Short self-assembling peptides as building blocks for modern nanodevices.
Short, self-assembling peptides form a variety of stable nanostructures used for the rational design of functional devices. Peptides serve as organic templates for conjugating biorecognition elements, and assembling ordered nanoparticle arrays and hybrid supramolecular structures. We are witnessing the emergence of a new phase of bionanotechnology, particularly towards electronic, photonic and plasmonic applications. Recent advances include self-assembly of photoluminescent semiconducting nanowires and peptide-conjugated systems for sensing, catalysis and energy storage. Concurrently, methods and tools have been developed to control and manipulate the self-assembled nanostructures. Furthermore, there is growing knowledge on nanostructure properties such as piezoelectricity, dipolar electric field and stability. This review focuses on the emerging role of short, linear self-assembling peptides as simple and versatile building blocks for nanodevices.


The mode of delivery in patients with preeclampsia at term subject to elective or emergency Cesarean section.
Preeclampsia is accompanied by high maternal and fetal morbidity and mortality. Thus, delivery needs to be planned carefully. The aim of this study was to determine the most favorable delivery for patients with preeclampsia between the week 37 and 41 of gestation. For this retrospective study, patient data from 2003 to 2011 was collected. Study participants were women having a Cesarean section during week 37 and 41 of gestation. The population was classified into four groups: patients without hypertensive disorders having an elective or emergency Cesarean section and patients suffering from preeclampsia with elective or emergency Cesarean section. Analysis included mode of delivery and neonatal outcome, defined by Apgar score, rate of NICU admission and pH value of the umbilical cord. A total of 130 cases of preeclampsia were recorded. Compared to the control group, we observed a significantly higher Apgar score in the study group with emergency Cesarean section. Furthermore, within the study group the Apgar score at 5 and 10 min was also significantly increased in cases delivered by emergency Cesarean section. Moreover, the pH value of the umbilical cord was significantly higher in the study group. Considering the delivery mode, significant differences were found in favor of the elective Cesarean section. There were no differences in the rate of NICU admission between the groups. The most frequent mode of delivery for women suffering from preeclampsia is elective Cesarean section; however, neonates delivered by emergency Cesarean section did not show an adverse neonatal outcome.


[Determination of major components in liuyingwan pills by supercritical fluid extraction(SFE)].
On the basis of SFE and CGC to establish a method for the qualitative and quantitative analysis of major components in Liuyingwan pills. Orthogonal design and variance analysis were used to optimize the four variables (temperature, pressure, volume of modifier and static extraction time) of SFE, and the quantification was completed by CGC. The optimized conditions are as follows: pressure 48.2 MPa, temperature 60 degrees C, 0.2 ml ethyl acetate as modifier and static extraction 10 min. The recoveries of borneol and eugenol are 101.93% (RSD 1.56%) and 98.43% (RSD 2.26%) respectively. Compared with conventional methods, SFE is rapid, convenient and accurate in determining borneol and eugenol.


Stress-induced impairment of macrophage tumoricidal function.
Several studies have shown the effect of stress on immune cells and their functions. The purpose of the present work was to investigate the influence of acute immobilization stress on macrophage nonspecific tumoricidal activity. Peritoneal macrophages were activated by nonspecific immunopotentiators such as interferon or bacterial lipopolysaccharide (LPS) and the killing of MBL-2 leukemic target cells was measured. Macrophages from mice submitted to stress showed decreased responsiveness to interferon or LPS. In addition, the role of corticosteroids as mediators in the phenomenon was also studied. Indeed, we observed that corticosteroids were able to inhibit macrophage cytotoxicity and could at least play some role. This data could contribute to a better understanding of the effect of stress on the host immunosurveillance against tumor development.


Posterior calf injury.
Acute injuries of the Achilles tendon are common among athletes and non-athletes alike. Injuries of other posterior calf muscles are far less common but should be considered in the differential, to ensure proper diagnosis and treatment of patients with calf injuries. This article focuses on these calf injuries, including injuries of the gastrocnemius, plantaris, soleus, and flexor hallucis longus, which may occasionally be mistaken for Achilles tendon disorders.


[Transient myeloproliferation and acute myeloid leukemia in infants with Down's syndrome].
Transient neonatal myeloproliferative disorders (TMD's) indistinguishable from acute leukaemia by clinical and morphological criteria have been described in neonates with Down's syndrome. To analyse its clinical significance, 10 infants under 1 year of age presenting with Down's syndrome and the morphological picture of acute myelogenous leukaemia were reviewed. 3 of these children had true AML leading to death after 2, 8 and 11 months. In the other 7 children the diagnosis TMD was suggested as spontaneous or in one case interferon-induced remission occurred within 4 to 25 weeks after diagnosis. The interferon-treated patient died of SIDS at the age of 11 months. Another one of the TMD children developed fatal erythroleukaemia at the age of 2 years. Regarding initial clinical and haematological parameters, TMD was indistinguishable from true congenital leukaemie. In all patients classification according to the FAB criteria was difficult, as mainly undifferentiated or poorly differentiated myeloid blasts were seen, sometimes with erythro- or megakaryocytic features. Because of the difficulties in the differential diagnosis of TMD and true AML it is recommended to delay specific cytostatic therapy in neonates with Down's syndrome, until definite progression of the leukaemic process is observed or cytogenetic analyses suggesting true AML are available.


Influenza and pneumococcal vaccination coverage levels among persons aged > or = 65 years--United States, 1973-1993.
Recommendations to provide annual influenza vaccination and one dose of pneumococcal vaccine to all persons aged > or = 65 years (1,2) are intended to reduce the high morbidity and mortality associated with influenza and pneumococcal disease. One of the national health objectives for the year 2000 is to increase influenza and pneumococcal vaccination levels to > or = 60% for persons at high risk for influenza and pneumococcal disease, including those aged > or = 65 years (objective 20.11) (3). This report summarizes 1) estimates of influenza vaccination coverage levels among persons aged > or = 65 years during 1973-1985 and pneumococcal vaccination coverage levels for 1984-1985 based on data from the United States Immunization Survey (USIS) and 2) influenza and pneumococcal vaccination coverage levels among persons aged > or = 65 years and for selected population subgroups during 1989-1993 based on data from the National Health Interview Survey (NHIS).


The Dominant Obesity Discourse Versus Children's Conceptualizations of Health: A Comparison Through Dialogue and Drawings.
The emphasis on childhood obesity reduction has been attributed to the dominant obesity discourse. However, some researchers argue that this discourse may be ineffective and even harmful for children. From a post-structuralist perspective, the dominant obesity discourse has the power to shape children's subjectivities, though subjectivities may also be influenced by personal experiences and other knowledge about bodies and health. There is limited research which explores how children's conceptualizations of health are informed by the dominant obesity discourse. To address this knowledge gap, qualitative data were collected from 8- to 11-year-old children ( n = 29) regarding their conceptualizations of health, healthy bodies, and health practices. Results suggest that children's conceptualizations reflected arguments embedded within the dominant obesity discourse, but at times, also contradicted or deviated from it. Study findings can be applied toward children's health promotion programming to offer a more holistic and inclusive perspective on health and well-being.


An analysis of perioperative cholangiography in one thousand laparoscopic cholecystectomies.
We undertook this retrospective study to ascertain the proper role of perioperative cholangiography in the management of 1002 patients undergoing laparoscopic cholecystectomy for symptomatic cholelithiasis. Nine hundred forty-one patients were categorized as being at high or low risk for choledocholithiasis according to the presence or absence of jaundice, pancreatitis, elevated bilirubin, alkaline phosphatase, serum glutamic-oxaloacetic transaminase, or radiographic evidence of common bile duct stones (CBDSs). Intraoperative cholangiography (IOCG) and preoperative endoscopic retrograde cholangiopancreatography (ERCP) were equivalent in the detection of CBDSs, and laparoscopic common bile duct exploration (CBDE) was successful in 12 of the 21 patients (57%) in whom it was attempted. The ducts of the other 52 patients with CBDSs were successfully cleared by preoperative or postoperative ERCP. Laparoscopic IOCG is successful in detecting CBDS in high-risk patients and half of these ducts can be cleared laparoscopically. The incidence of CBDS in low-risk patients is 1.7%, a risk that does not warrant routine cholangiography. These data suggest ERCP should be reserved for those at-risk individuals in whom IOCG or laparoscopic duct clearance has been unsuccessful.


Effects of natural products on several stages of the spore cycle of Clostridium difficile in vitro.
To investigate the effect of natural products on the spore cycle of Clostridium difficile in vitro. Twenty-two natural products were investigated using four C. difficile strains. Effects on sporulation, determined using microscopy and a conventional spore recovery assay, showed that fresh onion bulb extract (6·3% v v-1 ) and coconut oil (8% v v-1 ) inhibited sporulation in all four isolates by 66-86% and 51-88%, respectively, compared to untreated controls. Fresh ginger rhizome extract (25% v v-1 ) was also inhibitory, although to a lesser extent. Using a standard spore germination and outgrowth assay, germination was unaffected by the 22 products, whereas outgrowth was significantly reduced by artichoke extract (18·8 mg ml-1 ), fresh onion bulb extract (25% v v-1 ), Leptospermum honeys (8% w v-1 ) and allicin (75 mg ml-1 ; P < 0·01). Sporicidal activity, investigated using a standard plate recovery assay, was minimal. Three of the 22 natural products (13%) showed inhibitory effects on sporulation of C. difficile and six products (27%) reduced vegetative outgrowth of C. difficile. This study shows the potential of natural products to inhibit different stages of C. difficile sporulation and encourages further investigation in this field.


