Effects of frequency and airway pressure on gas exchange during interrupted high-frequency, positive-pressure ventilation in ponies.
Cardiovascular effects and pulmonary gas exchange were compared during conventional mechanical ventilation (CMV) and interrupted high-frequency, positive-pressure ventilation (IHFPPV) in 6 anesthetized ponies in dorsal recumbency. When the peak airway pressure (Paw) was held constant at control values attained during CMV (18 to 20 cm of H2O), and the ventilator frequency of IHFPPV was varied over the range, 2.5 to 12.5 Hz, significant (P less than 0.05) changes from control values were observed only in the ratio of dead-space volume to tidal volume (VD/VT) and in the respiratory minute volume (VE). The mean (+/- SEM) carbon dioxide excretion (VCO2) was 2.12 +/- 0.1 ml/kg/min during IHFPPV. Dead-space ventilation ranged from 40 to 73.7% of total ventilation and increased directly with increasing frequency. The VE also increased, from 89 ml/kg/min at a ventilatory frequency of 2.5 Hz to 145 ml/kg/min at a frequency of 12.5 Hz. Maintaining the frequency of IHFPPV constant at 12.5 Hz and increasing the Paw over the range of 5 to 30 cm of H2O caused significant (P less than 0.05) changes in arterial partial pressure of O2 (PaO2), VCO2, pulmonary shunt fraction (QS/QT), VE, arterial-alveolar differences in oxygen tension (AaDO2), VD/VT, and cardiac output, compared with CMV. The PaO2 and the VCO2 increased linearly with increasing Paw. With increasing Paw, VD/VT decreased directly with increasing Paw from 98 to 69.3%. Gas exchange at a Paw of 15 cm of H2O during IHFPPV was equivalent to conditions at Paw of 20 cm of H2O during CMV. At a higher Paw during IHFPPV, improvements over control values were observed in gas exchange.


A qualitative study of medical educators' perspectives on remediation: Adopting a holistic approach to struggling residents.
During residency, some trainees require the identification and remediation of deficiencies to achieve the knowledge, skills and attitudes necessary for independent practice. Given the limited published frameworks for remediation, we characterize remediation from the perspective of educators and propose a holistic framework to guide the approach to remediation. We conducted semistructured focus groups to: explore methods for identifying struggling residents; categorize common domains of struggle; describe personal factors that contribute to difficulties; define remediation interventions and understand what constitutes successful completion. Data were analyzed through conventional content analysis. Nineteen physicians across multiple specialties and institutions participated in seven focus groups. Thirteen categories emerged around remediation. Some themes addressed practical components of remediation, while others reflected barriers to the process and the impact of remediation on the resident and program. The themes were used to inform development of a novel holistic framework for remediation. The approach to remediation requires comprehensive identification of individual factors impacting performance. The intervention should not only include a tailored learning plan but also address confounders that impact likelihood of remediation success. Our holistic framework intends to guide educators creating remediation plans to ensure all domains are addressed.


Atypical endometrial hyperplasia: grounds for possible misdiagnosis of endometrial adenocarcinoma.
The diagnoses of atypical hyperplasia and well-differentiated adenocarcinoma imply totally different approaches because of clinical and patient-oriented ramifications, especially when morphological differences are not entirely conclusive. The purpose of this study was to examine the relationship between the diagnosis of atypical hyperplasia during curettage or endometrial biopsy and the definitive histological findings from hysterectomy material. 23 patients were found fit for the current study and subsequently their clinical histories were reviewed for relevant clinical data, histopathological profiling and type of therapeutic interventions. Adenocarcinoma was observed in 12 (52.17%) of 23 hysterectomy cases. The hyperplasia was found in 10 (43.47%) cases, although 4 of them lacked atypia and 1 case proved to be hyperplasia-free. Hysterectomy was prescribed as the next step in the diagnosis of atypical endometrial hyperplasia. Other wait-and-see approaches could have easily forfeited the chances of providing an adequate treatment for an operable and curable cancer in approximately half of the studied cases.


Simulation of dust particles in dual-frequency capacitively coupled silane discharges.
The behavior of nanoparticles in dual-frequency capacitively coupled silane discharges is investigated by employing a one-dimensional self-consistent fluid model. The numerical simulation tries to trace the formation, charging, growth, and transport of dust particles during the discharge, under the influences of the high- and low-frequency electric sources, as well as the gas pressure. The effects of the presence of the nanoparticles and larger anions on the plasma properties are also discussed, especially, for the bulk potential, electron temperature, and densities of various particles. The calculation results show that the nanoparticle density and charge distribution are mainly influenced by the voltage and frequency of the high-frequency source, while the voltage of the low-frequency source can also exert an effect on the nanoparticle formation, compared with the frequency. As the discharge lasts, the electric potential and electron density keep decreasing, while the electron temperature gets increasing after a sudden drop.


Nanomedicines: From Bench to Bedside and Beyond.
Advancing nanomedicines from concept to clinic requires integration of new science with traditional pharmaceutical development. The medical and commercial success of nanomedicines is greatly facilitated when those charged with developing nanomedicines are cognizant of the unique opportunities and technical challenges that these products present. These individuals must also be knowledgeable about the processes of clinical and product development, including regulatory considerations, to maximize the odds for successful product registration. This article outlines these topics with a goal to accelerate the combination of academic innovation with collaborative industrial scientists who understand pharmaceutical development and regulatory approval requirements-only together can they realize the full potential of nanomedicines for patients.


Serum Transaminases at Presentation and Association with Acute Dialysis in Children with Hemolytic Uremic Syndrome.
To determine whether serum transaminases at presentation predict the need for dialysis in children with hemolytic uremic syndrome (HUS). Single-center, retrospective chart review of pediatric patients with HUS. Data collected included demographics, clinical and laboratory parameters, and need for dialysis. These factors were compared between two groups: "dialysis" versus "no dialysis." Continuous data were compared using a t test whereas categoric data were compared by the chi-squared test. Multivariate logistic regression was performed on a prior set of variables to determine if serum transaminases independently predict the need for dialysis. A total of 70 children were included in the study, of which, 39 (27%) received dialysis. The no-dialysis group had a higher proportion of white patients compared with the dialysis group (74% dialysis versus 94% no dialysis). The only clinical sign at admission associated with dialysis was reduced urine output (56% versus 16%, P<0.001). Univariate logistic regression identified admission serum creatinine, aspartate transaminase (AST), and alanine transaminase (ALT) to be associated with the need for dialysis. Multivariate logistic regression showed serum AST and ALT to be independent predictors of the need for dialysis, with both improving the performance of the regression model. Sensitivity analysis showed a cutoff of 129 U/L for AST and 83 U/L for ALT with high specificity. Serum transaminases at presentation are independently associated with the subsequent need for dialysis in patients with HUS. Our study suggests that when both serum ALT and AST are normal, the likelihood to need dialysis is very low; alternatively, when both serum ALT and AST are more than two times the upper level of normal, the need for dialysis is very high.


Loeys-Dietz Syndrome Complicated by Right Coronary Artery Pseudoaneurysm.
Loeys-Dietz syndrome is a rare autosomal dominant connective tissue disorder notable for rapidly progressive vascular aneurysmal disease and craniofacial defects. Patients are at an increased risk for aneurysm rupture and dissection at younger ages compared to other aneurysmal syndromes. Early surgical intervention is important for prevention of ruptures and/or dissection. The coronary arterial tree is mostly involved as a result of postoperative complications of an aortic root repair. This fact has been sparsely reported. We report a unique case of LDS2 presenting with chest pain that was later diagnosed as a pseudoaneurysm as a result of a right coronary artery graft dehiscence.


Carbon nanotubes reinforced poly(L-lactide) scaffolds fabricated by thermally induced phase separation.
In tissue engineering, porous nanocomposite scaffolds can potentially mimic aspects of the nanoscale architecture of the extra-cellular matrix, as well as enhance the mechanical properties required for successful weight-bearing implants. In this paper, we demonstrate that highly porous thermoplastic poly(L-lactide) nanocomposite scaffolds containing different types of functionalized multi-walled carbon nanotubes (CNTs). The nanocomposite scaffolds were manufactured by a thermally induced phase separation method. This experiment produced an uniform distribution of CNTs throughout the scaffold without obvious aggregations for funtionalized CNTs filled scaffolds by scanning electron microscope observation. The CNTs were frequently located on the pore surface, forming rough, hairy nano-textures. The pore size was reduced with the increasing of CNT loading. Parts of PLLA matrix was induced into nanofibrous structures from solid-walled state, which reduced the crystallinity of the PLLA characterized by DSC measurement. The CNT incorporation significantly improved the compression modulus of the nanocomposite scaffolds, especially the functionalized CNTs. The capacity of protein adsorption is significantly improved when the concentration of the CNTs was higher than 1.0 wt.% and the cell attachment was also enhanced by the addition of CNTs, especially N-CNT.


Second salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer.
Salvage treatments for localized radiorecurrent prostate cancer can be performed safely when a focal and image guided approach is used. Due to the low toxicity, the opportunity exists to investigate a second salvage treatment when a second locally recurrent prostate cancer occurs. Here, we describe a second salvage treatment procedure of 4 patients. Four patients with a pathologically proven second local recurrence were treated in an outpatient magnetic resonance imaging (MRI)-guided setting with a single fraction of 19 Gy focal high-dose-rate brachytherapy (HDR-BT). Delineation was performed using choline-PET-CT or a 68Ga-PSMA PET in combination with multiparametric 3 Tesla MRI in all four patients. Toxicity was measured using common toxicity criteria for adverse events (CTCAE) version 4.0. With a median follow-up of 12 months (range, 6-15), there were 2 patients with biochemical recurrence as defined by the Phoenix-definition. There were no patients with grade 3 or more toxicity. In all second salvage HDR-BT treatments, the constraints for rectum, bladder, and urethra were met. Median treatment volume (GTV) was 4.8 cc (range, 1.9-6.6 cc). A median of 8 catheters (range, 6-9) were used, and the median dose to the treatment volume (GTV) was a D95: 19.3 Gy (SD 15.5-19.4 Gy). Second focal salvage MRI-guided HDR-BT for a select group of patients with a second locally recurrent prostate cancer is feasible. There was no grade 3 or more acute toxicity for these four patients.


