Poor tolerability of a transdermal nicotine treatment in Parkinson's disease.
Studies assessing the effect of transdermal nicotine in Parkinson's disease (PD) have generated mixed results regarding its efficacy to treat motor and cognitive deficits. These studies generally reported good tolerability in nonsmoking PD patients. The authors report the tolerability data of an open trial with transdermal nicotine in PD. Twenty-two therapeutically well-controlled nonsmoking PD patients received a transdermal nicotine treatment over 25 days according to the following fixed titration schedule: 7 mg for the first 11 days, 14 mg for the next 11 days, and 21 mg for the last 3 days. Fourteen PD patients (64%) had side effects such as nausea, vomiting, and dizziness, and 10 of them withdrew from the study. Factors such as age, body mass index, disease duration, and motor disability were not related to this intolerance. Transdermal nicotine can produce unpleasant adverse effects in patients with PD. Given that similar doses of nicotine were better tolerated in previous studies, the authors suspect the pharmacokinetic profile of the transdermal delivery system to be a determining factor in the effect of nicotine treatment in PD.


Parenting and Children's Executive Function Stability Across the Transition to School.
When children transition to school between the ages of 4 and 6 years, they must learn to control their attention and behavior to be successful. Concurrently, executive function (EF) is an important skill undergoing significant development in childhood. To understand changes occurring during this period, we examined the role of parenting in the development of children's EF from 4 to 6 years old. Participants were mother and child dyads (N = 151). Children completed cognitive tasks to assess overall EF at age 4 and age 6. At both time points, mothers and children completed interaction tasks which were videotaped and coded to assess various parenting dimensions. Results indicated that children with high EF at age 4 were more likely to have high EF at age 6. In addition, results suggested that higher levels of positive parenting across the transition to school promote stability of individual differences in EF.


Fusion of Substrate-Binding Domains Enhances the Catalytic Capacity of Keratinases and Promotes Enzymatic Conversion of Feather Waste.
The unique role of keratinases in keratin hydrolysis has garnered huge interest in the recovery of feather waste. However, owing to the high hydrophobicity of feather keratins, the catalytic capacity of keratinases for hydrolyzing feathers is typically low. In this study, we aimed to improve the keratinase feather hydrolysis efficiency by fusing a substrate-binding domain into the enzyme. We screened several carbohydrate-binding modules (CBMs) and linking peptides. We selected the most promising candidates to construct, clone, and express a fusion keratinase enzyme KerZ1/CBM-L8 with a feather hydrolysis efficiency of 7.8 × 10-8 g/U. Compared with those of KerZ1, KerZ1/CBM-L8 has a feather hydrolysis efficiency that is 2.71 times higher, a kcat value that is 179% higher, which translates to higher catalytic efficiency, and Km and binding constant (K) values that are lower, which indicate a higher KerZ1/CBM-L8-keratin binding affinity. Moreover, the number of binding sites to the substrate (N), determined using isothermal titration calorimetry, was 24.1 times higher than that of KerZ1. Thus, the fusion of the substrate-binding domain improved the binding ability of the keratinase enzyme to the hydrophobic substrate, which improved its feather hydrolysis efficiency. Therefore, using the fusion keratinase would significantly improve the recovery of feather waste.


[Automatic reading of microtitration plates: identification of Enterobacteriaceae and determination of their minimal inhibitory concentrations].
The authors evaluate an automatic microplate reader (Auto Reader Dynatech) and its application software. 291 strains of Enterobacteria belonging to 28 species were identified and 1,856 MIC were determined. The identifications made with the MIC 2000 tube were correct in terms of genus and species in 270 strains (92.8%) and in terms of genus in 274 strains (94.1%). The automated determination of the MIC was in complete agreement with visual reading in 90.6% of cases and with a deviation of +/- 1 dilution in 99.6% of cases. The programme was improved by the authors. This system is a new approach to automatization in microbiology.


Pharmacophore Alignment Search Tool (PhAST): Significance Assessment of Chemical Similarity.
Previously, we proposed a ligand-based virtual screening technique (PhAST) based on global alignment of linearized interaction patterns. Here, we applied techniques developed for similarity assessment in local sequence alignments to our method resulting in p-values for chemical similarity. We compared two sampling strategies, a simple sampling strategy and a Markov Chain Monte Carlo (MCMC) method, and investigated the similarity of sampled distributions to Gaussian, Gumbel, modified Gumbel, and Gamma distributions. The Gumbel distribution with a Gaussian correction term was identified as the most similar to the observed empirical distributions. These techniques were applied in retrospective screenings on a drug-like dataset. Obtained p-values were adjusted to the size of the screening library with four different methods. Evaluation of E-value thresholds corroborated the Bonferroni correction as a preferred means to identify significant chemical similarity with PhAST. An online version of PhAST with significance estimation is available at http://modlab-cadd.ethz.ch/.


Identification of polymorphisms in 12q24.1, ACAD10, and BRAP as novel genetic determinants of blood pressure in Japanese by exome-wide association studies.
We performed exome-wide association studies to identify genetic variants that influence systolic or diastolic blood pressure or confer susceptibility to hypertension in Japanese. The exome-wide association studies were performed with the use of Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays and with 14,678 subjects, including 8215 individuals with hypertension and 6463 controls. The relation of genotypes of 41,843 single nucleotide polymorphisms to systolic or diastolic blood pressure was examined by linear regression analysis. After Bonferroni's correction, 44 and eight polymorphisms were significantly (P < 1.19 × 10-6) associated with systolic or diastolic blood pressure, respectively, with six polymorphisms (rs12229654, rs671, rs11066015, rs2074356, rs3782886, rs11066280) being associated with both systolic and diastolic blood pressure. Examination of the relation of allele frequencies to hypertension with Fisher's exact test revealed that 100 of the 41,843 single nucleotide polymorphisms were significantly (P < 1.19 × 10-6) associated with hypertension. Subsequent multivariable logistic regression analysis with adjustment for age and sex showed that five polymorphisms (rs150854849, rs202069030, rs139012426, rs12229654, rs76974938) were significantly (P < 1.25 × 10-4) associated with hypertension. The polymorphism rs12229654 was thus associated with both systolic and diastolic blood pressure and with hypertension. Six polymorphisms (rs12229654 at 12q24.1, rs671 of ALDH2, rs11066015 of ACAD10, rs2074356 and rs11066280 of HECTD4, and rs3782886 of BRAP) were found to be associated with both systolic and diastolic blood pressure, with those at 12q24.1 or in ACAD10 or BRAP being novel determinants of blood pressure in Japanese.


Usefulness and limitations of convergent cross sorting and continuity scaling methods for their application in simulated and real-world time series.
Causality detection methods are valuable tools for detecting causal links in complex systems. The efficiency of continuity scaling (CS) and the convergent cross sorting (CSS) methods to detect causality was analysed. Usefulness and limitations of both methods in their application to simulated and real-world time series was explored under different scenarios. We find that CS is more robust and efficient than the CSS method for all simulated systems, even when increasing noise levels were considered. Both methods were not able to infer causality when time series with a marked difference in their main frequencies were analysed. Minimum time-series length required for the detection of a causal link depends on intrinsic system dynamics and on the method selected to detect it. Using simulated time series, only the CS method was capable to detect bidirectional causality. Causality detection, using the CS method, should at least include: (i) causality strength convergence analysis, (ii) statistical tests of significance, (iii) time-series standardization, and (iv) causality strength ratios as a strength indicator of relative causality between systems. Causality cannot be detected by either method in simulated time series that exhibit generalized synchronization.


Alterations in normal canine platelets during storage in EDTA anticoagulated blood.
Flow cytometric detection of platelet surface-associated IgG (PSAIgG) can be used to determine whether immunologic factors are contributing to thrombocytopenia in dogs. In vitro alterations in platelet activation and morphology, however, could impact the results of this test. The purpose of this study was to determine whether the PSAIgG test for immune-mediated thrombocytopenia was valid on whole blood in EDTA anticoagulant after 24-72 hours of storage, and to characterize other alterations in canine platelets that could impact immunologic testing. Platelets were harvested and analyzed immediately after blood collection and after 24, 48, and 72 hours of storage at 4 degrees C. Spontaneous and thrombin-induced changes in the following platelet parameters were evaluated using flow cytometric techniques: PSAIgG, platelet microparticle formation, membrane expression of P-selectin and glycoprotein CD61, exogenous IgG binding, surface-exposed phosphatidylserine, and fibrinogen binding. The amount of PSAIgG increased 6- to 9-fold in stored samples compared with fresh samples. Platelet microparticle formation was spontaneous in stored samples and increased significantly over time. Membrane phosphatidylserine, P-selectin, and fibrinogen binding were not altered by storage, indicating that platelet activation was minimal in stored samples. Although storage decreased the percentage of platelets positive for CD61 by 8- to 10-fold compared with fresh samples, activation by high-dose thrombin partially restored the percentage of CD61-positive platelets in 24-hour-old samples. In conclusion, even though platelets stored in EDTA for up to 72 hours remain in a resting state, aged platelets have an increased tendency to form microparticles and have increased surface IgG and decreased surface CD61, which may contribute to false-positive results for tests of immune-mediated thrombocytopenia.


Solar photocatalysis for treatment of Acid Yellow-17 (AY-17) dye contaminated water using Ag@TiO2 core-shell structured nanoparticles.
Wastewater released from textile industries causes water pollution, and it needs to be treated before discharge to the environment by cost effective technologies. Solar photocatalysis is a promising technology for the treatment of dye wastewater. The Ag@TiO2 nanoparticles comprising of Ag core and TiO2 shell (Ag@TiO2) have unique photocatalytic property of inhibition of electron-hole recombination and visible light absorption, which makes it a promising photocatalyst for use in solar photocatalysis and with higher photocatalytic rate. Therefore, in the present work, the Ag@TiO2 nanoparticles synthesized by one pot method with postcalcination step has been used for the degradation of Acid Yellow-17 (AY-17) dye under solar light irradiation. The Ag@TiO2 nanoparticles were characterized using thermogravimetric-differential thermal analysis, X-ray diffraction, transmission electron microscopy, selected area electron diffraction, and energy dispersive X-ray analysis. The catalyst has been found to be very effective in solar photocatalysis of AY-17, as compared to other catalysts. The effects of pH, catalyst loading, initial dye concentration, and oxidants on photocatalysis were also studied. The optimized parameters for degradation of AY-17 using Ag@TiO2 were found to be pH 3, dye/catalyst ratio of 1:10 (g/g), and 2 g/L of (NH4)2S2O8 as oxidant. Efficient decolorization and mineralization of AY-17 was achieved. The kinetics of color, total organic carbon, and chemical oxygen demand removal followed the Langmuir-Hinshelwood model. Ag@TiO2 catalyst can be reused thrice without much decline in efficiency. The catalyst exhibited its potential as economic photocatalyst for treatment of dye wastewater.


