House-dust mites and summer cottages.
Estimated indoor climate conditions in unheated summer cottages offers house-dust mites unfavorable temperature and feeding conditions while giving them optimum humidity conditions. We aimed to estimate the exposure level of house-dust mites in summer cottages. A total of 37 summer cottages were sampled for house dust and storage mites in three locations and the results compared with samples from 33 patients suspected of house-dust mite allergy and living in ordinary houses. The processed dust samples were investigated by microscopy and exposure levels given as number of mites per 0.1 g dust. The summer cottages were without exception all heavily infested with threefold or higher concentrations of both house dust and storage mites in comparison with ordinary houses. In unheated summer cottages were found tropical high concentrations of house dust and storage mites with a median concentration of house-dust mites in mattress dust of 2000 house-dust mites/g of dust which corresponds to an average of 40 microg allergen/g of mattress dust. As a probable consequence of high indoor air humidity conditions in unheated summer cottages in winter, dust samples contained threefold or higher concentrations of house dust and storage mites. Indoor humidity conditions thus more than compensated for lack of continuous supply of skin scales from human beings and an unfavorable low indoor air temperature. The uniform high mite exposure in summer cottages is likely to imply disease deterioration in patients already allergic to mites.


Wireless Implantable Sensor for Noninvasive, Longitudinal Quantification of Axial Strain Across Rodent Long Bone Defects.
Bone development, maintenance, and regeneration are remarkably sensitive to mechanical cues. Consequently, mechanical stimulation has long been sought as a putative target to promote endogenous healing after fracture. Given the transient nature of bone repair, tissue-level mechanical cues evolve rapidly over time after injury and are challenging to measure noninvasively. The objective of this work was to develop and characterize an implantable strain sensor for noninvasive monitoring of axial strain across a rodent femoral defect during functional activity. Herein, we present the design, characterization, and in vivo demonstration of the device's capabilities for quantitatively interrogating physiological dynamic strains during bone regeneration. Ex vivo experimental characterization of the device showed that it possessed promising sensitivity, signal resolution, and electromechanical stability for in vivo applications. The digital telemetry minimized power consumption, enabling extended intermittent data collection. Devices were implanted in a rat 6 mm femoral segmental defect model, and after three days, data were acquired wirelessly during ambulation and synchronized to corresponding radiographic videos, validating the ability of the sensor to noninvasively measure strain in real-time. Together, these data indicate the sensor is a promising technology to quantify tissue mechanics in a specimen specific manner, facilitating more detailed investigations into the role of the mechanical environment in dynamic bone healing and remodeling processes.


CYP2J2*7 single nucleotide polymorphism in a Chinese population.
Human cytochrome P450 2J2 (CYP2J2) is the major arachidonic acid epoxygenase that plays important roles in the pathogenesis of a variety of diseases such as cardiovascular disorders and cancers, this P450 also plays a role in the metabolism of some antihistamine drugs. Variability of CYP2J2 gene is highly constrained except for at its proximal promoter a relatively common and functionally relevant single nucleotide polymorphism, namely CYP2J2*7, with allele frequency being 17%, 5.49%, 13%, and 4.23% in African, White, Asian, and Korean, respectively. Since this genetic variation differs strikingly between ethnic groups, we characterized the CYP2J2*7polymorphism in Chinese. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assays were used to genotype CYP2J2*7 in a sample of 384 healthy Chinese Han subjects. In this Chinese population, 20 (5.21%) heterozygotes and no homozygote for CYP2J2*7 allele were observed, and the allelic frequency was 2.60%. The CYP2J2*7 variant represents a relatively rare polymorphism in Chinese, with the allele frequency being comparable to that of Korean, but significantly lower than those of African and White groups. This data may be informative to design population-based association study of genetic predisposition to CYP2J2 related diseases and treatments.


Intolerance of ambiguity in students entering medical school.
Intolerance of ambiguity is the perception of ambiguous situations as a threat. Medical students with differing levels of intolerance of ambiguity may select medical specialties based upon the amount of ambiguity existing in the practice of each specialty. A cross-sectional survey at one state university administered Budner's Intolerance of Ambiguity Scale to all entering first-year medical students for four consecutive years (N = 609) to investigate patterns of intolerance of ambiguity in relationship with demographic variables and initial medical specialty preference. The medical students in this study were more intolerant of ambiguity than those first studied by Budner in 1962. Students entering in 1985 were slightly more intolerant of ambiguity than students in 1988. Students age 23 and older were less intolerant of ambiguity than students 18-22 years old. Men and students with natural/physical science undergraduate majors were more intolerant of ambiguity than their counterparts. However, medical specialty preference was not related to intolerance of ambiguity. Intolerance of ambiguity may be a personality trait or a learned characteristic, and needs further investigation.


