Paclitaxel-loaded star-shaped copolymer nanoparticles for enhanced malignant melanoma chemotherapy against multidrug resistance.
Malignant melanoma (MM) is the most dangerous type of skin cancer with annually increasing incidence and death rates. However, chemotherapy for MM is restricted by low topical drug concentration and multidrug resistance. In order to surmount the limitation and to enhance the therapeutic effect on MM, a new nanoformulation of paclitaxel (PTX)-loaded cholic acid (CA)-functionalized star-shaped poly(lactide-co-glycolide) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (NPs) (shortly PTX-loaded CA-PLGA-TPGS NPs) was fabricated by a modified method of nanoprecipitation. The particle size, zeta potential, morphology, drug release profile, drug encapsulation efficiency, and loading content of PTX-loaded NPs were detected. As shown by confocal laser scanning, NPs loaded with coumarin-6 were internalized by human melanoma cell line A875. The cellular uptake efficiency of CA-PLGA-TPGS NPs was higher than those of PLGA NPs and PLGA-TPGS NPs. The antitumor effects of PTX-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that star-shaped PTX-loaded CA-PLGA-TPGS NPs were significantly superior to commercial PTX formulation Taxol®. Such drug delivery nanocarriers are potentially applicable to the improvement of clinical MM therapy.


Interaction of lithium and disulfiram in hexobarbital hypnosis: possible role of the 5-HT system.
The effects of lithium and disulfiram on the 5-hydroxytryptamine (5-HT) system and hexobarbital (HX)-induced hypnosis were studied. Treatment with lithium significantly prolonged HX hypnosis. Disulfiram, a potent inhibitor of brain aldehyde dehydrogenase, also produced a prolongation of HX hypnosis. A combination of lithium treatment for 3 days with disulfiram synergistically potentiated the HX hypnosis and reduced the brain HX levels on awakening. Furthermore, L-tryptophan loading significantly increased the HX sleeping time and reduced the brain HX level on awakening in lithium-pretreated rats, whereas it had not effect on HX hypnosis in controls rats. L-Tryptophan also potentiated HX hypnosis in disulfiram-treated rats. The combination of L-tryptophan, lithium and disulfiram caused the greatest prolongation of HX hypnosis. However, no synergism between lithium and disulfiram was observed in animals treated with lithium for 5 days. after 3 days of lithium treatment, the rate of synthesis of 5-HT was elevated, whereas it had returned to the control level after 5 days of lithium treatment. Tryptophan loading increased the rate of synthesis of 5-HT more than 2-fold in control animals. The increase in the rate of 5-HT synthesis caused by lithium was further potentiated by tryptophan loading. These results suggest that lithium and disulfiram exert their synergistic effect on HX hypnosis by acting on the 5-HT system and that an accumulation of 5-hydroxyindoleacetaldehyde, an active metabolite of 5-HT, may be responsible for the increase in the brain sensitivity to barbiturates caused by these drugs.


Morphological and mineral characteristics of peripheral blood in female polar fox in relation to age.
The aim of the study was to determine the values of selected haematological and biochemical parameters in peripheral blood of female polar fox in relation to the age of the animals. The research involved 50 polar fox females three months after the lactation period (i.e. the non-mating period). Animals were divided into 5 age groups (n = 10), ranging from 1 to 5 years of age. In blood samples the following parameters were determined: RBC, Ht, Hb, WBC, PLT, red blood cell parameters (MCV, MCH, MCHC) and the percentage of respective kinds of white blood cells in the total number of leukocytes. The content of Ca, Pi, Na, K, Cl, Mg, Fe, Cu and Zn as well as the ALP and ACP activity was determined in blood serum. In comparison with one year-old females, in peripheral blood of females from the remaining age groups an increase in RBC, Ht and Hb content was observed as well as a significant (P < 0.05) decrease in WBC level together with a lower number of lymphocytes and an increase in the relative content of granulocytes and monocytes. No distinct relationship between the content of Ca, Na, Cl, Mg, Cu, Zn, the activity of ALP and ACP and the age of the animals was observed. The highest concentration of Pi and K was found in the blood serum of one year-old females. The content of Fe decreased with age and was lowest in 5 year-old animals (P < 0.05).


Mechanism of O2 activation by cytochrome P450cam studied by isotope effects and transient state kinetics.
The early steps in dioxygen activation by the monooxygenase cytochrome P450cam (CYP101) include binding of O2 to ferrous P450cam to yield the ferric-superoxo form (oxyP450cam) followed by an irreversible, long-range electron transfer from putidaredoxin to reduce the oxyP450cam. The steady state kinetic parameter kcat/Km(O2) has been studied by a variety of probes that indicate a small D2O solvent isotope effect (1.21 +/- 0.08), a very small solvent viscosogen effect, and a 16O/18O isotope effect of 1.0147 +/- 0.0007. This latter value, which can be compared with the 16O/18O equilibrium isotope effect of 1.0048 +/- 0.0003 measured for oxyP450cam formation, is attributed to a primarily rate-limiting outer-sphere electron transfer from the heme iron center as O2 that has prebound to protein approaches the active site cofactor. The electron transfer from putidaredoxin to oxyP450cam was investigated by rapid mixing at 25 degrees C to complement previous lower-temperature measurements. A rate of 390 +/- 23 s-1 (and a near-unity solvent isotope effect) supports the view that the long-range electron transfer from reduced putidaredoxin to oxyP450cam is rapid relative to dissociation of O2 from the enzyme. P450cam represents the first enzymatic reaction of O2 in which both equilibrium and kinetic 16O/18O isotope effects have been measured.


The binding of an auditory target location to a judgement: A two-component switching approach.
In a two-component switching paradigm, in which participants switched between two auditory attention selection criteria (attention component: left vs. right ear) and two judgements (judgement component: number vs. letter judgement), we found high judgement switch costs in attention criterion repetitions, but low costs in attention criterion switches. This finding showed an interaction of components. Previous two-component switching studies observed differently emphasised interaction patterns. In the present study, we explored whether the strength of the interaction pattern reflects the strength of the binding of target location and judgement. Specifically, we investigated whether exogenous target location cueing led to weaker binding than endogenous cueing, and whether preparation for ear selection could influence the binding. Attention switches with auditory exogenous target location cues did not affect the component interaction pattern, whereas a prolonged preparation interval led to a more emphasised pattern. Binding between target location and judgement may therefore be rather automatic and may not necessarily require concurrent component processing. Sufficient time for target location switches with long preparation time may activate the previous trial's episode or facilitate switches of the subsequent judgement.


Infarcts in the anterior choroidal artery territory. Anatomical distribution, clinical syndromes, presumed pathogenesis and early outcome.
From a prospective registry of all consecutive patients with a supratentorial ischaemic stroke, those with a compatible CT lesion were selected to study topographical relationship, clinical syndrome, vascular risk factors, signs of large-vessel disease or cardiogenic embolism, and mortality in cases with an infarct in the anterior choroidal artery (AChA) territory in comparison with other infarct subtypes. First we identified the area supplied by the AChA: in accordance with the consensus in the literature the posterior two-thirds of the posterior leg of the internal capsule was considered as certain AChA territory. After reviewing CT scans, all presumed small deep AChA territory infarcts were displayed in a schematic composite picture of super-imposed areas of infarction in different shades of grey. Infarcts that were located largely outside the generally included territory were presumed to belong to a different vascular territory. Thus, 77 small deep infarcts were considered to be located within, and 83 outside the AChA territory. Twenty-nine AChA infarcts extended from the internal capsule upwards into the posterior paraventricular corona radiata region. Furthermore, the composite representation of 26 infarcts restricted to the posterior part of the paraventricular corona radiata region showed almost complete overlap with the area occupied by AChA infarcts that extended upwards. We therefore concluded that the posterior paraventricular area is most likely supplied by the AChA. The frequency of a clinical lacunar or a cortical syndrome did not differ between small deep AChA and remaining small deep infarcts. Comparison of vascular risk factors by way of multivariate regression analysis only showed that a significant carotid stenosis was more frequent (adjusted odds ratio 8.87; 95% confidence interval 1.44-54.50), and a cardioembolic source was less frequent (odds ratio 0.24; 95% confidence interval 0.07-0.92) in AChA infarcts than in the other small deep infarcts. Carotid stenosis and cardiac embolism were less frequent in AChA infarcts than in superficial infarcts (odds ratio 0.33, 0.23, respectively; 95% confidence interval 0.15-0.74, 0.09-0.52, respectively). One month and one year mortality were lower in small deep infarcts compared with superficial infarcts, but most favourable in the AChA group. However, this was probably related to younger age in the AChA patients. Larger AChA infarcts were infrequent in our series; six of such cases did not differ in any respect from superficial infarcts. We conclude that the posterior paraventricular corona radiata region is most likely supplied by the AChA, and that AChA infarcts do not constitute a separate brain infarct entity.(ABSTRACT TRUNCATED AT 400 WORDS)


A Single-Center, Randomized, Controlled Comparison of the Transradial vs Transfemoral Approach for Cerebral Angiography: A Learning Curve Analysis.
Purpose: To compare the characteristics and learning curve of the transfemoral approach (TFA) vs the transradial approach (TRA) for cerebral angiography. Materials and Methods: Between February 2016 and April 2017, 101 patients undergoing cerebral angiography were enrolled. Fifty-one patients (mean age 67 years; 40 men) were randomized to TFA and 50 (mean age 68 years; 41 men) to TRA using a computer-generated random table. The patients' demographic and angiographic data were recorded and analyzed. The learning curve of a novice interventionist was analyzed for procedure time, puncture time, fluoroscopy time, and contrast volume as markers of technical proficiency with TFA compared with TRA. Median values are given with the interquartile range (IQR). Results: Procedure time [35 (IQR 30, 47.5) vs 31.0 (IQR 25.0, 48.9) minutes, p=0.16), fluoroscopy time [10.3 (IQR 7.6, 13.9) vs 9.4 (IQR 6.1, 17.6) minutes, p=0.70], contrast volume [105 (IQR 92, 120) vs 95.5 (IQR 90, 111.3) mL, p=0.13), radiation exposure [390.2 (IQR 268.2, 617.9) vs 455.8 (IQR 286.8, 602.3) mGy, p=0.74], and the number of catheter exchanges [1 (IQR 1, 3) vs 1 (IQR 1, 1), p=0.06] were not significantly different between the TFA and TRA groups, respectively, but puncture time was shorter with TFA than with TRA [0.6 (IQR 0.5, 1.1) vs 1 (IQR 0.6, 1.9) minutes, p=0.01]. The learning curve was steeper with TRA than with TFA in the beginning stages of training, but with increasing experience, the procedure and fluoroscopy times were better for TRA than for TFA. Training progress was made earlier in TRA. Conclusion: TRA is a reasonable alternative to TFA for cerebral angiography. TRA has a shorter learning curve for novice interventionists.


