A cluster randomized controlled trial to assess the efficacy of a telehealth-based train-the-trainer mealtime intervention delivered by respite care center volunteers to caregivers of persons with dementia to improve nutritional outcomes and quality of life.
Persons with dementia with mild to moderate cognitive impairment are at risk for developing impairments with activities of daily living such as the ability to feed oneself, that negatively influence health. Lack of caregiver skills related to mealtime planning for persons with dementia and the ability to cope with dysfunctional behaviors are well-documented factors that influence nutritional status outcomes, lead to weight loss, poor quality of life, and impact their ability to remain at home. A cluster randomized controlled trial with a parallel mixed methods evaluation processes will be conducted to examine the efficacy of a train-the-trainer program using non-paid volunteers in respite care centers to deliver a telehealth mealtime intervention guided by the theory-based C3P Model-Change the Person, Change the People, Change the Place (C3P). In this six-month study, dyads of caregivers and persons with mild to moderate dementia receiving respite care services will be randomized to receive either the telehealth intervention or enhanced usual care. Within the intervention group, dyads will be partnered with a C3P trained volunteer who will work with caregivers via videoconference to devise and implement mealtime plans. Under usual care, dyads will receive standardized educational materials modified from The Savvy Caregiver Program for Alzheimer's disease. The primary outcomes include weight maintenance or gain of the person with dementia and quality of life of the caregiver. A multi-level evaluation process utilizing respite center administrators and directors, volunteers, and caregivers will explore intervention fidelity, acceptability and sustainability. Using both the CONSORT and SPIRIT checklists as guidance, the comprehensive study design is more fully described in this manuscript. In this trial, we will lay the groundwork to examine the efficacy and sustainability of a train-the-trainer telehealth program that could be widely disseminated by national Alzheimer's organizations and readily adopted by community agencies to provide additional resources to assist families in managing mealtimes at home, while promoting the quality of life of both the caregiver and the person with dementia. This study was registered with clinicaltrials.gov: NCT03622814 on August 9, 2018..


Molecular characteristics of fluoroquinolone-resistant avian pathogenic Escherichia coli isolated from broiler chickens.
Avian pathogenic Escherichia coli (APEC) is a major pathogen in the poultry industry worldwide including Korea. In this study, the phenotypic and genotypic characteristics of 33 fluoroquinolone (FQ)-resistant APEC isolates from broilers were analyzed. All FQ-resistant APEC isolates showed amino acid exchanges at both gyrA and parC and high minimal inhibitory concentrations for FQs. A total of 11 (33.3%) isolates were positive for the plasmid-mediated quinolone resistance (PMQR) genes, qnrA (8 isolates) and qnrS (3 isolates), and showed multidrug resistance. Among the 11 PMQR-positive isolates, 1 and 2 isolates carried blaCTX-1 and blaCTX-15, respectively, as extended-spectrum β-lactamase (ESBL) producers, and the non-ESBL gene, blaTEM-1, was found in 4 isolates. Among 3 aminoglycoside-resistant isolates, aac(3)-II was only detected in 1 isolate. All 8 APEC isolates with resistance to tetracycline carried the tetA gene. Overall, 6 of the 7 trimethoprim-sulfamethoxazole-resistant isolates carried the sul1 or sul2 genes, while only 2 of the 8 chloramphenicol-resistant isolates carried the catA1 gene. Although 9 isolates carried class I integrons, only 4 isolates carried the gene cassettes dfrA12-aadA2 (2 isolates), dfrA17-aadA5 (1 isolate), extX-psp-aadA2 (1 isolate), and dfrA27 (1 isolate). The most common plasmid replicon was FIB (8 isolates, 72.7%), followed by K/B (4 isolates, 36.4%). Antimicrobial resistance monitoring and molecular analysis of APEC should be performed continuously to surveil the transmission between poultry farms.


Grating-based x-ray differential phase contrast imaging with twin peaks in phase-stepping curves-phase retrieval and dewrapping.
X-ray differential phase contrast CT implemented with Talbot interferometry employs phase-stepping to extract information of x-ray attenuation, phase shift, and small-angle scattering. Since inaccuracy may exist in the absorption grating G2 due to an imperfect fabrication, the effective period of G2 can be as large as twice the nominal period, leading to a phenomenon of twin peaks that differ remarkably in their heights. In this work, the authors investigate how to retrieve and dewrap the phase signal from the phase-stepping curve (PSC) with the feature of twin peaks for x-ray phase contrast imaging. Based on the paraxial Fresnel-Kirchhoff theory, the analytical formulae to characterize the phenomenon of twin peaks in the PSC are derived. Then an approach to dewrap the retrieved phase signal by jointly using the phases of the first- and second-order Fourier components is proposed. Through an experimental investigation using a prototype x-ray phase contrast imaging system implemented with Talbot interferometry, the authors evaluate and verify the derived analytic formulae and the proposed approach for phase retrieval and dewrapping. According to theoretical analysis, the twin-peak phenomenon in PSC is a consequence of combined effects, including the inaccuracy in absorption grating G2, mismatch between phase grating and x-ray source spectrum, and finite size of x-ray tube's focal spot. The proposed approach is experimentally evaluated by scanning a phantom consisting of organic materials and a lab mouse. The preliminary data show that compared to scanning G2 over only one single nominal period and correcting the measured phase signal with an intuitive phase dewrapping method that is being used in the field, stepping G2 over twice its nominal period and dewrapping the measured phase signal with the proposed approach can significantly improve the quality of x-ray differential phase contrast imaging in both radiograph and CT. Using the phase retrieval and dewrapping methods proposed to deal with the phenomenon of twin peaks in PSCs and phase wrapping, the performance of grating-based x-ray differential phase contrast radiography and CT can be significantly improved.


Quadricuspid aortic valve.
A case of quadricuspid aortic valve is described. The anomaly was unexpectedly found during operation for aortic valve replacement in a 70-year-old woman. Macroscopic and histological examinations of the valve showed no sign of previous inflammatory disease. Quadricuspid aortic valve must be considered, therefore, a malformation capable of leading to severe valve failure in later life.


Compartment syndrome in patients with Buerger disease and anticardiolipin antibodies.
We report two cases of acute compartment syndrome in the anterior compartment of the lower limbs of patients with the diagnosis of Buerger disease associated with positive anticardiolipin antibodies. We comment on the rarity of the case and on the possibility of interference of two associated thrombogenic conditions. The need for early fasciotomy is emphasized since the progression to necrosis is time dependent. Fasciotomy was the only reperfusion surgery utilized on these patients with resolution of the ischemia.


Association of cardiovascular risk factors with the different presentations of acute coronary syndrome.
to identify the relationship between different presentations of acute coronary syndrome and cardiovascular risk factors among hospitalized individuals. cross-sectional study performed in a teaching hospital in São Paulo, in the State of São Paulo (SP). Socio-demographic, clinical and anthropometric data of 150 individuals hospitalized due to acute coronary syndrome were collected through interviews and review of clinical charts. Association between these data and the presentation of the syndrome were investigated. there was a predominance of ST segment elevation acute myocardial infarction. There was significant association of systemic hypertension with unstable angina and high values of low density lipoprotein with infarction, without influence from socio-demographic characteristics. arterial hypertension and high levels of low-density lipoprotein were associated with different presentations of coronary syndrome. The results can provide support for health professionals for secondary prevention programs aimed at behavioural changing.


Crystalline silica induces apoptosis in human endothelial cells in vitro.
We investigated whether incubation of cultured human aortic endothelial cells (HAEC) with crystalline silica at the concentration 1 cm2/ml (chosen on the basis of a pilot experiment) leads to alterations typical of apoptosis. The binding of annexin V as early, and DNA fragmentation as late events of apoptosis were measured besides the number of cells with depolarized mitochondria. The generation of reactive oxygen species (ROS) by HAEC in presence of silica was determined as well as silica ability to in vitro generate hydroxyl radicals was investigated. After 18 h of silica incubation, about 30% of viable cells bound annexin V. After 24 h of silica treatment, the percentage of cells with fragmented DNA (Tunel positive) was 27% and it increased up to 50% after 48 h, whereas in untreated cells this percentage was 7% and 11% after 24 and 48 h, respectively. The presence of fragmented DNA in cells treated with silica was confirmed by agarose gel electrophoresis. In agreement with these results showing an induction of HAEC apoptosis by silica incubation, the number of cells with depolarized mitochondria was significantly higher after silica treatment as compared to the control. Apoptosis was also obtained with silica added to aliquots of anti-C5a-absorbed-medium. In the cells exposed to silica there was a significant increasing of ROS generation in comparison to the untreated cells. Apoptosis might be due to peroxidative stress since silica can generate hydroxyl radicals.


[Morphologic changes in tissues of the spinal canal in the radicular syndromes of lumbar osteochondrosis].
Study of biopsy material obtained from 612 surgical patients with vertebrogenic diseases of spinal radicles at the lumbosacral level and collation of the morphologic findings with the clinical picture of the disease revealed a correlation between the clinical manifestations and the inflammatory process in the vascularized tissues of the vertebral column. The severity of pain was found to depend on the degree of inflammatory changes in the epidural cellular tissue and spinal membranes. The frequency and severity of inflammatory reactions make it possible to consider inflammation, along with compression and ischemia, an important pathogenetic mechanism of the development, progression and course of the discogenic radicular syndrome and to recommend the inclusion of antiinflammatory drugs in multiple modality treatment of the disease as a method of pathogenetic therapy.


Changes in thermal sensation in diabetic patients after treatment with gangliosides.
Thirty diabetic patients (mean age (+/- SD) 45.7 +/- 11.4 years, mean duration of diabetes 7.5 +/- 7.0 years, 17 insulin-dependent), were given 3 months of placebo injections followed by either 3-4 or 6 months injections of 100 mg mixed gangliosides (Cronassial) every weekday intramuscularly in a double-blind placebo-controlled study. There was an improvement of 0.77 +/- 1.25(10) degrees C and 0.65 +/- 1.05(10) degrees C in the thermal thresholds of the Cronassial treated group after 13-19 weeks and greater than 20 weeks respectively (p less than 0.22 from change of 0.04 +/- 0.59 degrees C in group treated with placebo. Compared to those with normal thresholds, patients with abnormal thermal thresholds (greater than 1.2 degrees C) improved significantly after Cronassial treatment for 13-19 weeks (-1.13 +/- 1.72(12) vs. 0.03 +/- 0.45(16) degrees C, p less than 0.006) and for greater than 20 weeks (-1.83 +/- 1.46(6) vs. 0.06 +/- 0.59(11), p less than 0.004) but this may have been related to the fact that the degree of improvement in thermal sensation was correlated with the initial thermal threshold (r = -0.80(28), p less than 0.001). There were no significant changes in electrophysiological measurements or vibration thresholds. Gangliosides are known to increase nerve sprouting and dendritogenesis and their effects in diabetic patients may be more easily seen using tests of small fibre function.