Nutrition in Children With Chronic Kidney Disease: How to Thrive?
The nutritional status and management of children with chronic kidney disease (CKD) are complex and require a combined pediatric nephrology team work approach with physicians, nutritionists, nurses, and physical/occupational therapists. Prospective observational studies such as Children with CKD in the US, the 4C study in Europe and the International Pediatric Peritoneal Dialysis Network have advanced the field. However, most recommendations and guidelines from international task forces such as Kidney Diseases Improving Global Outcomes and Pediatric Renal Nutrition Taskforce are opinion-based rather than evidence-based. There is exciting ongoing research to improve nutrition in children with CKD to help them thrive.


Biomarkers for Alzheimer's Disease: Where Do We Stand and Where Are We Going?
Alzheimer's disease (AD) is an age-related neurodegenerative and progressive disorder representing the most common form of dementia in older adults [...].


Uveitis: advances in understanding of pathogenesis and treatment.
Uveitis is a leading cause of blindness affecting individuals of all ages, genders, and races. Uveitis may be due to autoimmune, infectious, toxic, malignant, or traumatic processes. Some evidence supports an association between conditions previously presumed to be autoimmune and viral infectious agents. For autoimmune uveitis, therapy is nonspecific, typically beginning with corticosteroids. For nonresponsive disease or for corticosteroid sparing, recent reports on mycophenolate mofetil, infliximab, and interferon therapy show success for various forms of uveitis. Treatment of the complications of uveitis, especially cystoid macular edema, is difficult. Vitamin E appears to offer little benefit, whereas octreotide may be effective. Recent collaborative efforts at standardization in the field should enhance studies on these conditions.


Effects of Age and Middle Ear on the Frequency Tuning of the cVEMP and oVEMP.
Upward shift in the air conducted (AC) frequency tuning of vestibular evoked myogenic potentials (VEMPs) as an effect of aging is hypothesized to be due to the microstructural stiffening changes in the inner ear. However, with an AC stimulus, it may be possible that the shift in the frequency tuning of VEMPs as an effect of aging may also be due to contributions from the middle ear. The main aim of this study was to examine the effects of age on the frequency tuning of the cervical VEMP (cVEMP) and ocular VEMP (oVEMP) and determine the role of middle ear transmission characteristics in shaping these effects. Standard group comparison. One-hundred seven participants divided in three groups: young adult, middle-age, and older adults with "normal" middle ear and negative history of neurological or vestibular complaints. Middle ear measures included static admittance and middle ear resonant frequency. cVEMP and oVEMPs were elicited with AC tone bursts at 500, 750, and 1,000 Hz. No significant effect of age was observed on any of the middle ear measures. There was a significant effect of age on the amplitude of the cVEMP, but this effect was frequency specific. The age-related reduction in cVEMP corrected amplitude was only observed when the eliciting stimulus was 500 or 750 Hz, with no significant effect observed with a 1,000 Hz stimulus. For the oVEMP, the effects of age were apparent at all stimulus frequencies. We also observed a general upward shift in the frequency tuning of both the cVEMP and oVEMP for middle-age and older adults, with 750 and 1,000 Hz yielding higher response rates and larger amplitudes among middle-aged and older adults. Measurements of middle ear did not significantly contribute to the observed findings. The upward shift in frequency tuning of VEMPs among middle age and older adults could be due to the changes in the vestibular system and not from the middle ear. These results support the use of different frequency stimuli (i.e., 750 or 1,000 Hz) to elicit a VEMP if a response is absent using a 500 Hz stimulus, especially in patients over the age of 40.


