Bilateral sixth nerve palsy as a manifestation of Wernicke's encephalopathy in a patient with refractory vomiting.
To report a case of Wernicke's encephalopathy in a nonalcoholic woman with secondary hypoadrenalism. A 58-year-old Italian woman developed Wernicke's syndrome secondary to recurrent vomiting due to secondary hypoadrenalism. Recurrent vomiting and resulting malnutrition caused a depletion of the patient's body stores of thiamine and the development of mental confusion and an oculomotor deficit. On the diagnostic suspicion of encephalitis in this patient with immunosuppression due to prolonged cortisone-based therapy, she underwent magnetic resonance imaging, which showed typical bilateral abnormal lesions pathognomonic of Wernicke's encephalopathy. The patient improved after parenteral administration of vitamin B1. Wernicke's encephalopathy must be regarded as a medical emergency that should be suspected in all cases presenting with a sudden deficit or lack of coordination of the ocular movements associated with ataxia and general degeneration of the mental faculties, in patients who have suffered recurrent vomiting or malnutrition for different reasons.


Assessment of pepper spray product potency in Asian and Caucasian forearm skin using transepidermal water loss, skin temperature and reflectance colorimetry.
Historically, pepper spray product potency has been established using a taste test evaluation. A taste test is subjective and may not be appropriate for assessing pepper potency in skin. The current study evaluated chemically diverse pepper sprays in human forearm skin using three objective, noninvasive parameters: transepidermal water loss, skin surface temperature and erythema, as a means for assessing dermal pharmacology, toxicology and product potency. Five commercial pepper spray products containing various capsaicinoid analogs at various concentrations were evaluated in duplicate on volar forearms of six Caucasians and six Asians using a 10 min exposure. Mean surface skin temperature, transepidermal water loss results were highly variable and therefore did not demonstrate dose responsive behavior to increasing capsaicinoid concentrations. Erythema, as measured by increases in a* (reflected light in the red-to-green color spectrum) of the L*a*b* uniform color scale, was superior among parameters evaluated in discriminating pepper spray potency and correlated well with the relative and total capsaicinoid concentration in the products. Products containing greater than 16 mg ml(-1) capsaicinoid concentration produced greater erythema responses in Caucasians than Asians. Asians responded greater to the synthetic analog, nonivamide, than to mixtures of capsaicinoids, while Caucasians responded equally to both capsaicinoid analogs. Thus, pepper spray product potency in human skin reflects the total capsaicinoid concentration, the specific capsaicin analog(s) present, and the race of the individual exposed. The finding that the reflectance colorimeter a* scale can differentiate these parameters in skin will have a significant impact on evaluating the use and efficacy of pepper spray products in humans.


Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche.
Calcitonin receptor (Calcr) is expressed in adult muscle stem cells (muscle satellite cells [MuSCs]). To elucidate the role of Calcr, we conditionally depleted Calcr from adult MuSCs and found that impaired regeneration after muscle injury correlated with the decreased number of MuSCs in Calcr-conditional knockout (cKO) mice. Calcr signaling maintained MuSC dormancy via the cAMP-PKA pathway but had no impact on myogenic differentiation of MuSCs in an undifferentiated state. The abnormal quiescent state in Calcr-cKO mice resulted in a reduction of the MuSC pool by apoptosis. Furthermore, MuSCs were found outside their niche in Calcr-cKO mice, demonstrating cell relocation. This emergence from the sublaminar niche was prevented by the Calcr-cAMP-PKA and Calcr-cAMP-Epac pathways downstream of Calcr. Altogether, the findings demonstrated that Calcr exerts its effect specifically by keeping MuSCs in a quiescent state and in their location, maintaining the MuSC pool.


[Cytoplasmic tubuloreticular complexes and nuclear bodies in cells of rubella-infected human embryos and fetuses (author's transl)].
The range of single or multiple defects which might develop in the human embryo of fetus after an intra-uterine rubella infection has been documented by means of a large number of epidemiological, clinical and pathological investigations. Newborns with congenital rubella carry a number of defects, some of which could be the direct result of a virus-induced, intra-uterine vascular damage. In rubella-infected embryos and fetuses, vascular lesions are the most frequently observed histopathological finding. These changes have already been systematically investigated by means of the light microscope. Ultrastructural data are, however, not available at present.


Identifying need in care homes for people with dementia: the relationship between two standard assessment tools.
Considerable effort has been invested in improving assessment processes for older people, some of the most vulnerable of whom live in care homes. The paper compares two well-known assessment tools used in care homes, the CANE and the Minimum Data Set/Resident Assessment Instrument. There was poor agreement between the tools in terms of domains of need covered. Nineteen pairs of items could be compared, with agreement greater than 60% found on 11 items. Of the 15 items where kappa could be computed, seven significant values were found. High levels of agreement existed in relation to behaviour, psychological wellbeing, mood state, psychotic symptoms, incontinence, mobility and inadvertent self-harm (risk). The study suggests that tools commonly used for assessment are not interchangeable and that the selection of assessment tool should be determined by the setting in which it is used, the needs of the population being assessed, the skills and knowledge of those undertaking the assessment and the purpose of the assessment itself.


Conformational flexibility, hydration and state parameter fluctuations of fibroblast growth factor-10: effects of ligand binding.
Differential effects of ligand binding on local and global fibroblast growth factor-10 (FGF-10) flexibility and stability have been investigated utilizing a variety of experimental and computational techniques. Normal mode analysis was used to predict the low frequency motions and regional flexibility of FGF-10. Similarly, regional variations in local folding/unfolding equilibria were characterized with the COREX/BEST algorithm. Experimental adiabatic and isothermal compressibilities of FGF-10 alone and in the presence of polyanions are compared. Furthermore, the effect of polyanions on the coefficient of thermal expansion is compared. Measurements of density, heat capacity, compressibility, and expansibility were combined to calculate experimentally determined volume and enthalpy fluctuations. Global effects of polyanions on FGF-10 flexibility, thermodynamic fluctuations, and hydration vary depending on the size and charge density of the polyanion. Local effects of polyanions were investigated utilizing time-resolved fluorescence spectroscopy and red edge excitation spectroscopy (REES). Increased rigidity of the protein matrix or an increased solvent response surrounding the Trp residues is observed in the presence of polyanions. Similarly, time-resolved spectroscopy reveals increased ground state heterogeneity and increased dipole relaxation on the time scale of fluorescence for FGF-10 in the presence of polyanions. These polyanions increase heterogeneity, global flexibility, and fluctuations while increasing the melting temperature (Tm) of FGF-10.


Deep Compartment Syndrome Without Myonecrosis: A Case Report on a Rare Complication of Sickle Cell Disease.
Compartment syndrome is a rare manifestation of vaso-occlusive crisis, a serious complication of sickle cell disease (SCD), which is an inherited hemoglobinopathy. During a visit to Norway, an otherwise healthy, 20-year-old male from Ghana was admitted to Oslo University Hospital (Day 1) because of increasing pain in the hip and thighs that did not respond adequately to non-opioid painkillers. Despite initial treatment with intravenous fluids and opioids, his pain intensified. Careful clinical inspection supported by an MRI examination revealed focal, high-signal-intensity muscle edema of the anterior compartment of the thigh, almost exclusively limited to the vastus intermedius muscles. There were no MRI findings or blood biochemistry evidence for myonecrosis or rhabdomyolysis, and a diagnosis of deep compartment syndrome appeared to be the most likely explanation for his pain. We decided to continue with a conservative treatment approach, and the patient did not undergo a fasciotomy or blood transfusion therapy. On Day 7 after admission, his condition improved markedly, and he was discharged on Day 11 whereupon he returned to Ghana. This case is a reminder that, although rare, deep compartment syndrome can be a severe manifestation of vaso-occlusive crisis in SCD and should be considered in patients with severe, deep muscular pain in the absence of other explanatory factors.


Anterior sacral pyocele with meningitis: a rare presentation of occult spinal dysraphism with congenital dermal sinus.
The authors describe an interesting case of a hitherto asymptomatic occult spinal defect with a congenital sacral dermal sinus which proved to be the entry point for bacterial meningitis in an otherwise healthy 9-year-old female child. The patient presented with fever and neck stiffness, and a dermal sinus in the lumbosacral region was identified on examination. Cerebrospinal fluid analysis confirmed bacterial meningitis and a spinal magnetic resonance imaging scan revealed a dermal sinus tract with an anterior spinal meningocele, caudal regression syndrome, and a tethered spinal cord. In addition to administration of intravenous antimicrobial agents, surgical exploration of the sacral dermal sinus tract was performed and an anterior sacral pyocele was drained. The pyocele cavity was disconnected from the thecal sac, and the thickened and fatty filum terminale was sectioned. Although congenital sacral dermal sinus manifesting as bacterial meningitis is known, the occurrence of an anterior sacral pyocele has not yet been described in children.


Spatial confinement controls self-oscillations in polymer gels undergoing the Belousov-Zhabotinsky reaction.
Chemoresponsive gels undergoing the Belousov-Zhabotinsky (BZ) reaction exhibit self-sustained pulsations, which can be harnessed to perform mechanical work. In technological applications, the gels would typically be confined between hard surfaces and thus, it is essential to establish how confinement affects these distinctive oscillations. Using theory and simulation, we pinpoint regions in phase space where the dynamic behavior of BZ gels critically depends on the presence of confining walls. We then illustrate how the wave propagation within thin samples can be tailored by selectively introducing "cut outs" in the bounding surfaces. The oscillations in the latter films are localized in specified areas, so the system contains well-defined oscillatory and nonoscillatory regions. The cut outs provide an effective means of tuning the mechanical action within the film and provide a route for tailoring the functionality of the material.


Purulent Pericarditis Leading to Constriction.
We report a case of a previously healthy 61-year-old immunocompetent male who was found to have purulent bacterial pericarditis. The patient was initially diagnosed with pneumococcal pneumonia and bacteremia after presenting with chest pain and a productive cough. He was found to have a purulent pericardial effusion and underwent surgical washout and creation of a pericardial window. In short time he developed signs of right heart failure and a cardiac MRI revealed a severely thickened pericardium with evidence of constrictive pericarditis. The patient subsequently underwent pericardiectomy where the diagnosis of constriction was confirmed. Our patient recovered well and had no clinical evidence of heart failure on follow-up. This case demonstrates the importance of rapid identification of bacterial pericarditis and the high likelihood of progression to constriction.


