Intensity-modulated radiotherapy for the management of primary and recurrent chordomas: a retrospective long-term follow-up study.
Chordomas have a high risk of recurrence. Radiotherapy (RT) is required as adjuvant therapy after resection. Sufficient radiation doses for local control (LC) can be achieved using either particle therapy, if this technology is available and feasible, or intensity-modulated radiotherapy. 57 patients (age, 11.8-81.6 years) with chordomas of the skull base, spine and pelvis who received photon radiotherapy between 1995 and 2017 were enrolled in the study. Patients were treated at the time of initial diagnosis (68.4%) or during recurrence (31.6%). 44 patients received adjuvant radiotherapy and 13 received definitive radiotherapy. The median total dose to the physical target volume was 70 Gy equivalent dose in 2 Gy fractions (EQD2) (range: 54.7-82.5) in 22-36 fractions. LC was 76.4%, 58.4%, 46.7% and 39.9% and overall survival (OS) was 98.3%, 89%, 76.9% and 47.9% after 1, 3, 5 and 10 years, respectively, with a median follow-up period of 6.5 years (range, 0.5-24.3 years). Age, dose and treatment concept (post-operative or definitive) were significant prognostic factors for OS. Primary treatment, macroscopic tumour at RT and size of the irradiated volume were statistically significant prognostic factors for LC. Photon treatment is a safe and effective treatment for chordomas if no particle therapy is available. The best results can be achieved against primary tumours if the application of curative doses is possible due to organs at risk in direct proximity. We recommend high-dose radiotherapy, regardless of the resection status, as part of the initial treatment of chordoma, using the high conformal radiation technique if particle therapy is not feasible.


Recognition properties of an acyclic biphenyl-based receptor toward carbohydrates.
Biphenyl-based receptor 1, incorporating four heterocyclic recognition units, was synthesized, and its binding properties toward neutral sugars were determined. Receptor 1 is a representative of a new series of acyclic carbohydrate-binding receptors, which were designed to recognize disaccharides. The compound 1 has been established as a highly effective receptor for dodecyl beta-D-maltoside, showing successive 1:1 and 2:1 receptor/substrate complexation behavior toward the disaccharide. Both hydrogen bonding and interactions of the sugar CH's with the aromatic units of the receptor contribute to the stabilization of the receptor-maltoside complexes.


Serum levels of nesfatin-1 are increased in gestational diabetes mellitus.
To analyze the concentrations of nesfatin-1 in maternal and cord serum, to evaluate the expression of nesfatin-1 in subcutaneous adipose tissue (SAT) from pregnant women with gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT). We studied a total of 50 GDM and 50 NGT subjects. The clinical features, serum nesfatin-1, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profiles were measured at the third trimester of pregnancy. The expression of nesfatin-1 in the SAT was determined by western blot. Compared with the NGT group, the GDM group showed greater levels of serum nesfatin-1, adipocyte fatty acid binding protein (AFABP), and leptin; a greater level of cord blood nesfatin-1; and a higher level of expression in SAT (p < 0.05 or p < 0.01). Fasting insulin (FI) (b = 0.317, p= 0.022) and body mass index (BMI) before delivery (b = 0.367, p=0.008) were independently associated with serum nesfatin-1. Nesfatin-1 was the independent risk factor for GDM. The GDM group had higher levels of maternal serum and cord blood nesfatin-1, and greater nesfatin-1 expression in SAT. Nesfatin-1 is closely related to obesity and IR in pregnancy.


Radiation associated malignancies of the esophagus.
This report documents the experience of the authors with two patients who had received thoracic radiation for disseminated teratocarcinomas of the testis, survived their malignancies, and subsequently developed squamous cell carcinomas of the esophagus. To the authors' knowledge, only 11 other cases of esophageal malignancies arising in patients who had received previous mediastinal irradiation have been reported in the world literature. With increasingly successful mediastinal radiation for malignant disease resulting in prolonged patient survival, an increasing number of such patients with subsequent esophageal malignancies can be anticipated. Close follow-up of patients receiving radiation therapy to periesophageal tissues is recommended, and prompt evaluation of any symptoms of esophageal dysfunction is indicated.


Controlled Fabrication of Bioactive Microtubes for Screening Anti-Tongue Squamous Cell Migration Drugs.
The treatment of tongue squamous cell carcinoma (TSCC) faces challenges because TSCC has an aggressive biological behavior and manifests usually as widespread metastatic disease. Therefore, it is particularly important to screen out and develop drugs that inhibit tumor invasion and metastasis. Two-dimensional (2D) cell culture has been used as in vitro models to study cellular biological behavior, but growing evidence now shows that the 2D systems can result in cell bioactivities that deviate appreciably the in vivo response. It is urgent to develop a novel 3D cell migration model in vitro to simulate the tumor microenvironment as much as possible and screen out effective anti-migration drugs. Sodium alginate, has a widely used cell encapsulation material, as significant advantages. We have designed a microfluidic device to fabricate a hollow alginate hydrogel microtube model. Based on the difference in liquid flow rate, TSCC cells (Cal27) were able to be evenly distributed in the hollow microtubes, which was confirmed though fluorescence microscope and laser scanning confocal microscope (LSCM). Our microfluidic device was cheap, and commercially available and could be assembled in a modular way, which are composed of a coaxial needle, silicone hose, and syringes. It was proved that the cells grow well in artificial microtubes with extracellular matrix (ECM) proteins by LSCM and flow cytometry. Periodic motility conferred a different motor state to the cells in the microtubes, more closely resembling the environment in vivo. The quantitative analysis of tumor cell migration could be achieved simply by determining the position of the cell in the microtube cross-section. We verified the anti-migration effects of three NSAIDs drugs (aspirin, indomethacin, and nimesulide) with artificial microtubes, obtaining the same results as conventional migration experiments. The results showed that among the three NSAIDs, nimesulide showed great anti-migration potential against TSCC cells. Our method holds great potential for application in the more efficient screening of anti-migration tumor drugs.


Transitions between explosive and effusive phases during the cataclysmic 2010 eruption of Merapi volcano, Java, Indonesia.
Transitions between explosive and effusive activity are commonly observed during dome-forming eruptions and may be linked to factors such as magma influx, ascent rate and degassing. However, the interplay between these factors is complex and the resulting eruptive behaviour often unpredictable. This paper focuses on the driving forces behind the explosive and effusive activity during the well-documented 2010 eruption of Merapi, the volcano's largest eruption since 1872. Time-controlled samples were collected from the 2010 deposits, linked to eruption stage and style of activity. These include scoria and pumice from the initial explosions, dense and scoriaceous dome samples formed via effusive activity, as well as scoria and pumice samples deposited during subplinian column collapse. Quantitative textural analysis of groundmass feldspar microlites, including measurements of areal number density, mean microlite size, crystal aspect ratio, groundmass crystallinity and crystal size distribution analysis, reveal that shallow pre- and syn-eruptive magmatic processes acted to govern the changing behaviour during the eruption. High-An (up to ∼80 mol% An) microlites from early erupted samples reveal that the eruption was likely preceded by an influx of hotter or more mafic magma. Transitions between explosive and effusive activity in 2010 were driven primarily by the dynamics of magma ascent in the conduit, with degassing and crystallisation acting via feedback mechanisms, resulting in cycles of effusive and explosive activity. Explosivity during the 2010 eruption was enhanced by the presence of a 'plug' of cooled magma within the shallow magma plumbing system, which acted to hinder degassing, leading to overpressure prior to initial explosive activity.


Posttraumatic symptoms, marital intimacy, dyadic adjustment, and sexual satisfaction among ex-prisoners of war.
The aversive impact of combat and combat-induced posttraumatic stress disorder (PTSD) on marital intimacy and sexual satisfaction has been examined in several studies. Nevertheless, the toll of war captivity on marital intimacy in relation to dyadic adjustment and sexual satisfaction remains unknown. In particular, the mediating role of marital intimacy in the relationship between PTSD symptoms and dyadic adjustment and between PTSD symptoms and sexual satisfaction has not yet been systematically explored thus far. Aims. This study aimed to examine the interrelationships of PTSD symptoms, dyadic adjustment, sexual satisfaction, and marital intimacy among ex-prisoners of war (ex-POWs). A sample of Israeli veterans ex-POWs (ex-POWs: N = 105) from the 1973 Yom Kippur War and a matched comparison group of veterans who participated in the same war but were not held captive (control: N = 94) were compared in the study variables. The PTSD inventory, dyadic adjustment scale, index of sexual satisfaction, and capacity for intimacy questionnaire. Results. Findings revealed that ex-POWs reported higher levels of PTSD symptoms and lower levels of dyadic adjustment and sexual satisfaction than comparable controls. There were also differences between the groups in the pattern of relations between PTSD symptoms, dyadic adjustment, sexual satisfaction, and marital intimacy. Finally, for ex-POWs, marital intimacy partially mediated the relationships between PTSD symptoms and dyadic adjustment and sexual satisfaction outcome measures. PTSD symptoms are implicated in marital problems of ex-POWs. A significant relationship was found between the traumatized ex-POW's capacity for intimacy and both their sexual satisfaction and dyadic adjustment.


A 52-year-old male with visual changes.
A 52 year-old male with a history of Cushing's Disease at age 18 and bilateral adrenalectomy at age 23 presented with visual changes. An MRI scan showed a pituitary macroadenoma (Nelson's syndrome). Other than the development of diabetes mellitus at age 32, his disease was stable until presentation. Serum studies show markedly elevated ACTH levels, but he had no hyperpigmentation. The tumor was removed by endoscopic surgery. Microscopic examination showed a pituitary adenoma with strong immunostaining for ACTH. In addition, the tumor cells showed Crooke's hyaline change and stained strongly for cytokeratin (Crooke's Cell Adenoma). Normal pituitary was not present. Crooke's cell adenomas are extremely rare and have not been previously reported in Nelson's Syndrome.