Structural insights into the extracellular recognition of the human serotonin 2B receptor by an antibody.
Monoclonal antibodies provide an attractive alternative to small-molecule therapies for a wide range of diseases. Given the importance of G protein-coupled receptors (GPCRs) as pharmaceutical targets, there has been an immense interest in developing therapeutic monoclonal antibodies that act on GPCRs. Here we present the 3.0-Å resolution structure of a complex between the human 5-hydroxytryptamine 2B (5-HT2B) receptor and an antibody Fab fragment bound to the extracellular side of the receptor, determined by serial femtosecond crystallography with an X-ray free-electron laser. The antibody binds to a 3D epitope of the receptor that includes all three extracellular loops. The 5-HT2B receptor is captured in a well-defined active-like state, most likely stabilized by the crystal lattice. The structure of the complex sheds light on the mechanism of selectivity in extracellular recognition of GPCRs by monoclonal antibodies.


Purkinje cell survival in organotypic cultures: implication of Rho and its downstream effector ROCK.
Organotypic cultures of postnatal day 1 (P1) to P7 mouse cerebella are well-established models for studying cell survival. In the present work, we investigate the involvement of the Rho/ROCK intracellular pathway in Purkinje cell survival by using organotypic cultures of P3 Swiss mice. Specific inhibitors of Rho or ROCK were applied at different concentrations to the slice cultures, which were maintained for 5 days in vitro. We show that the bacterial exoenzyme C3 transferase, a specific inhibitor of the small GTPase Rho, increases Purkinje cell survival. There is a 4.5- and 2.5-fold increase in Purkinje cell survival when C3 intracellular uptake is promoted either by the PEP-1 peptide or by the C2IN carrier protein, respectively, and not with the commonly used TAT peptide. Moreover, treatment with Y27632 and H-1152, two specific inhibitors of the Rho kinase ROCK, also strongly reduces apoptotic cell death and results in 6.5- and 8.5-fold increases in cell survival, respectively. In immunohistochemical analysis, we also show that H-1152 did not change either glial fibrillary acidic protein or isolectin-B4 staining, indicating that this compound did not alter the cellular composition in our cultures. Thus, our data demonstrate that inhibition of Rho and its downstream effector ROCK may be used to enhance cell survival in neurodegenerative diseases.


Self-regulation mechanism for charged point defects in hybrid halide perovskites.
Hybrid halide perovskites such as methylammonium lead iodide (CH3NH3PbI3) exhibit unusually low free-carrier concentrations despite being processed at low-temperatures from solution. We demonstrate, through quantum mechanical calculations, that an origin of this phenomenon is a prevalence of ionic over electronic disorder in stoichiometric materials. Schottky defect formation provides a mechanism to self-regulate the concentration of charge carriers through ionic compensation of charged point defects. The equilibrium charged vacancy concentration is predicted to exceed 0.4% at room temperature. This behavior, which goes against established defect conventions for inorganic semiconductors, has implications for photovoltaic performance.


Malignancy after lung transplantation.
Lung transplantation is an established therapeutic option for selected patients with advanced lung diseases. As early outcomes after lung transplantation have improved, chronic medical illnesses have emerged as significant obstacles to long-term survival. Among them is post-transplant malignancy, currently representing the 2nd most common cause of death 5-10 years after transplantation. Chronic immunosuppressive therapy and resulting impairment of anti-tumor immune surveillance is thought to have a central role in cancer development after solid organ transplantation (SOT). Lung transplant recipients receive more immunosuppression than other SOT populations, likely contributing to even higher risk of cancer among this group. The most common cancers in lung transplant recipients are non-melanoma skin cancers, followed by lung cancer and post-transplant lymphoproliferative disorder (PTLD). The purpose of this review is to outline the common malignancies following lung transplant, their risk factors, prognosis and current means for both prevention and treatment.


[Duodenal lipoma is a rare cause of gastrointestinal bleeding].
Lipomas of the gastrointestinal tract are extremely rare, slow-growing and most often asymptomatic tumours. They are composed of highly differentiated fat cells surrounded by a fibrous capsule. Tumours larger than 2 cm can produce symptoms of abdominal pain and discomfort or cause anaemia due to ulceration and bleeding, or intestinal obstruction due to intussusception. This is a case report of a 73-year-old man with a bleeding duodenal lipoma situated at the papilla duodeni major which caused difficulty in the diagnostic process, and the endoscopic visualization raised suspicion of cancer of the papilla.


[Superoxide anion inhibit endothelium-dependent relaxation in rat mesenteric artery].
To explore the resistant arterial effect of superoxide anion and its possible mechanisms. The third branch of the superior mesenteric artery in male Sprague-Dawley (200-300 g) rats was rapidly excised. Periadventitial fats and connective tissues were removed and the artery was dissected into about 2 mm rings. Each ring was dispensed between two stainless steel wires (diameter 0.0394 mm) in a 5 ml organ bath (DMT 610 M, Danish Myo Technology, Denmark). Isometric force recording studies in vitro of rat mesenteric arterial rings were recorded by Powerlab Syetem. Exposure of arteries to superoxide was accomplished through the auto-oxidation of pyrogallol added to the artery baths. Then endothelium-dependent or independent relaxation was investigated, respectively. Exposure to pyrogallol (10, 100, 300, and 1 000 micromol/L) which could produce superoxide anion for 15 min resulted in a dose-dependent manner in a decrease of acetylcholine(ACh)-induced relaxation in rat mesenteric artery. Especially, the two predominant components of acetylcholine(ACh)-induced endothelium-dependent relaxation, EDHF component and NO component were both inhibited by superoxide anion from pyrogallol. However, exposure to superoxide anion from pyrogallol had no effect on the endothelium-independent relaxations to pinacidil or sodium nitroprusside (SNP) in rat mesenteric artery. These results indicate that superoxide anion can inhibit the endothelium-dependent relaxation in rat mesenteric artery, but has no effect on the endothelium-independent relaxation, in which the inhibited effect of EDHF and NO from endothelium is involved.


Fasting plasma ghrelin levels are reduced, but not suppressed during OGTT in obese African American adolescents.
Our study aimed to evaluate total plasma ghrelin (TGh) concentration and its correlation with leptin and insulin in obese African American (AA) adolescents with a family history of type 2 diabetes. Insulin, leptin, and TGh were measured for 15 non-obese controls in fasted state and 19 obese AA adolescents on samples collected during oral glucose tolerance test (OGTT) using radioimmunoassay kits. The hormonal concentrations were compared at fasting levels between obese and non-obese AA adolescents. Insulin, leptin, and TGh concentrations were also compared during OGTT in the obese group. Fasting TGh was significantly lower in obese AA adolescents compared to non-obese controls, while fasting leptin and insulin were significantly higher in obese AA adolescents compared to non-obese controls. During OGTT, for the obese group, TGh increased significantly and plasma leptin decreased significantly. A significant negative correlation was found between TGh and leptin at 30 and 120 min, but at no other time points (0, 60, and 90 min). A significant positive correlation was found between TGh and insulin at 30 min during OGTT, but no other time points. TGh was lower in obese AA adolescents with a family history of type 2 diabetes and a significant correlation occurred between TGh and leptin and TGh and insulin during OGGT at specific time points in our obese group. These findings indicate that insulin resistant obese AA adolescents have impaired ghrelin suppression.


Effects of differing response-force requirements on food-maintained responding in C57Bl/6J mice.
The effect of force requirements on response effort was examined using inbred C57BL/6J mice trained to press a disk with their snout. Lateral peak forces greater than 2 g were defined as responses (i.e., all responses above the measurement threshold). Different, higher force requirements were used to define criterion responses (a subclass of all responses) that exceeded the requirement and produced a reinforcer. The reinforcer was sweetened, condensed milk, delivered upon response termination. All mice were exposed to two ascending series of criterion force requirements (2, 4, 8, 16, and 32 g). Increasing the force requirement initially decreased criterion response rates, but criterion response rates recovered with continued exposure, except at the 32-g requirement. Response rates for all measured responses initially increased with increasing force requirements, but then decreased with continued exposure. The second exposure series produced more stable response rate changes than the first series. The time-integral of force (area under the force-time curve for individual responses, which is proportional to energy expenditure for each response) increased with the increase in the force requirement. The C57BL/6J inbred strain generated average force output similar to CD-1 outbred stock mice trained on the same force requirements. C57BL/6J inbred strain mice differed from CD-1 mice in initial response rates (for all responses above threshold) and had lower response rates at the 16 and 32 g requirements resulting in lower total force output. These data show for both mice types that increased force requirements resulted in increased overall responding (all measured responses), which contradicts a punishment interpretation of criterion response decrements. C57BL\6 inbred mice showed individual differences comparable to the outbred CD-1 stock. C57BL/6 mice did not maintain responding as well at the higher force requirements, which may be due to their small body size and weight, compared to the larger and heavier CD-1 mice.


Non-linear archetypal analysis of single-cell RNA-seq data by deep autoencoders.
Advances in single-cell RNA sequencing (scRNA-seq) have led to successes in discovering novel cell types and understanding cellular heterogeneity among complex cell populations through cluster analysis. However, cluster analysis is not able to reveal continuous spectrum of states and underlying gene expression programs (GEPs) shared across cell types. We introduce scAAnet, an autoencoder for single-cell non-linear archetypal analysis, to identify GEPs and infer the relative activity of each GEP across cells. We use a count distribution-based loss term to account for the sparsity and overdispersion of the raw count data and add an archetypal constraint to the loss function of scAAnet. We first show that scAAnet outperforms existing methods for archetypal analysis across different metrics through simulations. We then demonstrate the ability of scAAnet to extract biologically meaningful GEPs using publicly available scRNA-seq datasets including a pancreatic islet dataset, a lung idiopathic pulmonary fibrosis dataset and a prefrontal cortex dataset.


