailability of iron and zinc because metals are present as inorganic salts with low solubility. Riboflavin has the capacity to form complexes, and supplementation of riboflavin may result in increased absorption of zinc and iron, thus increasing the cellular transport. Therefore, riboflavin may have direct as well as indirect effects on growth. Using this as the conceptual basis, experiments were conducted on pregnant and lactating mice. Two groups, each of 12 mice (9 females and 3 males), were observed on a low-riboflavin rice-based diet (adequate in all other nutrients), one with and one without supplementation of 10 mg riboflavin/kg diet. There was significant improvement in the growth parameters like percent conception, mean weight gain in pregnancy, mean weight of pups at the age of 21 d, and percentage hemoglobin due to riboflavin supplementation (p < 0.05). Percent zinc absorption, for the low-riboflavin diet, the supplemented diet, and the synthetic control diet were 16.4+/-5.7, 33.7+/-8.9, and 44.6+/-4.0, respectively, indicating the beneficial effect of riboflavin supplementation on iron and zinc utilization.


Student Outcomes Associated with an Interprofessional Program Incorporating TeamSTEPPS®.
Interprofessional education (IPE) of health professions students is a starting point for developing collaborative-practice-ready healthcare professionals, ultimately leading to improved patient care. The purpose of this study was to develop and evaluate a novel, foundational, IPE pilot program that incorporates TeamSTEPPS® for health professions students. Students representing 13 different health professions programs participated in successive Level 1 and Level 2 "Foundations of Interprofessional Collaboration: Introduction to TeamSTEPPS®" half-day activities (n = 241). Students' satisfaction with the pilot program, changes in attitudes toward teamwork from before to after participation, TeamSTEPPS® knowledge acquisition, and anticipated future interprofessional collaboration-oriented behavior change were assessed through online surveys. Overall, students were highly satisfied with the pilot program and reported that learning from other professions was valuable. Statistically significant positive changes were noted in attitudes toward teamwork, most notably with the Level 1 pilot. Greater than 80% of students who completed the surveys demonstrated acquisition of TeamSTEPPS® knowledge. Students also reported feeling more prepared to collaborate interprofessionally in their future practice. This study demonstrated that the two-level foundational pilot program is feasible and had the intended effects with regards to moving health professions students toward becoming collaborative-practice-ready healthcare professionals.


Clinical longitudinal standards for height and height velocity for North American children.
Longitudinally-based height and height velocity charts for North American children are presented. Centiles are given for early, middle, and late maturers. The shape of the curves is taken from a review of longitudinal studies, and the prepubertal and adult centiles for height attained are taken from National Center for Health Statistics data. The charts are suitable for following an individual child's progress during observation or treatment throughout the growth period, including puberty.


Integrated genomic and DNA methylation analysis of patients with advanced non-small cell lung cancer with brain metastases.
Brain metastasis is a common and lethal complication of non-small cell lung cancer (NSCLC). It is mostly diagnosed only after symptoms develop, at which point very few treatment options are available. Therefore, patients who have an increased risk of developing brain metastasis need to be identified early. Our study aimed to identify genomic and epigenomic biomarkers for predicting brain metastasis risk in NSCLC patients. Paired primary lung tumor tissues and either brain metastatic tissues or cerebrospinal fluid (CSF) samples were collected from 29 patients with treatment-naïve advanced NSCLC with central nervous system (CNS) metastases. A control group comprising 31 patients with advanced NSCLC who died without ever developing CNS metastasis was also included. Somatic mutations and DNA methylation levels were examined through capture-based targeted sequencing with a 520-gene panel and targeted bisulfite sequencing with an 80,672 CpG panel. Compared to primary lung lesions, brain metastatic tissues harbored numerous unique copy number variations. The tumor mutational burden was comparable between brain metastatic tissue (P = 0.168)/CSF (P = 0.445) and their paired primary lung tumor samples. Kelch-like ECH-associated protein (KEAP1) mutations were detected in primary lung tumor and brain metastatic tissue samples of patients with brain metastasis. KEAP1 mutation rate was significantly higher in patients with brain metastasis than those without (P = 0.031). DNA methylation analysis revealed 15 differentially methylated blocks between primary lung tumors of patients with and without CNS metastasis. A brain metastasis risk prediction model based on these 15 differentially methylated blocks had an area under the curve of 0.94, with 87.1% sensitivity and 82.8% specificity. Our analyses revealed 15 differentially methylated blocks in primary lung tumor tissues, which can differentiate patients with and without CNS metastasis. These differentially methylated blocks may serve as predictive biomarkers for the risk of developing CNS metastasis in NSCLC. Additional larger studies are needed to validate the predictive value of these markers.


Vaginorectal Streptococcus porcinus in pregnancy: an emerging pathogen?
Streptococcus porcinus has previously been isolated from the genitourinary tract of reproductive-aged women. However, very little is known about the pathogenicity of this microorganism in pregnancy. The study aimed to report pregnancies complicated by vaginorectal S. porcinus and associated adverse outcomes. We present 2 patients with 3 pregnancies complicated by vaginorectal S. porcinus and preterm cervical change. The first patient lost a twin pregnancy to previable preterm rupture of membranes. During her subsequent pregnancy, again positive for S. porcinus, cervical shortening prompted antibiotic treatment and cerclage. The second patient delivered preterm despite cerclage placed for sonographic indications. Our cases suggest that S. porcinus may contribute to the pathogenesis of preterm rupture of membranes and cervical insufficiency.


Exosomes Derived from Endothelial Cells Inhibit Neointimal Hyperplasia Induced by Carotid Artery Injury in Rats via ROS-NLRP3 Inflammasome Pathway.
This study attempted to investigate whether exosomes derived from rat endothelial cells (EC-Exo) attenuate intimal hyperplasia after balloon injury using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence staining, Evans blue staining, and Western blotting. The results indicated that EC-Exo inhibited intimal hyperplasia in the carotid artery after balloon injury, promoted re-endothelialization, and reduced vascular inflammation and ROS-NLRP3-mediated cell pyroptosis. Thus, EC-Exo can inhibit neointimal hyperplasia after carotid artery injury in rats presumably by inhibiting the ROS-NLRP3 inflammasome and phenotypic transformation of vascular smooth muscle cells.


Outcomes of tongue-pressure strength and accuracy training for dysphagia following acquired brain injury.
The purpose of this study was to measure treatment outcomes in a group of six adults with chronic dysphagia following acquired brain injury, who each completed 24 sessions of tongue-pressure resistance training, over a total of 11-12 weeks. The treatment protocol emphasized both strength and accuracy. Biofeedback was provided using the Iowa Oral Performance Instrument. Amplitude accuracy targets were set between 20-90% of the patient's maximum isometric pressure capacity. Single subject methods were used to track changes in tongue strength (maximum isometric pressures), with functional swallowing outcomes measured using blinded ratings of a standard pre- and post-treatment videofluoroscopy protocol. Improvements were seen in post-treatment measures of tongue pressure and penetration-aspiration. No improvements were seen in pharyngeal residues, indeed worsening residue was seen in some patients.


Offspring preterm birth and birth size are related to long-term risk of maternal diabetes.
The aim of the study is to investigate the association between gestational age, birth size, and the long-term risk of maternal diabetes. We conducted a nation-wide prospective follow-up study of the cohort of all Danish women with a singleton delivery in 1982/1983 (index delivery) and no history of diabetes (n = 100,669). Registries were used to extract information on patients with a hospital or outpatient diagnosis of diabetes, subsequent deliveries, and death/emigration in the period from the index delivery until the end of 2006. The association between the maternal risk of diabetes and the index gestational age and index offspring birth size (birth weight adjusted for gestational age) was investigated by using Cox proportional hazards regression models stratified according to young (≤33 years) and old age (>33 years). During a median follow-up period of 24 years, 2,021 women (2.0 %) were diagnosed as having diabetes. The risk of maternal diabetes was positively associated with increasing index birth size and negatively associated with increasing duration of index gestation in both age strata. Among young women, the highest hazard ratios were found for the exposure category of large index offspring birth size (adjusted HR 9.0, 95 % CI 6.17-13.12) and a preterm delivery at 32-37 weeks (adjusted HR 2.22, 95 % CI 1.46-3.40). Offspring preterm birth and large size for gestational age at birth are associated with increased risk of maternal diabetes.