Metal ion effects on the cis/trans isomerization equilibrium of proline in short-chain peptides: a solution NMR study.
The effect of copper(II) ions on the probabilities of existence of the four detectable conformers of the tetrapeptide Tyr-Pro-Phe-Pro (beta-casomorphin 4) in [2H6]DMSO was investigated by 1H NMR spectroscopy. Integration of the Phe-NH signals provided the relative populations in the free state as tt/tc/ct/cc=28:34:29:9 at 293 K (c=cis, t=trans). Copper(II) was shown to bind to all four isomers, yielding complexes with two different structures, depending on the conformation of Pro(2). The interpretation of paramagnetic relaxation rates of Pro(2)-Halpha signals provided the corresponding isomeric probabilities in the metal-bound state as 13:36:20:31. The observed stabilization of the conformation with the lowest probability of existence (cc) may be relevant for the biological role of copper and other metal ions.


The potential of phage display virions expressing malignant tumor specific antigen MAGE-A1 epitope in murine model.
The tumor specific antigen epitope melanoma antigen A1(161--169) (MAGE-A1(161--169)) was displayed on the major protein (p VIII) of the filamentous bacteriophage (fd). The immune responses of the phage display particles expressing MAGE-A1(161--169) in mice were studied. Using phage display particles as vaccine was effective in affording protection from tumor growth, inducing growth control of established tumors and prolonging survival of tumor-bearing mice. The hybrid phage particles elicited MAGE-A1(161--169) specific CTL responses, NK activity and DTH. Our results showed that the phage display particles might be a new vaccine candidate for tumor-associated antigen epitope in cancer immunotherapy.


β-(1,4)-Galactan remodelling in Arabidopsis cell walls affects the xyloglucan structure during elongation.
Galactan turnover occurs during cell elongation and affects the cell wall xyloglucan structure which is involved in the interaction between cellulose and xyloglucan. β-(1,4)-Galactan is one of the main side chains of rhamnogalacturonan I. Although the specific function of this polymer has not been completely established, it has been related to different developmental processes. To study β-(1,4)-galactan function, we have generated transgenic Arabidopsis plants overproducing chickpea βI-Gal β-galactosidase under the 35S CaMV promoter (35S::βI-Gal) to reduce galactan side chains in muro. Likewise, an Arabidopsis double loss-of-function mutant for BGAL1 and BGAL3 Arabidopsis β-galactosidases (bgal1/bgal3) has been obtained to increase galactan levels. The characterization of these plants has confirmed the role of β-(1,4)-galactan in cell growth, and demonstrated that the turnover of this pectic side chain occurs during cell elongation, at least in Arabidopsis etiolated hypocotyls and floral stem internodes. The results indicate that BGAL1 and BGAL3 β-galactosidases act in a coordinate way during cell elongation. In addition, this work indicates that galactan plays a role in the maintenance of the cell wall architecture during this process. Our results point to an involvement of the β-(1,4)-galactan in the xyloglucan structure and the interaction between cellulose and xyloglucan.


Messenger RNA profile analysis deciphers new Esrrb responsive genes in prostate cancer cells.
Orphan nuclear receptor estrogen related receptor β (Esrrb or ERRβ) is well known in stem cells and early embryonic development. However, little is known about its function in cancer. We investigated the mRNA profile alterations induced by Esrrb expression and its synthetic ligand DY131 in human prostate cancer DU145 cells via RNA-Seq analysis. We distinguished 67 mRNAs differentially expressed by Esrrb alone. Although DY131 alone did not change any gene, treatment of DY131 in the presence of Esrrb altered 1161 mRNAs. These observations indicated Esrrb had both ligand-independent and ligand-dependent activity. When Esrrb was expressed, DY131 treatment further regulated 15 Esrrb-altered mRNAs. DY131 acted as an antagonist for 11 of 15 mRNAs (wdr52, f13a1, pxdn, spns2, loc100506599, tagln, loc441454, tkel1, sema3f, zcwpw2, sdc2) and as an agonist for 4 of the 15 mRNAs (rarres3, oasl, padi2, ddx60). Gene ontology analyses showed altered genes are related to transcription and translation regulation, cell proliferation and apoptosis regulation, and cellular metabolism. Our results characterized mRNA profiles in DU145 prostate cancer cells driven by Esrrb expression and Esrrb ligand DY131, and provided multiple markers to characterize Esrrb's function in Esrrb research.


Compression of a pressurized spherical shell by a spherical or flat probe.
Measuring the mechanical properties of cells and tissues often involves indentation with a sphere or compression between two plates. Different theoretical approaches have been developed to retrieve material parameters (e.g., elastic modulus) or state variables (e.g., pressure) from such experiments. Here, we extend previous theoretical work on indentation of a spherical pressurized shell by a point force to cover indentation by a spherical probe or a plate. We provide formulae that enable the modulus or pressure to be deduced from experimental results with realistic contact geometries, giving different results that are applicable depending on pressure level. We expect our results to be broadly useful when investigating biomechanics or mechanobiology of cells and tissues.