Self-management support and other alternatives to reduce the burden of asthma and chronic obstructive pulmonary disease.
While pharmacotherapy is important in the management of asthma and chronic obstructive pulmonary disease, it is also important to consider additional interventions that can further reduce the burden of ill health for patients, their families and the health care system. In this review, the evidence in favour of self-management support that leads to successful self-care by the patient is reviewed, and the key components of successful strategies are outlined; areas where more research is needed are identified. In addition to self-management support, other methods of delivering care, such as telemonitoring, admission avoidance, assisted discharge schemes and use of lay educators, are reviewed.


Anti-coagulation complications in pregnancies with severe pulmonary arterial hypertension.
Epoprostenol, a potent vasodilator, is the treatment of choice for severe pulmonary arterial hypertension (PAH) in pregnancy. However, its inhibition of platelet aggregation increases the risk of coagulation complications with conjunctive use of anti-coagulants for thromboprophylaxis. Case 1 demonstrates a pregnancy complicated by thrombocytopenia. Case 2 describes a pregnancy with newly diagnosed PAH at 35 weeks who delivered by repeat cesarean delivery complicated by a wound hematoma. Case 3 describes a patient who delivered at 32 weeks. She required extracorporeal membrane oxygenation and a heart-lung transplant. Her care was further complicated by severe thrombocytopenia with postpartum hemorrhage refractory to usual conservative measures. This case series describes three patients with severe PAH in pregnancy and the range of different complications that arose from anticoagulation in the setting of epoprostenol.


Seismic evidence for widespread western-US deep-crustal deformation caused by extension.
Laboratory experiments have established that many of the materials comprising the Earth are strongly anisotropic in terms of seismic-wave speeds. Observations of azimuthal and radial anisotropy in the upper mantle are attributed to the lattice-preferred orientation of olivine caused by the shear strains associated with deformation, and provide some of the most direct evidence for deformation and flow within the Earth's interior. Although observations of crustal radial anisotropy would improve our understanding of crustal deformation and flow patterns resulting from tectonic processes, large-scale observations have been limited to regions of particularly thick crust. Here we show that observations from ambient noise tomography in the western United States reveal strong deep (middle to lower)-crustal radial anisotropy that is confined mainly to the geological provinces that have undergone significant extension during the Cenozoic Era (since approximately 65 Myr ago). The coincidence of crustal radial anisotropy with the extensional provinces of the western United States suggests that the radial anisotropy results from the lattice-preferred orientation of anisotropic crustal minerals caused by extensional deformation. These observations also provide support for the hypothesis that the deep crust within these regions has undergone widespread and relatively uniform strain in response to crustal thinning and extension.


The science of nutrition - the metaphysics of food.
With respect for the differences between and among nations, there are universal principles on which public health nutrition policy should be based. An adequate food supply containing sufficient energy and all of the essential nutrients should be available and affordable. This may include nutrient-restored or fortified food products and supplements. The foods must be coherent with the cultural needs and desires of consumers. Public and private agencies, like schools and food industries, must provide exciting and accurate nutritional information in the classroom and by mass media. Individuals must have an accurate knowledge to make healthy dietary selections. The special needs of particular sub-populations, such as prenatal mothers, infants, children, adolescents, women, and the elderly, should be emphasized and addressed. Individuals should be encouraged to assume personal responsibility for their health. The avoidance through healthy lifestyles of obesity, anorexia and nutritional deficiencies should be encouraged. The sensual pleasures of food and the joy of eating with family and friends should be emphasized and enhanced. We should celebrate the complexity and diversity of our foods and cultures. We should be free to enjoy the foods that bring us health and pleasure. We should have scientific nutritional knowledge to maximize our human potential.


Effects of advancing age on the processing of semantic anomalies in adults: evidence from event-related brain potentials.
Age-related changes in the processing of sentence-embedded semantic anomalies were examined using auditory event-related potentials (ERPs). Semantically incongruous words elicited an N400 effect in middle-aged (50s: 55.6 years) and elderly (60s: 64.1 years) subjects, whereas in older elderly adults (70s: 74.9 years) this effect approached significance. N400 peak latencies were not delayed with advancing age; however, there was a reliable linear decrease in mean and peak amplitude, with slopes being similar to those previously reported for the visual N400 effect. A P600 effect was obtained in response to semantic anomalies and it was neither delayed in latency nor reduced in amplitude with advancing age. However, it was found to be larger over anterior sites in elderly and older elderly subjects.


[Integrated treatment of children with chronic renal insufficiency].
Early diagnosis of chronic renal failure in childhood is difficult, since the course of CRF shows in children with congenital renal diseases unspecific symptoms. The active cooperation of the practical pediatrician with a pediatric nephrologist enables this team for prevention of complications of chronic uremia. The integration of treatment between general pediatrician and specialist also prevents long hospitalisation and makes the prevention of the child for the best mode of treatment possible, i.g. ambulant hospital dialysis, home dialysis or CAPD. Pediatric dialysis should be performed in one of the established 14 pediatric dialysis centres in our country, because psychological, somatic and technical problems in children differ from those in adults. In dialysed children the general pediatrician should be further involved in treatment and may contribute worthy help in medical (control of drug compliance, hypertension) and psychosocial (school, employment) care of the chronic sick children. Even after successful renal transplantation the local pediatrician should continue to be involved in patient care, in spite of more frequent check up controls at hospital.


[Anesthetic management for microlaryngeal surgery with high frequency jet ventilation and intravenous application of pentazocine and propofol].
Microlaryngeal surgery was performed with total intravenous anesthesia using pentazocine and propofol in 20 patients. The patients were paralyzed by suxamethonium infusion and ventilated by high frequency jet ventilation via the laryngoscope. In place of the opioid analgesics commonly used in TIVA for microlaryngeal surgery, pentazocine was given. All but one of the patients received pentazocine 15 m.g. intramuscularly as a premedication and then another 15 m.g. intravenously for induction of anesthesia. Average time of surgeries was 33.6 minutes. Average doses of pentazocine and suxamethonium given during surgeries were 369 m.g. and 286 m.g., respectively. This technique allowed stable anesthesia to be achieved with rapid postoperative recovery, without serious complications like intraoperative return of awareness.


The origins of the vaccine cold chain and a glimpse of the future.
International efforts to eradicate smallpox in the 1960s and 1970s provided the foundation for efforts to expand immunization programmes, including work to develop immunization supply chains. The need to create a reliable system to keep vaccines cold during the lengthy journey from the manufacturer to the point of use, even in remote areas, was a crucial concern during the early days of the Expanded Programme on Immunization. The vaccine cold chain was deliberately separated from other medical distribution systems to assure timely access to and control of vaccines and injection materials. The story of the early development of the vaccine cold chain shows how a number of challenges were overcome with technological and human resource solutions. For example, the lack of methods to monitor exposure of vaccines to heat during transport and storage led to many innovations, including temperature-sensitive vaccine vial monitors and better methods to record and communicate temperatures in vaccine stores. The need for appropriate equipment to store and transport vaccines in tropical developing countries led to innovations in refrigeration equipment as well as the introduction and widespread adoption of novel high performance vaccine cold-boxes and carriers. New technologies also helped to make injection safer. Underlying this work on technologies and equipment was a major effort to develop the human resources required to manage and implement the immunization supply chain. This included creating foundational policies and a management infrastructure; providing training for managers, health workers, technicians, and others. The vaccine cold chain has contributed to one of the world's public health success stories and provides three priority lessons for future: the vaccine supply chain needs to be integrated with other public health supplies, re-designed for efficiency and effectiveness and work is needed in the longer term to eliminate the need for refrigeration in the supply chain.


[Cystic echinococcosis misdiagnosed as hepatic cyst: a case report].
This case report presents the diagnosis and treatment of a case of cystic echinococcosis misdiagnosed as hepatic cyst. The case had anaphylactic shock caused by extravasation of cyst fluid during extraction of hepatic cyst and suffered from postoperative recurrence of echinococcosis. This case report may provide insights into diagnosis and treatment of cystic echinococcosis among healthcare workers in non-endemic areas.


Sevoflurane Preconditioning Increases Stress Resistance via IMB-2/DAF-16 in Caenorhabditis Elegans.
Sevoflurane preconditioning has been proved to possess therapeutic effects on stress. However, the mechanism by which sevoflurane preconditioning protects against stress remains unclear. In this study, an acute model of heat stress in C.eleans was established. We investigated the dose-response of sevoflurane exposure on coordinated movement in C.elegans and time course for protection against heat stress of sevoflurane preconditioning to determine the optimal concentration and time point in the following experiments. EC99 of sevoflurane is 1.7% (1.3EC50) and sevoflurane preconditioning exerts the maximal protection at 6 hours after incubation, and these 2 parameters were used in our following experiments. We found that sevoflurane preconditioning increased DAF-16 nuclear translocation and enhanced the expression of DAF-16 during heat stress in N2 strain of C.elegans. DAF-16 mutation abolished the sevoflurane preconditioning-induced protection for heat stress. Furthermore, suppression of IMB-2 by RNAi prevented the upregulation of DAF-16 and enhancement of stress resistance caused by sevoflurane preconditioning. Overall, this work reveals that sevoflurane preconditioning increases the expression of DAF-16 via IMB-2 to enhance the stress resistance of C.elegans.


Brain sonography insight into the midbrain in myotonic dystrophy type 2.
The aim of this study was to analyze transcranial sonography (TCS) findings in genetically confirmed myotonic dystrophy type 2 (DM2) patients. Forty DM2 patients and 38 gender- and age-matched healthy controls (HCs) underwent TCS through the pre-auricular acoustic bone window. Substantia nigra hyperechogenicity was found in 20% of DM2 patients compared with 3% of HCs. Brainstem raphe (BR) hypoechogenicity was more common in DM2 patients compared with HCs (56% vs. 10%, P < 0.01), and it was more common in patients with fatigue and excessive daytime sleepiness (P < 0.05). Diameter of the third ventricle was increased in DM2 patients compared with HCs (5.8 ± 1.7 vs. 5.1 ± 1.0 mm, P < 0.05). Finding BR hypoechogenicity might have clinical implication because of the potential response to serotonin-reuptake inhibitors. TCS revealed alterations in brain structures previously not seen in MRI studies.