High recurrence rate of lymphadenitis due to nontuberculous mycobacteria and its association with concurrent Salmonella infection in Taiwan.
The objective of this study is to investigate the clinical characteristics of lymphadenitis due to nontuberculous mycobacteria (NTM) in Taiwan. We retrospectively reviewed the medical records of all patients who presented to the National Taiwan University Hospital with culture-positive NTM lymphadenitis during the period 2000-2010. Patients with concurrent extranodal involvement were excluded. From 2000 to 2010, 15 patients with lymphadenitis caused by nontuberculous mycobacteria were identified. Most patients (80%, n = 12) were infected with rapidly growing mycobacteria. Mycobacterium abscessus was the most common infective species (n = 8). Recurrence of infection involving multiple organs occurred 2-7 years after the completion of treatment in 11 (73%) patients. Five (33.3%) patients had concurrent Salmonella infections (4 patients with bacteremia and 1 patient with empyema thoracis) during the course of the disease. In Taiwanese patients, we found a high recurrence rate of NTM lymphadenitis that was closely associated with Salmonella infections. We also noted that the clinical and epidemiological manifestations of NTM lymphadenitis in Taiwan differed from their manifestations in western countries.


Intravascular Lithotripsy Enabled Transfemoral Transcatheter Aortic Valve Implantation via Percutaneous Axillary Access Approach.
Transfemoral (TF) access for transcatheter aortic valve implantation (TAVI) is the most commonly used site, however its use may be limited by prohibitive peripheral arterial disease. Although a number of alternative access techniques have been well described, each has been shown to be associated with increased risks when compared to a TF approach. Recently, planned treatment of iliofemoral artery disease using intravascular lithotripsy (IVL) has emerged as a means of preserving TF access. Ipsilateral or contralateral femoral artery access has been routinely used to perform IVL but its use may be limited in certain conditions. Here we describe the novel technique of using percutaneous axillary artery access to perform IVL of iliofemoral artery to facilitate its use for large bore access. We present a 78-year-old high surgical risk female with severe aortic stenosis who was found to have a prior stent in the contralateral iliac artery protruding into the aorta which limited a traditional 'up and over' approach, and thus axillary artery access was used to perform IVL. This is the first case in literature to describe the use of percutaneous axillary access to perform IVL of the iliac and common femoral artery to facilitate TF TAVI. Based on our previous experience we feel this technique holds promise for a routine use when use of other access sites is limited.


The extracranial portion of the pineal complex of the frog (frontal organ) is connected to the pineal, the hypothalamus, the brain stem and the retina.
The central connections of the frontal organ of the frog Rana esculenta were studied by means of the cobalt-filling technique using the cobaltic lysine complex. The results showed that the frontal organ has surprisingly more extended connections than those demonstrated after the application of other techniques. In fact, we found that it is connected to the pineal, the hypothalamus, the brain stem and the retina. These connections, which neuroanatomically have not been reported before, suggest that the frontal organ of the frog participates, in some way, in several different functions, such as neuroendocrine activities, motor responses and lateral eyes photoreception interaction.


A predictive model for increased hospital length of stay following geriatric hip fracture.
The purpose of this study was to identify the risk factors that are significantly associated with hospital length of stay (LOS) following geriatric hip fracture and to use these significant variables to develop a LOS calculator. This was a retrospective study examining 614 patients treated for geriatric hip fracture between January 2000 and December 2009 at an urban, Level 1 trauma center. A negative binomial regression analysis was used to identify perioperative variables associated with hospital LOS. 614 patients met the inclusion criteria, presenting with a mean age of 78 (±10) years. The most common pre-operative comorbidity was hypertension, followed by diabetes and COPD. After controlling for all collected comorbidities as well as demographics and operative variables, hypertension (IRR: 1.10, p = 0.029) and disseminated cancer (IRR: 1.24, p = 0.007) were found to be significantly associated with LOS. In addition, two demographic/presenting variables, admission to the medicine service (IRR: 1.48, p < 0.001) and male sex (IRR: 1.09, p = 0.034), were shown to be independent risk factors for prolonged LOS. These variables were synthesized into a LOS formula, which estimated LOS to within 3 days of the true length of stay for 0.758 of the series (95% confidence interval: 0.661 to 0.855). This study identified several comorbidity and perioperative variables that were significantly associated with LOS following geriatric hip fracture surgery. The resulting LOS model may have utility in the risk stratification of orthopaedic trauma patients presenting with hip fracture.


[Osteoradionecrosis and dental implants].
Osteoradionecrosis (ORN) is a severe complication of radiation therapy (RT). A triggering factor is frequently present. It is often a dental, periodental, or surgical traumatism. We report the case of a bilateral ORN: the first lesion appeared 3months after the end of RT around the osteosynthesis plate and was treated by mandibular resection. The second lesion appeared 40months after RT on the opposite side, due to peri-implantitis. Dental implants had been inserted 10years before cancer therapy. No case of ORN in post-implantation RT had been previously reported. A 75-year-old woman was admitted for a squamous cell carcinoma of the right cheek extending to the intermaxillary commissure, the maxillary tuberosity, the soft palate, the lingual junction, and the vestibule up to the second premolar area. There was no suspicious lymph node. She had undergone dental implant procedure 15 and 10 years before, respectively, one in the second premolar position of the right maxilla and four in the premolar and molar left mandible area. All of them were osseo-integrated and charged. A trans-mandibular buccopharyngectomy with modified radical neck dissection was performed, completed by RT. The total dose of irradiation was 65Gy in the oral cavity and 45Gy on cervical and supraclavicular areas. Delayed mucosal healing was observed on the right mandible and ORN appeared in this area 3months after the end of irradiation. Mandibular resection was necessary. Later, the right maxillary implant was lost, and multiple dental extractions were required. Forty months after RT, peri-implantitis was observed on the left side of the mandible, complicated by ORN and pathological fracture. No surgical reconstruction could be performed because of the patient's age and state. The patient was carrying a complete removable maxillary prosthesis on latest follow-up. This was the first case of ORN on dental implants placed before RT. RT is a risk factor of implant failure, a relatively rare and unpredictable event. Most often, it causes implant loss and exceptionally ORN. In our case, ORN was bilateral. The first lesion was probably due to surgical trauma. The second one, on the opposite side, was caused by peri-implantitis. Irradiation overdose on the alveolar mandibular ridge, close to the implant, may have been the cause. In our case, there was no severe pain, and slow evolution led to a pathological fracture.


Effects of ouabain on contractile response to norepinephrine in isolated rat aorta.
1. Inhibition of sodium(Na+), potassium(K+)-ATPase activity was dependent on the concentration of ouabain and inverse to the concentration of potassium ([K+]) in the reaction mixture. 2. Contractility of isolated rat aorta preparation in response to norepinephrine was augmented by ouabain and low [K+]. 3. Results suggest that inhibition of Na+,K(+)-ATPase activity will be correlated with augmentation of vascular contractility maybe through activation of Na(+)-calcium exchange system.


Evaluation of two-point Dixon water-fat separation for liver specific contrast-enhanced assessment of liver maximum capacity.
Gadoxetic acid-enhanced magnetic resonance imaging has become a useful tool for quantitative evaluation of liver capacity. We report on the importance of intrahepatic fat on gadoxetic acid-supported T1 mapping for estimation of liver maximum capacity, assessed by the realtime 13C-methacetin breathing test (13C-MBT). For T1 relaxometry, we used a respective T1-weighted sequence with two-point Dixon water-fat separation and various flip angles. Both T1 maps of the in-phase component without fat separation (T1_in) and T1 maps merely based on the water component (T1_W) were generated, and respective reduction rates of the T1 relaxation time (rrT1) were evaluated. A steady considerable decline in rrT1 with progressive reduction of liver function could be observed for both T1_in and T1_W (p < 0.001). When patients were subdivided into 3 different categories of 13C-MBT readouts, the groups could be significantly differentiated by their rrT1_in and rrT1_W values (p < 0.005). In a simple correlation model of 13C-MBT values with T1_inpost (r = 0.556; p < 0.001), T1_Wpost (r = 0.557; p < 0.001), rrT1_in (r = 0.711; p < 0.001) and rrT1_W (r = 0.751; p < 0.001), a log-linear correlation has been shown. Liver maximum capacity measured with 13C-MBT can be determined more precisely from gadoxetic acid-supported T1 mapping when intrahepatic fat is taken into account. Here, T1_W maps are shown to be significantly superior to T1_in maps without separation of fat.