Clinical characteristics and treatment of blow-out fracture accompanied by canalicular laceration.
Blow-out fracture and canalicular laceration can occur simultaneously as a result of the same trauma. Despite its importance, little research has been conducted to identify clinical characteristics or surgical techniques for repair of a blow-out fracture accompanied by canalicular laceration. The aim of this study was to evaluate the clinical characteristics, the surgical approach, and the outcomes. Thirty-four eyes of 34 patients who underwent simultaneous repair of canalicular laceration using silicone tube intubation and reconstruction of blow-out fracture were included. Medical records were retrospectively reviewed for patient demographics, nature of injury, affected canaliculus, location, and severity of blow-out fracture, associated facial bone fracture, ophthalmic diagnosis, length of follow-up period, and surgical outcome. Mean patient age was 40.0 years (range, 17-71 y). The mean follow-up was 7.3 months. Fist to the orbital area (10 patients, 29.4%) was the most common cause. There were 24 lower canalicular lacerations (70.6%), 6 upper canalicular lacerations (17.6%), and 4 upper and lower canalicular lacerations (11.8%). Isolated medial wall fractures were most common (area A4: 20/34, 58.8%). Fractures involving both the floor and medial wall and maxillo-ethmoidal strut (areas A1, A2, A3, and A4) were the second most common (6/34, 17.6%), and floor and medial wall with intact strut (areas A1, A2, and A4) were injured in 6 patients (17.6%). Pure inferior wall fractures were least frequent (areas A1 and A2: 2/34, 5.9%). The severity of the fracture was severe in most patients except for 1 linear fracture with tissue entrapment and 1 moderate medial wall fracture (32/34, 94.1%). There was lid laceration in 20 patients (58.8%). Nasal bone fracture (5/34, 14.7%) was the most common facial bone fracture. Tubes were removed at a mean of 3.3 months (range, 3-4 mo). In total, 31 patients (91.2%) achieved complete success in canalicular laceration and blow-out fracture repair. No significant complications were encountered. Fractures involving the medial wall with a lower canalicular laceration were the most common among concomitant blow-out fractures and canalicular lacerations. The severity of the fracture was most often classified as severe. Computed tomographic scan of the orbit and facial bones for identification of any additional injuries such as orbital wall and facial bone fractures should be performed in patients with canalicular laceration. To avoid disruption of the medial canthal area, repair of the canalicular laceration with silicone tube intubation was performed before reconstruction of the blow-out fracture through transconjunctival and transcaruncular approaches. Finally, the tube was fixed after blow-out fracture surgery, and these surgical orders yielded good surgical outcomes without complications.


The promiscuous MLL gene links chromosomal translocations to cellular differentiation and tumour tropism.
MLL is a promiscuous gene involved in a diversity of chromosomal fusions in haematological malignancies, usually resulting from chromosomal translocations. MLL-associated chromosomal rearrangements usually occur in tumours of specific haematological lineages, suggesting a crucial role for the MLL fusion partner in determining disease phenotype (or tumour tropism). The MLL gene is homologous to Drosophila trithorax, and is likewise involved in embryo pattern formation. Common themes linking several of the MLL partners include a possible involvement in embryo patterning via Hox gene regulation and chromatin remodelling. These findings reinforce the link between developmental regulation and chromosomal translocations, and indicate the role of chromosomal translocation in activating genes capable of determining tumour phenotype in leukaemias and sarcomas.


Career and Professional Satisfaction of Oral and Maxillofacial Surgery Residents, Academic Surgeons, and Private Practitioners: Does Gender Matter?
The aims of this study were to determine whether male vs. female oral and maxillofacial surgery (OMS) residents, academic surgeons (i.e., faculty members), and private practitioners in the U.S. differed in their general career satisfaction and job/professional satisfaction. Survey data were collected in 2011-12 from 267 OMS residents (response rate 55%), 271 OMS academic surgeons (response rate 31%), and 417 OMS private practitioners (response rates 13% web-based survey and 29% postal mail survey). The results showed that while the male vs. female OMS private practitioners and academic surgeons did not differ in their career satisfaction, the female residents had a lower career satisfaction than the male residents (on four-point scale with 4=most satisfied: 3.03 vs. 3.65; p<0.01). The male vs. female OMS private practitioners and academic surgeons also did not differ in their job satisfaction. However, the female residents agreed on average less that they were able to practice OMS in the way they want, felt less proud to be an oral and maxillofacial surgeon, were less satisfied with their career, and were more likely to consider a career change in the next five years than the male residents. While these male and female oral and maxillofacial surgeons in private practice and academia did not differ in their career and job satisfaction, the male and female residents differed significantly, with female residents reporting a significantly poorer career and job satisfaction than male residents. Future research needs to explore ways to improve career and professional satisfaction of female OMS residents.


C-reactive protein levels, haplotypes, and the risk of incident chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is characterized by substantial chronic inflammation in the pulmonary compartment as well as in the systemic circulation. To investigate potentially causal association, we examined whether serum levels of high-sensitivity C-reactive protein (hsCRP) and variations in the CRP gene are associated with the risk of developing COPD. This study is part of the Rotterdam Study, a prospective population-based cohort study among subjects aged 55 years or older. At baseline, 6,836 subjects without COPD had a blood sample available for assessment of hsCRP serum levels and haplotypes of the CRP gene. We analyzed the association between hsCRP levels, CRP gene haplotypes, and incident COPD with Cox proportional hazard models, adjusted for age, sex, and other confounders. High levels of hsCRP (>3 mg/L) were associated with a significantly increased risk of incident COPD (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.16-2.49) compared with persons with low levels (<1 mg/L). The risk remained increased after adjusting for potential confounders and introducing a latency period of 3 years. The risk was most pronounced in former smokers (HR, 2.2; 95% CI, 1.12-3.74). hsCRP was not a risk factor in never smokers. No CRP single nucleotide polymorphism or haplotype was associated with a significantly increased or decreased COPD risk. Increased hsCRP levels are predictive for the occurrence of COPD in smokers. However, haplotypes of the CRP gene, which influence hsCRP levels, are not associated with an altered risk of developing COPD.


Gut microbiota composition and its effects on obesity and insulin resistance.
Rising evidence suggest that variation in the gut microbiome at gene and species levels defines subsets of individuals who have increased risk of obesity-related metabolic disorders, including insulin resistance and type 2 diabetes, which is influenced by diet and genetic profile of the host. Our goal in this review is gathering the newest findings concerning gut microbiota composition and effects on host's metabolism. Dietary changes have been shown as the most prominent shaper of gut microbiota composition, reflecting major phenotypes, which can also be transmitted to other individuals, in spite of genetic variances. Gut microbiota composition has also been presented as diversity, which may have important implications in metabolite production and consequent interference with inflammatory activation, insulin resistance, and obesity. Specific approaches made it possible to comprehend some of the interactions between certain bacterial strains and their host, and how their metabolites may interfere with host's cell signaling, changing its metabolic profile. Herein, we discuss some of the mechanisms by which alterations in the gut microbiota composition may contribute to the pathophysiology of obesity and its related comorbidities.


Antibacterial effect of different concentrations of garlic (Allium sativum) extract on dental plaque bacteria.
Allium sativum, commonly known as garlic, exhibits antibacterial effects against a wide range of bacteria. The objective of this in vitro study was to assess the antibacterial effect of different concentrations of garlic extract against human dental plaque microbiota. Antibacterial activities of four different concentrations of garlic extract (5%, 10%, 20%, and 100%) were evaluated against Streptococcus mutans, Streptococcus sanguis, Streptococcus salivarius, Pseudomonas aeruginosa, and lactobacillus spp. using the disk diffusion method. Papers soaked in 0.2% concentration chlorhexidine gluconate and saline were used as positive and negative controls, respectively. The data were subjected to one-way ANOVA and the Tukey multiple comparisons test at a 5% significance level. All bacterial strains were inhibited by all test materials. The inhibition zones of the different concentrations of garlic extract were not significantly different for S. mutans, S. sanguis, and S. salivarius. For P. aeruginosa and lactobacillus spp. the inhibition zones of 5%, 10% and 20% concentrations were not significantly different from one another, but they were significantly more than that of the 100% extract. The 5%, 10%, 20%, and 100% concentrations of garlic extract had similar effects, so further studies seem to be indicated on the usefulness of the 5% extract.


Case report: intrahepatic portal-hepatic venous shunts associated with a huge pelvic leiomyoma.
We present a case of portal-systemic encephalopathy due to intrahepatic multiple portal-hepatic venous shunts. A 71-year-old woman was admitted to our hospital because of recurrent episodes of disturbed consciousness. She showed no clinical signs of portal hypertension. Liver function was normal, except for an indocyanine green retention rate of 34% at 15 min and blood ammonia level of 282 microg/dL. Portal venography revealed dilatation of the portal vein and multiple portal-hepatic venous shunts, and a liver biopsy specimen revealed almost normal liver. Further clinical examination revealed a huge pelvic tumour. At laparotomy, two dilated veins were seen to arise from the pelvic tumour with blood flow into the mesentery. The tumour was resected successfully and a histological diagnosis of leiomyoma was made. The blood ammonia concentration decreased to the normal range postoperatively. A follow-up portal venogram demonstrated decreased portal vein dilatation and minor portal-hepatic venous shunts, considered to be congenital in origin. It is concluded that hepatic encephalopathy was produced in this patient due to an excess portal blood flow from the huge pelvic leiomyoma via the mesentery, with portosystemic shunting through pre-existent (probably congenital) intrahepatic anastomoses.


Assessment of toxicological profiles of the municipal wastewater effluents using chemical analyses and bioassays.
The hazardous chemical contamination of untreated wastewater and secondary effluent from the wastewater treatment plant (WWTP) of the city of Zagreb, Croatia was comprehensively characterized using large-volume solid-phase extraction (SPE) and silica gel fractionation, followed by a detailed analysis of the resulting extracts by a combination of chemical and bioassay methods. Over 100 individual contaminants or closely related-contaminant groups were identified by high-resolution gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-QTOF). Ecotoxicity profiling of the investigated samples, including cytotoxicity, chronic toxicity and EROD activity; inhibition of the multixenobiotic resistance (MXR), genotoxicity and estrogenic potential, revealed the most significant contribution of toxic compounds to be present in polar fractions. Wastewater treatment using conventional activated sludge process reduced the initial toxicity of raw wastewater to various extents, ranging from 28% for algal toxicity to 73.2% for an estrogenic activity. The most efficient toxicity removal was observed for the polar compounds.