Environmental factors and spatiotemporal distribution characteristics of the global outbreaks of the highly pathogenic avian influenza H5N1.
The spread of highly pathogenic avian influenza H5N1 has posed a major threat to global public health. Understanding the spatiotemporal outbreak characteristics and environmental factors of H5N1 outbreaks is of great significance for the establishment of effective prevention and control systems. The time and location of H5N1 outbreaks in poultry and wild birds officially confirmed by the World Organization for Animal Health from 2005 to 2019 were collected. Spatial autocorrelation analysis and multidistance spatial agglomeration analysis methods were used to analyze the global outbreak sites of H5N1. Combined with remote sensing data, the correlation between H5N1 outbreaks and environmental factors was analyzed using binary logistic regression methods. We analyzed the correlation between the H5N1 outbreak and environmental factors and finally made a risk prediction for the global H5N1 outbreaks. The results show that the peak of the H5N1 outbreaks occurs in winter and spring. H5N1 outbreaks exhibit aggregation, and a weak aggregation phenomenon is noted on the scale close to 5000 km. Water distance, road distance, railway distance, wind speed, leaf area index (LAI), and specific humidity were protective factors for the outbreak of H5N1, and the odds ratio (OR) were 0.985, 0.989, 0.995, 0.717, 0.832, and 0.935, respectively. Temperature was a risk factor with an OR of 1.073. The significance of these ORs was greater than 95%. The global risk prediction map was obtained. Given that the novel coronavirus (COVID-19) is spreading globally, the methods and results of this study can provide a reference for studying the spread of COVID-19.


Bilateral persistent primitive hypoglossal arteries associated with unilateral symptomatic carotid thromboembolism.
We report the fifth case of bilateral persistent primitive hypoglossal arteries in the literature. This is also the first such case to be demonstrated on computerized tomography angiogram (CTA) and the first case to be associated with a symptomatic carotid thrombus. The sub-occlusive thrombus was distal to the take-off of the dominant persistent hypoglossal artery (PHA) from the internal carotid artery, thus sparing involvement of posterior circulation. Timely identification of the internal carotid artery thromboembolism in the setting of a PHA is important to allow for thrombectomy. Any intervention was not done in this case as the patient was out of the window and at an additional risk of inducing intracranial thromboembolism. Symptomatic carotid stenosis at the PHA take-off is typically treated with endovascular angioplasty and stenting due to the typically high level of the bifurcation in the neck.


Drugs & the Brain: Case-based Instruction for an Undergraduate Neuropharmacology Course.
In order to transform a traditional large non-majors general education (GE) neurobiology lecture (Drugs & the Brain) into an active learning course, we developed a series of directed mini-cases targeting major drug classes. Humorous and captivating case-based situations were used to better engage and motivate students to solve problems related to neuropharmacology and physiology. Here we provide directed cases, questions and learning outcomes for our opiates mini-cases. In addition, we describe how case studies were incorporated into our course and assessed using peer review and online quizzing. An in-depth analysis of the overall course transformation on student exam performance, opinions and instructor evaluations can be found in the JUNE article Don't Believe the Gripe! Increasing Course Structure in a Large Non-majors Neuroscience Course.


Budesonide versus systemic corticosteroids in IgA Nephropathy: A retrospective, propensity-matched comparison.
IgA Nephropathy (IgAN) is characterized by mesangial deposition of dominant, polymeric, galactose-deficient IgA1 molecules of gut-associated lymphoid tissue origin. We sought to evaluate the efficacy of targeting the mucosal immune system dysregulation underlying IgAN pathogenesis with a pH-modified formulation of budesonide with a maximum release of active compound in the distal ileum and proximal colon.We did a retrospective study evaluating the efficacy of budesonide (Budenofalk) in the treatment of IgAN. From a retrospective cohort of 143 patients with IgAN followed in our department we identified 21 patients that received treatment with budesonide. These patients received budesonide at a dose of 9 mg/d in the first 12 months, followed by a dose reduction to 3 mg/d for the subsequent period. Only patients that received a 24-month treatment with budesonide were included in the analysis (n = 18). We matched the budesonide-treated cohort to 18 patients with IgAN treated with systemic steroids from the same retrospective cohort. Efficacy was measured as change in proteinuria, hematuria and estimated glomerular filtration rate over a 24-month period.Treatment with budesonide was associated with a 24-month renal function decline of -0.22 (95%CI, -8.2 to 7.8) ml/min/1.73m, compared to -5.89 (95%CI, -12.2 to 0.4) ml/min/1.73m in the corticosteroid treatment group (p = 0.44, for between group difference). The median reduction in proteinuria at 24-month was 45% (interquartile range [IQR]: -79%; -22%) in the budesonide group and 11% (IQR: -39%; 43%) in the corticosteroid group, respectively (P = .009, for between group difference). The median reduction in hematuria at 24-month was 72% (IQR: -90%; -45%) in the budesonide group and 73% (IQR: -85%; 18%) in the corticosteroid group, respectively (P = .22, for between group difference). Treatment with budesonide was well tolerated with minimal side effects.Budesonide (Budenofalk) was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria, hematuria and preserving renal function over 24 months of therapy.


Fast screening of total nutrient contents in strawberry leaves and spent growing media using NIRS.
In closed-loop soilless cultivation, the main nutrient sinks are nutrients retained either by the crop or in spent growing media. Measurement of nutrients in spent growing media and in the aboveground vegetative plant biomass at crop termination can be a tool for assessing and optimizing nutrient efficiency. The first aim of this study was to test the potential of near-infrared reflectance spectroscopy (NIRS) to forecast the various nutrient contents in strawberry leaves, which would then allow for assessment of crop nutrient status and total nutrient uptake by strawberry plants. The second aim was to test NIRS as a high throughput technique for assessing the N, K, Ca, Mg and organic matter (OM) content and the pH, EC and C:N and C:P ratios for a dataset of composts, plant fibers and spent growing media. The NIRS prediction model for fast screening of the total nutrient contents in spent growing media was compared with a single extraction method. A database with 369 dried and ground strawberry leaf samples with known contents of N, P, K, Ca, and Mg were scanned using NIRS. The database covered a range of leaf contents of 6-35 g N/kg dry matter (DM), 0.7-6.3 g P/kg DM and 2-29 g K/kg DM. A dataset of 458 samples of different types of materials used in growing media was validated with a dataset of 109 samples. Validation for the strawberry leaves indicated potential for this application, with R2 values of 0.90 or higher for N, K and Ca, and R2 values higher than 0.85 for P and Mg. Validation for the dataset of composts, plant fibers and spent growing media also indicated the potential for this application, with R2 values of 0.90 or higher for organic matter, and with R2 values of 0.85 or higher for total Ca, pH and C:N. A first test indicated potential for the calibration based on fresh samples of compost, plant fiber as well as spent growing media or dried (not ground) samples. Use of NIRS on fresh samples would eliminate the need for drying and grinding the samples and would reduce screening time. The ammonium acetate extraction is a reliable alternative to NIRS for fast screening of the total P, K, Ca, and Mg contents in composts, plant fibers and spent growing media.


Quantitation of mitral annular oscillations and longitudinal "ringing" of the left ventricle: a new window into longitudinal diastolic function.
For diastolic function (DF) quantification, transmitral flow velocity has been characterized in terms of the geometric features of a triangle (heights, widths, areas, durations) approximating the E-wave contour, whereas mitral annular velocity has only been characterized by E'-wave peak amplitude. The fact that E-waves convey global DF information, whereas annular E'-waves provide longitudinal DF information, has not been fully characterized, nor has the physiological legitimacy of combining fluid motion (E)- and tissue motion (E')-derived measurements into routinely used indexes (E/E') been fully elucidated. To place these Doppler echo measurements on a firmer causal, physiological, and clinical basis, we examined features of the E'-wave (and annular motion in general), including timing, amplitude, duration, and contour (shape), in kinematic terms. We derive longitudinal rather than global indexes of stiffness and relaxation of the left ventricle and explain the observed difference between E- and E'-wave durations. On the basis of the close agreement between model prediction and E'-wave contour for subjects having normal physiology, we propose damped harmonic oscillation as the proper paradigm in which to view and analyze the motion of the mitral annulus during early filling. Novel, longitudinal indexes of left ventricular stiffness, relaxation, viscosity, and stored (end-systolic) elastic strain can be determined from the E'-wave (and any subsequent waves) by modeling annular motion during early filling as damped harmonic oscillation. A subgroup exploratory analysis conducted in diabetic subjects (n = 9) and nondiabetic controls (n = 12) indicates that longitudinal DF indexes differentiate between these groups on the basis of longitudinal damping (P < 0.025) and longitudinal stored elastic strain (P < 0.005).


Recent Advances in the Role of Arid5a in Immune Diseases and Cancer.
AT-rich interactive domain 5a (Arid5a) is a nucleic acid binding protein. In this review, we highlight recent advances in the association of Arid5a with inflammation and human diseases. Arid5a is known as a protein that performs dual functions. In in vitro and in vivo studies, it was found that an inflammation-dependent increase in Arid5a expression mediates both transcriptional and post-transcriptional regulatory effects that are implicated in immune regulation and cellular homeostasis. A series of publications demonstrated that inhibiting Arid5a augmented several processes, such as preventing septic shock, experimental autoimmune encephalomyelitis, acute lung injury, invasion and metastasis, immune evasion, epithelial-to-mesenchymal transition, and the M1-like tumor-associated macrophage (TAM) to M2-like TAM transition. In addition, Arid5a controls adipogenesis and obesity in mice to maintain metabolic homeostasis. Taken together, recent progress indicates that Arid5a exhibits multifaceted, both beneficial and detrimental, roles in health and disease and suggest the relevance of Arid5a as a potential therapeutic target.