Ecofriendly Elimination of Ni (II) Using Fabricated Nanocomposite Based on Chitosan/Silver Nanoparticles/Carbon Nanotubes.
Nickel ions are hazardous heavy metals that are non-biodegradable and can lead to allergic sensitivity and dermatitis. Nanomaterials are chosen for their effective elimination of impurities from water structures based entirely on the variety of therapy and degree of purification. The target of this work was the combination of the properties of biopolymers such as chitosan, silver nanoparticles (SNPs), and carbon nanotubes (CNTs) in one ecofriendly compound for Ni (II) uptake from the aqueous solution. To attain this target, the endeavor was made by creating a nanocomposite based on chitosan/SNPs/CNTs. The characterization of the structure of the fabricated nanocomposite (Chit-SNPs-CNTs) was carried out using different techniques. The removal of Ni (II) was examined by studying the adsorption of Ni (II) ions onto the fabricated nanocomposite by batch adsorption using UV, XRD, XPS, and ICP techniques. Moreover, we investigated the effect of the contact time, pH of the solution, and mass of the adsorbent on the efficiency of the adsorption of Ni (II). The results show that the adsorption capacity of Ni (II) increased by increasing the contact time with a neutral pH. The maximum removal of Ni (II) ions (99.70%) was found using 0.3 g of the (Chit-SNPs-CNTs) nanocomposite. In addition, the results indicate that the fabricated nanocomposite has a high adsorption effectivity, which is associated to the function of the chitosan, SNPs, and CNTs in upgrading the adsorption efficiency. Finally, the results in the existing work indicate that the ecofriendly nanocomposite organized here gave excessive effectivity closer to the elimination of Ni (II).


A Bayesian method for identifying genetic interactions.
An important challenge in the analysis of single nucleotide polymorphism (SNP) data is the identification of SNPs that interact in a nonlinear fashion in their association with disease. Such epistatic interactions among genetic variants at multiple loci likely underlie the inheritance of common diseases. We have developed a novel method called the Bayesian combinatorial method (BCM) for detecting combination of genetic variants that are predictive of disease. When compared with the multifactor dimensionality reduction (MDR), a widely used combinatorial method, BCM has significantly greater power to detect interactions and is computationally more efficient.


The increasing problem of motorcycle injuries in children and adolescents.
To quantify an anecdotally apparent increase in motorcycle-related injuries in children and adolescents across Victoria. Retrospective analysis of paediatric motorcycle injuries (1 July 2000 - 30 June 2004) from a statewide emergency department (ED) database (Victorian Emergency Minimum Dataset [VEMD]) and the Trauma Registry database at the Royal Children's Hospital (RCH), Melbourne. Trends in paediatric motorcycle-related injuries over time; patient demographics, circumstances of accidents (on or off road), and injury characteristics, including severity markers. The VEMD recorded 3163 patients aged < or = 16 years presenting to EDs with motorcycle injuries during the study period; population-based rates of these injuries increased by an average of 9.6% per year (95% CI, 6.2%-13.1%; P < 0.005). In the same period, there was a total of 167 motorcycle-related admissions to the RCH, increasing annually in line with statewide ED presentations. About a quarter of paediatric motorcycle accidents occurred in children aged under 10 years (VEMD, 22%; RCH, 27%) and most occurred off road (VEMD,89%; RCH, 71%). At the RCH, median length of stay was 3 days (interquartile range [IQR], 1-7 days) and the median Injury Severity Score was 9 (IQR, 4-10); 41% of patients required an operation, 13% were admitted to an intensive care unit, and two died. In Victoria, the incidence of motorcycle-related injuries is increasing in children and adolescents. Most of these injuries occur off road, outside of any legislative framework. There is an urgent need for coordinated legislative changes and educational efforts to decrease motorcycle injuries in children.


Effects of genotoxicity and its consequences at the population level in sexual and asexual Artemia assessed by analysis of inter-simple sequence repeats (ISSR).
There is considerable evidence that genetic damage in organisms occurs in the environment as a result of exposure to genotoxins and ionising radiation, but we have limited understanding of the extent to which this results in adverse consequences at a population level. We used inter-simple sequence repeat (ISSR) markers to quantify genotoxic effects of the mutagen ethylmethane sulfonate (EMS) on a sexual (Artemia franciscana) and an asexual (Artemia parthenogenetica) species of brine shrimp. The method provides information similar to that obtained with assessment of RAPD (random amplification of polymorphic DNA) but is more robust. Genetic damage was transmitted to the F1 generation in both Artemia species, but the sexual species showed a greater degree of recovery, as shown by higher values of genomic template stability. There was a strong correlation between DNA damage and effects on individual fitness parameters: size, survival, reproduction and population growth. These effects persisted into the F2 generation in A. parthenogenetica, but in the sexual A. franciscana only effects on fecundity continued beyond the exposed generation, even though there were substantial alterations in ISSR patterns in the F1 generation. Genetic biomarkers can thus be indicative of effects at the population level, but sexually reproducing species have a considerable assimilative capacity for the effects of genotoxins.


Evaluation of a new combined inactivated DPT-polio vaccine.
A new combined DPT-Poliovirus vaccine (DPTP) has been developed in France. It contains the DPT components mixed with poliovirus antigens, prepared by culture on vero cells on microcarriers, inactivated by formalin and formulated at a level of 40-8-32 D-antigen units for the type 1, 2 and 3 respectively. A clinical evaluation of this vaccine was conducted in Mali (West Africa) among 320 infants 3 to 24 months of age. The infants were randomly assigned to 3 groups. One group received 2 doses of DPTP, a second group 2 doses of DPT and poliovirus vaccine (IPV) given in two separate sites, the third group 2 doses of DPT and oral poliovirus vaccine (OPV). In each group the 2 doses were given 3 months a part. No severe adverse reactions were observed and no statistical difference was noticed between the three groups for minor side effects. A seroconversion rate of 100% was observed to poliovirus antigens in the groups who received IPV simultaneously or combined with DPT, as compared to 49 to 77% in the group who received OPV. A seroconversion rate of 100%, 100% and 92% was shown in the DPTP group respectively to diphtheria, tetanus and pertussis antigens. No statistical difference was recorded between the 3 groups in the serological response to DPT antigens. A follow-up could be performed in 74 children one year after primary vaccination and a dramatic response to a booster dose of DPTP was measured.(ABSTRACT TRUNCATED AT 250 WORDS)


Studies on the metabolism of a monoterpene ketone, R-(+)-pulegone--a hepatotoxin in rat: isolation and characterization of new metabolites.
1. The metabolic disposition of R-(+)-pulegone (I) was examined in rats following four daily oral doses (250 mg/kg). 2. Six metabolites, namely pulegol (II), 2-hydroxy-2-(1-hydroxy-1-methylethyl)-5-methylcyclohexanone (III), 3,6-dimethyl-7a-hydroxy-5,6,7,7a-tetrahydro-2(4H)-benzofuranone (IV), menthofuran (V), 5-methyl-2-(1-methyl-1-carboxyethylidene)cyclohexanone (VI), and 5-methyl-5-hydroxy-2-(1-hydroxy-1-carboxyethyl)cyclohexanone (VII) have previously been isolated from rat urine, and identified (Moorthy et al. (1989a). Eight new metabolites have now been isolated from rat urine, namely, 5-hydroxy-pulegone (VIII), piperitone (IX), piperitenone (X), 7-hydroxy-piperitone (XI), 8-hydroxy piperitone (XII), p-cresol (XIII), geranic acid (XIV) and neronic acid (XV). These were identified by n.m.r., i.r. and mass spectrometry. 3. Based on these results, metabolic pathways for the biotransformation of R-(+)-pulegone in rat have been proposed.


Prognostic value of pretreatment (18)F-FDG PET-CT in radiotherapy for patients with hepatocellular carcinoma.
The purpose of this study was to investigate the predictable value of pretreatment (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in radiotherapy (RT) for patients with hepatocellular carcinoma (HCC) or portal vein tumor thrombosis (PVTT). We conducted a retrospective analysis of 36 stage I-IV HCC patients treated with RT. (18)F-FDG PET-CT was performed before RT. Treatment target was determined HCC or PVTT lesions by treatment aim. They were irradiated at a median prescription dose of 50 Gy. The response was evaluated within 3 months after completion of RT using the Response Evaluation Criteria in Solid Tumors (RECIST). Response rate, overall survival (OS), and the pattern of failure (POF) were analyzed. The response rate was 61.1%. The statistically significant prognostic factor affecting response in RT field was maximal standardized uptake value (maxSUV) only. The high SUV group (maxSUV ≥ 5.1) showed the better radiologic response than the low SUV group (maxSUV < 5.1). The median OS were 996.0 days in definitive group and 144.0 days in palliative group. Factors affecting OS were the %reduction of alpha-fetoprotein (AFP) level in the definitive group and Child-Pugh class in the palliative group. To predict the POF, maxSUV based on the cutoff value of 5.1 was the only significant factor in distant metastasis group. The results of this study suggest that the maxSUV of (18)F-FDG PET-CT may be a prognostic factor for treatment outcome and the POF after RT. A %reduction of AFP level and Child-Pugh class could be used to predict OS in HCC.


Linear juvenile dermatomyositis: A segmental manifestation.
A 7-year-old girl presented with proximal muscle weakness and skin lesions. Physical examination revealed violaceous papules on the right forearm in a blaschkoid distribution. Her symptoms and test results were consistent with juvenile dermatomyositis. An unusual superimposed segmental manifestation of this disease is discussed.


What is the right dose of epinephrine?
To review the findings and discuss implications of studies on high-dose epinephrine (0.1 mg/kg) during cardiopulmonary resuscitation in children. A critical appraisal of "A Comparison of High-Dose and Standard-Dose Epinephrine in Children with Cardiac Arrest" by Perondi et al. (N Engl J Med 2004; 350:1722-1730), with literature review. Retrospective studies investigating the use of high-dose epinephrine during pediatric cardiopulmonary resuscitation demonstrate conflicting results with respect to return of spontaneous circulation and survival. The randomized controlled trial by Perondi et al. demonstrates decreased survival with the use of high-dose epinephrine and no difference in return of spontaneous circulation when compared with the standard dose. There is no benefit from the use of high-dose epinephrine in pediatric cardiopulmonary resuscitation. There is potential harm from such dosing. The cumulative evidence against the use of high-dose epinephrine during pediatric cardiopulmonary resuscitation is strong.