[Urinary cytology in office urology (author's transl)].
Urinary cytology is an effective method for the detection and control of urothelial tumors. The use of simple, fast staining and reliable techniques in the office for screening purposes may improve the early detection rate. A survey of simple microscopic and staining techniques is given. Prestained slides (Testsimplets and Sangodiff G) proved to be very suitable for office use. But the cytological analysis of the urinary sediment still needs a highly interested and trained examiner.


Integrated non-blocking optical router harnessing wavelength- and mode-selective property for photonic networks-on-chip.
In this paper, we propose and demonstrate a 4×4 non-blocking optical router utilizing 8 mode (de)multiplexers and a 4×4 microring-based grid network, which can passively assign signals carried by optical wavelength and mode channels from an arbitrary input port to corresponding output ports without additional switch time, realizing the non-blocking property. The proposed device is fabricated on a silicon-on-insulator platform using the standard Complementary Metal-Oxide-Semiconductor (CMOS) fabrication processes. The insertion loss is lower than 5.7 dB including the loss of the auxiliary mode (de)multiplexers (AMUXs), while the crosstalk is lower than -15.6 dB for all routing states. Moreover, the transmission spectra from the input ports to the next cascading device are also measured to demonstrate the feasibility of further expanding via cascading multiple blocks, with the insertion loss and crosstalk lower than 7.1 dB (including the mode coupling loss of AMUXs) and -16.4 dB, respectively. The 12 Gbps dynamic transmission experiment is demonstrated with clear and open eye diagrams, illustrating the utility of the device. The device has high geometrical symmetry and good scalability, we exhibit all solutions to expand the 4×4 optical router to 8×8 and 16×16 optical routers with the advantages and deficiencies of each solution discussed.


Comparative efficacies of imipenem, oxacillin and vancomycin for therapy of chronic foreign body infection due to methicillin-susceptible and -resistant Staphylococcus aureus.
The efficacies of imipenem when directed against methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains of Staphylococcus aureus were compared with those of oxacillin and vancomycin in a subcutaneous rat model, using chronically infected tissue cages. At three weeks after inoculation, stable chronic infections were established with average bacterial counts exceeding 10(6) cfu/mL tissue cage fluid for both strains. Intraperitoneal administration (twice a day for 7 days) of imipenem (80 mg/kg) or oxacillin (200 mg/kg) produced peak levels of 23 or 45 mg/L and through levels of < 0.1 and 5.7 mg/L, respectively. The therapeutic regimens of either imipenem (P < 0.001) or oxacillin (P < 0.02) administered for 7 days led to significant reductions in bacterial counts in the tissue cage fluids of animals chronically infected with MSSA. In contrast, imipenem was not effective against chronic MRSA tissue cage infections, despite the relatively low MIC of the infecting strain and the use of high dose (120 mg/kg) therapy. In-vitro susceptibility testings of MRSA performed before and after imipenem therapy demonstrated the emergence of a highly resistant subpopulation.


Superfluidity of trapped dipolar fermi gases.
We derive the phase diagram for ultracold trapped dipolar Fermi gases. Below the critical value of the dipole-dipole interaction energy, the BCS transition into a superfluid phase ceases to exist. The critical dipole strength is obtained as a function of the trap aspect ratio. Alternatively, for a given dipole strength there is a critical value of the trap anisotropy for the BCS state to appear. The order parameter exhibits a novel nonmonotonic behavior at the criticality.


Effects of metabolic inhibitors on spontaneous and interferon-boosted human natural killer cell activity.
Human natural killer (NK) cell activity can be augmented by pretreatment with partially purified preparations of human interferon (IF). Studies have now been performed to determine the metabolic processes required for and involved in spontaneous NK activity and augmentation of cytotoxicity. A 4-hr 51Cr release cellular cytotoxicity assay was used to measure the NK activity, and peripheral blood leukocyte cells (PBL) were treated with: a) x-ray or mitomycin C; b) actinomycin D; or c) emetine, cycloheximide, pactamyhcin, or puromycin to assess the roles of DNA, RNA, and protein synthesis, respectively, in spontaneous NK activity and in boosting by IF. Prolonged incubation (18 hr) of PBL after blockage of synthesis of DNA almost completely abrogated NK activity; however, NK activity could be partially or totally restored to these populations by incubation of the effector cells for 1 hr at 37 degrees C with IF. Blockage of DNA synthesis for 1 hr had no effect on spontaneous NK activity or on boosting by IF. Inhibition of RNA synthesis also had no effect on spontaneous NK activity. Treatment of PBL with actinomycin before exposure to IF prevented boosting, but treatment with the RNA synthesis inhibitor after boosting with IF for 5 to 6 hr no longer had an appreciable effect on cytotoxicity. The effect of protein synthesis inhibitors on spontaneous NK activity was dependent on the inhibitor selected. Emetine and puromycin totally abrogated spontaneous NK activity at concentrations of inhibitor that blocked 3H-leucine incorporation 90% or more. In contrast, cycloheximide and pactamycin had only minimal effects on spontaneous NK activity but totally abrogated the boosting of IF.


InAs quantum dots on nanopatterned GaAs (001) surface: the growth, optical properties, and device implementation.
This work reviews the growth, optical properties, and device implementation of InAs semiconductor quantum dots (QDs) selectively nucleated atop nano-faceted GaAs pyramidal structures grown by metal-organic chemical-vapor deposition. This site-controlled QD growth technique offers unique features and benefits subsequent device applications. First, GaAs pyramids, formed on a SiO2-masked and nanopatterned (001) GaAs substrate, are characterized by well-defined equilibrium crystal shapes (ECS). The controlled ECS formation is crucial to subsequent patterned QD (PQD) nucleation, which is highly preferential toward {11n} planes due to superior QD energy minimization. Second, PQD optical properties are thoroughly studied by monitoring room temperature (RT) photoluminescence (PL) and power-dependent low-temperature PL to verify the crystalline quality and the three-dimensional quantum confinement. The PQD ensembles formed on different GaAs pyramids, with different PL behavior, indicate lateral coupling within QD clusters and characteristics of isolated QD pairs. Then, PQDs embedded in a InGaAs quantum well, the so-called dot-in-the-well (DWELL) structure, are compared to a self-assembled QD (SAQD) DWELL structure, and shown to have a better emission efficiency, due to the distributed QW thickness profile on the faceted GaAs pyramid. Finally, broad-area light emitting diodes based on the PQD active region are fabricated. Linear current-voltage characteristics are observed with sharp turn-on, low leakage current and low forward resistance. Electroluminescence spectra show PQD intraband structure and low quenching of emission from 77 K to room temperature. Light-current measurements demonstrate external quantum efficiency per PQD comparable to SAQDs, despite the two regrowth steps in the fabrication processes.


Understanding kidney disease in rural central Uganda - Findings from a qualitative study.
As part of a multicentre study on kidney disease (ARK) undertaken in Malawi, South Africa and Uganda we undertook a social science component in Uganda to gather information on people's understandings and perceptions of a diagnosis of kidney dysfunction, treatment and treatment seeking. We recruited 46 people who had been given information about kidney dysfunction and had been found to have some, usually early, signs of mild impairment. Data were collected during two in-depth interviews. Most participants had heard of the condition, but half denied knowledge of the health status of their kidneys or receiving results of tests from the clinic team. This response may have been linked to a lack of symptoms, for those with early stage kidney dysfunction. The treatment people reported receiving caused some uncertainty about condition severity. This may be because several people were treated for other conditions (such as urinary tract infections) and did not require treatment specifically for kidney disease. In our study, participants assessed illness severity based on symptoms and treatment and compared with the progression of other conditions.


Cytogenetic findings and reproductive outcome of infertile couples referred to an assisted reproduction program.
It is still undefined whether all the couples entering an assisted reproduction program should undergo to karyotype analysis. The present study was conducted to determine the prevalence of chromosomal abnormalities in a non-selected sample of 1,146 couples referred to assisted reproduction technologies (ART), and to analyze the outcome of pregnancies from couples in whom cytogenetic anomalies were detected. Irrespective of the infertility factor, fertilization was achieved by intracytoplasmic sperm injection (ICSI). A total number of 35 karyotype anomalies were diagnosed, corresponding to an abnormality frequency of 1.52% (1.83% for men and 1.22% for women). As could be expected, the majority of men presenting karyotype anomalies had a low sperm count. Among women, the majority of cytogenetic anomalies were detected in individual not presenting risk factors for aberrant karyotype. Around 41% of pregnancies achieved in couples presenting chromosomal anomalies ended in spontaneous abortion. Information on fetal karyotype was limited. No major malformations were observed among newborns from parents with abnormal karyotype. In consideration of the elevated frequency of pregnancy loss, it seems advisable to recommend that chromosomal analysis be performed in all couples undergoing ART. This with the aim of identifying patients that would possibly benefit from pre-implantation genetic diagnosis.


[A case of Dieffenbachia poisoning].
A case is presented of poisoning with, even more frequently cultivated in flats, Dieffenbachia. The mechanism of toxic effect of the juice of this plant is discussed. Prophylactic and therapeutic guidelines are presented.


Acousto-plasmofluidics: Acoustic modulation of surface plasmon resonance in microfluidic systems.
We acoustically modulated the localized surface plasmon resonances (LSPRs) of metal nanostructures integrated within microfluidic systems. An acoustically driven micromixing device based on bubble microstreaming quickly and homogeneously mixes multiple laminar flows of different refractive indices. The altered refractive index of the mixed fluids enables rapid modulation of the LSPRs of gold nanodisk arrays embedded within the microfluidic channel. The device features fast response for dynamic operation, and the refractive index within the channel is tailorable. With these unique features, our "acousto-plasmofluidic" device can be useful in applications such as optical switches, modulators, filters, biosensors, and lab-on-a-chip systems.


Lymphoma-specific genetic aberrations in microvascular endothelial cells in B-cell lymphomas.
The growth of most tumors depends on the formation of new blood vessels. In contrast to genetically unstable tumor cells, the endothelial cells of tumor vessels are considered to be normal diploid cells that do not acquire mutations. Using a combined immunohistochemical and fluorescence in situ hybridization assay, we examined the endothelial cells in 27 B-cell lymphomas for cytogenetic alterations that are known to be present in the lymphoma cells. We found that 15 to 85 percent (median, 37 percent) of the microvascular endothelial cells in the B-cell lymphomas harbored lymphoma-specific chromosomal translocations. In addition, numerical chromosomal aberrations were shared by the lymphoma cells and the endothelial cells. Our findings suggest that microvascular endothelial cells in B-cell lymphomas are in part tumor-related and therefore reflect a novel aspect of tumor angiogenesis.