Serum adiponectin relates to shortened overall survival in men with squamous cell esophageal cancer treated with preoperative concurrent chemoradiotherapy: a pilot study.
The convergence of nutritional, genetic, and inflammatory factors plays a significant role in the pathophysiology of squamous cell esophageal cancer (SCEC). The parameters of inflammation, indices of nutritional status, and adipocyte-derived hormones such as leptin, adiponectin, and resistin have been shown to be prognostic factors in some gastrointestinal and pancreatic cancers. Forty-two patients with SCEC were subjected to a multimodal regimen of concurrent neoadjuvant chemoradiotherapy (CRT) followed by surgery. We retrospectively analyzed the impact of pretreatment values of serum leptin, adiponectin, resistin, soluble leptin receptor, C-reactive protein, TNF alpha, leukocytes, and indices of nutritional status (BMI, plasma total protein, albumin, cholesterol, and triacylglycerols) on overall survival (OS). Univariate analysis revealed significant a negative correlation between OS and serum adiponectin (p=0.027), and a positive relationship was found between serum albumin (p=0.002), cholesterol (p=0.049) level, and OS. In multivariate analysis, only the trend (p=0.086) for negative serum adiponectin association with the OS was observed. In men with SCEC treated by neoadjuvant concurrent CRT and esophagectomy, high pretreatment level of serum adiponectin was associated with shorter OS while the serum albumin and cholesterol were associated with longer OS.


[Foetomaternal transfusions after amniocentesis in early pregnancy - evaluation of 1,000 cases (author's transl)].
The foetal haemoglobin (HbF) content was determined before and 2 hours after amniocentesis in 1,000 cases of amniocentesis conditioned by genetic indication (between the 15th and 20th pregnancy week). HbF-identification was effected according to the method of Kleinhauer and Betke. In primarily (before amniocentesis) negative HbF findings, HbF positive findings after amniocentesis were obtained in 7.2% of the patients. However, if the HbF-determinations were positive already before amniocentesis, a quantitative increase of HbF-cells in the maternal blood smear after amniocentesis was observed in 15.9% of the patients. Patients with punctures in the case of placenta of the anterior wall showed and increase in HbF values after amniocentesis in 12.2% of the cases, compared against 8.9% only in patients with posterior wall placenta, but these differences were statistically not significant. Amniocentesis under ultrasonic visual control caused a drop in the number of repeated amniocentesis trials to 20/500, aspiration of bloodstained amniotic fluid to 3.6% and HbF-cell positive blood smears after amniocentesis to 7%. (Free-hand-needle-technique: amniocentesis failures 42/500, amniotic fluid samples contaminated with blood in 9.6% of the cases and increases in HbF-values after amniocentesis in 12.6% of the cases). A total of 82 Rh-negative patients were given conventional anti-D-prophylaxis independent of the localisation of placenta. No sensitization was observed in any of the cases. No boosting was caused by early amniocentesis in cases where a positive anti-body finding had been established (3 cases to date).


Treatment of middle ear ventilation disorders: sheep as animal model for stenting the human Eustachian tube--a cadaver study.
Eustachian tube disorders can lead to chronic otitis media with consecutive conductive hearing loss. To improve treatment and to develop new types of implants such as stents, an adequate experimental animal model is required. As the middle ear of sheep is known to be comparable to the human middle ear, the dimensions of the Eustachian tube in two strains of sheep were investigated. The Eustachian tube and middle ear of half heads of heathland and blackface sheep were filled with silicone rubber, blended with barium sulfate to induce X-ray visibility. Images were taken by digital volume tomography. The tubes were segmented, and a three-dimensional model of every Eustachian tube was generated. The lengths, diameters and shapes were determined. Additionally, the feasibility of endoscopic stent implantation and fixation was tested in cadaver experiments. The length of the tube between ostium pharyngeum and the isthmus and the diameters were comparable to published values for the human tube. The tube was easily accessible through the nose, and then stents could be implanted and fixed at the isthmus. The sheep appears to be a promising model for testing new stent treatments for middle ear ventilation disorders.


Targeting conserved co-opted host factors to block virus replication: Using allosteric inhibitors of the cytosolic Hsp70s to interfere with tomato bushy stunt virus replication.
To further our understanding of the pro-viral roles of the host cytosolic heat shock protein 70 (Hsp70) family, we chose the conserved Arabidopsis thaliana Hsp70-2 and the unique Erd2 (early response to dehydration 2), which contain Hsp70 domains. Based on in vitro studies with purified components, we show that AtHsp70-2 and AtErd2 perform pro-viral functions equivalent to that of the yeast Ssa1 Hsp70. These functions include activation of the tombusvirus RdRp, and stimulation of replicase assembly. Yeast-based complementation studies demonstrate that AtHsp70-2 or AtErd2 are present in the purified tombusvirus replicase. RNA silencing and over-expression studies in Nicotiana benthamiana suggest that both Hsp70-2 and Erd2 are co-opted by tomato bushy stunt virus (TBSV). Moreover, we used allosteric inhibitors of Hsp70s to inhibit replication of TBSV and related plant viruses in plants. Altogether, interfering with the functions of the co-opted Hsp70s could be an effective antiviral approach against tombusviruses in plants.


Hearing impairment in children.
Abnormal behavior in children may frequently be caused by impairment of hearing. Early detection of the impairment and of the cause are of utmost importance, not only to prevent irreversible changes where that is possible, but to permit early beginning of special training for children who are permanently deaf. Recent studies have shown that deafness of infants may follow rubella in the mother in early pregnancy, or kernicterus caused by Rh incompatibilities. Measures to control these disorders are being investigated. Adequate and careful treatment of diseases of the nose, as well as surgical drainage of infected ears when necessary, are important factors in the prevention of hearing loss in children.


The floppy infant: a practical approach.
Cerebral, non paralytic and peripheral paralytic hypotonia are briefly discussed. Criteria which help in the differential diagnosis are emphasized. In the usual cerebral hypotonia, muscle strength is preserved but muscle tone is decreased. However, there are a few conditions in which cerebral hypotonia is severe enough to resemble paralytic hypotonia. These conditions include the Prader-Willi syndrome (first phase), the Zellweger syndrome and some cases of congenital myotonic dystrophy. In peripheral or paralytic hypotonia muscle weakness and hypotonia go hand-in-hand. A few practical diagnostic criteria are given which allow the differentiation between anterior horn cell disease, polyneuropathy, neonatal myasthenia and myopathy. Finally, essential or benign hypotonia is briefly alluded to.


Identification of monofloral honeys using HPLC-ECD and chemometrics.
A total of 77 jujube, longan and chaste honey samples were collected from 18 different areas of China. Thirteen types of phenolic acids in the honey samples were analysed using high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Moreover, HPLC-ECD fingerprints of the monofloral honey samples were established. From the analysis of the HPLC-ECD fingerprints, common chromatography peak information was obtained, and principal component analysis and discriminant analysis were performed using selected common chromatography peak areas as variables. By comparing with phenolic acids as variables, using a chemometric analysis which is based on the use of common chromatography peaks as variables, 36 honey samples and 41 test samples could be correctly identified according to their floral origin.


Pre-settlement coral-reef fish larvae respond to magnetic field changes during the day.
Observations of coral-reef fish larvae have revealed remarkably consistent orientation behaviour while swimming offshore, requiring large-scale orientation cues. However, the mechanisms underlying this behaviour are still being investigated. One potential large-scale cue for orientation is the Earth's geomagnetic field. Here, we examined the effect of magnetic field manipulations on the orientation behaviour of coral-reef fish during the pelagic larval phase. In the absence of visual cues, individual larvae responded to a 90 deg shift of the horizontal component of the magnetic field within a Helmholtz coil with a comparable shift in orientation, demonstrating that they use a magnetic compass for orientation. Our findings suggest that geomagnetic field information guides swimming behaviour of larval fish in the pre-settlement phase. The ability to use large-scale sensory cues allows location-independent orientation of swimming, a behaviour that influences dispersal and connectivity of fish populations, which has important ecological implications for anthropogenic development of marine areas.


[Rational imaging strategies in laryngeal diseases].
Clinical information is indispensable for swift and cost-effective clarification of diseases of the larynx. While quality clarification of neurological changes in the area of the posterior cranial fossa and in the course of the vagus nerve as a cause of glottis malfunction is possible with MRI, localized disease of the larynx can more effectively be assessed with low-artifact CT. In the particularly difficult assessment of the post-operative larynx, a recurrence can be diagnosed only after a baseline study has been carried out after the end of therapy. With knowledge of the pretherapeutic findings, the findings immediately post-therapy, and the operation technique used, the optimal CT examination, which can be carried out quickly, will be able to provide more information about recurrence.


Phase I/II study of everolimus combined with mFOLFOX-6 and bevacizumab for first-line treatment of metastatic colorectal cancer.
Background This phase I/II trial evaluated toxicity and antitumor activity of everolimus plus mFOLFOX6 + bevacizumab for first-line treatment of metastatic colorectal cancer (mCRC). Methods A phase I, modified 3 + 3 Fibonacci schema determined the maximum tolerated dose (MTD) of everolimus, followed by phase II dose expansion. The phase II primary objective was progression-free survival at 6 months (PFS-6 m). Results The everolimus MTD was 10 mg daily with mFOLFOX6 + bevacizumab based on safety from phase I (n = 22). Twenty-five patients were treated in the phase II at 10 mg everolimus daily. Frequent grade 3-4 adverse events were neutropenia (64%), leukopenia (28%) and hypokalemia (26%). Grade 2 stomatitis was observed in 62% of patients. Two dose-limiting toxicities were observed with one attributed to everolimus 10 mg daily (grade 3 diarrhea, hypokalemia, and anorexia) and grade 3 coronary vasospasm attributed to fluorouracil. The objective response rate was 53% and was higher (86%) in those with PTEN deficiency. PFS-6 m was 96% (95% CI 89-99.9%) at the MTD (n = 35). The everolimus recommended phase II dose of this regimen is 7.5 mg daily due to frequent stomatitis and dose reductions. Conclusions Everolimus plus mFOLFOX-6 + bevacizumab is tolerable and demonstrated preliminary efficacy for first-line mCRC. Further studies are warranted in PTEN deficiency.


The detection and analysis of ventricular late potentials.
This paper introduces a ventricular late potentials (VLP) detecting and analyzing system and discusses the technique of detecting reference point used to align the QRS and the method for calculating diagnostic parameters. The AMDF algorithm fasts the correlation process. In order to eliminate analytical error, bidirectional digital filter is adopted.