Comparison of Treatment Results for Mallet Finger Fractures in Children Between Low-Intensity Pulsed Ultrasound Stimulation and Ishiguro's Method.
We compared the treatment results for displaced mallet finger fractures in children between low-intensity pulsed ultrasound (LIPUS) stimulation and Ishiguro's method, which involves extension block and arthrodesis of the distal interphalangeal (DIP) joint with pinning. Eleven cases (5 females and 6 males; average age, 13.5 years) of mallet finger were operated with Ishiguro's method, and 8 cases (3 females and 5 males; average age, 13.0 years) were treated with LIPUS stimulation. Lateral radiographs were used to determine the distance of fragment displacement and the percentage of the articular surface involved in the fragments. Functional outcomes in flexion and extension and those estimated using Crawford's evaluation criteria at the final visits were assessed in each group. The duration needed for fracture healing was longer, however, active extension and flexion of the DIP joint were significantly larger in the LIPUS group compared with those in the pinning group. Functional recovery was excellent in all cases in the LIPUS group; however, recovery was good in 3 cases and excellent in 8 cases in the pinning group. Extension of the DIP joint was significantly larger when pins were removed in 35 or lesser days postoperatively compared with cases in which pin fixation was continued for more than 35 days. LIPUS therapy may be recommended as an option to treat type I mallet finger in children for whom initiation of treatment was delayed up to 8 weeks. When Ishiguro's method is applied to the displaced mallet fracture in children, arthrodesis of the DIP joint for more than 5 weeks should be avoided to prevent flexion contracture.


Orexin 2 receptor-selective agonist danavorexton (TAK-925) promotes wakefulness in non-human primates and healthy individuals.
The orexin 2 receptor-selective agonist danavorexton (TAK-925) has been shown to produce wake-promoting effects in wild-type mice, narcolepsy-model mice, and individuals with narcolepsy type 1 and type 2. Here, we report wake-promoting effects of danavorexton in non-human primates and healthy men during their sleep phase. Electroencephalogram analyses revealed that subcutaneous administration of danavorexton significantly increased wakefulness in common marmosets (p < 0.05 at 0.1 mg kg-1 , and p < 0.001 at 1 mg kg-1 and 10 mg kg-1 ) and cynomolgus monkeys (p ≤ 0.05 at 1 mg kg-1 and 3 mg kg-1 ). In a phase 1b crossover, randomized, double-blind, placebo-controlled and active-controlled study in sleep-deprived healthy participants (ClinicalTrials.gov identifier: NCT03522506), modafinil 300 mg (used to demonstrate assay sensitivity) and continuous infusion of danavorexton 44 mg and danavorexton 112 mg showed statistically superior wake-promoting effects to placebo (n = 18). Measured using the Maintenance of Wakefulness Test, mean (standard deviation) sleep latencies during infusion of danavorexton 44 mg, danavorexton 112 mg and placebo were 21.4 (8.9), 31.8 (3.2) and 9.2 (6.4) min, respectively. Least-squares mean difference from placebo in average sleep latency was 16.8 min with danavorexton 44 mg and 30.2 min with danavorexton 112 mg (both p < 0.001). Karolinska Sleepiness Scale scores were statistically significantly lower (indicating decreased sleepiness) for participants receiving danavorexton than for those receiving placebo during infusion (danavorexton 44 mg, p = 0.010; danavorexton 112 mg, p < 0.001). Together, these results indicate that an orexin 2 receptor agonist increases wakefulness in non-human primates and healthy individuals during their sleep phase.


Functional mitral regurgitation: predictor for atrial substrate remodeling and poor ablation outcome in paroxysmal atrial fibrillation.
Functional mitral regurgitation (FMR) is not uncommon in atrial fibrillation (AF) patients. We sought to investigate the association between FMR and atrial substrate remodeling as well as the ablation outcome in paroxysmal AF (PAF) patients.We retrospectively analyzed a prospectively enrolled cohort of 132 patients (age 55.1 ± 9.6 years, 75.8% male) with symptomatic PAF who underwent initial ablation in our institute. Functional mitral regurgitation was defined as regurgitation jet area to left atrium (LA) area ratio ≥ 0.1 without any primary valvular disease. Voltage mapping of LA was performed under sinus rhythm. Low voltage zones (LVZs) were semi-quantitatively estimated and presented as low voltage index. Follow-up for AF recurrence ≥ 12 months was performed.In total, 40 patients (29.6%) were detected with FMR, who were older than the non-FMR patients (P = 0.007) and had larger LA diameters (P = 0.02). Left atrium LVZs were observed in 64.9% of patients with FMR versus 22.1% patients without FMR (P < 0.001). Functional mitral regurgitation independently predicted the presence of LVZs (OR 7.286; 95% CI 3.023-17.562; P < 0.001). During a mean follow-up of 22.9 ± 6.5 months, 38 patients (28.8%) experienced AF recurrence. The recurrence rate was 60.0% and 19.5% in FMR and non-FMR cohort, respectively (log rank P < 0.001). Multivariate analysis showed that FMR was an independent predictor for AF recurrence (HR 2.291; 95% CI 1.062-4.942; P = 0.03).Functional mitral regurgitation was strongly associated with atrial substrate remodeling. Furthermore, patients with FMR have substantial risk for AF recurrence post ablation.


Epithelial cell-enhanced metabolism by low-level laser therapy and epidermal growth factor.
Reepithelialization and wound closure are the desired outcome for several ulcerative conditions. Such resolution reduces the possibility of wound contamination and maintenance of the injury and improves the reestablishment of tissue morphology and functions. Investigators are seeking adjuvant therapies that can accelerate wound healing and are developing new strategies for clinical applications. This study compared the effects of epidermal growth factor (EGF) application and low-level laser therapy (LLLT) on cultured epithelial cells. Cells were seeded in 24-well plates. After a 24-h incubation, the epithelial cells were either treated with EGF (100 μM in serum-free DMEM for 72 h) or subjected to LLLT (780 nm, 25 mW, 0.5, 1.5, and 3 J/cm2) by three applications every 24 h. Seventy-two hours after cells were treated with EGF or LLLT, cell migration, viability, proliferation, and collagen synthesis were assessed. Cells treated with EGF showed increased cell viability, proliferation, and collagen synthesis compared with those cells that received no treatment. LLLT enhanced cell migration; however, no significant effects of laser irradiation on other cell functions were observed. Comparison of both therapies demonstrated that EGF and LLLT enhanced specific epithelial cell activities related to wound healing.


Skull base growth in children with Chiari malformation Type I.
The goal of this study was to establish whether children with Chiari malformation Type I (CM-I) have abnormal skull base geometry. Distances and angles between skull base landmarks were measured on preoperative magnetic resonance images obtained in 30 children (age range 36-204 months) with symptomatic isolated CM-I; 16 of them (53%) had syringomyelia. Comparisons were made with 42 children of similar age who comprised the control group by using one-way analysis of variance. The angle formed by the crista galli (CG), dorsum sellae (DS), and foramen magnum (FM) was larger than normal in individuals with CM-I than in those without (145 degrees in patients with CM-I but no syringomyelia and 151 degrees in those with CM-I and syringomyelia compared with 135 degrees in controls; p = 0.000). The angle formed by the left internal auditory meatus (IAM), FM, and right IAM was also larger than normal in the patients (122 degrees in patients with CM-I but no syringomyelia and 123 degrees in those with CM-I and syringomyelia compared with 110 degrees in controls; p = 0.001). The angle formed by the anterior clinoid process (ACP), CG, and right ACP was smaller than normal (29 degrees in all patients with CM-I compared with 34 degrees in controls; p = 0.000). The distance between the two IAMs was longer than normal (75 mm in patients with CM-I but no syringomyelia and 63 mm in those with CM-I and syringomyelia compared with 58 mm in controls; p = 0.000). The distance between the two ACPs was shorter than normal in the syringomyelia group (31 mm in patients with CM-I but no syringomyelia and 27 mm in those with CM-I and syrinx compared with 32 mm in controls; p = 0.001). Within the group of patients with CM-I, the DS-FM and left ACP-right ACP distances were smaller in the syringomyelia group (p = 0.009 and p = 0.037, respectively). Children with CM-I have abnormal geometrical measurements of their entire skull base, not only the posterior fossa, irrespective of presence of syringomyelia. This may indicate a mesodermal defect as a possible cause of the malformation.


Cyclometalated iridium(III) chelates-a new exceptional class of the electrochemiluminescent luminophores.
Recent development of the phosphorescent cyclometalated iridium(III) chelates has enabled, due to their advantageous electrochemical and photo-physical properties, important breakthroughs in many photonic applications. This particular class of 5d(6) ion complexes has attracted increasing interest because of their potential application in electroluminescence devices with a nearly 100 % internal quantum efficiency for the conversion of electric energy to photons. Similar to electroluminescence, the cyclometalated iridium(III) chelates have been successfully applied in the electricity-to-light conversion by means of the electrochemiluminescence (ECL) processes. The already reported ECL systems utilizing the title compounds exhibit extremely large ECL efficiencies that allow one to envisage many potential application for them, especially in further development of ECL-based analytical techniques. This review, based on recently published papers, focuses on the ECL properties of this very exciting class of organometallic luminophores. The reported work, describing results from fundamental as well as application-oriented investigations, will be surveyed and briefly discussed. Graphical abstract Depending on the chemical nature of the cyclometalated irdium(III) chelate different colours of the emitted light can be produced during electrochemical excitation.


ErbB2 and ErbB3 do not quantitatively modulate ligand-induced ErbB4 tyrosine phosphorylation.
The ErbB family of receptor tyrosine kinases consists of four members: the epidermal growth factor receptor (EGFR/ErbB1), ErbB2/HER2/Neu, ErbB3/HER3, and ErbB4/HER4. ErbB2 is an "orphan" for which there is no naturally occurring, soluble ligand. ErbB3 lacks tyrosine kinase activity. Thus, we hypothesized that ErbB2 enhances ligand-induced ErbB family receptor signalling through mass action. In contrast, we hypothesized that ErbB3 reduces ligand-induced ErbB family receptor signalling by forming receptor heterodimers that cannot undergo bidirectional cross-phosphorylation. We tested these hypotheses using three cell lines that express equal levels of ErbB4. One expresses ErbB4 alone, the second expresses ErbB2 and ErbB4, and the third expresses ErbB3 and ErbB4. We treated the cells with the ErbB4 ligands betacellulin (BTC) and neuregulin1beta (NRG1 beta) and assayed ErbB4 tyrosine phosphorylation. ErbB2 and ErbB3 do not affect the amount of ligand-induced ErbB4 tyrosine phosphorylation. We will discuss these findings within the context of a model for ErbB receptor signalling.