Tumor necrosis factor and endotoxin do not directly affect in vitro diaphragm function.
Ventilatory pump failure can occur in the setting of severe infection. Recent in vivo studies have shown a significant decrease in diaphragm force production in rats with pneumococcal sepsis and sepsis secondary to Escherichia coli endotoxin. We hypothesized that diaphragm impairment during sepsis may be mediated by a direct effect of tumor necrosis factor-alpha (TNF) or endotoxin. To test this hypothesis we studied the mechanical characteristics of isolated rat diaphragm strips in tissue baths containing rTNF-alpha or endotoxin and compared the results with control strips. The strips were stimulated to contract isometrically in the tissue baths that were aerated with 95% O2-5% CO2. Baseline force-frequency determinations were made at 60 min. Following this, the strips were fatigued over a 4-min period (20 Hz, 0.33-s trains, 1 train/s) and force-frequency relationships determined 30 s, 10 min, and 60 min post-fatigue. There were no significant differences found between control and experimental strips in any aspect of contractile function tested, including force-frequency characteristics, fatiguability, and recovery from fatigue. Using an isolated cell line assay (L929), we found evidence of attenuated cytotoxicity of TNF at 26 degrees C compared with 37 degrees C. Therefore, we repeated the experiments studying the effects of TNF on in vitro muscle at 37 degrees C. We once again found no effect of TNF on contractile function. We conclude that the impairment of diaphragm function during sepsis is not mediated by a direct effect of TNF or endotoxin.


Effect of Boswellia papyrifera on cognitive impairment in multiple sclerosis.
Cognitive impairment is one of the most crucial disorders among multiple sclerosis (MS) patients. Since MS is an inflammatory disease and Boswellia papyrifera has anti-inflammatory effects, the influence of B. papyrifera on cognitive impairment in MS patients has been investigated in the present study. In this clinical trial, 80 MS patients who referred to the clinic of Shafa Hospital, Kerman, Iran were selected. Having completed a written consent form, patients with relapsing remitting MS, with no occurrence of a new attack throughout 1 month before the study, with no pregnancy or breastfeeding entered the study. The patients were randomly divided into two groups; then Brief International Cognitive Assessment for MS (BICAMS) test was carried out. One group received B. papyrifera (capsule 300 mg, twice a day) while the other group received placebo with the same dose for 2 months. After 2 months of treatment, BICAMS was redone and changes were analyzed. The significant change value on the before-after BICAMS points were considered to be 8, 13, and 7 points for the symbol digit modality test (SDMT), the California verbal learning test (CVLT), and the brief visual-spatial memory test revised (BVMT-R), respectively. The patients' mean age was 36.58 8.50 years. The mean duration of disease was 7.41 4.13 years. About 84.2% (n = 64) of the patients was female. In the BVMT-R, 13 patients (34.2%), who had already taken B. papyrifera, were shown to have significant improvement compared to the placebo group with no improvement (P < 0. 001). About 12 and 8 patients in the treatment and placebo groups in the SDMT, respectively (P = 0.200) and 17 and 12 patients in the treatment and placebo groups in the CVLT, respectively (P = 0.170) had significant change values. B. papyrifera showed significant improvement in visuospatial memory, but had no effect on verbal memory and information processing speed.


[Presence and functional role of an epitope of the second receptor for IgE (FcE RII) in mast cells and basophils in the rat].
Mast cells and basophils express the high affinity IgE receptor (FcERI) whereas the low affinity receptor for monomeric IgE (FcE RII) is present on macrophages, lymphocytes, eosinophils, platelets and Langerhans cells. Recent studies confirmed that the two receptors were totally distinct. The present work shows that a monoclonal antibody (BB10), able to bind to FcE RII on different cell populations, interacts with FcE RI expressing cells: rat peritoneal mast cells and a rat basophilic leukemia cell line (RBL 2 H 3). The structure recognized by BB10 is distinct from FcE RI and modulates the IgE-dependent histamine release. In conclusion, it appears that a common epitope with FcE RII is present on mast cells and basophils and that a functional relation might exist between this structure and FcE RI.


Erbium:YAG laser-assisted cataract surgery.
To assess the safety and efficacy of erbium:YAG laser-assisted cataract removal. A total of 15 patients underwent cataractous lens removal. All the patients had a visual acuity of 20/50 or worse secondary to senile cataract. The endothelial cell count was calculated preoperatively and at 6 weeks postoperatively. A 2.94-micron-wavelength erbium: YAG laser with a zirconium-fluoride fiber optic and silica tip was used to fracture and emulsify the nucleus. The erbium:YAG laser was chosen due to its high absorption in water, a primary component of a cataractous lens. The postoperative visual acuity was 20/30 or better in all the eyes that were treated with surgery. The endothelial cell loss at 3 months was 0% to 10%. No laser-related complications were noted. A conversion to an ultrasound surgical technique was utilized in six cases. Vitreous loss occurred in one case due to the posterior extension of an anterior capsulotomy tear. This study demonstrated the ability of an erbium:YAG laser system to safely and effectively emulsify the lens nucleus. Laser-assisted cataract surgery is a promising new clinical procedure.


Neurosurgical Experience of Beirut Blast in the Era of Coronavirus Disease 2019 (COVID-19) from a Tertiary Referral Center.
In this paper, we shed the light on Beirut's blast that took place in the coronavirus disease 2019 (COVID-19) era. An explosion that ripped the heart of Beirut, it produced a destructive shock wave that left thousands of casualties and people homeless. This explosion, which had a mushroom-like cloud appearance similar to that of Hiroshima and Nagasaki, was described as the third-biggest explosion in human history. It was a blast that not only destroyed lives but also fell as a heavy burden on the shoulders of a country that was suffering from unprecedented economic crisis on top of the COVID-19 pandemic. Facing all this, health care providers were the first line of defense in what looked like an impossible mission. We seek to share with the medical community our experience and the challenges we faced, as a neurosurgery team, during this event, particularly that we were short of basic medical equipment as well as intensive care unit beds since we were in the middle of an economic crisis and the peak of the COVID-19 pandemic. This prohibited us from delivering proper care, whether in the triage of patients or in the operating room, as well as postoperative care. Now, 1 year after this sad event, we revisit the whole situation and examine all the pitfalls that could have been avoided. Thus, we discuss the importance of initiating a disaster response, in particular the neurosurgical emergency response, to be better prepared to face future potential events. The rate-limiting step in such disasters is definitely a well-prepared trained team with a prompt and fast response. And, since time is brain, then what saves the brain is proper timing.


Effects of quality of treatment on prognosis in primary breast cancer patients treated in daily practice.
Information on treatment outcome outside clinical trials is sparse. This is the first study that relates surgical and medical quality of care in daily practice with outcome. In a previous study we showed, that the quality of chemotherapy as described by a guideline and given in daily practice to premenopausal primary breast cancer patients was suboptimal with only 68% and 53% of the patients receiving chemotherapy with a dose intensity (DI) and relative dose intensity (RDI) of > or = 85%, respectively. Many invalid reasons for delay and dose reductions were identified. Premenopausal node-positive primary breast cancer patients treated from 1988 to 1992 were traced using two national registries. Relevant data were collected from their records. The following treatment-related variables were correlated with prognosis: type of surgery, number of investigated lymph nodes, radiotherapy, chemotherapy, interval between surgery and start of chemotherapy, DI, duration, delays and dose adjustments of chemotherapy and hospital size. Twenty-four of the 254 traced patients did not receive any chemotherapy, 230 received the recommended schedule of cyclophosphamide (C), methotrexate (M) and 5-fluorouracil (F). The median time of follow-up was 6.7 (range 0.9-10.2) years. The 5-year disease-free survival (DFS) and overall survival (OS) was 61% and 77%, respectively. In an univariate analysis DI < 65% correlated with a worse DFS and OS (p=0.05 and p=0.03, respectively). The use of chemotherapy correlated with a better DFS (p=0.03) than no use. In a multivariate analysis DI between 65 and 85% resulted in a better DFS (p=0.02) than DI > or = 85% and DI < 65%. The prognosis of the breast cancer patients in this population was comparable with the results of randomised trials using adjuvant CMF. The only treatment related variable of value for prognosis was DI. Unexpectedly DI between 65% and 85% resulted in the best prognosis in this population. The relevance of this observation remains unclear and warrants further investigation.


Leaf physiology and biomass allocation of backcross hybrid American chestnut (Castanea dentata) seedlings in response to light and water availability.
Partial canopy cover promotes regeneration of many temperate forest trees, but the consequences of shading on seedling drought resistance are unclear. Reintroduction of blight-resistant American chestnut (Castanea dentata (Marsh.) Borkh.) into eastern North American forests will often occur on water-limited sites and under partial canopy cover. We measured leaf pre-dawn water potential (Ψpd), leaf gas exchange, and growth and biomass allocation of backcross hybrid American chestnut seedlings from three orchard sources grown under different light intensities (76, 26 and 8% full photosynthetically active radiation (PAR)) and subjected to well-watered or mid-season water-stressed conditions. Seedlings in the water-stress treatment were returned to well-watered conditions after wilting to examine recovery. Seedlings growing under medium- and high-light conditions wilted at lower leaf Ψpd than low-light seedlings. Recovery of net photosynthesis (Anet) and stomatal conductance (gs) was greater in low and medium light than in high light. Seed source did not affect the response to water stress or light level in most cases. Between 26 and 8% full PAR, light became limiting to the extent that the effects of water stress had no impact on some growth and morphological traits. We conclude that positive and negative aspects of shading on seedling drought tolerance and recovery are not mutually exclusive. Partial shade may help American chestnut tolerate drought during early establishment through effects on physiological conditioning.


Restoration of the severely worn dentition using a systematized approach for a predictable prognosis.
Dental literature supports the concept that vertical dimension of occlusion is normally not lost in severely worn dentition, and the bite should generally not be opened to facilitate dental reconstruction. However, restoration of a periodontally sound but severely worn dentition, at existing vertical dimension, frequently presents unique challenges in patient management, diagnosis, treatment planning, and restorative methodology. This report reviews and demonstrates an integrated and planned approach to this complex treatment situation that can lead to a favorable and predictable prognosis. The approach also allows a practitioner free use of various techniques if certain goals of occlusion are followed.