Use of First-phase Insulin Secretion in Early Diagnosis of Thyroid Diabetes and Type 2 Diabetes Mellitus.
A relationship between hyperthyroidism and insulin secretion in type 2 diabetes mellitus (T2DM) has been reported. Therefore, this study explored the use of first-phase insulin secretion in the differential diagnosis of thyroid diabetes (TDM) and T2DM. In total, 101 patients with hyperthyroidism were divided into hyperthyroidism with normal glucose tolerance (TNGT), hyperthyroidism with impaired glucose regulation (TIGR), and diabetes (TDM) groups. Furthermore, 96 patients without hyperthyroidism were recruited as control groups (normal glucose tolerance [NGT], impaired glucose regulation [IGR], and T2DM). The following parameters were evaluated: homeostasis model assessment (HOMA)-IR, HOMA-β, modified β-cell function index (MBCI), peak insulin/fasting insulin (IP/I0), AUCins-OGTT, and AUCins-OGTT/AUCglu-OGTTfrom the oral glucose tolerance test (OGTT) insulin release test were utilized to assess the second-phase insulin secretion, while the IP/I0, AIR0'~10', and AUCins-IVGTTfrom the intravenous glucose tolerance test (IVGTT) insulin release test were used to assess the first-phase insulin secretion. In the OGTT, the HOMA-β values of the TNGT and TDM groups were higher than those of the NGT and T2DM groups (all P< 0.05). In the hyperthyroidism groups, the MBCI of the TDM group was lower than that of the TNGT and TIGR groups (all P< 0.05). Among the control groups, the MBCI values of the IGR and T2DM groups were lower than that of the normal glucose tolerance (NGT) group (all P< 0.05). In the IVGTT, insulin secretion peaked for all groups at 2-4 min, except for the T2DM group, which showed a low plateau and no secretion peak. The IP values of the TNGT, TIGR, and TDM groups were higher than those of the NGT, IGR, and T2DM groups (all P< 0.05). The Ip/I0, AIR0'~10', and AUCins-IVGTTvalues of the TDM group were higher than those of the T2DM group but were lower than those of the TNGT, TIGR, NGR, and IGR groups (all P< 0.05). Compared with the other five groups, the Ip/I0, AIR0'~10', and AUCins-IVGTTvalues of the T2DM group were significantly decreased (all P< 0.05). The Ip/I0and AUCins-IVGTTvalues of the TNGT group were higher than those of the NGT group (all P< 0.05). β-cell function in TDM patients is superior to that in T2DM patients. First-phase insulin secretion could be used as an early diagnostic marker to differentiate TDM and T2DM.


Selective HDAC3 Inhibitors with Potent In Vivo Antitumor Efficacy against Triple-Negative Breast Cancer.
HDAC3 modulation shows promise for breast cancer, including triple-negative cases. Novel pyrazino-hydrazide-based HDAC3 inhibitors were designed and synthesized. Lead compound 4i exhibited potent HDAC3 inhibition (IC50 = 14 nM) with at least 121-fold selectivity. It demonstrated strong cytotoxicity against triple-negative breast cancer cells (IC50: 0.55 μM for 4T1, 0.74 μM for MDA-MB-231) with least normal cell toxicity. Metabolically stable 4i displayed a superior pharmacokinetic profile. A dose-dependent therapeutic efficacy of 4i was observed in a tumor-bearing mouse model. The biomarker analysis with tumor tissues displayed enhanced acetylation on Ac-H3K9, Ac-H3K27, and Ac-H4K12 compared to Ac-tubulin and Ac-SMC3 indicating HDAC3 selectivity of 4i in vivo. The immunoblotting study with tumor tissue showed upregulation of apoptotic proteins caspase-3, caspase-7, and cytochrome c and the downregulation of proliferation markers Bcl-2, CD44, EGFR, and Ki-67. Compound 4i represents a promising candidate for targeted breast cancer therapy, particularly for cases with triple-negative breast cancer.


Responsiveness of continuous ratings of dyspnea during exercise in patients with COPD.
To examine the responsiveness of a new computerized method for patients to provide continuous ratings of dyspnea during exercise in patients with chronic obstructive pulmonary disease (COPD). In this randomized, double-blind study the effects of an inhaled bronchodilator (BD), albuterol/ipratropium bromide solution, were compared with normal saline (NS) in 30 patients with COPD (age, 66+/-9 yr; forced expiratory volume in 1 s, 48+/-14% pred). At visit 1, patients were familiarized with the cycle ergometer and computer, monitor, and mouse system to provide continuous ratings of dyspnea during exercise. At subsequent visits 2-3 d apart, patients performed pulmonary function tests followed by incremental ramp (15 W.min-1) and, 1 h later, constant work (at 55% of maximal work capacity) exercise tests. During incremental exercise the slopes of VO2:dyspnea and VE:dyspnea regressions were significantly lower, and patients exercised longer (Delta=0.4 min; P=0.003) with BD therapy compared with NS. During constant work exercise there was a significant reduction in dyspnea at the same exercise duration (5.0+/-2.8 vs 6.2+/-2.8 units on the 0-10 category-ratio scale; P=0.02) and patients exercised longer (Delta=0.9 min; P=0.04) with BD therapy. Changes in lung function at rest did not correlate significantly with changes in dyspnea ratings during exercise. Continuous ratings of dyspnea were responsive to inhaled bronchodilator therapy during both incremental and constant work exercise tests in patients with symptomatic COPD.


Ilizarov Method for Bone Lengthening and Defect Management Review of Contemporary Literature.
Since its origination in the middle of the past century, the Ilizarov method has advanced greatly and has become a viable method for bone lengthening, severe deformity correc- tion, and defect management. As the reported studies show, it remains one of the most used tools for bone reconstruction. The original method and its modifications continue to be the topic of interest for orthopaedic scientists as evidenced by the number of clinical studies on the Ilizarov method that have been published in orthopaedic journals in the period from 2000 through 2014, most of which present the out- comes of treating large series of patients using distraction osteogenesis for bone lengthening, defect management, and deformity correction. We made a review of contemporary clinical studies on the Ilizarov method used for bone length- ening and defect management.


A potent and highly efficacious Bcl-2/Bcl-xL inhibitor.
Our previously reported Bcl-2/Bcl-xL inhibitor, 4, effectively inhibited tumor growth but failed to achieve complete regression in vivo. We have now performed extensive modifications on its pyrrole core structure, which has culminated in the discovery of 32 (BM-1074). Compound 32 binds to Bcl-2 and Bcl-xL proteins with K(i) values of <1 nM and inhibits cancer cell growth with IC50 values of 1-2 nM in four small-cell lung cancer cell lines sensitive to potent and specific Bcl-2/Bcl-xL inhibitors. Compound 32 is capable of achieving rapid, complete, and durable tumor regression in vivo at a well-tolerated dose schedule. Compound 32 is the most potent and efficacious Bcl-2/Bcl-xL inhibitor reported to date.


Arteriovenous perfusion with the pulmonary assist membrane oxygenator.
The feasibility of employing a recently developed pulmonary assist membrane oxygenator for partial respiratory support in arteriovenous perfusion was studied using small mongrel dogs rendered hypoxic by oxygen depression. The unit is employed along with the conventional ventilation techniques (such as CPAP and PEEP) when the latter alone cannot maintain adequate gas exchange in the lung. The results indicate that poorly oxygenated arterial blood can be upgraded to life-sustaining levels when the bypass flow rate through the oxygenator is in the range of 18-33% of the total cardiac output. No cardiovascular derangements were noted at these arteriovenous flow rates for perfusion periods of four to six hours. The present results demonstrate the feasibility of providing partial support to pulmonary function using the pulmonary assist membrane oxygenator.


Culture media optimization for growth and phycoerythrin production from Porphyridium purpureum.
Porphyridium spp. is a red micro alga and is gaining importance as a source of valuable products viz., phycobiliproteins (PB), sulfated exopolysaccharides, and polyunsaturated fatty acids with potential applications in the food and pharmaceutical industries. In the present study, the effects of the major media constituents of Porphyridium species were studied using response surface methodology (RSM) on biomass yield, total PB and the production of phycoerythrin (PE). A second order polynomial can be used to predict the PB and PE production in terms of the independent variables. The independent variables such as the concentrations of sodium chloride, magnesium sulfate, sodium nitrate, and dipotassium hydrogen phosphate influenced the total PB and PE production. The optimum conditions showed that total PB was 4.8% at the concentration of sodium chloride 26.1 g/L, magnesium sulfate 5.23 g/L, sodium nitrate 1.56 g/L, and dipotassium hydrogen phosphate 0.034 g/L. In case of optimum PE production (3.3%), the corresponding values are 29.62, 6.11, 1.59, and 0.076 g/L, respectively. PE production depends greatly on the concentrations of chloride, nitrate, and sulfate as well as phosphate of which the former possess the maximum effect.


Internal urinary sphincter in maintenance of female continence.
The integrity of the bladder neck was assessed in 98 continent women. Radiological and physiological evidence showed that half of these women had an incompetent bladder neck, but they were still continent. These data devalue the urodynamic finding of an incompetent bladder neck as an indication for surgery for incontinence and question the physiological importance of the internal sphincter.


Improving RLRN image splicing detection with the Use of PCA and kernel PCA.
Digital image forgery is becoming easier to perform because of the rapid development of various manipulation tools. Image splicing is one of the most prevalent techniques. Digital images had lost their trustability, and researches have exerted considerable effort to regain such trustability by focusing mostly on algorithms. However, most of the proposed algorithms are incapable of handling high dimensionality and redundancy in the extracted features. Moreover, existing algorithms are limited by high computational time. This study focuses on improving one of the image splicing detection algorithms, that is, the run length run number algorithm (RLRN), by applying two dimension reduction methods, namely, principal component analysis (PCA) and kernel PCA. Support vector machine is used to distinguish between authentic and spliced images. Results show that kernel PCA is a nonlinear dimension reduction method that has the best effect on R, G, B, and Y channels and gray-scale images.


Identification and Structural Elucidation of New Process Impurity in Testosterone.
The main objective of this study is identification, isolation and characterization of potential impurity of testosterone. Testosterone was analyzed as per European pharmacopeial method for related substances by high-performance liquid chromatography (HPLC). One new unknown impurity was found along with other pharmacopeial impurities at a level more than 0.10%. This unknown impurity was isolated by preparative HPLC using Symmetry C18 column. The isolated impurity was spiked in sample containing impurities and was found to have the same retention time as that of this unknown impurity. This isolated impurity was fully characterized by different spectroscopic techniques such as LC-MS/MS, 1H, 13C NMR and DEPT as per the requirements of the ICH guidelines and was characterized as bisnoralcohol impurity.