Mouse lymphoma L5178Y thymidine kinase locus assay of 50 compounds.
Mutagenicity results are presented for 50 compounds tested in the mouse lymphoma TK+/(-)----TK-/- forward mutation assay. Test compounds were mostly from chemical classes not previously tested, to provide new information on the sensitivity of the assay; chemicals of low toxicity or thought to be non-carcinogenic and metabolic inhibitors, to indicate whether and under what conditions the assay can generate so-called false positive results. Twelve compounds that have been tested previously were included in this study to provide an indication of the reproducibility of the assay. Concordant results were obtained for nine of these, while disagreeing, positive results were seen with aniline, fluorene and pyrene. The following compounds belonging to the noncarcinogen category were positive at concentrations in the range 0.02-1 mol/l: dimethyl sulphoxide, EDTA, glucose, polyethyleneglycol, sodium chloride, sodium nitrite and urea. Measurements of the osmotic pressure indicated a lack of a simple relationship to mutagenic effects for these compounds. While the potent mutagenic/carcinogenic compounds tested gave greater than 4-fold increases in the mutation frequency, weak carcinogens or compounds not known to be carcinogenic that were positive in the assay gave increases of between 2- and 4-fold. Exceptions were aldehyde derivatives and chemicals that can lead to oxidative stress, which were detected with exaggerated sensitivity by the assay. Among the metabolic inhibitors tested, positive results were obtained with actinomycin D, cycloheximide, diethyl maleate, hydroxyurea and ouabain. Negative results were found with antimycin A. On the basis of the present results and previously published data it is concluded that a maximum limit for the test compound concentration can be set at 20 mmol/l and that testing to 20% total growth is adequate, with certain stipulations, to detect the mutagenic activity of test compounds. A similar analysis of the available test data shows that less than 4-fold increases in the mutation frequency have a lower predictivity for carcinogenicity.


Evaluation of Biomechanical Stability of Teeth Tissue According to Crown Materials: A Three-Dimensional Finite Element Analysis.
The biomechanical effects of dental tissue according to various dental crown materials were investigated using finite element analysis. Bone, prepared tooth, root canal, and periodontal ligament were modeled based on computed tomography. Depending on the characteristics of the crown material, it was classified into zirconia, hybrid ceramic, gold alloy, and acrylic resin. A loading force of 200 N was applied in the vertical direction to the occlusal surface of the crown, and analysis was performed under the condition that all interfaces were tied. The results demonstrate that the highest von Mises stress was shown in the prepared tooth of the acrylic resin model, which is a temporary prosthesis, and the pulpal pressure was also the highest. Additionally, among the final prosthesis, the highest stress was shown in the hybrid ceramic model prepared teeth. The properties of restoration materials can be a factor influencing the tooth structure. Thus, in order to make a correct decision when selecting a material for restorative treatment, it is necessary to understand, analyze, and evaluate the properties of these restoration materials.


Botulinum toxin testing in animals: the questions remain unanswered.
Questions are raised concerning the testing of botulinum toxin in animals, and the British Government's answers to Parliamentary Questions on this issue are reviewed, with an emphasis on the potential for reducing, refining and replacing the animal tests, which can involve substantial severity, and on the responsibility of the Home Office so see that the Three Rs approach is fully applied in this specific case.


Evaluation of extensive inflammatory conditions of the bowel using three-dimensional CT cinematic rendering: focus on inflammatory bowel disease.
Inflammatory conditions that affect long segments of bowel and/or the mesentery and mesenteric vasculature are a common cause of emergency department visits and evaluation by cross-sectional imaging. Inflammatory bowel disease, specifically Crohn disease and ulcerative colitis, can be unsuspected at presentation and may only be eventually diagnosed based on initial imaging findings. Traditional 2D axial reconstructions and multi-planar reformations can be limited in their ability to globally assess the extent of disease. 3D methods such as volume rendering (VR) are often used as adjunctive means of visualizing the pathology in such patients. Recently, a novel technique known as cinematic rendering (CR) has emerged, utilizing advanced lighting models and ray tracing to simulate photon interactions with tissues, resulting in realistic shadows and enhanced surface detail compared to VR. Generating CR images from select presets takes an experienced radiologist approximately 5 min, meaning that the technique can be incorporated into meaningful emergency department workflows. Given the apparent advantages of CR, we highlight its application in a series of cases in which patients had inflammatory conditions that affected long segments of bowel and/or involved the mesentery, particularly those patients with inflammatory bowel disease, but also including patients with mesenteric venous thrombosis and lymphedema. Those conditions included inflammatory bowel disease, mesenteric venous thrombosis, and bowel lymphedema. We present examples of those conditions in this pictorial essay and describe the potential of CR to visualize key findings. As CR exhibits possible advantages, further studies are warranted to support its broader clinical adoption and assess its efficacy in diagnosing and guiding managing of inflammatory conditions in emergency settings.


Diagnostic utility of a mouse monoclonal antibody (5-21-3) employed as a competitive probe in an immunoassay to detect antibody to HIV-1 gp41.
A mouse monoclonal antibody, designated 5-21-3, was raised against HIV-1 gp41 using detergent-disrupted virus as the immunogen. Antibody 5-21-3 was conjugated to horseradish peroxidase (HRP) and employed as a competitive probe against normal and HIV-1 antibody-positive sera in an immunoassay to detect the presence of antibody to HIV-1 gp41. The diagnostic utility of the competitive monoclonal immunoassay was assessed by correlation to a similar assay which employed HRP-labeled polyclonal IgG from a gp41-seropositive donor as the competitive probe. The monoclonal immunoassay was greater than 98% as sensitive and 99% as specific as the polyclonal immunoassay, regardless of the geographic source or disease state of the donor. The monoclonal immunoassay also was nearly as effective as the polyclonal immunoassay in detecting points of seroconversion in individuals enrolled in longitudinal studies. Of particular interest was the finding that the epitope recognized by monoclonal antibody 5-21-3 did not map to the well-characterized gp41 immunodominant region.


The retaining β-Kdo glycosyltransferase WbbB uses a double-displacement mechanism with an intermediate adduct rearrangement step.
WbbB, a lipopolysaccharide O-antigen synthesis enzyme from Raoultella terrigena, contains an N-terminal glycosyltransferase domain with a highly modified architecture that adds a terminal β-Kdo (3-deoxy-D-manno-oct-2-ulosonic acid) residue to the O-antigen saccharide, with retention of stereochemistry. We show, using mass spectrometry, that WbbB forms a covalent adduct between the catalytic nucleophile, Asp232, and Kdo. We also determine X-ray structures for the CMP-β-Kdo donor complex, for Kdo-adducts with D232N and D232C WbbB variants, for a synthetic disaccharide acceptor complex, and for a ternary complex with both a Kdo-adduct and the acceptor. Together, these structures show that the enzyme-linked Asp232-Kdo adduct rotates to reposition the Kdo into a second sub-site, which then transfers Kdo to the acceptor. Retaining glycosyltransferases were thought to use only the front-side SNi substitution mechanism; here we show that retaining glycosyltransferases can also potentially use double-displacement mechanisms, but incorporating an additional catalytic subsite requires rearrangement of the protein's architecture.


The spectrum and etiologies of lower urinary tract symptoms in postmenopausal women.
Although the prevalence of lower urinary tract symptoms (LUTS) is high in the female population, it is even higher in postmenopausal females. The frequency, severity, and etiology of LUTS vary among populations and individuals. This study aimed to define the characteristics of LUTS in postmenopausal women and their underlying etiologies. Overall, 74 postmenopausal patients presenting with LUTS in the urological outpatient department were included in the study. A detailed evaluation of LUTS and their underlying etiologies was performed. Patients were divided into 2 groups based on age (<65 and ≥65 years), and the variation in different factors was compared across the groups. Variables were compared using the t test and 1-way analysis of variance. Nocturia was the most common symptom (89.2%) followed by frequency (83.8%). Among voiding LUTS, the most common was a weak stream (63.5%). Frequency, nocturia, urgency, urge urinary incontinence (UI), stress UI, and nocturnal enuresis were more common in patients older than 65 years. Urgency and urge UI were recognized to be the most bothersome symptoms by 37% of the study population followed by straining (32%). The mean storage scores, incontinence scores, and quality of life (QoL) scores for patients younger than 65 years and 65 years or older were 6.9 and 8.5 (p < 0.01), 1.8 and 4.1 (p ≤ 0.01), 4.9 and 6.1, respectively. The most common diagnosis was bladder outlet obstruction due to urethral/meatal stenosis (40.5%) followed by an overactive bladder (32.4%), urinary tract infection (10.8%), cystocele (8.1%), urethral prolapse (4.1%), and urethral caruncle (4.1%). Storage LUTS were the most common and increased in both frequency and severity with age. The QoL was also more severely affected in older postmenopausal women. Bladder outlet obstruction due to meatal with or without distal urethral stenosis was the most common underlying cause of LUTS followed by an overactive bladder. Overactive bladder had the most severe impact on patients' QoL among all the etiologies.


Functional interaction between nuclear matrix-associated HBXAP and NF-kappaB.
Hepatitis B virus X-associated protein (HBXAP) is a plant homeodomain (PHD) finger-containing protein implicated in transcription regulation. However, the underlying molecular mechanism remains to be defined. Here, we show that HBXAP represses NF-kappaB-mediated gene activation in a dose-dependent manner. Our results showed that HBXAP and NF-kappaB colocalize to the nuclear matrix with specific physical interaction between them. HBXAP may depend on its nuclear matrix localization for its repression of NF-kappaB-mediated gene repression. A specific nuclear matrix targeting sequence of HBXAP was identified. The sequence is included in a region encompassing amino acids 688-722 that could form a coiled-coil structure. The 18-amino acid stretch lies at the core of that structure. The present results showed that either the coiled-coil conformation or the PHD finger domain is crucial for the transcription repression activity of HBXAP on NF-kappaB-mediated gene activation. Taken together, our results suggest that HBXAP may function as a negative regulator for TNF-alpha-induced, NF-kappaB-mediated gene activation.


Coherent transient transport of interacting electrons through a quantum waveguide switch.
We investigate coherent electron-switching transport in a double quantum waveguide system in a perpendicular static or vanishing magnetic field. The finite symmetric double waveguide is connected to two semi-infinite leads from both ends. The double waveguide can be defined as two parallel finite quantum wires or waveguides coupled via a window to facilitate coherent electron inter-wire transport. By tuning the length of the coupling window, we observe oscillations in the net charge current and a maximum electron conductance for the energy levels of the two waveguides in resonance. The importance of the mutual Coulomb interaction between the electrons and the influence of two-electron states is clarified by comparing results with and without the interaction. Even though the Coulomb interaction can lift two-electron states out of the group of active transport states the length of the coupling window can be tuned to locate two very distinct transport modes in the system in the late transient regime before the onset of a steady state. A static external magnetic field and quantum-dots formed by side gates (side quantum dots) can be used to enhance the inter-waveguide transport which can serve to implement a quantum logic device. The fact that the device can be operated in the transient regime can be used to enhance its speed.