Quantitative Fecal Lactoferrin as a Biomarker for Severe Clostridium difficile Infection in Hospitalized Patients.
The incidence and severity of Clostridium difficile infection (CDI) have increased over the past decade, especially among hospitalized patients. In this study, we determined the value of published criteria for severe CDI in predicting 3 month mortality, as well as the utility of fecal lactoferrin as a biomarker for severe CDI. Pilot Year 1 of IRB approved (HSR-IRB# 13630) prospective cohort study of hospitalized patients with CDI at US academic medical center (10/08-4/10). Medical records of hospitalized patients with clinically diagnosed CDI, via toxin assay, were evaluated to objectively define severe CDI based on current guidelines. A stool sample from CDI diagnosis was analyzed for amount of fecal lactoferrin (IBD-SCAN, TechLab, Inc.). Data was analyzed using SPSS for student's t-test and chi-squared, significance p ≤ 0.05. 79 subjects consented and enrolled, mean age was 64 years (standard deviation, sd, 17.2), 48 (61%) female, and average Charlson co-morbidity score was 5.8 (sd 3.8). Subjects with severe CDI were 5 times more likely to die within 3 months of diagnosis (Odds Ratio 5.66 (95% Confidence Interval 2.03-15.79), p=0.001) and had significantly more fecal lactoferrin (580.0 (sd 989.0) vs. 181.7 (sd 244.2) µg/mL, p=0.018), compared to those that did not meet severe CDI criteria. In this pilot study, subjects who meet defined criteria for severe CDI had higher mortality and more intestinal inflammation. These preliminary results were, however, underpowered to show a direct association of lactoferrin with mortality. Larger cohort studies are needed to optimize a criterion for severe CDI and evaluate a direct association of lactoferrin and mortality in hospitalized patients with CDI.


Reactive oxygen species increase neuronal excitability via activation of nonspecific cation channel in rat medullary dorsal horn neurons.
The caudal subnucleus of the spinal trigeminal nucleus (medullary dorsal horn; MDH) receives direct inputs from small diameter primary afferent fibers that predominantly transmit nociceptive information in the orofacial region. Recent studies indicate that reactive oxygen species (ROS) is involved in persistent pain, primarily through spinal mechanisms. In this study, we aimed to investigate the role of xanthine/xanthine oxidase (X/XO) system, a known generator of superoxide anion (O2·-), on membrane excitability in the rat MDH neurons. For this, we used patch clamp recording and confocal imaging. An application of X/XO (300 µM/30 mU) induced membrane depolarization and inward currents. When slices were pretreated with ROS scavengers, such as phenyl N-tert-butylnitrone (PBN), superoxide dismutase (SOD), and catalase, X/XO-induced responses decreased. Fluorescence intensity in the DCF-DA and DHE-loaded MDH cells increased on the application of X/XO. An anion channel blocker, 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), significantly decreased X/XO-induced depolarization. X/XO elicited an inward current associated with a linear current-voltage relationship that reversed near -40 mV. X/XO-induced depolarization reduced in the presence of La3+, a nonselective cation channel (NSCC) blocker, and by lowering the external sodium concentration, indicating that membrane depolarization and inward current are induced by influx of Na+ ions. In conclusion, X/XO-induced ROS modulate the membrane excitability of MDH neurons, which was related to the activation of NSCC.


Neural circuitry engaged during unsuccessful motor inhibition in pediatric bipolar disorder.
Deficits in motor inhibition may contribute to impulsivity and irritability in children with bipolar disorder. Studies of the neural circuitry engaged during failed motor inhibition in pediatric bipolar disorder may increase our understanding of the pathophysiology of the illness. The authors tested the hypothesis that children with bipolar disorder and comparison subjects would differ in ventral prefrontal cortex, striatal, and anterior cingulate activation during unsuccessful motor inhibition. They also compared activation in medicated versus unmedicated children with bipolar disorder and in children with bipolar disorder and attention deficit hyperactivity disorder (ADHD) versus those with bipolar disorder without ADHD. The authors conducted an event-related functional magnetic resonance imaging study comparing neural activation in children with bipolar disorder and healthy comparison subjects while they performed a motor inhibition task. The study group included 26 children with bipolar disorder (13 unmedicated and 15 with ADHD) and 17 comparison subjects matched by age, gender, and IQ. On failed inhibitory trials, comparison subjects showed greater bilateral striatal and right ventral prefrontal cortex activation than did patients. These deficits were present in unmedicated patients, but the role of ADHD in mediating them was unclear. In relation to comparison subjects, children with bipolar disorder may have deficits in their ability to engage striatal structures and the right ventral prefrontal cortex during unsuccessful inhibition. Further research should ascertain the contribution of ADHD to these deficits and the role that such deficits may play in the emotional and behavioral dysregulation characteristic of bipolar disorder.


The complete mitochondrial genome of a striped sole Zebrias zebrinus (Pleuronectiformes: Soleidae).
Zebrias zebrinus belongs in the family Soleidae of Pleuronectiformes. There are overlaps in the ranges of identification characters between Z. zebrinus and another striped sole Z. fasciatus. In this study, the complete mitochondrial genome of Z. zebrinus was first determined. The total length was 16,758 bp, including 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes (12S and 16S), as well as a putative control region and a putative L-strand replication origin (O(L)). Gene contents, locations, and arrangements were identical to those of typical bony fishes. The overall base composition of the mitogenome was 28.7%, 30.0%, 15.2%, and 26.1% for A, C, G, and T, respectively, with an A + T content of 54.8%. This result would expect the contribution to the molecular identification of this species and further phylogenetic study of Soleidae and Pleuronectiformes.


Secure biometric authentication with de-duplication on distributed cloud storage.
Cloud computing is one of the evolving fields of technology, which allows storage, access of data, programs, and their execution over the internet with offering a variety of information related services. With cloud information services, it is essential for information to be saved securely and to be distributed safely across numerous users. Cloud information storage has suffered from issues related to information integrity, data security, and information access by unauthenticated users. The distribution and storage of data among several users are highly scalable and cost-efficient but results in data redundancy and security issues. In this article, a biometric authentication scheme is proposed for the requested users to give access permission in a cloud-distributed environment and, at the same time, alleviate data redundancy. To achieve this, a cryptographic technique is used by service providers to generate the bio-key for authentication, which will be accessible only to authenticated users. A Gabor filter with distributed security and encryption using XOR operations is used to generate the proposed bio-key (biometric generated key) and avoid data deduplication in the cloud, ensuring avoidance of data redundancy and security. The proposed method is compared with existing algorithms, such as convergent encryption (CE), leakage resilient (LR), randomized convergent encryption (RCE), secure de-duplication scheme (SDS), to evaluate the de-duplication performance. Our comparative analysis shows that our proposed scheme results in smaller computation and communication costs than existing schemes.


A Survey on the Relationship between Emotional Intelligence and Level of Depression and Anxiety among Women with Breast Cancer.
Background: Emotional Intelligence (EQ) is positively associated with mental health and it can have a crucial role in mental disorder therapy by suitable coping mechanisms. The present study aimed to evaluate the relationship of EQ with anxiety and depression among the women with breast cancer. Subjects and Methods: During 2013 and in a cross-sectional study, 98 breast cancer patients (14 to 21 years old) entered into the study. For data collection, the following instruments were the Bar-On EQ inventory, Beck Depression Inventory and Cattle Anxiety Inventory. Results: There was an inverse relationship between anxiety with intrapersonal (p<0.01, r=0.39) and stress management (p<0.01, r=0.37) components and also between anxiety and total scores of EQ (p<0.05, r=0.22). There was an inverse significant association between depression and intrapersonal components (p<0.05, r=0.23), general mood (p<0.01, r=0.46) and adaptation (p<0.01, r=0.38) and also between depression and a total score of EQ (p<0.01, r=0.42). Conclusion: The results of this present study confirmed the important role of EQ. Also, the results can be an inspiration for the future studies regarding the training of EQ skills in the treatment of mental disorder (anxiety and depression) among patients with breast cancer.


Duration of Anti-Programmed Death-1 Therapy in Advanced Melanoma: How Much of a Good Thing Is Enough?
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 53-year-old healthy man presented with recurrent in-transit melanoma of the right lower extremity. Eight years prior he had undergone wide local excision and sentinel lymph node biopsy for invasive melanoma of the anteromedial aspect of the distal right thigh. Pathology revealed an ulcerated melanoma, Breslow depth 3.5 mm, and with one involved micrometastatic inguinal lymph node. Staging studies did not demonstrate distant metastases. Superficial inguinal node dissection was performed and did not identify any additional metastatic nodes of 14 retrieved for a final pathologic staging of T3bN1aM0 (stage IIIB) cutaneous melanoma. He received 12 months of adjuvant high-dose interferon alfa-2b. Two years later, he developed a 1.2-cm subcutaneous focus of in-transit recurrence approximately 4 cm proximal to the original melanoma site in the right thigh, which was treated with surgical resection followed by adjuvant radiotherapy. Over the next 4 years, he underwent six additional surgeries for isolated in-transit recurrences affecting the same limb. He was referred for therapeutic options at the time of his latest in-transit recurrence. Examination revealed three palpable subcutaneous nodules in the right thigh in the setting of lymphedema. A core biopsy confirmed recurrent melanoma (Fig 1). Whole-body fluorodeoxyglucose positron emission tomography imaging revealed at least 17 hypermetabolic cutaneous and subcutaneous nodules in the right thigh, four fluorodeoxyglucose-avid nodules below the right knee, but no distant metastases (Fig 2A). Brain magnetic resonance imaging was normal. His serum chemistry profile, including lactate dehydrogenase, was normal. Molecular analysis demonstrated presence of BRAF V600E mutation in the tumor. After multidisciplinary evaluation, an isolated limb infusion procedure of the right lower extremity was not believed to be feasible, secondary to the proximal extent of the recurrence. Therapy was initiated with pembrolizumab at 2 mg/kg intravenously every 3 weeks.


Tumor suppressor genetics.
The observation that mutations in tumor suppressor genes can have haploinsufficient, as well as gain of function and dominant negative, phenotypes has caused a reevaluation of the 'two-hit' model of tumor suppressor inactivation. Here we examine the history of haploinsufficiency and tumor suppressors in order to understand the origin of the 'two-hit' dogma. The two-hit model of tumor suppressor gene inactivation was derived from mathematical modeling of cancer incidence. Subsequent interpretations implied that tumor suppressors were recessive, requiring mutations in both alleles. This model has provided a useful conceptual framework for three decades of research on the genetics and biology of tumor suppressor genes. Recently it has become clear that mutations in tumor suppressor genes are not always completely recessive. Haploinsufficiency occurs when one allele is insufficient to confer the full functionality produced from two wild-type alleles. Haploinsufficiency, however, is not an absolute property. It can be partial or complete and can vary depending on tissue type, other epistatic interactions, and environmental factors. In addition to simple quantitative differences (one allele versus two alleles), gene mutations can have qualitative differences, creating gain of function or dominant negative effects that can be difficult to distinguish from dosage-dependence. Like mutations in many other genes, tumor suppressor gene mutations can be haploinsufficient, dominant negative or gain of function in addition to recessive. Thus, under certain circumstances, one hit may be sufficient for inactivation. In addition, the phenotypic penetrance of these mutations can vary depending on the nature of the mutation itself, the genetic background, the tissue type, environmental factors and other variables. Incorporating these new findings into existing models of the clonal evolution will be a challenge for the future.