No significant relationship exists between tumor size and prognosis in distant metastatic hepatocellular carcinoma: a propensity score matching analysis based on SEER database.
Previous studies have shown that tumor size has an impact on the prognosis of hepatocellular carcinoma (HCC). Whether tumor size is related to the prognosis of distant metastatic HCC is unclear. The purpose of this study was to investigate the effect of tumor size on the prognosis of distant metastatic HCC. Data on patients with HCC were collected from the (SEER) database of surveillance, epidemiology and final results. Propensity score matching (PSM) was used to reduce confounding factors and comprehensively evaluate the clinicopathological features and prognosis of distant metastatic HCC. There were 189 patients with distant metastatic HCC whose tumor size was ≤ 50 mm and 615 patients with a tumor size > 50 mm. The tumor sizes of distant metastatic HCC patients were associated with race, grade, surgical treatment, N and AFP. The Kaplan-Meier analysis showed that the mortality rate of patients with a tumor size > 50 mm was higher than that of patients with a tumor size ≤ 50 mm (p = 0.00062). However, there were no significant differences in mortality rates after adjusting for confounding variables by using propensity score matching (p = 0.23). This propensity score matching study provides the best data in support of the following assertions: tumor size is not an independent prognostic factor for distant metastatic HCC.


Bone marrow infiltration in hairy cell leukemia after interferon therapy detected by magnetic resonance imaging.
Magnetic resonance imaging (MRI) can detect bone marrow infiltration by neoplastic cells in many hematological malignancies. We studied 10 patients affected by hairy cell leukemia (HCL) and treated with interferon (IFN) with both MRI and bone marrow biopsy. T1-weighted MR scans of femurs and pelvis proved to be effective to score hairy cell infiltration, while less information was obtained from the study of the lumbar vertebral column. A good correlation (less than 10% difference) was noted between biopsy and MRI in over 90% of cases. MR scans showed, in general, a higher grade of infiltration. MR scan, however, can be useful for monitoring the course of HCL and the response to the treatment. Moreover, MRI evaluating a large amount of tissue, can detect a nodular type of infiltration which can be missed in biopsy specimens.


Integrated Two-Analyte Population Pharmacokinetic Model of Polatuzumab Vedotin in Patients With Non-Hodgkin Lymphoma.
A two-analyte integrated population pharmacokinetic (PK) model that simultaneously describes concentrations of antibody-conjugated monomethyl auristatin E (acMMAE) and unconjugated MMAE following repeated administrations of polatuzumab vedotin (pola) was developed based on data from four clinical studies of pola in patients with non-Hodgkin lymphoma. A two-compartment model with a nonspecific, time-dependent linear clearance, a linear time-dependent exponentially declining clearance, and a Michaelis-Menten clearance provided a good fit of the acMMAE plasma PK profiles. All three acMMAE elimination pathways contributed to the input to the central compartment of unconjugated MMAE, which was also described by a two-compartment model. Population PK parameters, covariate effects, and interindividual variability of model parameters were estimated. The impact of clinically relevant covariates on PK exposures of each analyte were quantified and reported to support key label claims.


Differential modulations of striatal tyrosine hydroxylase and dopamine metabolism by cannabinoid agonists as evidence for functional selectivity in vivo.
It is generally assumed that cannabinoids induce transient modulations of dopamine transmission through indirect regulation of its release. However, we previously described a direct cannabinoid-mediated control of tyrosine hydroxylase (TH) expression, in vitro. We herein report on the influence of cannabinoid agonists on the expression of this key enzyme in catecholamine synthesis as well as on the modification of dopamine content in adult rats. As expected for cannabinoid agonists, the exposure to either Δ(9)-THC, HU 210 or CP 55,940 induced both catalepsy and hypolocomotion. Supporting a possible long-lasting control on dopaminergic activity, we noticed a significant HU 210-mediated increase in TH expression in the striatum that was concomitant with an increase in striatal dopamine content. Surprisingly, while a similar trend was reported with Δ(9)-THC, CP 55,940 completely failed to modulate TH expression or dopamine content. Nevertheless, the access of CP 55,940 to brain structures was validated by determinations of drug concentrations in the tissue and by ex vivo binding experiments. Furthermore, confirming the central activity of CP 55,940, the analysis of dopamine metabolites revealed a reduction in striatal DOPAC concentrations. Consistent with the involvement of the CB(1) cannabinoid receptor in these different responses, both HU 210- and CP 55,940-mediated effects were prevented by SR 141716A. Therefore, the present data suggest that both HU 210 and CP 55,940 cause a delayed/persistent regulation of the dopamine neurotransmission system. Nevertheless, these commonly used cannabinoid agonists endowed with similar pharmacodynamic properties clearly triggered distinct biochemical responses highlighting the existence of functional selectivity in vivo.


Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target.
Sirtuin 1 (SIRT1), originally identified as a longevity gene, is induced by caloric restriction, and regulates various cellular functions including DNA repair, cell survival and metabolism via the deacetylation of target proteins such as histone and p53. These functions are considered to act dualistically as preventing or facilitating cancer. This study aimed to clarify the expression and role of SIRT1 in endometrial carcinoma. Because a high-calorie diet was a well-known risk factor for endometrial carcinoma, we first hypothesized that SIRT1 might be downregulated in normal endometrial glandular cells of obese women. However, no correlation was observed between the expression of SIRT1 and body mass index (BMI). In contrast, regardless of BMI, the immunohistochemical expression of SIRT1 was significantly higher in endometrial carcinoma (108 cases) than in normal endometria (60 cases) (P<0.05), and its overexpression was associated with a shorter survival (P<0.05). Our experiments in vivo revealed that SIRT1 accelerated the proliferation of endometrial carcinoma cell lines (HHUA, HEC151, and HEC1B). SIRT1 overexpression significantly enhanced the resistance for cisplatin and paclitaxel in HHUA cells. Although p53 is an important target protein for SIRT1, the selective SIRT1 inhibitor (EX527) significantly suppressed the proliferation and cisplatin resistance of three endometrial carcinoma cell lines regardless of the p53 mutation status. In addition, SIRT1 overexpression in HHUA cells accelerated tumor growth and cisplatin resistance in nude mice, and EX527 significantly suppressed the growth of tumors of HHUA and HEC1B cells. No adverse effect of EX527 was observed in these mice. In conclusion, SIRT1 is involved in the acquisition of the aggressive behavior associated with endometrial carcinoma, and the SIRT1 inhibitor, EX527, may be a useful agent for the treatment of this malignancy.


F3/Contactin acts as a modulator of neurogenesis during cerebral cortex development.
The expression of the cell recognition molecule F3/Contactin (CNTN1) is generally associated with the functions of post-mitotic neurons. In the embryonic cortex, however, we find it expressed by proliferating ventricular zone (VZ) precursors. In contrast to previous findings in the developing cerebellum, F3/Contactin transgenic overexpression in the early cortical VZ promotes proliferation and expands the precursor pool at the expense of neurogenesis. At later stages, when F3/Contactin levels subside, however, neurogenesis resumes, suggesting that F3/Contactin expression in the VZ is inversely related to neurogenesis and plays a role in a feedback control mechanism, regulating the orderly progression of cortical development. The modified F3/Contactin profile therefore results in delayed corticogenesis, as judged by downregulation in upper and lower layer marker expression and by BrdU birth dating, indicating that, in this transgenic model, increased F3/Contactin levels counteract neuronal precursor commitment. These effects also occur in primary cultures and are reproduced by addition of an F3/Fc fusion protein to wild type cultures. Together, these data indicate a completely novel function for F3/Contactin. Parallel changes in the generation of the Notch Intracellular Domain and in the expression of the Hes-1 transcription factor indicate that activation of the Notch pathway plays a role in this phenotype, consistent with previous in vitro reports that F3/Contactin is a Notch1 ligand.