Pd-catalyzed and CsF-promoted reaction of bromoalkynes with isocyanides: regioselective synthesis of substituted 5-iminopyrrolones.
The palladium-catalyzed and CsF-promoted annulation reaction of bromoalkynes and isocyanides regioselectively affords a diverse set of 5-iminopyrrolone derivatives. This chemistry presumably proceeds through the bromoacrylamide intermediates, which can be readily prepared from the nucleophilic addition reaction of isocyanides to bromoalkynes in the presence of CsF.


Histamine in the posterodorsal medial amygdala modulates cardiovascular reflex responses in awake rats.
Centrally injected histamine (HA) affects heart rate (HR), arterial blood pressure (BP), and sympathetic activity in rats. The posterodorsal medial amygdala (MePD) has high levels of histidine decarboxylase, connections with brain areas involved with the modulation of cardiovascular responses, and is relevant for the pathogenesis of hypertension. However, there is no report demonstrating the role of the MePD histaminergic activity on the cardiovascular function in awake rats. The aims of the present work were: 1) to study the effects of two doses (10-100 nM) of HA microinjected in the MePD on basal cardiovascular recordings and on baroreflex- and chemoreflex-mediated responses; 2) to reveal whether cardiovascular reflex responses could be affected by MePD microinjections of (R)-alpha-methylhistamine (AH3), an agonist of the inhibitory autoreceptor H3; and, 3) to carry out a power spectral analysis to evaluate the contribution of the sympathetic and parasympathetic components in the variability of the HR and BP recordings. When compared with the control group (microinjected with saline, 0.3 microl), HA (10 nM) promoted an increase in the MAP50, i.e. the mean value of BP at half of the HR range evoked by the baroreflex response. Histamine (100 nM) did not affect the baroreflex activity, but significantly decreased the parasympathetic component of the HR variability, increased the sympathetic/parasympathetic balance at basal conditions (these two latter evaluated by the power spectral analysis), and promoted an impairment in the chemoreflex bradycardic response. Microinjection of AH3 (10 microM) led to mixed results, which resembled the effects of both doses of HA employed here. Present data suggest that cardiovascular changes induced by baroreceptors and chemoreceptors involve the histaminergic activity in the MePD. This neural regulation of reflex cardiovascular responses can have important implications for homeostatic and allostatic conditions and possibly for the behavioral displays modulated by the rat MePD.


Risk of fracture amongst patients with Parkinson's disease and other forms of parkinsonism.
Postural instability, a core feature of parkinsonism, leads to an increased risk of falls and fractures. However, the risk of fracture has not been assessed in an incident cohort of Parkinson's disease and atypical parkinsonism. We determined the absolute and relative fracture risk and predictive variables in a prospective incident cohort of parkinsonian patients and controls. Fracture data for 326 incident parkinsonian cases (198 Parkinson's disease, 128 atypical parkinsonism) and 261 controls was recorded annually in the Parkinsonism Incidence in North-East Scotland study. Incidence rates were determined for all fractures and major fractures. Kaplan-Meier curves were used to determine time to first fracture for each group. Stepwise, multivariate Cox regression analysis was used to identify risk factors for fracture in parkinsonian patients. Mean age at recruitment was 74.5 years in all parkinsonian patients (age at diagnosis) and 75 years in controls. The incidence of any fracture was 5.5 (95% CI 4.3-7.0) and 2.0 (1.3-2.9)/100 participant-years for the parkinsonian and control groups respectively, whilst for major fractures due to falls it was 4.2 (3.2-5.5) and 1.4 (0.9-2.2)/100 participant-years respectively. Independent predictors for fractures in parkinsonian patients were osteoporosis, female gender and falling during the follow up period. There was no difference in fracture rates between those with Parkinson's disease and atypical parkinsonism. The fracture rate in parkinsonism from the time of diagnosis (about 5% per year) is over three times greater than controls. Fracture risk should be routinely assessed in all parkinsonian patients.