Peripheral vestibular loss in noise-exposed firefighters.
Occupational workers are increasingly aware of the risk of noise overexposure to the auditory system but lack awareness about potential risks to the vestibular system. The purpose of this study was to investigate changes in vestibular end organ function in a known at-risk noise-exposed population, firefighters compared to age- and sex-matched controls using electrophysiologic measures of cervical vestibular evoked myogenic potentials (cVEMP). A cross-sectional observational study compared cVEMP response characteristics in 38 noise-exposed firefighters. Firefighters were grouped by years of exposure in the fire service. The cVEMP responses were compared within firefighter groups and between firefighters and age- and sex-matched controls. Dependent variables included the response characteristics of amplitude, latency and threshold. cVEMP response amplitudes were significantly decreased in firefighters compared to their age- and sex-matched controls. Threshold of the cVEMP responses were significantly higher in firefighters compared to controls and firefighters had a higher incidence of absent cVEMP responses compared to controls. Response amplitudes decreased with increasing years in the fire-service at an increased rate compared to their age- and sex-matched controls. Latency of the cVEMP response was not significantly different in firefighters compared to controls. These findings are consistent with both animal and human studies suggesting noise-induced changes in the sacculocollic pathway. In the absence of any reported vestibular symptoms or auditory indicators of noise-induced hearing loss, these early effects on the vestibular system point to a potential hidden vestibular loss.


Using Quality Improvement to Improve Identification and Documentation of Malnutrition in Hospitalized Pediatric Patients.
Recent publications have highlighted the importance and impact of recognizing malnutrition in hospitalized children. After noting that patients with malnutrition frequently went unrecognized in our facility, we implemented an interprofessional intervention comprising hospital medicine physicians, dietitians, and the clinical documentation improvement team to improve recognition and documentation of malnutrition in these patients, thereby facilitating earlier intervention. We implemented three separate plan-do-study-act cycles to improve the identification and documentation of malnutrition among patients hospitalized at our facility. The cycles consisted of identifying malnutrition using z-scores, educating providers, and implementing smart text within the medical record to help with consistent documentation. In addition, real-time communication between the disciplines (nutrition services, clinical documentation improvement providers, and hospitalists) was also employed to improve documentation quality. After completing the plan-do-study-act cycles, charts were reviewed to evaluate the nutritional interventions received. Baseline data revealed that only 13% of patients with z-scores indicative of malnutrition were identified as such in attending physicians' documentation. Upon implementation of our plan-do-study-act cycles, documentation of these patients increased to greater than 64%. Patients with documented malnutrition received nutritional interventions at least 81% of the time, increasing from 35% at baseline. Our findings demonstrate that an interprofessional approach can dramatically enhance the identification and documentation of malnutrition in hospitalized children, leading to earlier intervention.


Behavior of polycatalytic assemblies in a substrate-displaying matrix.
We describe polycatalytic assemblies, comprising one or two streptavidin molecules and two to six attached nucleic acid catalysts (deoxyribozymes), with phosphodiesterase activity. When exposed to a matrix covered at high densities with oligonucleotide substrates, these molecules diffuse through the matrix continuously cleaving the substrate at rates comparable to those of individual catalysts in solution. Rates of diffusion (movement), processivity, and resident times of assemblies can be controlled through the number of catalytic units and the length of substrate/product recognition regions. The assemblies were characterized at the ensemble level using surface plasmon resonance.


Corticosteroids in Duchenne muscular dystrophy: a reappraisal.
Duchenne muscular dystrophy is the most common and most severe form of childhood muscular dystrophies, resulting in early loss of ambulation between the ages of 7 and 13 years and death in the teens and twenties. Despite the phenomenal advances made in the understanding of the molecular genetics of the disease, no definitive cure has been found. Of all of the therapeutic drugs studied in Duchenne muscular dystrophy, only prednisone seems to have the potential for providing interim functional improvement for boys with Duchenne muscular dystrophy while they wait for a cure with gene or cell therapy. There is still no consensus regarding recommending corticosteroids as standard therapy for boys. This is an evidence-based review of all of the studies of corticosteroids (prednisone, deflazacort, and oxandrolone) in Duchenne muscular dystrophy. From this review, it is clear that until a definitive treatment for Duchenne muscular dystrophy is available, the use of deflazacort and prednisone with judicious dietary control and close clinical monitoring for side effects seems the best intervention for interim preservation of function in such a common devastating disorder of young growing boys.


Obstetrical intervention rates and maternal and neonatal outcomes of women with gestational hypertension.
The purpose of this study was to determine the obstetrical intervention rates and maternal and neonatal outcomes of women with gestational hypertension. Induction and operative delivery rates and indices of maternal and neonatal morbidity were determined in women (37-41 completed weeks) with gestational hypertension (n = 979), preeclampsia (n = 165), chronic hypertension (n = 187), and control subjects (n = 11,434) in a retrospective review of St. Joseph's Health Care Perinatal Database from November 1, 1995, to October 31, 1999. Data were analyzed by chi-square test, analysis of variance, Dunnett's t -test, and pairwise chi-square tests with Bonferroni correction. The induction and cesarean delivery rates in gestational hypertension were similar to preeclampsia and chronic hypertension groups and almost double of control subjects. The length of labor and postpartum stays and the incidence of operative vaginal delivery, postpartum hemorrhage, and neonatal intensive care involvement were greater in the gestational hypertension group than in the control subjects. Women with gestational hypertension had obstetrical intervention rates much higher than control subjects and similar to those with preeclampsia and chronic hypertension.


Prevalence of Peroneal Tendon Instability in Calcaneus Fractures: A Systematic Review and Meta-Analysis.
Peroneal tendon instability associated with an intraarticular calcaneal fracture is a common injury that still often passes undiscovered by both radiologists and orthopedic surgeons. Timely identification of this injury will guide the choice of surgical technique used and treatment of patients. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, several databases were searched through June 2017 for any observational or experimental studies that reported the prevalence/incidence of peroneal tendon subluxation/dislocation with a calcaneus fracture with regard to fracture classifications and the significance of the fleck sign. Nine studies were included, with 1027 patients and 1050 calcaneus fractures. The overall prevalence of peroneal instability (PI) in association with a calcaneus fracture was 29.3%. An increasing prevalence of PI increased the severity of the calcaneus fractures, 5.4% in Sanders I, 19% in Sanders II, 39.4% in Sanders III, and 49.5% in Sanders IV. The presence of a fleck sign is a strong indicator of PI, with a prevalence of 54.7%. The computed tomography findings can overestimate the presence of PI compared with the intraoperative findings. The global reported prevalence of peroneal tendon instability associated with intraarticular calcaneal fractures is high and increases with increasing severity of the calcaneus fracture.


Imaging features of pulmonary Kaposi sarcoma-associated immune reconstitution syndrome.
The purpose of this study was to analyze the radiologic features of pulmonary Kaposi sarcoma-associated immune reconstitution syndrome. The syndrome is a phenomenon characterized by clinical deterioration of the condition of HIV-positive patients after initiation of highly active antiretroviral therapy. The study included four patients at our institution who fulfilled the diagnostic criteria for pulmonary Kaposi sarcoma-associated immune reconstitution syndrome from 2001 to 2006. All patients were men (mean age, 43 years; range, 31-59 years). Images reviewed included chest radiographs obtained before highly active antiretroviral therapy, radiographs and chest CT scans obtained at appearance of the symptoms of Kaposi sarcoma-associated immune reconstitution syndrome, and follow-up radiographs and chest CT scans during immune reconstitution syndrome. The radiographic findings of Kaposi sarcoma-associated immune reconstitution syndrome included reticular and reticulonodular opacities (n = 4), areas of consolidation (n = 3), septal lines (n = 3), and pleural effusion (n = 3). The CT findings in all four patients were ill-defined pulmonary nodules and interlobular septal thickening. Three of the patients had a CT halo sign, areas of consolidation, ground-glass opacities, lymphadenopathy, and pleural effusion. The areas of consolidation in three subjects who did not receive chemotherapy increased markedly after 14-20 days. CT performed during the initial symptoms of immune reconstitution syndrome in these three subjects showed less than 5% parenchymal involvement. Follow-up CT showed 26-50% involvement in two patients and more than 50% involvement in one patient. The radiologic findings of pulmonary Kaposi sarcoma-associated immune reconstitution syndrome are similar to the findings described in patients with Kaposi sarcoma without the syndrome, but the extent of abnormalities tends to increase with the development of the syndrome.


Stereoselective synthesis of annular 9-cis-retinoids and binding characterization to the retinoid X receptor.
Analogues of 9-cis-retinoic acid incorporating an alicyclic ring between the C19 and C10 positions have been synthesized and evaluated as ligands for the RXRalpha nuclear receptor. The stereocontrolled synthesis of these configurationally constrained retinoids combines a Stille cross-coupling and the Wittig reaction as key bond-forming steps. The palladium-catalyzed cross-coupling reaction of the beta-bromo-alpha,beta-unsaturated aldehydes 5 to dienylstannane 6 is very fast at room temperature, and takes place with preservation of the dienylstannane geometry. A highly stereoselective Wittig reaction afforded the C7-C8 bond connecting the hydrophobic ring to the retinoid side chain. The binding affinities of these compounds for the receptor were determined, and the structural and energetic rationale behind the affinity profile of the cyclic 9-cis-retinoic acid derivatives for the RXRalpha nuclear receptor was characterized by using Molecular Mechanics protocols.


Effectiveness of a 24-hour access outpatient clinic for patients with chronic conditions in hospital outpatient follow-up: a registry-based controlled cohort study of healthcare utilisation and mortality.
To evaluate the effectiveness of a 24-hour telephone access outpatient clinic (24-hour access clinic) in terms of healthcare utilisation and mortality in patients with five chronic conditions (chronic obstructive pulmonary disease, atrial fibrillation/flutter, congestive heart failure, inflammatory bowel disease and chronic liver disease). This was a registry-based controlled cohort study. The 24-hour access clinic was established at Silkeborg Regional Hospital in Central Denmark Region. The five other regional hospitals served as comparison hospitals. The 24-hour access clinic allowed patients with five chronic conditions with ongoing hospital outpatient follow-up to call the hospital outpatient clinic in case of an exacerbation. Outcomes were use of hospital admissions, length of stay (LOS), outpatient visits, contacts to general practice and all-cause mortality during 18 months of follow-up. The study included 992 the 24-hour access patients and 3878 usual care patients. For the five conditions combined, the 24 hours access patients had fewer all-cause admissions (incidence rate ratio (IRR) 0.81, 95% Cl 0.71 to 0.92), general practice out-of-hours contacts (IRR 0.81, 95% C 0.71 to.92) and shorter LOS (IRR 0.71, 95% CI 0.57 to 0.88). The rate of all-cause outpatient visits tended to be higher (IRR 1.07, 95% CI 0.99 to 1.15). General practice daytime contacts were similar between the groups, and there was no significant difference in mortality. The results suggest that a 24-hour telephone access clinic may lead to enhanced integration of care measured as unplanned acute care substituted with planned outpatient care.