Uric acid-based ratios for predicting renal failure in Chinese IgA nephropathy patients.
Objective: The uric acid/albumin ratio (UAR), a novel, simple, and compositive laboratory biomarker, has recently attracted attention for predicting disease prediction and disease prognosis. However, whether uric acid-related biomarkers (especially UAR) could serve as prognostic indicator for IgAN is unclear. Methods: In this retrospective cohort study, biopsy-confirmed IgAN patients from 2009 to 2017 from West China Hospital were evaluated. The optimal cutoff value of UAR for renal outcome was defined using the Youden index by the area under receiver operating characteristic curve (AUC). The patients were then categorized into the high UAR group and the low UAR group. Renal endpoints were defined as progression to ESRD, eGFR decreased ≥50% of the baseline level, or initiation of renal replacement treatment. Kaplan‒Meier survival analysis and Cox regression analysis were used to identify factors influencing IgAN outcomes. Results: A total of 1143 patients with a median age of 33.0 (26.0-42.0) (44.2% men) were included in the study. The best cut-off UAR concerned with renal survival was determined to be 9.94 with a specificity of 77.5% and a sensitivity of 61.5% (J, 0.390; AUC, 0.750). Then, the patients were divided into two groups labelled as low and high UAR ratios (≥ 9.94 and <9.94, respectively). More severe clinical manifestations and pathological lesions were observed in the high UAR group. Multivariate Cox regression analysis after adjusted for important clinicopathological parameters manifested that a high UAR was an independent prognostic biomarker for IgAN. (p = 0.036, HR =2.56, 95% CI: 1.07-6.16). Conclusion: UAR might be a novel predictor for renal progression and contribute to targeted management.


Airpnp: Auto- and Integrated Regulation of Polynucleotide Phosphorylase.
The properties and expression of polynucleotide phosphorylase (PNPase), capable of both RNA degradation and polymerization, have been studied for 60 years. In this issue of the Journal of Bacteriology, Park et al. (H. Park, H. Yakhnin, M. Connolly, T. Romeo, and P. Babitzke, J Bacteriol 197:3751-3759, 2015, http://dx.doi.org/10.1128/JB.00721-15) write the latest chapter on the complex regulation of pnp gene expression involving CsrA. I describe how this new piece of the puzzle fits into the global scheme of PNPase autoregulation and how this is influenced by central carbon metabolism at both the posttranscriptional level and that of enzyme activity.


Biosurfactins production by Bacillus amyloliquefaciens R3 and their antibacterial activity against multi-drug resistant pathogenic E. coli.
In this work, the anti-Escherichia coli activity of the bioactive substances produced by Bacillus amyloliquefaciens R3 was examined. A new and cheap medium for production of the anti-E. coli substances which contained 20.0 g L(-1) soybean powder, 20.0 g L(-1) wheat flour, pH 6.0 was developed. A crude surfactant concentration of 0.48 mg mL(-1) was obtained after 27 h of 10-L fermentation, and the diameter of the clear zone on the plate seeded with the pathogenic E. coli 2# was 23.3 mm. A preliminary characterization suggested that the anti-E. coli substances produced by B. amyloliquefaciens R3 were the biosurfactins (F1, F2, F3, F4, and F5) with amino acids (GLLVDLL) and hydroxy fatty acids (of 12-15 carbons in length). It was found that all the strains of the pathogenic E. coli showed resistance to several different antibiotics, suggesting that they were the multi-drug resistance and all the strains of the pathogenic E. coli were sensitive to the biosurfactins, indicating that the biosurfactins produced by B. amyloliquefaciens R3 had a broad spectrum of antibacterial activity against the pathogenic E. coli with multi-drug resistant profiles. After the treatment with the purified biosurfactin (F1), the cell membrane of both the whole cells and protoplasts of the E. coli 2# was damaged and the whole cells of the bacterium were broken.


Impact of a personalized versus moderate-intensity exercise prescription: a randomized controlled trial.
Effective approaches to promote adolescent physical activity are needed. Moreover, a one-size-fits-all approach has been minimally successful to date. This randomized controlled trial evaluates a theory-based personalized exercise prescription to enhance motivation for being active and physical activity participation among adolescent reluctant exercisers. Adolescents were characterized by affective style as reluctant (predisposed to negative affect during exercise) or latent (predisposed to positive affect during exercise) exercisers based on their affective response to an acute exercise task, and then randomly assigned to an exercise prescription of either a personalized or a moderate intensity. Assignment was double-blind. Assessments were pre- and post- the 8-week intervention. Participants were an ethnically diverse group of adolescents (19 % non-Latino White) in a public middle-school. The exercise intensity manipulation and assessments took place at the school site during regular Physical Education. Participants were assigned to either a moderate-intensity exercise prescription [target heart rate (HR) range 60-80 % of HR max] or a personalized exercise prescription corresponding to an intensity that "feels good" to the individual for 8 weeks during daily Physical Education. Outcome measures included exercise-related intrinsic motivation (via questionnaire), and daily moderate-to-vigorous physical activity (MVPA; via accelerometer). The exercise intensity manipulation did not yield actual differences in exercise intensity during PE, and had no effect on either Intrinsic Motivation or MVPA. There was no significant interaction between affective style and group assignment in predicting Intrinsic Motivation or MVPA. This study did not find support for a link between affective experiences during exercise and physical activity participation. Providing adolescents with a personalized exercise intensity prescription and asking them to follow the prescription during PE was not an effective strategy to manipulate their affective experience of exercise. A more rigorous test of affective manipulation may require supervised exercise sessions during which exercise intensity can be directly observed and controlled.


Regulated expression of putative membrane progestin receptor homologues in human endometrium and gestational tissues.
Rapid non-genomic actions of progesterone are implicated in many aspects of female reproduction. Recently, three human homologues of the fish membrane progestin receptor (mPR) have been identified. We combined bioinformatic analysis with expression profiling to define further the role of these mPRs in human reproductive tissues. Sequence analysis confirmed that the mPRs belong to a larger, highly conserved family of proteins, termed 'progestin and adiponectin receptors' (PAQRs). A comparison of the expression of mPR transcripts with that of two related PAQR family members, PAQRIII and PAQRIX, in cycling endometrium and pregnancy tissues revealed markedly divergent expression levels and profiles. For instance, endometrial expression of mPRalpha and gamma and PAQRIX was cycle-dependent whereas the onset of parturition was associated with a marked reduction in myometrial mPRalpha and beta transcripts. Interestingly, mPRalpha and PAQRIX were most highly expressed in the placenta, and the tissue expression levels of both genes correlated inversely with that of the nuclear PR. Phylogenetic analysis demonstrated that PAQRIX belongs to the mPR subgroup of proteins. We also validated a polyclonal antibody raised against the carboxy-terminus of human mPRalpha. Immunohistochemical analysis demonstrated more intense immunoreactivity in placental syncytiotrophoblasts than in endometrial glands or stroma. The data suggest important functional roles for mPRalpha, and possibly PAQRIX, in specific reproductive tissues, particularly those that express low levels of nuclear PR.


The Smallest Form Factor UWB Antenna with Quintuple Rejection Bands for IoT Applications Utilizing RSRR and RCSRR.
In this paper, we present the smallest form factor microstrip-fed ultra-wideband antenna with quintuple rejection bands for use in wireless sensor networks, mobile handsets, and Internet of things (IoT). Five rejection bands have been achieved at the frequencies of 3.5, 4.5, 5.25, 5.7, and 8.2 GHz, inseminating four rectangular complementary split ring resonators (RCSRRs) on the radiating patch and placing two rectangular split-ring resonators (RSRR) near the feedline-patch junction of the conventional ultra-wideband (UWB) antenna. The design guidelines of the implemented notched bands are provided at the desired frequency bands and analyzed. The measured results demonstrate that the proposed antenna delivers a wide impedance bandwidth from 3 to 11 GHz with a nearly omnidirectional radiation pattern, high rejection in the multiple notched-bands, and good radiation efficiency over the entire frequency band except at the notched frequencies. Simulated and measured response match well specifically at the stop-bands.


A Magnetic Resonance Imaging-Based Radiomic Model for the Noninvasive Preoperative Differentiation Between Transitional and Atypical Meningiomas.
Preoperative distinction between transitional meningioma and atypical meningioma would aid the selection of appropriate surgical techniques, as well as the prognosis prediction. Here, we aimed to differentiate between these two tumors using radiomic signatures based on preoperative, contrast-enhanced T1-weighted and T2-weighted magnetic resonance imaging. A total of 141 transitional meningioma and 101 atypical meningioma cases between January 2014 and December 2018 with a histopathologically confirmed diagnosis were retrospectively reviewed. All patients underwent magnetic resonance imaging before surgery. For each patient, 1227 radiomic features were extracted from contrast-enhanced T1-weighted and T2-weighted images each. Least absolute shrinkage and selection operator regression analysis was performed to select the most informative features of different modalities. Subsequently, stepwise multivariate logistic regression was chosen to further select strongly correlated features and build classification models that can distinguish transitional from atypical meningioma. The diagnostic abilities were evaluated by receiver operating characteristic analysis. Furthermore, a nomogram was built by incorporating clinical characteristics, radiological features, and radiomic signatures, and decision curve analysis was used to validate the clinical usefulness of the nomogram. Sex, tumor shape, brain invasion, and four radiomic features differed significantly between transitional meningioma and atypical meningioma. The clinicoradiomic model derived by fusing the above features resulted in the best discrimination ability, with areas under the curves of 0.809 (95% confidence interval, 0.743-0.874) and 0.795 (95% confidence interval, 0.692-0.899) and sensitivity values of 74.0% and 71.4% in the training and validation cohorts, respectively. The clinicoradiomic model demonstrated good performance for the differentiation between transitional and atypical meningioma. It is a quantitative tool that can potentially aid the selection of surgical techniques and the prognosis prediction and can thus be applied in patients with these two meningioma subtypes.