Prothrombin kringle-2 activates cultured rat brain microglia.
Microglia, the major immune effector cells in the CNS, become activated when the brain suffers injury. In this study, we observed that prothrombin, a zymogen of thrombin, induced NO release and mRNA expression of inducible NO synthase, IL-1beta, and TNF-alpha in rat brain microglia. The effect of prothrombin was independent of the protease activity of thrombin since hirudin, a specific inhibitor of thrombin, did not inhibit prothrombin-induced NO release. Furthermore, factor Xa enhanced the effect of prothrombin on microglial NO release. Kringle-2, a domain of prothrombin distinct from thrombin, mimicked the effect of prothrombin in inducing NO release and mRNA expression of inducible NO synthase, IL-1beta, and TNF-alpha. Prothrombin and kringle-2 both triggered the same intracellular signaling pathways. They both activated mitogen-activated protein kinases and NF-kappaB in a similar pattern. NO release stimulated by either was similarly reduced by inhibitors of the extracellular signal-regulated kinase pathway (PD98059), p38 (SB203580), NF-kappaB (N-acetylcysteine), protein kinase C (Go6976, bisindolylmaleimide, and Ro31-8220), and phospholipase C (D609 and U73122). These results suggest that prothrombin can activate microglia, and that, in addition to thrombin, kringle-2 is a domain of prothrombin independently capable of activating microglia.


Atopic Glaucoma: Clinical and Pathophysiological Analysis.
Open-angle glaucoma associated with severe atopic dermatitis (atopic glaucoma) tends to be severe and difficult to treat because of ocular surface/eye lid inflammation. To determine the validity of regarding atopic glaucoma as a clinical entity, we carried out retrospective analysis and pathologic investigations. Forty-five cases (62 eyes) of atopic glaucoma were reviewed retrospectively. During surgical treatment, aqueous humor and trabeculectomy specimens were obtained. The aqueous humor samples were analyzed by multiplex cytokine assay. The surgical specimens were analyzed histologically. Atopic glaucoma was often associated with atopic cataracts (43 eyes) and retinal detachments (19 eyes). A history of glucocorticoid medications was absent in 12 cases. A total of 50 eyes required surgical interventions because of advanced visual field defects and/or high intraocular pressures. Bleb-associated postsurgical infections were observed in 7 eyes. Elevated levels of inflammatory cytokines (IL-8 and CCL2) were observed in the aqueous humor samples obtained from atopic glaucoma patients compared with those from senile cataract patients. Ultrastructural analysis of trabecular meshwork tissues obtained from atopic glaucoma patients showed abnormal accumulation of 10 to 30 nm fibers in the corneoscleral meshwork. We would like to propose atopic glaucoma as a new clinical entity, ranging from pure atopic glaucoma to a mixed type of atopic/steroid-induced glaucoma that should be considered as one of the clinical features of atopic ocular complications.


Exploiting the diversity of tomato: the development of a phenotypically and genetically detailed germplasm collection.
A collection of 163 accessions, including Solanum pimpinellifolium, Solanum lycopersicum var. cerasiforme and Solanum lycopersicum var. lycopersicum, was selected to represent the genetic and morphological variability of tomato at its centers of origin and domestication: Andean regions of Peru and Ecuador and Mesoamerica. The collection is enriched with S. lycopersicum var. cerasiforme from the Amazonian region that has not been analyzed previously nor used extensively. The collection has been morphologically characterized showing diversity for fruit, flower and vegetative traits. Their genomes were sequenced in the Varitome project and are publicly available (solgenomics.net/projects/varitome). The identified SNPs have been annotated with respect to their impact and a total number of 37,974 out of 19,364,146 SNPs have been described as high impact by the SnpEeff analysis. GWAS has shown associations for different traits, demonstrating the potential of this collection for this kind of analysis. We have not only identified known QTLs and genes, but also new regions associated with traits such as fruit color, number of flowers per inflorescence or inflorescence architecture. To speed up and facilitate the use of this information, F2 populations were constructed by crossing the whole collection with three different parents. This F2 collection is useful for testing SNPs identified by GWAs, selection sweeps or any other candidate gene. All data is available on Solanaceae Genomics Network and the accession and F2 seeds are freely available at COMAV and at TGRC genebanks. All these resources together make this collection a good candidate for genetic studies.


Changes in optical properties of electroporated cells as revealed by digital holographic microscopy.
Changes in optical and shape-related characteristics of B16F10 cells after electroporation were investigated using digital holographic microscopy (DHM). Bipolar rectangular pulses specific for electrochemotherapy were used. Electroporation was performed in an "off-axis" DHM set-up without using exogenous markers. Two types of cell parameters were monitored seconds and minutes after pulse train application: parameters addressing a specifically defined area of the cell (refractive index and cell height) and global cell parameters (projected area, optical phase shift profile and dry mass). The biphasic behavior of cellular parameters was explained by water and mannitol dynamics through the electropermeabilized cell membrane.


The Austria-Czech Republic co-operation in the field of radiation-emergency preparedness.
An overview on the long-term information exchange and co-operation between Austria and the Czech Republic in the field of radiation emergency preparedness and evaluation of radiological consequences of NPP accidents is provided. Initiated by the 'Melk Protocol' between the Czech and Austrian governments in December 2000 and its follow-up activities, the information exchange and co-operation between the Czech Republic and Austria in the field of radiation-emergency preparedness have been extended. Among others, a Working Group to compare radiological consequences of Beyond Design Basis Accident with a detailed inter-comparison program concerning atmospheric dispersion models, dose assessment methods and counter- measures was established. Based on this experience, an area for future co-operation in the field of emergency preparedness and information exchange between the Czech Republic and Austria is discussed.


[Febrile infection-related status epilepticus in a child after a common infection].
A 13-year-old boy developed seizures and intractable status epilepticus a week after having had a sore throat. Ketogenic diet possibly had some effect. Antibodies to calmodulin dependent protein kinase II were found and could possibly suggest an immunologic aetiology.


Nucleosome position-dependent and -independent activation of HIS7 epression in Saccharomyces cerevisiae by different transcriptional activators.
ARO4 and HIS7 are two tandemly orientated genes of Saccharomyces cerevisiae that are transcribed into the same direction. The ARO4 terminator and the HIS7 promoter regions are sensitive to Micrococcus nuclease (Mnase) and separated by a positioned nucleosome. The HIS7 promoter is target for the transcription factors Gcn4p and Bas1p/Bas2p that activate its transcription upon amino acid starvation and purine limitation, respectively. Activation of the HIS7 gene by Gcn4p overexpression but not by Bas1p/Bas2p releases an ordered nucleosome distribution to yield increased Mnase sensitivity throughout the intergenic region. This remodeling is SNF2 dependent but mostly GCN5 independent. Accordingly, SNF2 is necessary for the Gcn4p-mediated transcriptional activation of the HIS7 gene. GCN5 is required for activation upon adenine limitation by Bas1p/Bas2p. Our data suggest that activation of HIS7 transcription by Gcn4p and Bas1p/Bas2p is supported by a nucleosome position-dependent and -independent mechanism, respectively. Whereas Gcn4p activation causes Swi/Snf-mediated remodeling of the nucleosomal architecture at the HIS7 promoter, the Bas1p/Bas2p complex presumably activates in combination with Gcn5p-dependent histone acetylation.


Quantum yield measurement in a multicolor chromophore solution using a nanocavity.
Using our nanocavity-based method for precise determination of the absolute quantum yield values, we measure the quantum yield of each of the three different chromophores types with strongly overlapping absorption spectra in a multicolor solution, which is impossible to do by any other existing technique. By measuring the modification of the radiative rate of the chromophores at different cavity lengths, we extract the quantum yield of CdSe/ZnS semiconductor nanocrystals emitting at three different wavelengths and excited by a single wavelength in the multicolor solution. Using several detection channels, we show that only one measurement is needed for determining the quantum yield values of all the types of chromophores in the sample. The obtained results show a very good agreement with the values commonly observed using other techniques. The nanocavity-based method opens up new opportunities of determining fluorescence quantum yields in complex systems and can be used for a big variety of fluorescence studies where multichromophore samples are involved.


A Case of Anterior Spinal Artery Syndrome Caused by Streptococcus mitis Endocarditis.
Infectious endocarditis (IE) typically occurs in the setting of intravenous drug use, prosthetic heart valves, or rheumatic heart disease. However, there are a few reports of IE occurring in the setting of immunosuppression secondary to cancer and/or chemotherapy. Here, we present a case of a cancer patient who developed anterior spinal artery (ASA) syndrome secondary to a septic embolus from IE. A 78-year-old male with a history of gastroesophageal cancer treated with chemotherapy and radiation presented to the hospital after a fall at home. He reported experiencing dyspnea and orthopnea for two weeks prior to presentation. In the ED, his vital signs were stable, and his examination was significant for a flaccid paralysis of the right lower extremity. Diagnosis of septic emboli secondary to IE was made after the echocardiogram showed the presence of vegetations on the aortic valve, blood cultures were positive for Streptococcus mitis, and thoracic spine MRI was indicative of an infarction at T10. This case highlights the presence of IE in the setting of cancer and chemotherapy. Although cancer is a rare cause of IE, clinicians must maintain a high index of suspicion in order to minimize the sequelae of IE.


Progesterone receptor action in leiomyoma and endometrial cancer.
Progesterone is a key hormone in the regulation of uterine function. In the normal physiological context, progesterone is primarily involved in remodeling of the endometrium and maintaining a quiescent myometrium. When pathologies of the uterus develop, specifically, endometrial cancer and uterine leiomyoma, response to progesterone is usually altered. Progesterone acts through mainly two isoforms of the progesterone receptor (PR), PRA and PRB which have been reported to exhibit different transcriptional activities. Studies examining the expression and function of the PRs in the normal endometrium and myometrium as well as in endometrial cancer and uterine leiomyoma are summarized here. The clinical use of progestins and the transcriptional activity of the PR on genes specific to endometrial cancer and leiomyoma are described. An increased understanding of the differential expression of PRs and response to progesterone in these two diseases is critical in order to develop more efficient and targeted therapies.