Synergistic effect of ethaselen and selenite treatment against A549 human non-small cell lung cancer cells.
In this study, we aimed to evaluate the growth inhibitory effect of the combination of ethaselen (BBSKE) and low fixed dose of selenite against A549 human non-small cell lung cancer cells in vitro. Growth inhibitory effects against A549 cells were determined by SRB assay. Combination index (CI) values were calculated based on Chou-Talalay median-effect analyses. Dose reduction index (DRI) values were applied to calculate dose reduction of selenite. Contents of free thiols and GSH were determined by DTNB assay and intracellular ROS levels by DCFH-DA fluorescence labeling. Compared with BBSKE or selenite single treatment, the combined application of ethaselen and a low fixed dose of selenite shortened the onset time of sodium selenite, reduced IC50 values, and increased the maximum inhibition rates, suggesting a possible molecular mechanism of the synergism. Obvious synergistic effects were observed after different times of combination treatment, especially after 24 h. Compared with selenite single treatment, dosage of selenite could be remarkably reduced in combination therapy to gain the same inhibitory effect on cell proliferation. Compared with BBSKE single treatment, the content of free thiols and GSH were significantly reduced and ROS levels greatly elevated in the combination group. For the combination treatment, cell viability increased as greater concentrations of GSH were added. All these results indicate that the combination treatment of BBSKE and selenite showed synergism to inhibit A549 cell proliferation in vitro, and also reduced the selenite dosage to mitigate its toxicity which is very meaningful for combination chemotherapy of lung cancer. The synergism was probably caused by the accelerated exhaustion of intracellular reductive substances, such as free thiols and GSH, which ultimately leads to enhanced oxidative stress and apoptosis.


Monte Carlo modeling of a holder for irradiation of dosimeters in beta radiation beams.
A study of the influence of a dosimetric holder and its cover for the irradiation of the dosimeters in the Beta Secondary Standard BSS2 radiation fields is reported. The correction factors for attenuation or scattering were calculated taking into account the BSS2 beta source energy, as well as the detector source distance. The study and the determination of these factors were carried out using the Monte Carlo Method. The results of the correction factors showed that the absorption and scattering of the electrons depend greatly on the energy of beta radionuclides. The determined correction factors are in agreement with the international report ISO 6980.


Molecular modeling and crystal structure of ERK2-hypothemycin complexes.
Resorcylic acid lactones containing a cis-enone-such as hypothemycin-are susceptible to Michael addition reactions and are potent and specific inhibitors of about 45 of the known Ser/Thr/Tyr protein kinases. These inhibitors bind reversibly, and then form a covalent adduct with a completely conserved cysteine in the ATP binding site of their target kinases. As a paradigm for the structures of the cis-enone resorcylic acid lactone complexes with this subset of kinases, we have modeled the structure of ERK2-hypothemycin reversible and covalent complexes using docking and extended molecular dynamics simulations. Subsequently, we determined the 2.5A resolution crystal structure of the complex that was in excellent accord with the modeled structure. The results were used to discuss structure-activity relationships, and provide a structural template for the development of irreversible inhibitors that complement the ATP binding site of kinases.


Influence of acute potassium loading on renal phosphate transport in the rat kidney.
This study examined 1) whether potassium-induced depression of phosphate excretion is a parathyroid hormone-dependent phenomenon, and 2) whether such stimulation of tubular phosphate reabsorption capacity involves increased phosphate reabsorption in the distal tubule. Potassium was infused into intact rats (25 mumol X min-1 X kg-1) during stepwise addition of phosphate to the infusion and led to a significant drop in phosphate excretion; this effect was abolished in thyroparathyroidectomized (TPTX) animals. In intact rats the maximal tubular Pi reabsorption per milliliter of glomerular filtrate (max TRPi/ml GF) was significantly higher in the potassium group (2.54 +/- 0.06 mumol/ml GF) compared with the control group (2.31 +/- 0.06 mumol/ml GF) (means +/- SE). In TPTX rats no difference in max TRPi/ml GF was observed: 3.44 +/- 0.07 and 3.49 +/- 0.07 mumol/ml GF during potassium and sodium infusion, respectively. Free-flow micropuncture was carried out on superficial distal tubules of intact rats and fluid samples were analyzed for [3H]inulin and phosphorus (electron microprobe). Phosphorus delivery into the distal tubule was similar in control and potassium-loaded rats. Whereas net phosphorus reabsorption along the distal tubule was absent in the control group, intravenous potassium administration stimulated distal phosphorus reabsorption. potassium stimulates renal phosphate reabsorption capacity, an effect that is abolished after TPTX. The potassium effect on phosphate occurs along the distal tubule.


[Female prostate cancer?]
We present a case of a female patient who had a clinically suspected advanced urothelial carcinoma of the urethra. Histopathological examination surprisingly revealed a malignant tumor with morphological and immunohistochemical features of prostate cancer, leading to the diagnosis of the extremely rare entity of Skene's gland adenocarcinoma.


Modulation of SERCA: implications for the failing human heart.
Human heart failure is characterized by distinct alterations in the intracellular homeostasis and key regulators of the sarcoplasmic reticulum Ca2+ sequestration mechanisms. Systolic peak Ca2+ is reduced, diastolic Ca2+ levels are increased and diastolic Ca2+ decay is prolonged. Recently specific changes in the expression, function and modulation of SR Ca2+-ATPase (SERCA) have been elucidated. As such, in a variety of studies SERCA expression appeared to be decreased in the failing human heart, although these findings have been discussed controversially depending on the studied tissue, especially with respect to the non-failing samples and regional variation in the obtained samples. However, consistent findings of a diminished Ca2+ dependent SERCA activation were found. Increasing evidence has been provided that one of the underlying mechanisms for a decreased activation of SERCA is its altered regulation. With respect to this, the modulations through phospholamban and Ca2+-dependent protein kinase II (CaMK II) play a detrimental role in regulating SERCA function. Phospholamban phosphorylation of SERCA at the serine-16 and threonine-17 site is diminished in human heart failure resulting in decreases in the apparent affinity for Ca2+ of the SR Ca2+ uptake rates. In contrast, activation of CaMK II leads to an increased maximal velocity of SR Ca2+ sequestration that may enhance SR Ca2+-load. Additional regulation has been recently elucidated by changes in the apparent coupling ratio of Ca2+ transported per ATP hydrolysed. This review summarizes recent advances in the understanding how SERCA is modulated under physiological and pathophysiological conditions.


The phylogenetic approach for viral infectious disease evolution and epidemiology: An updating review.
In the last decade, the phylogenetic approach is recurrent in molecular evolutionary analysis. On 12 May, 2019, about 2 296 213 papers are found, but typing "phylogeny" or "epidemiology AND phylogeny" only 199 804 and 20 133 are retrieved, respectively. Molecular epidemiology in infectious diseases is widely used to define the source of infection as so as the ancestral relationships of individuals sampled from a population. Coalescent theory and phylogeographic analysis have had scientific application in several, recent pandemic events, and nosocomial outbreaks. Hepatitis viruses and immunodeficiency virus (human immunodeficiency virus) have been largely studied. Phylogenetic analysis has been recently applied on Polyomaviruses so as in the more recent outbreaks due to different arboviruses type as Zika and chikungunya viruses discovering the source of infection and the geographic spread. Data on sequences isolated by the microorganism are essential to apply the phylogenetic tools and research in the field of infectious disease phylodinamics is growing up. There is the need to apply molecular phylogenetic and evolutionary methods in areas out of infectious diseases, as translational genomics and personalized medicine. Lastly, the application of these tools in vaccine strategy so as in antibiotic and antiviral researchers are encouraged.


Cervical pedicle screw insertion: assessment of safety and accuracy with computer-assisted image guidance.
We used a commercially available computer-assisted image-guidance system for cervical pedicle screw insertion in both the laboratory and in a preliminary clinical setting. Nine plastic cervical spine models (C2-C7) were used in the laboratory test. The StealthStation was used to create the preoperative plan for each screw such that it would be inserted down the center of the pedicle, parallel to the long axis. Using a light-emitting diode-equipped drill guide, 2-mm holes were drilled in 108 pedicles. A total of 108 pedicle holes were drilled. The mean trajectory deviation from the surgical plan in the axial plane was 1.7+/-1.7 degrees (range, 0 to 8 degrees), and the mean deviation of the position of the hole was 1.7+/-0.6 mm (range, 0.1 to 2.9 mm). Eighty-three drill holes (76.9%) were contained within the pedicles, whereas partial cortical perforation was noted in 25 pedicles (23.1%). In the clinical setting, 36 cervical pedicle screws were inserted in nine patients using the image-guided system. Within the limits of imaging artifact, all 36 pedicle screws appear to have been inserted accurately by postoperative computed tomographic examination. No neurologic or vascular complications were encountered.


Natriuretic effects of calcium antagonists. Clinical implications.
An important characteristic which distinguishes calcium antagonists from traditional vasodilators is their natriuretic rather than antinatriuretic action. Evidence that all classes of calcium antagonists have a natriuretic effect has been provided by intravenous administration in animal experiments. After single oral doses, all calcium antagonists have some natriuretic effect, but its extent differs with different compounds; dihydropyridines have a greater immediate natriuretic response than verapamil or gallopamil. Recent experiments by our group using the newer dihydropyridine derivative, isradipine, indicate that the natriuretic response may occur at even lower doses than the antihypertensive effect. Indeed, doses of 2.5mg, 5.0mg and 7.5mg of this compound caused an increasingly larger fall in blood pressure, while the natriuretic and diuretic effects peaked with the 2.5mg dose. The natriuretic effect is associated with no or a very small change in glomerular filtration rate and with a more consistent increase in renal plasma flow. The duration of the natriuretic action of calcium antagonists is debated. Our studies have shown that this action is evident during the first 2 days of administration of a dihydropyridine, and then seems to disappear; however, a small negative sodium balance persists, an observation that accounts for the absence of any increase in bodyweight or fluid volumes with long term administration of calcium antagonists, despite their vasodilating action. Recent data have shown that under long term treatment with isradipine sodium clearance was still increased a few hours after administration.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum high sensitivity C-reactive protein and cognitive function in elderly women.
Inflammation has been linked to cognitive impairment. However, limited data are available on the association between inflammatory markers and cognitive function. We tested the hypothesis that elevated serum concentration of high sensitivity C-reactive protein (hs-CRP), an established marker of low-grade inflammation, predicts cognitive impairment in elderly women. A 12-year population-based follow-up study. A total of 97 women between 60 and 70 years of age at baseline. Serum hs-CRP concentration was measured by a high sensitivity assay. Global cognitive function was measured with the Mini-Mental State Examination (MMSE), and memory and cognitive speed were measured with a detailed cognitive test battery. Higher baseline hs-CRP was associated with poorer memory at 12-year follow-up without adjustment and after adjustment for age, education and depression (standardised regression coefficient beta -0.842, 95% confidence interval -1.602 to -0.083, P = 0.030), and further adjustment for the use of hormone replacement therapy, smoking, serum LDL cholesterol and body mass index (standardised regression coefficient beta -0.817, 95% confidence interval -1.630 to -0.004, P = 0.049). Memory at 12-year follow-up worsened linearly with increasing hs-CRP at baseline (P = 0.048 for linear trend). There was no association between hs-CRP at baseline and cognitive speed or MMSE score at 12-year follow-up. High serum hs-CRP concentration predicts poorer memory 12 years later in elderly women. Hs-CRP may be a useful biomarker to identify individuals at an increased risk for cognitive decline.