Increased protective activity against acid precipitation of poly(U) in the serum of tumor-bearing mice.
Transplantation of leukemia L1210 cells into DBA/2 mice and of Ehrlich ascites tumor cells into BALB/C mice resulted in a significant increase of protective activity against acid precipitation of poly (U) in the serum. The increase was observed as early as one day after the tumor transplantation and seems to be connected with cancer growth, since inoculation of L1210 cells into BALB/C mice did not affect the protective activity, evidently as a result of their well established inability to cause cancer in this strain. Furthermore, no increase of activity was observed when bacteria were inoculated into mice, or when the latter were partially hepatectomized. The results suggest that the protective activity against acid precipitation of poly (U) could prove to be a tumor marker for the early detection of cancer growth.


Naproxen-Induced Evans Syndrome.
Evans syndrome is an autoimmune disorder characterized by the simultaneous occurrence of autoimmune hemolytic anemia and immune thrombocytopenic purpura. It can further be classified as primary Evans syndrome when it occurs by itself, or secondary Evans syndrome when it is associated with other autoimmune and lymphoproliferative disorders. Corticosteroids and immunoglobulins are the first-line treatments for primary Evans syndrome, and subsequent options include other immunosuppressive medications. Medical literature provides little information about the triggers of primary Evans syndrome. Knowing such information, however, is essential to recognize, treat and prevent the recurrence of the disease effectively. We report a 68-year-old female who presented with shortness of breath, cough, bruises, scleral icterus, and dark urine after several days of naproxen therapy for pain. Further workup noted direct antiglobulin test positive for IgG, anemia, and thrombocytopenia. Imaging studies showed deep venous thrombosis. She was diagnosed with Evans syndrome and improved following prompt treatment with corticosteroids, anticoagulants, blood transfusion therapies, and discontinuation of naproxen. The prognosis of Evans syndrome is poor, variable, and characterized by relapses. Early diagnosis and treatment are therefore associated with better prognosis. This case is critical because it shines a light on one of the major causes of Evans syndrome, reports a practical approach to treating the condition, and paves the way for future research on Evans syndrome. This case is also the first reported naproxen-induced Evans syndrome in the world's literature.


Identification and counting of asbestos fibers.
A combined analytical electron microscopic/optical count method for the determination of airborne asbestos fibers was tested for precision and bias. A modified phase contrast microscopic count method (NIOSH Method 7400) was used to determine total fiber content. The analytical electron microscope (AEM) procedure was added to identify the fraction of amosite asbestos fibers in airborne, laboratory-generated samples containing amosite and wollastonite fibers. Then this fraction was applied to the routine optical counts of all the samples in the set to estimate the asbestos fiber concentration. The effects of sample to sample, wedge to wedge, within wedge and between and counter variability were examined. In addition, the variabilities of the elemental ratio within a fiber and between fibers was also determined to find their possible influence on the ability to identify the fiber as amosite in the presence of other silicate fibers. A precision of 20.1% relative standard deviation (RSD) and a bias of -9.1% for the AEM count method compared with the optical count procedure were found for these mixed fiber samples.


[Moderately differentiated squamous cell carcinoma associated pilonidal cyst].
Malignant degeneration of pilonidal sinus is a rare complication observed mainly in recurrent chronic cases of the disease, associated to a very bad prognosis. In the world's literature we find it like an infrequent entity. In Spain had reviewed 367 patients with simple and complicated pilonidal cysts. We found three cases (0.81%) of epidermoid carcinoma. Men's 60 years of age, with clinical picture of 50 years of evolution with the presence of sacral tumor, is resection and histopathological reporting of pilonidal cyst; taking evolution at healing, with necrotic edges; resection of these will decide and report is squamous cell carcinoma. Pilonidal sinus epidermoid carcinoma is an infrequent disease predicting for very poor outcome.


A Multicomponent Neuronal Response Encodes the Larval Decision to Pupariate upon Amino Acid Starvation.
Organisms need to coordinate growth with development, particularly in the context of nutrient availability. Thus, multiple ways have evolved to survive extrinsic nutrient deprivation during development. In Drosophila, growth occurs during larval development. Larvae are thus critically dependent on nutritional inputs; but after critical weight, they pupariate even when starved. How nutrient availability is coupled to the internal metabolic state for the decision to pupariate needs better understanding. We had earlier identified glutamatergic interneurons in the ventral ganglion that regulate pupariation on a protein-deficient diet. Here we report that Drosophila third instar larvae (either sex) sense arginine to evaluate their nutrient environment using an amino acid transporter Slimfast. The glutamatergic interneurons integrate external protein availability with internal metabolic state through neuropeptide signals. IP3-mediated calcium release and store-operated calcium entry are essential in these glutamatergic neurons for such integration and alter neuronal function by reducing the expression of multiple ion channels.SIGNIFICANCE STATEMENT Coordinating growth with development, in the context of nutrient availability is a challenge for all organisms in nature. After attainment of "critical weight," insect larvae can pupariate, even in the absence of nutrition. Mechanism(s) that stimulate appropriate cellular responses and allow normal development on a nutritionally deficient diet remain to be understood. Here, we demonstrate that nutritional deprivation, in postcritical weight larvae, is sensed by special sensory neurons through an amino acid transporter that detects loss of environmental arginine. This information is integrated by glutamatergic interneurons with the internal metabolic state through neuropeptide signals. These glutamatergic interneurons require calcium-signaling-regulated expression of a host of neuronal channels to generate complex calcium signals essential for pupariation on a protein-deficient diet.


Isolation, characterization and chromosome localization of repetitive DNA sequences in bananas (Musa spp.).
Partial genomic DNA libraries were constructed in Musa acuminata and M. balbisiana and screened for clones carrying repeated sequences, and sequences carrying rDNA. Isolated clones were characterized in terms of copy number, genomic distribution in M. acuminata and M. balbisiana, and sequence similarity to known DNA sequences. Ribosomal RNA genes have been the most abundant sequences recovered. FISH with probes for DNA clones Radkal and Radka7, which carry different fragments of Musa 26S rDNA, and Radka14, for which no homology with known DNA sequences has been found, resulted in clear signals at secondary constrictions. Only one clone carrying 5S rDNA, named Radka2, has been recovered. All remaining DNA clones exhibited more or less pronounced clustering at centromeric regions. The study revealed small differences in genomic distribution of repetitive DNA sequences between M. acuminata and M. balbisiana, the only exception being the 5S rDNA where the two Musa clones under study differed in the number of sites. All repetitive sequences were more abundant in M. acuminata whose genome is about 12% larger than that of M. balbisiana. While, for some sequences, the differences in copy number between the species were relatively small, for some of them, e.g. Radka5, the difference was almost thirty-fold. These observations suggest that repetitive DNA sequences contribute to the difference in genome size between both species, albeit to different extents. Isolation and characterization of new repetitive DNA sequences improves the knowledge of long-range organization of chromosomes in


[Influence of Changing Respirator Pattern on Dynamic Tumor Tracking Accuracy with Gimbaled Linac System Using a Digital Camera].
It is important for high-precision radiation therapy that tracking accuracy in dynamic tumor tracking (DTT) using the gimbal X-ray head. We evaluated the tracking accuracy under various respiratory patterns differ from a correlation model [four-dimensional model (4D-model)] in real-time using a digital camera. A sheet of paper with luminous line was placed on the programmable respiratory motion table (CIRS Inc.) and operated with the laser projector. The luminous line was defined as a target and the laser was defined as a gimbal. Motion table was operated at a period of 4 s and amplitude of ±10 mm to create 4D-modeling. This movement was defined as the basic operation. To investigate the tracking accuracy, target and gimbal positions were recorded using a digital camera under amplitudes (±5-20 mm) and periods (2-8 s) and analyzed by ImageJ software (NIH). The maximum tracking errors under various period and amplitude were 1.7-0.9 mm and 0.4-1.9 mm, respectively. From the creation of 4D-modeling, it was confirmed that when the period has shortened and the amplitude has increased, tracking accuracy was reduced.


Computational and experimental model of transdermal iontophorethic drug delivery system.
The concept of iontophoresis is often applied to increase the transdermal transport of drugs and other bioactive agents into the skin or other tissues. It is a non-invasive drug delivery method which involves electromigration and electroosmosis in addition to diffusion and is shown to be a viable alternative to conventional administration routs such as oral, hypodermic and intravenous injection. In this study we investigated, experimentally and numerically, in vitro drug delivery of dexamethasone sodium phosphate to porcine skin. Different current densities, delivery durations and drug loads were investigated experimentally and introduced as boundary conditions for numerical simulations. Nernst-Planck equation was used for calculation of active substance flux through equivalent model of homogeneous hydrogel and skin layers. The obtained numerical results were in good agreement with experimental observations. A comprehensive in-silico platform, which includes appropriate numerical tools for fitting, could contribute to iontophoretic drug-delivery devices design and correct dosage and drug clearance profiles as well as to perform much faster in-silico experiments to better determine parameters and performance criteria of iontophoretic drug delivery.


Advancing Health Literacy Among Hispanic Immigrants: The Intersection Between Education and Health.
Health literacy is a priority issue in both medicine and public health, as it refers to the capacity to obtain and understand basic health information and services and to make appropriate health decisions. Health literacy has been associated with a variety of health care and health outcomes such as hospital admissions, use of preventive services, management of chronic conditions, and mortality. There is also evidence of the connection between low health literacy and health disparities. Despite federal and private efforts, improving health literacy has proven to be an enormous challenge. The negative health consequences of low health literacy are being experienced by most minority groups; however, health literacy is particularly relevant to Spanish speakers. Although disparities in health literacy among language minorities have been sufficiently identified and reported, there continue to exist fundamental research gaps. This article discusses health literacy research and practice gaps affecting Spanish speakers and recommends educational opportunities as an effective strategy for improving the health literacy level of Hispanic immigrants.