Supine-to-standing transcranial Doppler test in patients with multiple system atrophy.
Supine-to-standing test, a transcranial Doppler (TCD) based technique, has been recently developed to evaluate cardiovascular dysautonomia. We explored the value of supine-to-standing TCD test in predicting the course of multiple system atrophy (MSA) with orthostatic hypotension (OH). By monitoring the signals of middle cerebral artery during supine-to-standing posture changes, the trend curves of cerebral blood flow velocities, pulsatility index and resistance index were obtained from 38 MSA patients with OH and 31 healthy subjects. The correlation between TCD findings and the clinical outcome of the patients, which was determined by follow-up structured phone interview, was analyzed. Adverse outcome was defined if a patient died, was in bed-ridden state or had recurrent syncope (>1 per month). Two characteristic TCD findings were revealed in the MSA patients but not in the controls, i.e. a blunted cerebral blood flow velocity rebound after standing and/or sustained higher pulsatility index upon standing than supine baseline. Structured phone interview was completed in 31 of the 38 patients (mean follow-up time, 20 ± 11 months). While no subject had recurrent syncope before enrollment, 12 patients developed an adverse outcome during follow-up. The coexistence of two characteristic TCD findings predicted adverse outcomes with positive predictive value 66.7% and negative predictive value 87.5%. Supine-to-standing TCD test is valuable in predicting the course of MSA with OH at early stage. We hypothesize baroreflex failure effects and paradoxical cerebral vasoconstriction in response to OH may account for the TCD findings in MSA patients.


The drunken driver: a psychosocial study.
A self-administered questionnaire was used to compare selected psychosocial variables of 306 convicted male drunk drivers with those of 294 alcoholics and 253 controls. The drunk driver group fell between the other groups on many parameters but resembled the alcoholic group on many others. While over 68% of the drunk drivers appeared to be alcoholics, in general they showed significantly less psychosocial incapacity than the alcoholic comparison group. The differences between the alcoholic and presumed non-alcoholic drunk drivers were not sufficient to clearly dichotomize the drunk driver group.


Growth phase-dependent proteins of the Ehrlich ascites tumor analyzed by one- and two-dimensional electrophoresis.
The decrease of the growth rate of the Ehrlich ascites tumor is correlated with changes in the de novo synthesis and abundance of several proteins as is shown by electrophoretic methods. The synthesis of a number of these growth-dependent proteins can be induced in vitro by incubation of the tumor cells in the presence of serum.


Role of progestogens for the prevention of premature birth.
Premature birth represents a major cause of perinatal morbidity and mortality. The short- and long-term sequelae of prematurity have serious consequences for newborn survival and health in later life. In addition, prematurity is a major problem with regard to health expenditure. Despite major progress in obstetrics, perinatology and neonatology, the percentage of premature birth persists and there is even a tendency towards a slight increase. Therefore, besides screening programmes for the detection of vaginal infections, additional therapeutic opportunities must be sought. According to previously published data, vaginal progesterone and intramuscular 17alpha-hydroxyprogesterone caproate should be considered possible treatment options for the prevention of preterm delivery.


Fluorine-containing 6,7-dialkoxybiaryl-based inhibitors for phosphodiesterase 10 A: synthesis and in vitro evaluation of inhibitory potency, selectivity, and metabolism.
Based on the potent phosphodiesterase 10 A (PDE10A) inhibitor PQ-10, we synthesized 32 derivatives to determine relationships between their molecular structure and binding properties. Their roles as potential positron emission tomography (PET) ligands were evaluated, as well as their inhibitory potency toward PDE10A and other PDEs, and their metabolic stability was determined in vitro. According to our findings, halo-alkyl substituents at position 2 of the quinazoline moiety and/or halo-alkyloxy substituents at positions 6 or 7 affect not only the compounds' affinity, but also their selectivity toward PDE10A. As a result of substituting the methoxy group for a monofluoroethoxy or difluoroethoxy group at position 6 of the quinazoline ring, the selectivity for PDE10A over PDE3A increased. The same result was obtained by 6,7-difluoride substitution on the quinoxaline moiety. Finally, fluorinated compounds (R)-7-(fluoromethoxy)-6-methoxy-4-(3-(quinoxaline-2-yloxy)pyrrolidine-1-yl)quinazoline (16 a), 19 a-d, (R)-tert-butyl-3-(6-fluoroquinoxalin-2-yloxy)pyrrolidine-1-carboxylate (29), and 35 (IC50 PDE10A 11-65 nM) showed the highest inhibitory potential. Further, fluoroethoxy substitution at position 7 of the quinazoline ring improved metabolic stability over that of the lead structure PQ-10.