Primary care patients in psychiatric clinical trials: a pilot study using videoconferencing.
While primary care physicians play a pivotal role in the treatment of depression, collaboration between primary care and psychiatry in clinical research has been limited. Primary care settings provide unique opportunities to improve the methodology of psychiatric clinical trials, by providing more generalizable and less treatment-resistant patients. We examined the feasibility of identifying, recruiting, screening and assessing primary care patients for psychiatric clinical trials using high-quality videoconferencing in a mock clinical trial. 1329 patients at two primary care clinics completed a self-report questionnaire. Those screening positive for major depression, panic, or generalized anxiety were given a diagnostic interview via videoconference. Those eligible were provided treatment as usual by their primary care physician, and had 6 weekly assessments by the off-site clinician via videoconferencing. 45 patients were enrolled over 22 weeks, with 36 (80%) completing the six-week study with no more than two missed appointments. All diagnostic groups improved significantly; 94% reported they would participate again, 87% would recommend participation to others, 96% felt comfortable communicating via videoconference, and 94% were able to satisfactorily communicate their feelings via video. Results showed that primary care patients will enroll, participate in and complete psychiatric research protocols using remote interviews conducted via videoconference.


Molecular dynamics free energy simulations of ATP:Mg2+ and ADP:Mg2+ using the polarizable force field AMOEBA.
ATPases and GTPases are two important classes of protein that play critical roles in energy transduction, cellular signaling, gene regulation and catalysis. These proteins use cofactors such as nucleoside di and tri-phosphates (NTP, NDP) and can detect the difference between NDP and NTP which then induce different protein conformations. Mechanisms that drive proteins into the NTP or NDP conformation may depend on factors such as ligand structure and how Mg2+ coordinates with the ligand, amino acids in the pocket and water molecules. Here, we have used the advanced electrostatic and polarizable force field AMOEBA and molecular dynamics free energy simulations (MDFE) to examine the various binding mechanisms of ATP:Mg2+ and ADP:Mg2+.We compared the ATP:Mg2+ binding with previous studies using non-polarizable force fields and experimental data on the binding affinity. It was found that the total free energy of binding for ATP:Mg2+ (-7.00 ± 2.13 kcal/mol) is in good agreement with experimental values (-8.6 ± .2 kcal/mol)1. In addition, parameters for relevant protonation states of ATP, ADP, GTP and GDP have been derived. These parameters will allow for researchers to investigate biochemical phenomena involving NTP's and NDP's with greater accuracy than previous studies involving non-polarizable force fields.


Synthesis and biological activity of 1 alpha,23,25,26-tetrahydroxyvitamin D3.
The metabolic pathway from 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] to 1 alpha,25-dihydroxyvitamin D3-26,23-lactone includes the formation of 1 alpha,23,25-26-tetrahydroxyvitamin D3 [1 alpha,23,25,26-(OH)4D3]. The aim of the current study was to explore the as yet unknown biological properties of this vitamin D3 sterol. The four diastereoisomers of 1 alpha,23,25,26-(OH)4D3 were chemically synthesized. They were compared to 1 alpha,25-(OH)2D3 in terms of their affinity for the chick intestinal 1 alpha,25-(OH)2D3 receptor and their biologic activity in vivo (stimulation of intestinal calcium absorption and mobilization of calcium from bone in vitamin D-deficient rats). The 1,25-(OH)2D3 receptor binding affinities of 1 alpha,23(R)25(R)26-(OH)4D3, 1 alpha,23(S)25(S)26-(OH)4 D3, 1 alpha,23(S)25(R)26-(OH)4D3, and 1 alpha,23(R)25(S)26-(OH)4D3 were 11, 100, 216, and 443 times weaker than the binding affinity of 1 alpha,25-(OH)2D3, respectively. Compared to 1 alpha,25-(OH)2D3, the relative capacities of the 1 alpha,23,25,26-(OH)4D3 compounds to stimulate intestinal calcium absorption were 1/4 for 1 alpha,23(R)25(R)26-(OH)4D3; 1/19 for 1 alpha,23(S)25(S)26-(OH)4D3; 1/90 for 1 alpha,23(S)25(R)26-(OH)4D3; and 1/136 for 1 alpha,23(R)25(S)26-(OH)4D3. Maximal stimulation of intestinal calcium transport occurred 8 h after administration of vitamin D3 metabolites. Mobilization of calcium from bone was quantitated by serum calcium concentration measurements. The activities of 1 alpha,23(R)25(R)26-(OH)4D3, 1 alpha,23(S)25(S)26-(OH)4D3, 1 alpha,23(S)25(R)26-(OH)4D3, and 1 alpha,23(R)25(S)26-(OH)4D3 to increase serum calcium were estimated to be 4, 13, 43, and 69 times weaker than that of 1 alpha,25-(OH)2D3, respectively. These results illustrate the stereospecificity of the chicken intestine 1 alpha,25-(OH)2D3 receptor for binding of 1 alpha,23,25,26-(OH)4D3 and suggest that the 1 alpha,23,25,26-(OH)4D3 exerts its biological activity in the rat through an interaction with 1,25-(OH)2D3 receptors. In summary, the 1 alpha,23,25,26-(OH)4D3 had a markedly lower biological activity than 1 alpha,25-(OH)2D3.


Cryopreservation of spermatozoa of black marlin, Makaira indica (Teleostei: Istiophoridae).
As a first step towards the development of a method for the cryopreservation of black marlin spermatozoa, this study investigated the effect of dimethylsulfoxide (DMSO) concentration and pellet size on post-thaw spermatozoal motility. Spermatozoa were recovered from the spermatic duct of testes retrieved post-mortem from four adult black marlin caught in the Coral Sea spawning grounds of Australia. Undiluted spermatozoa were stored on ice for 4 to 10 hours during transport to shore, then evaluated for motility after activation in seawater (1:10 v:v). Spermatozoa were prepared for cryopreservation in pellets by extension (1:3 v:v) in a defined fish Ringer's solution to give two final DMSO concentrations of 2.5% or 5.0%. Diluted spermatozoa were frozen directly on a dry ice block in pellet sizes of either 0.25 ml or 0.50 ml. Frozen pellets were thawed in a water bath at 40 degrees C for 60 seconds and assessed for post-thaw motility following activation in seawater. Spermatozoa recovered within 50 minutes of death and chilled on ice for 4 to 10 hours showed a mean (+/- SEM) motility immediately following activation of 91.6 +/- 7.9%. 50% of the spermatozoa remained motile for approximately 4 to 5 minutes. Following cryopreservation, mean motility declined significantly across all cryoprotectant and pellet size combinations (P < 0.001) but spermatozoa frozen in 2.5% DMSO showed higher motility than those frozen in 5.0% DMSO (P = 0.014). Pellet size had no effect on post-thaw motility (P = 0.179).


Development of a procedure for discriminating among Escherichia coli isolates from animal and human sources.
Counts of Escherichia coli cells in water indicate the potential presence of pathogenic microbes of intestinal origin but give no indication of the sources of the microbial pollution. The objective of this research was to evaluate methods for differentiating E. coli isolates of livestock, wildlife, or human origin that might be used to predict the sources of fecal pollution of water. A collection of 319 E. coli isolates from the feces of cattle, poultry, swine, deer, goose, and moose, as well as from human sewage, and clinical samples was used to evaluate three methods. One method was the multiple-antibiotic-resistance (MAR) profile using 14 antibiotics. Discriminant analysis revealed that 46% of the livestock isolates, 95% of the wildlife isolates, and 55% of the human isolates were assigned to the correct source groups by the MAR method. Amplified fragment length polymorphism (AFLP) analysis, the second test, was applied to 105 of the E. coli isolates. The AFLP results showed that 94% of the livestock isolates, 97% of the wildlife isolates, and 97% of the human isolates were correctly classified. The third method was analysis of the sequences of the 16S rRNA genes of the E. coli isolates. Discriminant analysis of 105 E. coli isolates indicated that 78% of the livestock isolates, 74% of the wildlife isolates, and 80% of the human isolates could be correctly classified into their host groups by this method. The results indicate that AFLP analysis was the most effective of the three methods that were evaluated.


Phase-II study with the combination of cisplatin and doxorubicin in advanced malignant mesothelioma of the pleura.
The effectiveness of combination chemotherapy with doxorubicin and cisplatin was studied in patients with advanced malignant pleuramesothelioma. 19 patients were treated intravenously with cisplatin 60 mg/m2/day on days 1 and 2, and with adriamycin 40 mg/m2 on day 3 every 4 weeks. 8/19 patients (46%) responded to chemotherapy; 2 achieved complete remissions (CR), and 6 went into partial remissions (PR). Median duration of response was 222 days. Median survival time of all patients was 370 days compared to a median survival of 273 days in a historical control group consisting of 30 patients treated by surgery only. Substantial toxicity was observed, mainly gastrointestinal. We conclude that the combination of cisplatin and adriamycin is effective in malignant pleuramesothelioma. However, the duration of treatment is limited by gastrointestinal toxicity.


Highly luminescent hybrid SiO2-coated CdTe quantum dots: synthesis and properties.
Novel hybrid SiO2-coated CdTe quantum dots (QDs) were created using CdTe QDs coated with a hybrid SiO2 shell containing Cd(2+) ions and a sulfur source via a sol-gel process in aqueous solution. Aqueous CdTe QDs with tunable emitting color created through a reaction between cadmium chloride and sodium hydrogen telluride was used as cores for the preparation of hybrid SiO2-coated CdTe QDs. In our experiments we found that the surface state of the cores and preparation conditions that affect the formation of the hybrid SiO2 shell also greatly affect photoluminescence of the hybrid SiO2-coated CdTe QDs. The generation of CdS-like clusters in the vicinity of the CdTe QDs, caused the quantum size effect of the QDs to be greatly reduced, which changes photoluminescence properties of the hybrid QDs fundamentally. Namely, the novel hybrid SiO2 shell played an important role in generating a series of specific optical properties. In addition, the novel hybrid SiO2 shell can be created if no CdTe QD is added. In order to gain an insight into the inter structure of the hybrid shell, we characterized the hybrid SiO2-coated CdTe QDs using X-ray diffraction analysis and discuss the formation mechanism of such a hybrid structure. This work is significant because the novel hybrid SiO2-coated CdTe QDs with its excellent properties can be used in many applications, such as biolabeling and optoelectronic devices.