Decidual Interleukin-22-Producing CD4+ T Cells (Th17/Th0/IL-22+ and Th17/Th2/IL-22+, Th2/IL-22+, Th0/IL-22+), Which Also Produce IL-4, Are Involved in the Success of Pregnancy.
Trophoblast expressing paternal HLA-C resembles a semiallograft, and could be rejected by maternal T cells. IL-22 seems to be involved in allograft rejection and thus could be responsible for miscarriages. We examined the role of decidual IL-22-producing CD4+ T on human pregnancy. In those experiencing successful pregnancy and those experiencing unexplained recurrent abortion (URA), the levels of IL-22 produced by decidual CD4+ T cells are higher than those of peripheral blood T cells. We found a correlation of IL-22 and IL-4 produced by decidual CD4+ T cells in those experiencing successful pregnancy, not in those experiencing URA. The correlation of IL-22 and IL-4 was also found in the serum of successful pregnancy. A prevalence of CD4+ T cells producing IL-22 and IL-4 (Th17/Th2/IL-22+, Th17/Th0/IL-22+, Th17/Th2/IL-22+, and Th0/IL-22+ cells) was observed in decidua of those experiencing successful pregnancy, whereas Th17/Th1/IL-22+ cells, which do not produce IL-4, are prevalent in those experiencing URA. Th17/Th2/IL-22+ and Th17/Th0/IL-22+ cells are exclusively present at the embryo implantation site where IL-4, GATA-3, IL-17A, ROR-C, IL-22, and AHR mRNA are expressed. T-bet and IFN-γ mRNA are found away from the implantation site. There is no pathogenic role of IL-22 when IL-4 is also produced by decidual CD4+ cells. Th17/Th2/IL-22+ and Th17/Th0/IL-22+ cells seem to be crucial for embryo implantation.


A Comparison of Manual and Three-Dimensional Modalities in Predicting Nellix Polymer Volume.
Achieving an effective seal with the Nellix endovascular aneurysm system is dependent on filling the stent bags with an appropriate volume of polymer. Calculating this volume preoperatively is essential and can be performed manually or using three-dimensional (3D) software. The aim of this project was to compare the accuracy of these two methods relative to the actual polymer volume used. Consecutive patients undergoing Nellix aneurysm repair were included in this retrospective study. Operation notes were analysed for the polymer volume used intra-operatively. Predicted volumes for all patients had been calculated on picture archiving and communication system (PACS) using a manual 'segmental cylinder' method. Computed tomography angiograms were then re-analysed using the Synapse 3D PACS update. The difference between groups was assessed using a paired t-test. Twenty-eight patients were included in the analysis; 26 men (92.9%) and 2 women (7.1%); median age 80.9 years (interquartile range, 72.5-84.5 years). The mean volume of polymer used was 103 mL. The mean manual-derived prediction was 100.1 mL (P=0.365) and 3D-derived prediction 110.2 mL (P<0.001). Manual prediction led to an average 2.8% underestimate of polymer volume whilst 3D prediction led to an average 7.0% overestimate. Calculating predicted polymer volume for the Nellix system is more accurate using a manual approach then the 3D alternative. Whilst this method is more time-consuming, there is no significant difference when compared to the actual volume used. Quicker 3D software predictions can be utilised, but their tendency to overestimate should be recognized and taken into account during planning.


An empirical investigation into the conceptual structure of chest radiograph findings.
A method of investigating the conceptual structure of findings is presented, in which: 1) finding statements are extracted manually from free text, 2) the main concepts in each finding are manually identified and classified, and 3) the resulting sets of classes are examined for insights into finding structure. This study applies the method to chest radiograph reports. Although the subjects of the findings studied fall into seven classes, the same conceptual structure can be used for most of them.


Effects of RNA splicing and post-transcriptional regulation on HIV-1 growth: a quantitative and integrated perspective.
Despite major advances over the last two decades in our understanding of RNA splicing and (post-) transcriptional regulation in human immunodeficiency virus type-1 (HIV-1), debate continues on the mechanisms and effects of Rev protein on HIV-1 growth. Moreover, arguments that HIV-1 has been optimised for growth have been largely based on speculation. Here, we begin systematically to address these issues by developing a detailed kinetic model for HIV-1 intracellular development. The model accounts for transcription, successive steps in RNA splicing, nuclear export of mRNAs, translation and shuttling of Rev and Tat, Tat-mediated transactivation of transcription, thresholds on Rev in its effects on nuclear export of mRNA, and inhibitory effects of Rev on splicing. Using the model, we found that inefficient splicing of HIV-1 mRNA was generally beneficial for HIV-1 growth, but that an excessive reduction in the splicing efficiency could be detrimental, suggesting that there exists a splicing efficiency that optimises HIV-1 growth. Further, we identified two key contributors to splicing efficiency, the intrinsic splicing rate and the extent of Rev-mediated splicing inhibition, and we showed how these should be balanced for HIV-1 to optimise its growth. Finally, we found that HIV-1 growth is relatively insensitive to different levels of the Rev export threshold, and we suggest that this mechanism evolved to delay viral growth, perhaps to enable evasion of host defensive responses. In summary, our model provides a quantitative and qualitative framework for probing how constituent mechanisms contribute to the complex, yet logical, process of HIV-1 growth.


BU-4794F, a new beta-1,3-glucan synthase inhibitor.
New beta-1,3-glucan synthase inhibitor (BU-4794F) was isolated from the culture broth of Gilmaniella sp. FA4459. Structural studies indicated that it was a novel member of the papulacandin group of antibiotics.


A unique configuration of genome-wide DNA methylation patterns in the testis.
In the mammalian lifecycle, the two periods of genome-wide epigenetic reprogramming are in the early embryo, when somatic patterns are set, and during germ cell development. Although some differences between the reprogrammed states of somatic and germ cells have been reported, overall patterns of genomic methylation are considered to be similar. Using restriction landmark genomic scanning to examine approximately 2,600 loci distributed randomly throughout the genome, we find that the methylation status of testicular DNA is highly distinct, displaying eightfold the number of hypomethylated loci relative to somatic tissues. Identification and analysis of >300 loci show that these regions are generally located within nonrepetitive sequences that are away from CpG islands and 5' regions of genes. We show that a contributing factor for these differences is that the methylation state of non-CpG-island DNA is correlated with the regional level of GC content within chromosomes and that this relationship is inverted between the testis and somatic tissues. We also show that in Dnmt3L-deficient mice, which exhibit infertility associated with abnormal chromosomal structures in germ cells, this unique testicular DNA methylation pattern is not established. These special properties of testicular DNA point to a broad, distinct epigenetic state that may be involved in maintaining a unique chromosomal structure in male germ cells.


Technology in the Management of Spinal Cord Injuries.
Injury to the spinal cord is catastrophic and usually permanent. Whereas other injured tissues, such as bone, skin, blood vessels and peripheral nerves, are capable of being repaired and resuming near normal function, such is not the case with the spinal cord. Thus far, all attempts to repair the cord using every conceivable technique has ended in failure. The physician and other members of the treatment team involved with a patient with spinal cord injury, must deal with permanent, long-term consequences of the injury.


Roles for BLyS family members in meeting the distinct homeostatic demands of innate and adaptive B cells.
B-1 and B-2 B cell populations have different progenitors, receptor diversity, anatomic location, and functions - suggesting vastly differing requisites for homeostatic regulation. There is evidence that the B lymphocyte stimulator (BLyS) family of cytokines and receptors, key factors in the homeostatic regulation of B-2 B cell subsets, is also a major player in the B-1 compartment. Here we review the development and differentiation of these two primary B cell lineages and their immune functions. We discuss evidence that BLyS or a proliferation-inducing ligand (APRIL) availability in different anatomic sites, coupled with signature BLyS receptor expression patterns on different B cell subsets, may be important for homeostatic regulation of B-1 as well as B-2 populations. Finally, we extend our working model of B cell homeostasis to integrate B-1s.


The Development of the Korean Lung Cancer Registry (KALC-R).
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related deaths worldwide. Globally, there were an estimated 1.8 million new cases and 1.59 million deaths in 2012. In Korea, the incidence of lung cancer is increasing and 24,267 (47.6/100,000) patients with lung cancer were registered at the Korea Central Cancer Registry in 2015. Previous nationwide surveys of lung cancer were performed in 1998 by the Korean Academy of Tuberculosis and Respiratory Diseases and in 2007 by the Korean Association for Lung Cancer (KALC), but the studies faced difficulties in maintaining lung cancer registry because of limitations regarding the Private Information Protection Act. To produce unbiased and reliable epidemiological data, the KALC and Korean Central Cancer Registry developed a detailed lung cancer registry (KALC-R) data structure. Following a pilot survey of 489 lung cancer cases in 2013, about 10% of the sampled lung cancer cases from the Korean Central Cancer Registry are surveyed each year. With the analysis of detailed data from the KALC-R, an important epidemiological background for scientific research or policy development is expected to be generated.


Whole metagenome profiles of particulates collected from the International Space Station.
The built environment of the International Space Station (ISS) is a highly specialized space in terms of both physical characteristics and habitation requirements. It is unique with respect to conditions of microgravity, exposure to space radiation, and increased carbon dioxide concentrations. Additionally, astronauts inhabit a large proportion of this environment. The microbial composition of ISS particulates has been reported; however, its functional genomics, which are pertinent due to potential impact of its constituents on human health and operational mission success, are not yet characterized. This study examined the whole metagenome of ISS microbes at both species- and gene-level resolution. Air filter and dust samples from the ISS were analyzed and compared to samples collected in a terrestrial cleanroom environment. Furthermore, metagenome mining was carried out to characterize dominant, virulent, and novel microorganisms. The whole genome sequences of select cultivable strains isolated from these samples were extracted from the metagenome and compared. Species-level composition in the ISS was found to be largely dominated by Corynebacterium ihumii GD7, with overall microbial diversity being lower in the ISS relative to the cleanroom samples. When examining detection of microbial genes relevant to human health such as antimicrobial resistance and virulence genes, it was found that a larger number of relevant gene categories were observed in the ISS relative to the cleanroom. Strain-level cross-sample comparisons were made for Corynebacterium, Bacillus, and Aspergillus showing possible distinctions in the dominant strain between samples. Species-level analyses demonstrated distinct differences between the ISS and cleanroom samples, indicating that the cleanroom population is not necessarily reflective of space habitation environments. The overall population of viable microorganisms and the functional diversity inherent to this unique closed environment are of critical interest with respect to future space habitation. Observations and studies such as these will be important to evaluating the conditions required for long-term health of human occupants in such environments.


Surface plasmon laser based on metal cavity array with two different modes.
The phenomenon of surface plasmon (SP) laser based on a square array of rectangular cavities cut into a metal substrate has been investigated. Both main resonant modes of the proposed structure can be used to realize SP laser while the working mechanism is different. We study the origin of these differences and propose an efficient design that exploits them. Besides, the effect of the sample size on SPP mode lasing is also discussed.