(Fluorocyclopropyl)quinolones. 2. Synthesis and Stereochemical structure-activity relationships of chiral 7-(7-amino-5-azaspiro[2.4]heptan-5-yl)-1-(2-fluorocyclopropyl)quinolone antibacterial agents.
A series of novel chiral 7-(7-amino-5-azaspiro[2.4]heptan-4-yl)-8-chloro-1-(2-fluo rocyclopropyl)- quinolones were synthesized as a continuation of a research project of 1-(2-fluorocyclopropyl)-quinolones by considering stereochemical and physicochemical properties of the molecule. Absolute configurations of the 1-(cis-2-fluorocyclopropyl) moiety and the 7-(7-amino-5-azaspiro-[2.4]heptan-5-yl) moiety were determined by X-ray crystallographic analysis. Stereochemical structure-activity relationship studies indicated that 1-[(1R,2S)-2-fluorocyclopropyl] and 7-[(7S)-amino-5-azaspiro[2.4]heptan-5-yl] derivatives are more potent against Gram-positive and Gram-negative bacteria than the other stereoisomers and 7-[(7S)-7-amino-5-azaspiro[2.4]-heptan-5-yl]-8-chloro-1-[(1R ,2S)-2- fluorocyclopropyl]quinolone (33) is the most potent of all stereoisomers. Pharmacokinetic profiles and physicochemical properties of the selected compounds were also examined, and it was found that 33 (DU-6859a) possesses moderate lipophilicity and good pharmacokinetic profiles.


Tailor-made PAT platform for safe syngas fermentations in batch, fed-batch and chemostat mode with Rhodospirillum rubrum.
Recently, syngas has gained significant interest as renewable and sustainable feedstock, in particular for the biotechnological production of poly([R]-3-hydroxybutyrate) (PHB). PHB is a biodegradable, biocompatible polyester produced by some bacteria growing on the principal component of syngas, CO. However, working with syngas is challenging because of the CO toxicity and the explosion danger of H2 , another main component of syngas. In addition, the bioprocess control needs specific monitoring tools and analytical methods that differ from standard fermentations. Here, we present a syngas fermentation platform with a focus on safety installations and process analytical technology (PAT) that serves as a basis to assess the physiology of the PHB-producing bacterium Rhodospirillum rubrum. The platform includes (i) off-gas analysis with an online quadrupole mass spectrometer to measure CO consumption and production rates of H2 and CO2 , (ii) an at-line flow cytometer to determine the total cell count and the intracellular PHB content and (iii) different online sensors, notably a redox sensor that is important to confirm that the culture conditions are suitable for the CO metabolization of R. rubrum. Furthermore, we present as first applications of the platform a fed-batch and a chemostat process with R. rubrum for PHB production from syngas.


Tree-ring isotope records of tropical cyclone activity.
The destruction wrought by North Atlantic hurricanes in 2004 and 2005 dramatically emphasizes the need for better understanding of tropical cyclone activity apart from the records provided by meteorological data and historical documentation. We present a 220-year record of oxygen isotope values of alpha-cellulose in longleaf pine tree rings that preserves anomalously low isotope values in the latewood portion of the ring in years corresponding with known 19th and 20th century landfalling/near-coastal tropical storms and hurricanes. Our results suggest the potential for a tree-ring oxygen isotope proxy record of tropical cyclone occurrence extending back many centuries based on remnant pine wood from protected areas in the southeastern U.S.


An examination of suicide research and funding in New Zealand 2006-16: implications for new research and policies.
Objective Suicide is a significant public health problem in New Zealand, with the youth suicide rate being one of the highest among developed countries. Increased suicide rates in recent years suggest that the evidence base and research priorities for New Zealand suicide prevention need to be reassessed. To inform policy development, the aim of the present study was to evaluate all peer-reviewed New Zealand published suicide research and major grant allocations from 2006 to 2016. Methods The methodology duplicated a recent Australian review of suicide prevention research and funding. Publications and grant funding allocations were assessed independently. Key research databases were searched in April 2016 for all suicide-related publications. Identified papers were then classified by research type, population focus and type of self-injurious behaviour. Citation indices were obtained for each publication. Annual reports, newsletters and summary data from four major New Zealand funding bodies (the Health Research Council of New Zealand, Marsden Fund, Lottery Health Research and the Ministry of Health) were reviewed for funding allocations. Identified grants were coded for type of project, type of self-injurious behaviour and target population. Descriptive analyses were performed. Results In all, 104 published articles and 27 grants met review criteria. Total funding was NZ$12677261.62. Most published articles were epidemiological in nature and the most common type of grant was for an intervention. Conclusions In the past decade, a substantial number of articles has been published and significant funding was invested in New Zealand's suicide research. The present review suggests that future research investments should focus on effective translation of research findings into suicide prevention programs. Several pragmatic recommendations are proposed to help improve the evidence base and reduce New Zealand's suicide rates. What is known about the topic? Suicide prevention continues to be a national public health priority for New Zealand. Although much is known about the prevalence of suicidal behaviours in New Zealand, less is known about how well suicide research has addressed prevention priorities and specific target populations. Australian research found that research funding and publications were dominated by epidemiological studies rather than evaluation or intervention studies. It is yet to be determined whether these research and funding trends also apply for New Zealand. What does this paper add? This study examined all peer-reviewed and published suicide research and all major suicide prevention projects that have been funded in New Zealand between 2006 and 2016. The purpose of the review was to summarise the evidence base, evaluate funding and determine the ability of the evidence base to inform policy development. The findings demonstrate that the New Zealand research trends are similar to those found in Australia, with most studies being epidemiological and few representative of interventions. What are the implications for practitioners? This review highlights that there were few intervention and evaluation studies. Partnerships between practitioners and/or community organisations implementing interventions and researchers to systematically evaluate existing interventions and develop new evidence-based interventions would help improve the evidence base for New Zealand suicide prevention.


Theoretical Analysis of Fas Ligand-Induced Apoptosis with an Ordinary Differential Equation Model.
Upon the treatment of Fas ligand, different types of cells exhibit different apoptotic mechanisms, which are determined by a complex network of biological pathways. In order to derive a quantitative interpretation of the cell sensitivity and apoptosis pathways, we have developed an ordinary differential equation model. Our model is intended to include all of the known major components in apoptosis pathways mediated by Fas receptor. It is composed of 29 equations using a total of 49 rate constants and 13 protein concentrations. All parameters used in our model were derived through nonlinear fitting to experimentally measured concentrations of four selected proteins in Jurkat T-cells, including caspase-3, caspase-8, caspase-9, and Bid. Our model is able to correctly interpret the role of kinetic parameters and protein concentrations in cell sensitivity to FasL. It reveals the possible reasons for the transition between type-I and type-II pathways and also provides some interesting predictions, such as the more decisive role of Fas over Bax in apoptosis pathway and a possible feedback mechanism between type-I and type-II pathways. But our model failed in predicting FasL-induced apoptotic mechanism of NCI-60 cells from their gene-expression levels. Limitations in our model are also discussed.


Skull Base Osteomyelitis After Nasopharyngeal Cyst Excision.
We present a case of an 80-year-old male who developed skull base osteomyelitis after nasopharyngeal cyst removal. A review of the literature regarding complications after nasopharyngeal cyst removal was performed. We describe the difficulty of diagnosing an osteomyelitis infection and the best approach to recognizing osteomyelitis before complications worsen.


Influence of Defects on Excited-State Dynamics in Lead Halide Perovskites: Time-Domain ab Initio Studies.
This Perspective summarizes recent research into the excited-state dynamics in lead halide perovskites that are of paramount importance for photovoltaic and photocatalytic applications. Nonadiabatic molecular dynamics combined with time-domain ab initio density functional theory allows one to mimic time-resolved spectroscopy experiments at the atomistic level of detail. The focus is placed on realistic aspects of perovskite materials, including point defects, surfaces, grain boundaries, mixed stoichiometries, dopants, and interfaces. The atomistic description of the quantum dynamics of electron and hole trapping and recombination, provided by the time-domain ab initio simulations, generates important insights into the mechanisms of charge and energy losses and guides the development of high-performance perovskite solar cell devices.


Photo-elastic investigation of influence of dental implant shape and prosthetic materials to patterns of stress distribution.
Occlusal loading has to be considered a key factor influencing bone resorption due to the stress transmitted to surrounding tissues by the implant-abutment structure. The aim of this study was to evaluate, through a photo-elastic investigation, the patterns of tensions distribution of two different implant shapes, which were cylindrical and conical. A 100N load was applied to two implant-abutment structures (with and without a metal-ceramic crown) incorporated in photo-elastic resin. Modification in light refraction were recorded and analyzed through a computerized software. Measurements of stripe extension and position were evaluated. Stress distribution around tapered implant was evaluated to be more uniform than in cylindrical one which demonstrated a high stress concentration at the more cervical region and in the apical region. The presence of a metal-ceramic crown caused an increase in tensions at the implant-resin interface. Conical implants distributed stresses to a larger and well-defined volume of resin and this can cause a decrease of forces acting at the interface. This could be due to the "wedge effect" of this fixture shape which could be considered superior in terms of stress distribution than cylindrical one.


FoxO1 inhibits leptin regulation of pro-opiomelanocortin promoter activity by blocking STAT3 interaction with specificity protein 1.
Leptin controls food intake and energy expenditure by regulating hypothalamic neuron activities. Leptin exerts its actions through complex signaling pathways including STAT3 phosphorylation, nuclear translocation, and binding to target gene promoter/cofactor complexes. Deficient or defective leptin signaling leads to obesity, which may be caused by insufficient leptin levels and/or resistance to leptin signaling. To understand the molecular mechanisms of leptin resistance, we studied the regulation of pro-opiomelanocortin (POMC) gene expression by leptin. We show that phospho-STAT3 activates POMC promoter in response to leptin signaling through a mechanism that requires an SP1-binding site in the POMC promoter. Furthermore, FoxO1 binds to STAT3 and prevents STAT3 from interacting with the SP1.POMC promoter complex, and consequently, inhibits STAT3-mediated leptin action. Our study suggests that leptin action could be inhibited at a step downstream of STAT3 phosphorylation and nuclear translocation, and provides a potential mechanism of leptin resistance in which an increased FoxO1 antagonizes STAT3-mediated leptin signaling.