NHC-mediated cross-coupling of sugar-derived cyclic nitrones with enals: general and efficient synthesis of polyhydroxylated pyrrolizidines and indolizidines.
A general and efficient method for the synthesis of polyhydroxylated pyrrolizidines and indolizidines has been developed based on the NHC-catalyzed cross-coupling of sugar-derived cyclic nitrones with enals, which afforded the key intermediates, γ-hydroxyl amino esters, in good to excellent yields. Thus, a variety of polyhydroxylated pyrrolizidines and indolizidines have been synthesized and assayed against various glycosidases, which showed that aryl or alkyl substituents at C-7 of pyrrolizidines or at C-8 of indolizidines reduced the potency of the glycosidase inhibition of these bicyclic iminosugars.


Video game addiction and college performance among males: results from a 1 year longitudinal study.
This study explored the pattern of video game usage and video game addiction among male college students and examined how video game addiction was related to expectations of college engagement, college grade point average (GPA), and on-campus drug and alcohol violations. Participants were 477 male, first year students at a liberal arts college. In the week before the start of classes, participants were given two surveys: one of expected college engagement, and the second of video game usage, including a measure of video game addiction. Results suggested that video game addiction is (a) negatively correlated with expected college engagement, (b) negatively correlated with college GPA, even when controlling for high school GPA, and (c) negatively correlated with drug and alcohol violations that occurred during the first year in college. Results are discussed in terms of implications for male students' engagement and success in college, and in terms of the construct validity of video game addiction.


[Large aneurysms of the internal carotid artery in its infraclinoidal intracranial portion (author's transl)].
Two new cases of large aneurysms of the infraclinoidal intracranial portion of the internal carotid artery are reported. After a survey of the literature, the authors emphasize the rarity of these malformations, their particular clinical picture with involvement of the cranial nerves. Among the various surgical techniques which were suggested for the management of these large aneurysms, the ligation of the internal carotid artery in the neck is favoured by the authors as the best procedure.


Effect of interferon-alpha on the expression of tumour necrosis factor-alpha by metastatic malignant melanoma in vivo.
To our knowledge modulation of the expression of tumour necrosis factor-alpha (TNF-alpha) in malignant melanoma metastases in vivo has not been reported. The expression of TNF-alpha by malignant melanoma cells was studied immunohistochemically using an anti-TNF-alpha antibody. The specificity of the staining reaction was demonstrated by absorption of the TNF-alpha antibody with human recombinant TNF-alpha, which inhibited the staining reaction. The TNF-alpha expression was also verified by in situ hybridization for mRNA. Metastases from 37 patients were studied, 21 of whom were treated with IFN-alpha. All 16 metastases from untreated patients were positive for TNF-alpha. Based on the average staining intensity of the melanoma cells for TNF-alpha, the metastases were classified into two groups. The expression of TNF-alpha varied considerably between metastases from different patients and also within the same metastasis. Melanoma cells in areas with low cellularity and large numbers of infiltrating inflammatory cells were generally weakly stained. This is in good agreement with a low staining score for TNF-alpha in metastases showing marked histopathological regression. Seven out of 13 patients with a low staining score for TNF-alpha showed a marked regression of their tumours. In contrast one out of five patients with a high staining score for TNF-alpha showed a marked tumour regression, suggesting that tumour cells sensitive to immune-mediated regression express less TNF-alpha. Interferon-alpha (IFN-alpha) appears to modulate the expression of TNF-alpha. Significantly more patients treated with IFN-alpha had metastases with a low TNF-alpha staining score compared with untreated patients. Thus, seven out of 21 patients treated with IFN-alpha showed a high expression of TNF-alpha in contrast to 13 out of 16 in the untreated group (P = 0.01).


Effects of periodic weight support in a simulated weightless environment in preventing bone demineralisation.
Anti Orthostatic Hypokinetic posture in rats by tail suspension for 15 days (d) simulates the deconditioning effects of weightlessness on the weight bearing bones. The present study evaluates the effects of daily 4 hour (h) weight support (WS) during simulated weightlessness (S-W) in preventing these changes. Adult male albino rats were divided into three groups as (i) Control (CON, n = 12), (ii) Hind limb unweighing by tail suspension for 15 d (HU, n = 18), (iii) HU with daily 4 h WS (4 HRWS, n = 11). After 15 d tibia from all the animals were removed and subsequently dried, ashed and then calcium content of the bones were determined. HU showed reductions in the water content by 35.8%, organic matrix by 12.2% and calcium content by 33.4% of tibia. 4 h WS during S-W resulted in complete prevention of water loss and organic matrix loss and partial prevention of the loss of calcium content. Calcium content of tibia in 4 HRWS remained 15.2% less as compared to CON. These findings indicate that 4 h WS is partially successful in preventing the demineralisation effects of S-W on weight bearing bone tibia.


Theory and methodology for utilizing genes as biomarkers to determine potential biological mixtures.
Genetically determined mixture information can be used as a surrogate for physical or behavioral characteristics in epidemiological studies examining research questions related to socially stigmatized behaviors and horizontally transmitted infections. A new measure, the probability of mixture discrimination (PMD), was developed to aid mixture analysis that estimates the ability to differentiate single from multiple genomes in biological mixtures. Four autosomal short tandem repeats (STRs) were identified, genotyped and evaluated in African American, European American, Hispanic, and Chinese individuals to estimate PMD. Theoretical PMD frameworks were also developed for autosomal and sex-linked (X and Y) STR markers in potential male/male, male/female and female/female mixtures. Autosomal STRs genetically determine the presence of multiple genomes in mixture samples of unknown genders with more power than the apparently simpler X and Y chromosome STRs. Evaluation of four autosomal STR loci enables the detection of mixtures of DNA from multiple sources with above 99% probability in all four racial/ethnic populations. The genetic-based approach has applications in epidemiology that provide viable alternatives to survey-based study designs. The analysis of genes as biomarkers can be used as a gold standard for validating measurements from self-reported behaviors that tend to be sensitive or socially stigmatizing, such as those involving sex and drugs.


Carcinoma of the common bile duct with superficial spread to the intrahepatic segmental bile ducts: a case report.
A 54-year-old woman presented with jaundice. Percutaneous transhepatic biliary drainage, cholangiography via a percutaneous transhepatic biliary, drainage catheter, and percutaneous transhepatic cholangioscopy were performed to alleviate the jaundice and to evaluate her biliary system. A diffuse-type tumor was detected in the common bile duct. The tumor had spread superficially up to the right anterior segmental duct and the left hepatic duct and involved the caudate branches. Curative surgery, which included a right anterior segmentectomy, total caudate lobectomy, and pylorus-preserving pancreatoduodenectomy, was performed. The histopathologic diagnosis was moderately differentiated tubular adenocarcinoma originating at the common bile duct. The extent of the superficial spread of the tumor corresponded to our preoperative determination. Her postoperative recovery was uneventful. In this case report, we discuss the accurate preoperative diagnosis and rational surgical treatment of bile duct carcinoma with superficial spread.


Cell receptor-independent infection by a neurotropic murine coronavirus.
The cellular receptors for a coronavirus, mouse hepatitis virus (MHV), have been recently identified as one or more members of the carcinoembryonic antigen (CEA) family. The neurotropic JHM strain of MHV (MHV-JHM) possesses a highly fusogenic surface (S) glycoprotein. This protein is now shown to promote the spread of MHV into cells lacking the specific CEA-related MHV receptor. Resistant cells are recruited into MHV-induced syncytium with consequent production of progeny virus. Cell-to-cell spread of virus via membrane fusion without the requirement for specific cell surface receptor offers a novel way for virus to spread within infected hosts.


Olanzapine and pregnancy.
This report focuses on the case of a pregnant woman with a bad obstetric history who developed psychosis at the 23 rd week of gestation. She was treated with olanzapine from the 24th week until 10 days prior to delivery. No adverse events occurred during pregnancy or delivery. The Apgar score was 8/10 at one minute and 9/10 at 5 minutes.


The validation of a computer-adaptive test (CAT) for assessing health-related quality of life in children and adolescents in a clinical sample: study design, methods and first results of the Kids-CAT study.
Recently, we developed a computer-adaptive test (CAT) for assessing health-related quality of life (HRQoL) in children and adolescents: the Kids-CAT. It measures five generic HRQoL dimensions. The aims of this article were (1) to present the study design and (2) to investigate its psychometric properties in a clinical setting. The Kids-CAT study is a longitudinal prospective study with eight measurements over one year at two University Medical Centers in Germany. For validating the Kids-CAT, 270 consecutive 7- to 17-year-old patients with asthma (n = 52), diabetes (n = 182) or juvenile arthritis (n = 36) answered well-established HRQoL instruments (Pediatric Quality of Life Inventory™ (PedsQL), KIDSCREEN-27) and scales measuring related constructs (e.g., social support, self-efficacy). Measurement precision, test-retest reliability, convergent and discriminant validity were investigated. The mean standard error of measurement ranged between .38 and .49 for the five dimensions, which equals a reliability between .86 and .76, respectively. The Kids-CAT measured most reliably in the lower HRQoL range. Convergent validity was supported by moderate to high correlations of the Kids-CAT dimensions with corresponding PedsQL dimensions ranging between .52 and .72. A lower correlation was found between the social dimensions of both instruments. Discriminant validity was confirmed by lower correlations with non-corresponding subscales of the PedsQL. The Kids-CAT measures pediatric HRQoL reliably, particularly in lower areas of HRQoL. Its test-retest reliability should be re-investigated in future studies. The validity of the instrument was demonstrated. Overall, results suggest that the Kids-CAT is a promising candidate for detecting psychosocial needs in chronically ill children.