Secondhand Smoke Induces Inflammation and Impairs Immunity to Respiratory Infections.
Despite advocacy to reduce smoking-related diseases, >1 billion people worldwide continue to smoke. Smoking is immunosuppressive and an important etiological factor in the development of several human disorders including respiratory diseases like chronic obstructive pulmonary disease. However, there is a critical gap in the knowledge of the role of secondhand smoke (SHS) in inflammation and immunity. We therefore studied the influence of SHS on pulmonary inflammation and immune responses to respiratory infection by nontypeable Haemophilus influenzae (NTHI) recurrently found in chronic obstructive pulmonary disease patients. Chronic SHS-exposed mice were chronically infected with NTHI and pulmonary inflammation was evaluated by histology. Immune cell numbers and cytokines were measured by flow cytometry and ELISA, respectively. Chronic SHS exposure impaired NTHI P6 Ag-specific B and T cell responses following chronic NTHI infection as measured by ELISPOT assays, reduced the production of Abs in serum and bronchoalveolar lavage, and enhanced albumin leak into the bronchoalveolar lavage as determined by ELISA. Histopathological examination of lungs revealed lymphocytic accumulation surrounding airways and bronchovasculature following chronic SHS exposure and chronic infection. Chronic SHS exposure enhanced the levels of inflammatory cytokines IL-17A, IL-6, IL-1β, and TNF-α in the lungs, and impaired the generation of adaptive immunity following either chronic infection or P6 vaccination. Chronic SHS exposure diminished bacterial clearance from the lungs after acute NTHI challenge, whereas P6 vaccination improved clearance equivalent to the level seen in air-exposed, non-vaccinated mice. Our study provides unequivocal evidence that SHS exposure has long-term detrimental effects on the pulmonary inflammatory microenvironment and immunity to infection and vaccination.


Blood pressure response and renin release following 4 days of treatment with dihydralazine and urapidil in conscious dogs.
The magnitude and the persistence of blood pressure reduction by dihydralazine and urapidil were investigated following treatment over a period of 4 days. The experiments were performed on six normotensive dogs, trained to submit to puncture of the femoral artery and to stand quietly in a special frame. The first-dose effects of orally administered dihydralazine (1.42, 7.1 mg X kg-1) and urapidil (2.0, 10.0 mg X kg-1) on heart rate, arterial blood pressure and plasma renin activity (PRA) were compared with the effects of the substances after 4 days of treatment. Both compounds caused a dose-dependent decrease in blood pressure but in contrast to urapidil the effect of dihydralazine was accompanied by large increases in heart rate and PRA. Dose-dependent tolerance to dihydralazine but not to urapidil was observed after treatment over only 4 days. However, basal blood pressure was significantly lowered after 4 days of treatment with urapidil at the high dosage and no further reduction was achieved on the fifth day. The importance of persistent counterregulation in the development of tolerance to the antihypertensive effect of dihydralazine is discussed.


Combustion of volatile organic compounds over composite catalyst of Pt/γ-Al₂O₃ and beta zeolite.
Catalytic oxidation of volatile organic compounds (VOCs) was carried out over a composite catalyst comprising Pt/γ-Al₂O₃ and protonated beta zeolite. The conversion of several VOCs such as ethyl acetate, butyl acetate, 2-propanol, 1,2-dichloroethane, and chloroethane over the composite catalyst was higher than the conversion over the conventional Pt/γ-Al₂O₃ catalyst, indicating a remarkable improvement in the oxidation activity of the composite. On the other hand, no difference in the conversion of methyl ethyl ketone, methyl isobutyl ketone, toluene, benzene, and chloroethylene was observed for the composite catalyst versus the Pt/γ-Al₂O₃ catalyst. To clarify the role of the zeolite component, the reaction products obtained using the composite catalyst were compared with those obtained using the Pt/γ-Al₂O₃ catalyst. For the cases in which considerable improvement in the oxidation activity was observed with the composite, it was revealed that the conversion of VOCs to intermediate compounds took place over the acidic sites of the zeolite; the intermediates tended to be easily oxidized to CO₂ on the Pt/γ-Al₂O₃ catalyst. In addition, the composite catalyst also exhibited high durability. High catalytic activity was maintained even after aging at 600°C for more than 1000 h.


Echoes of the Past: Recognizing Co-occurring Alcohol Use Disorder and Posttraumatic Stress Disorder in the American Veteran Population.
The aim of this editorial is to explore and highlight the importance of identifying both the alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) in the veteran population. Determining if the patient has military experience can assist in both an accurate and complete assessment. Being aware of the patient's military service time can help better understand some of the presenting physical and mental complaints that may incorrectly be attributed to substances. Although not all veterans had trauma exposure while in the military, asking about PTSD may help identify additional issues needing attention. Having a PTSD diagnosis increases the likelihood that there is an underlying substance use disorder. Veterans with PTSD have a 65% likely comorbidity with alcohol use (Smith, Goldstein, & Grant, 2016). Recognition of PTSD as a co-occurring disorder with AUD can begin the dialogue to address treatment of both disorders to optimize recovery.


[Diagnostic value of clinical study methods in syringomyelia].
Between 1968 and 1981 52 patients with syringomyelia were investigated clinically and with several additional procedures. The introduction of computerized axial tomography (CAT) has led to a change in diagnostic measurements in this disease. Therefore it has become necessary to evaluate the usefulness of additional investigations made in recent past. From own experiences the following measurements are indicated in patients with presumed syringomyelia: X-rays of the cervical and thoracal spinal column and the skull have to be complemented by automatic computerized transverse axial tomography (ACTA) of the spinal canal. CSF should be investigated before metrizamide myelography combined with computerized tomography--the so called computed assisted myelography--is done. These methods both the automatic computerized transverse axial tomography of the spinal canal and the computed assisted myelography allow a differentiation between communicating and non communicating syringomyelia. Computerized axial tomography of the skull is indicated to detect interval hydrocephalus that may be associated with communicating syringomyelia. The other methods evaluated in this study cannot be used to ascertain diagnosis. These measurements combined with clinical and radiological findings may only support diagnosis. Their significance lies in the critical examination of lost functions in the individual case. Especially electrodiagnostic test--as electromyelography and measurement of nerve conduction velocity--show the extension and distribution of the involved peripheral nervous system. These methods are necessary for the critical evaluation of both the spontaneous clinical course and the results of therapeutic procedures. The electromyography findings show the process of denervation already occurred and the degree of motor activity yet available. The measurement of nerve conduction velocity indicates the localization of involved peripheral nerves. The determination of evoked potentials yields informative findings. But at present the value of this method cannot yet be estimated finally. The indication of the discussed investigations depends on the clinical findings in the individual case with the exception of the radiological procedures.


Reduced high shear platelet adhesion to the vascular media: defective von Willebrand factor binding to the interstitial collagen.
Fibrillar collagen serves as a thrombogenic surface for platelet adhesion mediated by von Willebrand factor (vWf) at high shear. Although abundant throughout the arterial wall, vWf-dependent platelet deposition to artery cross-sections from perfused citrated blood is localized to the adventitia of the vessel wall. Here we describe a similarly skewed distribution of vWf-binding sites in artery cross-sections. Binding of vWf-coated fluorescent beads, as well as detection of plasma vWf bound to artery cross-section at 3350 s(-1) shear rate with indirect particle-immunofluorescence or immunoelectron microscopy demonstrate vWf binding sites in the adventitia, but not in the media. A monoclonal anti-vWf antibody that interferes with vWf-binding to collagen in a microplate ELISA inhibits vWf-binding to both the adventitia and sections of collagen fibrils. Our data suggest that the media, despite its fibrillar collagen content, evidenced by electron microscopy, is defective for vWf-binding, which may explain its thromboresistant nature at high shear rates.


Hearing restoration after resection of an intracanalicular vestibular schwannoma: a role for emergency surgery? Case report and review of the literature.
Patients with vestibular schwannomas (VSs) most commonly present with sensorineural hearing loss, which is often insidious or gradual. Up to 26% of patients may present with sudden hearing loss, however, which poses an important surgical challenge. Sudden hearing loss has been attributed to spasm or occlusion of the labyrinthine artery resulting from tumor compression, and it is usually treated with corticosteroids. Hearing preservation surgery is not usually attempted in patients who have poor or nonserviceable hearing preoperatively. The authors describe a 68-year-old man with complete deafness of the left ear since childhood, who developed sudden, profound sensorineural hearing loss in the right ear. Magnetic resonance imaging revealed a small right-sided intracanalicular tumor. Treatment with high-dose corticosteroids produced only minimal improvement in hearing. Subsequent emergency decompression and resection of a VS resulted in rapid improvement and restoration of hearing, with facial nerve preservation. Although most neurotologic lesions in patients with hearing in only one ear are managed nonsurgically, resection of small tumors in the setting of sudden hearing loss should be considered in selected cases. This finding indicates that a therapeutic window may exist during which sudden hearing loss caused by intracanalicular tumors is reversible.


Lactate Dehydrogenase: A Marker of the Severity of Vaso-Occlusive Crisis in Children with Sickle Cell Disease Presenting at the Emergency Department.
The aim of this study was to describe the characteristics of vaso-occlusive crises (VOC) in children with sickle cell disease and to identify factors associated with greater severity. We performed a prospective observational study from August 2012 to January 2014. The study population comprised patients with sickle cell disease who consulted at the emergency department (ED) for VOC. We recorded demographic variables, history of complications related to the disease, and data on usual treatment. We also assessed pain, analgesia at home, need for admission, length of stay, and analgesia during admission. Analytical parameters were collected. A total of 29 patients with VOC were included. The patient's usual treatment was hydroxyurea (HU) in 69.0%, and 7.0% required chronic transfusions. In the ED, 90.0% had moderate or severe pain, even though 86.0% had received analgesia at home (41.4% minor opioids). Overall, 27 of the 29 patients were admitted, and 56.0% needed major opioids. Higher lactate dehydrogenase (LDH) levels were related to the use of major opioids during admission (p = 0.038). A significant difference was recorded between the median number of days of admission for patients receiving non-steroidal anti-inflammatory drugs and for those requiring intravenous opioids (p = 0.005). Most patients with VOC were admitted to hospital. Lactate dehydrogenase level in the ED was a predictor of severity and was associated with the need for major opioids during admission and more days of admission.


[Experimental study on xue-bao capsules against injury of radiation or cyclophosphamide in mice].
To explore the effects of xue-bao capsules on injury of radio-or chemo-therapy in mice, in order to provide rationale behind clinical trials. xue-xu (deficiency of blood) model in mice was induced by radiation or cyclophosphamide. Leucocyte (WBC), erythrocyte (RBC), hemoglobin (Hb) and platelet (Pt) in peripheral blood as well as CFU-E and CFU-Gm in bone marrow were counted. CFU-E and CFU-Gm in normal mice were promoted by this drug. The reduction of WBC, RBC and Hb in peripheral blood as well as CFU-E and CFU-Gm in bone marrow owing to the 3.5 Gy of 60Co radiation were antagonized by the drug. It had also antagonized cyclophosphamide induced the reduction of WBC, RBC and Pt in peripheral blood. xue-bao capsules has the effects against the adverse reactions of radio-or-chemo-therapy.