Health education provided by nurses to children and young people: parents' assessment.
Healthy literacy is a determinant key children/teenager's health and health outcomes. The aim of this study to identify the parents' assessment about Health Education practice to children and teenagers. We opted for a descriptive, quantitative and cross-sectional research, with a non-probabilistic convenience sample. The inclusion criteria were: being a parent who uses attending children health appointments in primary health care; being a parent who has a child hospitalized and is accompanying him/her in the pediatric hospital inpatient ward. A questionnaire survey was built with three sections: sample characterization, Health Education practices performed by nurses (5 questions) and a scale that measured Health Education Assessment Scale (HEAS), which contained 48 items and was validated. It was applied from September to December 2018. The survey was filled in by 113 parents. The results showed that 100% (n = 113) of the parents feel comfortable to talk with nurses about children/teenagers health; 79.6% (n = 90) consider that nurses have time availability for the doubts clarification; 61.9% (n = 70) point out that nurses identify child/teenager needs; Healthy eating" (60.2%; n = 68), the "National Vaccination Plan" (53.1%; n = 60) and "Harmful behaviors prevention" (46.9%; n = 53) are the most important topics; 56.6% (n = 64) of the parents, when in doubt, turn first to the pediatrician, and 66.4% (n = 75) considered that this practice was equal important, compared with other nursing interventions. This study shows that Health Education provided by nurses is based on the need's identification, with a perspective of involvement and participation, promoting health and conscious changes which reinforces the nurses' position as health educators.


Regional distribution of a high-affinity enkephalin-degrading peptidase ('enkephalinase') and effects of lesions suggest localization in the vicinity of opiate receptors in brain.
The distribution of a high affinity enkephalin-dipeptidylcarboxypeptidase between regions of mouse brain is markedly heterogenous and parallels that of opiate receptors. Furthermore intrastriatal administration of kainic acid as well as interruption of the nigrostriatal dopaminergic pathway by 6-hydroxydopamine (6-OHDA) lead to similar decreases in this peptidase activity and in the number of opiate receptors. On the contrary, no correlation was found between low affinity enkephalin degrading enzymes and opiate receptors.


Differential staining of western blots of avian egg white glycoproteins using diverse lectins.
Avian egg white glycoproteins which differ in structure and carbohydrate composition, vary in their interactions with diverse lectins. Generally, wheat germ agglutinin (WGA) and concanavalin A (Con A) are used for the identification and separation of those of the chicken. In the present study, interactions of a battery of lectins, including: the above two, several galactophilic lectins (from Aplysia gonad (AGL), Erythrina corallodendron (ECorL), peanut (PNA) and Pseudomonas aeruginosa (PA-IL)), and fucose-binding lectins (from Ulex europaeus (UEA-I), Ulva lactuca (ULL) and P. aeruginosa (PA-IlL), which also binds mannose) with chicken, quail and pigeon egg white glycoproteins, were examined using both hemagglutination inhibition and Western blot analyses. The chicken egg white glycoproteins interacted most strongly with WGA, followed by Con A >> AGL = PA-IlL. The quail glycoprotein order of affinities was: Con A >> WGA = AGL = PA-IlL, while that of the pigeon was: AGL > PA-IL > WGA > Con A = PA-IlL. The blocking of the other lectins by the egg whites were insignificant. The results demonstrated the selectivity and efficiency of the five most reactive lectins for differential tagging of avian egg white glycoproteins and unveiled the profound heterogeneity of the latter, as well as the possible potential lectin usage for improving purification and quality control of the desired glycoproteins.


Rhinomanometry in the selection for adenoidectomy and its relation to preoperative radiology.
Recent work has shown that resolution of otitis media with effusion (OME) following adenoidectomy may be related to certain preoperative radiographic parameters. This study was performed to investigate the relationship between the total nasal resistance (TNR), adenoid volume and the radiographic palatal airway and adenoid depth in children with OME. Fifty-six children underwent anterior active rhinomanometry and 40 completed the investigation. There was a significant association between the Palatal Airway and the TNR, and in the 27 who subsequently underwent adenoidectomy this was nearly so with respect to adenoid volume and TNR. The relationship demonstrated was not strong enough for TNR to be of use in selection of children for adenoidectomy based on radiographic parameters. Rhinomanometry can be difficult and time-consuming to perform in children. In its present form it is unlikely to be of routine clinical use in this context.


