Neuroendocrine control of reproduction and its therapeutic manipulation with GnRH and its analogs.
The hypothalamus mediates the neuroendocrine control of reproduction in both males and females through pulsatile secretion of GnRH. The anterior pituitary gland, in turn, appears to require this episodic GnRH stimulation in order to secrete the gonadotropins LH and FSH in a physiologic fashion. Deficiency of GnRH manifests as a failure to attain puberty in both sexes, and in females it may also produce amenorrhea and/or anovulation. Replacement regimens of GnRH which employ an episodic pattern of delivery correct the deficiency of endogenous GnRH secretion and stimulate gonadotropin secretion, gonadal steroidogenesis and gametogenesis. However, continuous occupancy of the GnRH receptor by native GnRH and/or its long-acting analogs paradoxically inhibits pituitary gonadotropin secretion. GnRH analogs have been synthesized which exhibit greater affinity and prolonged occupancy on the GnRH receptor and can produce pituitary desensitization of gonadotropin secretion. Chronic administration of these GnRH analogs is capable of producting a selective "medical castration." Thus, by altering the frequency of episodic GnRH administration or by utilizing long-acting GnRH analogs it is possible to stimulate or suppress the neuroendocrine control of reproduction. The use of GnRH or its long-acting analogs has demonstrated a profound clinical impact in restoring or inhibiting fertility.


Fresh frozen plasma-to-red blood cell ratio is an independent predictor of blood loss in patients with neuromuscular scoliosis undergoing posterior spinal fusion.
In major trauma with massive blood loss, higher fresh frozen plasma (FFP)-to-red blood cell (RBC) ratios have been associated with improved morbidity and mortality. Our population of patients with neuromuscular scoliosis undergoing posterior spinal fusion (PSF) often lose volumes of blood considered massive, that is, half a blood volume in 3 hours. In this retrospective cohort study, we examined the association of FFP ratio with blood loss in this elective surgical population. Patients with neuromuscular scoliosis undergoing PSF with unit rod fixation were identified from our anesthesia cases database. The patients were divided into two groups: the low FFP group received FFP-to-RBC≤0.5, and the high FFP group received FFP-to-RBC>0.5. After controlling for a false discovery rate in the univariate analysis, a logistic and linear regression was performed to understand the contribution of the significant factors associated with increased blood loss. Risk estimation showed that patients in the low FFP group were more likely to lose >120% blood volume (odds ratio, 3.87; 95% confidence interval, 2.03-7.38). Linear regression revealed that each unit of increase in FFP-to-RBC ratio was associated with a 27.5% (95% confidence interval, -43.12-11.89) mean reduction in blood volume loss. In our retrospective study, we found that FFP-to-RBC ratio was significant independent predictor of blood loss in this group of complex spine patients undergoing PSF. Thus, in patients with neuromuscular scoliosis undergoing posterior spine fusion, use of higher ratio of FFP to RBC may decrease blood loss.


Enterococci from foods.
Enterococci have recently emerged as nosocomial pathogens. Their ubiquitous nature determines their frequent finding in foods as contaminants. In addition, the notable resistance of enterococci to adverse environmental conditions explains their ability to colonise different ecological niches and their spreading within the food chain through contaminated animals and foods. Enterococci can also contaminate finished products, such as fermented foods and, for this reason, their presence in many foods (such as cheeses and fermented sausages) can only be limited but not completely eliminated using traditional processing technologies. Enterococci are low grade pathogens but their intrinsic resistance to many antibiotics and their acquisition of resistance to the few antibiotics available for treatment in clinical therapy, such as the glycopeptides, have led to difficulties and a search for new drugs and therapeutic options. Enterococci can cause food intoxication through production of biogenic amines and can be a reservoir for worrisome opportunistic infections and for virulence traits. Clearly, there is no consensus on the acceptance of their presence in foodstuffs and their role as primary pathogens is still a question mark. In this review, the following topics will be covered: (i) emergence of the enterococci as human pathogens due to the presence of virulence factors such as the production of adhesins and aggregation substances, or the production of biogenic amines in fermented foods; (ii) their presence in foods; (iii) their involvement in food-borne illnesses; (iv) the presence, selection and spreading of antibiotic-resistant enterococci as opportunistic pathogens in foods, with particular emphasis on vancomycin-resistant enterococci.


Pre/post-natal exposure to microplastic as a potential risk factor for autism spectrum disorder.
In common with the increase in environmental pollution in the past 10 years, there has also been a recent increase in the prevalence of autism spectrum disorder (ASD). In this regard, we hypothesized that exposure to microplastics is a potential risk factor for ASD. To evaluate the validity of this hypothesis, we initially examined the accumulation of polyethylene (PE) in the brains of mice and then assessed the behavioral effects using mouse models at different life stages, namely, prenatal, post-weaning, puberty, and adult models. Based on typical behavioral assessments of autistic traits in the model mice, we established that ASD-like traits were induced in mice after PE feeding. In addition, we examined the induction of ASD-like traits in response to microplastic exposure using positron emission tomography, magnetic resonance spectroscopy, quantitative real-time polymerase chain reaction, microarray, and microbiome analysis. We believe these findings provide evidence in microplastics as a potential risk factor for ASD.


Muscle Oxygenation during Repeated Cycling Sprints in a Combined Hot and Hypoxic Condition.
The aim of the present study was to examine the effects of a combined hot and hypoxic environment on muscle oxygenation and performance during repeated cycling sprints. In a single-blind, counterbalanced, cross-over research design, 10 male athletes performed three sets of 3 × 10-s maximal pedaling interspersed with 40-s recovery between sprints under four different environments. Each condition consisted of a control (CON; 20°C, 20.9% FiO2), normobaric hypoxia (HYP; 20°C, 14.5% FiO2), hot (HOT; 35°C, 20.9% FiO2), and combined hot and normobaric hypoxia (HH; 35°C, 14.5% FiO2). Power output and vastus lateralis muscle oxygenation were measured. Peak power output was significantly higher in HOT (892±27 W) and HH (887±24 W) than in CON (866±25 W) and HYP (859±25 W) during the first set (p<0.05). The increase in total hemoglobin during recovery periods was larger in HH than in HYP (p<0.05), while change in tissue saturation index was smaller in HYP than in CON and HOT (p<0.05). The findings suggest that the combination of hot and hypoxia during repeated cycling sprints presented different characteristics for muscle metabolism and power output compared to temperature or altitude stressor alone.


Design and synthesis of novel N-acetylgalactosamine-terminated glycolipids for targeting of lipoproteins to the hepatic asialoglycoprotein receptor.
A novel glycolipid has been prepared that contains a cluster glycoside with an unusually high affinity for the asialoglycoprotein receptor (ASGPr) and a bile acid moiety that mediates stable incorporation into lipidic particles. The glycolipid spontaneously associated with low-density lipoproteins (LDL) and high-density lipoproteins (HDL) within human and murine plasma, and loading of lipoproteins with this glycolipid resulted in an efficient dose-dependent recognition and uptake of LDL and HDL by the liver (and not by spleen) upon intravenous injection into wild-type mice. Preinjection with asialoorosomucoid largely inhibited the uptake, establishing that both HDL and LDL were selectively recognized and processed by the ASGPr on liver parenchymal cells. Finally, repeated intravenous administration of the glycolipid to hyperlipidemic LDL receptor-deficient mice evoked an efficient and persistent cholesterol-lowering effect. These results indicate that the glycolipid may be a promising alternative for the treatment of hyperlipidemic patients who do not respond sufficiently to current cholesterol-lowering therapies.


The probability of abnormal preimplantation development can be predicted by a single static observation on pronuclear stage morphology.
This retrospective study was undertaken to determine whether further developmental progression of two-pronucleated (2PN) zygotes can be predicted by a single, non-invasive examination of pronuclei, with the use of criteria based on the number and distribution of nucleolar precursor bodies in each pronucleus. The normal range of pronuclear variability was defined by analysis of zygotes giving rise to embryos transferred in 100%-implantation cycles (pattern 0). Morphological patterns differing from pattern 0 were classified as patterns 1-5. The frequency of developmental arrest of pattern 0 zygotes was only 8.5% as compared with 31.6, 21.9, 30.0, 20.5 and 24. 1% for patterns 1-5 respectively. Relationships of pronuclear patterns with blastomere multinucleation and cleaving embryo morphology were also noted. Clinical pregnancy was achieved in 22 of 44 (50%) treatment cycles in which at least one pattern 0 embryo was transferred, but only in two of 23 (9%) cycles in which only pattern 1-5 embryos were transferred. These data present new evaluation criteria which can be used to predict the developmental fate of human embryos as early as the pronuclear stage, without requiring repeated observations or an exact timing of pronuclear zygote inspection. Further prospective study is needed for clinical validation of these criteria.


ERM protein moesin is phosphorylated by advanced glycation end products and modulates endothelial permeability.
Advanced glycation end products (AGEs) accumulated in different pathological conditions have the potent capacity to alter cellular properties that include endothelial structural and functional regulations. The disruption of endothelial barrier integrity may contribute to AGE-induced microangiopathy and macrovasculopathy. Previous studies have shown that AGEs induced the rearrangement of actin and subsequent hyperpermeability in endothelial cells (ECs). However, the mechanisms involved in this AGE-evoked EC malfunction are not well understood. This study directly evaluated the involvement of moesin phosphorylation in AGE-induced alterations and the effects of the RhoA and p38 MAPK pathways on this process. Using immortalized human dermal microvascular ECs (HMVECs), we first confirmed that the ezrin/radixin/moesin (ERM) protein moesin is required in AGE-induced F-actin rearrangement and hyperpermeability responses in ECs by knockdown of moesin protein expression with small interfering RNA. We then detected AGE-induced moesin phosphorylation by Western blot analysis. The mechanisms involved in moesin phosphorylation were analyzed by blocking AGE receptor binding and inhibiting Rho and MAPK pathways. AGE-treated HMVECs exhibited time- and dose-dependent increases in the Thr(558) phosphorylation of moesin. The increased moesin phosphorylation was attenuated by preadministrations of AGE receptor antibody, Rho kinase (ROCK), or p38 inhibitor. Suppression of p38 activation via the expression of dominant negative mutants with Ad.MKK6b or Ad.p38alpha also decreased moesin phosphorylation. The activation of the p38 pathway by transfection of HMVECs with an adenoviral construct of dominant active MKK6b resulted in moesin phosphorylation. These results suggest a critical role of moesin phosphorylation in AGE-induced EC functional and morphological regulations. Activation of the ROCK and p38 pathways is required in moesin phosphorylation.