Evaluation of Side Effects Associated with COVID-19 Vaccines in Pregnant Women.
A variety of vaccinations have been developed to fight the coronavirus disease 2019 (Covid-19) 2 years after the coronavirus epidemic spread globally. During clinical studies, these vaccinations were linked to mild to severe side effects. This study aimed to evaluate the short-term side effects of Covid-19 vaccination in pregnant women in Zabol (Iran). This cross-sectional study was conducted between August and October 2021 to collect data on the adverse side effects of Covid-19 vaccinations among 117 pregnant women in Zabol (Iran). A questionnaire was used to collect demographic data, vaccination information, and vaccine complications. SPSS software Version 22 was used to analyze the data at 2 levels descriptive and inferential statistics. A total of 117 pregnant women aged 27.67 ± 5.14 years were included. After the first and second doses of Covid-19 vaccinations, 91 (86.7%) and 84 (71.8%) pregnant women, respectively, suffered adverse effects. Moreover, after the first dose, 55(51.4%) and 60 (56.1%) of pregnant women reported fatigue and headache, and after the second dose, 39 (33.3%) and 37 (31.6%) reported fatigue and headache, respectively. The side effects reported in our study after receiving Covid-19 vaccinations in pregnant women were similar to those described in clinical studies of vaccines and were mild to moderate, showing that injectable vaccines had safe profiles. More research is needed, however, to assess the long-term side effects of existing vaccines.


Atrioventricular block in childhood caused by mesothelioma.
The case of a girl who was first seen at 3.5 years of age with longstanding asymptomatic heart block is reported. Electrophysiological study disclosed a block proximal to the His bundle. She grew up normally until the age of 11.5 years, when a syncopal attack occurred. Before a pacemaker could be inserted, she suffered a second fatal attack. Necropsy revealed a tumor of the atrioventricular node diagnosed as mesothelioma. Our findings are compared to the 38 cases already described in the literature.


Levetiracetam Induced Increase in Creatine Phosphokinase Levels.
Levetiracetam is an antiepileptic drug used for the treatment of generalised or partial seizures, either alone or in a combination therapy. Adverse effects have been reported with its clinical use, including headache, dizziness, liver failure etc. A rare but an important adverse effect is an increase in creatine phosphokinase (CPK) levels with its use. Herein, we present a case of 43-year male, known intravenous (IV) drug abuser with a history of decompressive craniotomy. Patient presented with severe behavioural disorder for which risperidone was given. Five days later, he started having high grade fever, hyperventilation and uncontrolled generalised tonic-clonic seizures (GTCS). After initial management of seizures, levetiracetam was started in combination with topiramate for seizure control. Seizures remained subsided but CPK levels, which were normal at the start of therapy, began to rise and reached tremendous levels of 29,000 mg/dl within a span of a week. Levetiracetam, suspected as a cause of this increase CPK levels, was stopped immediately and the levels returned to baseline within one week. This report provided us with an important step in the management of seizures with levetiracetam.


Molecular understanding of cytokine-steroid hormone dialogue: implications for human diseases.
Highly sophisticated mechanisms confer upon the immune system the capacity to respond with a certain degree of autonomy. However, the final outcome of an adaptative immune response depends on the interaction with other systems of the organism. The immune-neuroendocrine systems have an intimate cross-communication, making possible a satisfactory response to environmental changes. Part of this interaction occurs through cytokines and steroid hormones. The last step of this crosstalk is at the molecular level. In this article we will focus on the physical and functional interrelationship between cytokine signaling pathway-activated transcription factors (TFs) and steroid receptors in different cell models, where the signals triggered by cytokines and steroid hormones have major roles: (1) the ligand-dependent-activated glucocorticoid receptor (GR) influence the genetic program that specifies lineage commitment in T helper (Th) cell differentiation. How posttranslational modifications of several TFs as well as nuclear hormone receptors could be implicated in the molecular crosstalk between the immune-neuroendocrine messengers is discussed. (2) glucocorticoid (GC) antagonism on the TCR-induced T cell apoptosis. (3) estrogen receptor/TGF-beta family proteins molecular interaction implicated on pituitary prolactinomas pathogenesis. The functional crosstalk at the molecular level between immune and steroids signals is essential to determine an integrative response to both mediators (which in the last instance results in a new gene activation/repression profile) and constitutes the ultimate integrative level of interaction between the immune and neuroendocrine systems.


Experimental infection of domestic ducks and rodents by Notocotylus attenuatus (Trematoda: Notocotylidae).
In order to study transmission patterns of Notocotylus attenuatus five 3-wk-old domestic ducks, five 8-wk-old rats and ten 4-wk-old mice were infected with the parasite. All ducks became infected and all flukes were recovered from the intestinal ceca. Worms moved down the length of the cecum during development and as the parasites grew they changed their method of attachment. Flukes became gravid by day 16 post-infection, after which growth ceased. Egg filaments appear to play a role in the formation and movement of worm egg clusters from the distal portion of the cecum to the lumen of small intestine. Rodents also became infected with the parasite producing granulomatous nodular lesions in the lower small intestine but all flukes in the granulomata were dead. It is unlikely that transmission of this trematode can depend on mice and rats.


Osteosynthesis of Neck of Femur Fracture below 65 years of Age: does timing of surgery influence osteonecrosis, nonunion and functional outcome?
Background Influence of timing of injury surgery interval in outcome of osteosynthesis of neck of femur has always been a matter of debate. Patients in our set up have been surgically treated for neck of femur fracture with wide range of injury surgery interval which could have resulted in varied functional outcome and radiological outcome. Objective To evaluate the difference in functional outcome, femoral head osteonecrosis and non-union in fracture neck of femur fixed within and after twenty-four hours. Method All patients, who had undergone osteosynthesis for the neck of femur fractures via open or closed technique from 2010 to 2018 were analyzed retrospectively. The cases were examined and evaluated in terms of injury surgery interval, fracture union, functional status using Modified Harris Hip Score, complications like femoral head osteonecrosis and non-union. Result Fifty patients with an average injury surgery interval of 34±28 hours were evaluated. Twenty three (46%) cases were included in early surgery group (< 24 hours) and 27 (54%) patients were included in delayed (> 24 hours) surgery group. Incidence of femoral head osteonecrosis was reported in two (4%) cases, both being in delayed fixation group (p=0.49). Non-union was reported in four (8%) patients, one in early fixation group and three in delayed fixation group (p=0.61). The average Modified Harris Hip Score in early fixation group was 87 and in delayed fixation group was 84 (p=0.1). Forty two (84%) cases had a good quality of reduction and eight (16%) had a poor reduction. Non-union and functional outcome significantly differed between the good and poor reduction group (p=0.001 and 0.004 respectively). Conclusion There is no significant difference in the functional and radiological outcome of cases operated before and after 24 hours for osteosynthesis of neck of femur fractures in patients 16 to 65 years age group. However, poor reduction is significantly associated with the increased rate of non-union and poor functional outcome.


Going beyond 2D: Following membrane diffusion and topography in the IgE-Fc[Epsilon]RI system using 3-dimensional tracking microscopy.
The ability to follow and observe single molecules as they function in live cells represents a major milestone for molecular-cellular biology. Here we present a tracking microscope that is able to track quantum dots in three dimensions and simultaneously record time-resolved emission statistics from a single dot. This innovative microscopy approach is based on four spatial filters and closed loop feedback to constantly keep a single quantum dot in the focal spot. Using this microscope, we demonstrate the ability to follow quantum dot labeled IgE antibodies bound to FcεRI membrane receptors in live RBL-2H3 cells. The results are consistent with prior studies of two dimensional membrane diffusion (Andrews et al., Nat. Cell Biol., 10, 955, 2008). In addition, the microscope captures motion in the axial (Z) direction, which permits tracking of diffusing receptors relative to the "hills and valleys" of the dynamically changing membrane landscape. This approach is uniquely capable of following single molecule dynamics on live cells with three dimensional spatial resolution.


Replication and differentiation of olfactory receptor neurons following axotomy in the adult hamster: a morphometric analysis of postnatal neurogenesis.
Regeneration of olfactory receptor neurons following unilateral olfactory nerve section was studied in Syrian golden hamsters by morphometric procedures. Characteristic structural and histochemical features of olfactory receptor neurons were compared on the sectioned and intact sides of the nasal septum at 6, 12, 18, 33, and 130 days following axotomy. The parameters measured were epithelial thickness and the numbers of nuclei, hematoxylin-staining olfactory vesicles, olfactory marker protein (OMP)-containing neuronal perikarya, and OMP-containing olfactory vesicles. The olfactory receptor neuron population was severely depleted 6 days after axotomy. In the succeeding 12-day period there was an initially rapid, then slower return of receptor neuron numbers. Though the regenerating olfactory epithelium appeared normal by gross inspection 33 days after the lesion, morphometric analysis revealed a substantial increase in the number of olfactory receptor neurons between 33 and 130 days postlesion. At our longest survival interval, all quantitative parameters had returned to 91-99% of control values. The numbers of OMP-containing perikarya and olfactory vesicles on the sectioned side were unchanged between the sixth and 12th postlesion days, thus suggesting that neural turnover was depressed for several days following surgery. Marker protein developed in newly formed receptor neurons between 6 and 12 days after the formation of the olfactory vesicle. Consequently, the ratio between OMP-containing olfactory vesicles and hematoxylin-staining vesicles (O/H) was used as an index of neural differentiation. The O/H ratio on the sectioned side was minimal 12 days following axotomy when stem-cell division was well under way but OMP antigenicity had not yet been expressed in newly formed neurons. At 33 days postlesion, O/H ratios were slightly but significantly greater than the control value, reflecting a degree of synchrony in the regenerating receptor neuron population. The average O/H ratio on the unlesioned side was 0.667. This value, together with our other observations, was used to derive an estimate of the life span of hamster olfactory receptor neurons, approximately 25-35 days.


p75(NTR) activation of NF-kappaB is involved in PrP106-126-induced apoptosis in mouse neuroblastoma cells.
Neuronal death is a pathological hallmark of prion diseases. Synthetic prion peptide PrP106-126 can convert PrP(C) into protease-resistant aggregates, which can cause neurotoxicity in vivo and in vitro. Various cell surface proteins can participate in the infection process of prions. p75(NTR) can interact with PrP106-126 and has a neurotoxic effect on neurons. However, for p75(NTR) lacking intrinsic catalytic activity domain in cytoplasm, p75(NTR) -associated signaling molecular and the signaling events in cytoplasm in p75(NTR)-mediated apoptosis responding to PrP106-126 remain still unknown. Thus p75(NTR) -associated NF-kappaB signaling pathway was investigated in this study. Herein PrP106-126-induced apoptosis in mouse neuroblastoma cell line N2a, PrP106-126 significantly up-regulated p75(NTR) expression on mRNA and protein levels. For the first time we found that PrP106-126 induced activation of NF-kappaB by Western blot assay, and blocking the interaction of p75(NTR) with PrP106-126 by p75(NTR) polyclonal antibody sc-6189 or pretreatment with inhibitor NF-kappaB SN50 reduced the activation of NF-kappaB and attenuated the apoptotic effect by PrP106-126. This study offers a possible interpretation that NF-kappaB signaling pathway was activated by the interaction of PrP106-126 with p75(NTR), and NF-kappaB activity showed the pro-apoptotic effect in PrP106-126-induced apoptosis in N2a cells. Involvement of NF-kappaB signaling pathway in p75(NTR)-mediated apoptosis may partially account for the PrP106-126-induced neurotoxicity in N2a cells.