Biomedical knowledge graph learning for drug repurposing by extending guilt-by-association to multiple layers.
Computational drug repurposing aims to identify new indications for existing drugs by utilizing high-throughput data, often in the form of biomedical knowledge graphs. However, learning on biomedical knowledge graphs can be challenging due to the dominance of genes and a small number of drug and disease entities, resulting in less effective representations. To overcome this challenge, we propose a "semantic multi-layer guilt-by-association" approach that leverages the principle of guilt-by-association - "similar genes share similar functions", at the drug-gene-disease level. Using this approach, our model DREAMwalk: Drug Repurposing through Exploring Associations using Multi-layer random walk uses our semantic information-guided random walk to generate drug and disease-populated node sequences, allowing for effective mapping of both drugs and diseases in a unified embedding space. Compared to state-of-the-art link prediction models, our approach improves drug-disease association prediction accuracy by up to 16.8%. Moreover, exploration of the embedding space reveals a well-aligned harmony between biological and semantic contexts. We demonstrate the effectiveness of our approach through repurposing case studies for breast carcinoma and Alzheimer's disease, highlighting the potential of multi-layer guilt-by-association perspective for drug repurposing on biomedical knowledge graphs.


Stimulation of neuronal cells by culture supernatant of T lymphocytes triggered by anti-CD3 mAb followed by propagation in the presence of interleukin-2.
Performance status (PS) frequently improves occurs in cancer patients who have been infused with their own lymphokine-activated killer T cells (LAK-T). In the present study, a culture supernatant of LAK-T (LAK-T sup) administered to 8-week-old rats caused neurogenesis as evidenced by increased 5-ethynyl-2'-deoxyuridine staining of brain tissues. Intravenous injection of granulocyte-macrophage colony stimulating factor (GM-CSF), a major cytokine in LAK-T sup, had a similar effect. Furthermore, LAK-T sup induced Ca(++) increase in rat hippocampal brain slices that was detected in neuronal cells by emission of Fluo-8 NW at 520 nm. The same effect was observed with an rGM-CSF solution. GM-CSF may activate neuronal cells by stimulating the glial cells that surround and attach to them. If so, GM-CSF and LAK-T sup may improve the motor neurons of patients with amyotrophic lateral sclerosis. The neurogenerative effect of GM-CSF in LAK-T sup may also help improve brain function in aged adults including those with dementia such as Alzheimer's disease.


SMARCA4-Deficient Thoracic Sarcomatoid Tumors Represent Primarily Smoking-Related Undifferentiated Carcinomas Rather Than Primary Thoracic Sarcomas.
Highly aggressive thoracic neoplasms characterized by SMARCA4 (BRG1) deficiency and undifferentiated round cell or rhabdoid morphology have been recently described and proposed to represent thoracic sarcomas. However, it remains unclear whether such tumors may instead represent sarcomatoid carcinomas, and how their clinicopathologic characteristics compare with those of nonsarcomatoid SMARCA4-deficient non-small cell lung carcinomas (SD-NSCC). We identified 22 SMARCA4-deficient thoracic sarcomatoid tumors (SD-TSTs) with round cell and/or rhabdoid morphology and 45 SD-NSCCs, and comprehensively analyzed their clinicopathologic, immunohistochemical, and genomic characteristics using 341-468 gene next-generation sequencing and other molecular platforms. The relationship of SD-TSTs with NSCC was supported by (1) the presence of NSCC components juxtaposed with sarcomatoid areas in five cases, (2) focal expression of NSCC lineage markers TTF1 or p40 in four additional cases, (3) smoking history in all except one patient (mean = 51 pack-years), accompanied by genomic smoking signature, and (4) high tumor mutation burden (mean = 14.2 mutations per megabase) and mutations characteristic of NSCC in a subset. Compared with SD-NSCCs, SD-TSTs exhibited considerably larger primary tumor size (p < 0.0001), worse survival (p = 0.004), and more frequent presentation at younger age (30-50 years) despite heavier smoking history. Distinctive pathologic features of SD-TSTs included consistent lack of adhesion molecule claudin-4, SMARCA2 (BRM) codeficiency, and frequent expression of stem cell markers. SD-TSTs represent primarily smoking-associated undifferentiated/de-differentiated carcinomas rather than primary thoracic sarcomas. Despite their histogenetic relationship with NSCC, these tumors have unique clinicopathologic characteristics, supporting their recognition as a distinct entity. Further studies are warranted to determine therapeutic approaches to this novel class of exceptionally aggressive thoracic tumors.