Anxiety sensitivity within the anxiety disorders: disorder-specific sensitivities and depression comorbidity.
The tendency to perceive anxious states as aversive and harmful is hypothesized to confer vulnerability to the development of anxiety disorders. The most commonly used measure of anxiety sensitivity, the Anxiety Sensitivity Index [ASI; Reiss, S., Peterson, R.A., Gursky, D.M., & McNally R.J. (1986). Anxiety sensitivity, anxiety frequency, and the prediction of fearfulness. Behavior Research and Therapy, 24, 1-8], is composed of multiple lower-order factors, assessing fear of physical symptoms, fear of publicly observable anxious symptoms, and fear of cognitive dyscontrol. This study examined the convergent validity of the lower-order anxiety sensitivity dimensions in DSM-IV diagnosed anxiety disorders. Participants with primary diagnoses of panic disorder with agoraphobia, social phobia, and generalized anxiety disorder (GAD) completed the ASI and measures of anxiety and depression severity. Support was found for the convergent validity of all ASI dimensions in reference to thematically related anxiety disorders and in the identification of patients presenting with and without secondary major depressive disorder (MDD). The ASI-fear of cognitive dyscontrol dimension displayed strong and nonredundant associations with GAD, dimensional depression scores, and secondary diagnoses of MDD. The conceptual implications of the shared importance of fear of cognitive dyscontrol in GAD and MDD are discussed.


Shade tolerance: when growing tall is not an option.
Two different plant strategies exist to deal with shade: shade avoidance and shade tolerance. All shade-exposed plants optimize photosynthesis to adapt to the decrease in light quality and quantity. When shaded, most species in open habitats express the shade-avoidance syndrome, a growth response to escape shade. Shade-tolerant species from forest understories cannot outgrow surrounding trees and adopt a tolerance response. Unlike shade avoidance, virtually nothing is known about regulation of shade tolerance. In this opinion article, we discuss potential modes of molecular regulation to adopt a shade-tolerance rather than a shade-avoidance strategy. We argue that molecular approaches using model and non-model species should help identify the molecular pathways that underpin shade tolerance, thus providing knowledge for further crop improvement.


Transcriptome and proteome analyses in response to 2-methylhydroquinone and 6-brom-2-vinyl-chroman-4-on reveal different degradation systems involved in the catabolism of aromatic compounds in Bacillus subtilis.
Bacillus subtilis is exposed to a variety of antimicrobial compounds in the soil. In this paper, we report on the response of B. subtilis to the fungal-related antimicrobials 6-brom-2-vinyl-chroman-4-on (chromanon) and 2-methylhydroquinone (2-MHQ) using proteome and transcriptome analyses. Chromanon, a derivative of aposphaerins from Aposphaeria species caused predominant protein damage in B. subtilis as indicated by the induction of the HrcA, CtsR, and Spx regulons. The expression profile of the ganomycin-related substance 2-MHQ was similar to that of catechol as reflected by the common induction of the thiol-specific oxidative stress response. Several putative ring-cleavage dioxygenases and oxidoreductases were differentially up-regulated by 2-MHQ, catechol, and chromanon including yfiDE, ydfNOP, yodED, ycnDE, yodC, and ykcA. The nitroreductase encoding yodC gene is induced in response to catechol, 2-MHQ, and chromanon, which depend on the MarR-type repressor YodB. The yfiDE (catDE) operon encodes a catechol-2,3-dioxygenase which is most strongly induced by catechol. The yodED (mhqED), ydfNOP (mhqNOP) operons, and ykcA (mhqA) respond most strongly to 2-MHQ and encode putative hydroquinone-specific extradiol dioxygenases. The ycnDE operon was most strongly induced by chromanon. Mutational analyses revealed that the putative hydroquinone-specific dioxygenases MhqO and MhqA confer resistance to 2-MHQ in B. subtilis.


Chemical composition and content of antinutritional factors in Polish cultivars of peas.
The seeds of 15 Polish pea varieties contained from 221 to 281 g/kg crude protein with a mean of 240.2 +/- 3.5 g/kg dry matter (DM). The weight of 1000 pea seeds, depending on cultivar, ranged from 209.4 to 280.4 g. No interactive effect between the seed mass and the crude protein content was detected. The highest significant negative correlation between weight of seeds and dietary fiber content was r = -0.815XX. The content of dietary fiber ranged from 161.5 to 209.9 g/kg with a mean of 187.9 +/- 3.8 g/kg. The mean gross energy of seeds was 18.1 +/- 0.28 MJ/kg. Amino acid composition of all the cultivars was similar, which was indicated by a similar index of essential amino acids (EAAI) of about 69.7 +/- 0.25. Trypsin inhibitor content in seeds was from 2.83 to 7.32 TIU/mg and the content of phytates ranged from 6.32 to 13.36 mg/g DM. The mean content of polyphenols and flavanols in analysed pea cultivars was 0.92 and 0.46 mg/g, respectively. In the seeds of most cultivars little or no pyrimidine glucosides, i.e. vicine and convicine, were found. The overall mean oligosaccharide content was 64.3 +/- 1.8 g/kg, of which alpha-galactosides were 46.8 +/- 2.0 g/kg. The antinutritional factor content was not significantly correlated with protein content. No statistical relationship was found between crude protein and dietary fiber content. It was observed that pea cultivars with higher trypsin inhibitor activity contained significantly less flavanols (r = -0.607X) and alpha-galactosides (r = -0.617X). The varieties with higher seed content of dietary fiber contained the highest amount of alpha-galactosides (r = 0.514X).


Morphine and methadone-induced antinociception in rats permanently depleted of brain dopamine.
The purpose of the present study was to evaluate the role of brain norepinephrine (NE) and/or dopamine (DA) in the production of the antinociceptive effects of morphine and methadone. Rats were permanently depleted of brain NE and/or DA via 6-hydroxydopamine (6-OHDA) treatments at two weeks of age. Six to eight weeks later, the antinociceptive activity of morphine and methadone was determined in control, NE and DA-depleted, and DA-depleted rats by tail-flick methods. Both dose-response and time-duration studies were conducted. The data obtained suggested that DA was important to morphine, but not to methadone-induced antinociception. However, this relationship appeared contingent upon the level of DA-depletion. An antagonism of morphine's effects was observed when DA levels were down by at least 85% whereas a facilitation of morphine's effect occurred when DA levels were 50% or less. These findings were discussed in relation to more recent concepts suggesting that: 1) DA-related behaviors are contingent upon a balance between excitatory and inhibitory DA neuron pools, and 2) antinociception may (in relation to DA) also be controlled via a balance between this system (DA) and NE systems. Thus, it was suggested that the potency of morphine's antinociceptive effects appears contingent upon a balance between one or more of these neuron pathways.


Quantitative measurement of fusion between human immunodeficiency virus and cultured cells using membrane fluorescence dequenching.
Human immunodeficiency virus (HIV) was purified by sucrose gradient centrifugation and labeled with octadecylrhodamine B-chloride (R-18) under conditions resulting in 90% quenching of the fluorescence label. Incubation of R-18-labeled HIV (R-18/HIV) with CD4-positive CEM and HUT-102 cells, but not with CD4-negative MLA-144 cells, resulted in fluorescence dequenching (DQ, increase in fluorescence) of 20-25%. Similar level of DQ was observed upon incubation of CEM cells with R-18-labeled Sendai virus. DQ was observed when R-18/HIV was incubated with CD4+ cells at 37 degrees C, but not at 4 degrees C. Most of the increase in fluorescence occurred within 5 min of incubation at 37 degrees C and was independent of medium pH over the range of pH 5-8. Preincubation of cells with the lysosomotropic agent NH4Cl had no inhibitory effect on DQ. Complete inhibition was observed when target cells were fixed with glutaraldehyde prior to R-18/HIV addition. Our results demonstrate application of membrane fluorescence dequenching method to a quantitative measurement of fusion between HIV and target cell membranes. As determined by DQ, HIV penetrates into target cells by a rapid, pH-independent, receptor-mediated and specific process of fusion between viral envelope and cell plasma membrane, quite similar to that observed with Sendai virus.


The year 2017 in the European Heart Journal-Cardiovascular Imaging: Part I.
The European Heart Journal - Cardiovascular Imaging was launched in 2012. It has gained an impressive impact factor of 8.336 during its first 6 years and is now established as one of the top 10 cardiovascular journals in the world and the most important cardiovascular imaging journal in Europe. The most important studies published in the journal in 2017 will be highlighted in two reports. Part I will focus on studies about myocardial function, coronary artery disease and myocardial ischaemia, and emerging techniques and applications in cardiovascular imaging, whereas Part II will focus on valvular heart disease, heart failure, cardiomyopathies, and congenital heart disease.


Jinmaitong alleviates the diabetic peripheral neuropathy by inducing autophagy.
To observe the deregulation of autophagy in diabetic peripheral neuropathy (DPN) and investigate whether Jinmaitong ( JMT) alleviates DPN by inducing autophagy. DPN models were established by streptozotocin-induced diabetic rats and Schwann cells (SCs) cultured in high glucose medium. The pathological morphology was observed by the improved Bielschowsky's nerve fiber axonal staining and the Luxol fast blue-neutral red myelin staining. The ultrastructure was observed by the transmission electron microscopy. Beclin1 level was detected by immunohistochemistry and Western blot. The proliferation of cultured SCs was detected by methylthiazolyldiphenyl-tetrazolium bromide. Diabetic peripheral nerve tissues demonstrated pathological morphology and reduced autophagic structure, accompanied with down-regulation of Beclin1. JMT apparently alleviated the pathological morphology change and increased the autophagy [in vivo, Beclin1 integral optical density (IOD) value of the control group 86.6±17.7, DM 43.9±8.8, JMT 73.3 ±17.8, P<0.01 or P<0.05, in vitro Beclin1 IOD value of the glucose group 0.47±0.25 vs the control group 0.88±0.29, P<0.05]. Consequently, inhibition of autophagy by 3-methyladenine resulted in a time- and concentration-dependent decrease of the proliferation of SCs (P<0.05, P<0.01). Down-regulation of autophagy in SCs might contribute to the pathogenesis of DPN. JMT alleviates diabetic peripheral nerve injury at least in part by inducing autophagy.