New experimental evidence about secondary processes in phenylphthalein-dimethylether and 1,1'-bis(p-methoxyphenyl)cyclohexane.
The slow secondary (beta) process of 1,1'-bis (4-methoxyphenyl) cyclohexane and phenolphthalein dimethylether has been investigated by dielectric spectroscopy. New experimental results about the pressure dependence of the two processes are reported, as well as new data about the dependence of the characteristic relaxation frequency on the cooling rate used to vitrify the system in isobaric conditions. Previous investigations on these systems suggested that the first one is not a true Johari-Goldstein relaxation and both processes should originate from the flip flop motion of the phenyl ring. The results herein reported evidence that the characteristic frequency of the beta process of phenolphthalein dimethylether is more sensitive to pressure variation and to the vitrification procedure than that of 1,1'-bis (4-methoxyphenyl) cyclohexane. Such results suggest an intermolecular origin for the secondary process in phenolphthalein dimethylether and an intramolecular origin for the other one, which do not completely agree with the previous interpretation. We evidence that the microscopic mechanism at the basis of these two processes is still an open question, which should be debated on the basis of new experimental investigations.


Efficacy of piperazine dihydrochloride against Ascaris suum and Oesophagostomum species in naturally infected pigs.
A controlled trial was performed to evaluate the efficacy of piperazine dihydrochloride in a new granular formulation (Ascarex D) against naturally occurring infections with Ascaris suum, Oesophagostomum dentatum and O quadrispinulatum. Treatment effects were estimated on the basis of parasites recoverable from the intestinal contents. Given orally at 200 mg per kg body weight the compound showed an efficacy of 99 to 100 per cent against A suum and the nodular worms. Egg excretion of the respective species was reduced by 98 per cent and 100 per cent six days after treatment. No adverse reactions were observed after the treatment.


Dissociable prototype learning systems: evidence from brain imaging and behavior.
The neural underpinnings of prototype learning are not well understood. A major source of confusion is that two versions of the prototype learning task have been used interchangeably in the literature; one where participants learn to categorize exemplars derived from two prototypes (A/B task), and one where participants learn to categorize exemplars derived from one prototype and noncategorical exemplars (A/non-A). We report results from an fMRI study of A/B and A/non-A prototype learning that allows for a direct contrast of the two learning methods. Accuracy in the two tasks did not correlate within subject despite equivalent average difficulty. The fMRI results revealed neural activation in a network of regions consistent with episodic memory retrieval for the A/B task while greater activation of a nondeclarative learning network was observed for the A/non-A task. The results demonstrate that learning in these two tasks is mediated by different neural systems and that recruitment of each system is dictated by the context of learning rather than the actual category structure.


High carbonate level of apatite in kidney stones implies infection, but is it predictive?
The presence of infectious microorganisms in urinary stones is commonly inferred from stone composition, especially by the presence of struvite in a stone. The presence of highly carbonated apatite has also been proposed as a marker of the presence of bacteria within a stone. We retrospectively studied 368 patients who had undergone percutaneous nephrolithotomy (PCNL), and who also had culture results for both stone and urine. Urine culture showed no association with stone mineral content, but stone culture was more often positive in struvite-containing stones (73 % positive) and majority apatite stones (65 %) than in other stone types (54 %, lower than the others, P < 0.02). In 51 patients in whom the carbonate content of apatite could be measured, carbonate in the apatite was weakly predictive of positive stone culture with an optimal cutoff value of 13.5 % carbonate (sensitivity 0.61, specificity 0.80). In positive cultures of stones (all mineral types combined), organisms that characteristically produce urease were present in 71 % of the cases, with no difference in this proportion among different types of stone. In summary, the type of mineral in the stone was predictive of positive stone culture, but this correlation is imperfect, as over half of non-struvite, non-apatite stones were found to harbor culturable organisms. We conclude that mineral type is an inadequate predictor of whether a stone contains infectious organisms, and that stone culture is more likely to provide information useful to the management of patients undergoing PCNL.


Osmotic fragility of leukaemic and normal lymphocytes.
The osmotic fragility of cord blood lymphocytes (CBLs), normal adult lymphocytes (NALs) and leukaemic cells was studied using hypotonic saline. Leukaemic cells were more resistant to hypotonic treatment than cord blood or adult lymphocytes. At low hypotonic saline concentrations (less than 0.2% NaCl), almost all of the NALs and CBLs were lysed after thirty minutes at 4 degrees C, whilst a large proportion of chronic lymphatic leukaemia cells remained intact. This phenomenon could conceivably be used to separate tumour cells from normal lymphoid cells.


Self-assembly of Hyaluronic Acid-Cu-Quercetin flavonoid nanoparticles: synergistic chemotherapy to target tumors.
In this study, a natural compound quercetin (Qu) was investigated for its various antitumor effects. However, due to its poor water solubility and low bioavailability, its clinical application is limited. To overcome this constraint, a modification was to Qu, which resulted in the creation of novel flavonoid self-assembling nanoparticles (HCQ NPs). HCQ NPs were synthesized by a self-assembly method and characterized using transmission electron microscopy, the Malvern Zetasizer instrument, X-ray photoelectron spectroscopy (XPS), the ultraviolet-visible spectrophotometric method (UV-vis), Fourier transform infrared (FITR) and inductively coupled plasma mass spectrometry. Extracellular, methylene blue spectrophotometric analysis was used to determine the ability of HCQ NPs to react with different concentrations of H2O2 to form hydroxyl radicals (•OH). Intracellular, DCFH-DA staining was used to detect the ability of HCQ NPs to react with H2O2 to generate reactive oxygen species. Flow cytometry was used to detect the uptake of HCQ NPs by MDA-MB-231 cells at different time points. The biocompatibility of HCQ NPs was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Calcein AM/PI double staining and the CCK-8 assay were used to evaluate the synergistic antitumor effect of HCQ NPs and H2O2. HCQ NPs showed uniformly sized analogous spherical shapes with a hydrodynamic diameter of 55.36 ± 0.27 nm. XPS revealed that Cu was mainly present as Cu2+ in the HCQ NPs. UV-vis absorption spectrum of the characteristic peak of HCQ NPs was located at 296 nm. Similarly, FTIR spectroscopy revealed a complex formation of Qu and Cu2+ that substantially changed the wavenumber of the 4-position C = O characteristic absorption peak. Based on the proportion of Qu and Cu2+ (1:2), the total drug loading of Qu and Cu2+ in the HCQ NPs for therapeutic purposes was calculated to be 9%. Methylene blue spectrophotometric analysis of •OH indicated that Cu can lead to the generation of •OH by triggering Fenton-like reactions. HCQ NPs rapidly accumulated in MDA-MB-231 cells with the extension of time, and the maximum accumulation concentration was reached at about 0.5 h. Calcein AM/PI double staining and CCK-8 revealed synergistic antitumor effects of HCQ NPs including the chemotherapeutic effect of Qu and chemodynamic therapy by Cu2+ in a simulated tumor microenvironment. HCQ NPs demonstrated very low toxicity in LO2 cells in the biocompatibility experiment. This study show cases a new method of creating self-assembled flavonoid HCQ NPs that show great for fighting cancer.


Nonlinear trajectory of GFR in children before RRT.
GFR decline in patients with CKD has been widely approximated using linear models, but this linearity assumption is not well validated. We conducted a matched case-control study in children from the Chronic Kidney Disease in Children (CKiD) cohort ages 1-16 years with mild to moderate CKD to assess whether GFR decline follows a nonlinear trajectory as CKD approaches ESRD. Children (n=125) who initiated RRT (cases) during follow-up were individually matched by CKD stage at baseline and glomerular/nonglomerular diagnosis with children (n=125) who remained RRT-free when the corresponding case initiated RRT (controls). GFR trajectories were compared using log-linear and piecewise log-linear mixed effects models adjusted for baseline characteristics. From study entry to 18 months before RRT, GFR declined 7% faster among cases compared with controls. However, GFR declined 26% faster among cases compared with controls (P<0.001) during the 18 months before RRT. Nonlinearity in the rate of kidney function loss, which was shown in this cohort, may preclude accurate clinical prediction of the timing of RRT and adequate patient preparation. This study should prompt the characterization of predictive factors that may contribute to an acceleration of kidney function decline.


Structural analysis of the molecular evolution of some gastro-entero-pancreatic hormones.
By means of a statistical analysis of the occurrence of amino-acid residues in the polypeptide chains of several gastro-entero-pancreatic (GEP) hormones an investigation was undertaken to determine whether any of these hormones might be related to each other--possibly from an evolutionary point of view. Particular interest was paid to the occurrence of small charged segments, i.e. those with acidic or basic amino acid residues, since such segments can be presumed to play a role in hormonal receptor binding mechanisms. By this method hormonal relationships were suggested by the observation that these small charged amino-acid sequences, contained in the hormonal structures, match as a result of non-randomness. It was found that hagfish and human insulin were related on a molecular level not only to the newly discovered (avian, bovine, human) pancreatic polypeptide (PP) but also to some other GEP hormones (VIP, GIP, glucagon) as well as to calcitonin and to the alpha-subunit of the glycoprotein hormones. Interpretation of the statistical data suggests that all these peptide hormones are related by a common hexapeptide sequence which contributed, at an evolutionary point, to their molecular architecture. A hexapeptide segment of APP is statistically related to a sequence of equal size in the carboxy terminal region of the A-chain of both hagfish and human insulin, providing the first instance of their structural similarity. Correlations between PP, insulin, glucagon, VIP, and calcitonin provide a tentative basis for predicting the production of one or more of these peptide hormones by immature or de-differentiated cells of neoplasms and non-neoplastic pathologic lesions of the GEP endocrine system.


ALLocator: an interactive web platform for the analysis of metabolomic LC-ESI-MS datasets, enabling semi-automated, user-revised compound annotation and mass isotopomer ratio analysis.
Adduct formation, fragmentation events and matrix effects impose special challenges to the identification and quantitation of metabolites in LC-ESI-MS datasets. An important step in compound identification is the deconvolution of mass signals. During this processing step, peaks representing adducts, fragments, and isotopologues of the same analyte are allocated to a distinct group, in order to separate peaks from coeluting compounds. From these peak groups, neutral masses and pseudo spectra are derived and used for metabolite identification via mass decomposition and database matching. Quantitation of metabolites is hampered by matrix effects and nonlinear responses in LC-ESI-MS measurements. A common approach to correct for these effects is the addition of a U-13C-labeled internal standard and the calculation of mass isotopomer ratios for each metabolite. Here we present a new web-platform for the analysis of LC-ESI-MS experiments. ALLocator covers the workflow from raw data processing to metabolite identification and mass isotopomer ratio analysis. The integrated processing pipeline for spectra deconvolution "ALLocatorSD" generates pseudo spectra and automatically identifies peaks emerging from the U-13C-labeled internal standard. Information from the latter improves mass decomposition and annotation of neutral losses. ALLocator provides an interactive and dynamic interface to explore and enhance the results in depth. Pseudo spectra of identified metabolites can be stored in user- and method-specific reference lists that can be applied on succeeding datasets. The potential of the software is exemplified in an experiment, in which abundance fold-changes of metabolites of the l-arginine biosynthesis in C. glutamicum type strain ATCC 13032 and l-arginine producing strain ATCC 21831 are compared. Furthermore, the capability for detection and annotation of uncommon large neutral losses is shown by the identification of (γ-)glutamyl dipeptides in the same strains. ALLocator is available online at: https://allocator.cebitec.uni-bielefeld.de. A login is required, but freely available.