Bilateral Complete and Incomplete Fusion of Incisors and its Management.
This case report highlights the management of a case of bilateral complete and incomplete fusion of maxillary incisors in a 10-year-old child. A mock-up was done on the diagnostic cast. Pretreatment esthetic evaluation was done using bis-acryl composite temporaries which were transferred intraorally from the diagnostic cast using a putty index. An incisal overlap veneer preparation was done, following which, an IPS e-max veneer was cemented. A digital mock-up was carried out using the Adobe Photoshop and Corel Draw softwares to aid in laboratorial fabrication of the veneer.


Monoclonal antibodies against heparin and heparinoids.
The antigenicity of glycosaminoglycans and galactosaminoglycans is very weak. Accordingly, only a few reports on the successful production of monoclonal antibodies against glycosaminoglycans and galactosaminoglycans have been published. Antibodies have been raised against the heparinlike compounds heparan sulfate, chondroitin sulfate, and keratan sulfate. The production of heparin antibodies was reported. But further analysis showed that the antibodies were not directed against native heparin but against heparin conjugates or chemically modified heparins. After immunization with a heparin-bovine serum albumin conjugate, prepared by reductive amination, a monoclonal antibody against heparin and heparin fractions was obtained (Huhle et al: Semin Thromb Hemostas 20:193-204, 1995). For further analysis, tyramine, which was covalently bound to low-molecular-mass heparin (LMMH) by endpoint attachment (Malsch et al: Anal Biochem 217:255-264, 1994), was labeled with iodine-125 at the aryl residue. The tracer antibody complex was immunoprecipitated by goat anti-mouse immunoglobulin IgG. H1.18 recognized specifically intact heparin and heparin fractions. The lower detection limit for heparin preparations was 100 ng/mL. The H1.18 antibody was purified by ammonium sulfate precipitation. H1.18 remained biologically and functionally active after purification. The smallest disaccharide that was detected by H1.18 was found to be iduronic acid-anhydromannose, obtained by nitrous acid degradation of LMMH. Endpoint attachment of tyramine to anhydromannose did not modify the binding of the disaccharide to H1.18, indicating the importance of iduronic acid for binding of glycosaminoglycans to the antibody.


Modeling retrospective attribution of responsibility to hazard-managing institutions: an example involving a food contamination incident.
Perceptions of institutions that manage hazards are important because they can affect how the public responds to hazard events. Antecedents of trust judgments have received far more attention than antecedents of attributions of responsibility for hazard events. We build upon a model of retrospective attribution of responsibility to individuals to examine these relationships regarding five classes of institutions that bear responsibility for food safety: producers (e.g., farmers), processors (e.g., packaging firms), watchdogs (e.g., government agencies), sellers (e.g., supermarkets), and preparers (e.g., restaurants). A nationally representative sample of 1,200 American adults completed an Internet-based survey in which a hypothetical scenario involving contamination of diverse foods with Salmonella served as the stimulus event. Perceived competence and good intentions of the institution moderately decreased attributions of responsibility. A stronger factor was whether an institution was deemed (potentially) aware of the contamination and free to act to prevent or mitigate it. Responsibility was rated higher the more aware and free the institution. This initial model for attributions of responsibility to impersonal institutions (as opposed to individual responsibility) merits further development.


The superiority of an extracellular fluid solution over Euro-Collins' solution for pulmonary preservation.
Limited donor supply is the major factor restricting the application of lung transplantation. A uniformly reliable method of lung preservation would improve donor organ availability. At present, Euro-Collins' solution, an intracellular fluid-type solution, is most widely used in organ preservation. However, we have previously shown that initial pulmonary flush with an extracellular-type solution (low-potassium dextran solution [LPD]) provided better pulmonary preservation than Euro-C. In the present study, we used an in vitro-ventilated, blood-perfused rabbit lung model to examine whether the mechanism for this improvement was related to the effect of LPD during pulmonary flush or its effect during storage. Rabbit lungs were harvested and stored after pulmonary flush with different solutions (group 1: 400 ml of LPD; group 2: 400 ml of Euro-C; group 4: 300 ml of Euro-C followed by 100 ml of LPD; n = 5 in each group). The lungs were then preserved at 10 degrees C for 18 hr and reperfused with fresh venous blood. After 10 min of reperfusion, lungs in group 1 showed the highest PO2 (group 1: 124.4 +/- 7.7 mmHg; group 2: 46.2 +/- 9.4 mmHg P less than 0.01). Lungs in both group 3 and group 4 showed better lung function and lower wet/dry weight ratio than those in group 2. We conclude that LPD provides better lung preservation by its effects both on pulmonary flush and on storage.


Characterization of a saporin mitotoxin specifically cytotoxic to cells bearing the granulocyte-macrophage colony-stimulating factor receptor.
When granulocyte-macrophage colony-stimulating factor (GM-CSF) is chemically conjugated to the ribosome-inactivating protein saporin, the resulting protein conjugate is highly toxic for cells expressing the GM-CSF receptor. Structural and Western blot analyses of the purified conjugate establish that it contains equimolar amounts of the starting materials and is free of any contamination by the non-conjugated components. The resulting bifunctional reagent is specifically cytotoxic to cells expressing the GM-CSF receptor, but is ineffective to cells that do not express the receptor. The cytotoxic activity is inhibited in a dose-dependent manner by GM-CSF, but not by any one of five other peptide growth factors. This is the first report of a mitotoxin for cells that express the GM-CSF receptor and which promises to be a valuable tool to study the expression of the GM-CSF receptor in normal and pathological states.


Survey on number and size distribution of treatment wetlands in Austria.
In Austria, 1,840 wastewater treatment plants (WWTPs) with design size >50 population equivalent (PE) serve about 95% of the population. The remaining 5% of the population live in single houses and small settlements that require on site and decentralized wastewater treatment technologies. There is no common database on small WWTPs with design size <50 PE; thus data had to be collected from the Austrian federal states and compiled in a database. The total number of small WWTPs in Austria is about 28,700 comprising 1,300 WWTPs with design size 51-500 PE and 27,400 with design size <50 PE, respectively. The total number of treatment wetlands implemented in Austria is 5,450. Due to legal requirements (nitrification), only vertical flow wetlands are implemented in Austria. From the 5,450 treatment wetlands, about 100 are of design size larger than 50 PE and about 2,800 treatment wetlands have a design size of 5-10 PE. The peak of wetland implementation was in the years 2007-2011 with 2,200 implemented systems in 5 years. Since about 2000, about 30-40% of the new implemented small WWTPs are treatment wetlands.


Spontaneous closure of postinfarction ventricular septal rupture. A case report.
Spontaneous closure of a postinfarction ventricular septal rupture is extremely rare. We present such a case in which the postinfarction ventricular septal rupture closed spontaneously during follow-up. We postulate that the spontaneous closure of the ventricular septal rupture was probably due to thrombosis in the apical and septal aneurysm.


[The design of a fiber optic hygrometer using in patient monitor].
Fiber optic sensor is a kind of newly developed sensory technology in recent ten years. With intrinsic security and wide application, it is superior to the traditional point sensors. This paper presents the design of a kind of fiber optic hygrometer using in patient monitor.


Acerogenin C from Acer nikoense exhibits a neuroprotective effect in mouse hippocampal HT22 cell lines through the upregulation of Nrf-2/HO-1 signaling pathways.
Oxidative stress contributes to neuronal death in the brain, and neuronal death can cause aging or neurodegenerative disease. Heme oxygenase 1 (HO-1) serves a vital role in the regulation of biological reactions, including oxidative stress associated with reactive oxygen species. In the present study, acerogenin C isolated from the Aceraceae plant Acer nikoense, which is used as a Japanese folk medicine for hepatic disorders and eye diseases. However, there have been no studies on the mechanisms underlying the antineurodegenerative biological activities of acerogenin C. In the present study, acerogenin C demonstrated neuroprotective action against glutamate‑induced cell death in hippocampal HT22 cells through the upregulation of HO‑1 expression. These effects were also associated with nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the activation of phosphoinositide 3‑kinase/protein kinase B. Taken together of the efficacy researches, this study determines that the Nrf2/HO‑1 pathways denotes a biological mark and that acerogenin C might contribute to prevention of neurodegenerative disorders.


Core-shell nanofibers as drug delivery systems.
Core-shell nanofibers have grown in popularity over the last decade owing to their special features and their many applications in biomedicine. They can be produced by electrospinning of immiscible polymer blends or emulsions through a single nozzle or by electrospinning using a coaxial nozzle. Several of the electrospinning parameters allow great versatility for the compositions and diameters of core-shell nanofibers to be produced. Morphology of core-shell nanofibers can be investigated using transmission electron microscopy and, in some cases, scanning electron microscopy. Several studies have shown that core-shell nanofibers have some advantages over monolithic nanofibers, such as better drug, protein, gene or probiotic incorporation into the nanofibers, greater control over drug release, and maintenance of protein structure and activity during electrospinning. We herein review the production and characterization of core-shell nanofibers, the critical parameters that affect their development, and their advantages as delivery systems.


SIRT1 promotes the proliferation and metastasis of human pancreatic cancer cells.
SIRT1 plays an important role in human malignant progression, inducing cancer cell proliferation and metastasis by regulating downstream gene expressions. However, little is known about the underlying mechanisms in which SIRT1 promotes pancreatic cancer tumorigenesis. The aim of this study is to investigate the SIRT1 expression levels and biological functions in promoting pancreatic cancer progression. We first investigated the expression of SIRT1 in a series of pancreatic cancer tissues as well as in a panel of pancreatic cancer cell lines. The effect of SIRT1 on cell activity was explored by knockdown experiments. Cell growth was measured using the MTT assay and colony-formation assay. Migration and invasion were tested using transwell assay. Our results showed that the expression of SIRT1 was significantly up-regulated both in pancreatic cancer tissues and cell lines. Knockdown of SIRT1 suppressed cell proliferation and migration of pancreatic cancer cells. This is the first report to disclose the role of SIRT1 in regulation of pancreatic cancer cell proliferation and migration, which may provide a potential therapeutic target for pancreatic cancer patients.