Evaluation of proteinase-activated receptor-1 (PAR1) agonists and antagonists using a cultured cell receptor desensitization assay: activation of PAR2 by PAR1-targeted ligands.
We developed a calcium signaling-based assay, using cultured human embryonic kidney cells (HEK), that evaluates simultaneously, the activation/desensitization or blockade of the proteinase-activated receptors, PAR1 and PAR2. Using this assay, we analyzed the actions of a number of previously described putative PAR1-targeted peptide agonists and antagonists. We found that most of the previously described PAR1-targeted agents can also activate/desensitize PAR2, and most of these peptides can also activate a calcium signaling pathway in a target cell that possesses PAR2 along with PAR1. Furthermore, we used this assay to develop a PAR1 receptor-activating probe [Ala-parafluoroPhe-Arg-Cha-Cit-Tyr-NH2 (Cit-NH2)], which displays a high degree of specificity for PAR1 over PAR2, and we used the assay to quantitate the ability of trypsin to disarm the activation of PAR1 by thrombin. The abilities of the PAR1-targeted agents to desensitize or block PAR1 in the HEK cell assay were compared with their activities in a human platelet aggregation assay. Our data illustrate the usefulness of the HEK cell assay for evaluating the PAR1/PAR2 selectivity of PAR-activating agonists. The PAR1-selective agonist that we developed using the assay should prove useful for studying the effects of selectively activating PAR1 in vivo.


Bone formation in axial spondyloarthritis.
The success of targeted therapies directed against tumor necrosis factor for patients with spondyloarthritis has shifted the focus of physicians and scientists towards the prevention of structural damage to the involved structures, in particular the sacroiliac joints and the spine, to avoid loss of function and disability. Structural damage to the skeleton as witnessed by radiography mainly consists of new bone formation potentially progressively leading to spine or joint ankylosis. This important long-term outcome parameter has been difficult to study, not alone because the time window for change may be long but also because human tissues with direct translational relevance are rarely available. Data from rodent models have identified growth factor signaling pathways as relevant targets. Both human and animal studies have tried to understand the link between inflammation and new bone formation. At the current moment, most evidence points towards a strong link between both but with the question still lingering about the sequence of events, disease triggers, and the interdependence of both features of disease. New discoveries such as a masterswitch T cell population that carries the IL23 receptor and the analysis of auto-antibodies directed again noggin and sclerostin are contributing to innovative insights into the pathophysiology of disease. Long-term data with tumor necrosis factor (TNF) inhibitors also suggest that some window of opportunity may exist to inhibit structural disease progression. All these data provide support for a further critical analysis of the available datasets and boost research in the field. The introduction of novel disease definitions, in particular the characterization of non-radiographic axial spondyloarthritis patients, will likely be instrumental in our further understanding of structural damage.


[Cutaneous lupus erythematosus and skin manifestations in systemic lupus erythematosus].
Skin manifestations are frequently observed in lupus erythematosus (LE) and are manifold. Nonspecific and specific symptoms can be differentiated with the latter belonging to the dermatologically well-characterized clinical entities of acute cutaneous, subacute cutaneous, chronic cutaneous as well as intermittent cutaneous LE. These forms are differentially related to systemic LE. Patient history and clinical examinations, laboratory and immunoserological findings as well as organ imaging results determine the time point as well as the intensity of therapy. Apart from cessation of smoking and alcohol consumption as well as stringent UV protection, topical therapy with corticosteroids or calcineurin inhibitors may suffice with limited forms of the disease. In many cases, however, systemic treatment with antimalarial drugs as a basic treatment is mandatory. Several immunosuppressive agents can alternatively be used in conjunction with systemic corticosteroids. Early and effective therapy is important to prevent irreversible scarring of the skin and to avoid internal organ damage.


Egg-protein-induced villous atrophy.
The effect of egg protein on the small bowel mucosa of a 9-month-old infant with a history of intolerance to egg protein was studied. Within 24 h of ingestion of egg protein marked villous atrophy, depletion of mucosal oligosaccharidases, impaired absorption of xylose, and depressed serum complement levels were observed. The study demonstrates that egg protein is yet another cause of flat mucosa of the small intestine in infants.


Quantifying Inter-Residue Contacts through Interaction Energies.
The validity and accuracy of protein modeling is dependent on constructing models that account for the inter-residue interactions crucial for protein structure and function. Residue interaction networks derived from interatomic van der Waals contacts have previously demonstrated usefulness toward designing protein models, but there has not yet been evidence of a connection between network-predicted interaction strength and quantitative interaction energies. This work evaluates the intraprotein contact networks of five proteins against ab initio interaction energies computed using symmetry-adapted perturbation theory. To more appropriately capture the local chemistry of the protein, we deviate from traditional protein network analysis to redefine the interacting nodes in terms of main chain and side chain functional groups rather than complete amino acids. While there is no simple correspondence between the features of the contact network and actual interaction strength, random forest models constructed from minimal structural, network, and chemical descriptors are capable of accurately predicting interaction energy. The results of this work serve as a foundation for the development and improvement of functional group-based contact networks.


The role of cortical connectivity in Alzheimer's disease pathogenesis: a review and model system.
Here we review current evidence in support of the cortical disconnection/cortical connectivity model of Alzheimer disease (AD) pathogenesis, a model which predicts that one of the first events in AD is damage to the entorhinal cortex and/or subiculum resulting in the disconnection of the hippocampal formation and neocortex, and the subsequent progression of the disease in a stepwise fashion along cortico-cortical connections. Much of the evidence for this model has been obtained from studies involving the limbic system where investigators have demonstrated a precise correspondence between established patterns of connectivity and the degenerative changes associated with AD. In addition, some studies of the distribution of neuritic plaques (NP) and neuro-fibrillary tangles (NFT) in the neocortex and subcortical structures have yielded corroborative data. The validity of the cortical disconnection/connectivity model in the neocortex remains to be established or refuted. We propose that testing of this model can be accomplished with systematic studies of the laminar and regional distribution of NP and NFT in a series of sequentially interconnected cytoarchitectural regions that also form part of two functional hierarchies--the paralimbic and occipitotemporal visual systems. To adequately control for variation between brains affected by AD, it is imperative that such studies be conducted in a large but varied population of AD cases exhibiting differences in several variables, including clinical and/or neuropathological severity of the disease, temporal duration of the disease, and clinical/neuropsychological profile. We believe that further understanding of the relationship between characteristic AD pathology and intrinsic anatomico-functional circuits will contribute not only to our comprehension of AD pathogenesis but also to our general knowledge of the human brain.


Childhood victimization and risk for alcohol and drug arrests.
Using data from a prospective cohorts design study, this paper examines the relationship between early childhood victimization and subsequent arrest for alcohol- and/or drug-related offenses. Complete official criminal histories are compared for cases of childhood physical and sexual abuse and neglect (n = 908) and a control sample (n = 667). After controlling for relevant demographic characteristics, logistic regression analyses indicate that childhood maltreatment is a significant predictor of adult, but not juvenile, arrests for alcohol- and/or drug-related offenses. Differential responses to maltreatment by race and gender are discussed as well as limitations of the findings and future directions for research.


Reproducibility of measurements with a new slit lamp-mounted ocular blood flow tonograph.
To assess the reliability of measurements of intraocular pressure (i.o.p.), pulse amplitude (PA), and pulsatile ocular blood flow (POBF) and the validity of measurements of IOP with a new ocular blood flow tonograph. Intraocular pressure pulse was assessed with pneumatic tonometry. In this study, we used the OBF Labs ocular blood flow tonograph with two different pneumatic probes, a modified Langham probe and a newly developed probe. One ophthalmologist compared two machines, first with the modified Langham probe and secondly with the newly developed probe (40 volunteers). Additionally, two ophthalmologists performed measurements on different days and in different sequence (34 volunteers). Furthermore, results of IOP measurements performed with this tonograph were compared to those of Goldmann applanation tonometry (213 volunteers). Using the modified Langham probe, POBF and PA were associated with the machine used for the test. However, using the newly developed pobe, no relevant or statistically significant differences were found for any variables, and reliability coefficients were between 0.70 and 0.90. Linear regression analysis of the Goldmann applanation tonometer on the measurements of IOP with the tonograph showed a regression coefficient of 0.765. Results of measurements performed with this ocular blood flow tonograph and the newly developed probe are expected to be reliable and comparable.


Variants of 11β-hydroxysteroid dehydrogenase (HSD11B) gene type 1 and 2 in Chinese obese adolescents.
To investigate the relationship between 11β-hydroxysteroid dehydrogenase (HSD11B) gene type 1 and 2 and obesity in Chinese children. A total of 400 obese and 200 healthy adolescents were enrolled as obese and control groups. Seven SNPs in HSD11B1 (rs4393158, rs2235543, rs10082248, rs10863782, rs2236903, rs2298930, rs4545339) and four variants in HSD11B2 gene (rs28934592, rs28934591, rs28934594 and rs28934593) were measured by automated platform MassArray. The rs28934592 in HSD11B2 and rs10863782 in HSD11B1 were excluded as false positive or HWE P < 0.05. Moreover, one allele type was found in the other three locations of HSD11B2. The minor allele frequency of rs2235543 and rs10082248 was higher in patients than that in controls (P = 0.045, P = 0.041, respectively). The rs10082248, rs2298930 and rs4545339 were associated with the risk of obesity in the recessive model (P < 0.05, respectively). Moreover, the total cholesterol in patients with GG or AG genotype was significantly higher than that in patients with AA genotype in rs10082248. The rs4393158 was associated with the hypertension in log-additive model test (P = 0.037), and glucose abnormal and hypercholesteremia in dominant model test (P < 0.05, respectively), while the rs2235543 was associated with hypercholesteremia in overdominant model test (P = 0.017). The polymorphism of HSD11B1 may be a cause of childhood obesity, or even associated with the complication of childhood obesity. However, variants of HSD11B2 may be not a cause of obesity.