Artificial neural network for the classification of nanoparticles shape distributions.
A new methodology, to the best of our knowledge, is developed to determine the shape distribution profile of gold nanoparticles (NPs) from optical spectroscopic measurements. Indeed, an artificial neural network (ANN) approach was introduced to classify Au NP shape distributions from their normalized absorption spectra. This ANN quantitatively analyzes the absorption spectra and provides the posterior probability to have a bimodal or unimodal shape distribution. Several colloidal suspensions were considered to investigate the robustness of the ANN approach. The comparison between ANN classification and TEM analysis was also given and discussed. We demonstrate that ANN classification is a suitable tool to inspect rapidly Au colloidal suspensions after their synthesis.


Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX.
In mammalian cells, DNA double-strand breaks (DSBs) cause rapid phosphorylation of the H2AX core histone variant (to form gamma-H2AX) in megabase chromatin domains flanking sites of DNA damage. To investigate the role of H2AX in mammalian cells, we generated H2AX-deficient (H2AX(Delta)/Delta) mouse embryonic stem (ES) cells. H2AX(Delta)/Delta ES cells are viable. However, they are highly sensitive to ionizing radiation (IR) and exhibit elevated levels of spontaneous and IR-induced genomic instability. Notably, H2AX is not required for NHEJ per se because H2AX(Delta)/Delta ES cells support normal levels and fidelity of V(D)J recombination in transient assays and also support lymphocyte development in vivo. However, H2AX(Delta)/Delta ES cells exhibit altered IR-induced BRCA1 focus formation. Our findings indicate that H2AX function is essential for mammalian DNA repair and genomic stability.


Chart Mining: A Survey of Methods for Automated Chart Analysis.
Charts are useful communication tools for the presentation of data in a visually appealing format that facilitates comprehension. There have been many studies dedicated to chart mining, which refers to the process of automatic detection, extraction and analysis of charts to reproduce the tabular data that was originally used to create them. By allowing access to data which might not be available in other formats, chart mining facilitates the creation of many downstream applications. This paper presents a comprehensive survey of approaches across all components of the automated chart mining pipeline, such as (i) automated extraction of charts from documents; (ii) processing of multi-panel charts; (iii) automatic image classifiers to collect chart images at scale; (iv) automated extraction of data from each chart image, for popular chart types as well as selected specialized classes; (v) applications of chart mining; and (vi) datasets for training and evaluation, and the methods that were used to build them. Finally, we summarize the main trends found in the literature and provide pointers to areas for further research in chart mining.


Intramuscular Tranexamic Acid Administration on the Battlefield.
Tranexamic acid (TXA) is routinely administered intravenously (IV) and intraosseously (IO) in response to exsanguination. This report describes a patient who sustained multiple high-powered rifle gunshot wounds that received battlefield-environment intramuscular (IM) administration of TXA due to inability to obtain IV / IO access. This case represents the unlikely positive outcome in the setting of multiple remarkable obstacles, which may have been ameliorated by novel administration of TXA. Cases of IM TXA administration as a primary intervention are not well represented in the current body of medical literature. This case report highlights a clinical scenario where IM TXA was utilized as part of first-line treatment that led to a positive clinical outcome. Although IM TXA is not yet endorsed by current trauma guidelines, this case suggests that IM route administration of TXA should be further investigated. If indeed IM administration of TXA proves just as efficacious as alternative routes, this would hold considerable advantageous implications for austere situations were sterility and IV / IO placement are impractical. This would also represent another avenue by which to decrease the time-to-TXA for patients, allowing sooner correction of hemorrhage and trauma-associated coagulopathy.


Creating reverse flow arteriovenous fistulas with a forearm cannulation target.
Establishing a forearm arteriovenous fistula (AVF) offers preferred cannulation sites and preserves proximal access opportunities. When a radiocephalic AVF at the wrist is not feasible and the upper arm cephalic and median cubital veins are inadequate, an AV graft or more complex access procedure is often required. Creating a retrograde flow forearm AVF (RF-AVF) is a valuable alternative where the mid-forearm median antebrachial or cephalic vein is adequate, offering forearm cannulation zones with AVF outflow through deep and superficial collaterals. We report our technique and results. We retrospectively reviewed our vascular access data base of consecutive patients during an 11-year study period where a RF-AVF established the only available cannulation target in the forearm. In addition to physical examination, all patients had ultrasound vessel mapping. A forearm access was established with a RF-AVF as the only opportunity for cannulation in 48 patients. Ages were 14-86 years (median = 62 years). Forty-four percent female, 63% diabetic, 13% obese, and 29% had previous access operations. Inflow was proximal radial artery in 47 individuals and one proximal ulnar. Nine AVFs (19%) failed at 2-66 months (median 14 months). One RF-AVF was ligated due to arm edema. Follow-up was 2-111 months (median = 23.5 months). Primary and cumulative patency rates were 62% and 91% at 12 months, and 46% and 85% at 24 months. Five patients were lost to follow-up with functioning RF-AVFs (mean 41 months). Twenty-three patients (48%) died during F/U of causes unrelated to access procedures (mean 25 months). Establishing a reverse flow forearm AVF offers a successful autogenous access option in the forearm for selected patients with an inadequate distal radial artery and/or cephalic vein at the wrist, avoiding more complex or staged procedures and preserving upper arm sites for future use. A proximal radial artery inflow procedure is recommended.


Electrolyte metabolic changes in rats during and after exposure to hypokinesia.
The objective of this study was to determine fluid-electrolyte changes in male Wistar rats during 90 days of hypokinesia (decreased motor activity) and 15 days posthypokinesia. The animals were divided into two groups: rats subjected to hypokinesia served as experimental animals and rats placed under vivarium conditions served as control animals. The hypokinetic effect was carried out by keeping the experimental rats in small individual cages which restricted all their movements without hindering food and water intake. Determination was made of body weight, fluid consumed and eliminated in urine, sodium and potassium excretion in urine, concentrations of sodium and potassium in urine, the hematocrit level and water content in blood, and plasma concentration of sodium and potassium. During the experimental period body weight, water intake, urinary sodium and potassium content, and water content in blood decreased significantly, while electrolyte excretion in urine, plasma electrolyte concentration, hematocrit content and fluid excretion in urine increased significantly in the hypokinetic animals when compared with the control animals. During the initial seven days of the postexperimental period, water intake increased significantly while hematocrit level, water content in blood, and electrolyte plasma concentration remained markedly higher, and the fluid electrolyte excretion and electrolyte concentration thereof in urine decreased significantly. However, all these changes reverted back to the control level by the end of the post-experimental period. It was concluded that prolonged hypokinesia (HK) and the initial stages of post hypokinesia are associated with significant sodium and potassium changes and water consumption and elimination disturbances.


Towards atomic site-selective sensitivity in tip-enhanced Raman spectroscopy.
Depending on each nitrogen atom of adenine molecule to which a silver atom of a metallic tip approaches, tip-enhanced near-field Raman spectroscopy may show a potential to achieve atomic site-selective detection sensitivity. Molecular vibrational calculations show that silver atoms and adenine molecule create several isomers generating specific vibrational modes of each isomer that are shifted or not observable in isolated adenine molecule itself. Here, the authors observe the specific vibrational modes and spectral shifts of isomers experimentally and are in good agreement with their calculations.


Preferences of women in difficult life situations for a physical activity programme: protocol of a discrete choice experiment in the German NU-BIG project.
The BIG project ('Bewegung als Investition in die Gesundheit', ie, 'Movement as Investment in Health') was developed in 2005 as a community-based participatory research programme to offer accessible opportunities for physical activity to women in difficult life situations. Since then, the programme has been expanded to eight sites in Germany. A systematic evaluation of BIG is currently being conducted. As part of this effort, we strive to understand the preferences of participating women for different aspects of the programme, and to analyse their willingness to pay. In this protocol, we describe the development and analysis plan of a discrete choice experiment (DCE) to investigate participants' preferences for a physical activity programme for women in difficult life situations. The experiment will be embedded in a questionnaire covering several aspects of participation in the programme (eg, reach, efficacy and further effects) and the socioeconomic characteristics of all active participants. After a thorough search of the literature, BIG documents review and expert interviews, we identified five important attributes of the programme: course times, travel time to the course venue, additional social activities organised by BIG, consideration of wishes and interests for the further planning of courses and costs per course unit. Thereafter, we piloted the experiment with a sample of participants from the target group. After data collection, the experiment will be analysed using a conditional logit model and a latent class analysis to assess eventual heterogeneity in preferences. Understanding women's preferences will provide useful insights for the further development of the programme and ultimately increase participation and retention. The questionnaire, the included DCE and the pretest on participants received ethical approval (application no. 20-247_1-B). We plan to disseminate the results of the DCE in peer-reviewed journals, national conferences and among participants and programme coordinators and organisers.