Use of differential levels of mean observed heterozygosity in microsatellite loci of commercial varieties of sugarcane (Saccharum spp).
In this study, we measured the genetic diversity within and among a set of 9 commercial sugarcane varieties used for alcohol and sugar production using 17 microsatellite DNA markers. The UGSM148 and UGSM59 primers were monomorphic for all 74 sugarcane samples. The estimated proportion of simple sequence repeated (SSR) polymorphic loci was 88.23%; 17 alleles were detected. The mean gene diversity of all SSR loci was 0.7279. The highest observed heterozygosity (HO) value was found in the RB72454 variety, whereas the lowest HO value was recorded in the SP813250 variety. The SP813250, RB845210, and RB835054 sugarcane varieties were the most genetically uniform varieties. An extremely high level of population differentiation was detected in the varieties exhibiting similar agronomic characteristics. Analysis of the genetic structure of the 9 sugarcane varieties using SSR markers was especially important to identify SSR loci with high levels of heterozygosity and to identify varieties showing the highest levels of heterozygosity. The monomorphic primers may be used to evaluate the genetic stability of sugarcane during cycles of vegetative multiplication, i.e., propagation via rhizomes.


Acute oesophageal necrosis in a patient with recent SARS-CoV-2.
A 57-year-old Hispanic man with diabetes presented with dyspnoea. He had a positive SARS-CoV-2 PCR. He was intubated for severe hypoxia and treated with intermittent pressors, methylprednisolone and supportive care. He was extubated on hospital day (HD) 9 and discharged to a skilled nursing facility (SNF) on HD 18. Approximately 1 month later, he presented with melena. Endoscopy revealed two large 1.5-2 cm wide-based distal oesophageal ulcers without active bleeding. Histology showed ulcerated squamous mucosa with extensive necrosis extending to the muscularis propria and coccoid bacterial colonies with rare fungal forms suggestive of Candida He was treated with fluconazole and pantoprazole and was discharged to a SNF. Approximately 3 weeks later, he was readmitted for complications. Repeat endoscopy demonstrated improvement and histology revealed chronic inflammation with reactive epithelial changes. Incidentally, SARS-CoV-2 PCR was positive during this visit without any respiratory symptoms.


Persistent fluorescence-assisted TiO₂-xNy-based photocatalyst for gaseous acetaldehyde degradation.
Photocatalytic technologies were utilized to develop an environment-friendly system that is capable of removing and oxidizing organic pollutants from an air stream. A series of long-afterglow phosphors emitting long lifetime fluorescence was adapted to prepared TiO(2)-based composite photocatalysts for the photodegradation of gas-phase acetaldehyde. Although the photocatalytic reaction by an undoped titania (Degussa P25) was stopped immediately after turning off the irradiation light, the long-afterglow phosphor/nitorogen-doped TiO(2) (TiO(2-x)N(y)) composites maintained the acetaldehyde photodegradation ability even after turning off the light for a long time. This novel photocatalytic property may be attributed to the presence of the long-afterglow phosphor, which can reserve the light energy and generate the persistent fluorescence afterward as the light source for the photocatalytic reaction with the visible-light responsive TiO(2-x)N(y). The substitution of the undoped TiO(2) with TiO(2-x)N(y) was essential to use the fluorescence as a light source for photocatalysis. Such a self-fluorescence-assisted system could enhance the performance of photocatalysts for environmental cleanup.


Leadless cardiac pacemaker implantations after infected pacemaker system removals in octogenarians.
Management of pacemaker (PM) infections among advanced aged patients possesses particular clinical challenges due to higher rates of concurrent cardiovascular disease and medical comorbidities. Novel leadless cardiac pacemakers (LCPs) may provide new opportunities for better management options in this population, however, there is limited data especially in Asian populations to guide the decision making. We reviewed 11 octogenarians (median age: 86 [minimum 82-maximum 90] years; male: 73%; median body mass index (BMI): 20.1 kg/m2) who received Micra Transcatheter Pacing System (Medtronic Inc, Minneapolis, MN) implantations following transvenous lead extractions (TLEs) for PM infections. All patients had more than two medical comorbidities (average 3.7 comorbidities). The indications for LCP implantations were atrioventricular block in four patients, atrial fibrillation bradycardia in five, and sinus node dysfunction in two. Eight patients (73%) were bridged with temporary pacing using active fixation leads (median interval of 14.0 days), while one with severe dementia underwent a concomitant LCP implantation and TLE during the same procedure. Successful TLEs and LCP implantations were successfully accomplished in all without any complications. The median time from the TLE procedure to discharge was 22 days (minimum 7-maximum 136). All patients remained free of infections during a mean follow-up period of 17.2 ± 6.5 months. LCP implantations were safe and effective after removing the entire infectious PM system in all octogenarians. The novel LCP technology may offer an alternative option for considering a re-implantation strategy after transvenous PM infections in elderly patients, particularly those with severe frailty and PM dependency.


Interrater reliability and intrarater reliability of lateral scapular slide tests of females in their 20s.
[Purpose] The purpose of the present study was to examine the intrarater reliability and intrarater reliability of lateral scapular slide tests among young females. [Subjects and Methods] A total of 60 female students in U University in Gyeongsangbuk-do, South Korea participated in this study. Lateral scapular slide tests (LSST) were conducted to identify interrater & intrarater reliability. In the LSSTs, the distance from the inferior angle of the scapula to thoracic vertebral spinous process T8 was measured in three positions (shoulder joint 0°, 45°, and 90° abduction) using tape measures. [Results] Intrarater reliability is shown to be moderate with scores not lower than 0.7 in left positions 1 and 3 and is shown to be excellent with scores not lower than 0.9 in the remaining positions. Interrater reliability is shown to be excellent with scores not lower than 0.9 in all three left and right positions. [Conclusion] LSST is sufficiently high to be accepted as an objective tool in the results of general previous studies. In addition, it can be considered useful at clinics because the measuring tool and method are simple.


GROMACS in the Cloud: A Global Supercomputer to Speed Up Alchemical Drug Design.
We assess costs and efficiency of state-of-the-art high-performance cloud computing and compare the results to traditional on-premises compute clusters. Our use case is atomistic simulations carried out with the GROMACS molecular dynamics (MD) toolkit with a particular focus on alchemical protein-ligand binding free energy calculations. We set up a compute cluster in the Amazon Web Services (AWS) cloud that incorporates various different instances with Intel, AMD, and ARM CPUs, some with GPU acceleration. Using representative biomolecular simulation systems, we benchmark how GROMACS performs on individual instances and across multiple instances. Thereby we assess which instances deliver the highest performance and which are the most cost-efficient ones for our use case. We find that, in terms of total costs, including hardware, personnel, room, energy, and cooling, producing MD trajectories in the cloud can be about as cost-efficient as an on-premises cluster given that optimal cloud instances are chosen. Further, we find that high-throughput ligand-screening can be accelerated dramatically by using global cloud resources. For a ligand screening study consisting of 19 872 independent simulations or ∼200 μs of combined simulation trajectory, we made use of diverse hardware available in the cloud at the time of the study. The computations scaled-up to reach peak performance using more than 4 000 instances, 140 000 cores, and 3 000 GPUs simultaneously. Our simulation ensemble finished in about 2 days in the cloud, while weeks would be required to complete the task on a typical on-premises cluster consisting of several hundred nodes.


Clinical utility of a new immobilization method in image-guided intensity-modulated radiotherapy for breast cancer patients after radical mastectomy.
To investigate clinical utility of a new immobilization method in image-guided intensity-modulated radiotherapy (IMRT) for breast cancer patients after radical mastectomy. Forty patients with breast cancer who underwent radical mastectomy and postoperative IMRT were prospectively enrolled. The patients were randomly and equally divided into two groups using both a carbon-fiber support board and a hollowed-out cervicothoracic thermoplastic mask (Group A) and using only the board (Group B). An iSCOUT image-guided system was used for acquiring and correcting pretreatment setup errors for each treatment fraction. Initial setup errors and residual errors were obtained by aligning iSCOUT images with digitally reconstructed radiograph (DRR) images generated from planning CT. Totally 600 initial and residual errors were compared and analyzed between two groups, and the planning target volume (PTV) margins before and after the image-guided correction were calculated. The initial setup errors of Group A and Group B were (3.14±3.07), (2.21±1.92), (2.45±1.92) mm and (3.14±2.97), (2.94±3.35), (2.80±2.47) mm in the left-right (LAT), superior-inferior (LONG), anterior-posterior (VERT) directions, respectively. The initial errors in Group A were smaller than those in Group B in the LONG direction (P < 0.05). No significant difference was found in the distribution of three initial error ranges (≤3 mm, 3-5 mm and > 5 mm) in each of the three translational directions for the two groups (P > 0.05). The residual errors of Group A and Group B were (1.74±1.03), (1.62±0.92), (1.66±0.91) mm and (1.70±0.97), (1.68±1.18), (1.58±0.98) mm in the three translational directions, respectively. No significant difference was found in the residual errors between two groups (P > 0.05). With the image-guided correction, PTV margins were reduced from 8.01, 5.44, 5.45 mm to 3.54, 2.99, 2.89 mm in three translational directions of Group A, respectively, and from 8.14, 10.89, 6.29 mm to 2.67, 3.64, 2.74 mm in those of Group B, respectively. The use of hollowed-out cervicothoracic thermoplastic masks combined with a carbon-fiber support board showed better inter-fraction immobilization than the single use of the board in reducing longitudinal setup errors for breast cancer patients after radical mastectomy during IMRT treatment course, which has potential to reduce setup errors and improve the pretreatment immobilization accuracy for breast cancer IMRT after radical mastectomy.


Impact Damage Localisation with Piezoelectric Sensors under Operational and Environmental Conditions.
Guided-wave structural health monitoring (SHM) systems with piezoelectric sensors are investigated for localisation of barely visible impact damage in CFRP plates under vibration and different thermal conditions. A single baseline set is used in a delay-and-sum algorithm with temperature correction for damage localisation in a large temperature range. Damage localisation is also demonstrated under transient thermal conditions, with signals recorded while the temperature is rapidly decreased. Damage severity due to successive impact events is studied under constant temperature. Damage is also localised when the plate is subjected to random vibration.