WA3 Room for death - international museum - visitors' preferences regarding the end of their life.
Just as pain medications aim to relieve physical suffering, supportive surrounding for death and dying may facilitate well-being and comfort. However, little has been written of the experience of or preferences for settings for death and dying. We investigate preferences for and reflections about settings for end-of-life (EoL) in an international sample of museum visitors. Data derive from a project teaming artists and craftspeople together to create prototypes of space for difficult conversations in EoL settings. These prototypes were presented in a museum exhibition, "Room for Death", in Stockholm in 2012. As project consultants, we contributed a question to the public viewing the exhibition: "How would you like it to be around you when you are dying?" and analysed responses with a phenomenographic approach. Five-hundred twelve responses were obtained from visitors from 46 countries. Responses were categorised in the following inductively- derived categories of types of deaths: The "Familiar", "Larger-than life", "Lone", "Mediated" "Calm and peaceful", "Sensuous", "'Green'", and "Distanced" death. Responses could relate to one category or be composites uniting different categories in individual combinations. These data provide insight into different facets of contemporary reflections about death and dying. Despite the selective sample, the findings give reason to consider how underlying assumptions and care provision in established forms for EoL care may differ from people's preferences. This project can be seen as an example of innovative endeavours to promote public awareness of issues related to death and dying, within the framework of health-promoting palliative care.


Dual Role of Mitochondrial Porin in Metabolite Transport across the Outer Membrane and Protein Transfer to the Inner Membrane.
The mitochondrial inner membrane harbors a large number of metabolite carriers. The precursors of carrier proteins are synthesized in the cytosol and imported into mitochondria by the translocase of the outer membrane (TOM) and the carrier translocase of the inner membrane (TIM22). Molecular chaperones in the cytosol and intermembrane space bind to the hydrophobic precursors to prevent their aggregation. We report that the major metabolite channel of the outer membrane, termed porin or voltage-dependent anion channel (VDAC), promotes efficient import of carrier precursors. Porin interacts with carrier precursors arriving in the intermembrane space and recruits TIM22 complexes, thus ensuring an efficient transfer of the precursors to the inner membrane translocase. Porin channel mutants impaired in metabolite transport are not disturbed in carrier import into mitochondria. We conclude that porin serves distinct functions as outer membrane channel for metabolites and as coupling factor for protein translocation into the inner membrane.


Indigenous and non-indigenous child oral health in three Australian states and territories.
To explore the prevalence and severity of Indigenous and non-Indigenous child dental disease in relation to age, sex, residential location and socio-economic status in three Australian states and territories. Children aged 4-14 years who were enrolled in a school dental or screening service in New South Wales, South Australia and the Northern Territory, Australia, were randomly selected to take part in this cross-sectional study. Bivariate and multivariate analyses were used to assess outcomes. A total of 328,042 children were included, of which 10,517 (3.2%) were Indigenous. Some 67.1% of Indigenous children lived in rural areas and 47.3% lived in areas of high disadvantage. About 37.5% of 4- to 10-year-old Indigenous children had no experience of dental disease in the primary dentition while 70.7% of 6- to 14-year-old Indigenous children had caries-free permanent dentitions. The mean number of decayed, missing and filled primary teeth (dmft) of Indigenous 4- to 10-year-old children was 2.9 (SD; 3.4) while the mean DMFT of Indigenous 6- to 14-year-old children was 0.8 (SD; 1.6). Across all age-groups, Indigenous children living in the most deprived areas had higher dmft and DMFT levels than their more socially advantaged counterparts, while rural-dwelling Indigenous children had higher levels of dental disease experience than metropolitan-dwelling Indigenous children. After adjusting for potential confounding, Indigenous children aged 4-10 years were over twice as likely to have caries in the deciduous dentition than similarly aged non-Indigenous children (OR: 2.25, CI: 2.14-2.36), and 6- to 14-year-old Indigenous children were over one and a half times more likely to have decay in the permanent dentition (OR: 1.68, CI: 1.60-1.77) than their non-Indigenous counterparts. Indigenous children experienced higher caries prevalence and severity than non-Indigenous children, irrespective of other socio-demographic factors. Factors concerning Indigenous social capital may have influenced our findings.


UVA1 impairs the repair of UVB-induced DNA damage in normal human melanocytes.
The exact correlation between melanoma and sun-light is still a controversially debated issue. Although natural sunlight contains various ratios of UVA and UVB, most investigators so far focused on the effects of single solar wavebands and neglected possible interactions. Therefore, in this study primary human melanocytes of three donors were simultaneously exposed to physiologic doses of UVA1 and UVB. Effects on apoptosis were analysed using annexin V assays and cell death ELISAs, and effects on DNA damage were investigated using southwestern slot blots. While UVA1 did not influence UVB-induced apoptosis, UVA1 impaired the repair of UVB-induced cyclobutane pyrimidine dimers (CPD) as the amount of CPD was 1.8 times higher in UVA1 + UVB than in UVB only exposed melanocytes six hours after irradiation. We conclude that UVA1 might contribute to melanomagenesis as it partially inhibits the repair of UVB-induced CPD in human melanocytes while it does not affect UVB-mediated apoptosis.


Uninvolved immunoglobulins predicting hematological response in newly diagnosed AL amyloidosis.
Immunoparesis serves as a marker for elevated risk for progression in plasma cell proliferative disorders. However, the impact of immunoparesis in AL amyloidosis has not been addressed. Immunoparesis was defined qualitatively as any decrease below the low reference levels of the uninvolved immunoglobulins and quantitatively, as the relative difference between the uninvolved immunoglobulins and the lower reference values. Forty-one newly diagnosed AL amyloidosis patients were included. Sixty-six percent of patients had a suppression of the uninvolved immunoglobulins. The median relative difference of the uninvolved immunoglobulins was 18% above the low reference levels [range (-71%)-210%]. Ninety percent of the patients were treated with novel agents-based regimens, mostly bortezomib-containing regimens. Nineteen percent of the patients did not attain response to first line treatment. Patients with relative difference of uninvolved immunoglobulins below -25% of the low reference levels were less likely to respond to first line treatment compared to patients with a relative difference of -25% and above [odds ratio for no response vs. partial response and better 30 [(95% CI 4.1-222.2), P=0.0004]. Patients who failed first line treatment were successfully salvaged with lenalidomide-based treatment. Immunoparesis, if assessed quantitatively, may serve as a predictor of response in AL amyloidosis patients treated with bortezomib-containing regimens.


PFOS-induced hepatic steatosis, the mechanistic actions on β-oxidation and lipid transport.
Perfluorooctane sulfonate (PFOS) was produced by various industries and was widely used in diverse consumer products. Human sample analysis indicated PFOS contamination in body fluids. Animal studies revealed that PFOS tends to accumulate in livers and is able to induce hepatomegaly. However the underlying mechanism of PFOS-elicited hepatotoxicity has not yet been fully addressed. The objective of this study is to identify the cellular target of PFOS and to reveal the mechanisms of PFOS-induced toxicity. In this study, mature 8-week old male CD-1 mice were administered 0, 1, 5 or 10 mg/kg/day PFOS for 3, 7, 14 or 21 days. Histological analysis of liver sections, and biochemical/molecular analysis of biomarkers for hepatic lipid metabolism were assessed. PFOS-induced steatosis was observed in a time- and dose-dependent manner. The gene expression levels of fatty acid translocase (FAT/CD36) and lipoprotein lipase (Lpl) were significantly increased by 10 and/or 5 mg/kg PFOS. Serum levels of very-low density lipoprotein were decreased by 14 days of PFOS exposure (p<0.05). The rate of mitochondrial β-oxidation was also found to be significantly reduced, leading to the restriction of fatty acid oxidation for energy production. Taken together, the disturbance of lipid metabolism leads to the accumulation of excessive fatty acids and triglycerides in hepatocytes. Since PFOS-elicited pathological manifestation resembles one of the most common human liver diseases-nonalcoholic fatty liver disease, environmental exposure to PFOS may attribute to the disease progression.


Impulse response due to jumping on shoes of various stiffness and damping.
The human body is a dynamic system with dynamic behaviour. Linear and nonlinear models of a standing human are investigated. The models simulated the body by 15-lumped masses connected by springs and dampers. A square wave impulse input is applied at the shoes and the lumbar spine response is presented as an example. The results show that the mechanical response is affected by the kind of representation (linear or nonlinear model) and the shoes stiffness and damping coefficients.


Turner's syndrome in adulthood.
Turner's syndrome is the most common chromosomal abnormality in females, affecting 1:2,500 live female births. It is a result of absence of an X chromosome or the presence of a structurally abnormal X chromosome. Its most consistent clinical features are short stature and ovarian failure. However, it is becoming increasingly evident that adults with Turner's syndrome are also susceptible to a range of disorders, including osteoporosis, hypothyroidism, and renal and gastrointestinal disease. Women with Turner's syndrome have a reduced life expectancy, and recent evidence suggests that this is due to an increased risk of aortic dissection and ischemic heart disease. Up until recently, women with Turner's syndrome did not have access to focused health care, and thus quality of life was reduced in a significant number of women. All adults with Turner's syndrome should therefore be followed up by a multidisciplinary team to improve life expectancy and reduce morbidity.


[Epidermoid splenic cysts and partial splenectomy].
We communicate two cases of epidermoid splenic cyst of great size in four and six years old children, with pain in right hypochondrium in one of them, having been casual the discovery of the other one in ultrasound study of the abdomen. In both cases the abdominal ultrasound study was the most useful exploration for its diagnosis. The surgical treatment by means of partial splenectomy and conservation of more than a third of the organ it has been feasible in both patients, with a favorable evolution and without complications. The histopathologic study confirmed the discovery of epidermoid spleen cysts. Later on a clinical, analytic pursuit has been made and of these patients image with a very satisfactory evolution.


Individual goal achievement in group psychotherapy: The roles of psychological mindedness and group process in interpretive and supportive therapy for complicated grief.
The ability to infer psychological meaning in behaviour-referred to as psychological mindedness-has been posited as a patient characteristic that contributes to the therapy process and consequently to therapeutic success. The present study was developed to examine the relationship between patients' psychological mindedness and improvement in patients' personal treatment goals in interpretive and supportive group therapies for complicated grief, along with patients' importance to group process. The study was conducted with a clinical sample of 109 patients (79% female; average 45 years old) receiving treatment for complicated grief. Patients provided severity of distress ratings for individual target objectives at pretreatment and posttreatment. Psychological mindedness was assessed prior to treatment using the video-based, interviewer-rated Psychological Mindedness Assessment Procedure. Patients' importance to the therapy process was rated by therapists and other patients in interpretive and supportive group therapy for complicated grief. Conditional process modelling tested whether psychological mindedness would contribute to patients' goal achievement through patients' importance to group process, moderated by type of therapy. A significant, conditional indirect effect was observed for psychological mindedness as a predictor of improvement in individual target objectives, through patients' importance to group process as rated by therapists, specifically in interpretive therapy. The findings indicate that patients' psychological mindedness significantly contributes to their achievement of individual goals through their contributions to group process in interpretive group therapy. Further research is needed to understand the facilitation of individual goal achievement in supportive therapy.