Human experimental exposure to glyphosate and biomonitoring of young Swedish adults.
Glyphosate (GLY), N-(phosphonomethyl) glycine, is the most widely used herbicide in the world. It is a broad-spectrum herbicide, also used in crop desiccation. Agricultural workers may be occupationally exposed and general populations may be exposed to GLY mainly through diet. We studied the kinetics of GLY by measuring the parent compound and its metabolite aminomethylphosphonic acid (AMPA) in urine samples of three volunteers after an experimental oral exposure. We further examined GLY exposure by measuring GLY and AMPA in spot urine samples of 197 young adults in the general population in Scania, southern Sweden. Urine samples were analyzed using LC-MS/MS. In the experimental exposure, three healthy volunteers received an oral dose equivalent to 50% of the ADI for GLY. Urinary samples were collected up to 100 h after the exposure. The excretion of GLY to urine seemed to follow first-order kinetics and a two-phase excretion. The excretion half-life of GLY (density adjusted) was 6-9 h in the rapid phase and 18-33 h in the slower phase. The total dose recovered as unchanged GLY in the urine samples of volunteers was 1-6%. The metabolite AMPA was found to be 0.01-0.04% of the total dose of GLY. In the population of young adults, the median concentration was below 0.1 μg/L and a maximum concentration being 3.39 μg/L (density adjusted). AMPA was generally detected in lower concentrations (maximum = 0.99 μg/L). A moderate correlation (Spearman's ρ = 0.56) was observed between GLY and AMPA concentrations. Overall, the results may suggest that GLY and AMPA partly originate from separate exposures and that unchanged GLY is a more suitable biomarker of exposure.


Vaccinia virus uracil DNA glycosylase has an essential role in DNA synthesis that is independent of its glycosylase activity: catalytic site mutations reduce virulence but not virus replication in cultured cells.
Previous findings that the vaccinia virus uracil DNA glycosylase is required for virus DNA replication, coupled with an inability to isolate a mutant with an active site substitution in the glycosylase gene, were surprising, as such enzymes function in DNA repair and bacterial, yeast, and mammalian null mutants are viable. To further study the role of the viral protein, we constructed recombinant vaccinia viruses with single or double mutations (D68N and H181L) in the uracil DNA glycosylase conserved catalytic site by using a complementing cell line that constitutively expresses the viral enzyme. Although these mutations abolished uracil DNA glycosylase activity, they did not prevent viral DNA replication or propagation on a variety of noncomplementing cell lines or human primary skin fibroblasts. In contrast, replication of a uracil DNA glycosylase deletion mutant occurred only in the complementing cell line. Therefore, the uracil DNA glycosylase has an essential role in DNA replication that is independent of its glycosylase activity. Nevertheless, the conservation of the catalytic site in all poxvirus orthologs suggested an important role in vivo. This idea was confirmed by the decreased virulence of catalytic-site mutants when administered by the intranasal route to mice.


Applications of molecular engineering in T-cell-based immunotherapies.
Harnessing an individual's immune cells to mediate antitumor and antiviral responses is a life-saving option for some patients with otherwise intractable forms of cancer and infectious disease. In particular, T-cell-based engineered immune cells are a powerful new class of therapeutics with remarkable efficacy. Clinical experience has helped to define some of the major challenges for reliable, safe, and effective deployment of T-cells against a broad range of diseases. While poised to revolutionize immunotherapy, scalable manufacturing, safety, specificity, and the development of resistance are potential roadblocks in their widespread usage. The development of molecular engineering tools to allow for the direct or indirect engineering of T-cells to enable one to troubleshoot delivery issues, amplify immunomodulatory effects, integrate the synergistic effects of different molecules, and home to the target cells in vivo. In this review, we will analyze thus-far developed cell- and material-based tools for enhancing T-cell therapies, including methods to improve safety and specificity, enhancing efficacy, and overcoming limitations in scalable manufacturing. We summarize the potential of T-cells as immune modulating therapies and the potential future directions for enabling their adoption for a broad range of diseases. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Cells at the Nanoscale.


Influence of particle wettability on foam formation in honey.
The rising level of obesity is often attributed to high sugar and/or fat consumption. Therefore, the food industry is constantly searching for ways to reduce or eliminate sugar or fat in food products. Therefore, honey foam, which contains little sugar and no fat, can be used as cake, cracker or bread spread instead of butter or margarine which contains a substantial amount of fat or jam that contains a substantial amount of sugar. Small solid particles (nanometers to micrometers) of suitable wettability are now considered outstanding foam-stabilizing agents. However, while the degree of particle wettability necessary to obtain very stable aqueous and nonaqueous foams is well-known, that needed to obtain very stable honey foam is unknown. In this study, the influence of the degree of wettability of fumed silica particles, indicated by their % SiOH (14-100), was investigated in honey in relation to foam formation and foam stability. The honephilic particles (61%-100% SiOH) formed particle dispersion in honey, while foams were obtained with the honephobic particles (14%-50% SiOH). The thread-off between particle dispersion and foam formation occurs at 50% SiOH, meaning foam formation in honey is possible when the particles are at least 50% honephobic. At relatively low particle concentration <1 wt.%, foam volume decreases with increasing honephobicity, but increases with honephobicity at relatively high concentration >1 wt.%. Also, as particle concentration increases, the shape of the air bubbles in the foam changes from spherical to non-spherical. After a little drainage, the foams remain stable to drainage and did not coalesce substantially for more than six months. These findings will guide the formulation of edible Pickering honey foams.


Association between human papillomavirus and EGFR mutations in advanced lung adenocarcinoma.
Previous studies have demonstrated an association between human papillomavirus (HPV) and mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer patients; however, few studies have investigated this association in advanced lung adenocarcinoma patients undergoing gefitinib treatment. The present study investigated the association between HPV and EGFR mutations in advanced lung adenocarcinoma patients. A total of 95 advanced lung adenocarcinoma patients were enrolled in the study. The HPV infection status and presence of EGFR mutations in tumor tissue was evaluated. Patient clinical characteristics were also determined and compared with HPV infection and EGFR mutation status to analyze their impact on progression-free survival. HPV DNA was identified in 27/95 (28.4%) lung adenocarcinoma tumors and was most common in patients with lymph node metastasis (P=0.016). A total of 44/95 (46.3%) cases exhibited EGFR mutations, which were predominantly observed in female patients and non-smokers. The presence of HPV DNA was significantly associated with EGFR mutations (P=0.012) and multivariate analysis also revealed that HPV DNA was significantly associated with EGFR mutations (odds ratio=3.971) in advanced lung adenocarcinoma. Patients with both HPV infections and EGFR mutations exhibit a marked decrease in the risk of lung cancer progression when compared with those without HPV infection or EGFR mutations (adjusted HR=0.640; 95% confidence interval: 0.488-0.840; P=0.001). HPV infection was significantly associated with EGFR mutations in advanced lung adenocarcinoma patients. Furthermore, patients with HPV infections exhibited the longest progression-free survival times, which may be due to good response to tyrosine kinase inhibitor- or platinum-based-adjuvant therapy in these patients. Patients with EGFR mutations exhibited a better prognosis when compared with those exhibiting wild-type EGFR, regardless of HPV status.


Tuberculosis of the pancreas.
Tuberculosis of the pancreas is extremely rare. We report a case which demonstrates the diagnostic confusion which may arise in this condition. A 55-year-old alcoholic caucasian man presented with loss of weight and obstructive jaundice. Ultrasonography, endoscopic retrograde cholangiopancreatography and computed tomography showed a mass lesion in the head of the pancreas, diagnosed as probably malignant. He underwent a Whipple's pancreatoduodencetomy and made a good recovery. Histological examination showed typical features of tuberculosis. In the absence of other foci of active disease chemotherapy was not given. He remains well 12 months after operation.


[Antro-choanal polyp in children. Our experience since 1997].
The antro-choanal polyp is a rather common pathology in children. To discuss the diagnostic modalities, the risk factors, the differential diagnoses and treatment options. This study was performed in an ENT department of a 3rd referal center Fifteen patients, 12 males and 3 females (8 to 16 year old), were treated for an antro-choanal polyp (Killian's polyp) between 1997 and 2007. All patients presented a nasal obstruction. Other signs of discovery were a rhinorrhea, a maxillary pain or a pharyngeal mass. Two patients presented a recurrence after a surgery in another center Atopy did not seem to be a risk factor. The imaging evaluation showed a tissular process developed in the maxillary sinus and extending through the maxillary ostium, or an accessory ostium, toward the nose. All patients were treated by intranasal endoscopic surgery. The middle meatal antrostomy was systematic, associated with a inferior antrostomy in 3 cases, with an anterior ethmoidectomy in one case and with a vestibular approach (Caldwell-Luc procedure) in 4 cases. Two patients presented a recurrence which necessited a new surgery. The antro-choanal polyp must be suspected in front of nasal obstruction in children. The imaging evaluation eliminates the main differential diagnoses. The endo-nasal removal seems to be the best procedure.


Overview of QTL detection in plants and tests for synergistic epistatic interactions.
Improvements in the usefulness of QTL analysis arise from better statistical methods applied to the problem, ability to analyze more complex mating designs, and the fitting of less simplified genetic models. Here we review the advantages of different plant mating designs in QTL analysis and conclude that diallel designs have several favorable properties. We then turn to the detection of systematic genome-wide synergistic epistasis. This form of epistasis has important implications from evolutionary (maintenance of sexual reproduction and concealment of cryptic genetic variation) and practical perspectives (response to pyramided favorable alleles). We develop two methods for detecting systematic synergistic epistasis, one based on analyzing interactions between locus effects and predicted individual genotypic values and one based on analyzing pairwise locus interactions. Using the first method we detect synergistic epistasis in a barley and a wheat dataset but not in a maize dataset. We fail to detect synergistic epistasis with the second method. We discuss our results in the light of theoretical questions concerning the mechanisms of synergistic epistasis.


Competition among molecular fragmentation channels described with Siegert channel pseudostates.
To describe multiple interacting fragmentation continua, we develop a method in which the vibrational channel functions obey outgoing wave Siegert boundary conditions. This paper demonstrates the utility of the Siegert approach, which uses channel energy eigenvalues that possess a negative imaginary part. The electron scattering energy in each such channel is rotated upward, giving it an equal and opposite imaginary part. This permits a natural inclusion of vibrational continua without requiring them to appear as explicit channels in the scattering matrix. Calculations illustrate the application of this theory to photoionization, photodissociation, and dissociative recombination.