Radioimmunoassay for normalized thyroxine with use of Sephadex columns.
We describe a reproducible radioimmunoassay, with use of Sephadex columns, for measuring normalized thyroxine. In comparison with a competitive protein-binding procedure, the present method is more specific because antibody rather than thyroxine-binding globulin is responsible for the competition between endogeneous and tracer thyroxine. In barbital buffer, various concentrations of thyroxine binding pre-albumin and albumin had no influence on the results. Values obtained by the present method correlated well with those by the free thyroxine index and a generally accepted thyroxine normalized method.


Defining the concept of self-care.
Self-care is a concept frequently referred to in both the theory and the clinical practice of nursing. This article presents an overview of self-care theory as described by Henderson, Hall, and Orem. Self-care theory operates on the assumption that all individuals have a need to care for themselves. While this premise may be true, it poses difficult questions for the nurse who must intervene with patients who refuse to achieve their maximum level of independence. When a disease process occurs that alters self-image, some patients (particularly elderly females who have cared for others most of their adult lives) may consciously opt to become the ones cared for. This choice gives them a temporary sense of control over a situation in which they feel helpless. When nursing care is directed toward returning control of the situation to the patient, the process of self-care and healing can begin.


Spontaneous Intracranial Hypotension Presenting as a "Pseudo-Chiari 1.
Spontaneous intracranial hypotension (SIH) is classified as a decrease in cerebrospinal fluid (CSF) pressure secondary to a CSF leakage and consequent descent of the brain into the foramen magnum. Diagnosing SIH can be difficult due to its overlapping findings with Arnold-Chiari type 1 Malformation (CM1) where the cerebellar tonsils herniate into the foramen magnum. The similarity of both conditions calls for a more reliable imaging technique to localize the CSF leak which could narrow the differential diagnosis and aid in choosing the correct treatment. Here, we present a case of a 28-year-old female, ten weeks post-partum with symptoms similar to SIH. MRI of the brain was remarkable for tonsillar herniation below the foramen magnum. Literature was reviewed for additional neuroradiology techniques that would aid in narrowing our differential diagnosis. Interestingly, computed tomography-, digital subtraction-, and magnetic resonance myelography with intrathecal gadolinium are the preferred techniques for diagnosis of high flow and low flow CSF leaks, respectively. These modalities further aid in choosing the correct treatment while avoiding complications. Literature suggests that treatment for CM1 involves posterior fossa decompression, whereas the mainstay of treatment for SIH involves an epidural blood patch (EBP). Thus, our patient was treated with an EBP and recovered without complication.


Generation of cell type-specific monoclonal antibodies for the planarian and optimization of sample processing for immunolabeling.
Efforts to elucidate the cellular and molecular mechanisms of regeneration have required the application of methods to detect specific cell types and tissues in a growing cohort of experimental animal models. For example, in the planarian Schmidtea mediterranea, substantial improvements to nucleic acid hybridization and electron microscopy protocols have facilitated the visualization of regenerative events at the cellular level. By contrast, immunological resources have been slower to emerge. Specifically, the repertoire of antibodies recognizing planarian antigens remains limited, and a more systematic approach is needed to evaluate the effects of processing steps required during sample preparation for immunolabeling. To address these issues and to facilitate studies of planarian digestive system regeneration, we conducted a monoclonal antibody (mAb) screen using phagocytic intestinal cells purified from the digestive tracts of living planarians as immunogens. This approach yielded ten antibodies that recognized intestinal epitopes, as well as markers for the central nervous system, musculature, secretory cells, and epidermis. In order to improve signal intensity and reduce non-specific background for a subset of mAbs, we evaluated the effects of fixation and other steps during sample processing. We found that fixative choice, treatments to remove mucus and bleach pigment, as well as methods for tissue permeabilization and antigen retrieval profoundly influenced labeling by individual antibodies. These experiments led to the development of a step-by-step workflow for determining optimal specimen preparation for labeling whole planarians as well as unbleached histological sections. We generated a collection of monoclonal antibodies recognizing the planarian intestine and other tissues; these antibodies will facilitate studies of planarian tissue morphogenesis. We also developed a protocol for optimizing specimen processing that will accelerate future efforts to generate planarian-specific antibodies, and to extend functional genetic studies of regeneration to post-transcriptional aspects of gene expression, such as protein localization or modification. Our efforts demonstrate the importance of systematically testing multiple approaches to species-specific idiosyncracies, such as mucus removal and pigment bleaching, and may serve as a template for the development of immunological resources in other emerging model organisms.


New method to evaluate water-soluble antioxidant activity based on protein structural change.
A simple method to evaluate antioxidant activities of water-soluble ingredients of foods has been developed. Protective effects of antioxidants against hypochlorite radical or hydroxyl radical have been studied by comparing changes in absorbance of myoglobin (a standard reference) at 409 nm. Protective ratio, defined by absorbance changes of myoglobin with or without the antioxidant, was a good indicator to quantitatively evaluate the antioxidant activity against the hypochlorite radical or the hydroxyl radical, respectively. Radar charts indicating the antioxidant activities against DPPH (1,1-diphenyl-2-picrylhydrazyl), hypochlorite radical, and hydroxyl radical clearly differentiated the characteristics of five antioxidants including carnosine, glutathione, and vitamin C. By comparison of the radar charts, antioxidant activity of bonito meat hydrolysate was found to have similar characteristics to that of carnosine. The simple method proposed in this study would be useful for evaluating and characterizing the activities of water-soluble antioxidants contained in various food materials.


A New Model Trypanosomatid, Novymonas esmeraldas: Genomic Perception of Its "Candidatus Pandoraea novymonadis" Endosymbiont.
The closest relative of human pathogen Leishmania, the trypanosomatid Novymonas esmeraldas, harbors a bacterial endosymbiont "Candidatus Pandoraea novymonadis." Based on genomic data, we performed a detailed characterization of the metabolic interactions of both partners. While in many respects the metabolism of N. esmeraldas resembles that of other Leishmaniinae, the endosymbiont provides the trypanosomatid with heme, essential amino acids, purines, some coenzymes, and vitamins. In return, N. esmeraldas shares with the bacterium several nonessential amino acids and phospholipids. Moreover, it complements its carbohydrate metabolism and urea cycle with enzymes missing from the "Ca. Pandoraea novymonadis" genome. The removal of the endosymbiont from N. esmeraldas results in a significant reduction of the overall translation rate, reduced expression of genes involved in lipid metabolism and mitochondrial respiratory activity, and downregulation of several aminoacyl-tRNA synthetases, enzymes involved in the synthesis of some amino acids, as well as proteins associated with autophagy. At the same time, the genes responsible for protection against reactive oxygen species and DNA repair become significantly upregulated in the aposymbiotic strain of this trypanosomatid. By knocking out a component of its flagellum, we turned N. esmeraldas into a new model trypanosomatid that is amenable to genetic manipulation using both conventional and CRISPR-Cas9-mediated approaches. IMPORTANCENovymonas esmeraldas is a parasitic flagellate of the family Trypanosomatidae representing the closest insect-restricted relative of the human pathogen Leishmania. It bears symbiotic bacteria in its cytoplasm, the relationship with which has been established relatively recently and independently from other known endosymbioses in protists. Here, using the genome analysis and comparison of transcriptomic profiles of N. esmeraldas with and without the endosymbionts, we describe a uniquely complex cooperation between both partners on the biochemical level. We demonstrate that the removal of bacteria leads to a decelerated growth of N. esmeraldas, substantial suppression of many metabolic pathways, and increased oxidative stress. Our success with the genetic transformation of this flagellate makes it a new model trypanosomatid species that can be used for the dissection of mechanisms underlying the symbiotic relationships between protists and bacteria.


Repetitive transcranial magnetic stimulation of the supplementary motor area in treatment-resistant obsessive-compulsive disorder: An open-label pilot study.
Obsessive-compulsive disorder (OCD) is a severely distressing disorder represented by obsessions and compulsions. A significant proportion of OCD patients fail to improve with conventional treatment methods. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an alternative for OCD treatment. Functional neuroimaging studies indicate that OCD is associated with increased activity in the supplementary motor area (SMA), a region that plays an important role in the pathophysiology of this disorder. In this study, we assessed the efficacy of augmentation with 1Hz rTMS over the SMA in treatment-resistant OCD patients. The participants received 1Hz rTMS over the SMA in 20 daily sessions for 4weeks. We observed significant reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score at the 4th week of the treatment. Reduction in compulsion contributed to the reduction of global Y-BOCS whereas there was no significant reduction in obsession. Clinical global impression-global improvement also showed significant change at the 2nd and 4th week of the treatment. No additional significant changes or significant adverse effects were seen. These findings suggest that 1Hz rTMS over the SMA can be an efficient and safe add-on therapeutic method in treatment-resistant patients with OCD. Further controlled studies in larger samples are required to confirm the effect of 1Hz rTMS over the SMA in OCD.