Oxerutins (Venoruton): efficacy in chronic venous insufficiency--a double-blind, randomized, controlled study.
The aim of this study was to confirm the clinical efficacy of oxerutins by evaluation of venous parietal tone and microvascular perfusion in a double-blind, randomized, placebo-controlled study. The study included 60 patients. Venous tone was evaluated by air-plethysmography (APG) in patients with venous insufficiency (CVI). Forty patients were treated with oxerutins and 20 with placebo for 4 weeks. The dose of the first 2 weeks was higher than that of the following 2 weeks. The age range was between 18 and 65 years. Randomized patients received treatment (oxerutins or placebo) according to the grade of CVI. Patients with grade I CVI received 2 g/day in the first 2 weeks of treatment and 1 g/day in the following weeks. Patients with grade II CVI received 3 g/day in the first 2 weeks and 2 g/day in the following 2 weeks. Visits were scheduled at baseline time (visit 1), at 2 weeks (visit 2) and at 4 weeks (visit 3). They were assessed with the following: (1) APG; (2) light reflection rheography (LRR); (3) capillaroscopy; (4) liquid crystals thermography. CVI signs/symptoms--heavy legs, edema, paresthesia, and cramps--were evaluated following a 4-point rating scale (0 = no symptom; 3 = severe symptoms). At visit 3 a final opinion on efficacy was provided by both patients and investigators, based on a 4-point scale (none, fairly good, good, excellent). The two groups were homogeneous for age, sex, and clinical distribution. The changes in venous capacity, were significant (p<0.01) in the oxerutins group at visits 2 and 3; values in the placebo group remained unchanged. The changes in LRR were significant in the treatment group at visits 2 (p<0.05) and 3 (p<0.01); values in the placebo group remained unchanged. Changes in temperature were significant in the oxerutins group at visits 2 (p<0.05) and 3 (p<0.01); changes in the placebo group were not significant at the end of the study. Capillaroscopy showed an improvement in patients treated with oxerutins. The results of the analysis of signs/symptoms favored active treatment. The overall effects of oxerutins were significantly better than the effects of placebo. Considering both noninvasive tests and clinical evaluation, oxerutins is effective in controlling chronic venous hypertension, without side effect, and with good tolerability.


Primary cell cultures arising from normal kidney and renal cell carcinoma retain the proteomic profile of corresponding tissues.
Renal cell carcinoma (RCC) tissue is composed of a mixture of neoplastic and normal cells, which complicate proteome analysis. The aim of our study was to investigate whether it is feasible to establish primary cell cultures of RCC and of renal cortex maintaining the tissue phenotype along with a more homogeneous and enriched cytological material. Fourteen (82.3%) primary cultures from 17 surgical cases were established and characterized by morphology, growth rate, immunocytochemistry, and molecular analysis performed by Real-time PCR, Western blotting, two-dimensional electrophoresis (2-DE), and mass spectrometry. Cultures showed >90% cytokeratine-positive epithelial cells. In primary tumor cultures, the molecular phenotype of manganese superoxide dismutase and heat shock protein 27 was the same as that found in tumor tissues with overexpression and increased number of isoforms. Moreover, 27 out 28 specific proteins and their isoforms, present in spots excised from 2-DE gel of cortex or RCC cultures, corresponded to those identified on the 2-DE tissue cortex reference map, suggesting that these primary cultures retain the proteomic profile of the corresponding tissues.


Growth of Bacillus coagulans in chemically defined media.
A nutritional study was made of five strains of Bacillus coagulans obtained from various culture collections. These five strains were descendants of two original isolates; three had been derived from one parent culture in years past and the other two were transfers from another parent culture. Therefore, the five cultures should have represented two distinct groups of genetically identical cultures. Three of the strains obtained from one culture collection had become methyl red-negative and sorbitol-negative and had gained abilities to hydrolyze gelatin and ferment arabinose. Nutritional requirements of the five cultures, determined at 37, 45, and 55 C, differed considerably among strains; however, thiamine and biotin were required by all cultures at all temperatures. Aspartic acid was stimulatory at 37 C and was required at 45 C; folic acid, basic amino acids, and certain other nutrilites were required at 55 C. Adenine supplementation was necessary for two strains at 55 C to prevent autolysis; this phenomenon is discussed. The response of these organisms to both serine and the basic amino acids at the three growth temperatures seems especially significant. The media devised for the growth of the five strains of B. coagulans used in this study permit excellent growth at three incubation temperatures.


Failure of scintigraphy lymphatic mapping in endometrial cancer. Causes and solutions.
To evaluate the effect of technical problems and patient characteristics on sentinel lymph node (SLN) scintigraphic detection and mapping success in early stages of endometrial cancer (EC). Patients with clinical early stage EC (IA-IB) underwent SLN mapping using technetium-99m-nanocolloid,between September 2011 and February 2020. were included. There were excluded cases with technical problems, 92 patients were included for the analysis of the diagnostic performance and the relation of mapping failure (pelvic unilateral or not detected SLN) with patient (age, body mass index, previous pelvic disease or surgery) and disease characteristics (histology, grade, myometrial invasion, lymphovascular space infiltration, tumor size, and lymphatic infiltration risk). The overall detection rate was 79%. Lymph node metastases were diagnosed in 7 patients. Age (p=0.01), depth of myometrial invasion ≥ 50% (p=0.04) and high risk of lymphatic infiltration (p=0.02) were positively associated with mapping failure. In multivariate analysis, age was significantly associated with mapping failure [odds ratio=1.63, 95%CI: 1.06-2.50; p=0.027]. Age, depth of myometrial invasion and high risk of lymphatic infiltration were the factors associated with higher mapping failure. An individualized injection technique, optimizing the methodology, could minimize the detection failures.


Magnetic resonance imaging evidence of hippocampal injury after prolonged focal febrile convulsions.
Magnetic resonance imaging (MRI) was performed after complex febrile convulsions (CFCs) in 27 infants. Definite MRI abnormalities were seen in 6 of the 15 infants with focal or lateralized CFCs and in none of the 12 infants with generalized CFCs. In 2 of the 6 infants with lateralized CFCs and abnormal MRIs, the MR images showed preexisting bilateral hippocampal atrophy consistent with the history of perinatal insults in these infants. However, the remaining 4 infants with MRI abnormalities and lateralized CFCs had significantly longer seizures than other infants and had MRI changes suggesting acute edema with increased hippocampal T2-weighted signal intensity and increased volume predominantly in the hippocampus in the hemisphere of seizure origin. Of those with acute edema, 1 had electrographical seizure activity recorded in the temporal region and another had a choroid fissure cyst displacing the affected hippocampus; both infants had follow-up MRIs showing that hippocampal atrophy had developed. These patients demonstrate that prolonged and focal CFCs can occasionally produce acute hippocampal injury that evolves to hippocampal atrophy. Finally, evidence of preexisting hippocampal abnormalities in several infants and electrographical temporal lobe seizure activity in 1 suggests the possibility that CFCs actually originated in the temporal lobes in some patients.


[Bacteriological study on juvenile periodontitis].
The predominant cultivable microflora of 23 pockets in 15 juvenile periodontitis (JP) patients was studied for the first time in China using the current anaerobic methodology. Samples were taken with sterile paper points and dispersed on a vortex mixer. Then the diluted samples were plated on the non-selective blood agar plates and selective MGB medium which favors the growth of Actinobacillus actimycetemcomitans (Aa) and incubated in anaerobic chamber for 5 days. From each sample 15 or more isolated colonies were picked in sequence without selection and subcultured. The isolates were identified mainly by Schrechenberger's 4 hour rapid methods for biochemical and fermentative tests and the chromatographic analysis of acid end products using ion-chromatography. The results were as follows: 1. The microflora of healthy sulci of 7 healthy young subjects was significantly different from that in the pocket of JP patients. The predominant species in healthy sulci were Streptococcus spp and Capnocytophaga gingivalis. 2. The species increased significantly in JP patients in prevalence and proportions was Eubacterium. Other species in high proportions were Bacteroides oris, B. melaninogenicus, B. gingivalis, Capnocytophaga sputigena, and Actinomyces meyeri, etc. 3. Actinobacillus actinomycetemcomitans was not detected in any of the samples.


In vitro selection of Giardia duodenalis for Albendazole resistance identifies a β-tubulin mutation at amino acid E198K.
Benzimidazole-2-carbamate (BZ) compounds, including Albendazole (Alb), are one of just two drug classes approved to treat the gastrointestinal protist Giardia duodenalis. Benzimidazoles bind to the tubulin dimer interface overlapping the colchicine binding site (CBS) of β-tubulin, thereby inhibiting microtubule polymerisation and disrupting microtubule networks. These BZ compounds are widely used as anthelmintic, anti-fungal and anti-giardial drugs. However, in helminths and fungi, BZ-resistance is widespread and caused by specific point mutations primarily occurring at F167, E198 and F200 in β-tubulin isoform 1. BZ-resistance in Giardia is reported clinically and readily generated in vitro, with significant implications for Giardia control. In Giardia, BZ mode of action (MOA) and resistance mechanisms are presumed but not proven, and no mutations in β-tubulin have been reported in association with Alb resistance (AlbR). Herein, we undertook detailed in vitro drug-susceptibility screens of 13 BZ compounds and 7 Alb structural analogues in isogenic G. duodenalis isolates selected for AlbR and podophyllotoxin, another β-tubulin inhibitor, as well as explored cross-resistance to structurally unrelated, metronidazole (Mtz). AlbR lines exhibited co-resistance to many structural variants in the BZ-pharmacophore, and cross-resistance to podophyllotoxin. AlbR lines were not cross-resistant to Mtz, but MtzR lines had enhanced survival in Alb. Lastly, Alb analogues with longer thioether substituents had decreased potency against our AlbR lines. In silico modelling indicated the Alb-β-tubulin interaction in Giardia partially overlaps the CBS and corresponds to residues associated with BZ-resistance in helminths and fungi (F167, E198, F200). Sequencing of Giardia β-tubulin identified a single nucleotide polymorphism resulting in a mutation from glutamic acid to lysine at amino acid 198 (E198K). To our knowledge, this is the first β-tubulin mutation reported for protistan BZ-resistance. This study provides insight into BZ mode of action and resistance in Giardia, and presents a potential avenue for a genetic test for clinically resistance isolates.


Methodology Series Module 9: Designing Questionnaires and Clinical Record Forms - Part II.
This article is a continuation of the previous module on designing questionnaires and clinical record form in which we have discussed some basic points about designing the questionnaire and clinical record forms. In this section, we will discuss the reliability and validity of questionnaires. The different types of validity are face validity, content validity, criterion validity, and construct validity. The different types of reliability are test-retest reliability, inter-rater reliability, and intra-rater reliability. Some of these parameters are assessed by subject area experts. However, statistical tests should be used for evaluation of other parameters. Once the questionnaire has been designed, the researcher should pilot test the questionnaire. The items in the questionnaire should be changed based on the feedback from the pilot study participants and the researcher's experience. After the basic structure of the questionnaire has been finalized, the researcher should assess the validity and reliability of the questionnaire or the scale. If an existing standard questionnaire is translated in the local language, the researcher should assess the reliability and validity of the translated questionnaire, and these values should be presented in the manuscript. The decision to use a self- or interviewer-administered, paper- or computer-based questionnaire depends on the nature of the questions, literacy levels of the target population, and resources.