Prevalence of Articular Cartilage Lesions and Surgical Clinical Outcomes in Football (Soccer) Players' Knees: A Systematic Review.
To systematize the available scientific literature on the prevalence of articular cartilage and/or osteochondral lesions in football (soccer) players' knees, and overview the surgical procedures and functional outcomes and return to sports. A comprehensive search using Pubmed, Cochrane Library, SPORTDiscus, and CINAHL databases was carried out until September 30, 2015. All English language studies that assessed the outcomes of a surgical technique for the treatment of articular cartilage lesions in football players' knees, with a minimum follow-up of 12 months, were included. The reference list of the most relevant papers was screened. The main outcomes of interest were the clinical, arthroscopy or imaging primary outcomes and the return to sports rate. The methodological and reporting qualities were assessed according to Coleman methodology score. The search provided 485 titles and abstracts. Five studies were eligible for inclusion (mean Coleman score of 37.2 points), comprising a total of 183 football players with a mean age of 25.7 years. A total of 217 articular cartilage and/or osteochondral lesions were reported, where the medial and lateral femoral condyles were the most common sites of lesion. The surgical procedures investigated were mosaicplasty, microfracture, autologous chondrocyte implantation, and chondral debridement. No definitive conclusion could be made in respect to the best current surgical technique for articular cartilage and osteochondral lesions. Microfracture and mosaicplasty can provide a faster return to competition and faster clinical and functional results, whereas autologous chondrocyte implantation and/or matrix-induced autologous chondrocytes implantation procedures can enhance longstanding clinical and functional results. Level IV, systematic review of Level III and IV studies.


An fMRI study of implicit language learning in developmental language impairment.
Individuals with developmental language impairment can show deficits into adulthood. This suggests that neural networks related to their language do not normalize with time. We examined the ability of 16 adults with and without impaired language to learn individual words in an unfamiliar language. Adults with impaired language were able to segment individual words from running speech, but needed more time to do so than their normal-language peers. ICA analysis of fMRI data indicated that adults with language impairment activate a neural network that is comparable to that of adults with normal language. However, a regional analysis indicated relative hyperactivation of a collection of regions associated with language processing. These results are discussed with reference to the Statistical Learning Framework and the sub-skills thought to relate to word segmentation.


Role of laparoscopic nephrectomy for refractory hypertension in poorly functioning kidneys.
Hypertension is a common medical problem mainly treated by effective antihypertensive drugs. Persistent hypertension can be difficult to manage and have detrimental effect on vital organs. Nephrectomy of poorly functioning kidneys may be indicated in a minority of such cases. We performed laparoscopic nephrectomy on 12 patients with refractory hypertension. Eight had complete response, three had partial response and one had no response. Laparoscopic nephrectomy has a role in carefully selected adult patients with refractory hypertension due to non-functioning kidney. Patients need to understand the surgical risks as well as the small risk of failure to treat hypertension.


[Post launch studies].
Evidence Based Medicine (EBM) is a growing concept in Japan as it is elsewhere. Central to improving the use of EBM is generation of data through well conducted controlled clinical studies. There are many problems associated with conduct of clinical studies after launch in Japan, and many initiatives are ongoing to improve the situation. Development of Clinical Research Coordinators (CRO) and central Data Management centers are key to improving the quality of clinical research in Japan. Currently Japan has an undeveloped legal system with regard to post-launch trials and off-label use of registered drugs. There is no reimbursement for off-label and various restrictions imposed on the recipients of the Ministry of Health, Labour and Welfare's (MHLW) funds. Maybe the biggest problem is the high cost of post-marketing studies sponsored by pharmaceutical manufacturers. A high quality system to support post launch clinical studies need a solid financial base. There is a need for a suitable review system for investigator initiated multi-centre studies, as the current IRB system is not sufficient. There are also challenges regarding the differences, perceived or real, in treatment practice and available registrations in Japan and in the West, causing problems in choosing suitable comparators and study designs. At the present time it is not clear whether investigator initiated trials will be acceptable for registration purposes in Japan. The agreed first priority is to build a suitable and strong infrastructure within the academic community to support researchers to investigate important questions with or without pharmaceutical company support. Despite all these issues, several groundbreaking projects are under way throughout Japan, in many different areas and by different collaborative groups, some with government support. In fact, researcher-initiated clinical trials achieved a rapid growth in Japan in the past year.


Liposome-mediated gene therapy in the kidney.
Gene therapy directed to the kidney has been attempted to improve renal disorders such as inherited kidney diseases and common renal diseases that cause interstitial fibrosis, tubular atrophy, and glomerulosclerosis. Viral and non-viral vectors have been tried and been modulated to obtain sufficient transgene expression. However, gene delivery to the kidney is usually difficult because of characteristics of renal cell biology. Among non-viral vectors, the liposome system is a promising procedure for kidney-targeted gene therapy. Using cationic liposome, tubular cells were effectively transduced by retrograde injection of liposome/cDNA complex. Although transgene expression was reportedly modest using cationic liposomes, this method improved renal disease models such as carbonic anhydrase II deficiency and unilateral ureteral obstruction. In contrast, HVJ-liposome system is an effective transfection method to glomerular cells using intra-renal arterial infusion and improved glomerular disease models such as glomerulonephritis and glomerulosclerosis. In addition, intra-renal pelvic injection of DNA by HVJ-liposome system showed transgene expression in interstitial fibroblasts. In kidney-targeted gene therapy, liposome-mediated gene transfer is an attractive method because of its simplicity and reduced toxicity. In spite of modest transgene expression, several renal disease models were successfully modulated by liposome system. Although one limitation of liposome-mediated gene delivery is the duration of transgene expression, the liposome/cDNA complex can be repeatedly administered due to the absence of an immune response.


A new custom-made plate preparation method for bony mallet finger treatment and a comparison with extension block technique.
In this study, we aimed to describe a new hook plate technique (HPT) and to compare our results with the conventional extension block technique (EBT) with a Kirschner wire (K-wire) for bony mallet finger treatment. Between April 2015 and January 2018, a total of 19 patients including 10 who were treated with EBT (7 males, 3 females; mean age: 30.1±7.3 years; range, 17 to 48 years) and nine who were treated with HPT (6 males, 3 females; mean age: 31.7±11.3 years; range, 19 to 42 years) for bony mallet finger with distal interphalangeal (DIP) joint subluxation and/or fracture fragment larger than one-third of distal phalanx (Wehbe-Schneider type 1/b, 2/a, 2/b, 3/a) joint were retrospectively analyzed. The DIP range of motion (ROM), Warren and Crawford scores, time to return to work/daily activity, operation time, the number of fluoroscopy shots, cost and complications were compared. No significant difference was found in the DIP ROM (p=0.708) and the Warren/Norris and Crawford scores (p=0.217 and p=0.175, respectively) between the two groups. Operation time and material cost were higher with HPT (p=0.006, p=0.001). There was no significant difference in the number of fluoroscopy shots (p=0.344). Although DIP joint motion was started at two weeks in the HPT group and at eight weeks in the EBT group, no significant difference was observed in the time of return to work and normal daily life in both groups (p=0.859). Complications were observed in two patients in the EBT group and in three patients in the HPT group. No significant difference in total complications was observed between the two groups (p=0.666). Bony mallet finger treatment with a custom-made hook plate prepared from 1.3-mm AO plates appeared to be clinically and radiologically similar to EBT. Additionally, HPT had the advantages of allowing early ROM to DIP joint and eliminating the need for a secondary surgery such as K-wire removal. On the other hand, hardware cost with HPT was higher than EBT.


Suppressing the Initial Growth of Sidewall GaN by Modifying Micron-Sized Patterned Sapphire Substrate with H₃PO₄-Based Etchant.
Micron-sized patterned sapphire substrates (PSS) are used to improve the performance of GaN-based light-emitting diodes (LEDs). However, the growth of GaN is initiated not only from the bottom c-plane but also from the sidewall of the micron-sized patterns. Therefore, the coalescence of these GaN crystals creates irregular voids. In this study, two kinds of nucleation layers (NL)-ex-situ AlN NL and in-situ GaN NL-were used, and the growth of sidewall GaN was successfully suppressed in both systems by modifying the micron-sized PSS surface.


Indole-3-carbinol suppresses tumor-induced angiogenesis by inhibiting tube formation and inducing apoptosis.
Indole-3-carbinol (I3C) has been reported to exert anticancer activity in vivo. However, its anticancer mechanism has not been fully elucidated. In this study, we demonstrate that I3C suppressed tumor-induced angiogenesis and tube formation of endothelial cells. I3C also induced apoptosis in endothelial cells by activating the caspase cascade. We propose that I3C exerts its anticancer effect through the induction of endothelial apoptosis.


SHP-2-Mediated Upregulation of ZEB1 Is Important for PDGF-B-Induced Cell Proliferation and Metastatic Phenotype in Triple Negative Breast Cancer.
Background: Triple negative breast cancer (TNBC), a fatal malignant tumor, is characterized by a lack of estrogen and progesterone hormone receptors and overexpression of HER2. Due to its characteristics, there are no effective targeted therapies for TNBC. Therefore, it is critical to identify the crucial factors that participate in modulating TNBC progression and explore the underlying molecular mechanism. Methods: CCK-8, bromodeoxyuridine incorporation, western blotting, qPCR, and transwell assays were utilized to evaluate breast cancer cell proliferation, migration, and invasion. Results: Activation of platelet-derived growth factor (PDGF)-B/PDGF receptor (PDGFR) promoted the proliferation and metastatic phenotype of TNBC cells; however, these effects were attenuated by SHP-2 knockdown. Moreover, PDGF-B promoted the expression of zinc finger E-box binding homeobox 1 (ZEB1) by downregulating the expression of miR-200. Furthermore, knockdown of ZEB1 mitigated the promoting effects of PDGF-B on cell proliferation and migration. In addition, the regulatory effects of PDGF-B on miR-200 and ZEB1 were mediated through the SHP-2/Akt pathway. Conclusion: Our findings highlight the important roles of PDGF-B/PDGFR and their downstream signaling pathways in regulating cell proliferation and metastatic phenotype in TNBC. Hence, these molecules may serve as novel therapeutic targets for TNBC in the future.