Inhibition of SGK1 enhances mAR-induced apoptosis in MCF-7 breast cancer cells.
Functional membrane androgen receptors (mAR) have previously been described in MCF-7 breast cancer cells. Their stimulation by specific testosterone albumin conjugates (TAC) activate rapidly non-genomic FAK/PI3K/Rac1/Cdc42 signaling, trigger actin reorganization and inhibit cell motility. PI3K stimulates serum and glucocorticoid inducible kinase SGK1, which in turn regulates the function of mAR. In the present study we addressed the role of SGK1 in mAR-induced apoptosis. TAC-stimulated mAR activation elicited apoptosis of MCF-7 cells, an effect significantly potentiated by concomitant incubation of the cells with TAC and the specific SGK1 inhibitors EMD638683 and GSK650394. In line with this, TAC and EMD638683 activated caspase-3. These effects were insensitive to the classical androgen receptor (iAR) antagonist flutamide, pointing to iAR-independent, mAR-induced responses. mAR activation and SGK1 inhibition further considerably augmented the radiation-induced apoptosis of MCF-7 cells. Moreover, TAC- and EMD638683 triggered early actin polymerization in MCF-7 cells. Blocking actin restructuring with cytochalasin B abrogated the TAC- and EMD638683-induced pro-apoptotic responses. Further analysis of the molecular signaling revealed late de-phosphorylation of FAK and Akt. Our results demonstrate that mAR activation triggers pro-apoptotic responses in breast tumor cells, an effect significantly enhanced by SGK1 inhibition, involving actin reorganization and paralleled by down-regulation of FAK/Akt signaling.


Monitoring transfected cells without selection agents by using the dual-cassette expression EGFP vectors.
Conventional methods of selecting gene transfected cells by toxic agents may yield ambiguous results. It is difficult to determine whether cell death is due to selection agents or gene transfection, owing to the substantial overlap of the time-courses for both effects. Therefore, to determine transfection-induced cell toxicity, the mammalian expression vector pEGFP-N1 (CLONTECH Lab., Palo Alto, CA, USA) has been modified to the dual-cassette expression vectors named pEGFP-Ks by the relocation of its EGFP expression cassette. We have precisely monitored the cells transfected with this vector on our custom culture dishes, thereby bypassing the need for selection agent or fluorescent cell sorting. This is a useful method to screen genes encoding potential toxic or useful proteins without performing undesirable selection agent and also can be used to monitor the transfected cells for various purposes, either the inhibition or proliferation of mammalian cells for applications in biotechnology.


Effect of head position on postoperative chemosis after prone spinal surgery.
Conjunctival swelling is a common finding in patients positioned prone. The purpose of this study was to evaluate the effect of head position on postoperative chemosis after prone spinal surgery. On the basis of the head position, 108 patients scheduled for prone lumbar surgery were randomly allocated to 1 of 2 groups: head neutral group (n=54) versus head down (HD) group (n=54). Head position was defined as neutral when the imaginary line from the occipital protuberance to the top of C7 spine process is parallel to the operating table. HD position was maintained by adjusting the height of the prone headrest 5 cm lower than neutral position. Chemosis was evaluated after surgery. The severity of chemosis, which was graded as none, mild, moderate, and severe, showed statistically significant difference between the head neutral group [24 (44%), 25 (46%), 3 (6%), 2 (4%), respectively] and HD group [10 (19%), 23 (43%), 17 (31%), 4 (7%), respectively, P<0.01]. Positive fluid balance and duration of surgery were risk factors for the development of postoperative chemosis. This result suggested that neutral head position, smaller fluid administration, and shorter duration of surgery were useful in decreasing the development of postoperative chemosis after prone spinal surgery.


V804M RET mutation and familial medullary thyroid carcinoma: report of a large family with expression of the disease only in the homozygous gene carriers.
Only 9 families with familial medullary thyroid carcinoma due to V804M mutation have been reported until now. We describe a large kindred with not only heterozygous but also homozygous members with the V804M mutation. This is, to our knowledge, the first report of a homozygous RET mutation. Fifty-three members from 4 successive generations of a family with a high level of consanguinity underwent genetic analysis. The pentagastrin provocative test and biochemical screening to rule out either hyperparathyroidism or pheochromocytoma were performed only on gene carriers of the mutation. Twenty-six gene carriers for V804M mutation were identified (4 homozygous and 22 heterozygous). Three of 4 homozygous patients underwent total thyroidectomy. In 1 patient neither medullary thyroid carcinoma nor C-cell hyperplasia was detected, and in another patient only 3 small foci of C-cell hyperplasia were found on the histologic examination. The pentagastrin stimulation test result was within the normal range in all the heterozygous gene carriers and, consequently, thyroidectomy was not indicated. The screening for both hyperparathyroidism and pheochromocytoma was negative in all patients. In the family reported, the V804M mutation in heterozygous patients seems not to be enough to express the full disease. This finding strongly supports the concept of the indolent behavior of V804M RET proto-oncogene mutation. In addition, our results suggest that when counseling for preventive total thyroidectomy, the specific mutation of RET proto-oncogene and also the natural history of the disease within a particular family should be considered.


The Essential Role of Tick Salivary Glands and Saliva in Tick Feeding and Pathogen Transmission.
As long-term pool feeders, ticks have developed myriad strategies to remain discreetly but solidly attached to their hosts for the duration of their blood meal. The critical biological material that dampens host defenses and facilitates the flow of blood-thus assuring adequate feeding-is tick saliva. Saliva exhibits cytolytic, vasodilator, anticoagulant, anti-inflammatory, and immunosuppressive activity. This essential fluid is secreted by the salivary glands, which also mediate several other biological functions, including secretion of cement and hygroscopic components, as well as the watery component of blood as regards hard ticks. When salivary glands are invaded by tick-borne pathogens, pathogens may be transmitted via saliva, which is injected alternately with blood uptake during the tick bite. Both salivary glands and saliva thus play a key role in transmission of pathogenic microorganisms to vertebrate hosts. During their long co-evolution with ticks and vertebrate hosts, microorganisms have indeed developed various strategies to exploit tick salivary molecules to ensure both acquisition by ticks and transmission, local infection and systemic dissemination within the vertebrate host.


An optimization design proposal of automated guided vehicles for mixed type transportation in hospital environments.
The aim of this paper is to present an optimization proposal in the automated guided vehicles design used in hospital logistics, as well as to analyze the impact of its implementation in a real environment. This proposal is based on the design of those elements that would allow the vehicles to deliver an extra cart by the towing method. So, the proposal intention is to improve the productivity and the performance of the current vehicles by using a transportation method of combined carts. The study has been developed following concurrent engineering premises from three different viewpoints. First, the sequence of operations has been described, and second, a proposal of design of the equipment has been undertaken. Finally, the impact of the proposal has been analyzed according to real data from the Hospital Universitario Rio Hortega in Valladolid (Spain). In this particular case, by the implementation of the analyzed proposal in the hospital a reduction of over 35% of the current time of use can be achieved. This result may allow adding new tasks to the vehicles, and according to this, both a new kind of vehicle and a specific module can be developed in order to get a better performance.


A novel role for farnesyl pyrophosphate synthase in fibroblast growth factor-mediated signal transduction.
Farnesyl pyrophosphate synthase (FPPS) catalyses the formation of a key cellular intermediate in isoprenoid metabolic pathways. Here we describe a novel role for this enzyme in fibroblast growth factor (FGF)-mediated signalling. We demonstrate the binding of FPPS to FGF receptors (FGFRs) using the yeast two-hybrid assay, pull-down assays and co-immunoprecipitation. The interaction between FPPS and FGFR is regulated by the cellular metabolic state and by treatment with FGF-2. Overexpression of FPPS inhibits FGF-2-induced cell proliferation, accompanied by a failure of the FGF-2-mediated induction of cyclins D1 and E. Overexpression of FPPS in fibroblasts also promotes increased farnesylation of Ras, and temporally extends FGF-2-stimulated activation of the Ras/ERK (extracellular-signal-regulated kinase) cascade. These data suggest that, in addition to its role in isoprenoid biosynthesis, FPPS may function as a modulator of the cellular response to FGF treatment.


[A case of non-Hodgkin lymphoma with complete remission achieved by carboplatin].
The patient was a 63-year-old female, who was admitted to the National Nagoya Hospital with complaints of left cervical and bilateral axillary lymphadenopathy on 12 May, 1987. Since May 1985, with the diagnosis of non-Hodgkin lymphoma, she had been successfully treated with combination chemotherapy (VEPA) and radiotherapy at another hospital. Left axillary lymphode biopsy revealed a diagnosis of non-Hodgkin lymphoma, diffuse large cell type. Then, she was given intravenous administration of carboplatin (400 mg/body) on 26 May, 1987. After a single course of this regimen, the lymphnode swelling subsided, and she achieved complete remission on 6 June. Thereafter, she was placed on the maintenance chemotherapy of carboplatin (400 mg/body) every 5 weeks. Through the whole course of this patient, the serum levels of blood urea nitrogen and creatinine were normal, and she did not notice nausea, vomiting and peripheral neuropathy. To our knowledge, this is the first report of complete response by the administration of carboplatin for non-Hodgkin lymphoma.


Popliteal artery war injuries.
The early postoperative results of 44 surgically treated popliteal arterial injuries from the Yugoslav civil war are reported. Of these patients, 41 (93%) were males and three (7%) were females, average age was 28 (range 6-45) years. Twenty patients (45%) had gunshot wounds and 24 (55%) explosive wounds. Twelve (28%) suffered isolated vascular damage, while 32 (72%) suffered concomitant bone fractures. Isolated arterial lesions were found in 24 (55%) cases, and concomitant arterial and venous lesions in 20 (45%). Twenty-four (55%) had primary reconstructions after haemostasis in the initial war hospital, and 20 (45%) secondary reconstructions after inadequate primary reconstruction in a regional war hospital. Artery procedures included 19 reverse saphenous vein graft interpositions, 10 reverse saphenous vein bypasses, 12 'in situ' saphenous vein bypasses and five lateral subcutaneous saphenous vein bypasses. The early graft patency rate was 100%, and limb salvage 72%. Major amputation was performed in 28%. Concomitant bone fractures, secondary reconstructions, secondary haemorrhage from an infected graft, and explosion wounds significantly increased the amputation rate (P < 0.01). Eleven amputations were performed after an anatomic, and only one after an extra-anatomic reconstruction (P < 0.01). The authors recommend an in situ or lateral subcutaneous reconstruction in cases of complicated popliteal artery injuries, such as concomitant bone fractures accompanied by massive soft tissue damage, and this type of reconstruction should also be used if infection is present or the procedure is delayed.