The influence of chirality, physicochemical properties, and permeation enhancers on the transdermal permeation of amlodipine across rat skin.
This study was aimed at investigating the possible relationship between the physical properties and the permeation of S-amlodipine and RS-amlodipine and studying the possible enantioselectivity of permeation of amlodipine in the presence and absence of enhancers, such as terpene enhancers and ethanol. The solubility of S-amlodipine and RS-amlodipine was measured using the shake-flask method. The thermodynamic properties were investigated by differential scanning calorimetry (DSC). The type of racemate amlodipine was investigated by DSC and Fourier transform infrared spectroscopy (FTIR). The permeability of racemate and enantiomers of amlodipine through rat epidermis in vitro was investigated using the modified Franz diffusion cell. The aqueous solubility of S-amlodipine was higher than that of RS-amlodipine. The melting temperature and enthalpy of fusion of S-amlodipine were lower than those of RS-amlodipine. RS-amlodipine was a racemic compound. The permeation of the enantiomers of amlodipine from RS-amlodipine reservoir showed no significant differences in the presence and absence of enhancers, but the permeation of S-amlodipine from S-amlodipine reservoir was significantly higher than that of RS-amlodipine from RS-amlodipine reservoir 30% ethanol, 50% ethanol, and terpene enhancers could not influence the difference in permeation between S-amlodipine and RS-amlodipine, but 75% ethanol could reduce the difference. These results suggested that there was no enantioselectivity of the enantiomers of amlodipine from RS-amlodipine reservoir in the presence and absence of enhancers, but the differences in physical properties between S-amlodipine and RS-amlodipine led to the difference in permeation across rat skins.


Syphilis: an important cause of infectious hepatitis.
The UK incidence of infectious syphilis has risen sharply over the last 10 years; however, its diagnosis can be overlooked in patients who fail to disclose risk factors for its acquisition. This patient presented with hepatitis as part of a multisystemic illness and was investigated extensively before being diagnosed with secondary syphilis. The delay to diagnosis and treatment resulted in irreversible disablement. Syphilis should be considered in the differential diagnosis of hepatitis of uncertain aetiology. In addition, due to the similar presentation and risk factors for acquisition, we suggest that syphilis serology should be performed concomitant to all HIV tests, particularly those from outside the genitourinary medicine clinic setting.


Lymphatic vessels: new targets for the treatment of inflammatory diseases.
The lymphatic system plays an important role in the physiological control of the tissue fluid balance and in the initiation of immune responses. Recent studies have shown that lymphangiogenesis, the growth of new lymphatic vessels and/or the expansion of existing lymphatic vessels, is a characteristic feature of acute inflammatory reactions and of chronic inflammatory diseases. In these conditions, lymphatic vessel expansion occurs at the tissue level but also within the draining lymph nodes. Surprisingly, activation of lymphatic vessel function by delivery of vascular endothelial growth factor-C exerts anti-inflammatory effects in several models of cutaneous and joint inflammation. These effects are likely mediated by enhanced drainage of extravasated fluid and inflammatory cells, but also by lymphatic vessel-mediated modulation of immune responses. Although some of the underlying mechanisms are just beginning to be identified, lymphatic vessels have emerged as important targets for the development of new therapeutic strategies to treat inflammatory conditions. In this context, it is of great interest that some of the currently used anti-inflammatory drugs also potently activate lymphatic vessels.


[Endocrinology and fertility in stage I testicular tumor].
The situation of endocrinology and fertility of patients suffering from testicular cancer stage I (Peckham) with good survival rates were evaluated before semicastration. The value of beta-hCG is of great importance. According to this criteria 3 groups were formed. beta-hCG positive tumors, beta-hCG positive tumors out of the blood sample of the vena spermatica after ablation of the testis tumor and beta-hCG negative tumors. The histology is of secondary importance. 54 patients with testicular cancer were evaluated in this study. From 37 patients it was possible to get a spermiogram before semicastration. For the analysis of the spermiogram the values of LH, FSH, Testosterone and E2 are responsible. The values of beta-hCG in the serum from the periphery is of great importance, while a single elevation of beta-hCG in the serum out of the v.spermatica does not change the endocrinology. The question of kryosperm conservation is according to these parameters better evaluable.


1-Aminocyclopropane-1-carboxylic acid and abscisic acid during the germination of sugar beet (Beta vulgaris L.): a comparative study of fruits and seeds.
The control of sugar beet (Beta vulgaris L.) germination by plant hormones was studied by comparing fruits and seeds. Treatment of sugar beet fruits and seeds with gibberellins, brassinosteroids, auxins, cytokinins, and jasmonates or corresponding hormone biosynthesis inhibitors did not appreciably affect radicle emergence of fruits or seeds. By contrast, treatment with ethylene or the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) promoted radicle emergence of fruits and seeds. Abscisic acid (ABA) acted as an antagonist of ethylene and inhibited radicle emergence of seeds, but not appreciably of fruits. High endogenous contents of ACC and of ABA were evident in seeds and pericarps of dry mature fruits, but declined early during imbibition. ABA-treatment of seeds and fruits induced seed ACC accumulation while ACC-treatment did not affect the seed ABA content. Transcripts of ACC oxidase (ACO, ethylene-forming enzyme) and ABA 8'-hydroxylase (CYP707A, ABA-degrading enzyme) accumulate in fruits and seeds upon imbibition. ABA and ACC and the pericarp did not affect the seed CYP707A transcript levels. By contrast, seed ACO transcript accumulation was promoted by ABA and by pericarp removal, but not by ACC. Quantification of the endogenous ABA and ACC contents, ABA and ACC leaching, and ethylene evolution, demonstrate that an embryo-mediated active ABA extrusion system is involved in keeping the endogenous seed ABA content low by 'active ABA leaching', while the pericarp restricts ACC leaching during imbibition. Sugar beet radicle emergence appears to be controlled by the pericarp, by ABA and ACC leaching, and by an ABA-ethylene antagonism that affects ACC biosynthesis and ACO gene expression.


Using mentorship activities to assist nurses and midwives with their revalidation requirements.
Before the Nursing and Midwifery Council (NMC) introduced revalidation in 2016, the proposed model for revalidation was piloted in 19 healthcare organisations in the UK. Aneurin Bevan University Health Board (ABUHB) was among the pilot sites, and invited more than 1,000 registered nurses and midwives to take part. One of these participants, a member of the ABUHB practice facilitator team, used this experience to identify links between mentorship activities and the NMC requirements for revalidation. This article discusses how becoming a mentor and maintaining mentor status can provide registered nurses and midwives with evidence to assist them in their revalidation.


Maurice Ravel and right-hemisphere musical creativity: influence of disease on his last musical works?
The problem of finding correspondence between a particular neuronal organization and a specific function of the human brain remains a central question of neuroscience. It is sometimes thought that language and music are two sides of the same intellectual coin, but research on brain-damaged patients has shown that the loss of verbal functions (aphasia) is not necessarily accompanied by a loss of musical abilities (amusia). Amusia without aphasia has also been described. This double dissociation indicates functional autonomy in these mental processes. Yet verbal and musical impairments often occur together. The global picture that emerges from studies of music and its neural substrate is by no means clear and much depends on which subjects and which aspect of musical abilities are investigated. An illustration of these concepts is provided by the case of the French composer Maurice Ravel, who suffered from a progressive cerebral disease of uncertain aetiology, with prominent involvement of the left hemisphere. As a result, Ravel experienced aphasia and apraxia and became unable to compose. The available facts favour a clinical diagnosis of primary progressive aphasia (PPA), with the possibility of an overlap with corticobasal degeneration (CBD). In view of Ravel's clinical history, we propose that two of his final compositions, the Bolero and the Concerto for the Left Hand, include certain patterns characteristic of right-hemisphere musical abilities and may show the influence of disease on the creative process.


Sensitivity and efficiency of selected coproscopical methods-sedimentation, combined zinc sulfate sedimentation-flotation, and McMaster method.
Coproscopical methods used in veterinary-parasitological diagnostics were validated according to their sensitivity (Se) and egg recovery rate [efficiency (Ef)]. Validation of the combined sedimentation-flotation method and the modified McMaster method was performed by using feces spiked with eggs of Ancylostoma caninum, Uncinaria stenocephala, Cooperia oncophora, cyathostomins, Ascaris suum, Toxascaris leonina, Toxocara canis, Trichuris vulpis, Moniezia expansa, and Anoplocephala perfoliata. For validation of the sedimentation method, Fasciola hepatica eggs were used. With the combined sedimentation-flotation method using ZnSO4 as flotation medium [specific gravity (SG) 1.30], 5 g fecal samples of all tested parasite species (concentration levels 1, 5, 10, 20, 40, 60, and 80 epg) were reproducibly detected "positive" (100 % Se) as of 80 epg. The Ef of the combined sedimentation-flotation method, defined as percentage of rediscovered eggs, revealed clear differences between parasites and showed the highest value for cyathostomins and the lowest for U. stenocephala and T. leonina eggs. The average Ef for all parasite species at 80 epg was 1.50 %. With the McMaster method (concentration levels 1, 30, 50, 80, 100, 500, and 1000 epg), all tested parasite species were detected reliably positive as of 500 epg with a mean Ef of 46.4 %. When evaluating the sedimentation method (concentration levels 1, 5, 10, 15, 20, 25, and 30 epg), F. hepatica eggs were reproducibly found in 5 g fecal samples as of 20 epg with 20.0 % Ef. The result that the combined zinc sulfate sedimentation-flotation method (SG 1.30) as flotation medium provides diagnostic certainty only as of 80 epg has to be considered at preventing zoonoses. If pet owners wish to prevent any zoonotic infection ("zero tolerance"), a monthly anthelminthic treatment should be advised instead of monthly fecal examinations.