Human lens cholesterol concentrations in patients who used lovastatin or simvastatin.
To determine whether long-term therapeutic use of the hypocholesterolemic drugs lovastatin and simvastatin significantly alters the distribution and concentration of cholesterol in the human lens. Such changes might precede observable alterations in lens structure. Pairs of lenses (9-13 pairs) from patients (age range, 46-81 years) who had been taking lovastatin or simvastatin before their death (estimated for the previous 2-4 years) and lenses from similarly aged control subjects were divided into outer cortex and inner cortex plus nucleus by dissolution in a detergent-containing buffer. Ten minutes of dissolution removed 17% to 19% of the lens total volume, which accounted for about 20% of the width of the equatorial cortex and 75% of the width of the sagittal cortex. This fraction plus the residual lens was homogenized, saponified, and assayed for cholesterol by gas-liquid chromatography. The cortex of adult control lenses contained about 4 microg of cholesterol per cubic millimeter of volume. This concentration increased to 10 to 15 microg/mm3 in the adult nucleus and decreased to about 6 microg/mm3 in the juvenile and fetal nucleus. Treatment with neither lovastatin nor simvastatin significantly altered the concentration of cholesterol in either the cortex or nuclear fractions. Variations in concentration of cholesterol along the radii of the lens reflect differences in the density or packing of fiber cell membranes. The observed distribution of cholesterol supports the recent model of the adult lens structure, which, from surface to center, is the cortex, adult nucleus,juvenile nucleus, fetal nucleus, and embryonic nucleus. Finding no significant changes in concentration of cholesterol in the cortex formed during treatment with lovastatin or simvastatin reinforces the results of clinical studies that indicate a high lenticular safety of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Nevertheless, caution is encouraged in assuming a similar ocular safety in newer drugs that inhibit cholesterol synthesis at later metabolic steps. Does clinical use of hypocholesterolemic drugs alter lens cholesterol?


Nitric Oxide (NO) Measurements in Stomatal Guard Cells.
The quantitative measurement of nitric oxide (NO) in plant cells acquired great importance, in view of the multifaceted function and involvement of NO as a signal in various plant processes. Monitoring of NO in guard cells is quite simple because of the large size of guard cells and ease of observing the detached epidermis under microscope. Stomatal guard cells therefore provide an excellent model system to study the components of signal transduction. The levels and functions of NO in relation to stomatal closure can be monitored, with the help of an inverted fluorescence or confocal microscope. We can measure the NO in guard cells by using flouroprobes like 4,5-diamino fluorescein diacetate (DAF-2DA). This fluorescent dye, DAF-2DA, is cell permeable and after entry into the cell, the diacetate group is removed by the cellular esterases. The resulting DAF-2 form is membrane impermeable and reacts with NO to generate the highly fluorescent triazole (DAF-2T), with excitation and emission wavelengths of 488 and 530 nm, respectively. If time-course measurements are needed, the epidermis can be adhered to a cover-glass or glass slide and left in a small petri dishes. Fluorescence can then be monitored at required time intervals; with a precaution that excitation is done minimally, only when a fluorescent image is acquired. The present method description is for the epidermis of Arabidopsis thaliana and Pisum sativum and should work with most of the other dicotyledonous plants.


Unilateral single-port thoracoscopic surgery for bilateral pneumothorax or pulmonary bullae.
Rapid rehabilitation surgery has become a widely accepted approach. Thoracic surgeons have attempted in many ways to make surgery less invasive. We combined tubeless technology, single-port technology and mediastinum approach for the treatment of simultaneous bilateral primary spontaneous pneumothorax(PSP)or pulmonary bullae. And we evaluated its therapeutic effect. This study aimed to investigate if tubeless single-port video-assisted thoracic surgery (Tubeless-SPVATS) via anterior mediastinum can be used as an alternative surgical treatment for bilateral lung diseases, especially for concurrent or contralateral recurrence PSP. From November 2014 to December 2016, 18 patients with simultaneous bilateral PSP or pulmonary bullae were treated with tubeless -SPVATS via anterior mediastinum. They were 13 males and 5 females with an average age of 20.2 ± 2.3 years (17 to 24 years). They all had preoperative chest CT and were diagnosed with simultaneous bilateral PSP or pulmonary bullae. Fifteen patients underwent bilateral bullae resection with Tubeless-SPVATS via anterior mediastinum. Three patients underwent bilateral single-port video-assisted thoracic surgery. No thoracotomy was performed. No death and grade 3-4 mobidity were found. All the patients started eating 6 hours after surgery. The average operation time was 44.56±17.8min. The patients were discharged 3. 5±1.0 days postoperatively. Tubeless-SPVATS via anterior mediastinum is a safe and feasible treatment for patients with simultaneous bilateral PSP or pulmonary bullae. However,contralateral thoracic is not explored fully enough. And when contralateral lung bullae are located near the hilum, endoscopic linear stapler cannot be easily used to conduct suture. Thus, the recurrence rate after performing Tubeless-SPVATS may be increased compared to performing thoracotomy. However, compared to bilateral thoracic surgery, this method reduced postoperative pain. And it took significantly less time than bilateral thoracic surgery. Thus, this method has some clinic value.


Capacitative calcium entry supports calcium oscillations in human embryonic kidney cells.
Treatment of human epithelial kidney (HEK293) cells with low concentrations of the muscarinic agonist methacholine results in the activation of complex and repetitive cycling of intracellular calcium ([Ca(2+)](i)), known as [Ca(2+)](i) oscillations. These oscillations occur with a frequency that depends on the concentration of methacholine, whereas the magnitude of the [Ca(2+)](i) spikes does not. The oscillations do not persist in the absence of extracellular Ca(2+), leading to the conclusion that entry of Ca(2+) across the plasma membrane plays a significant role in either their initiation or maintenance. However, treatment of cells with high concentrations of GdCl(3), a condition which limits the flux of calcium ions across the plasma membrane in both directions, allows sustained [Ca(2+)](i) oscillations to occur. This suggests that the mechanisms that both initiate and regenerate [Ca(2+)](i) oscillations are intrinsic to the intracellular milieu and do not require entry of extracellular Ca(2+). This would additionally suggest that, under normal conditions, the role of calcium entry is to sustain [Ca(2+)](i) oscillations. By utilizing relatively specific pharmacological manoeuvres we provide evidence that the Ca(2+) entry that supports Ca(2+) oscillations occurs through the store-operated or capacitative calcium entry pathway. However, by artificial introduction of a non-store-operated pathway into the cells (TRPC3 channels), we find that other Ca(2+) entry mechanisms can influence oscillation frequency in addition to the store-operated channels.


Efficacy and Safety of Bilastine in the Treatment of Allergic Rhinitis: A Systematic Review and Meta-analysis.
Bilastine is a non-sedating second generation H1 oral antihistamine (OAH) for treating allergic rhinitis (AR) patients. The effect of bilastine has not previously been evaluated in a meta-analysis. The aim of this review was to determine the efficacy and safety of bilastine in treating AR. An electronic literature search was performed using Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Science Direct and Google Scholar up to March 2021. Randomized controlled trials comparing bilastine with placebo and standard pharmacotherapy were included. The included studies must have diagnosis of AR established by clinicians and the outcomes must have a minimum of 2 weeks of follow-up period. The primary outcomes assessed were total symptom score (TSS), nasal symptom score (NSS) and non-nasal symptom score (NNSS). The secondary outcomes were discomfort due to rhinitis, quality of life (QOL) and adverse events. The risk of bias and quality of evidence for all studies were appraised. The meta-analysis was done using Review Manager 5.3 software based on the random-effects model. The search identified 135 records after removal of duplicates. Following screening and review of the records, fifteen full-text articles were assessed for eligibility. Five trials involving 3,329 patients met the inclusion criteria. Bilastine was superior to placebo in improving TSS, NSS, NNSS, rhinitis discomfort score and QOL but has comparable efficacy with other OAHs in TSS, NSS, NNS, rhinitis discomfort score and QOL. There was no difference in adverse effects when bilastine was compared against placebo and other OAHs except for somnolence. Bilastine has fewer incidence of somnolence compared to cetirizine. The overall quality of evidence ranged from moderate to high quality. Bilastine is effective and safe in treating the overall symptoms of AR with comparable efficacy and safety with other OAHs except somnolence. Whilst bilastine has similar efficacy to cetirizine, somnolence is notably less in bilastine.


Ruthenium-catalyzed selective monoamination of vicinal diols.
The monoamination of vicinal diols in the presence of in situ generated ruthenium catalysts has been investigated. Among the various phosphines tested in combination with [Ru(3)(CO)(12)], N-phenyl-2-(dicyclohexyl-phosphanyl)pyrrole showed the best performance. After optimization of the reaction conditions this system was applied to different secondary amines and anilines as well as a number of vicinal diols. With the exception of ethylene glycol, monoamination of the vicinal diols occurred selectively and the corresponding amino alcohols were obtained in good yields, producing water as the only side product.


Validated high-performance liquid chromatographic enantioseparation of selenomethionine using isothiocyanate based chiral derivatizing reagents.
A high-performance liquid chromatographic (HPLC) method for enantioseparation of selenomethionine (SeMet) was developed using two isothiocyanate-based chiral derivatizing reagents [(R)-methyl benzyl isothiocyanate (MBIC) and (S)-1-(1-naphthyl) ethyl isothiocyanate (NEIC)] and UV detection. Diastereomers of selenomethionine were synthesized either via stirring (using MBIC) or by microwave irradiation (using NEIC). Derivatization conditions were optimized and the synthesized diastereomers were successfully resolved using triethyl ammonium phosphate buffer and acetonitrile on a reversed-phase column. The method was validated for accuracy, precision and limit of detection. The mechanism of separation is also discussed.