[Influence of Patients' Profession on Therapeutical Outcome of Patients with Primary Extrinsic Shoulder Impingement].
Shoulder complaints are an important reason for inability to work. There are few considerations that link the effect of kind of therapy with ability to work in connection with kind of employment. This prospective, comparative clinical follow-up study examines the influence of occupational activity with conservative and operative therapy on the outcome of therapy in terms of function, pain and ability to work. In this study, 97 patients (women: n=22, men: n=75, mean age: 43.1±10.1 years) with a primary extrinsic shoulder impingement syndrome were included. Patients were divided into blue and white collar workers. Further on the subgroups of conservative and operative therapy were considered. Either a sole conservative therapy or an operative therapy with physiotherapeutic follow-up treatment took place. The conservative therapy was carried out as a structured re-coordination of muscles of the shoulder girdle under supervision of a physiotherapist. In the surgical cohorts an arthroscopic subacromial decompression was performed. Follow-up examinations were passed 3, 6 and 12 months after starting the intervention. Function (Constant Score), pain (NRS) and the duration of inability to work were assessed. The statistical analysis was performed using mixed-design ANOVA to calculate main effect and interactions (therapy*kind of employment*time) adjusted with age, sex and body mass index. There was no statistically significant difference in terms of function and pain between blue and white collar workers. Office workers showed a significantly longer inability to work 3 months after surgical treatment compared with conservative treatment (7.3±0.8 weeks vs. 0.5±7.3 weeks; p<0.001). Further the group of white collars with operative therapy was significantly longer inable to work than the group of blue collar workers after operative therapy 3 months after surgical treatment (3.0±1.1 weeks vs. 7.3±0.8 weeks; p=0.002). On the one hand, working in an office could be seen as a negative predictor for durance of inability to work. On the other hand, surgical treatment itself was a negative predictor for the durance of inability to work. Furthermore, no difference between conservative and surgical therapy could be observed in function and pain one year after starting the treatment.


An electrochemical paper-based hydrogel immunosensor to monitor serum cytokine for predicting the severity of COVID-19 patients.
Analysis of cytokines levels in human serum is critical as it can be a "symptom diagnostic biomarker" in COVID-19, giving real-time information about human health status. Here, we present the construction and performance of a low-price immunosensor (∼US$0.428 per test) based on microfluidic paper-based system to detect cytokine for predicting the health status of COVID-19 patients. Interleukin-6 (IL-6) was selected as the detection model for the close relationship between IL-6 and COVID-19. The assay, which we integrated into foldable paper system, leverages the magnetic immunoassay, the streptavidin-horseradish peroxidase (HRP) associated with tetramethyl benzidine/hydrogen peroxide (TMB/H2O2) to amplify the signal for electrochemical readout. To improve the sensitivity of cytokine detection, a hybrid of gold nanoparticles (AuNPs) and polypyrrole (PPy) hydrogel was modified on the working electrode to increase the conductivity and improve the electron transfer rate. With our prototypic origami paper-based immunosensor operated in differential pulse voltammetry (DPV) mode, we achieved excellent results with a dynamic range from 5 to 1000 pg/mL and a lower detection limit (LOD) of 0.654 pg/mL. Furthermore, we evaluated the capability of the clinical application of the proposed immunosensor using human serum samples from a hospital. The results indicate that our proposed immunosensor has great potential in early diagnosing high-risk COVID-19 patients.


Interplay between EZH2/β-catenin in stemness of cisplatin-resistant HNSCC and their role as therapeutic targets.
The Wnt/β-catenin signaling pathway is associated with the regulation of cancer stem cells, and it can be driven by epigenetic modifications. Here, we aim to identify epigenetic modifications involved in the control of the Wnt/β-catenin signaling and investigate the role of this pathway in the accumulation of cancer stem cells (CSC) and chemoresistance of Head and Neck Squamous Cell Carcinoma (HNSCC). Quantitative-PCR, western blot, shRNA assay, viability assay, flow cytometry assay, spheres formation, xenograft model, and chromatin immunoprecipitation were employed to evaluate the Wnt/β-catenin pathway and EZH2 in wild-type and chemoresistant oral carcinoma cell lines, and in the populations of CSC and non-stem cells. We demonstrated that β-catenin and EZH2 were accumulated in cisplatin-resistant and CSC population. The upstream genes of the Wnt/β-catenin signaling (APC and GSK3β) were decreased, and the downstream gene MMP7 was increased in the chemoresistant cell lines. The inhibition of β-catenin and EZH2 combined effectively decreased the CSC population in vitro and reduced the tumor volume and CSC population in vivo. EZH2 inhibition increased APC and GSK3β, and the Wnt/β-catenin inhibition reduced MMP7 levels. In contrast, EZH2 overexpression decreased APC and GSK3β and increased MMP7. EZH2 and β-catenin inhibitors sensitized chemoresistant cells to cisplatin. EZH2 and H3K27me3 bounded the promoter of APC, leading to its repression. These results suggest that EZH2 regulates β-catenin by inhibiting the upstream gene APC contributing to the accumulation of cancer stem cells and chemoresistance. Moreover, the pharmacological inhibition of the Wnt/β-catenin combined with EZH2 can be an effective strategy for treating HNSCC.


Functional hypoparathyroidism in infantile hypocalcaemic stage I vitamin D deficiency rickets.
Nine infants with stage I rickets were found to have an inappropriate functional hypoparathyroidism with severe hypocalcaemia. Possible mechanisms, therapy and prevention are discussed.


Assessing and managing venous irritation associated with vinorelbine tartrate (Navelbine)
To determine the effect of duration of infusion time on venous irritation in patients receiving vinorelbine tartrate (Navelbine, Burroughs Wellcome Co., Research Triangle Park, NC) in combination with cisplatin or mitomycin. Prospective and descriptive. Five outpatient hematology/oncology units in southern Louisiana and Mississippi. 96 patients receiving vinorelbine in combination with cisplatin or mitomycin through a peripheral vein. Nurses completed the Venous Irritation Record (VIR), on which they documented the incidence of irritation reactions on the day of infusion as well as 24 hours and one to two weeks later. Incidence and severity of venous irritation as well as the duration of administration. Significantly lower incidence of venous irritation at 6-10 minute infusion rate was observed (p < 0.05). No difference in incidence was observed when vinorelbine was given with a vesicant (mitomycin) or a nonvesicant (cisplatin) drug. Although venous irritation is a problem associated with peripherally administered vinorelbine, it does not necessitate central line placement. Incidence of this problem can be reduced with a shorter duration of administration. The VIR was feasible, easy to use, and could be adapted for other drugs and other toxicities. The National Cancer Institute Common Toxicity Criteria are not adequate for grading venous irritation reactions. Vinorelbine should be administered in accordance with the manufacturer's recommendations as a 6-10 minute infusion. Determination of this rate came as a result of clinical nursing research. Nurses involved in clinical trials can and should play a role in describing emergent toxicities and investigating methods to prevent or minimize those toxicities.


Rehabilitation Strategies After Shoulder Arthroplasty in Young and Active Patients.
A well-designed and sensibly progressed rehabilitation program is vital to successful shoulder arthroplasty outcomes. This article describes the protocol suggested by ONS clinicians to treat the growing young, active patient population undergoing anatomic shoulder arthroplasty. This protocol includes an immediate postoperative phase, early strengthening phase, resistance strengthening and proprioception phase, and advanced sport-specific and goal-specific strengthening and proprioception phase. These patients may progress more quickly than older patients and require more challenging exercises aimed at regaining strength and mobility for activity, thus this protocol emphasizes incorporating full-body training to prevent undue stress on the repair on return to activity.


The role of stomata in sensitivity of Betula papyrifera seedlings to SO2 at different humidities.
Stomata of paper birch (Betula papyrifera Marsh.) seedlings were more open at high humidity than at low humidity and responded rapidly to changes in vapor pressure deficit. SO2 at 0.2 or 0.8 μl l-1 caused partial stomatal closure. Seedlings fumigated with SO2 at 0.2 or 0.5 μl l-1 for 30 h or 0.2 μl l-1 for 75 h took up more SO2 at high than at low humidity. Differences in pollutant uptake could be explained by stomatal conductance with no need to invoke changes in mesophyll conductance. Betula seedlings were more sensitive to SO2 when fumigated at high humidity, as manifested in more leaf necrosis, increased leaf abscission, and greater growth inhibition compared to seedlings fumigated at low humidity. Amount of injury to leaves increased with rate of SO2 uptake, and inhibition of root growth increased with total SO2 uptake.