Ischemia-reperfusion selectively impairs nitric oxide-mediated dilation in coronary arterioles: counteracting role of arginase.
A reduction in L-arginine availability has been implicated in the impairment of endothelium-dependent nitric oxide (NO)-mediated vasodilation by ischemia-reperfusion (I/R). However, the mechanisms contributing to dysregulation of the L-arginine pool remain unknown. Because endothelial cells can metabolize L-arginine via two major enzymes, that is, NO synthase (NOS) and arginase, we hypothesized that up-regulation of arginase during I/R reduces L-arginine availability to NOS and thus impairs NO-mediated vasodilation. To test this hypothesis, a local I/R was produced in the porcine heart by occlusion of a small branch of left anterior descending artery for 30 min, followed by reperfusion for 90 min. Arterioles (60-110 microm) isolated from non-ischemic and ischemic regions of subepicardium were cannulated and pressurized without flow for in vitro study. Vessels from both regions developed similar levels of basal tone. Although the dilation of I/R vessels to endothelium-independent agonist sodium nitroprusside was not altered, the endothelium-dependent NO-mediated dilations to adenosine and serotonin were attenuated. I/R not only inhibited arteriolar production of NO but also increased arteriolar arginase activity. Arginase inhibitor alpha-difluoromethylornithine enhanced NO production/dilation in normal vessels and also restored the NO-mediated function in I/R vessels. Treating I/R vessels with L-arginine also restored vasodilations. Immunohistochemical data revealed that I/R up-regulated arginase but down-regulated NOS expression in the arteriolar endothelium. Pretreating the animals with protein synthesis inhibitor cycloheximide prevented I/R-induced arginase up-regulation and also preserved NO-mediated vascular function. These results suggest that one mechanism by which I/R inhibits NO-mediated arteriolar dilation is through increased arginase activity, which limits the availability of L-arginine to NOS for NO production. In addition, the inability of arginase blockade or L-arginine supplementation to completely restore vasodilatory function may be attributable to the down-regulation of endothelial NOS expression.


Methyl Jasmonate Regulates Podophyllotoxin Accumulation in Podophyllum hexandrum by Altering the ROS-Responsive Podophyllotoxin Pathway Gene Expression Additionally through the Down Regulation of Few Interfering miRNAs.
Podophylloxin (ptox), primarily obtained from Podophyllum hexandrum, is the precursor for semi-synthetic anticancer drugs viz. etoposide, etopophos, and teniposide. Previous studies established that methyl jasmonate (MeJA) treated cell culture of P. hexandrum accumulate ptox significantly. However, the molecular mechanism of MeJA induced ptox accumulation is yet to be explored. Here, we demonstrate that MeJA induces reactive oxygen species (ROS) production, which stimulates ptox accumulation significantly and up regulates three ROS-responsive ptox biosynthetic genes, namely, PhCAD3, PhCAD4 (cinnamyl alcohol dehydrogenase), and NAC3 by increasing their mRNA stability. Classic uncoupler of oxidative phosphorylation, carbonylcyanide m-chlorophenylhydrazone, as well as H2O2 treatment induced the ROS generation and consequently, enhanced the ptox production. However, when the ROS was inhibited with NADPH oxidase inhibitor diphenylene iodonium and Superoxide dismutase inhibitor diethyldithio-carbamic acid, the ROS inhibiting agent, the ptox production was decreased significantly. We also noted that, MeJA up regulated other ptox biosynthetic pathway genes which are not affected by the MeJA induced ROS. Further, these ROS non-responsive genes were controlled by MeJA through the down regulation of five secondary metabolites biosynthesis specific miRNAs viz. miR172i, miR035, miR1438, miR2275, and miR8291. Finally, this study suggested two possible mechanisms through which MeJA modulates the ptox biosynthesis: primarily by increasing the mRNA stability of ROS-responsive genes and secondly, by the up regulation of ROS non-responsive genes through the down regulation of some ROS non-responsive miRNAs.


MHC class II molecules bind indiscriminately self and non-self peptide homologs: effect on the immunogenicity of non-self peptides.
Synthetic peptides spanning the entire sequence of both human and mouse beta 2-microglobulin (beta 2M) have been tested for their capacity to bind to three different mouse (I-Ad, I-Ed, and I-Ak) or human (DR1, DR2, and DR5) class II molecules. The results demonstrate that class II molecules do not discriminate between self and non-self peptides. When the immunogenicity of the human beta 2M peptides was measured by their ability to prime H-2d mice for in vitro T cell proliferation, it was found that peptides incapable of binding class II molecules in vitro were also non-immunogenic in vivo. Interestingly, however, several binders, including the human beta 2M peptide 1-16, the best binder in this series to Iad molecules, were found to be non-immunogenic. Since the corresponding mouse beta 2M peptide 1-16 was also capable of binding to Iad molecules, this suggested that lack of responsiveness to the non-self peptide could arise either from central or peripheral tolerance induced by the self homolog. Alternatively, lack of responsiveness could arise from other mechanisms, such as negative selection by other non-homolog sequences or lack of suitable T cell receptor genes. To discriminate between these possibilities, H-2d mice with disrupted beta 2M genes were immunized with the human beta 2M peptide 1-16. This peptide also failed to prime for T cell responsiveness in beta 2M-negative mice, suggesting that a hole in the T cell repertoire for this antigen was not mediated by negative selection or peripheral tolerance induced by self beta 2M peptides.


A systematic review and meta-analysis of pollutants in environmental media.
Environmental pollutants are ubiquitous in our environmental media, resulting in detrimental impacts on both humans and the environment. An evidence-based review, particularly a systematic review and meta-analysis, performs a crucial function in assessing the pollution status of pollutants in environmental media at national and global scales. We selected and thoroughly investigated 76 papers focusing on systematic reviews and meta-analyses of contaminants in environmental media. The need to broaden the scope of studies was observed with an increase in the total number of publications, and there were greater focuses on food safety, water pollution, biological pollution, and environmental risks. Furthermore, this review outlined the fundamental procedures involved in a systematic review and meta-analysis, including literature searching, screening of articles, study quality analysis, data extraction and synthesis, and meta-analysis. A meta-analysis typically comprises fixed- and/or random-effects meta-analysis, identifying and measuring heterogeneity, sensitivity analysis, publication bias, subgroup analysis, and meta-regression. We specifically explored the application of meta-analysis to assess the presence of contaminants in environmental media based on two different pollutant categories, namely, non-biological and biological pollutants. The mean value is commonly utilized to assess the pooled concentration of non-biological pollutants, while the prevalence serves as the effect size of biological pollutants. Additionally, we summarized the innovative applications, frequent misuses, and problems encountered in systematic reviews and meta-analyses. Finally, we proposed several suggestions for future research endeavors.


The urine-blood PCO gradient as a diagnostic index of H(+)-ATPase defect distal renal tubular acidosis.
Urine pH during acidemia and urine PCO2 upon alkalization both may be useful to indicate H+ secretion from collecting ducts. The urine anion gap has been used to detect urinary NH4+ for differential diagnosis of hyperchloremic metabolic acidosis. We have previously demonstrated that the lack of normal H(+)-ATPase may underlie secretory defect distal renal tubular acidosis (dRTA). In this study we evaluated the diagnostic value of the urine-blood (U-B) PCO2 in H(+)-ATPase defect dRTA, and compared it with that of urine pH and urine anion gap during acidemia. In H(+)-ATPase defect dRTA, the diagnostic values of three urinary parameters were evaluated: (1) urine pH measured after acid (NH4Cl) loading; (2) urine-to-blood carbon dioxide tension gradient (U-B PCO2) during alkali (NaHCO3) loading; and (3) urine anion gap during acidemia. Seventeen patients were diagnosed as having H(+)-ATPase defect dRTA based on reduced urinary NH4+ and an absolute decrease in H(+)-ATPase immunostaining in intercalated cells on renal biopsy. Eight patients with non-dRTA renal disease served as control patients. Upon NaHCO3 loading, U-B PCO2 was < or =30 mm Hg in all 17 dRTA patients and >30 mm Hg in all 8 control patients. With NH4Cl loading, urine pH was >5.4 in 15 of 17 dRTA patients and < or =5.4 in 7 of 8 control patients, and the urine anion gap was >5 mmol/L in 13 of 17 dRTA patients and< or =5 mmol/L in 6 of 8 control patients. Therefore, the sensitivity and specificity of U-B PCO2 < or =30 mm Hg during NaHCO3 loading were both 100%, whereas those of urine pH >5.4 or urine anion gap >5 mmol/L during NH4Cl loading were below 90%. In control patients, the U-B PCO2 was found to be well correlated with the urinary NH4+ (r= 0.79, P < 0.05). The U-B PCO2 during NaHCO3 loading is an excellent diagnostic index of H(+)-ATPase defect dRTA.


[Recent development of nucleic acid drug].
Oligonucleotides and their analogs have been utilized for the regulation of gene expression since mid-1970. The so-called antisense strategy has recently acquired its reality of the application to clinical therapeutic uses. In the course of the development, it has been found that nucleic acids might have broad variety of abilities to regulate gene expression. The abilities are classified as ribozymes, antigenes, decoy DNAs (or RNAs) and aptamers, and they can be applied to clinical uses as nucleic acid drugs in the near future.


Two new Tytthoscincus Linkem, Diesmos, Brown (Squamata; Scincidae) from Peninsular Malaysia and another case of microsyntopy between ecologically specialized, unrelated, leaf-litter species.
Two new species of diminutive, sympatric, lowland, leaf-litter skinks of the genus Tytthoscincus Linkem, Diesmos Brown from the Sekayu region of Hulu Terengganu, Terengganu State in northeastern Peninsular Malaysia are described on the basis genetic and morphological data. One of the new species, T. monticolus sp. nov., was collected in a hilly riparian area along Sungai (=river) Bubu and is most closely related to an undescribed species from the Tembak Reservoir area. The other, T. keciktuek sp. nov. collected along Sungai Peres, is most closely related to T. perhentianensis Grismer, Wood, Grismer from Pulau (=island) Perhentian Besar. Sympatry and syntopy of multiple, specialized, unrelated, leaf-litter species of Tytthoscincus was previously only known from upland areas and these new species represent the first example of lowland of sympatry. More importantly, however, these endemic species add to a growing body of research and discoveries that continue to underscore the unrealized biodiversity of the riparian systems of Hulu Terengganu and the Sekayu region and their need for protection and continued study.