Determination of dietary fibre as non-starch polysaccharides with gas-liquid chromatographic, high-performance liquid chromatographic or spectrophotometric measurement of constituent sugars.
Methods for the measurement of dietary fibre as non-starch polysaccharides (NSP) are described. A common enzymic removal of starch and acid hydrolysis of the NSP to their constituent sugars are followed by one of three alternative techniques, gas-liquid chromatography, high-performance liquid chromatography or spectrophotometry, for measurement of the released sugars. The results obtained by the three methods are in good agreement for a wide range of raw and processed foods. NSP compose approximately 90% of the plant cell-wall material and are therefore a good index of this material. Values for NSP therefore provide a good marker for a diet rich in fruit, vegetables and high-extraction cereal products associated with health and recommended in dietary guidelines. Values for total, soluble and insoluble NSP may be obtained with any of the end-point techniques, and the detailed information obtained from the chromatographic methods is useful in studies of the relationship between the intakes of various types of NSP and health. The causes of some potential interferences in the spectrophotometric assay, especially from processed foods, have been identified and eliminated. The rapid spectrophotometric version is suitable for food labelling purposes and for quality control, and the changes described have made it more robust.


11q13 allelotype analysis in 27 northern American MEN1 kindreds identifies two distinct founder chromosomes.
We analyzed constitutional and tumor DNA from 27 MEN1 kindreds not known to be related to each other. Disease allele haplotypes were constructed for each pedigree based on shared alleles from two or more affected members and from determination of allelic loss patterns in their tumors. Analysis of disease allele haplotypes showed unexpected linkage disequilibrium at marker PYGM. Further haplotype analysis indicated this could be explained by the presence of two founder chromosomes, one in four families, the other in three. A shared disease haplotype was not observed among two MEN1 kindreds with the prolactinoma phenotype of MEN1.


Characterization of QTL for oil content in maize kernel.
Kernel oil content in maize is a complex quantitative trait. Phenotypic variation in kernel oil content can be dissected into its component traits such as oil metabolism and physical characteristics of the kernel, including embryo size and embryo-to-endosperm weight ratio (EEWR). To characterize quantitative trait loci (QTL) for kernel oil content, a recombinant inbred population derived from a cross between normal line B73 and high-oil line By804 was genotyped using 228 molecular markers and phenotyped for kernel oil content and its component traits [embryo oil content, embryo oil concentration, EEWR, embryo volume, embryo width, embryo length, and embryo width-to-length ratio (EWLR)]. A total of 58 QTL were identified for kernel oil content and its component traits in 26 genomic regions across all chromosomes. Eight main-effect QTL were identified for kernel oil content, embryo oil content, embryo oil concentration, EEWR, embryo weight, and EWLR, each accounting for over 10 % of the phenotypic variation in six genomic regions. Over 90 % of QTL identified for kernel oil content co-localized with QTL for component traits, validating their molecular contribution to kernel oil content. On chromosome 1, the QTL that had the largest effect on kernel oil content (qKO1-1) was associated with embryo width; on chromosome 9, the QTL for kernel oil content (qKO9) was related to EEWR (qEEWR9). Embryo oil concentration and embryo width were identified as the most important component traits controlling the second largest QTL for kernel oil content on chromosome 6 (qKO6) and a minor QTL for kernel oil content on chromosome 5 (qKO5-2), respectively. The dissection of kernel oil QTL will facilitate future cloning and/or functional validation of kernel oil content, and help to elucidate the genetic basis of kernel oil content in maize.


[Simultaneous determination of seven avermectin residues in aquatic products by modified QuEChERS combined with high-performance liquid chromatography-tandem mass spectrometry].
A method was established for the simultaneous determination of seven avermectin (AVMs) residues, such as avermectin, ivermectin, doramectin, selamectin, eprinomectin, moxidectin and emamectin, in aquatic products using modified QuEChERS and high-performance liquid chromatography -tandem mass spectrometry (HPLC-MS/MS). The samples were extracted with 0.2% (v/v) ammoniate acetonitrile, and then 3 g of anhydrous magnesium sulfate and 2 g of anhydrous sodium sulfate were added to remove moisture and precipitate proteins. The samples were purified with 100 mg of C18 and 500 mg of anhydrous magnesium sulfate. The mobile phases comprised of acetonitrile (containing 0.1% (v/v) formic acid and 5 mmol/L ammonium acetate) and water (containing 0.1% (v/v) formic acid and 5 mmol/L ammonium acetate). The prepared samples were separated on a Varian Pursuit ULTRA C8 column (100 mm×2.0 mm, 2.8 μm) and determined using heated electrospray ionization (HESI) in the positive ion multiple reaction monitoring (MRM) mode. The analytes were quantified using external standard with the matrix-matched standard calibration curve method. The results showed that the solvent and matrix-matched standard curves for avermectin, ivermectin, doramectin, selamectin, eprinomectin and moxidectin in the range of 2-200 μg/L and for emamectin in the range of 0.2-20 μg/L were all linear, and the correlation coefficients (r) were ≥ 0.9972. The recoveries were 71.6%-112.8% with the relative standard deviations in the range of 4.7%-13.1%. The limits of quantification (LOQs) for avermectin, ivermectin, doramectin, selamectin, eprinomectin and moxidectin were all 5 μg/kg and for emamectin was 0.25 μg/kg. The present method is simple, repeatable, and suitable for the simultaneous determination of the residues of the seven avermectins in aquatic products.


Charge Blinking Statistics of Semiconductor Nanocrystals Revealed by Carbon Nanotube Single Charge Sensors.
We demonstrate the relation between the optical blinking of colloidal semiconductor nanocrystals (NCs) and their electrical charge blinking for which we provide the first experimental observation of power-law statistics. To show this, we harness the performance of CdSe/ZnS NCs coupled with carbon nanotube field-effect transistors (CNTFETs), which act as single charge-sensitive electrometers with submillisecond time resolution, at room temperature. A random telegraph signal (RTS) associated with the NC single-trap charging is observed and exhibits power-law temporal statistics (τ(-α), with α in the range of ∼1-3), and a Lorentzian current noise power spectrum with a well-defined 1/f(2) corner. The spectroscopic analysis of the NC-CNTFET devices is consistent with the charging of NC defect states with a charging energy of Ec ≥ 200 meV. These results pave the way for a deeper understanding of the physics and technology of nanocrystal-based optoelectronic devices.


Structural evolution of medium-sized Pd(n) (n=15-25) clusters from density functional theory.
Four types of possible structural motifs of the medium-sized Pd(n) (n=15-25) clusters i.e., fcc like, decahedron based, icosahedron based, and prolate ellipsoid based, have been generated from an empirical genetic algorithm search and further investigated using spin-polarized density functional theory calculations. fcc-like structures based on Pd(19) octahedron dominate the growth pathway of Pd(n) clusters (n=15-23). For larger clusters such as Pd(24) and Pd(25), a prolate ellipsoid-based geometry and a structure consisting of three interpenetrating decahedra are energetically favorable, respectively. The size-dependent cluster properties as well as the correlation between electronic properties and cluster geometry are also discussed, suggesting a particular stability cluster at Pd(19) with a fcc-like octahedron structure.


[New morphometric criteria in the study of pathogenesis of normal-tension glaucoma].
Studying the factors that contribute to the disturbance of transmembrane pressure gradient is a topical task in the research of pathogenesis of normal-tension glaucoma (NTG). To measure and compare the thickness and depth of lamina cribrosa (LCT and LCD), as well as optic nerve subarachnoid space width (ONSASW) in patients with NTG and healthy individuals. The first group included 12 patients (23 eyes) aged from 58 to 74 years (average age 66.8±3.2 years) with NTG who all had normal intraocular pressure and arterial hypotension. The second (control) group consisted of 11 healthy individuals (22 eyes) aged from 51 to 69 years (average age 56.2±4.2 years). All patients underwent structural and functional assessment of the optic nerve head using OCT RTVue-100 (Optovue, USA), as well as Humphrey Visual Field Analyzer (HFA II 745i, Germany-USA) and our modification of Frequency Doubling Technology perimetry. In all subjects the central corneal thickness (CCT) was measured by Pentacam HR (Oculus, Germany), the LCT and LCD were measured by EDI (Enhanced Depth Imaging) mode of Topcon 3D OCT 2000 (Japan). To measure the ONSASW we used a cross-sectional image of the optic nerve taken 3 mm behind the eyeball with Magnetic Resonance Imaging (Siemens Magnetom Symphony 1.5 T, Germany). Statistically significant difference was found between the 1st and 2nd groups in the average LCT (217.60±36.92 and 345.86±33.29 μm respectively; p=0.0000), LCD (435.00±86.31 and 367.31±87.00 μm, respectively; p=0.014) and ONSASW (1.27±0.13 and 1.44±0.19 mm respectively; p=0.004); the difference wasn't significant in the average CCT (543.26±31.52 and 557.50±24.92 μm respectively; p=0.11). Patients with NTG had significantly higher value of the LCD with significantly lower values of the LCT and ONSASW compared with healthy individuals, which confirms the importance of these morphometric criteria in the study of NTG pathogenesis.


Pharmacokinetics and efficacy of ifosfamide or trofosfamide in patients with intraocular lymphoma.
The prognosis of intraocular lymphoma (IOL) is poor, and the optimal treatment has not yet been defined. The study assesses ifosfamide (IFO) and trofosfamide (TRO) for treating IOL. We prospectively evaluated the efficacy and aqueous penetration of intravenous IFO, oral TRO and their active 4-hydroxy (4-OH) metabolites in 10 patients with IOL. Doses varied from 1500 to 2000 mg/m2/day on days 1-3 for IFO and from 150 to 400 mg/day (continuous or intermittent administration) for TRO. Four patients had newly diagnosed disease, and six had relapsed after pretreatment. All patients responded to first treatment with IFO or TRO, and both of two patients responded to re-treatment with IFO on ocular relapse. Progression-free survival from the first treatment with IFO or TRO was > or = 6-18 months. In six of six patients, 4-OH metabolites were detected in the aqueous humor at a concentration of 0.32-1.56 microM immediately after IFO infusion with an aqueous/serum ratio of 0.19-0.54. 4-OH metabolites could be detected in one of three patients at a concentration of 7.2 microM 3-16 h after ingestion of TRO. IFO and TRO are active in IOL. IOL patients evidence aqueous penetration of 4-OH metabolites after intravenous administration of IFO.