Role of interleukin-1 in 4-hydroperoxycyclophosphamide toxicity to bone marrow progenitor cells: a review.
We have demonstrated that in vitro preincubation with IL-1 or TNFa for 20 hours can protect human hematopoietic progenitors from lethal doses of 4-HC. On the other hand, preincubation with IL-6 or IL-3, in a similar fashion, did not provide any protection but in fact demonstrated a slight increase in 4-HC toxicity in the same experiments. The observation that IL-1 was still protective even when a purified cell population depleted of accessory cells was used is suggestive of a direct effect of IL-1. Our data also suggest that early progenitor cells including the replatable B;-CFC are the main target of that protection. We believe that using this in vitro assay system will enable us to investigate the possible mechanisms responsible for the protection of these primitive progenitors. From a clinical perspective, future studies should attempt to clarify whether protection by IL-1 is selective for normal hematopoietic cells versus malignant cells and whether these protected primitive progenitors represent the pluripotent stem cells responsible for engraftment of transplanted bone marrow by using an animal model system.


Application of plan-do-check-act management to improve first-attempt insertion success rates of internal jugular vein catheterization for standardized training residents in an intensive care unit.
In the intensive care unit (ICU), internal jugular vein puncture and catheterization are basic rescue operations that physicians need to complete quickly and independently. It is necessary to improve the first-attempt success rate of internal jugular vein catheterization, shorten the catheterization duration and reduce the incidence of complications for standardized training residents (STRs). To improve first-attempt insertion success rates of internal jugular vein catheterization for STRs. Based on the PDCA cycle management method and current situation investigation, the PDCA management objectives were set, and the implementation content, monitoring items and continuous improvement plan were formulated. The data of residents who were trained in the ICU of Fangcun Hospital, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, from January 2016 to April 2016 and managed by the PDCA cycle (PDCA group), were compared with the data of residents trained in the same department from August 2015 to November 2015 before the implementation of PDCA (historic control group), the first-attempt success rate of puncture and catheterization, the duration of puncture and catheterization, and the incidence of complications were analysed. Thirty-six cases of internal jugular vein catheterization were performed by the PDCA group, 21 cases (58%) were performed by residents in the third year of standardized training, and 15 cases (42%) were performed by residents in the second year of standardized training. Compared with the historic control group, there was no significant difference in the seniority of residents (X2 = 0.240, P = 0.625) or the 'majors of the residents (X2 = 1.306, P = 0.835). The first-attempt success rate of puncture in the PDCA group was 94% (34/36), which was significantly higher than that of the historic control group (55% (11/20) (P = 0.001). In the PDCA group, the first-attempt success rate of puncture among third-year standardized training residents was 95% (20/21), and the first-attempt success rate in the second-year was 93% (14/15), which were significantly higher than the corresponding rates of 62% (8/13) and 43% (3/7) respectively, in the historic control group (all P = 0.021). The duration of catheterization was [4 (3,5)] min after PDCA, which was significantly shorter than that in the historic control group [9 (6.25,13.00)] min (Z = - 5.214, P < 0.001). The incidence rate of complications in the PDCA group was 0% (0 /36), which was significantly lower than the rate of 20% (4 / 20) in the historic control group (P < 0.013). PDCA cycle management can help improve the first-attempt success rate of internal jugular vein puncture and catheterization, shorten the duration of puncture and catheterization, and reduce the incidence of complications. The idea and method of PDCA cycle management can be applied to other training and management protocols for STRs.


Influence of growth hormone therapy on germinoma survivors.
Due to the effectiveness of growth hormone therapy (GHT), the number of cancer survivors receiving GHT has increased. Previous studies had indicated that GHT was not associated with the increasing risks of tumor recurrence and development with second neoplasm (SN) in cancer survivors. However, to date, research on those risks in germinoma survivors is still limited. The aim of this study is to evaluate the impact of GHT in relation to tumor recurrence and development with SN in pure germinoma survivors. This retrospective cohort study was approved by the Ethical Committee for Epidemiology of our institution. Seventy-three consecutive patients who underwent a biopsy of the lesion and were diagnosed with pure germinoma were retrospectively studied. They (median age, 15.0 years) were followed up more than 1 year after biopsy (median follow-up period, 14.3 years). The following data was obtained from the medical records of the patients: age, sex, preoperative magnetic resonance imaging findings, hormonal replacement, and events including tumor recurrence and/or SN. In our patient series, 16 patients (21.9%) who were more likely to have neurohypophysial lesion and receive multiple hormonal therapies had received GHT. No significant differences in the rates of tumor recurrence and development with SN were observed between the patients who had and had not received GHT. Moreover, the recurrence-free survival and overall survival rates were not different between the patients who had and had not received GHT. GHT did not increase the risks of tumor recurrence and development with SN in pure germinoma survivors.


Steroid regulation of C. elegans diapause, developmental timing, and longevity.
Hormones play a critical role in driving major stage transitions and developmental timing events in many species. In the nematode C. elegans the steroid hormone receptor, DAF-12, works at the confluence of pathways regulating developmental timing, stage specification, and longevity. DAF-12 couples environmental and physiologic signals to life history regulation, and it is embedded in a rich architecture governing diverse processes. Here, we highlight the molecular insights, extraordinary circuitry, and signaling pathways governing life stage transitions in the worm and how they have yielded fundamental insights into steroid regulation of biological time.


Advanced Research on Glucosinolates in Food Products.
Glucosinolate-containing foods, such as vegetables from the plant order Brassicales and its derivative products, are valued for their health-beneficial properties [...].


Behavioral changes in migrants with dementia : Experiences of professional caregivers.
Professional caregivers take care of an increasing number of migrants with dementia who may show behavioral changes. Insight into the experiences of professional caregivers concerning the care for people with a migration background who suffer from dementia and behavioral changes. Semi-structured interviews with 20 professional caregivers providing community and residential care. The caregivers' experiences focus on behavioral changes itself and on their efforts to offer person-centered care. Caregivers are aware of the mismatch between the cultural background of the client and their relatives and the professional care context. The different care perspectives of relatives and professionals sometimes result in conflict and poor collaboration. Over time, the reflections on experiences result in an awareness that more expertise and support is needed. Professional caregivers deserve support in their aim to provide high quality care for migrants with dementia and behavioral changes.


Radioactive nano-oxygen generator enhance anti-tumor radio-immunotherapy by regulating tumor microenvironment and reducing proliferation.
Oxygen (O2) is the substance irreplaceable of the body's metabolism, which is not only the primary consumable of life activities, but also provide the input energy for the whole body. Importantly, the O2 supply will act as an important role in the field of tumor theranostics. Herein, we successfully construct a radioactive nano-oxygen generator (177Lu-APPs-PEG) with superior properties, which can not only realize a high-performance radioisotope labelling, but also unfreeze the limitation of O2 dependence of internal radioisotope therapy (IRT). More importantly, such nano-oxygen generator also can effectively enhance the infiltration of cytotoxic T cells (CTLs) in distant tumors and reduce tumor metastasis. Meanwhile, the increase of O2 in tumor-site can affect the metabolism of tumor cells and regulatory T (Treg) cells to reduce cancer cells proliferation by down-regulating the expression of hypoxia-inducible factor-1α (HIF-1α) and c-Myc. In short, the strategies we designed provide a new idea for the influence of nano-enzymes on tumor metabolism and immunotherapy.


Circulation and seasonality of influenza viruses in different transmission zones in Africa.
Influenza is responsible for more than 5 million severe cases and 290,000 to 650,000 deaths every year worldwide. Developing countries account for 99% of influenza deaths in children under 5 years of age. This paper aimed to determine the dynamics of influenza viruses in African transmission areas to identify regional seasonality for appropriate decision-making and the development of regional preparedness and response strategies. We used data from the WHO FluMart website collected by National Influenza Centers for seven transmission periods (2013-2019). We calculated weekly proportions of positive influenza cases and determined transmission trends in African countries to determine the seasonality. From 2013 to 2019, influenza A(H1N1)pdm2009, A(H3N2), and A(H5N1) viruses, as well as influenza B Victoria and Yamagata lineages, circulated in African regions. Influenza A(H1N1)pdm2009 and A(H3N2) highly circulated in northern and southern Africa regions. Influenza activity followed annual and regional variations. In the tropical zone, from eastern to western via the middle regions, influenza activities were marked by the predominance of influenza A subtypes despite the circulation of B lineages. One season was identified for both the southern and northern regions of Africa. In the eastern zone, four influenza seasons were differentiated, and three were differentiated in the western zone. Circulation dynamics determined five intense influenza activity zones in Africa. In the tropics, influenza virus circulation waves move from the east to the west, while alternative seasons have been identified in northern and southern temperate zones. Health authorities from countries with the same transmission zone, even in the absence of local data based on an established surveillance system, should implement concerted preparedness and control activities, such as vaccination.


Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications.
For nearly 50 years the proximal tubule (PT) has been known to reabsorb, process, and either catabolize or transcytose albumin from the glomerular filtrate. Innovative techniques and approaches have provided insights into these processes. Several genetic diseases, nonselective PT cell defects, chronic kidney disease (CKD), and acute PT injury lead to significant albuminuria, reaching nephrotic range. Albumin is also known to stimulate PT injury cascades. Thus, the mechanisms of albumin reabsorption, catabolism, and transcytosis are being reexamined with the use of techniques that allow for novel molecular and cellular discoveries. Megalin, a scavenger receptor, cubilin, amnionless, and Dab2 form a nonselective multireceptor complex that mediates albumin binding and uptake and directs proteins for lysosomal degradation after endocytosis. Albumin transcytosis is mediated by a pH-dependent binding affinity to the neonatal Fc receptor (FcRn) in the endosomal compartments. This reclamation pathway rescues albumin from urinary losses and cellular catabolism, extending its serum half-life. Albumin that has been altered by oxidation, glycation, or carbamylation or because of other bound ligands that do not bind to FcRn traffics to the lysosome. This molecular sorting mechanism reclaims physiological albumin and eliminates potentially toxic albumin. The clinical importance of PT albumin metabolism has also increased as albumin is now being used to bind therapeutic agents to extend their half-life and minimize filtration and kidney injury. The purpose of this review is to update and integrate evolving information regarding the reabsorption and processing of albumin by proximal tubule cells including discussion of genetic disorders and therapeutic considerations.


Adsorption of Cu(II), Cd(II), Hg(II), Pb(II) and Zn(II) from aqueous single metal solutions by guanyl-modified cellulose.
A novel chemically guanyl-modified cellulose (Gu-MC) - material has been synthesized for the adsorption of Cu2+, Cd2+, Hg2+, Pb2+ and Zn2+ metal ions from aqueous solution. Cellulose was pretreated with periodate prior to its condensation with aminoguanidine for the formation of cellulose aldehyde-guanyl Schiff's. The synthesized material was characterized by Fourier transform infrared spectra (FTIR), elemental analysis, scanning electron microscope (SEM) and thermogravimetric analysis (TGA). Moreover, the effect of contact time, pH, adsorbent dosage, interfering ions and initial concentration of metal ions on the adsorption capacity were investigated. At optimum conditions, the adsorption capacities of Cu2+, Zn2+, Cd2+, Pb2+ and Hg2+ were 83, 78, 68, 52, and 48mgg-1, respectively. The kinetic of adsorption adopted to the second-order model and kinetic model showed that the chemical adsorption is the rate limiting step. The proposed material has been successfully applied for the adsorption of the target metal ions from different real samples with satisfactory results.


Micturition habits and incontinence at age 17--reinvestigation ofa cohort studied at age 7.
To study the epidemiology of micturition disturbances in teenagers. A subsample of 1034 teenagers previously evaluated at age 7 years was reinvestigated 10 years later. A postal questionnaire was used and a response rate of 71% (736) obtained. Those who reported bladder symptoms were contacted by telephone for a detailed history concerning imperative urge, daytime incontinence, emptying difficulties and bedwetting. There was a general decrease in the frequency and intensity of symptoms from 7 to 17 years of age. At age 17 at least one symptom was reported by 5.9% of the girls and 0.9% of the boys. Overall the symptoms were regarded as mild or moderate. At age 17 years, micturition disturbances were reported infrequently and few subjects wanted medical help.


Phytohemagglutinin-stimulated calcium signal in lymphocytes of alcoholics before, during and after detoxification.
Acute and chronic exposure to ethanol influences intracellular calcium homeostasis via NMDA receptors, direct regulation of calcium channels or the phosphoinositide pathway. To explore the influence of alcohol withdrawal on calcium metabolism, we have investigated the resting and phytohemagglutinin (PHA) stimulated [Ca2+]i in lymphocytes of 10 alcoholics before, during and after withdrawal. Our findings suggest that both compartments of the PHA-stimulated signal are affected in alcoholics, with flattening of the initial peak and sustained calcium influx, as long as severe vegetative signs are present. MANOVA results showed significant interaction effects for both measurement points, for the initial peak, 40 s after stimulation (P = 0.05), and especially for the sustained influx at the end of the observation period (P = 0.001). The detailed mechanisms of this disturbed calcium homeostasis need further investigation.


Development and Validation of a Mutational Burden-Associated LncRNA Signature for Improving the Clinical Outcome of Hepatocellular Carcinoma.
Long non-coding RNAs (lncRNAs) modulate numerous cellular processes, including DNA damage repair. Here, we investigated the clinical importance of lncRNAs associated with mutational burden in hepatocellular carcinoma (HCC). Prognosis-related lncRNAs associated with mutational burden were screened and determined to score the mutational burden-associated lncRNA signature (MbLncSig) from TCGA. Prognostic values and predictive performance of the MbLncSig score were analysed. Four mutational burden-associated lncRNAs (AC010643.1, AC116351.1, LUCAT1 and MIR210HG) were identified for establishing the MbLncSig score. The MbLncSig score served as an independent risk factor for HCC prognosis in different subgroup patients. The predictive performance of one-year and three-year OS was 0.739 and 0.689 in the entire cohort, respectively. Moreover, the MbLncSig score can further stratify the patient survival in those with TP53 wild type or mutation. This study identified a four-lncRNA signature (the MbLncSig score) which could predict survival in HCC patient with/without TP53 mutation.


Persistent Idiopathic Dentoalveolar Pain: Is It a Central Pain Disorder?
The International Classification of Orofacial Pain (ICOP) describes idiopathic pain as "unilateral or bilateral intraoral or facial pain in the distribution(s) of one or more branches of the trigeminal nerve(s) for which the etiology is unknown. Pain is usually persistent, of moderate intensity, poorly localized and described as dull, pressing or of burning character." Several diagnoses are included in the ICOP Idiopathic pain section, burning mouth syndrome and persistent idiopathic facial and dentoalveolar pain. This article, with a representative case presentation, briefly discusses common features that may lead to a common central cause for a variety of peripheral complaints.


Decreased Diversity of the Oral Microbiota of Patients with Hepatitis B Virus-Induced Chronic Liver Disease: A Pilot Project.
Increasing evidence suggests that altered gut microbiota is implicated in the pathogenesis of hepatitis B virus-induced chronic liver disease (HBV-CLD). However, the structure and composition of the oral microbiota of patients with HBV-CLD remains unclear. High-throughput pyrosequencing showed that decreased oral bacterial diversity was found in patients with HBV-CLD. The Firmicutes/Bacteroidetes ratio was increased significantly, which indicated that dysbiosis of the oral microbiota participated in the process of HBV-CLD development. However, the changing patterns of the oral microbiota in patients with HBV-induced liver cirrhosis (LC) were almost similar to patients with chronic hepatitis B (CHB). HBV infection resulted in an increase in potential H2S- and CH3SH-producing phylotypes such as Fusobacterium, Filifactor, Eubacterium, Parvimonas and Treponema, which might contribute to the increased oral malodor. These key oral-derived phylotypes might invade into the gut as opportunistic pathogens and contribute to altering the composition of the gut microbiota. This study provided important clues that dysbiosis of the oral microbiota might be involved in the development of HBV-CLD. Greater understanding of the relationships between the dysbiosis of oral microbiota and the development of HBV-CLD might facilitate the development of non-invasive differential diagnostic procedures and targeted treatments of HBV-CLD patients harbouring specific oral phylotypes.


[Psychological rehabilitation after stroke].
Stroke often causes psychological trauma as a result of dealing with serious, life-threatening disease. While each patient reacts differently, conversion disorders such as sideration are commonly observed. These can be managed by resilient psychological rehabilitation therapy with the various caregivers.