Ceftriaxone for the Treatment of Methicillin-susceptible Staphylococcus aureus Bacteremia: A Case Series.
Methicillin-susceptible Staphylococcus aureus (MSSA) causes 45% of S. aureus bloodstream infections (BSI) and is the most important cause of BSI-associated death. The standard of care therapy is an anti-staphylococcal penicillin or cefazolin, but dosing frequencies for these agents are often infeasible; multiple daily doses tie up infusion lines and are impractical for outpatient antibiotic infusion. Ceftriaxone represents a promising alternative, with once daily dosing and a short infusion time. Currently, treatment with ceftriaxone for invasive MSSA infections is infrequent, with minimal data supporting the clinical utility of ceftriaxone for MSSA BSI. In this case series, we identified 15 patients receiving ceftriaxone for treatment of MSSA BSI, either following standard of care therapy or as initial therapy. Patients were evaluated for clinical cure (CC)(clearance of BSI and normalization of white blood cell count) and microbiological cure (MC)(clearance of blood cultures and no recurrence of organism within 60 days). CC was observed in seven patients, with MC observed in all patients. Only one patient was readmitted to the hospital. This case series provides vital data to support ceftriaxone for treatment of MSSA BSI. With few readmissions and recurrences of infection, ceftriaxone was an effective option for maintenance therapy after resolution of the BSI. Ceftriaxone appears to be a viable alternative for the treatment of MSSA BSI.


Retrograde exchange of heavily encrusted ureteric stents via the ileal conduit: a technical report.
We describe two cases of retrograde ureteric stent exchange of heavily encrusted ureteric stents (JJ) via tortuous ileal conduits. The blocked ureteric stents were snared from inside the conduit so they could be accessed and a wire inserted. The lumens of the stents were unblocked with a wire but the stents could not be withdrawn due to heavy encrustation of the ureteric stent in the renal pelvis. A stiff wire was inserted to provide support and a 9 French peel away sheath was used to remove the encrustations allowing the stents to be withdrawn and exchanged. This is a safe and successful technique allowing ureteric stents to be removed when heavily encrusted.


Overexpression of long noncoding RNA HOXC13-AS and its prognostic significance in hepatocellular carcinoma.
The long noncoding RNA HOXC13 antisense RNA (HOXC13-AS) was overexpressed in several tumor specimens, and its overexpression was correlated with cells metastasis of tumors. However, its effects in other tumors remained largely unclear. In this work, we aimed to identify whether HOXC13-AS was abnormally expressed in hepatocellular carcinoma (HCC) and further explore its prognostic value. QRT-PCR was applied for the examination of HOXC13-AS levels in 197 paired HCC specimens and matched non-tumor specimens. Chi-square tests were carried out for the verification of the relations between the levels of HOXC13-AS and the clinicopathologic features of HCC patients. The Kaplan-Meier methods were applied for the exploration of the prognostic value of HOXC13-AS. Multivariate analysis was performed using the Cox proportional hazard assays. Up-regulation of HOXC13-AS was observed in HCC tissues compared to matched normal tissues (p < 0.01). Higher levels of HOXC13-AS were associated with TNM stage (p = 0.024) and lymph node metastasis (p = 0.043). Survival assays showed that HCC patients with high-HOXC13-AS expressions had significantly shorter overall survival (p < 0.0106) and disease-free survival (p < 0.0066) compared to their counterparts with low-HOXC13-AS expressions. Multivariate analyses suggested HOXC13-AS as an independent prognostic factor for HCC patients. We showed that HOXC13-AS might serve as a promising biomarker for prognosis prediction of HCC.


Long non-coding RNA prostate cancer-associated transcript 6 inhibited gefitinib sensitivity of non-small cell lung cancer by serving as a competing endogenous RNA of miR-326 to up-regulate interferon-alpha receptor 2.
The critical roles of lncRNAs in drug resistance of malignancies have been widely recognized. This investigation aims to study the function of lncRNA PCAT6 in the resistance of non-small cell lung cancer (NSCLC) to gefitinib. In our study, we demonstrated that prostate cancer-associated transcript 6 (PCAT6) was upregulated in gefitinib-resistant NSCLC. PCAT6 knockdown inhibited gefitinib resistance of NSCLC, as indicated by decreased IC50 value, proliferation, and metastasis, and increased cell apoptosis. Besides, PCAT6 could directly target miR-326 in gefitinib-resistant NSCLC cells and augment NSCLC resistance to gefitinib by serving as ceRNA of miR-326. Furthermore, interferon-alpha receptor 2 (IFNAR2) was validated as a downstream target of miR-326 and miR-326 reduced resistance to gefitinib by inhibiting IFNAR2 expression. Our investigation identified that PCAT6 enhanced gefitinib resistance of NSCLC via miR-326/IFNAR2 axis, which might offer a new therapeutic strategy against gefitinib resistance of NSCLC patients.


[Surgical experience of ureteral varices].
Ureteral varices have been considered to be a relatively rare disease. Recently, reports on varices have been increasing with the development of X-ray examination, especially with the popularization of renal phlebography. We diagnosed left ureteral varices in 8 cases by renal venography. In 7 of these cases, gross hematuria was the main symptom, and varicocele accompanied it in the other case. In 7 cases of hematuria, surgery, ligation and removal of the varices was performed as palliative therapy for symptom; and, in all 7 cases, the gross hematuria disappeared in 7 to 18 months postoperatively. Ureteral varices should be classified into idiopathic and secondary types. In the case of idiopathic varices, a regional operation is sufficient to prevent venous reflux of the ureteral vein, and extensive surgery is needed in cases of collateral circulation on the venograms and secondary varices because of the unchangeable postoperative venous hypertension. We concluded that surgical treatment of ureteral varices is effective and is a useful palliative procedure in spite of the short postoperative follow up.


Characterization of a soybean leaf protein that is related to the seed lectin and is increased with pod removal.
Levels of several polypeptides in addition to the vegetative storage protein (VSP) increase in soybean leaves following depodding. Two of these polypeptides interact specifically with antibodies raised against the seed lectins of Phaseolus vulgaris and soybean. The two polypeptides, which had apparent molecular masses of 29,000 daltons and 33,000 daltons, were present in the sink-deprived plants but not in control podded plants and were the subunit polypeptides of a glycoprotein designated lectin-related protein (LRP). Soybean LRP was purified to near homogeneity by a combination of ammonium sulfate precipitation and gel filtration. Dialysis of the resuspended ammonium sulfate precipitate caused LRP to reprecipitate, and LRP was soluble only in the presence of molar NaCl. The native relative molecular mass of LRP was 119,000 daltons, a size consistent with a tetrameric organization of the two polypeptides. LRP precipitated during dialysis in association with a 28,000 dalton polypeptide. The protein coprecipitating with LRP was identified as the dimer of the 28,000 dalton subunit of VSP, one of three native isomeric forms of VSP occurring in leaves of depodded plants. Although the specific association between LRP and VSP was intriguing, an in vivo interaction between LRP and VSP was doubtful. LRP was shown to be immunologically similar to soybean agglutinin but did not have detectable hemagglutinating activity. LRP also was shown to be made up of polypeptides distinct from soybean agglutinin.


The role of human TFIIB in transcription start site selection in vitro and in vivo.
The general transcription factor TFIIB plays a crucial role in selecting the transcription initiation site in yeast. We have analyzed the human homologs of TFIIB mutants that have previously been shown to affect transcription start site selection in the yeast Saccharomyces cerevisiae. Despite the distinct mechanisms of transcription start site selection observed in S. cerevisiae and humans, the role of TFIIB in this process is similar. However, unlike their yeast counterparts, the human mutants do not show a severe defect in supporting either basal transcription or transcription stimulated by an acidic activator in vitro. Transient transfection analysis revealed that, in addition to a role in transcription start site selection, human TFIIB residue Arg-66 performs a critical function in vivo that is bypassed in vitro. Furthermore, although correct transcription start site selection is dependent upon an arginine residue at position 66 in human TFIIB, innate function in vivo is determined by the charge of the residue alone. Our observations raise questions as to the evolutionary conservation of TFIIB and uncover an additional function for TFIIB that is required in vivo but can be bypassed in vitro.


Oxidative stress status and RNA expression in hippocampus of an animal model of Alzheimer's disease after chronic exposure to aluminum.
It is well established that aluminum (Al) is a neurotoxic agent that induces the production of free radicals in brain. Accumulation of free radicals may cause degenerative events of aging such as Alzheimer's disease. On the other hand, melatonin (Mel) is a known antioxidant, which can directly act as free radical scavenger, or indirectly by inducing the expression of some genes linked to the antioxidant defense. In this study, AbetaPP female transgenic (Tg2576) (Tg) and wild-type mice (5 months of age) were fed with Al lactate supplemented in the diet (1 mg Al/g diet). Simultaneously, animals received oral Mel (10 mg/kg) dissolved in tap water until the end of the study at 11 months of age. Four treatment groups were included for both Tg and wild-type mice: control, Al only, Mel only, and Al+Mel. At the end of the period of treatment, hippocampus was removed and processed to examine the following oxidative stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Moreover, the gene expression of Cu-ZnSOD, GR, and CAT was evaluated by real-time RT-PCR. Aluminum concentration in hippocampus was also determined. The biochemical changes observed in this tissue suggest that Al acts as a pro-oxidant agent. Melatonin exerts an antioxidant action by increasing the mRNA levels of the antioxidant enzymes SOD, CAT, and GR evaluated in presence of Al and Mel, with independence of the animal model.


Cost-effective complete genome sequencing using the MinION platform for identification of recombinant enteroviruses.
By employing a cost-effective approach for complete genome sequencing, the study has enabled the identification of novel enterovirus strains and shed light on the genetic exchange events during outbreaks. The success rate of genome sequencing and the scalability of the protocol demonstrate its practical utility for routine enterovirus surveillance. Moreover, the study's findings of recombinant strains of EVA71 and CVA2 contributing to epidemics in Malaysia and Taiwan emphasize the need for accurate detection and characterization of enteroviruses. The investigation of the whole genome and upstream ORF sequences has provided insights into the evolution and spread of enterovirus subgenogroups. These findings have important implications for the prevention, control, and surveillance of enteroviruses, ultimately contributing to the understanding and management of enterovirus-related illnesses.