In vivo evaluation of Vivere bovine pericardium valvular bioprosthesis with a new anti-calcifying treatment.
The objective of this study was to evaluate the effect of chemical treatment with glutamic acid to avoid calcification of biological cardiac valves. The bovine pericardium (BP) tissues were fixed with 0.5% glutaraldehyde (BP/GA), followed by treatment with glutamic acid (BP/GA + Glu) for neutralization of the free aldehyde groups. Microscopic analysis showed that the wavy structure of collagen fibrils was preserved, but changes in elastin's integrity occurred. However, the treatment did not promote undesirable changes in the thermal and mechanical properties of the modified BPs. These samples were systematically studied in rat subcutaneous tissue: control (BP/GA) and anticalcificant (BP/GA + Glu). After 60 days, both groups induced similar inflammatory reactions. In terms of calcification, BP/GA + Glu remained more stable with a lower index (3.1 ± 0.2 μg Ca2+ /mg dry tissue), whereas for BP/GA it was 5.7 ± 1.3 μg Ca2+ /mg dry tissue. Bioprostheses made from BP/GA + Glu were implanted in the pulmonary position in sheep, and in vivo echocardiographic analyses revealed maintenance of valvar function after 180 days, with low gradients and minimal valve insufficiency. The explanted tissues of the BP/GA + Glu group had a lower average calcium content 3.8 ± 3.0 μg Ca2+ /mg dry tissue. The results indicated high anticalcification efficiency of BP/GA + Glu in both subcutaneous implant in rats and in the experimental sheep model, which is an advantage that should encourage the industrial application of these materials for the manufacture of bioprostheses.


Glomerular filtration rate estimation: performance of serum cystatin C-based prediction equations.
Serum creatinine measurement is a mainstay in the routine laboratory evaluation of renal function, despite of having several disadvantages. Cystatin C, on the other hand, suffers less influence of gender and muscle mass and has been proposed as a more sensitive marker for glomerular filtration rate. However, serum endogenous markers should not be used alone to assess glomerular filtration rate. Creatinine-based equations such as the modification of diet in renal disease (MDRD) and Cockcroft-Gault are widely used despite their limitations. A large number of cystatin C-based prediction equations were developed in recent years, in diverse populations, with different laboratory assays and methods. Several studies demonstrated that cystatin C-based equations are reliable markers of glomerular filtration rate and can be used for diagnosis, evaluation and follow-up of kidney disease. They are simpler than creatinine-based equations and have at least the same accuracy and precision for glomerular filtration rate estimation. In conclusion, diabetes mellitus, cystic fibrosis, kidney transplantation, HIV-infection, and cirrhosis are clinical situations where cystatin C-based equations can be useful. Extremes of age such as childhood and advanced age have also been evaluated with favorable results.


[An appropriate distal resection margin for lower rectal cancer after preoperative chemoradiotherapy].
In recent years, with the increase in the adoption of anus-preserving surgery, understanding of residual lower rectal cancer distribution to the anal side after chemoradiotherapy (CRT) has become an increasingly important issue. We aimed to clarify the pathological safe distal resection margin for lower rectal cancer after preoperative CRT. This study included 36 patients with lower third rectal cancer, who underwent preoperative CRT. We classified the gross tumor appearance as type 0-II like, Borrmann type 2, and Borrmann type 5. Whole-mount sections were used for pathological examination. We examined all slides and measured the extent of residual cancer spread. In many cases, residual cancer was observed in the deeper layers of the lesion, and in none of the cases was the cancer limited to the superficial layer. With regard to lateral distribution, tumors with a type 0-II like appearance showed a wider extent of lateral cancer spread from the optimal margin. In conclusion, although CRT contributes to tumor reduction, attention should be paid to both circumferential and lateral residual cancer spread. Our results suggest that the lateral distribution of residual cancer spread could be predicted by gross tumor appearance. This is an ongoing study.


An atomic beam source for fast loading of a magneto-optical trap under high vacuum.
We report on a directional atomic beam created using an alkali metal dispenser and a nozzle. By applying a high current (15 A) pulse to the dispenser at room temperature we can rapidly heat it to a temperature at which it starts dispensing, avoiding the need for preheating. The atomic beam produced is capable of loading 90% of a magneto-optical trap (MOT) in less than 7 s while maintaining a low vacuum pressure of <10(-11) Torr. The transverse velocity components of the atomic beam are measured to be within typical capture velocities of a rubidium MOT. Finally, we show that the atomic beam can be turned off within 1.8 s.


Strategies to improve dendritic cell-based immunotherapy against cancer.
Dendritic cells (DCs) play a pivotal role in T cell-mediated immunity and have been shown to induce strong antitumor immune responses in vitro and in vivo. Various approaches utilizing different vaccine cell formats, cell numbers, vaccination schedule, site of vaccination and maturation stages of DCs were investigated worldwide. While clinical trials have demonstrated the safety of such strategies, the clinical outcome was less than expected in most cases. This is due to in part host immunodeficiency imposed by tumors and immunoediting of tumor cells. To overcome these obstacles, new approaches to improve DC-mediated immunotherapeutic strategies are under investigation. First, functional enhancement of monocyte-derived DCs can be generated with using flt3-ligand (FL). Second, diverse antigenic determinants from heat shock-treated tumor cells may improve the immunogenicity of DC-based vaccines. Third, inclusion of ex vivo expanded NK/NKT cells in DC-based vaccines could be beneficial since the bidirectional interaction of these two cell types are known to enhance NK cell effector function and to induce DC maturation. Application of these approaches may induce a broadened antitumor immune response and thereby promote the elimination of tumor antigen-negative variant clones that had escaped immunosurveillance or undergone immunoediting. We are currently examining the feasibility of these immunotherapeutic approaches using a murine pancreatic cancer model system.


A hybrid electron cyclotron resonance metal ion source with integrated sputter magnetron for the production of an intense Al⁺ ion beam.
A metal ion source prototype has been developed: a combination of magnetron sputter technology with 2.45 GHz electron cyclotron resonance (ECR) ion source technology-a so called magnetron ECR ion source (MECRIS). An integrated ring-shaped sputter magnetron with an Al target is acting as a powerful metal atom supply in order to produce an intense current of singly charged metal ions. Preliminary experiments show that an Al(+) ion current with a density of 167 μA/cm(2) is extracted from the source at an acceleration voltage of 27 kV. Spatially resolved double Langmuir probe measurements and optical emission spectroscopy were used to study the plasma states of the ion source: sputter magnetron, ECR, and MECRIS plasma. Electron density and temperature as well as Al atom density were determined as a function of microwave and sputter magnetron power. The effect of ECR heating is strongly pronounced in the center of the source. There the electron density is increased by one order of magnitude from 6 × 10(9) cm(-3) to 6 × 10(10) cm(-3) and the electron temperature is enhanced from about 5 eV to 12 eV, when the ECR plasma is ignited to the magnetron plasma. Operating the magnetron at constant power, it was observed that its discharge current is raised from 1.8 A to 4.8 A, when the ECR discharge was superimposed with a microwave power of 2 kW. At the same time, the discharge voltage decreased from about 560 V to 210 V, clearly indicating a higher plasma density of the MECRIS mode. The optical emission spectrum of the MECRIS plasma is dominated by lines of excited Al atoms and shows a significant contribution of lines arising from singly ionized Al. Plasma emission photography with a CCD camera was used to prove probe measurements and to identify separated plasma emission zones originating from the ECR and magnetron discharge.


Neuropsychological outcome following near-drowning in ice water: two adult case studies.
Two men, 56 and 33 years old, (case 1 and case 2) were examined neuropsychologically after successful resuscitation from circulatory arrest following extreme accidental hypothermia and near drowning. After submersion in ice water for at least 20 minutes they received CPR for 45 to 60 minutes. Body-core temperature at start of CPB was 24 degrees C and 22 degrees C, respectively. A neuropsychological examination was performed within two months after the accident and 1 year later. An additional follow-up interview was made 3 years after the accidents. Both had severe problems with memory, visuospatial performance, executive function, and verbal fluency. The follow-up demonstrated improvement in the visuospatial test in both and in the verbal learning, recall, and logical reasoning tests in case 2. Both still had problems with executive function, and case 2 also in verbal fluency. Case 1 also had problems with flexibility, planning and abstract ability. Despite the protective effects of hypothermia and gradual improvement of symptoms over time, some of the deficits were permanent. A thorough neuropsychological examination of patients suffered from anoxia is advisable, because gross neurological examination and MRI scans may not always reveal underlying brain dysfunction.


[Development and evaluation of a novel placenta-specific gene manipulation method using lentiviral vectors].
The placenta plays numerous important roles to support fetal development such as gas exchange, nutrient supply, and hormone production. Placental defects underlie many aspects of pregnancy losses and complications; thus understanding and regulating gene function during placentation is of high clinical relevance. However, the lack of a facile and efficient method for placenta-specific gene manipulation has hampered study of the placenta. We have previously shown that transduction of fertilized mouse eggs with lentiviral (LV) vectors efficiently generates transgenic animals; however, transgene expression occurred in both the fetus and the placenta. In the present study, we transduced zona-free blastocysts with LV vectors expecting placenta-specific gene expression, since most placental cells differentiate from trophoblast cells that form the outermost layer of the blastocyst. Transgene expression was observed in trophoblast cells from preimplantation stages and in the placenta throughout gestation. All the analyzed placentas carried the transgene, while none of the fetuses became transgenic. By applying this method, embryonic lethality caused by placental defects in several knockout animal models was substantially rescued. This technology provides a powerful system for gene manipulation exclusively in placental organogenesis with implications for the treatment of placental dysfunction.


Impact of Early Decompressive Craniectomy Following Blunt Traumatic Brain Injury on Mortality: Propensity Matched Analysis.
Background The purpose of this study was to evaluate the impact of the early craniectomy on mortality. Hypothesis Early craniectomy within 4 hours of hospital arrival will reduce in-hospital mortality. Methods Data were retrieved from the National Trauma Data Bank data set (RDS_2007-RDS_2010). All craniectomies performed on patients with a blunt mechanism of head injury within 24 hours of admission were included in the study. In-hospital mortality was the main outcome of interest. Results A total of 942 patients qualified for the study. Overall, 669 patients (71%) underwent a craniectomy within 4 hours (early group), and 273 patients (29%) had a craniectomy performed between > 4 hours to 24 hours following hospital arrival (late group). Propensity matched analysis identified 268 pairs of patients in both groups. The mean standardized differences were < 10% after matching. There were no significant differences in mortality (odds ratio: 1.018; confidence interval [CI], 0.689-1.506; p = 1.00), absolute risk reduction (0.004; 95% CI, - 0.078 to 0.085; p = 1.00), and length of stay (LOS) between the groups (hazard ratio: 0.770; 95% CI, 0.56-1.059; p = 0.108). Conclusion No differences were seen on in-hospital mortality and hospital LOS between patients operated within 4 hours versus patients operated between 4 and 24 hours of admission.