Characteristics of the microwave pyrolysis and microwave CO2-assisted gasification of dewatered sewage sludge.
Microwave drying-pyrolysis or drying-gasification characteristics were examined to convert sewage sludge into energy and resources. The gasification was carried out with carbon dioxide as a gasifying agent. The examination results were compared with those of the conventional heating-type electric furnace to compare both product characteristics. Through the pyrolysis or gasification, gas, tar, and char were generated as products. The produced gas was the largest component of each process, followed by the sludge char and the tar. During the pyrolysis process, the main components of the produced gas were hydrogen and carbon monoxide, with a small amount of hydrocarbons such as methane and ethylene. In the gasification process, however, the amount of carbon monoxide was greater than the amount of hydrogen. In microwave gasification, a large amount of heavy tar was produced. The largest amount of benzene in light tar was generated from the pyrolysis or gasification. Ammonia and hydrogen cyanide, which are precursors of NOx, were also generated. In the microwave heating method, the sludge char produced by pyrolysis and gasification had pores in the mesopore range. This could be explained that the gas obtained from the microwave pyrolysis or gasification of the wet sewage sludge can be used as an alternative fuel, but the tar and NOx precursors in the produced gas should be treated. Sludge char can be used as a biomass solid fuel or as a tar removal adsorbent if necessary.


A metric of our own: Failure to rescue after trauma.
Failure to rescue (FTR) is defined as death after an adverse event. The original metric was derived in elective surgical populations and reclassifies deaths not preceded by recorded adverse events as FTR cases under the assumption these deaths resulted from missed adverse events. This approach lacks face validity in trauma because patients often die without adverse events as a direct result of injury. Another common approach simply excludes deaths without recorded adverse events, but this approach reduces the reliability of the FTR metric. We hypothesized that a hybrid metric excluding expected deaths but otherwise including patients without recorded adverse events in FTR analysis would improve face validity and reliability relative to existing methods. Using 3 years of single-state adult trauma registry data from 30 trauma centers, we constructed 3 FTR metrics: (1) excluding deaths not preceded by adverse events (FTR-E), (2) reclassifying deaths not preceded by adverse events (FTR-R), and (3) including deaths not preceded by adverse events in FTR analysis except those with predicted mortality or greater than 50% (FTR-T). Mortality, adverse event, and FTR rates were calculated under each method, and reliability was tested using Spearman correlation for split-sample center rankings. A total of 89,780 patients were included (median age, 57 years [interquartile range, 26-73 years]; 85% were white; 59% were male; 92% had blunt mechanism of injury; median Injury Severity Score, 9 [interquartile range, 5-14]). The FTR rates varied by metric (FTR-E, 11.2%; FTR-R, 31.2%; FTR-T, 21.4%), as did the proportion of deaths preceded by adverse events (FTR-E, 28%; FTR-R, 100%; FTR-T, 60%). Spit-sample reliability was higher FTR-T than FTR-E (ρ = 0.59 vs. = 0.27, p < 0.001). A trauma-specific FTR metric increases face validity and reliability relative to other FTR methods that may be used in trauma populations. Future trauma outcomes studies examining FTR rates should use a metric designed for this cohort. Retrospective cohort study, outcomes, level III.


A real-world clinical validation for AI-based MRI monitoring in multiple sclerosis.
Modern management of MS targets No Evidence of Disease Activity (NEDA): no clinical relapses, no magnetic resonance imaging (MRI) disease activity and no disability worsening. While MRI is the principal tool available to neurologists for monitoring clinically silent MS disease activity and, where appropriate, escalating treatment, standard radiology reports are qualitative and may be insensitive to the development of new or enlarging lesions. Existing quantitative neuroimaging tools lack adequate clinical validation. In 397 multi-center MRI scan pairs acquired in routine practice, we demonstrate superior case-level sensitivity of a clinically integrated AI-based tool over standard radiology reports (93.3% vs 58.3%), relative to a consensus ground truth, with minimal loss of specificity. We also demonstrate equivalence of the AI-tool with a core clinical trial imaging lab for lesion activity and quantitative brain volumetric measures, including percentage brain volume loss (PBVC), an accepted biomarker of neurodegeneration in MS (mean PBVC -0.32% vs -0.36%, respectively), whereas even severe atrophy (>0.8% loss) was not appreciated in radiology reports. Finally, the AI-tool additionally embeds a clinically meaningful, experiential comparator that returns a relevant MS patient centile for lesion burden, revealing, in our cohort, inconsistencies in qualitative descriptors used in radiology reports. AI-based image quantitation enhances the accuracy of, and value-adds to, qualitative radiology reporting. Scaled deployment of these tools will open a path to precision management for patients with MS.


Hip fracture surgery: does time of the day matter? A case-controlled study.
A prevailing perception regarding night time surgery is that the probability of complications may be higher due to decreased availability of support staff, surgeon fatigue and other logistical factors. However there is little data supporting this notion in hip fracture surgery and we studied this in the context of Inter-trochanteric fractures fixed with dynamic hip screws (DHS). All patients who underwent DHS fixation for inter-trochanteric fracture from January 2005 to December 2010 were included. Patients were divided into two groups. An after-hours group was defined as an operation done between 5:00 P.M. to 7:00 A.M. and a daytime group was defined as surgery done between 7:00 A.M. to 5:00 P.M. Data was analyzed using SPSS version 19. During this period 194 patients underwent DHS fixation. One hundred and fourteen patients were included in the daytime group and 80 patients in the after-hours group. There was no difference in the rates of wound infection, length of hospital stay, postoperative ambulation status, intra op blood loss, type of anesthesia, and mortality between the two groups. Tip apex index was found to be similar between the two groups. Two patients in the daytime surgery required revision surgery compared to 5 patients in the after-hours group, however this difference was not statistically significant. Outcomes in terms of adequacy of fixation, post-operative complications and post-operative 30-day mortality are comparable to routine day time surgery while offering the benefits of early fixation and mobilization to the patient. This also has a positive impact on the financial burden on this population as early fixation translates into decreased length of stay and reduced cost of treatment.


Camptothecin induced DDX5 degradation increased the camptothecin resistance of osteosarcoma.
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Unfortunately, chemo-resistance is a huge obstacle in the treatment of OS. However, the underlying molecular mechanisms of OS chemo-resistance still remain unknown. Here we reported that the resistance to camptothecin (cpt) therapy was driven by degradation of DDX5. DDX5 knockdown decreased cell death and DNA damage and recovered cell proliferation in cpt treated 143B cells. Furthermore, we found that DDX5 bound to NONO, a kind of DNA repairing protein, and regulated NONO functions. Our data verified that cpt-induced degradation of DDX5 following by breaking down the protein bound of NONO, which participated in the resistance of cpt. In the summary, according to our results, DDX5 might be a potential therapeutic target for improving clinical outcomes of cpt in OS.


miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesis.
miR-375 is a tumor-suppressive microRNA (miRNA) in gastric cancer (GC). However, its molecular mechanism remains unclear. The aim of this study is to comprehensively investigate how miR-375 is involved in Hippo pathway by targeting multiple oncogenes. miR-375 expression in gastric cancer cell lines and primary GC was investigated by qRT-PCR. The regulation of YAP1, TEAD4, and CTGF expression by miR-375 was evaluated by qRT-PCR, western blot, and luciferase reporter assays, respectively. The functional roles of the related genes were examined by siRNA-mediated knockdown or ectopic expression assays. The clinical significance and expression correlation analysis of miR-375, YAP1, and CTGF were performed in primary GCs. TCGA cohort was also used to analyze the expression correlation of YAP1, TEAD4, CTGF, and miR-375 in primary GCs. miR-375 was down-regulated in GC due to promoter methylation and histone deacetylation. miR-375 downregulation was associated with unfavorable outcome and lymph node metastasis. Ectopic expression of miR-375 inhibited tumor growth in vitro and in vivo. Three components of Hippo pathway, YAP1, TEAD4 and CTGF, were revealed to be direct targets of miR-375. The expression of three genes showed a negative correlation with miR-375 expression and YAP1 re-expression partly abolished the tumor-suppressive effect of miR-375. Furthermore, CTGF was confirmed to be the key downstream of Hippo-YAP1 cascade and its knockdown phenocopied siYAP1 or miR-375 overexpression. YAP1 nuclear accumulation was positively correlated with CTGF cytoplasmic expression in primary GC tissues. Verteporfin exerted an anti-oncogenic effect in GC cell lines by quenching CTGF expression through YAP1 degradation. In short, miR-375 was involved in the Hippo pathway by targeting YAP1-TEAD4-CTGF axis and enriched our knowledge on the miRNA dysregulation in gastric tumorigenesis.


Synthesis and catalytic activity of iron complexes with bidentate NHC ligands.
A family of well-defined Fe(II) complexes of the type {BnN(N-CH2(CH2)n-N'-tert-butyl-imidazole-2-ylidene)2}FeCl2 (Bn = benzyl; n = 1 (1) or 2 (2)), {BnN(N-CH2(CH2)n-N'-methylbenzimidazole-2-ylidene)2}FeCl2 (n = 1 (3) or 2 (4)) and {BnN(N-CH2CH2CH2-N'-methylbenzimidazole-2-ylidene)2}FeBr2 (5) has been synthesized. These complexes are rare examples of Fe species supported by bidentate NHC ligands. Complexes 2, 3, 4 and 5 were characterized by X-ray crystallography and in all cases a distorted tetrahedral geometry is observed around the Fe center. The magnetic data is consistent with the complexes containing non interacting high spin Fe(II) centers (S = 2) and indicates that a large zero-field splitting (D) is present. The new complexes are highly active pre-catalysts for the homo-coupling of Grignard reagents.


[Selective proximal vagotomy with and without pyloroplasty--results of a randomized clinical study of duodenal ulcer 5 and 8 years after surgery].
Selective proximal vagotomy (SPV) with pyloroplasty (n = 39) and without (n = 39) were compared five and eight years after surgery in a randomized clinical study. Pyloroplasty according to Finney had no effect on ulcer recurrence rates after both periods of time (7.9:7.9 or 10.8:8.3 per cent). Additional pyloroplasty, too, had no statistically significant effect on incidence and severity of post-vagotomy syndrome, dumping and diarrhoea, though some trend towards an increase was discernible in wake of pyloroplasty. Occurrence of the lactase deficit syndrome after SPV with pyloroplasty was increased with statistical significance. Lasting loss of senses of appetite and saturation was observed for the first time after SPV, on top of the lactase deficit syndrome. Clinical results recorded after five and eight years did not reveal any significant difference between both groups. These findings are likely to suggest that SPV without pyloroplasty is sufficient for surgical treatment of duodenal ulcer. However, pyloroplasty in combination with SPV has continued to be fully indicated for no-resection therapy of ulcerogenic pyloric stenosis.