Is it safe to perform endoscopic vein harvest?
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: in [patients undergoing coronary revascularisation] is [endoscopic vein harvest] superior to [open harvest] in improving [clinical outcome and cost effectiveness]? Altogether >166 papers were found using the reported search, of which eight represented the best evidence to answer the clinical question. All papers agree that endoscopic vein harvesting (EVH) reduces the level of postoperative pain (pain score for EVH=0.52+/-0.95; open technique=1.02+/-1.51; P=0.03) and wound complications (range from 3 to 7.4% for EVH and 13 to 19.4% for conventional technique). These clinical benefits were associated with a high level of patient satisfaction. On average, four papers found that the length of hospital stay was reduced in the EVH group [weighted mean difference (WMD) -1.04 to -0.85; confidence interval (CI) -1.92 to -0.16; P=0.02]. The overall occlusion rates of venous grafts after six months were 21.7% for EVH and 17.6% for open technique. There were no differences in the six months occlusion and disease rates between EVH and conventional vein harvest (CVH), as determined by means of univariate analysis (P=0.584). However, some papers (PREVENT-IV sub-analysis and Yun et al.) called into question EVH by reporting high vein occlusion rates. At six months, this was 21.7% for EVH and 17.6% for open technique rising to 46.7% vs. 38.0% (P<0.001) at 12-18 months. At three years, endoscopic harvesting was also associated with higher rates of death, myocardial infarction, or repeat revascularisation (20.2% vs. 17.4%; P=0.04), death or myocardial infarction (9.3% vs. 7.6%; P=0.01), and death (7.4% vs. 5.8%; P=0.005). We conclude that EVH reduces the level of postoperative pain and wound complication, with a high-level of patient satisfaction but a sub-analysis of a large RCT has recently called into question the medium- to long-term patency of grafts endoscopically harvested.


Skeletal muscle metastasis from a conventional renal cell carcinoma, two years after nephrectomy: a case report.
In this paper, we describe a case of skeletal muscle metastasis from a conventional (clear cell) renal cell carcinoma, two years after nephrectomy. Our first clinical tentative diagnosis was soft tissue tumour, showing the mimicking capacity of renal cell carcinoma. A review of literature shows that skeletal muscle metastases from renal cell carcinoma are extremely rare: only 16 cases have been described. In 5/16, the muscle mass was the initial manifestation of the renal tumour. In the other 11/16, the muscle masses were metachronous (10 months-16 years). We conclude that, when confronted with a patient with a muscle mass and a history of renal cell carcinoma, one should always keep in mind the possibility of a (late) renal cell carcinoma metastasis.


Self-assembly of a "double dynamic covalent" amphiphile featuring a glucose-responsive imine bond.
Glucose binding via boronate ester linkages selectively triggers imine bond formation between 4-formylphenylboronic acid and octylamine, leading to the formation of vesicular aggregates in aqueous solutions. This "double dynamic covalent assembly" allows the facile selective sensing of glucose against the otherwise serious interferant fructose, without the need to resort to synthetic effort.


Safety and efficacy of IMP (disodium 5'-inosinate) produced by fermentation with Corynebacterium stationis KCCM 80161 for all animal species.
Following a request from the European Commission, the Panel on Additives and Products or substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of disodium 5'-inosinate (IMP) produced by fermentation using Corynebacterium stationis KCCM 80161 when used as a sensory additive (flavouring compound) in feed and water for drinking for all animal species. The production strain is not genetically modified. Viable cells of the production strain were not detected in the final additive. The additive does not give rise to any safety concern regarding the production strain. IMP produced using C. stationis KCCM 80161 is considered safe for the target species, for the consumer and for the environment. IMP produced using C. stationis KCCM 80161 is considered not toxic by inhalation, not irritant to skin or eyes and not a dermal sensitiser. The FEEDAP Panel expressed reservations on the use of the additive in water for drinking due to concerns on its impact on the hygienic conditions of the water. The Panel concluded that the additive is efficacious to contribute to the flavour of feed.


Prevention and detection of prostate cancer: a pilot intervention in a resource--poor South African community.
Prostate cancer is a global health problem strongly linked to the Western lifestyle and its health risks. South Africa, like many African countries, has no population-based screening for this disease. The purpose of this study was to develop and pilot test an intervention focused on the prevention and detection of prostate cancer in a resource-poor community in Tshwane, South Africa. Personal invitations for screening were extended to 122 men 40 years or older. Those presenting for screening received health education on prostate cancer and were screened using digital rectal examination and a prostate-specific antigen (PSA) test. Follow-up appointments were also arranged. Only 53.3% (n = 65) of the invitees reported for screening, with 38 (58.5%) returning to the clinic to learn the results of the PSA test. Knowledge of prostate cancer improved significantly after the intervention. Abnormal findings were detected in 6.2% (n = 4) of the participants, and elevations in PSA levels, in 12.3% (n = 8). Disappointing results in terms of screening uptake and the number of men lost to follow-up were achieved. The strategies to improve knowledge were successful and resulted in a significant increase in knowledge of prostate cancer. The success of a cancer prevention and detection service is determined by participation and screening uptake. The reasons for not accepting the screening invitation and not returning to learn the findings of the PSA test should be explored. Preventative strategies should be developed and tested as part of a second pilot study testing the refined intervention.


Development of a new international classification of health interventions based on an ontology framework.
: The WHO International Classification of Diseases is used in many national applications to plan, manage and fund through case mix health care systems and allows international comparisons of the performance of these systems. There is no such measuring tool for health interventions or procedures. To fulfil this requirement the WHO-FIC Network recommended in 2006 to develop an International Classification of Health Interventions (ICHI). This initiative is aimed to harmonise the existing national classifications and to provide a basic system for the countries which have not developed their own classification systems. It is based on the CEN/ISO ontology framework standard named Categorial Structure defined from a non formal bottom up ontology approach. The process of populating the framework is ongoing to start from a common model structure encompassing the ICD 9CM Volume 3 granularity.


Uranyl Solvation by a Three-Dimensional Reference Interaction Site Model.
We report an implementation of the three-dimensional reference interaction site model (3D RISM) that in particular addresses the treatment of the long-range Coulomb field of charged species, represented by point charges and/or a distributed charge density. A comparison of 1D and 3D results for atomic ions demonstrates a reasonable accuracy, even for a moderate size of the unit cell and a moderate grid resolution. In an application to uranyl complexes with 4-6 explicit aqua ligands and an implicit bulk solvent modeled by RISM, we show that the 3D technique is not susceptible to the deficiencies of the 1D technique exposed in our previous work [Li, Matveev, Krüger, Rösch, Comp. Theor. Chem. 2015, 1051, 151]. The 3D method eliminates the artificial superposition of explicit aqua ligands and the RISM medium and predicts essentially the same values for uranyl and uranyl-water bond lengths as a state-of-the-art polarizable continuum model. With the first solvation shell treated explicitly, the observables are nearly independent of the order of the closure relationship used when solving the set of integral equations for the various distribution functions. Furthermore, we calculated the activation barrier of water exchange with a hybrid approach that combines the 3D RISM model for the bulk aqueous solvent and a quantum mechanical description (at the level of electronic density functional theory) of uranyl interacting with explicitly represented water molecules. The calculated result agrees very well with experiment and the best theoretical estimates.


Recovery-oriented psychopharmacology: redefining the goals of antipsychotic treatment.
The traditional goals of psychopharmacology stem from the medical model. Rehabilitation interventions attempt to improve aspects of functioning in patients with chronic illnesses that are not responsive to biological intervention. Recovery is a concept emanating from the consumer self-help movement. It describes a move away from the patient role defined by a diagnostic label toward community membership defined by relationships and responsibilities in the community. Comprehensive care for people with psychotic disorders can include attention to each realm. This article provides an overview of the 3 models of care and describes a role for the psychopharmacologist in each as well as his or her unique potential to incorporate all 3. We outline potential synergistic benefits of integrating recovery-, rehabilitation-, and medical-model thinking into the practice of psychopharmacology and explore implications for the goals and outcomes of treatment for people with psychotic disorders.


[Double-primary cancer of the lung and trachea].
A 70-year-old woman with no history of smoking was admitted to the hospital because of a persistent cough and pneumonia in the right lower lobe. Examination with a fiberoptic bronchoscope revealed an intratracheal polypoid tumor and a polypoid tumor almost completely obstructing the right bronchus B(8). Biopsies were done, and histological diagnosis of both tumors was squamous cell carcinoma. A sleeve resection of the trachea with end-to-end anastomosis and right lower lobectomy were done. Examination of specimens resected from both tumors revealed moderately differentiated squamous cell carcinoma. Synchronous double-primary cancer (both squamous cell carcinoma) of the lung and trachea in a non-smoker is very rare.


Survival Analysis of 3 Different Age Groups and Prognostic Factors among 402 Patients with Skeletal High-Grade Osteosarcoma. Real World Data from a Single Tertiary Sarcoma Center.
Age is a known prognostic factor for many sarcoma subtypes, however in the literature there are limited data on the different risk profiles of different age groups for osteosarcoma survival. This study aims to provide an overview of survival in patients with high-grade osteosarcoma in different age groups and prognostic variables for survival and local control among the entire cohort. In this single center retrospective cohort study, 402 patients with skeletal high-grade osteosarcoma were diagnosed and treated with curative intent between 1978 and 2017 at the Leiden University Medical Center (LUMC). Prognostic factors for survival were analyzed using a Cox proportional hazard model. In this study poor overall survival (OS) and event-free survival (EFS) were associated with increasing age. Age groups, tumor size, poor histopathological response, distant metastasis (DM) at presentation and local recurrence (LR) were important independent prognostic factors influencing OS and EFS. Differences in outcome among different age groups can be partially explained by patient and treatment characteristics.


Fluorescent Indicator Displacement Assay: Ultrasensitive Detection of Glutathione and Selective Cancer Cell Imaging.
This Research Article reports the development of nanohybrid comprising of anionic carbon dots (ACD) protected gold nanoparticle (GNP). ACD directly cap GNP through its anionic surface functionalization leading to the formation of stable aqueous GNP dispersion. This newly developed ACD-GNP nanohybrid has been thoroughly characterized by different spectroscopic and microscopic techniques. This nanohybrid is successfully employed toward the selective sensing of glutathione (GSH). The mechanism of GSH sensing by this nanosensor is based on the GSH triggered displacement of fluorescent indicator ACD from the GNP surface. Upon capping GNP, intrinsic fluorescence of ACD gets quenched. Addition of GSH displaces the fluorescent indicator ACD from GNP surface and restores the fluorescence signal of ACD. This nanosensor exhibits very high selectivity as well as sensitivity toward glutathione over the other biothiols and can detect as low as 6 nM of GSH. More importantly, selective imaging of the cancer cells over the noncancerous cells was achieved by this ACD-GNP hybrid implying its potential applications in biosensing, as well as in cancer diagnosis.