Molecular junctions: from tunneling to function.
Thanks to the development of appropriate experimental techniques, molecular devices and their electrical transport properties have recently been the focus of a major research effort. This brief review describes how individual molecules can be contacted with metallic electrodes to form molecular junctions and addresses their basic formation mechanisms. An extension to molecular junctions networks is also discussed. Functionality could be demonstrated in such systems, and examples where conductance modulation using light or chemical stimuli was achieved will be presented.


Improved 225Ac daughter retention in InPO4 containing polymersomes.
Alpha-emitting radionuclides like actinium-225 (225Ac) are ideal candidates for the treatment of small metastasised tumours, where the long half-life of 225Ac enables it to also reach less accessible tumours. The main challenge lies in retaining the recoiled alpha-emitting daughter nuclides, which are decoupled from targeting agents upon emission of an alpha particle and can subsequently cause unwanted toxicity to healthy tissue. Polymersomes, vesicles composed of amphiphilic block copolymers, are capable of transporting (radio)pharmaceuticals to tumours, and are ideal candidates for the retention of these daughter nuclides. In this study, the Geant4 Monte Carlo simulation package was used to simulate ideal vesicle designs. Vesicles containing an InPO4 nanoparticle in the core were found to have the highest recoil retention, and were subsequently synthesized in the lab. The recoil retention of two of the daughter nuclides, namely francium-221 (221Fr) and bismuth-213 (213Bi) was determined at different vesicle sizes. Recoil retention was found to have improved significantly, from 37 ± 4% and 22 ± 1% to 57 ± 5% and 40 ± 2% for 221Fr and 213Bi respectively for 100nm polymersomes, as compared to earlier published results by Wang et al. where 225Ac was encapsulated using a hydrophilic chelate (Wang et al. 2014). To better understand the different parameters influencing daughter retention, simulation data was expanded to include vesicle polydispersity and nanoparticle position within the polymersome. The high retention of the recoiling daughters and the 225Ac itself makes this vesicle design very suitable for future in vivo verification.


Embedding and self-organization of nanoparticles in phospholipid multilayers.
Multilayers of various phospholipids on silicon substrates are used to induce spontaneous embedding of nanoparticles deposited from the gas phase. The resulting nanoparticle arrangement on the substrate surface is characterized using atomic force and scanning electron microscopy. In the intermediate phase and the liquid crystalline phase of the lipid, a monolayer is formed around individual nanoparticles which leads to an increase in interparticle distances. At the same time, the molecular mobility of the multilayers allows for self-assembly of the particles in regular two-dimensional arrangements.


Heterogeneous assembly of water from the vapor phase-Physical experiments and simulations with binding trifunctional organosilanes at the vapor/solid interface.
A trace amount of interfacial water is required to initiate hydrosilation reactions of trifunctional organosilanes to form surface assemblies. In recent studies, we have learned that water also has a critical role in directing molecular placement on surfaces because water can react with silicon to provide oxygenated sites for surface binding. Consequently, the wettability nature of substrates influences the placement and density of organosilane films formed by vapor-phase reactions. Nanopatterning protocols were designed using vapor-phase organosilanes and colloidal lithography to compare the wettability differences of hydrophilic mica(0001) compared to relatively hydrophobic Si(100) as a strategy for tracking the location of water on surfaces. The competition between hydrophobic and hydrophilic domains for the adsorption and coalescence of water condensed from vapor can be mapped indirectly by mapping the organosilanes, which bind to water at the solid interface, using atomic force microscopy. Trifunctional octadecyltrichlorosilane (OTS) was used as a marker molecule to map out the areas of the surface where water was deposited. The effect of systematic changes in film thickness and surface coverage of OTS was evaluated at the vapor/solid interface by adding an incremental amount of water to sealed reaction vessels to wet the surface and assessing the outcome after reaction with vapor-phase trichlorosilane. Reactive molecular dynamics simulations of the silicon-water vapor interface combined with electronic structure calculations of oxygenated silicon clusters with methyltrichlorosilane provided insight of the mechanism for surface binding, toward understanding the nature of the interface and wettability factors, which influence the association and placement of silane molecules on surfaces.


The in vitro and in vivo effects of a fast-dissolving mucoadhesive bi-layered strip as topical anesthetics.
To overcome pain on injection, the dentist can apply a topical anesthetic spray. Despite the convenience, it is not easy to apply it locally. So, we developed an oral mucoadhesive bi-layer film containing an anesthetic. We used polyvinylpyrrolidone (PVP)/hydroxypropyl methylcellulose (HPMC) and HPMC-only layer as the drug-containing layer and ethyl cellulose (EC) as the backing layer. The lidocaine released was tested in vitro together with the adhesion time and cytotoxicity of the film. Mucosa permeability was tested in vivo. Statistical analysis was performed, with p at 0.05 taken to be significant. The lidocaine was released significantly faster in the PVP/HPMC than HPMC-only group and 80% of the drug was released within 1 min (p<0.05) and they attached at least 3 h. The test groups showed no toxicity and the drug effectively permeated the mucosa (p<0.05). We suggest this new mucoadhesive anesthetic may reduce dental phobia.


Chronic subdural hematoma management: clarifying the definitions of outcome measures to better understand treatment efficacy - a systematic review and meta-analysis.
A long history of inconsistencies in the definitions of the outcome measures for chronic subdural hematomas (CSDHs) has contributed to the controversy over the optimal surgical strategy for CSDH treatment. Clarifying these definitions, reassess the available data, and systematically review the prior literature may provide better insight into the differences in treatment efficacy for CSDH. The clinical course of CSDH was described with a series of strictly defined outcome measures. PubMed, Cochrane Library, and ScienceDirect databases were searched for comparative studies of two main surgical techniques for CSDH, including burr hole craniotomy (BHC) and twist drill craniotomy (TDC). Data were collected with uniform criteria and analyzed using a random-effects model to estimate the mortality, recurrence, operative failure, and cure rates of each treatment. Twelve comparative studies that examined 2,027 CSDH patients were included. The analysis results indicated that TDC and BHC treatments were similar in the mortality rates (RR, 1.25; 95% CI, 0.83-1.87; I2 = 0%; p = 0.28) and the recurrence rates (RR, 1.29; 95% CI, 0.87-1.92; I2 = 13%; p = 0.21) for CSDH patients. However, TDC had a significantly higher operative failure rate compared with BHC (RR, 0.35; 95% CI, 0.15-0.83; I2 = 0%; p = 0.02), whereas patients treated by a TDC approach tended to achieve higher cure rates compared with BHC (RR, 0.92; 95% CI, 0.86-0.99; I2 = 55%; p = 0.02). The clarification of the definitions related to CSDH outcome facilitates the interpretation of differences in treatment efficacy. The TDC approach manifested a significantly higher operative failure rate compared with the BHC approach; however, TDC showed a tendency in achieving a long-term neurologic cure.


Saccharomyces cerevisiae mating pheromones specifically inhibit the synthesis of proteins destined to be N-glycosylated.
alpha Factor specifically inhibits the synthesis of N-glycosylated proteins in Saccharomyces cerevisiae mating type a cells but not in alpha cells or in a/alpha diploids. a Factor has the same effect of alpha cells. The synthesis of O-glycosylated proteins is not inhibited. Although the mating pheromones act like a 'physiological tunicamycin', the mechanism of inhibition is different: not the glycosylation of proteins as such but rather the synthesis of those proteins destined to be N-glycosylated is inhibited. Thus none of a number of glycosylating enzymes tested in vitro is reduced in activity in alpha-factor-treated cells. The synthesis of the glycoprotein carboxypeptidase Y, on the other hand, is strongly inhibited by tunicamycin as well as by alpha factor; but only in the former case did carbohydrate-free protein accumulate in the cells. alpha Factor causes maximal inhibition of glycoprotein formation after as little as 30 min, long before all cells in the population are arrested in G1; moreover, release from this inhibition precedes the increase in budding index (resumption of cell division). It is postulated, therefore, that N-glycosylated proteins are required for the G1/S-phase transition in the yeast cell cycle. This is supported by previous reports that first cycle arrest in G1 occurs when (a) tunicamycin is added to growing cultures, and (b) a temperature-sensitive N-glycosylation mutant is shifted to its restrictive temperature.


The atmospheric photolysis of E-2-hexenal, Z-3-hexenal and E,E-2,4-hexadienal.
The atmospheric photolysis of E-2-hexenal, Z-3-hexenal and E,E-2,4-hexadienal has been investigated at the large outdoor European Photoreactor (EUPHORE) in Valencia, Spain. E-2-Hexenal and E,E-2,4-hexadienal were found to undergo rapid isomerization to produce Z-2-hexenal and a ketene-type compound (probably E-hexa-1,3-dien-1-one), respectively. Both isomerization processes were reversible with formation of the reactant slightly favoured. Values of j(E-2-hexenal)/j(NO(2)) = (1.80 +/- 0.18) x 10(-2) and j(E,E-2,4-hexadienal)/j(NO(2)) = (2.60 +/- 0.26) x 10(-2) were determined. The gas phase UV absorption cross-sections of E-2-hexenal and E,E-2,4-hexadienal were measured and used to derive effective quantum yields for photoisomerization of 0.36 +/- 0.04 for E-2-hexenal and 0.23 +/- 0.03 for E,E-2,4-hexadienal. Although photolysis appears to be an important atmospheric degradation pathway for E-2-hexenal and E,E-2,4-hexadienal, the reversible nature of the photolytic process means that gas phase reactions with OH and NO(3) radicals are ultimately responsible for the atmospheric removal of these compounds. Atmospheric photolysis of Z-3-hexenal produced CO, with a molar yield of 0.34 +/- 0.03, and 2-pentenal via a Norrish type I process. A value of j(Z-3-hexenal)/j(NO(2)) = (0.4 +/- 0.04) x 10(-2) was determined. The results suggest that photolysis is likely to be a minor atmospheric removal process for Z-3-hexenal.