Lacosamide diminishes dryness-induced hyperexcitability of corneal cold sensitive nerve terminals.
Lacosamide is an anti-epileptic drug that is also used for the treatment of painful diabetic neuropathy acting through voltage-gated sodium channels. The aim of this work was to evaluate the effects of acute application of lacosamide on the electrical activity of corneal cold nerve terminals in lacrimo-deficient guinea pigs. Four weeks after unilateral surgical removal of the main lachrimal gland in guinea pigs, corneas were excised and superfused in vitro at 34°C for extracellular electrophysiological recording of nerve terminal impulse activity of cold thermosensitive nerve terminals. The characteristics of the spontaneous and the stimulus-evoked (cooling ramps from 34°C to 15°C) activity before and in presence of lacosamide 100µM and lidocaine 100µM were compared. Cold nerve terminals (n=34) recorded from dry eye corneas showed significantly enhanced spontaneous activity (8.0±1.1 vs. 5.2±0.7imp/s; P<0.05) and cold response (21.2±1.7 vs. 16.8±1.3imp/s; P<0.05) as well as reduced cold threshold (1.5±0.1 vs. 2.8±0.2 Δ°C; P<0.05) to cooling ramps compared to terminals (n=58) from control animals. Both lacosamide and lidocaine decreased spontaneous activity and peak response to cooling ramps significantly (P<0.05). Temperature threshold was increased by the addition of lidocaine (P<0.05) but not lacosamide (P>0.05) to the irrigation fluid. In summary, the application of lacosamide results in a significant decrease of the augmented spontaneous activity and responsiveness to cold of corneal sensory nerves from tear-deficient animals. Based on these promising results we speculate that lacosamide might be used to reduce the hyperexcitability of corneal cold receptors caused by prolonged ocular surface dryness due to hyposecretory or evaporative dry eye disease.


[Transferability of biapenem (L-627) to cerebrospinal fluid in rabbits with meningitis caused by Staphylococcus aureus].
The transferability of biapenem (L-627) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean plasma concentration was 192 +/- 12.8 micrograms/ml at 15 minutes after intravenous administration of the drug at a dose level of 100 mg/kg. The mean concentration in CSF was maximum at 45 minutes after administration at 11.4 +/- 2.19 micrograms/ml. Pharmacokinetic parameters calculated from these values were as follows, Cmax (CSF/plasma): 5.96%; AUC (CSF/plasma): 8.15% between 15 and 60 minutes, 12.1% between 15 and 120 minutes and 15.0% between 15 and 180 minutes; T1/2 for L-627 in CSF: 152 minutes; T1/2 (CSF/plasma): 3.34. In comparison with those of other beta-lactam antibiotics that were obtained in the same way, the transferability of L-627 was intermediate, and in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worthwhile of running clinical trials for this drug.


Stretch marks: a visible expression of connective's involvement in autism spectrum disorders.
In autism spectrum disorders (ASDs) in the pediatric population, skin manifestations are generally attributable to the concomitance of allergic forms or to accidental, self-inflicted or abusive lesions. However, clinical evidence has highlighted the presence of an increasing number of abdominal stretch marks, probably caused by the increase in the number of obesity cases in the pediatric population, in general, and therefore also among children with ASD. Stretch marks are often attributed to obesity, as they have an incidence of more than 50% in obese individuals. In the first part of this article we hypothesized that in addition to obesity there are other factors, such as a structural alteration on the skin in people with ASD, which can contribute/aggravate the phenomenon of stretch marks. Despite the high frequency with which stretch marks are found in children with ASD, this aspect has never been studied, the structure of the skin of children with ASD is not known. Furthermore, it is not known whether this structure is different from that of subjects without ASD. In the second part of the article, we hypothesized the mechanisms of the negative impact of simple abdominal stretch marks on the symptomatic picture of children with ASD. The presence of stretch marks, altered tactile perception, altered sensitivity to clothing fabrics can be a combination that influences development and determines negative consequences in the neurological picture of a child with ASD, as it is already known that the altered sensory perception in children with ASD contributes to the deterioration of social behavior. Furthermore, the presence of stretch marks may play a role in the postural and motor defects of children with ASD.


Diagnosis and treatment of superior mesenteric artery syndrome.
Superior mesenteric artery syndrome (SMAS) is a rare clinical condition. Eleven cases of SMAS treated surgically are reported after follow-up periods of 6 months to 6 years. The value of hypotonic duodenography in the diagnosis of the syndrome is emphasized.


Morphological, biochemical, and electrophysiological characterization of a clonal cell (H9c2) line from rat heart.
Morphological, electrophysiological, and biochemical properties of H9c2 cells, a permanent cell line derived from rat cardiac tissue, were studied. Although the lectin binding pattern revealed similar sugar residues in the surface coat of H9c2 cells and isolated rat cardiocytes, heart-specific morphological structures could not be detected in H9c2 cells. Under physiological ionic conditions, H9c2 cells exhibited an outwardly rectifying, transient K+ current. When this current component was blocked by Ba2+ and Cs+, we observed an inward current through Ca2+ channels (15.8 +/- 2.2 pA/pF, n = 18, measured as Ba2+ current) that showed all characteristics of cardiac L-type currents. The activation kinetics were fast, and the current was stimulated by isoproterenol. The effect of isoproterenol was mimicked by forskolin or intracellularly applied cAMP. In radioligand binding experiments, we identified a specific, saturable, stereoselective and reversible high-affinity [3H]-(+)PN 200-110 binding with a dissociation constant Kd = 0.53 +/- 0.28 nM and a maximal specific binding of Bmax = 129.3 +/- 16.1 fmol/mg protein. There was an additional low-affinity/high-capacity binding site, which is unlikely to be related to a Ca2+ channel protein. Signal-transducing G proteins in membranes were characterized by [32P]ADP-ribosylation catalyzed by bacterial toxins and by the use of various antibodies. Cholera toxin substrates of 42 and 45 kd were identified that apparently correlated to Gs alpha-subunits. Pertussis toxin substrates of 40-41 kd were tentatively identified as Gi alpha-subunits. The G protein Go was absent or at least extremely low in concentration.


Patient information: confidentiality and the electronic record.
The rise of the electronic record now allows nurses to access a large archive of patient information that was more difficult to obtain when records consisted of manually held paper files. There have been several instances where curiosity and, occasionally, more malicious motivations have led nurses to access these records and read the notes of a celebrity or a person they know. In this article, Richard Griffith considers whether nurses' accessing and reading of the record of someone who is not in their care is in breach of their duty of confidentiality.


Association Between Serum 25-Hydroxyvitamin D Levels and Dry Eye in Korean Adults: A Study Based on Korean National Health and Nutrition Examination Survey, 2010-2011.
Dry eye is a common disease. Many patients continue to experience residual symptoms despite optimal treatment. Thus, new treatment options are required. The purpose of this study was to evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and dry eye. This study was performed using data from the fifth Korean National Health and Nutrition Examination Survey, which is a cross-sectional study of the Korean population that was conducted from 2010 to 2011. We included adults aged >19 years who underwent ophthalmologic interviews and examinations. We excluded subjects who had comorbid conditions (rheumatoid arthritis, thyroid disease, chronic kidney disease, or depression) that are associated with dry eye. The subjects were divided into normal and dry eye groups. The dry eye group consisted of those who had clinically diagnosed dry eye syndrome or symptoms. Multiple logistic regression analysis was conducted to determine the association between serum 25(OH)D levels and dry eye. In the univariate model, the 25(OH)D levels were lower in the dry eye group than in the normal group (P=0.01). A significant association was found between severe vitamin D deficiency (<10 ng/mL) and dry eye (P=0.04). However, after multivariate adjustment, the statistical significance of the association disappeared (P-values= 0.49, vitamin D insufficiency; P=0.33, vitamin D deficiency; P=0.18, severe vitamin D deficiency). Severe vitamin D deficiency was associated with dry eye in an unadjusted model, but the association was not statistically significant after adjustment.


Protein kinase C mediates the calcium-induced activation of rat colonic particulate guanylate cyclase.
Calcium can influence the cGMP/guanylate cyclase system in many tissues, including rat colon. The mechanisms involved in this phenomenon, however, are unclear. To further elucidate the mechanisms involved in the Ca(2+)-induced activation of rat colonic particulate guanylate cyclase, isolated colonocytes were incubated with Ca2+ or other agents, and crude membrane prepared and analyzed for particulate guanylate cyclase activity. Alternatively, the test agents were directly added to the guanylate cyclase reaction mixture containing isolated membranes. The results of these studies demonstrated: (i) extracellular Ca2+ (1 and 2 mM) increased basal particulate guanylate cyclase activity; (ii) increases in intracellular Ca2+ induced by 10 microM thapsigargin activated this enzyme; (iii) preincubation of the cells with 50 nM staurosporine, a broad-spectrum inhibitor of protein kinases, including protein kinase C (PKC), or 5 microM U73122, a specific inhibitor of phosphoinositide-phospholipase C-dependent processes, blocked the Ca(2+)-induced increase in particulate guanylate cyclase activity; (iv) incubation of cells with 1 microM 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of PKC, stimulated guanylate cyclase; (v) no additivity in stimulation of this enzyme was observed when cells were concomitantly incubated with 1 microM TPA and 2 mM extracellular Ca2+; (vi) incubation of membranes with 250 nM TPA, in the presence of 0.2 mM Ca2+, 6 mM Mg2+, and 1 mM ATP, activated guanylate cyclase; and (vii) incubation of membranes with purified rat brain PKC further augmented this stimulation. These results indicate that Ca2+ activates rat colonic particulate guanylate cyclase, at least in part, via a PKC-dependent mechanism.


[Diagnosis of tuberculous lymphadenitis based on the fine needle aspiration samples analysis].
Tuberculous lymphadenitis is one of the most common extrapulmonary manifestations of tuberculosis. The most common lymph nodes involved are in the cervical region. Lymphadenitis due to M. tuberculosis generally presents with enlarging neck lymph nodes over weeks or months associated with fever, weight loss and fatigue. Fine needle aspiration (FNA) of affected lymph nodes has been shown to yield a high sensitivity and specificity in the diagnosis of tuberculous lymphadenitis. Specimens should be examined cytologically, as well as by AFB smear and cultures. The time between the onset of symptoms, clinical presentation and final diagnosis is often too long. We present a case of 60 years old man with tuberculous lymphadenitis, initially suspected of lymphoproliferative disease.