Familial ALS in Germany: origin of the R115G SOD1 mutation by a founder effect.
Mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) account for approximately 20% of patients with familial amyotrophic lateral sclerosis (FALS). In this study, sequence analysis of exons 1-5 of SOD1 in a large German cohort with FALS was performed. Among 75 affected patients, who were not obviously related probands with a positive family history, nine had missense mutations in SOD1. Four of the nine probands carry the same R115G mutation in exon 4 of the SOD1 gene. Genotyping with markers from the SOD1 locus revealed a common haplotype and shared allelic characteristics in these patients. These findings suggest that the R115G mutation in the German population originates from a common founder.


Structure of an anti-Lewis X Fab fragment in complex with its Lewis X antigen.
The Lewis X trisaccharide is pivotal in mediating specific cell-cell interactions. Monoclonal antibody 291-2G3-A, which was generated from mice infected with schistosomes, has been shown to recognize the Lewis X trisaccharide. Here we describe the structure of the Fab fragment of 291-2G3-A, with Lewis X, to 1.8 A resolution. The crystallographic analysis revealed that the antigen binding site is a rather shallow binding pocket, and residues from all six complementary determining regions of the antibody contact all sugar residues. The high specificity of the binding pocket does not result in high affinity; the K(D) determined by isothermal calorimetry is 11 microM. However, this affinity is in the same range as for other sugar-antibody complexes. The detailed understanding of the antibody-Lewis X interaction revealed by the crystal structure may be helpful in the design of better diagnostic tools for schistosomiasis and for studying Lewis X-mediated cell-cell interactions by antibody interference.


Structure and age jointly influence rates of protein evolution.
What factors determine a protein's rate of evolution are actively debated. Especially unclear is the relative role of intrinsic factors of present-day proteins versus historical factors such as protein age. Here we study the interplay of structural properties and evolutionary age, as determinants of protein evolutionary rate. We use a large set of one-to-one orthologs between human and mouse proteins, with mapped PDB structures. We report that previously observed structural correlations also hold within each age group - including relationships between solvent accessibility, designabililty, and evolutionary rates. However, age also plays a crucial role: age modulates the relationship between solvent accessibility and rate. Additionally, younger proteins, despite being less designable, tend to evolve faster than older proteins. We show that previously reported relationships between age and rate cannot be explained by structural biases among age groups. Finally, we introduce a knowledge-based potential function to study the stability of proteins through large-scale computation. We find that older proteins are more stable for their native structure, and more robust to mutations, than younger ones. Our results underscore that several determinants, both intrinsic and historical, can interact to determine rates of protein evolution.


[Cytological methods for the diagnosis of pleuritis].
Data are presented on a cytological examination of 2948 patients with pleuritis carried out during 7 years. Routine methods alongside centrifuging, cytological material staining, immunocytochemical and morphometric procedures were used. Each stage of the investigation was evaluated. Thanks to use of complex procedures, sensitivity of cytological methods for pleuritis diagnosis was raised to 95.2%, specificity--to 100%.


Evaluation of jejunal pouch interposition after proximal gastrectomy for early gastric cancer in the upper third of the stomach.
Proximal gastrectomy has two problems, reflux esophagitis and curability. This study evaluates postoperative outcomes focusing on reflux esophagitis and curability of proximal gastrectomy with jejunal pouch interposition for early gastric cancer in the upper third of the stomach. One hundred and thirty nine patients who underwent jejunal pouch interposition between 1996 and 2011, 10 esophago-gastrostomy and 20 jejunal interposition at our institution were compared retrospectively to examine heart burn and reflux esophagitis. Furthermore, we examined the remote outcomes of jejunal pouch interposition patients. There were significantly fewer cases of heart burn; the numbers of cases of reflux esophagitis based on endoscopic findings were significantly small in jejunal pouch interposition. Carcinoma of the remnant stomach after jejunal pouch interposition was observed in 9 patients, curative treatment was possible with endoscopic therapy in 6 patients and surgical treatment in 3 patients. There are 119 survivals and 20 deaths at present Death caused primary disease is only 2 patients. Both recurrent patterns were peritoneal metastasis and the histopathological diagnosis was not indicated for proximal gastrectomy. Jejunal pouch interposition after proximal gastrectomy for early upper third gastric cancer proves beneficial and favorable modality achieving prevention of reflux esophagitis and high curability.


Information literacy skills of occupational therapy graduates: a survey of learning outcomes.
The purpose of this study is to assess whether recent graduates of the Ohio State University's Occupational Therapy division are applying information-seeking skills they learned as undergraduates, and to seek their advice on ways to improve information-literacy instruction for current and future occupational therapy students. A survey was sent to a sample of graduates from 1995-2000. The results were entered into an SPSS database, and descriptive and inferential results were calculated to determine the information-seeking patterns of these recent graduates. A majority of the occupational therapy graduates who responded to the survey prefer to use information resources that are readily available to them, such as advice from their colleagues or supervisors (79%) and the Internet (69%), rather than the evidence available in the journal literature. Twenty-six percent (26%) of the graduates have searched MEDLINE or CINAHL at least once since they graduated. Formal library instruction sessions were considered useful by 42% of the graduates, and 22% of the graduates found informal contacts with librarians to be useful. Librarians and occupational therapy faculty must intensify their efforts to convey the importance of applying research information to patient care and inform students of ways to access this information after they graduate. In addition to teaching searching skills for MEDLINE and CINAHL, they must provide instruction on how to assess the quality of information they find on the Internet. Other findings suggest that occupational therapy practitioners need access to information systems in the clinical setting that synthesize the research in a way that is readily applicable to patient-care issues.


Extranuclear Translocation of High-Mobility Group A1 Reduces the Invasion of Extravillous Trophoblasts Involved in the Pathogenesis of Preeclampsia: New Aspect of High-Mobility Group A1.
High-mobility group A1 (HMGA1) protein is known to express in trophoblast; however, the role of migration has not been reported to date. In this study, we investigated the role of HMGA1 on the pathogenesis of preeclampsia using immortalized human trophoblast cell (HTR-8/SVneo). We investigated HMGA1 expression in cytotrophoblasts derived from our preeclampsia model mouse, the CD40L mouse, using immunofluorescence. Wound healing and transwell migration assays were also performed using HTR-8/SVneo (extravillous trophoblast) cells transfected with DNA or siRNA of HMGA1. The effect of extranuclear translocation of HMGA1 on the migration of extravillous trophoblastic cells was evaluated using deoxycholic acid (DCA). HMGA1 was expressed exclusively in the nuclei of trophoblasts derived from control mice; cytoplasmic expression was observed only in CD40L mice with preeclampsia. Furthermore, overexpression of HMGA1 in the nuclei of HTR-8/SVneo cells stimulated cell proliferation and migration. Translocation of nuclear HMGA1 to cytoplasm treated with DCA reduced cell migration. Collectively, these findings demonstrate that proper subcellular localization of HMGA1 is important for its function in trophoblast cells, and suggest that aberrant cytoplasmic expression of HMGA1 contributes to the pathogenesis of preeclampsia through impairment of trophoblast migration.


Survival in miliary tuberculosis complicated by respiratory distress.
An immigrant from India presented with a three months history of fever, weight loss, cough and hepatomegaly which were rapidly diagnosed as miliary tuberculosis when gastric lavage revealed acid-fast bacilli. One day after antituberculous therapy was commenced, the patient developed adult respiratory distress syndrome and disseminated intravascular coagulation which were successfully treated by corticosteroids, fresh frozen plasma and mechanical ventilation. Ten other survivors of miliary tuberculosis and adult respiratory distress syndrome were reviewed and the association of adult respiratory distress syndrome with the antimicrobial therapy is discussed.


Synchronous bilateral fluorescein angiography. A new technique.
Simultaneous angiography of both eyes allows the synchronous measurement of the arm-retina-time and the retinal circulation time in each eye. The dye-filling pattern of retinal arteries, choroid, disc, and cilioretinal vessels can be compared. A new method of simultaneous fluorescein angiography of both eyes, using two fundus cameras, is demonstrated. Each camera is operated by a separate power unit, thereby providing sufficient light energy for one picture every 0.6 second. The fluorescein is injected by means of an automatic injector in order to create a compact dye bolus. Simultaneous angiograms of a healthy patient and of a patient with unilateral carotid occlusion are shown.


[New research on the oral vaccination of wild animals].
Successful oral immunization of wildlife against rabies has strongly stimulated research in the past decade. New approaches have been developed for vaccine production (e.g.: use of recombinant vaccines) as well as for better potency or safety testing procedures. It appears that Man should also consider two important phenomena which already existed in nature before his research. The first one is an adaptation of the rabies virus, by serial passages, which favours the spreading of the disease among a sole animal species. Bites of this species vaccinate other species more often than they kill them, leading sometimes, to the mutual exclusion of potential vector. The next phenomenon is the self-control of the first one due to an over-adaptation of the virus to its vector species. It leads to unappropriate level, or delay, of reexcretion of the virus, therefore to the transformation of a rabies epizootics into rabies enzootics. Oral vaccination would thus appear as an useful tool to eradicate the disease after it reached this enzootic stage.


99mTc-labeled field bean protease inhibitor can function as an efficient tumor detecting agent.
Purified field bean protease inhibitor (FBPI) was labeled with 99mTcO4- to ascertain its ability to locate tumors in tumor-bearing rat models. The labeling was done with Sn2+ as a reducing agent and the yield was 95%. It was stable for 2 hr at ambient temperature. The biodistribution study of the intravenously injected radiolabeled FBPI in normal Wistar rats at various time intervals showed a rapid blood clearance from the systemic circulation (approximately 5hr). The complex was predominantly excreted through the renal and the hepatobiliary systems. In vivo distribution and scintiimaging of 99mTc-FBPI were carried out in rats bearing carcinogen-induced mammary tumor or transplanted C6-gliomas. The results obtained were compared with conventional tumor-seeking radiopharmaceuticals such as 99mTc-(V)dimercaptosuccinic acid (DMSA), 201Thallous chloride (TICI) and 99mTc-Citrate. The tumor to muscle (T/M) ratios obtained with 99mTc-FBPI in rat C6 glioma was nearly 2 to 5-fold higher than obtained with all the three conventional tumor-seeking agents. The T/M ratio obtained with 99mTc-FBPI in rat mammary tumor on the other hand appeared to be 2-3-fold higher than noted with 99mTc(V)-DMSA and 201TlCl. The ratio was however comparable with that obtained with 99mTc-Citrate. The study indicated that 99mTc-FBPI has the specific potentials for imaging gliomas and possibly other tumors as well.