White Grape Juice Elicits a Lower Breath Hydrogen Response Compared with Apple Juice in Healthy Human Subjects: A Randomized Controlled Trial.
Diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPS) are used to manage symptoms in individuals with irritable bowel syndrome. Although effective at reducing symptoms, the diet can be complex and restrictive. In addition, there are still large gaps in the literature and many foods with unclear effects in the gastrointestinal (GI) tract, like fruit juice. Although many fruits are allowable on a low-FODMAP diet, consumption of all fruit juice is generally cautioned due to the large fructose load contained in juice, regardless of the glucose concentration. Very little research exists regarding the importance of limiting fructose load during a low-FODMAP diet; therefore, individuals following a low-FODMAP diet may be unnecessarily restricting their diets. To determine whether there is a difference in GI tolerance between juice from a high-FODMAP fruit (apple juice) and juice from a low-FODMAP fruit (white grape juice) in healthy human subjects. The goal is to provide insight into the role of juice in a low-FODMAP diet. A double-blind, randomized, controlled crossover study was conducted with 40 healthy adults. Fasted subjects consumed 12 oz of either apple juice or white grape juice. Breath hydrogen measures were taken at baseline, 1, 2, and 3 hours. Subjective GI tolerance surveys were completed at the same time intervals and at 12 and 24 hours. Breath hydrogen and GI symptoms were assessed with area under the curve analysis. Significance was determined with a two-sided t test with a P value <0.05. Consumption of apple juice resulted in a greater mean breath hydrogen area under the curve at 23.3 ppm/hour (95% CI 13.0 to 33.6) compared with white grape juice at 5.8 ppm/hour (95% CI -4.6 to 16.1) (P<0.001). No differences in reported GI symptoms were seen between treatments. Both juices were well tolerated and neither produced any severe symptoms in healthy adults. White grape juice consumption resulted in only a small rise in breath hydrogen, which may suggest excluding foods only because of the high fructose load could be unnecessarily restrictive. The results of this study suggest that the fructose-to-glucose ratio is likely more important than the total fructose load of the food when considering the acceptability of a food on a low-FODMAP diet. More research is needed in individuals with irritable bowel syndrome to determine whether white grape juice and other juices from low-FODMAP fruits could be additional beverage options for individuals following a low-FODMAP diet.


Interaction of astrocytes and newly formed oligodendrocytes in resolving multiple sclerosis lesions.
Cells resembling oligodendrocytes are sometimes seen within reactive astrocytes in fresh lesions in multiple sclerosis. Using immunostained paraffin and epoxy sections of fresh plaques obtained at autopsy from a series of cases of short clinical duration, it was found that small cells with round nuclei are commonly observed within reactive astrocytes in some hypercellular plaques and that these cells are phenotypically undifferentiated oligodendrocytes, i.e., nonmyelinating cells expressing intensely the oligodendrocyte determinants 2',3'-cyclic nucleotide 3'-phosphohydrolase and the carbohydrate epitope present on the family of cell adhesion molecules recognized by monoclonal antibody HNK-1. They also stain positively for IgG. This unusual astrocyte-oligodendrocyte interaction, which appears to be restricted to nonmyelinating oligodendrocytes in lesions of several weeks' to several months' duration, has not been described during normal oligodendrocyte differentiation or in experimental central remyelinating lesions. It bears some resemblance, however, to a pattern of slow oligodendrocyte destruction seen previously in organotypic perinatal central nervous tissue cultures exposed to multiple sclerosis serum. It is concluded that the evolution of some multiple sclerosis lesions early in the course of the disease is associated with abnormal binding and/or destruction of newly generated oligodendrocytes by reactive astrocytes. These observations raise new questions concerning mechanisms underlying failed remyelination in multiple sclerosis, including the novel possibility of an immune response directed against a developmentally restricted oligodendrocyte antigen.


Physical activity in patients with metabolic syndrome: at screening and three years thereafter.
Metabolic syndrome is a cluster of risk factors for cardiovascular disease and type 2 diabetes. Physical activity can decrease these risks. Many randomized clinical trials to increase physical activity have demonstrated disappointing results, and implementation in daily practice appeared to be difficult. The aim of this study was to investigate whether 3 years of usual care with available guidelines in a primary care setting result in change in physical activity in patients with screen-detected metabolic syndrome. After a population-based screening, 473 patients were diagnosed with metabolic syndrome and received advice to increase physical activity. Three years later, they were invited for follow-up. Physical activity was measured by means of the validated SQUASH questionnaire. The primary outcome measure was: % of metabolic syndrome patients that fulfill the Dutch Physical Activity Guideline (DPAG) criterion (30 min of moderately intensive physical activity at least 5 days per week) at screening and follow-up. In the final study population (n=168), the proportion of patients fulfilling the DPAG criterion did not significantly increase between screening (56.0%) and follow-up (60.7%) (P=0.29). Female gender [odds ratio (OR)=3.59; 95% confidence interval (CI) 1.24-10.39] and body mass index (BMI) at baseline (OR=0.82; 95% CI 0.69-0.97) appeared to be independent predictors of increase in physical activity. In this real-world setting, despite the advice to increase physical activity, the number of metabolic syndrome patients with sufficient physical activity did not significantly increase after 3 years. This finding confirms the need for an intensified approach to achieve an increase in physical activity in this group, with special attention to men and patients with higher BMI values.


Cognitive impairment in type 2 diabetes patients with and without diabetic peripheral neuropathy: a mismatch negativity study.
To assess the cognitive impairment in patients with type 2 diabetes mellitus (T2DM) using mismatch negativity (MMN) and to explore the relationship between cognitive impairment and diabetic peripheral neuropathy (DPN). Sixty-six T2DM patients and 40 healthy controls were included. For each participant, mini-mental state examination (MMSE) was applied to assess the general cognitive function and MMN was elicited. T2DM patients were divided into two subgroups: subgroup DPN-, patients without DPN; subgroup DPN+, patients with DPN. The MMSE scores, MMN amplitudes and latencies were compared between the T2DM group and the control group using univariate analysis of variance procedures, and also among the controls, subgroup DPN- and subgroup DPN+. Pearson's correlation coefficients (r) were used to analyze potential confounding clinical factors associated with MMN. T2DM patients had significantly lower MMSE scores compared with controls (23.25 ± 2.86 vs. 27.15 ± 1.83; P < 0.01), whereas those of the two subgroups were not significantly different. Both subgroup DPN+ and DPN- had longer latencies and lower amplitudes of MMN than the controls. The latencies of MMN were significantly longer in subgroup DPN+ compared with subgroup DPN-. The latency of MMN was positively correlated with the duration of the disease. Cognitive decline exists in patients with T2DM irrespective of the presence of DPN. Patients with DPN may have more severe cognitive dysfunction than those without DPN. MMN may be a promising tool for evaluating cognitive function.


Common causes of knee effusions in spinal cord injury: a random study.
Patients with spinal cord injury are predisposed to knee effusions owing to osteoporosis, heterotopic ossification, trauma, and benign hydrarthrosis. This retrospective review discusses 11 patients with spinal cord injury and knee effusions seen during two years. One objective is to correlate the initial diagnosis based on clinical findings with the final diagnosis based on synovial fluid analysis and radiographic studies. Another is to describe the variety and complexity of clinical situations that involve knee effusions in spinal cord injury. The initial diagnosis was different from the final diagnosis in all of our cases. The final diagnoses were trauma (6 cases), pseudogout (2 cases), spasticity, fracture of the tibial plateau, septic joint, and tears of the anterior cruciate and lateral collateral ligaments. Knee effusions in this unique population must be carefully investigated to avoid erroneous diagnoses based on the initial clinical presentation, which can be complicated by multiple medical problems.


Tagged fragment method for evolutionary structure-based de novo lead generation and optimization.
Here we describe a computer-assisted de novo drug design method, EAISFD, which combines the de novo design engine EA-Inventor with a scoring function featuring the molecular docking program Surflex-Dock. This method employs tagged fragments, which are preserved substructures in EA-Inventor used for base fragment matching in Surflex-Dock, for constructing ligand structures under specific binding motifs. In addition, a target score mechanism is adopted that allows EAISFD to deliver a diverse set of desired structures. This method can be used to design novel ligand scaffolds (lead generation) or to optimize attachments on a fixed scaffold (lead optimization). EAISFD has successfully suggested many known inhibitor scaffolds as well as a number of new scaffold types when applied to p38 MAP kinase.


Varied-mapping conjunction search: evidence for rule-based learning.
Five experiments were carried out to examine whether top-down processes can aid search, even when targets and distractors are variably mapped. Experiments 1a and 1b determined that effortless VM search can be obtained in Contrast Polarity X Orientation and Color X Orientation conjunction search when one feature dimension remains consistently mapped across blocks. Experiment 2 showed that efficient VM search is possible when both dimensions are variably mapped. In Experiment 3, efficient VM search was found when target-distractor reversals occurred on a trial-wise basis. Experiments 4 and 5 found that VM search deteriorates when target identity is not known prior to display onset. These studies demonstrate the role of top-down mechanisms in the development of efficient VM search and present several challenges to strength-theoretic views on the mechanisms underlying automaticity.


Microglia activation triggers oligodendrocyte precursor cells apoptosis via HSP60.
Reactive microglia are present in lesions of myelin‑associated white matter disorders resulting in injuries to oligodendrocyte precursor cells (OPCs). Therefore, protection of OPCs from injury due to excessive activation of microglia is important in treating these diseases. Heat shock protein 60 (HSP60) has been demonstrated to be released extracellularly in the failing heart upon stress or injury. However, the role of HSP60 in the central nervous system and whether it participates in the toxic effects of microglia on OPCs remains unclear. The present study used the co‑culture, cell death assays, binding assays, immunochemistry, western blot and ELISA. HSP60 was demonstrated to be released extracellularly by LPS‑activated microglia and to bind to OPCs, triggering OPC apoptosis. When pretreated with toll‑like receptor (TLR) 4 blocking antibody, the viability of OPCs increased, while the expression of nuclear factor κB (NFκB), caspase 3 and the release of proinflammatory cytokines triggered by HSP60 decreased. These results suggest that HSP60 released by microglia may mediate OPC apoptosis through binding to TLR4 on the surface of OPCs and subsequently activating the TLR4‑NFκB signaling pathway. HSP60 may, therefore, serve as a potential target for treatment of myelin‑associated neurodegenerative diseases that are accompanied by microglia activation.