Precise Synthesis and Thermoresponsive Property of Poly(ethyl glycidyl ether) and Its Block and Statistic Copolymers with Poly(glycidol).
In this paper, we describe a comprehensive study of the thermoresponsive properties of statistic copolymers and multiblock copolymers synthesized by poly(glycidol)s (PG) and poly(ethyl glycidyl ether) (PEGE) with different copolymerization methods. These copolymers were first synthesized by ring-opening polymerization (ROP), which was initiated by tert-butylbenzyl alcohol (tBBA) and 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)phosphoranylidenamino]-2Λ5,4Λ5-catenadi(phosphazene) (t-Bu-P4) as the catalyst, and then the inherent protective groups were removed to obtain the copolymers without any specific chain end groups. The thermoresponsive property of the statistic copolymer PGx-stat-PEGEy was compared with the diblock copolymer PGx-b-PEGEy, and the triblock copolymers were compared with the pentablock copolymers. Among them, PG-stat-PEGE, PG-b-PEGE-b-PG-b-PEGE-b-PG, and PEGE-b-PG-b-PEGE-b-PG-b-PEGE, and even the specific ratio of PEGE-b-PG-b-PEGE, exhibited LCST-type phase transitions in water, which were characterized by cloud point (Tcp). Although the ratio of x to y affected the value of the Tcp of PGx-stat-PEGEy, we found that the disorder of the copolymer has a decisive effect on the phase-transition behavior. The phase-transition behaviors of PG-b-PEGE, part of PEGE-b-PG-b-PEGE, and PG-b-PEGE-b-PG copolymers in water present a two-stage phase transition, that is, firstly LCST-type and then the upper critical solution temperature (UCST)-like phase transition. In addition, we have extended the research on the thermoresponsive properties of EGE homopolymers without specific α-chain ends.


Therapy Dog Presence in an Undergraduate Nursing Program.
Research supports the use of animal-assisted interactions and pet therapy in various settings. Undergraduate nursing students experience high levels of stress and anxiety which often continue as they become professional nurses. Entering the workforce equipped with positive coping strategies may help newly licensed nurses to combat stressors. This qualitative descriptive study examined the experiences of undergraduate nursing students with the presence of a therapy dog. Four major themes regarding the role of therapy dogs were identified: as a coping strategy, as a mood moderator, as a positive distraction, and for community building.


Thresholds for second formant transitions in front vowels.
Formant dynamics in vowel nuclei contribute to vowel classification in English. This study examined listeners' ability to discriminate dynamic second formant transitions in synthetic high front vowels. Acoustic measurements were made from the nuclei (steady state and 20% and 80% of vowel duration) for the vowels /i, I, e, epsilon, ae/ spoken by a female in /bVd/ context. Three synthesis parameters were selected to yield twelve discrimination conditions: initial frequency value for F2 (2525, 2272, or 2068 Hz), slope direction (rising or falling), and duration (110 or 165 ms). F1 frequency was roved. In the standard stimuli, F0 and F1-F4 were steady state. In the comparison stimuli only F2 frequency varied linearly to reach a final frequency. Five listeners were tested under adaptive tracking to estimate the threshold for frequency extent, the minimal detectable difference in frequency between the initial and final F2 values, called deltaF extent. Analysis showed that initial F2 frequency and direction of movement for some F2 frequencies contributed to significant differences in deltaF extent. Results suggested that listeners attended to differences in the stimulus property of frequency extent (hertz), not formant slope (hertz/second). Formant extent thresholds were at least four times smaller than extents measured in the natural speech tokens, and 18 times smaller than for the diphthongized vowel /e/.


Ethics Position and Leadership Style in a Mayor's Office.
Recent cases of unethical behavior in organizations indicate the need to carry out empirical research about it. Determine the existence of a relationship between ethics and leadership, demanded by society and prescribed by various academic theories.Method: For this reason, through the conduction of non-experimental, cross-sectional, quantitative research, it is sought to make a process of falsification of the theoretical proposals in the context of a municipal mayoralty. In the development of the research, the responses of 219 leaders were satisfactorily received, answering questions from two psychometric instruments of wide recognition and academic validity, the Ethics Position Questionnaire and the Multifactor Leadership Questionnaire. They were carried out both through an exploratory data analysis and a confirmatory factor analysis, and a model of structural equations that tested the existence of a relation between the ethical position and the styles of leadership. It was also possible to identify the influence exerted by the different ethical positions in each one of the styles of leadership in a local public administration. These findings facilitate the identification of ethical leadership models in local public organizations and contribute towards the empirical demonstration of the current discussion on the relationship between ethics and leadership in organizations.


Separation of liposomes from plasma components using fast protein liquid chromatography.
We describe an efficient method for separating liposomes (large unilamellar vesicles, 120-150 nm diameter) from plasma lipoproteins employing fast protein liquid chromatography (FPLC). This method resolves very low density lipoprotein (VLDL), low-density lipoprotein, high-density lipoprotein, and other plasma components. Selective detection of liposomes (large unilamellar vesicles, 120-150 nm diameter) was achieved using either radiolabeled or fluorescent lipid probes. The liposomes were found to coelute with the earliest FPLC-eluting lipoprotein fraction, VLDL. The remaining plasma lipoprotein and protein components eluted at later times and were resolved from liposomes and VLDL. In order to separate VLDL from liposomes, we selectively precipitated the VLDL fraction from plasma using tungstophosphoric acid and magnesium chloride, prior to separation by FPLC. Furthermore, we demonstrate that this technique can be used to separate liposomes from lipoproteins in plasma samples collected after intravenous administration of liposomes to mice. This technique has wide application in studies of liposome stability in blood and, in particular, for the characterization of liposomal drug carrier systems.


Modified Ride-on Car Use by Children With Complex Medical Needs.
The purpose of this report was to determine the feasibility of short-term modified ride-on car (ROC) use for exploration and enjoyment by children with complex medical needs. A single-subject research design was used (n = 3; age, 6 months to 5 years). Children were video-recorded using their modified ROC. All children successfully learned how to independently drive a modified ROC. Two of the 3 children demonstrated high levels of enjoyment during use of a modified ROC. Modified ROC use is a feasible and enjoyable powered mobility device for children with complex medical needs.


Early Infant Diagnosis: A New Tool of HIV Diagnosis in Children.
Standard assay has limited utility in diagnosing HIV reactivity among infants till the age of 18 months by which time, many HIV-infected infants expire. The test for diagnosing infant and children below 18 months is DNA polymerase chain reaction (DNAPCR) either by dried blood spot (DBS) or whole blood sample (WBS). Early infant diagnosis (EID) project is implemented in 18 districts of Gujarat through 33 PPTCT centers from 1st April 2010. Present analysis is done to evaluate factors curbing mother to child HIV transmission. Study included all children (< 18 months) who are born to HIV-positive mothers or referred children with signs/ symptoms of HIV with unknown parent status or children already on anti-retroviral therapy whose status could not be confirmed by antibody tests. Data was compiled and analyzed according to the infant's age at testing, type of feeding, history of Anti retero viral (ARV) prophylaxis, and type of delivery. Data compiled between April and August 2010 was used for the analysis. Cohort of 326 infants was followed up, fewer infants (14/270) who received ARV prophylaxis tested positive than those who did not (23/56). Transmission was more in normal delivery (29/252) than cesarean (8/74). Low transmission rate was seen in replacement feeding (13/208) than breast/mixed feeding (24/94). Out of 37 samples found positive by the DBS, 17 were sent for WBS and all were found to be positive. DBS test results were found as accurate as WBS. So DBS (less cumbersome and cost effective) can be used in future exclusively. Nevirapine administration at birth as mother baby pair showed 36% decrease in MTCT.


Surface-enhanced Raman scattering microchip fabricated by femtosecond laser.
We report a surface-enhanced Raman scattering (SERS) microchip that is capable of measuring SERS signals of liquid samples with high sensitivity. The microdevice is an integration of a silicon-based SERS substrate, a multimode optical fiber (MMF), and a microchannel embedded in the photosensitive glass fabricated by the femtosecond laser followed by thermal treatment, wet etching, and annealing. The performance of the SERS microchip is evaluated by measuring rhodamine 6G using a 632.8 nm He-Ne laser at 4.3 mW excitation power, which reveals that the detection limit is lower than 10(-10) M at a 1 s short accumulation time.


Purification and characterization of the common yolk protein, vitellin, from the estuarine amphipod Leptocheirus plumulosus.
Vitellin is a major yolk protein that plays a significant role in the embryonic development of crustacean embryos. This protein was rapidly purified from embryos of the estuarine amphipod, Leptocheirus plumulosus, by subjecting the crude protein homogenate to high affinity column chromatography. SDS-PAGE revealed a single band with an approximate molecular weight of 200,000 daltons. Vitellin was characterized by SDS-PAGE techniques and amino acid composition analysis. L. plumulosus vitellin is a lipoglycophosphoprotein with serine, glutamic acid/glutamine, alanine, and aspartic acid/asparagine accounting for almost 66% of all amino acid residues. Polyclonal antibodies were raised against L. plumulosus vitellin and antibody reactivity was verified by dot-blotting and immuno-fluorescence confocal microscopy. These antibodies are specific for purified vitellin and show little cross-reactivity with other embryonic proteins.


Detection and molecular diversity of spike gene of porcine epidemic diarrhea virus in China.
Since late 2010, porcine epidemic diarrhea virus (PEDV) has rapidly disseminated all over the China and caused considerable morbidity and high mortality (up to 100%) in neonatal piglets. 79.66% (141 of 177) pig farms in 29 provinces (excluding Tibet and Hainan, China) and 72.27% (417 of 577) samples were positive for PEDV confirmed by reverse transcription-polymerase chain reaction (RT-PCR). The full-length S genes of representative field strains were sequenced. 33 field strains share 93.5%-99.9% homologies with each other at the nucleotide sequence level and 92.3%-99.8% homologies with each other at the amino acids sequence level. Most field strains have nucleotide deletion and insertion regions, and show lower homologies (93.5%-94.2%) with Chinese classical strain CH/S, however higher homologies (97.1%-99.3%) with recent strain CHGD-1. The phylogenetic analysis showed there are classical strains and variants prevailing in pig herd in China. PEDV has a high detection rate in pig herds in China. Sequence analysis indicated the S genes of recent field strains have heterogeneity and the variants are predominant.