Effect of dialysis initiation for preemptively listed candidates in the revised kidney allocation policy.
The new allocation policy for deceased donor kidneys in the United States is expected to begin in late 2014. As part of this policy, prioritization to the highest quality deceased donor kidneys is dependent on candidate's estimated posttransplant survival (EPTS) score. In particular, candidates with low (≤20%) EPTS (indicating better estimated survival) will have greater access to donor offers. We evaluated the effect of dialysis initiation on preemptively listed candidates' EPTS score. Using current estimates, approximately 10% (n = 19,406) of candidates placed on the waiting list between 2008 and 2013 were listed preemptively and would have qualified for top 20% status. These patients were more likely younger, female, Caucasian and nondiabetic compared to other candidates. Among nondiabetic preemptively listed candidates, dialysis initiation decreases EPTS score (indicating better estimated survival and higher allocation priority) for approximately 5 months. In contrast, diabetic patients' EPTS score significantly increases (approximately 6%) immediately upon dialysis initiation. Our results reveal a counterintuitive aberration in the EPTS formula, which is important for decision making regarding organ selection and timing of dialysis initiation in the new allocation system. Revision of the EPTS formula should be considered to address these findings and further understanding of the impact of the new allocation system on candidates' prognosis is important.


Glucose infusion rates from various complex carbohydrates estimated from two models.
Due to the importance of diet in the management of noninsulin dependent diabetes, we are interested in constructing a model to study the glycemic response to different foods in normal and diabetic subjects. In this study, serum glucose and insulin values from individual normal subjects (Diab. 26, 1178) following the ingestion of different foods (corn, rice, bread, potato) high in complex carbohydrate were analyzed to determine glucose infusion rates (J) into the blood from the gut as a function of time following the ingestion of the food item. A Modular Modeling Program was designed to allow selection of data, curve fit, model, and tuning of parameters. The two models used were from Ackerman et al (Phys. Med. Biol. 9, 203) and the minimal model (VI) from Bergman and Cobelli (Fed. Proc. 39,110). The models were modified so that glucose and insulin values were used as input and J was the output. There was a good correspondence between the shape of the J curves predicted by the two models. While the J curves resembled serum glucose curves, they generally reached a peak earlier and declined more rapidly. Two peaks occurred in the J curves for bread, corn and rice. The second peaks may correspond to a delay in the release of glucose during digestion. The resulting infusion rate characterization of these foodstuffs maybe useful for modeling responses in diabetic patients with normal gut function but with impaired peripheral glucose utilization and in detecting abnormal gut function.


Social Media Awareness and Implications in Nursing Leadership.
Many nursing professionals-may be reluctant to engage in or are confused about appropriate use of social media in a clinical, research, or policy context. To address this issue, we developed a study to enhance nurse leaders' facility with social media in the context of a national professional meeting. This study examined a social media campaign at the 2015 American Academy of Nursing conference. The campaign was intended to bridge the gap between active social media users and nonusers attending the conference. Following a targeted social media campaign at the American Academy of Nursing 2015 Transforming Health, Driving Policy Conference, responses to the conference evaluation questions about social media were reviewed and analyzed. Overall, evaluations were positive about the campaign; however, some conference attendees were not aware of its various components. Despite perceived barriers to its use, there is significant curiosity about social media use among nurse leaders. With the engagement of these leaders, there may be opportunities to enhance social media use at professional meetings and to make broader use of this valuable tool throughout the nursing profession.


Alternative organization of speech perception deficits in children.
Children's first-language perception base takes shape gradually from birth onwards. Empirical research has confirmed that children may continue to fall short of age-based expectations in their speech perception. The purpose of this study was to assess the contribution of various perception processes in both reading and learning disabled children. A series of experiments was carried out with 450 Hungarian-speaking schoolchildren: learning disabled, reading disabled and typically developing control first-, second-, and third-graders. Data from seven perception tasks - focusing on acoustic, phonetic and phonological perception processes - were analysed. Results revealed that (i) there is no linear development in all groups across ages, (ii) correct performance is characteristic of both the perception process and the type of disability, and (iii) a specific pattern of organization can be drawn up as a factor in development.


Proposed metrics for the determination of rheumatoid arthritis outcome and treatment success and failure.
Patients with rheumatoid arthritis (RA) and their physicians often disagree as to the success of RA treatment or RA outcomes. However, guidelines (such as EULAR criteria for DAS scores) are heavily weighted toward joint counts and laboratory tests, and no guidelines exist for patient reported outcomes. Our aims were (1) to provide a patient-based definition of successful RA outcome or of treatment success and failure; (2) to describe the characteristics of patients meeting this definition; (3) to describe how external states such as disability and comorbidity influence definitions of health outcome; and (4) to derive surrogate-measure cutpoints for the definition. A total of 20,268 patients with RA (5132 without comorbidity) were studied by recursive partitioning and regression methods to determine best dividing points between RA treatment and outcome success and non-success using 0-10 visual analog scales (VAS) for patient global assessment, pain, fatigue, and RA activity, and a Health Assessment Questionnaire (HAQ) scale. 14.5% of all patients and 22.9% of those without comorbidity were very satisfied with their health (success). Patient global at a level<or=1.25 best separated success from failure. Mean and median scores for those who were very satisfied were HAQ (0-3 scale) 0.36, 0.12; pain (0-10) 1.1, 0.5; global (0-10) 0.9, 0.5; and fatigue (0-10) 1.5, 1.0. VAS scores increased by approximately 0.5 units for each comorbid condition. Patient global at a level<or=1.25 best separates patients who are very satisfied with their health from those not very satisfied, regardless of the presence of comorbidity. All scores increase with increasing comorbidity, which must be accounted for when assessing individual patients. Values identified here suggest patients require better outcomes than are found in patients who are in Disease Activity Score-28 remission or OMERACT low disease activity states.


Suicidal Behavior Among Elderly Inpatients: its Relation to Functional Disability and Pain.
Suicidal behavior (SB) among elderly inpatients has exhibited a growing global drift. This study aimed to establish the prevalence of SB among elderly inpatients and identify the relationship between SB and depression and functional disability. This cross-sectional study included 136 randomly selected elderly inpatients aged 60 years and older who were hospitalized in a tertiary referral center in Kuala Lumpur, Malaysia. The study utilized the following scales as the assessment tools: The Columbia Suicide Severity Rating Scale (CSSRS), Geriatric Depression Scale (GDS-15), Mini International Neuropsychiatric Interview (M.I.N.I.), the Modified Barthel Index (Shah version) (MBI), and visual analog scale. The rates of current major depressive disorder (MDD), recurrent MDD, passive suicidal ideation (SI), and active SI were 24.3%, 8.8%, 27.9%, and 5.9%, respectively. Depressed elderly had 6 to 17 times higher risk of developing passive or active SI. "Wish to be dead," ie, passive SI was associated with admission to oncology or surgical ward and the presence of current MDD. The findings of the study revealed that active SI was associated with being over 80 years old (p = 0.027), being single (p = 0.042), admission to the oncology ward (p = 0.012) or orthopedic ward (p = 0.032), having positive GDS (p = 0.049), and the presence of current MDD (p = 0.019) or recurrent MDD (p = 0.010). According to the study findings, no association has been observed between passive and active SI and level of independence and acute pain. The risk of depressed elderly inpatients having passive and active SI is high. Hence, screening for depression and SI is crucial for prompt treatment and management.


Significance of gamma-glutamyltranspeptidase in exocrine pancreatic amino acid transport.
The exocrine pancreas is rich in gamma-glutamyltranspeptidase (GGT, EC 184.108.40.206) and exhibits high rates of amino acid transport and protein synthesis. The role of the gamma-glutamyl cycle in mediating neutral amino acid transport in the isolated perfused rat pancreas was investigated using acivicin, an inhibitor of GGT, and a rapid dual isotope dilution technique. When treatment in vivo with acivicin (50 mg/kg) was followed 1 h later by continuous perfusion of the isolated pancreas with 10 microM acivicin, GGT levels decreased from 53 +/- 3 IU/g to 4.9 +/- 1.5 IU/g. This marked inhibition of GGT activity was not associated with decreased uptake for either L-alanine or L-glutamine, suggesting that the gamma-glutamyl cycle plays a negligible role in amino acid transport across the basolateral membrane of the pancreatic epithelium.


Professional oral health care for preventing nursing home-acquired pneumonia: A cost-effectiveness and value of information analysis.
Professional oral health care (POHC) prevents nursing home-acquired pneumonia (NHAP) and its related mortality. We assessed the cost-effectiveness of POHC versus no POHC (nPOHC) and the monetary value of eliminating uncertainty by future research. A German public-private payer perspective was adopted. A Markov model was used, following long-term care residents from admission to death. Cost-effectiveness was estimated as Euro/disability-adjusted life year (DALY) using Monte Carlo microsimulations. Value-of-information analyses were performed. The willingness-to-pay threshold/DALY was assumed to be 66% (range 50%-100%) of per-capita gross domestic product (GDP). nPOHC was less costly (€3,024) but also less effective (0.89 DALYs) than POHC (€10,249, 0.55 DALYs). For most presumed payers, POHC was cost-effective. The cost-effectiveness of POHC was higher in smokers, underweight or pulmonary disease patients. Eliminating uncertainty about the NHAP costs, NHAP incidence/mortality, and POHC effectiveness would result in an expected net value of 47 million €/year (and even higher values at lower GDP thresholds), and is likely to decrease with time. Within the chosen setting and on the basis of current evidence, POHC was cost-effective. Given the detected uncertainty, further research seems warranted.


Probiotic level effects on growth performance, carcass traits, blood parameters, cecal microbiota, and immune response of broilers.
Probiotic effects on growth performance, carcass traits, blood parameters, cecal microbiota, and immune response of broilers were studied. Two hundred one-day-old male chickens were allocated to one of five treatments (four replicates of 10 birds per treatment): control, and the same control diet supplemented with 0.005%, 0.01%, 0.015% and 0.02% probiotics. Probiotics in feed at 0.01% or higher levels of supplementation improved body weight gain (+12%) and feed conversion rate (-5%) compared with the control. There were no effects on carcass traits, but the relative weights of drumsticks and wings showed increasing and decreasing linear responses, respectively, to probiotic supplementation level. Blood plasma glucose and albumin contents linearly increased (from 167.1 to 200.5 mg dl-1, and from 1.70 to 3.25 g dl-1) with increasing probiotic supplementation. Triglycerides and cholesterol contents were lower in probiotic supplemented treatments (average contents 71.3 and 125.3 mg dl-1 vs. 92.6 and 149.9 mg dl-1 in the control). Probiotics decreased cecal Escherichia coli counts, but had no effects on immunity related organs or immune response. The linear trends, either positive or negative, observed in many of the parameters studied, suggest that more studies are needed to establish the optimal concentration of probiotics in broiler feed.