Understanding determinants of patients' decisions to attend their family physician and to take antibiotics for upper respiratory tract infections: a qualitative descriptive study.
Although antibiotics have little or no benefit for most upper respiratory tract infections (URTIs), they continue to be prescribed frequently in primary care. Physicians perceive that patients' expectations influence their antibiotic prescribing practice; however, not all patients seek antibiotic treatment despite having similar symptoms. In this study, we explored patients' views about URTIs, and the ways patients manage them (including attendance in primary care and taking antibiotics). Using a qualitative descriptive design, adult English-speaking individuals at a Canadian health center were recruited through convenient sampling. The participants were interviewed using semi-structured interview guide based on the Common Sense-Self-Regulation Model (CS-SRM). The interviews were transcribed verbatim and coded according to CS-SRM dimensions (illness representations, coping strategies). Sampling continued until thematic saturation was achieved. Thematic analysis related to the dimensions of CS-SRM was applied. Generally, participants had accurate perception about the symptoms of URTIs, as well as how to prevent and manage them. However, some participants revealed misconceptions about the causes of URTIs. Almost all participants mentioned that they only visited their doctor if their symptoms got progressively worse and they could no longer self-manage the symptoms. When visiting a doctor, most participants reported that they did not seek antibiotics. They expected to receive an examination and an explanation for their symptoms. Our participants reported good understanding regarding the likely lack of benefit from antibiotics for URTIs. Developing interventions that specifically help patients discuss their concerns with their physicians, instead of providing more education to public may help in reducing the use of unnecessary antibiotics.


Core-shell PbI2@WS2 inorganic nanotubes from capillary wetting.
Multiwall WS(2) nanotube templates were used as hosts to prepare core-shell PbI(2)@WS(2) nanotubes by a capillary-wetting method. Conformal growth of PbI(2) layers on the inner wall of the relatively wide WS(2) nanotubes (i.d. ca. 10 nm) leads to nanotubular structures which were not previously observed in narrow carbon nanotube templates. Image simulation after structural modeling (see picture) showed good agreement with the experimental HRTEM image.


One-Dimensional Anhydrous Proton Conducting Channel Formation at High Temperature in a Pt(II)-Based Metallo-Supramolecular Polymer and Imidazole System.
One dimensional (1D) Pt(II)-based metallo-supramolecular polymer with carboxylic acids (polyPtC) was synthesized using a new asymmetrical ditopic ligand with a pyridine moiety bearing two carboxylic acids. The carboxylic acids in the polymer successfully served as apohosts for imidazole loaded in the polymer interlayer scaffold to generate highly ordered 1D imidazole channels through the metallo-supramolecular polymer chains. The 1D structure of imidazole loaded polymer (polyPtC-Im) was analyzed in detail by thermogravimetric analysis, powder X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and ultraviolet-visible and photoluminescence spectroscopic measurements. PolyPtC-Im exhibited proton conductivity of 1.5 × 10-5 S cm-1 at 120 °C under completely anhydrous conditions, which is 6 orders of magnitude higher than that of the pristine metallo-supramolecular polymer.


Acute effect of zoledronic acid infusion on atrial fibrillation development in patients with osteoporosis.
There is ongoing controversy related to the relationship between bisphosphonates and atrial fibrillation (AF). Our aim in this study was to evaluate the potential acute effect of zoledronic acid (ZA) infusion on AF development by using 24-hour Holter recordings. The study was designed to be a self-controlled case series study, and 33 consecutive patients with osteoporosis (29 females, age: 62.3±9.0 years) who were scheduled to receive ZA infusion constituted the study population. Patients underwent 24-hour Holter rhythm recordings at two different times; the first one was 48 hours before the planned ZA infusion, and the second one was on the morning of the infusion day. Heart rate, frequency and type of arrhythmias, as well as heart rate variability (HRV) from the two recordings were compared. There were no episodes of AF greater than 30 sec in any of the 24-hour Holter recordings obtained before and on the day of drug infusion. Holter recordings before drug infusion showed that only 1 patient had an atrial run of 3 beats long. Holter recordings obtained on the day of drug infusion revealed that 5 patients (15.2%) had atrial runs with lengths ranging between 3 and 12 beats (p=0.046). Regarding HRV variables, SDANN values were found to be significantly depressed on the day of ZA infusion (113.6±26.9 vs. 98.2±29.9, p=0.007). None of the patients developed AF during or early after ZA infusion. However, there was an increase in atrial ectopy in some patients, which might be due to alterations in cardiac autonomic activity.


Oral Health Status and Dental Treatment Needs of 5-12-year-old Children with Disabilities Attending Special Schools in Western Maharashtra, India.
The individuals suffering from various disabilities form a considerable proportion of the community. The psychological reactions associated with a deformity can be devastating to the disabled, parents, caregivers, and family which often lead to attitudes of hopelessness in the lives of these disabled individuals. To assess the oral health status and treatment needs among 5-12-year-old children attending special school in Western Maharashtra, India. A descriptive cross-sectional study was conducted among 5-12-year-old children attending specials school in Western Maharashtra, India. The study group consisted of 100 children (62 males and 38 females). The oral health status was assessed by using decayed, missing, and filled teeth (DMFT) index, Community Periodontal Index, Dentition status and treatment needs. Information on disability status, intelligent quotient, and systemic diseases were recorded. The mean age of the study population was 9.35 ± 2.92 years. There were 62 (62%) males and 38 (38%) females in the study population. Among the total children examined, 50% of the children were suffering from mental retardation (MR), followed by MR with cerebral palsy (20%). The overall mean decayed and filled teeth and DMFT scores were 3.53 ± 1.02 and 3.89 ± 1.30, respectively, and decayed component had the highest score in both the groups. A statistically significant difference has been observed among the gender (P < 0.001). There is a high proportion of dental treatment needs required for these children which reflect the barriers to access and utilize oral health care among these children. As dentist, we should emphasize on health education, periodic recall, and monitoring among these individuals.


Chidamide and Oxaliplatin Synergistically Inhibit Colorectal Cancer Growth by Regulating the RPS27A-MDM2-P53 Axis.
The present study explored the anti-tumor effects of chidamide plus oxaliplatin on colorectal cancer (CRC) and examined its underlying mechanism. First, the Combination Index (CI) of chidamide and oxaliplatin was evaluated via CCK-8 assay. Second, the effects of chidamide and oxaliplatin monotherapy and the combined treatment on cell proliferation, invasion, migration, and apoptosis were detected. Third, whole-transcriptome RNA sequencing (RNA-seq) was performed to seek the potential targeted gene by which chidamide plus oxaliplatin exerted anti-tumor effects. Fourth, the validation of the targeted gene and the signal pathway it regulated were performed. Finally, the anti-tumor effect of chidamide plus oxaliplatin on mice xenograft was examined. Chidamide and oxaliplatin acted synergistically to inhibit CRC growth in vitro and in vivo (CI<1). Besides, compared with oxaliplatin monotherapy, chidamide could significantly enhance oxaliplatin-induced inhibition in cell proliferation, invasion, and migration, and promotion in HCT-116 and RKO cell apoptosis (P<0.05). The RNA-seq displayed that, compared to oxaliplatin monotherapy, RPS27A mRNA was evidently decreased in HCT-116 cells treated with chidamide plus oxaliplatin (P<0.001). Then, we found RPS27A was highly expressed in CRC tissues and CRC cell lines (P<0.001). Silence of RPS27A attenuated proliferation and induced apoptosis in HCT-116 and RKO cells via downregulation of MDM2 expression and upregulation of P53. Next, RPS27A overexpression could partially reverse chidamide plus oxaliplatin induced growth inhibition and apoptosis in HCT-116 and RKO cells (P<0.01). RPS27A overexpression could promote the upregulation of MDM2 and downregulation of P53 after the combined treatment of chidamide with oxaliplatin. Chidamide and oxaliplatin acted synergistically to suppress CRC growth by the inhibition of the RPS27A-MDM2-p53 axis.


Cerebral metabolism assessed with microdialysis in uncontrolled hemorrhagic shock after penetrating liver trauma.
In a porcine model of uncontrolled hemorrhagic shock, we evaluated the effects of fluid resuscitation versus arginine vasopressin (AVP) combined with hypertonic-hyperoncotic hydroxyethyl starch solution (HHS) on cerebral perfusion pressure (CPP) and on cerebral metabolism using intracerebral microdialysis. Sixteen anesthetized pigs were subjected to uncontrolled liver bleeding until hemodynamic decompensation, followed by resuscitation using either fluid (n = 8) or AVP/HHS (n = 8). Thirty minutes after drug administration, bleeding was controlled by manual compression, and colloid and crystalloid solutions were administered in both groups. All surviving animals were observed for one hour. After hemodynamic decompensation, fluid resuscitation resulted in a smaller increase of CPP than did AVP/HHS (mean +/- sem; 24 +/- 5 vs 45 +/- 7 mm Hg; P < 0.01). Mean (+/- sem) cerebral venous partial pressure of oxygen was significantly decreased (P < 0.01) 5 min after fluid compared with 5 min after AVP/HHS administration (36 +/- 3 vs 64 +/- 4 torr). Cerebral metabolism was comparable in both groups. In conclusion, AVP/HHS proved to be superior to fluid in the initial phase of therapy with respect to CPP and cerebral oxygenation, but was comparable to fluid regarding cerebral metabolism and secondary cell damage in surviving animals.


Interventional effect of dietary fiber on blood glucose and pregnancy outcomes in patients with gestational diabetes mellitus.
To investigate the effect of dietary fiber on blood glucose and pregnancy outcomes in patients with gestational diabetes mellitus (GDM). One hundred and twelve patients with GDM in the second trimester of pregnancy were recruited from Women's Hospital, Zhejiang University School of Medicine. Patients were randomized into two groups with 56 in each group: the control group received basic nutrition support; while the dietary fiber group were given additional dietary fiber ( total dietary fiber per day) before meals in addition to basic nutrition support. Intervention for all cases lasted for 8 weeks. Fasting blood glucose and postprandial blood glucose (2 h BG) were measured every week, and oral glucose tolerance test (OGTT) was performed at 42 d postpartum to evaluate the glycemic outcomes. Perinatal outcomes were recorded. The dietary fiber intervention markedly improved 2 h BG in patients with GDM and significantly elevated the glucose compliance rate from the 3rd to 8th week compared to the control group ( <0.05 or <0.01). OGTT 2 h glucose and the incidence of impaired glucose tolerance in the dietary fiber group were significantly lower than those in the control group, while the glucose compliance rate was significantly higher than that in the control group (all <0.01). Moreover, the rates of adverse perinatal outcomes, such as premature rupture of membranes and neonatal hyperbilirubinemia were declined in the dietary fiber group (<0.05 or <0.01). Dietary fiber intervention can ameliorate hyperglycemia in GDM patients, improve perinatal outcomes and reduce the incidence of postpartum impaired glucose tolerance.