Mortality versus improvement in severe chronic asthma: physiologic and psychologic factors.
Improved outcome (1 to 10 years) of 140 asthmatic children retrospectively correlated with 8 of 49 variables in admission evaluation: (1) age of onset, (2) IgE, (3) night/early AM bronchospasm, (4) aggression, (5) severely disrupted family circumstances, (6) severe psychopathology, (7) psychotic signs, and (8) I.Q. Patients with fatal outcome (6% to 12%) deviated in the last three variables; most were 12.1 to 16.5 years, male, Black/Hispanic, aggressive, depressed and/or anxious. Clinical implications include high-risk identification on the basis of psychologic and physiologic variables, preventative measures, and consideration of residential treatment.


Lipofilling, an efficient solution for breast sequelae after cardiothoracic surgery.
Evolutions in pediatric cardiovascular surgery have allowed the treatment of a various range of cardiovascular malformations in infants. It is a difficult branch of surgery, with vital impact, which can also leave residual thoracic scars, possible sources for thoracomammary deformities in adults. Most thoracomammary deformities after thoracotomy are observed at puberty, when they appear as breast asymmetries. The main cause is the breast bud injured during thoracotomy. Several techniques have been suggested for breast reconstruction, but none give satisfying results. We have been practicing lipofilling since 1998 for breast reconstruction. Since 2001, we have started applying it to breast deformities. The final result is constant in time, natural, and has a good volume filler effect. We describe the fat grafting technique, an original technique, as a solution for this kind of deformities. The technique is illustrated by two clinical cases. In conclusion, fat grafting has really improved breast asymmetry due to iatrogenic deformation. Even if those cases are rare, surgeons have to know this kind of procedure. It is indeed a simple and efficient solution for those patients after childhood, with natural and long standing results.


Why teach crime scene management to forensic university students?
Despite enhanced forensic collaborations between law enforcement agencies and universities, crime scene management remains a domain seen more as technical than scientific, largely carried out by sworn police officers qualified as scene of crime officers (SOCOs), confining forensic graduates to specialized expertise fields. Under such circumstances, we must ask ourselves why and how do we provide a generalised dedicated course to academic pupils who are not primarily intended to join such teams, excepting sometimes to assist them on a specialized field (explosion, arson, etc.)? Currently in Quebec, forensic graduates cannot join crime scene units attached to police forces, mainly because of unions, which argue about the need to be an experienced police officer before qualifying for a crime scene course. Based on the operational experience of the author, who created the foundational graduate forensic programme in Quebec, Canada, this paper will explain why such an academic course is still of high importance, its rationale within an academic curriculum, its goal and its implementation. Challenges are still to be considered, but selected feedback from students who understood that the aim of this course is distinct from their formal support disciplines, encourage such an approach.


Building a safety buffer for European food security: the role of small-scale food production and local ecological and gastronomic knowledge in light of COVID-19.
The lockdown caused by the coronavirus 2019 disease (COVID-19) has created a situation in which food availability is affected not only by the availability of money but also by the availability of food itself. On the basis of five pillars, including 1) supporting community-based farming, 2) defending small firms, 3) developing narratives on the high value of local food, 4) encouraging subsistence gardening and foraging in the wild, and 5) promoting local ecological and gastronomic knowledge, the essay points a way forward to attain greater sustainability and resilience of safe food chains that starts with reassessing the relevance of local food systems.


The association between viral load and concurrent human papillomavirus infection at the genital and anal sites of young women and the impact of vaccination.
Concurrent genital-anal human papillomavirus (HPV) infections may impose an increased anal cancer risk in women with HPV-related genital lesions. High viral load may facilitate genital-anal HPV concurrence. Genital and anal HPV is reduced by a bivalent HPV16/18 vaccine, yet the effect on concurrent genital-anal HPV remains unclear. This study analyzed viral load in concurrent genital-anal HPV infections, relative to genital-only and anal-only HPV infections and the impact of vaccination in young women. We included 1074 women, who provided both genital and anal swabs. HPV detection and genotyping was performed using the SPF10-DEIA-LiPA25. HPV copy numbers were measured with type-specific qPCRs and corrected for cellular content to obtain the viral load. Concurrent genital-anal HPV often had significantly higher genital viral load (0.09-371 c/cell) than genital-only HPV (3.17E-04-15.9 c/cell, p < 0.0001 to p < 0.05). Moreover, nearly all concurrent genital-anal HPV types had higher genital copy numbers per PCR reaction (157-416E04 c/rxn) than anal copy numbers (0.90-884E01 c/rxn, p < 0.0001 to p < 0.001). Vaccinated women had significantly less infections with HPV16/18 vaccine-types (2.8% vs 13.7%, p < 0.0001) and HPV31/35/45 cross-protective types (7.4% vs 21.1%, p < 0.0001) than unvaccinated women. In conclusion, particularly high genital viral load is found in concurrent genital-anal HPV infections, which are effectively reduced by vaccination.


Maintenance of chicken embryonic stem cells in vitro.
In this chapter, we describe the methods we have used to show that chicken leukemia inhibitory factor (LIF) maintains chicken embryonic stem (ES) cells in an undifferentiated state in culture. Recombinant chicken LIF (rchLIF) was expressed as a fusion protein linked to glutathione S-transferase (GST) and purified to greater than 90% purity in two chromatography stages, the first an affinity step using the GST tail, which was cleaved before further purification by gel chromatography. Chicken ES cells were obtained by culturing chicken blastodermal cells isolated from stage X embryos of freshly laid chicken eggs. These cells can be maintained in media containing rchLIF for at least 9 d without any other cytokines or feeder cells. Chicken ES cells were characterized by the expression of alkaline phosphatase activity, stage-specific embryonic antigen (SSEA)-1 and embryonal carcinoma cell monoclonal antibody-1. In addition, the phosphorylation of signal transducers and activators of transcription-3 by LIF, which is sufficient to maintain the undifferentiated state of ES cells, was detected by Western blotting analysis.


The impact of methadone on consumption of inpatient care and mortality, with special reference to HIV status.
This study investigates the impact of methadone treatment on inpatient care admissions and mortality among 331 methadone-maintained patients compared with 1,483 similar untreated opiate misusers. The methadone patients manifested a lower mortality during treatment than the comparison group and those patients who had left their treatment. The annual incidence rate decreased from 1.4 inpatient care admissions per year for those who had stayed 0-1 year, less than 1 for those who stayed more than 2 years, and 0.3 for those who had stayed longer (>4 years) in methadone treatment. A similar decrease occurred in both sexes. The incidence rate decreased more among the HIV-negative than the HIV-positive patients. The low incidence of inpatient care during treatment may be due to treatment but may also be partly due to selection factors.


A neural network model for generating complex birdsong syntax.
The singing behavior of songbirds has been investigated as a model of sequence learning and production. The song of the Bengalese finch, Lonchura striata var. domestica, is well described by a finite state automaton including a stochastic transition of the note sequence, which can be regarded as a higher-order Markov process. Focusing on the neural structure of songbirds, we propose a neural network model that generates higher-order Markov processes. The neurons in the robust nucleus of the archistriatum (RA) encode each note; they are activated by RA-projecting neurons in the HVC (used as a proper name). We hypothesize that the same note included in different chunks is encoded by distinct RA-projecting neuron groups. From this assumption, the output sequence of RA is a higher-order Markov process, even though the RA-projecting neurons in the HVC fire on first-order Markov processes. We developed a neural network model of the local circuits in the HVC that explains the mechanism by which RA-projecting neurons transit stochastically on first-order Markov processes. Numerical simulation showed that this model can generate first-order Markov process song sequences.


Incidence and treatment of budding yeasts in canine otitis externa.
Budding yeasts were present in the majority of cases of otitis externa examined. A reddish-brown, dry, waxy discharge was the typical exudate. A successful treatment of yeast-infected ears was multiple otic lavages using a combination of an aqueous solution of poloxamer-iodine and application of an antifungal-antibiotic-corticosteroids ointment.


[Cellular and regional localization of the neurospecific antigen 10-40-4 in the human brain].
Cellular and regional localization of neurospecific protein 10-40-4 in human brain was studied by immunofluorescent staining and immunoenzymatic assay. Intense fluorescence of perikaryons of the medulla oblongata, thalamus and pons neurons was demonstrated. The same structures showed the maximal concentration of the protein (15-18% of water-soluble proteins). In the cortex of the hemispheres, in the cerebellum and hypothalamus the fluorescence intensity was not different from the background level. The concentration of the protein in these structures was minimal (1-4% of water-soluble proteins).