Maillard reaction involved in the steaming process of the root of Polygonum multiflorum.
The steaming process is one of traditional Chinese medicine's processing approaches for many herbs. A new HPLC peak was found in the root of Polygonum multiflorum Thunb. (PM) after steaming. 2,3-dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (DDMP) and 5-hydroxymethyl furfural (5-HMF) were confirmed in the new peak. Additionally, two other compounds, butanedioic acid and 3,5-dihydroxy-2-methyl- 4(H)-pyran-4-one (hydroxymaltol), were isolated in the processed root of PM. An increase in DDMP concentration was observed during the first 24 h of steaming, followed by a constant decrease until 64 h of steaming. The amount of 5-HMF increased gradually throughout the steaming process. Changes to 16 kinds of amino acid were found after the steaming process. Drastic changes in the concentration of D-glucose, D-fructose, and sucrose were observed during the first 16 h, followed by steady value changes to 64 h of steaming using HPLC-ELSD. The pH values decreased from 6.28 to 5.61 during the 64-h steaming process. The production of DDMP, 5-HMF, butanedioic acid, and hydroxymaltol and the changes in amino acid, sugar, and pH values suggest that the Maillard reaction was involved in the steaming process of the root of PM, which may contribute to the activity differences between the root of PM and the processed root.


Physiological effects of exercise on stroke survivors.
This study investigated the physiological responses of stroke survivors to a 16-week program of moderate aerobic and anaerobic exercise. Forty participants who were a minimum of 6 months post stroke underwent physiological testing over the course of 2 days that included a maximal VO(2) stress test, a Biodex strength assessment, and a blood lipid panel. The participants were then randomly assigned to two groups, an aerobic training only (ATO) group and an aerobic and strength training (A&ST) group. Both groups were then required to exercise aerobically for 20 minutes for 3 days a week at a moderate intensity for 16 weeks. Only the A&ST group was required to do a series of eight strength-training activities as part of their exercise protocol. Once the 16-week protocol was completed, all tests were repeated. These results were compared to the pretest data. Statistically significant changes in VO(2max) were noted in the A&ST group, while positive but not significant changes were noted in the ATO group. Both groups saw significant increases in knee flexion but not in knee extension. The A&ST group showed significant increases in both shoulder flexion and extension, while the ATO group only had significant increases in shoulder extension. We concluded that aerobic exercise produced positive metabolic changes in both groups, but only the A&ST group had statistically significant changes. Both groups demonstrated significant changes in functional strength, but the A&ST group experienced larger increases, likely due to the strength component of their training protocol.


Femoral access site closure without prior femoral angiography : A retrospective analysis.
Although guideline recommendations have shifted towards a transradial route, femoral puncture is still an established vascular access, especially for complex coronary interventions. The FemoSeal™ vascular closure device (FVCD) helps to reduce femoral compression time and access site complications after removal of the catheter sheath. To ensure safe use, an angiography of the femoral artery prior to FVCD deployment is recommended by the manufacturer. We postulate that omitting this angiography does not relevantly increase the risk for vascular complications. In this retrospective analysis of an all-comers population (n = 1923) including patients receiving a percutaneous coronary intervention (PCI), we could show that combined vascular complication rates without femoral angiography were low (primary endpoint 4.6%) and comparable to a randomized clinical trial that did perform angiography of the vascular access site in a cohort of patients receiving diagnostic coronary angiography only. In addition to this analysis, we could demonstrate that patients with an acute coronary syndrome, receiving periprocedural anticoagulation or anti-platelet therapy had an increased risk for the formation of arterial pseudoaneurysms; however, we did not observe any ischemic vascular event after FVCD deployment. Closure of the femoral access site after coronary angiography using the FVCD can be safely performed without femoral angiography; however, due to an increased risk for the formation of pseudoaneurysms we recommend the transradial access in situations with increased bleeding risk.


Mechanically induced solid-state generation of phosphorus ylides and the solvent-free Wittig reaction.
We describe the nearly quantitative preparation of phosphorus ylides and the Wittig reaction occurring in the solid sate during high-energy mechanochemical processing. Initial insights into the details of the discovered chemical transformations indicate that high-energy mechanical processing supports the interaction of reacting centers by breaking crystallinity of the reactants and by providing mass transfer without a solvent.


Multifocal chorioretinitis with progressive subretinal fibrosis in a young child.
Progressive subretinal fibrosis with uveitis (PSFU) syndrome is a rare clinical entity presenting with multifocal granulomatous chorioretinitis and subsequently developing extensive subretinal fibrosis over weeks or months. Subretinal fibrosis affecting the macula may cause profound and permanent vision loss. We report the presentation and management of this condition in a child, to our knowledge, the youngest reported. The condition caused substantial visual loss and required high-dose systemic corticosteroid and immunosuppression with methotrexate and ciclosporin to control aggressive intraocular inflammation.


Isolation, Identification, and Immunomodulatory Mechanism of Peptides from Lepidium meyenii (Maca) Protein Hydrolysate.
Maca is a protein-enriched edible plant with immunomodulatory activity. However, the role of proteins in the immunomodulatory activity of maca is unclear. In this study, peptide products of maca proteins obtained through in vitro gastrointestinal digestion were isolated and purified, and the immunomodulatory activities of these peptides were assessed in macrophages (RAW 264.7 cells). The results show that the maca protein hydrolysate enhanced the phagocytic capacity and NO, TNF-α, and IL-6 secretion of RAW 264.7 cells. Forty-five peptides from known proteins of maca or the cruciferous family were identified by ultraperformance liquid chromatography-tandem mass spectrometry in the hydrolysate, and the peptide RNPFLP exhibited the strongest immunomodulatory activity. Antibody blocking, siRNA, pathway inhibitors, and western blot assays showed that RNPFLP-activated RAW 264.7 cells through the NF-κB and MAPK signaling pathways mediated by TLR2 and TLR4 receptors. An analysis of the structure-activity relationship showed that the N9-H60 active site in arginine plays an important role in the immunomodulatory activity of RNPFLP. This study provides a new understanding of the immunomodulatory activity of maca.


Original Research: Hydroxytyrosol, an ingredient of olive oil, reduces triglyceride accumulation and promotes lipolysis in human primary visceral adipocytes during differentiation.
Hydroxytyrosol has various pharmacological properties, including anti-oxidative stress and anti-inflammatory activities, preventing hyperglycemia, insulin resistance, and the metabolic syndrome. The present study is focused on the anti-adipogenic and lipolytic activity of hydroxytyrosol on primary human visceral adipocytes. Pre-adipocytes were analyzed after 10 (P10) and 20 (P20) days of treatment during differentiation and after 7 (A7) days of treatment when they reached mature shape. The treatment with hydroxytyrosol extract significantly (P < 0.001) increased apoptosis in P10 and P20 cells in comparison to control and A7 cells; significantly (P < 0.001) reduced triglyceride accumulation in P20 cells compared to P10 and control cells; and significantly (P < 0.001) increased lipolysis in P20 cells in comparison to control cells and A7 mature adipocytes. Hydroxytyrosol-treated P20 cells significantly (P < 0.05) increased expression of genes involved in inhibition of adipogenesis, such as GATA2, GATA3, WNT3A, SFRP5, HES1, and SIRT1. In contrast, genes involved in promoting adipogenesis such as LEP, FGF1, CCND1, and SREBF1 were significantly down-regulated by hydroxytyrosol treatment. These data suggest that hydroxytyrosol promotes lipolysis and apoptotic activity in primary human visceral pre-adipocytes during differentiation and does not affect already mature adipocytes.


Anchor balloon, buddy wire, and wire and sheath techniques to deploy percutaneous pulmonary valves in tetralogy of fallot patients.
Advances in surgical techniques in tetralogy of Fallot (TOF) patients have improved survival of these patients into adulthood. The procedure requires right ventricular outflow tract or trans-annular patch with resultant pulmonary stenosis and/or regurgitation. As such, adult patients seen with this condition may have increasing right ventricular hypertrophy and/or right ventricular dilation. Recently, the Sapien XT valve (Edwards Lifesciences, CA) was approved by the FDA for pulmonary implantation. In some cases, advancing the valve in right ventricular outflow tract is difficult. This is a case series of delivering Sapien XT valves in TOF patients with severe pulmonary regurgitation and/or stenosis, using the anchor balloon, buddy wire, and the novel, wire and sheath techniques. © 2017 Wiley Periodicals, Inc.


Managing external genital warts: practical aspects of treatment and prevention.
Rising rates of human papillomavirus (HPV) infections in recent decades, including external genital warts (EGWs), underscore the need for effective management of this common sexually transmitted disease. Although treatment is a vital aspect that aims primarily to resolve physical symptoms, health care providers must also address the psychosocial burden that typically accompanies diagnosis, treatment, remission, and recurrence. Education and counseling are integral components of care to address the cascade of negative emotional reactions that follow diagnosis, which often include anger, shame, stigma, frustration, and fear. Health care providers should offer patient information that is clear and simple, both verbally and in written form. Research to date has shown that information is most helpful when it is conveyed in a supportive tone and avoids stigmatization. Treatment decisions should consider the patient's preferences and the clinician's ability to offer certain therapies. A locally relevant algorithm and an individualized treatment approach are recommended by various treatment guidelines to improve the chances of compliance and treatment success. Given that success rates are variable, monitoring treatment is also necessary to gauge the patient's response to treatment, local reactions, and the potential need to switch treatments. Patients diagnosed with EGWs should also be screened for other sexually transmitted diseases because coinfection is common. Vaccination is becoming an increasingly important aspect of prevention strategies for HPV infections and should be considered for eligible patients.


Capturing Human Naïve Pluripotency in the Embryo and in the Dish.
Although human embryonic stem cells (hESCs) were first derived almost 20 years ago, it was only recently acknowledged that they share closer molecular and functional identity to postimplantation lineage-primed murine epiblast stem cells than to naïve preimplantation inner cell mass-derived mouse ESCs (mESCs). A myriad of transcriptional, epigenetic, biochemical, and metabolic attributes have now been described that distinguish naïve and primed pluripotent states in both rodents and humans. Conventional hESCs and human induced pluripotent stem cells (hiPSCs) appear to lack many of the defining hallmarks of naïve mESCs. These include important features of the naïve ground state murine epiblast, such as an open epigenetic architecture, reduced lineage-primed gene expression, and chimera and germline competence following injection into a recipient blastocyst-stage embryo. Several transgenic and chemical methods were recently reported that appear to revert conventional human PSCs to mESC-like ground states. However, it remains unclear if subtle deviations in global transcription, cell signaling dependencies, and extent of epigenetic/metabolic shifts in these various human naïve-reverted pluripotent states represent true functional differences or alternatively the existence of distinct human pluripotent states along a spectrum. In this study, we review the current understanding and developmental features of various human pluripotency-associated phenotypes and discuss potential biological mechanisms that may support stable maintenance of an authentic epiblast-like ground state of human pluripotency.