Growth hormone: its physiology and control.
Growth hormone (GH) is a protein hormone produced by the somatotrophs of the anterior pituitary gland of birds and other vertebrates. The secretion of GH in birds is under hypothalamic control; it involves three peptidergic releasing factors: growth hormone-releasing factor (GRF) (stimulatory); thyrotropin-releasing hormone (TRH) (stimulatory); and somatostatin (SRIF) (inhibitory). In addition, there is evidence for effects of biogenic amines (including serotonin and norepinephrine) and prostaglandins at the level of the hypothalamus and possibly also the pituitary gland. In all avian species examined, plasma concentrations of GH are high in young posthatching chicks but low in the adult and embryo. The difference in plasma concentrations of GH between young and adult birds is due to both greater GH secretion and reduced clearance. The lower secretion of GH in adult birds reflects fewer somatotrophs in the pituitary, changes in somatotroph structure, and reduced GH responses to TRH or GRF administration. There is only limited data on the role of GH in birds. GH appears to be required for normal growth; acting at least in part by increasing somatomedin production. However, plasma concentrations of GH do not necessarily correlate with growth rate. For instance, in chicks with reduced growth rate owing to either goitrogen or protein deficiency in the diet, plasma concentrations of GH are elevated. GH also can influence lipid metabolism by increasing lipolysis, decreasing lipogenesis, and stimulating the uptake of glucose by adipose tissue. The physiological significance of these actions is, however, not established. In addition, GH affects the secretion of other hormones, the immune system, and perhaps also the reproductive system.


Community structure and fibrolytic activities of anaerobic rumen fungi in dromedary camels.
Anaerobic fungi colonize the rumen and degrade cellulose and hemicellulose, which enable them to be key players in the lignocellulose fermentation. Consequently, an expansion of knowledge about rumen fungi could increase animal productivity, utilization of lignified forages like alfalfa hay, and enhance fibrolytic enzymes production. Here, we used an Internal Transcribed Spacer 1 (ITS1) clone library to investigate the anaerobic rumen fungi in camel and to investigate their ability to produce cellulase and xylanase in vitro. Rumen fluid was collected from camels fed Egyptian clover (n = 14), and wheat straw (n = 7) and fecal samples were collected from camels fed wheat straw and concentrates (n = 5), or natural grazing plants (n = 10). Neocallimastix and Cyllamyces were the most abundant anaerobic fungi in all camel groups. An anaerobic rumen fungi media containing alfalfa hay as a carbon source was inoculated by rumen and fecal samples to assess the ability of anaerobic rumen fungi in camel gut to produce cellulase and xylanase. The anaerobic gut fungi in the camel is diverse and has cellulolytic and xylanolytic activities, fungal culture from rumen samples of camel fed wheat straw (R2) exhibited highest cellulase production. In addition, many of the sequences in the current study have no equivalent cultured representative, indicating a novel diversity within the camel gut.


Targeted therapy with trastuzumab in dysplasia and adenocarcinoma arising in Barrett's esophagus: a translational approach.
Human epidermal growth factor receptor (HER2) protooncogene, overexpressed/ amplified in preneoplastic lesions and in adenocarcinoma (ADC) of the esophagus, can be considered a target for treatment of esophageal dysplasia/ADC. The aim of this study was to evaluate the therapeutic role of the anti-HER2 monoclonal antibody, trastuzumab, in the management of ADC originating from HER2-positive Barrett's esophagus (BE). Two patients with high-grade dysplasia and ADC of the esophagus after esophageal mucosectomy and no metastatic disease were studied. Patients were not eligible for radical surgery or chemo-radiotherapy because of age and comorbidities. HER2 status was assessed by immunohistochemistry and fluorescence in situ hybridization. Additional immunohistochemical analyses were performed. The whole panel was analysed at baseline, after treatment and at follow-up. At baseline, the two patients showed HER-2 overexpression/amplification in all areas of dysplasia and ADC but not in BE. Six months after treatment no significant differences in terms of endoscopical and histological patterns of the disease were found. HER-2, EGFR, TOPOII-alpha and anti-ssDNA analysis demonstrated a down-regulation of these markers and increased apoptosis. This study demonstrates that this treatment is feasible. No clear evidence of dysplasia regression was observed. However, HER2 and TopoII-alpha downregulation and induction of apoptosis occurring 6 months after treatment encourages further investigation.


The role of OSHA violations in serious workplace accidents.
California accident investigations for 1976 show that violations of the Occupational Safety and Health Administration's safety standards were a contributing factor in 13% to 19% of the 645 deaths reported to the workers' compensation program during that year. However, a panel of safety engineers judged that only about 50% of these violations could have been detected if an inspector had visited the day before the accident. These findings indicate that the potential gains from stronger enforcement of current standards are limited but not insignificant. The likelihood that a violation contributed to a serious accident varied considerably among accident types, industries, and size classes of plants. These findings can be used to increase the efficiency and effectiveness of the OSHA program by means of better targeting of inspections and accident investigations, more intelligent assessment of which violations should be penalized most heavily, and the provision of information to employers and workers about which violations are most consequential.


Differential benefits of amoxicillin-metronidazole in different phases of periodontal therapy in a randomized controlled crossover clinical trial.
The specific advantage of administering systemic antibiotics during initial, non-surgical therapy or in the context of periodontal surgery is unclear. This study assesses the differential outcomes of periodontal therapy supplemented with amoxicillin-metronidazole during either the non-surgical or the surgical treatment phase. This is a single-center, randomized placebo-controlled crossover clinical trial with a 1-year follow-up. Eighty participants with Aggregatibacter actinomycetemcomitans-associated moderate to advanced periodontitis were randomized into two treatment groups: group A, antibiotics (500 mg metronidazole plus 375 mg amoxicillin three times per day for 7 days) during the first, non-surgical phase of periodontal therapy (T1) and placebo during the second, surgical phase (T2); and group B, placebo during T1 and antibiotics during T2. The number of sites with probing depth (PD) >4 mm and bleeding on probing (BOP) per patient was the primary outcome. A total of 11,212 sites were clinically monitored on 1,870 teeth. T1 with antibiotics decreased the number of sites with PD >4 mm and BOP per patient significantly more than without (group A: from 34.5 to 5.7, 84%; group B: from 28.7 to 8.7, 70%; P <0.01). Twenty patients treated with antibiotics, but only eight treated with placebo, achieved a 10-fold reduction of diseased sites (P = 0.007). Consequently, fewer patients of group A needed additional therapy, the mean number of surgical interventions was lower, and treatment time in T2 was shorter. Six months after T2, the mean number of residual pockets (group A: 2.8 ± 5.2; group B: 2.2 ± 5.0) was not significantly different and was sustained over 12 months in both groups. Giving the antibiotics during T1 or T2 yielded similar long-term outcomes, but antibiotics in T1 resolved the disease quicker and thus reduced the need for additional surgical intervention.


Expression of hepatocyte growth factor in normal and carbon tetrachloride-treated monkeys.
We examined hepatocyte growth factor-producing organs in normal and carbon tetrachloride-treated Japanese monkeys, a species more related to human beings than rats, by measuring hepatocyte growth factor protein and hepatocyte growth factor mRNA in various tissues. Hepatocyte growth factor protein and hepatocyte growth factor mRNA levels were determined by use of an enzyme-linked immunosorbent assay for human hepatocyte growth factor and Northern-blot analysis using human hepatocyte growth factor cDNA as a probe, respectively. Although very slight amounts of hepatocyte growth factor protein were found in various organs of normal monkeys, the hepatocyte growth factor protein levels were remarkably increased only in the livers and spleens of carbon tetrachloride-treated monkeys. Hepatocyte growth factor mRNA was distinctly detected in the livers, spleens, lungs, intestinal tracts, adrenal glands and aortas of normal monkeys. After the administration of carbon tetrachloride, the hepatocyte growth factor mRNA levels in the liver, spleen and gastrointestinal tract were markedly increased; the level in the lung was unchanged, differing from the findings in rats; and the levels in adrenal gland and aorta were unaltered. These results indicate that the liver is an important hepatocyte growth factor-producing organ in monkeys during liver regeneration and that hepatocyte growth factor induced in the liver may stimulate hepatocyte proliferation by way of a paracrine mode.


Gas concentration profiles along airways of dog lungs during high-frequency ventilation.
Following equilibration with inert gases (He and SF6), dog lungs were partially washed out, either by high-frequency ventilation (HFV) or by conventional mechanical ventilation (CMV), to varied inert gas clearance levels, at which expirograms were recorded by mass spectrometry. Relative alveolar slopes were distinctly positive for HFV and tended to increase with lung clearance; they were, however, smaller than those of CMV and were smaller for He than for SF6 during both ventilatory modes. Fowler dead space was smaller for HFV than for CMV, with significant differences between test gases only during CMV. Plots of concentration against linear distance between measuring site and alveolar region showed that most of the total concentration drop during HFV occurred, with nearly linear slope, along the endotracheal tube and the upper airways, with no difference between He and SF6. In the alveolar region, on the other hand, relative concentration gradients were similar for HFV and CMV, both showing separation of He and SF6. The data suggest that gas transport in the upper airways during HFV is not diffusion limited. Gas mixing in alveolar regions, although more complete for HFV than for CMV, is limited by diffusion; however, this incomplete gas mixing does not appreciably limit overall gas transport during HFV.


Forming new sex partnerships while overseas: findings from the third British National Survey of Sexual Attitudes & Lifestyles (Natsal-3).
Travelling away from home presents opportunities for new sexual partnerships, which may be associated with sexually transmitted infection (STI) risk. We examined the prevalence of, and factors associated with, reporting new sexual partner(s) while overseas, and whether this differed by partners' region of residence. We analysed data from 12 530 men and women aged 16-74 years reporting ≥1 sexual partner(s) in the past 5 years in Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability survey undertaken 2010-2012. 9.2% (95% CI 8.3% to 10.1%) of men and 5.3% (4.8% to 5.8%) of women reported new sexual partner(s) while overseas in the past 5 years. This was strongly associated with higher partner numbers and other sexual and health risk behaviours. Among those with new partners while overseas, 72% of men and 58% of women reported partner(s) who were not UK residents. Compared with those having only UK partners while abroad, these people were more likely to identify as 'White Other' or 'Non-White' (vs White British ethnicity), report higher partner numbers, new partners from outside the UK while in the UK and paying for sex (men only) all in the past 5 years. There was no difference in reporting STI diagnosis/es during this time period. Reporting new partners while overseas was associated with a range of sexual risk behaviours. Advice on sexual health should be included as part of holistic health advice for all travellers, regardless of age, destination or reason for travel.