[[Perinatal mortality rates in single and multiple births, and the effects of maternal age, birthweight, and other factors on the perinatal mortality rates in Japan]].
"The perinatal mortality rate (PMR) was analyzed using... Vital Statistics for 1950-1991 in Japan. Secular changes in the PMRs were analyzed according to sex and single-multiple births. This paper also investigated the effects of maternal age, birth order, gestational age, and birthweight on the PMR." (SUMMARY IN ENG)


Laparoscopic placement of the Chait cecostomy device via appendicostomy.
The authors describe their experience with a series of 11 patients in whom they have carried out Chait cecostomy catheter insertion into a laparoscopically formed appendicostomy. This technique has several advantages compared with percutaneous insertion and we now insert the device at the primary procedure. The authors have had one minor complication in their 11 patients, with mean follow-up of 8 months. This technique is recommended for the management of refractory constipation, for etiologies including spina bifida, anorectal malformation, distal intestinal obstruction syndrome, and slow-colonic transit.


Impact of immune activation on stored sperm viability in ant queens.
Ant queens mate on a single occasion early in life and store millions of sperm cells in their spermatheca. By carefully using stored sperm to fertilize eggs, they can produce large colonies of thousands of individuals. Queens can live for decades and their lifetime reproductive success is dependent on their ability to keep stored sperm alive. Maintaining high sperm viability requires metabolic energy which could trade-off with other costly processes such as immunity. We tested the impact of immune activation on the survival of stored sperm by prompting Lasius niger ant queens to mount a melanization response and subsequently measuring sperm viability in their spermatheca. Since queens face different challenges that influence energy allocation depending on the life stage of their colony, we measured sperm viability after immune activation in both newly mated queens (incipient) and in queens 1 year after mating (established). We found that immune activation reduced sperm viability in established queens but not in incipient queens, showing that the cost of immunity on sperm preservation depends on the life stage. Unexpectedly, established queens had significantly higher sperm viability in their spermatheca compared to incipient queens suggesting that ant queens are able to remove dead sperm from their spermatheca.


Chemical study of triterpenoid resinous materials in archaeological findings by means of direct exposure electron ionisation mass spectrometry and gas chromatography/mass spectrometry.
A systematic study of standard triterpenes (alpha-amyrine, oleanolic acid, betulin, lupeol, betulinic acid and lupenone) and of raw resinous materials (frankincense resin, mastic resin and birch bark pitch) was performed using direct exposure electron ionisation mass spectrometry (DE-MS) and gas chromatography/mass spectrometry (GC/MS). DE-MS provides a mass spectral fingerprint of organic materials in a few minutes which highlights the compounds that are the main components in the sample. The application of principal component analysis (PCA) on DE-MS data in the mass ranges m/z 181-260 and m/z 331-500, corresponding to the fragmentation of triterpenoid molecules, enabled us to distinguish between different triterpenoid materials such as mastic resin, frankincense resin and birch bark pitch, and to graphically plot the resinous substances in three separate clusters, retaining 89% of the total variance. GC/MS analysis of the same materials has permitted us to elucidate in detail the molecular composition and to identify minor components and species that act as markers of the degradation undergone by the materials. The paper also reports the results for the organic residues contained in an Egyptian censer (5th-7th century AD) which was recovered in the excavation of the Necropolis of Antinoe (Egypt), and for the hafting material found on a Palaeolithic tool recovered at the site of Campitello (Arezzo, Tuscany), dating back to the Mid-Pleistocene period. Although DE-MS was found to be a fast analytical tool, it failed to give any information on the presence of less abundant compounds when applied to mixtures of different materials: only mastic resin was found in the residues from the Roman censer, whereas GC/MS analysis identified the presence of a vegetable oil from Brassicaceae seeds and Pinaceae resin. Birch bark pitch as a pure material was identified in the sample from the Palaeolithic flint flake using both procedures.


[Neonatal mortality in the Czech Republic 1998-1999].
To evaluate neonatal mortality rate (NMR) in 1998 and 1999 years in the Czech Republic. Retrospective epidemiological study of all alive newborns born in 1998 and 1999 in the Czech Republic. 12 perinatological centers of nine regions of Bohemia and Moravia. All alive, died, died with congenital defects newborns were registered and results of neonatal mortality rate and specific neonatal mortality rate were calculated. The main causes of death were divided into four groups (intraventricular hemorrhage grade III-IV, infection, acute respiratory failure and others) and evaluated comparatively. In 1999 the NMR of newborns with birth weight below 500 g and their survival were introduced for the first time in the Czech Republic. The fluent decrease of NMR during nineties was stopped in 1999. Increase of NMR from 2.8@1000 in 1998 to 3.0@1000 in 1999 was mainly caused by arise of specific neonatal mortality rate in newborns weighing > or = 2000 g. Comparing 1998 and 1999 years, two times more these newborns without serious congenital defects died in 1999 (28 vs. 56). Specific neonatal mortality rate of extremely low birth weight newborns further decreased (359@1000 vs. 279@1000) especially in the newborns with birth weight between 500-749 g (543@1000 vs. 373@1000). The most frequent main causes of death still has been intraventicular haemorrhage grade III-IV and infection in very low birth weight newborns, and serious congenital defects and infection in newborns weighing > or = 1500 g. The concentration of very low birth weight newborns to perinatological centers by transfer in uterus was 81% in 1998 and 83% in 1999. The differences in neonatal mortality rates between nine regions of Bohemia and Moravia has been getting equal but has been still great in specific neonatal mortality rate of extremely low birth weight newborns between the best and worst regions (147@1000 vs. 458@1000). There were registered 19 newborns weighing < or = 500 g surviving more than 24 hours after delivery in the Czech republic. Specific neonatal mortality rate of these newborns was 316@1000 and 527@1000 survived. Reserves for further lowering of NMR are improving the care after extremely low birth weight newborns in the regions with below average results and decreasing the mortality of newborns with birth weight > or = 2000 g by introducing of group B streptococcus prophylaxis, improving prenatal diagnostics of serious congenital defects and early and more quality postnatal transport of newborns suffered from acute respiratory failure to centers disposing of the latest methods of treatment.


Farmers' perceptions of pesticides, and resultant health problems from exposures.
As part of an evaluation study of the impacts of the Indonesian integrated pest management (IPM) Farmer Field Schools on farmers' health, focus group discussions were conducted with rice farmers who grew shallots in rotation. Farmers who had previously participated in IPM rice field schools and who were at the time participating in IPM shallot field schools were compared with farmers who had had no experience with IPM methods. The study found that farmers' knowledge concerning the health dangers of pesticides is not sufficient to change their behaviors. Their overriding concern is crop damage that leads to economic loss, not health. IPM field-school training offers farmers a viable alternative by concretely demonstrating the health, agricultural, environmental, and economic advantages of eliminating unnecessary pesticide use. If public health professionals aim to change behaviors through interventions, they must employ appropriate methods, meet the community's priorities and values, and offer feasible alternatives.


Accessory bones of the elbow: Prevalence, localization and modified classification.
Accessory bones in the region of the elbow are rare variants with high clinical significance as they may be confused with avulsion fractures. We investigated their prevalence and performed a statistical analysis to support their congenital origin. Their localization was mapped to show their exact site of occurrence. We evaluated anteroposterior and lateral X-ray images of 2413 elbows in a Central European population from which a group of accessory bony structures was selected. Their character was evaluated, and accessory bones were identified. We used logistic regression to evaluate the potential relationship between the occurrence of accessory bones, the age of patients, and the occurrence of calcar olecrani. The prevalence of accessory bones of the elbow in the sample was 0.77%. Our results did not show a statistically significant relationship with the occurrence of calcar olecrani or with the age of patients. The most common type was os subepicondylare mediale (type V) in 0.46%, which was located distal to the medial epicondyle of the humerus, followed by os subepicondylare laterale (type III; 0.21%), situated laterally to the lateral epicondyle of the humerus. In comparison with previous reports, os sesamoideum mediale (type IV) was located more distally. Our data suggest that congenital accessory bones are a rare entity. Knowledge of their exact localization should be considered during diagnosis of avulsion fractures and other unclear diagnoses including accessory bony structures in the elbow region.


Passive Control of Viscous Flow via Elastic Snap-Through.
We demonstrate the passive control of viscous flow in a channel by using an elastic arch embedded in the flow. Depending on the fluid flux, the arch may "snap" between two states-constricting and unconstricting-that differ in hydraulic conductivity by up to an order of magnitude. We use a combination of experiments at a macroscopic scale and theory to study the constricting and unconstricting states, and determine the critical flux required to transition between them. We show that such a device may be precisely tuned for use in a range of applications, and, in particular, has potential as a passive microfluidic fuse to prevent excessive fluxes in rigid-walled channels.


Flexibility and binding affinity in protein-ligand, protein-protein and multi-component protein interactions: limitations of current computational approaches.
The recognition process between a protein and a partner represents a significant theoretical challenge. In silico structure-based drug design carried out with nothing more than the three-dimensional structure of the protein has led to the introduction of many compounds into clinical trials and numerous drug approvals. Central to guiding the discovery process is to recognize active among non-active compounds. While large-scale computer simulations of compounds taken from a library (virtual screening) or designed de novo are highly desirable in the post-genomic area, many technical problems remain to be adequately addressed. This article presents an overview and discusses the limits of current computational methods for predicting the correct binding pose and accurate binding affinity. It also presents the performances of the most popular algorithms for exploring binary and multi-body protein interactions.


Distinct effects of high-glucose conditions on endothelial cells of macrovascular and microvascular origins.
Recent studies implicate hyperglycemia as an important cause of macrovascular and ocular complications in diabetes mellitus. In this study, the authors examined the effect of high glucose on macrovascular and microvascular endothelial cell viability and apoptosis in culture. Human aortic endothelial cells (HAECs) and human retinal endothelial cells (HRECs) were exposed to normal-glucose conditions (NG) and high-glucose conditions (NG supplemented with 25 mM D-glucose) for 72 h in vitro. D-Mannitol was used as an osmotic control. Cell viability was assessed by methlythiazolydiphenyltetrazolium bromide (MTT) assay, and induction of apoptosis was assessed by Hoechst staining. Statistics were analyzed by paired t tests. In HAECs, cell viability was decreased by 12.9% in high-glucose conditions, and apoptotic cells were significantly increased by 77%. However, in HRECs, cell viability was increased by 14.9% in high-glucose conditions, and apoptotic cells were significantly decreased by 33.3%. Mannitol did not show any effect on cell survival or apoptosis ruling out an osmotic effect. High-glucose conditions reduce cell viability and induce apoptosis in HAECs, which may contribute to macrovascular complications associated with diabetes. In contrast, high-glucose increases viability in HRECs and inhibits apoptosis, which may contribute to the development of diabetic retinopathy.