Gemcitabine-induced severe peripheral edema in a patient with lung cancer.
Gemcitabine, alone or in combination with a platinum-based agent, is indicated for the first-line treatment of patients with locally advanced or metastatic non-small-cell lung cancer. It is generally a well-tolerated drug. Despite its lack of significant toxicity, the most commonly reported side effects include myelosuppression, gastrointestinal disturbances (eg, nausea and vomiting), influenza-like symptoms, skin rash with pruritus, and elevation of liver transaminase enzymes. Peripheral edema has rarely been described as an adverse effect. Herein, we report a patient with advanced non-small-cell lung cancer who experienced severe peripheral edema after gemcitabine administration. Immediate gemcitabine discontinuation and the administration of diuretics resulted in definite regression of peripheral edema.


Age at puberty in relation to age at marriage and parenthood: a national longitudinal study.
A longitudinal study of a British cohort has collected information on puberty, judged by menarcheal age for the girls and the pubertal stage of the boys at age 14 3/4. This information has now been related to the ages at which these young people married and became parents. For the young men there was evidence of a direct relationship between degree of sexual maturity at age 14 3/4 and their ages at entry into marriage and fatherhood. For the young women, if pregnancy did not intervene between menarche and marriage, there was evidence of a direct relationship between menarcheal age and marriage age. But there was no evidence that these earlier-maturing young women became mothers at earlier ages than later maturers. This arose through the later-maturing young women having shorter first birth intervals than the earlier maturers. Premarital conceptions were also more prevalent amongst the later maturers.


Human-like maternal left-cradling bias in monkeys is altered by social pressure.
About 66-72% of human mothers cradle their infants on their left side. Given that left-cradling exposes the baby's face to the mother's left visual field (i.e., mainly projected to her right hemisphere) and is altered by emotional states such as stress, maternal left-cradling was interpreted as reflecting right-hemispheric dominance for emotional processing. Whether this phenomenon is unique to human evolution is still in debate. In the present study we followed 44 olive baboon (Papio anubis) mothers and their infants in different social groups. We found that a maternal cradling bias exists and is predominantly towards the left in a similar proportion as in humans, but shifts toward a right bias in mothers living in high density groups. The sensitivity of left-cradling to social pressure highlights its potential links with the mother's stress as reported in humans. Our finding clearly illustrates the phylogenetic continuity between humans and Old-World monkeys concerning this lateralization and its potential links with hemispheric specialization for emotions, inherited from a common ancestor 25-35 million years ago.


Leprosy - one of the many forgotten tropical diseases.
Leprosy or Hansen disease is caused by an infection of Mycobacterium leprae. The large number of undetected cases (2000-2012 years 4 mln people) remains a threat to the elimination of leprosy. Leprosy is an unheard in Poland and generally is considered a condition so "exotic" that it is not worth to spend more attention to it. Forgotten disease in developed countries still thrives in an environment of poor and uneducated. Regardless of the conclusion that in the 21st century none infectious disease should not be treated as a disease on the designated regions of the world, other than our own, it should be recalled that the M. leprae was discovered in Europe, where for many years there were leprosaria and still infectious hospitals in Great Brittan, France or Spain get patients suspected of leprosy. The mobility of the inhabitants of the globe caused by wars, ethnic conflicts or a simple tourism causes that any infectious disease can not be treated as solely limited to distant us regions. The best proof of this were the viral diseases, formerly found in only in Asia or Africa, and currently transmitted to Europe [1]. At any moment, we can stand up against the problem of diagnostics of humans toward leprosy. Many medical reports indicate that leprosy as a disease with many symptoms encountered difficulties in its diagnosis. Only the experience of medical professionals and good microbiological diagnosis may speed up the diagnosis of leprosy.


A rare mutation in UNC5C predisposes to late-onset Alzheimer's disease and increases neuronal cell death.
We have identified a rare coding mutation, T835M (rs137875858), in the UNC5C netrin receptor gene that segregated with disease in an autosomal dominant pattern in two families enriched for late-onset Alzheimer's disease and that was associated with disease across four large case-control cohorts (odds ratio = 2.15, Pmeta = 0.0095). T835M alters a conserved residue in the hinge region of UNC5C, and in vitro studies demonstrate that this mutation leads to increased cell death in human HEK293T cells and in rodent neurons. Furthermore, neurons expressing T835M UNC5C are more susceptible to cell death from multiple neurotoxic stimuli, including β-amyloid (Aβ), glutamate and staurosporine. On the basis of these data and the enriched hippocampal expression of UNC5C in the adult nervous system, we propose that one possible mechanism in which T835M UNC5C contributes to the risk of Alzheimer's disease is by increasing susceptibility to neuronal cell death, particularly in vulnerable regions of the Alzheimer's disease brain.


No Mental Health without Oral Health.
The poor physical health faced by people with mental illness has been the subject of growing attention, but there has been less focus on the issue of oral health even though it is an important part of physical health. This article discusses the two-way association between oral and mental health. In one direction, the prospect of dental treatment can lead to anxiety and phobia. In the other, many psychiatric disorders, such as severe mental illness, affective disorders, and eating disorders, are associated with dental disease: These include erosion, caries, and periodontitis. Left untreated, dental diseases can lead to teeth loss such that people with severe mental illness have 2.7 times the likelihood of losing all their teeth, compared with the general population. Possible interventions include oral health assessments using standard checklists that can be completed by nondental personnel, help with oral hygiene, management of iatrogenic dry mouth, and early dental referral.


Functional characterization of Sporothrix schenckii glycosidases involved in the N-linked glycosylation pathway.
Protein glycosylation pathways are conserved metabolic processes in eukaryotic organisms and are required for cell fitness. In fungal pathogens, the N-linked glycosylation pathway is indispensable for proper cell wall composition and virulence. In Sporothrix schenckii sensu stricto, the causative agent of sporotrichosis, little is known about this glycosylation pathway. Here, using a genome-wide screening for putative members of the glycosyl hydrolase (CAZy - GH) families 47 and 63, which group enzymes involved in the processing step during N-linked glycan maturation, we found seven homologue genes belonging to family 47 and one to family 63. The eight genes were individually expressed in C. albicans null mutants lacking either MNS1 (for members of family 47) or CWH41 (for the member of family 63). Our results indicate that SsCWH41 is the functional ortholog of CaCWH41, whereas SsMNS1 is the functional ortholog of CaMNS1. The remaining genes of family 47 encode Golgi mannosidases and endoplasmic reticulum degradation-enhancing alpha-mannosidase-like proteins (EDEMs). Since these GH families gather proteins used as target for drugs to control cell growth, identification of these genes could help in the design of antifungals that could be used to treat sporotrichosis and other fungal diseases. In addition, to our knowledge, we are the first to report that Golgi mannosidases and EDEMs are expressed and characterized in yeast cells.


What is the most relevant standard of success in assisted reproduction? Singleton live births should also include preterm births.
An intensive debate is ongoing in this journal concerning the most appropriate endpoint after assisted reproduction techniques. The endpoint suggested by the first authors was Birth Emphasizing a Successful Singleton at Term (BESST). We have evaluated the most appropriate endpoint from different perspectives: patients, public, health authorities, obstetric and IVF clinics. We find singleton live birth highly relevant as an outcome parameter as multiple pregnancies are the main factor responsible for the overall poorer obstetric and neonatal outcome in IVF pregnancies, and multiple pregnancies are mostly an avoidable iatrogenic complication. However, our proposal is that both preterm and term singletons should be included since the prematurity rate is an outcome that is largely uninfluenced by the IVF clinics. In conclusion, we propose singleton live birth per cycle initiated as the most appropriate main outcome after assisted reproduction. Prematurity should in addition be reported separately as a secondary outcome.


Experimental hemosiderosis: relationship between skin pigmentation and hemosiderin.
Iron (totalling 7.5 mg per mouse in three doses) was injected into hairless mice to determine the relationship between skin pigmentation and hemosiderin deposition. The skin color reached its maximum 24 to 48 hours after the last injection and then gradually faded over the subsequent 8 months. In the skin, hemosiderin granules were present extracellularly between collagen bundles as well as within dermal macrophages, Langerhans cells and indeterminate dendritic cells of the epidermis. A larger amount of iron was deposited in the facial than in the dorsal skin, resulting in darker pigmentation of the former. This study suggests that brownish discoloration of skin in hemochromatosis might be attributable in some degree to accumulation of hemosiderin and that pronounced hyperpigmentation of the face in hemochromatosis might be due to increased activation of melanocytes by a high content of hemosiderin.


A promiscuous split intein with expanded protein engineering applications.
The protein trans-splicing (PTS) activity of naturally split inteins has found widespread use in chemical biology and biotechnology. However, currently used naturally split inteins suffer from an "extein dependence," whereby residues surrounding the splice junction strongly affect splicing efficiency, limiting the general applicability of many PTS-based methods. To address this, we describe a mechanism-guided protein engineering approach that imbues ultrafast DnaE split inteins with minimal extein dependence. The resulting "promiscuous" inteins are shown to be superior reagents for protein cyclization and protein semisynthesis, with the latter illustrated through the modification of native cellular chromatin. The promiscuous inteins reported here thus improve the applicability of existing PTS methods and should enable future efforts to engineer promiscuity into other naturally split inteins.


Chondrogenesis mediates progression of ankylosing spondylitis through heterotopic ossification.
Ankylosing spondylitis (AS) is chronic inflammatory arthritis with a progressive fusion of axial joints. Anti-inflammatory treatments such as anti-TNF-α antibody therapy suppress inflammation but do not effectively halt the progression of spine fusion in AS patients. Here we report that the autoimmune inflammation of AS generates a microenvironment that promotes chondrogenesis in spine ligaments as the process of spine fusion. Chondrocyte differentiation was observed in the ligaments of patients with early-stage AS, and cartilage formation was followed by calcification. Moreover, a large number of giant osteoclasts were found in the inflammatory environment of ligaments and on bony surfaces of calcified cartilage. Resorption activity by these giant osteoclasts generated marrow with high levels of active TGF-β, which induced new bone formation in the ligaments. Notably, no Osterix+ osteoprogenitors were found in osteoclast resorption areas, indicating uncoupled bone resorption and formation. Even at the late and maturation stages, the uncoupled osteoclast resorption in bony interspinous ligament activates TGF-β to induce the progression of ossification in AS patients. Osteoclast resorption of calcified cartilage-initiated ossification in the progression of AS is a similar pathologic process of acquired heterotopic ossification (HO). Our finding of cartilage formation in the ligaments of AS patients revealed that the pathogenesis of spinal fusion is a process of HO and explained why anti-inflammatory treatments do not slow ankylosing once there is new bone formation in spinal soft tissues. Thus, inhibition of HO formation, such as osteoclast activity, cartilage formation, or TGF-β activity could be a potential therapy for AS.