Light perception in plants: cytokinins and red light join forces to keep phytochrome B active.
Plant growth and development is modulated by internal cues such as rhe hormonal balance and external factors. Plants are particularly sensitive to their light environment, which they scrutinize with at least three classes of photoreceptors. In recent years, it has become increasingly clear that light and hormonal signaling interact at several levels. A cytokinin receptor was recently identified together with several elements acting in this signaling pathway. ARR4, a response regulator working downstream of a cytokinin receptor, has been shown to regulate phytochrome B-mediated light signaling.


Psoriatic arthritis.
Despite the fact that psoriatic arthritis has been recognized as an entity for almost five decades, there are still no valid criteria for either its diagnosis or classification. Several sets of criteria have been proposed but none was studied. None the less, investigators have been able to study the condition and describe its unique features and its natural course and prognosis. However, in order to facilitate further studies, it would be worthwhile to develop an internationally accepted and validated set of criteria, both for the diagnosis and classification of the disease, as well as for the assessment of damage. These criteria would help set up appropriate therapeutic trials in this condition as well.


Mode of action and substrate specificity of a purified exo-1,4-beta-D-glucosidase cloned from the cellulolytic bacterium Ruminococcus albus AR67.
A gene encoding exo-1,4-beta-D-glucosidase, from Ruminococcus albus AR67, was cloned in Escherichia coli, restriction mapped, and shown to be expressed from sequences within the insert that function as a promoter in E. coli. The cloned enzyme was located predominantly in the cytoplasm (40%) and attached to insoluble cell components (48%). After purification to homogeneity, the enzyme (Mr = 64,000, monomeric) was specific for substrates with beta-D-glucopyranosyl configuration and was inactive against alpha-glucosides, lactosides and xylosides. Km values of the enzyme decreased with increasing chain length (G2-G5). Glucose was the major product of hydrolysis from cellodextrins. Preference for longer chain cellodextrins is consistent with exo-1,4-beta-D-glucan glucohydrolase mode of action [E.C. 22.214.171.124].


Late complications of nickel-titanium alloy stent in tracheal stenosis.
To investigate and treat the late complications of using nickel-titanium alloy stents in laryngotracheal, bronchial, and esophageal stenosis patients who developed severe laryngotracheal stenosis (SLS). Retrospective clinical study. Thirteen patients with SLS or tracheoesophageal fistula secondary to insertion of a nickel-titanium alloy stent for treatment of laryngotracheal, bronchial, or esophageal stenosis treated between May 2004 and March 2010 were retrospectively analyzed. Of the 13 total patients, nine had one stent placed, and four had two stents placed. The late complications observed were glottic and/or subglottic extension of cervical tracheal stenosis (n = 6), new stricture of the thoracic trachea (n = 4), severe left bronchial stricture with massive left pulmonary collapse (n = 1), and cervical tracheoesophageal fistula (n = 2). Six patients with glottic and/or subglottic to cervical tracheal stenosis underwent successful laryngotracheal reconstruction. Two patients with subglottic and upper thoracic tracheal stenosis were successfully treated by staged operation for the stenosis. Two patients with subglottic and distal thoracic tracheal stenosis are still undergoing treatment. One patient with severe left bronchial stricture and massive left pulmonary collapse has been treated but has not achieved full recovery. One patient with cervical tracheoesophageal fistula underwent successful repair but died later from metastatic disease. One patient with tracheoesophageal fistula died from massive hemorrhage and asphyxiation induced by the stent, which had not been removed. The nickel-titanium alloy stents should be used with extreme caution in patients with laryngotracheal, bronchial, or esophageal stenosis treatment that can be corrected by surgical therapy.


Pseudoexfoliative fibrillopathy in the conjunctiva. A relation to elastic fibers and elastosis.
Pseudoexfoliative (PSX) material in the conjunctiva was found to have a close association with elements of the elastic system in 13 eyes of patients with PSX disease studied ultrastructurally. Pseudoexfoliation aggregates were rare within vascular walls but frequent in proximity to the plasmalemma of stromal fibroblasts. No amyloid was found. A striking feature was the association of PSX fibers with the elastosis seen in many of the specimens. Typical PSX fibers were present in clumps of oxytalan and around small elastic fibers. In five cases with more advanced elastosis, the aggregates of PSX fibers were larger and their usual loose fibrogranular matrix was extensively replaced by a dense elastotic one. Morphology of PSX here varied from typical to thicker, fragmented, and sometimes nondiagnostic fibers. This intermingling of PSX and elastotic materials suggested that PSX fibrillopathy is itself a type of elastosis, possibly resulting from abnormal aggregation of components related to elastic microfibrils.


Permittivity measurements for raw and boiled quinoa seeds versus temperature, bulk density, and moisture content.
Quinoa is a nutrient-rich pseudocereal that is gaining popularity in European countries since it is gluten-free and an interesting source of fat, proteins, minerals, and amino acids. However, up to date, the electric permittivity of quinoa seeds has not been measured and, therefore, this hampers the possibility of designing optimized recipes for its microwave processing. In this work, the permittivity of both raw and boiled quinoa seeds is measured around 2.45 GHz at several conditions for temperature, moisture content, and bulk density. The grain kernel permittivity is also estimated from the Complex Refractive Index (CRI) mixture equation and different bulk density measurements. The obtained results show different temperature behaviours for raw and boiled seeds, whereas the permittivity of quinoa seeds versus moisture content and bulk density was as expected: the permittivity (both the dielectric constant and loss factor) levels increased as the observed variables did. From the measured data, it can be concluded that both raw and boiled quinoa can be processed with microwave technology, although care must be taken with raw quinoa grain kernels since the permittivity increases significantly with temperature, and a thermal runaway may occur.


Enhancement of immune response towards non-lipidized Borrelia burgdorferi recombinant OspC antigen by binding onto the surface of metallochelating nanoliposomes with entrapped lipophilic derivatives of norAbuMDP.
Lyme disease caused by spirochete Borrelia burgdorferi sensu lato, is a tick-born illness. If the infection is not eliminated by the host immune system and/or antibiotics, it may further disseminate and cause severe chronic complications. The immune response to Borrelia is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies associated with Th1 cell activation. A new experimental vaccine was constructed using non-lipidized form of recombinant B. burgdorferi s.s. OspC protein was anchored by metallochelating bond onto the surface of nanoliposomes containing novel nonpyrogenic lipophilized norAbuMDP analogues denoted MT05 and MT06. After i.d. immunization, the experimental vaccines surpassed Alum with respect to OspC-specific titers of IgG2a, IgG2b isotypes when MT06 was used and IgG3, IgM isotypes when MT05 was used. Both adjuvants exerted a high adjuvant effect comparable or better than MDP and proved themselves as nonpyrogenic.


Site-specific familial aggregation of prostate cancer.
Over the last decade, epidemiologic evidence has accumulated in favor of a significant but heterogeneous hereditary component in prostate cancer (PC) susceptibility. In order to map and clone PC susceptibility genes, stratification of PC families into genetically homogeneous groups appears to be a key issue. Subset definition based on age at diagnosis, presumed mode of inheritance, number of affecteds per family and coaggregation of PC with other cancers has already proven successful in some studies. Previously, the finding of the coaggregation of malignancies of the central nervous system within PC families helped to link a prostate-brain cancer susceptibility gene (CAPB) to chromosome 1p36. In this study, we evaluate the risk of PC and malignancies at other sites among first-degree relatives of a large population-based group of Dutch PC patients. A population-based family case-control study was initiated that included Caucasian PC patients newly diagnosed between July 1996 and December 1999. Information on 12,575 first-degree relatives of 704 PC patients and 1,371 controls was collected through postal questionnaires and telephone interviews. All reported PC in first-degree relatives was verified through medical records. In our population, PC has a strong familial component that is reflected by a 2.9-fold increased risk (95% CI = 2.2-3.9) of PC for first-degree relatives of PC patients. This familial risk was somewhat higher among brothers (hazard ratio = 3.9; 95% CI = 2.4-6.4) compared to fathers (hazard ratio = 2.5; 95% CI = 1.7-3.6). Cancers at other sites did not coaggregate with PC. Our data suggest that familial PC, at least in this Western European population, is site-specific, not part of an inherited cancer syndrome.