A ganglion causing the tarsal tunnel syndrome: report of a case.
The tarsal tunnel syndrome is a complex of symptoms affecting the foot produced by compression neuropathy of the posterior tibial nerve on the medial aspect of the ankle, within the fibrous osseous "tunnel" that has the posteromedial aspect of the tibia as its floor and the flexor retinaculum as its roof. Keck first drew attention to this entity in 1962, and was followed by Lam in the same year. Despite sporadic reports following these documentations, the clinical recognition of the syndrome is often delayed. It is still frequently misdiagnosed as acute foot strain or plantar fasciitis at its initial presentation (Kopell and Thompson, 1963; Lam, 1962, 1967). In this paper we report a case of tarsal tunnel syndrome caused by compression of the posterior tibial nerve by a ganglion at the ankle.


Introducing donor human milk to the NICU: lessons for Australia.
There is an increased use of pasteurised donor human milk (PDHM) in North American neonatal intensive care units (NICU) in order to achieve exclusive human milk (EHM) feeding for preterm infants. Australia, on the other hand, is relatively new to reintroducing PDHM to NICUs. Very little is known about the perception of multidisciplinary NICU teams toward PDHM. This article reports on a survey of 89 NICU clinicians that was implemented during the first weeks of PDHM use in an American NICU, and was repeated 6 months later. Their knowledge and opinions of PDHM in addition to their inclination to recommend its use were evaluated using thematic coding and descriptive statistics. We found that after a 6-month trial, preparedness to recommend PDHM increased to 93%. We found that NICU clinicians' support for PDHM exceeded their knowledge about its risks and benefits and clinicians requested education about various aspects of PDHM. This research in this article aims to assist clinical staff educators as they go about introducing PDHM in NICUs.


Alzheimer's Disease Diagnosis Using Landmark-Based Features From Longitudinal Structural MR Images.
Structural magnetic resonance imaging (MRI) has been proven to be an effective tool for Alzheimer's disease (AD) diagnosis. While conventional MRI-based AD diagnosis typically uses images acquired at a single time point, a longitudinal study is more sensitive in detecting early pathological changes of AD, making it more favorable for accurate diagnosis. In general, there are two challenges faced in MRI-based diagnosis. First, extracting features from structural MR images requires time-consuming nonlinear registration and tissue segmentation, whereas the longitudinal study with involvement of more scans further exacerbates the computational costs. Moreover, the inconsistent longitudinal scans (i.e., different scanning time points and also the total number of scans) hinder extraction of unified feature representations in longitudinal studies. In this paper, we propose a landmark-based feature extraction method for AD diagnosis using longitudinal structural MR images, which does not require nonlinear registration or tissue segmentation in the application stage and is also robust to inconsistencies among longitudinal scans. Specifically, first, the discriminative landmarks are automatically discovered from the whole brain using training images, and then efficiently localized using a fast landmark detection method for testing images, without the involvement of any nonlinear registration and tissue segmentation; and second, high-level statistical spatial features and contextual longitudinal features are further extracted based on those detected landmarks, which can characterize spatial structural abnormalities and longitudinal landmark variations. Using these spatial and longitudinal features, a linear support vector machine is finally adopted to distinguish AD subjects or mild cognitive impairment (MCI) subjects from healthy controls (HCs). Experimental results on the Alzheimer's Disease Neuroimaging Initiative database demonstrate the superior performance and efficiency of the proposed method, with classification accuracies of 88.30% for AD versus HC and 79.02% for MCI versus HC, respectively.


Demonstrating frequency-dependent transmission of sarcoptic mange in red foxes.
Understanding the relationship between disease transmission and host density is essential for predicting disease spread and control. Using long-term data on sarcoptic mange in a red fox Vulpes vulpes population, we tested long-held assumptions of density- and frequency-dependent direct disease transmission. We also assessed the role of indirect transmission. Contrary to assumptions typical of epidemiological models, mange dynamics are better explained by frequency-dependent disease transmission than by density-dependent transmission in this canid. We found no support for indirect transmission. We present the first estimates of R0 and age-specific transmission coefficients for mange in foxes. These parameters are important for managing this poorly understood but highly contagious and economically damaging disease.


Maternal age and reproductive function in female Sprague-Dawley rats.
We investigated the age-related changes in reproductive function in female rats of the Crl:CD(SD) strain. The estrous cycles were monitored from 6 to 42 weeks of age. Other females were mated with males at 6, 8, 10, 15, 19, 23, 27, 31, 35 and 40 weeks of age and caesarean section was performed on day 20 of gestation to examine their fetuses, and then reproductive parameters were calculated and fetal growth was observed. The percentage of rats exhibiting irregular estrous cycles increased from 23 weeks of age. The copulatory and fertility indices decreased from 35 and 27 weeks of age, respectively. Dams at 6 weeks of age showed low numbers of corpora lutea and implantation sites. Although the number of corpora lutea was not affected by advanced maternal age, number of implantation sites decreased from 27 weeks of age. The pre- and post-implantation loss rates increased from 23 and 31 weeks of age, respectively, and the number of live fetuses decreased from 27 weeks of age. Fetal growth retardation was observed in maternal rats older than 31 weeks of age. The external observations on the fetuses revealed umbilical hernia at 35 to 40 weeks of age. These data indicated that maternal aging affected reproductive function and fetal development from 23 and 31 weeks of age, respectively. It was considered that the appropriate age of Crl:CD(SD) female rats for the assessment of reproductive toxicity were 8 to 22 weeks.


Predisposing Conditions to Pediatric Hepatocellular Carcinoma and Association With Outcomes: Single-center Experience.
Hepatocellular carcinoma (HCC) has been linked to chronic viral or metabolic liver disease and other conditions. The characteristics of children with HCC have not been fully elucidated and outcomes in children with predisposing liver disease are not well defined. Patients ≤21 years old with HCC managed at our institution and through external consultation between 1996 and 2016 were included. Demographics, clinical history, and pathology were tabulated. Fisher exact test and Wilcoxon test were employed for subgroup comparison, and survival differences were evaluated by Kaplan-Meier method. Sixty-one cases of HCC were identified. Seven of 16 patients (44%) at our institution and 18 of 45 consult patients (40%) had a predisposing condition: cryptogenic cirrhosis/steatosis (9), genetic (7), biliary pathology (4), viral hepatitis (1), and other (4). Thirteen of 27 patients with de novo HCC had fibrolamellar HCC. Clinical characteristics were grouped by presence or absence of predisposing conditions: age at diagnosis (7.2 vs 10.2 years, P < 0.05), metastatic disease at presentation (15% vs 44%, P = n.s), and tumor size >4 cm (20% vs 100%, P < 0.05). In patients treated at our institution, 5 of 7 with predisposing conditions received liver transplant and achieved complete remission, whereas only 3 of 9 patients with de novo HCC received curative surgery and this group had decreased median overall survival (P < 0.05). The majority of children with HCC did not have predisposing liver or associated disease. These patients were diagnosed later with more advanced stage disease and had significantly decreased overall survival.


Regulation of Cell Polarity by Exocyst-Mediated Trafficking.
One requirement for establishing polarity within a cell is the asymmetric trafficking of intracellular vesicles to the plasma membrane. This tightly regulated process creates spatial and temporal differences in both plasma membrane composition and the membrane-associated proteome. Asymmetric membrane trafficking is also a critical mechanism to regulate cell differentiation, signaling, and physiology. Many eukaryotic cell types use the eight-protein exocyst complex to orchestrate polarized vesicle trafficking to certain membrane locales. Members of the exocyst were originally discovered in yeast while screening for proteins required for the delivery of secretory vesicles to the budding daughter cell. The same eight exocyst genes are conserved in mammals, in which the specifics of exocyst-mediated trafficking are highly cell-type-dependent. Some exocyst members bind to certain Rab GTPases on intracellular vesicles, whereas others localize to the plasma membrane at the site of exocytosis. Assembly of the exocyst holocomplex is responsible for tethering these vesicles to the plasma membrane before their soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated exocytosis. In this review, we will focus on the role and regulation of the exocyst complex in targeted vesicular trafficking as related to the establishment and maintenance of cellular polarity. We will contrast exocyst function in apicobasal epithelial polarity versus front-back mesenchymal polarity, and the dynamic regulation of exocyst-mediated trafficking during cell phenotype transitions.


[Report of experiences on the use of cyclosporin A].
In September 1985 in our kidney transplantation centre for the first time ciclosporin A was used. Up to now altogether 50 patients received this new form of immunosuppression. During the sand immune application no essential side effects occurred. The success of the change of the therapy was independent of the degree of the serum creatinine level at the time of conversion. In the period of observation we performed altogether 106 kidney transplantations. With 88% of grafts functioning normally at the discharge under application of ciclosporin A we achieved a clear improvement of the results of transplantation in comparison with the classical immunosuppression (53.6%) in the period of observation.


Linoleic-acid-induced growth suppression induces quiescent cancer cell nests in nude mice.
We examined the effect of linoleic acid (LA) on tumor formation. Cell growth was suppressed by LA in a dose-dependent manner in MKN28 and Colo320 cells. Continuous treatment with LA provided growth arrest in both cells at 5-7 weeks after the treatment. LA-pretreated MKN28 and Colo320 cells showed higher tumorigenicity (9/10 and 10/10, respectively) than nontreated cells (2/10 and 3/10, respectively; p < 0.01) in nude mice. In contrast, LA-pretreated MKN28 and Colo320 cells showed more suppressed tumor growth than nontreated cells (p < 0.01). LA-pretreated MKN28 and Colo320 cells with LA administration after the inoculation did not form macroscopic tumors. Histological examination revealed small cancer cell aggregations, which showed no proliferative activity. In LA-treated MKN28 and Colo320 cells, protein production of Bcl-2 was increased, whereas Bak, EGFR and VEGF levels were decreased. These findings suggest that LA might induce quiescence and subsequent dormancy in cancer cells.


Detection of DNA oligonucleotides with base mutations by terahertz spectroscopy and microstructures.
DNA oligonucleotides with a 5-base mutation at the 3'-terminus were investigated by terahertz (THz) spectroscopy in a marker-free manner. The four single-stranded oligonucleotides with 17nt have been detected with specificity on a microfluidic chip, and corroborated by spectral measurements with split-ring resonators. The number of hydrogen bonds formed between the oligonucleotide and its surrounding water molecules, deemed a key contribution to the THz absorption of biological solutions, was explored by molecular dynamics simulations to explain the experimental findings. Our work underlies the feasibility of THz spectroscopy combined with microstructures for marker-free detection of DNA, which may form the basis of a prospective diagnostic tool for studying genic mutation.