[Water decontamination in the swimming pools: standardization and practice].
Practical examples were used to analyze possible ways and regimens of water decontamination with chlorine and ozone in the swimming pools when oxidants substantially interacted with the mineral and albuminoid ammonias that were present in the water. Ozone water decontamination was shown to be more effective than water chlorination and to rule out the generation of chloramines that were responsible for their strong irritating activity. Redox potential measurement used as an auxiliary method substantially alleviates on-line technological monitoring of the efficiency of water decontamination at the critical control point during chlorination and, during ozonation, makes up the existing gap of the current SanPiN 184.108.40.2068-03.


Brief interventions for hazardous and harmful alcohol consumption in accident and emergency departments.
The prevalence of alcohol abuse among patients treated in accident and emergency departments (A&E) is considered as substantial. This paper is a narrative review of studies investigating the effectiveness of brief interventions (BI) for hazardous and harmful alcohol consumption in A&E. A&E departments in hospitals (and other health care infrastructures) are commonly the place where serious consequences of alcohol drinking are seen and need to be tackled, supporting the suggested theoretical usefulness of delivering BI in this environment. Available research shows that BI may be considered a valuable technique for dealing with alcohol-related problems. However, it is suggested that the usefulness of BI may depend significantly on the target population to be dealt with. BI have proved to be beneficial for male individuals and those patients who do not abuse other psychoactive substances. In contrast, evidence indicates that BI in A&E settings are not effective at all when dealing with men admitted as a consequence of a violence-related event. In addition, some studies were unable to confirm the effectiveness of BI in female population, in emergency setting. Studies investigating the association between drinking patterns and the effectiveness of BI also present inconsistent results. Most studies assessing the effectiveness of BI in A&E settings only adopted a short perspective (looking at the impact up to a maximum of 12 months after the BI was delivered). When assessing the effects of BI, both the amount of alcohol consumed and expected reductions in alcohol consequences, such as injuries, can be taken into account. Evidence on the implementation of brief intervention in emergency departments remains inconclusive as to whether there are clear benefits. A variety of outcome measures and assessing procedures were used in the different studies, which have investigated this topic.


[Laparoscopic unilateral retroperitoneal lymphadenectomy in non-seminomatous neoplasms of the testis in clinical stage I].
Since June 1993, unilateral laparoscopic retroperitoneal lymph node dissection (LRPLND) was performed in 6 patients diagnosed with clinical stage I nonseminomatous germ cell tumors (NSGCT). All of the patients had undergone prior radical orchiectomy. The testicular cancer was left-sided in three cases and right-sided in three cases. Preoperative staging by means of tumor markers assessment, computerized tomography scan (CT) of the chest and abdomen and chest X-ray was unremarkable for metastatic disease. All procedures were accomplished without any complications in a mean time of 325 min (275 to 420 min). The estimated peri- and postoperative blood loss was minimal. Of note, the comparison between the hematocrit and hemoglobin decrease of LRPLND and RPLND showed a statistically significant reduction (3.1 vs 11.1% P < 0.01 and 1.1 vs 3.2 g/dl P < 0.01). None of the patients required blood transfusion. In the case of the first patient the hospital stay was 18 days due to a widespread subcutaneous emphysema. In the remaining five cases the average hospitalization was 4.8 days ranging between 4 and 6 days. The patients resumed normal activities within 12 to 27 days (mean 16.2 days) postoperatively. Mean number of lymph nodes removed was 6.8, ranging between 5 and 9. Histologic examination of the dissected lymph nodes revealed microscopic metastases from embryonal carcinoma in two patients. Both of these patients were subject to adjuvant chemotherapy. The mean follow-up period is 33.3 months, ranging between 18 and 48 months. To date, no relapses have been observed. In accordance with other reports, we believe that LRPLND is both feasible and effective. However, larger and more comprehensive studies with long-term follow-up are required to determine whether this approach is reliable and definitely superior to standard open surgery in the management of clinical stage I NSGCT.


Onset of synchronization in systems of globally coupled chaotic maps.
We study the transition to coherence of an ensemble of globally coupled chaotic maps allowing for ensembles of nonidentical maps and for noise. The transition coupling strength is determined from a kind of transfer function of the perturbation evolution. We present analytical results, and we test these results using numerical experiments for several large systems consisting of ensembles of many coupled maps. The later includes ensembles of identical noiseless maps, identical maps subject to noise, and ensembles of nonidentical maps. One of our examples suggests that the validity of the perturbation theory approach can be problematic for an ensemble of noiseless identical maps if the maps are nonhyperbolic. However, for such a case, noise and/or parameter spread seems to have a regularizing effect restoring the validity of perturbation theory.


New techniques in diagnosis, assessment of progression and research in muscular dystrophy.
A number of imaging techniques has been used in Duchenne muscular dystrophy and other neuromuscular conditions. Ultrasound reflects the changes occurring in muscle and allows differentiation between myopathies and neuropathies. It may also be of help in deciding where to take a needle biopsy. Computerized tomography (CT) has been used to assess progression over a 6 month period in Duchenne dystrophy. The density changes observed on CT scans give an accurate indication of progression and will be a useful tool in clinical trials. CT scans of obligate carriers of Duchenne dystrophy showed lower muscle densities than male controls. Magnetic resonance imaging also accurately reflects pathological changes in muscle. A pilot project to improve respiratory muscle strength and endurance showed that it was possible to improve endurance. A longer term project is currently being carried out to improve respiratory muscle endurance by the use of computer games connected to a thermistor. A certain inspiratory effort is required to continue the games, which provide the motivating factor.


[Coronary artery bypass grafting under beating heart without cardiopulmonary bypass].
Recently coronary artery bypass grafting under beating heart without cardiopulmonary bypass has been widely accepted for patients with associated risks of standard bypass surgery. Between October 1995 and October 1997, we performed this procedure on 40 (11 reoperative procedures). There were 26 single-vessel (9 reoperative procedures), 12 double-vessel (2 reoperative procedures) and 2 triple-vessel bypass procedures. Major risk factors and concomitant disorders were as follows: chronic hemodialysis, 3; poor renal function, 5; poor lung function, 6; reoperative procedure, 11; elder patient (age > or = 75 y), 4. Twenty-five patients were operated through a mediansternotomy, 11 through left thoracotomy (small thoracotomy 7), 1 through a small right thoracotomy, 3 through a laparotomy with the diaphragm approach, 1 through both a left thoracotomy and a laparotomy with the diaphragm approach. Fifty-three grafts were used during this course (internal thoracic artery [ITA] = 42, gastroepiploic artery [GEA] = 7, saphenous vein [SV] = 4) and the sequential bypass was performed with 2 LITA grafts. In selected patients this procedure is very safe, cost-effective and required less blood loss compared to standard bypass surgery. This procedure was considered to be very effective for patient with chronic hemodialysis. Also, left thoracotomy (a small thoracotomy) and laparotomy with the diaphragm approach showed particular effectiveness to reoperative procedures in order to preserve the patent grafts.


The association between receipt of home care rehabilitation services and acute care hospital utilization in clients with multimorbidity following an acute care unit discharge: a retrospective cohort study.
Individuals experiencing multimorbidity have more complex healthcare needs, use more healthcare services, and access multiple service providers across the healthcare continuum. They also experience higher rates of functional decline. Rehabilitation therapists are well positioned to address these functional needs; however, little is known about the influence of rehabilitation therapy on patient outcomes, and subsequent unplanned healthcare utilization for people with multimorbidity. The aims of this study were to: 1) describe and compare the characteristics of people with multimorbidity receiving: home care rehabilitation therapy alone, other home care services without rehabilitation therapy, and the combination of home care rehabilitation therapy and other home care services, and 2) determine the association between home care rehabilitation therapy and subsequent healthcare utilization among those recently discharged from an acute care unit. This retrospective cohort study used linked health administrative data housed within ICES, Ontario, Canada. The cohort included long-stay home care clients experiencing multimorbidity who were discharged from acute care settings between 2007-2015 (N = 43,145). Descriptive statistics, ANOVA's, t-tests, and chi-square analyses were used to describe and compare cohort characteristics. Multivariable logistic regression was used to understand the association between receipt of rehabilitation therapy and healthcare utilization. Of those with multimorbidity receiving long-stay home care services, 45.5% had five or more chronic conditions and 46.3% required some assistance with ADLs. Compared to people receiving other home care services, those receiving home care rehabilitation therapy only were less likely to be readmitted to the hospital (OR = 0.78; 95% CI: 0.73-0.83) and use emergency department services (OR = 0.73; 95% CI: 0.69-0.78) within the first 3-months following hospital discharge. Receipt of rehabilitation therapy was associated with less unplanned healthcare service use when transitioning from hospital to home among persons with multimorbidity. These findings suggest rehabilitation therapy may help to reduce the healthcare burden for individuals and health systems. Future research should evaluate the potential cost savings and health outcomes associated with providing rehabilitation therapy services for people with multimorbidity.


Three new species of Chaetomium from soil.
Chaetomium macrostiolatum sp. nov., Chaetomium olivicolor sp. nov. and Chaetomium tarraconensis sp. nov. isolated from Nigerian, Indian, and Spanish soils respectively, are described and illustrated. The first species is characterized by ascomata with a very broad ostiole and yellow hairs, and limoniform ascospores; the second by its thermotolerant growth, inconspicuous and short straight ascomatal hairs and fusiform ascospores; and the last by its unusual, irregularly-shaped ascospores and subglobose ascomata with flexuous to undulate, unbranched ascomatal hairs.