Consensual pupillary light reflex in the pigmented rat.
We measured the pupillary light reflex (PLR) in 5 pigmented, Long Evans rats (under urethan sedation) in three conditions: direct stimulation, consensual stimulation, and a control condition designed to measure the effects of stray light. The average constriction (maximal amplitude) produced by a ganzfeld stimulus delivering 1.6 log quanta absorbed per rod per sec for a duration of 3 sec was measured to be 0.78 +/- 0.07 mm for the direct PLR, 0.67 +/- 0.06 mm for the consensual PLR, and 0.07 +/- 0.029 mm for the control condition. We corrected the consensual measurement for each rat by subtracting the value of the control (stray-light induced) constriction. A comparison of the corrected consensual constriction to the direct constriction showed that, on average, the consensual constriction attained an amplitude of 78% of the direct constriction. Our findings contradict claims that the consensual pupillary light reflex is absent in rodents. Although our results are in agreement with findings showing bilateral projections of the retina to the pretectum (which subserves the pupillary light reflex) in the rat, the consensual-to-direct ratio we report is higher than might be expected from anatomical estimates of the overall proportion of uncrossed to crossed optic fibers in the rat.


Temporal spectrum of beam wander for Gaussian Shell-model beams propagating in atmospheric turbulence with finite outer scale.
The temporal spectrum of beam wander is formulated by considering a Gaussian Schell-model beam passing through atmospheric turbulence with a finite outer scale. Two simpler asymptotic formulas for the temporal spectrum of beam wander within the high- and low-frequency ranges are derived, respectively. Based on the formulations, the effects of the initial partial coherence of the beam, finite outer scale of turbulence, initial beam radius, and initial phase front radius of curvature on the temporal spectrum of beam wander are analyzed by numerical examples.


Synovial Fluid Biomarkers for the Diagnosis of Periprosthetic Joint Infection-A Systematic Review and Meta-Analysis of Their Diagnostic Accuracy According to Different Definitions.
Different synovial fluid biomarkers have emerged to improve periprosthetic joint infection (PJI) diagnosis. The goals of this paper were (i) to assess their diagnostic accuracy and (ii) to evaluate their performance according to different PJI definitions. A systematic review and meta-analysis was performed using studies that reported diagnostic accuracy of synovial fluid biomarkers using validated PJI definitions published from 2010 to March 2022. A database search was performed through PubMed, Ovid MEDLINE, Central, and Embase. The search identified 43 different biomarkers with four being the more commonly studied, with 75 papers overall: alpha-defensin; leukocyte esterase; synovial fluid C-reactive protein; and calprotectin. Overall accuracy was higher for calprotectin, followed by alpha-defensin, leukocyte esterase, and synovial fluid C-reactive protein with sensitivities of 78 to 92% and specificities of 90 to 95%. Their diagnostic performance was different according to which definition was adopted as the reference. Specificity was consistently high across definitions for all four biomarkers. Sensitivity varied the most with lower values for the more sensitive European Bone and Joint Infection Society or Infectious Diseases Society of America definitions with higher values for the Musculoskeletal Infection Society definition. The International Consensus Meeting 2018 definition showed intermediate values. All evaluated biomarkers had good specificity and sensitivity, making their use acceptable in the diagnosis of PJI. Biomarkers perform differently according to the selected PJI definitions.


Spontaneous idiopathic intratesticular hemorrhage as a differential diagnosis for acute scrotal pain.
Spontaneous idiopathic testicular hemorrhage is an extremely rare entity with few published reports in the literature. We report a case of a 15-year-old boy who had been experiencing intense, left scrotal pain for the previous twelve hours. No previous history of trauma or bleeding disorders. The left testis was enlarged and tender. Left orchiectomy was performed. The entire testis was dusty and dark grossly. Microscopic sections show diffuse intratesticular bleeding with intact seminiferous tubules and spermatogenesis. Spontaneous idiopathic testicular hemorrhage should be considered when evaluating patients with acute scrotal pain. Clinical and ultrasonographic findings and histopathologic evaluation are mandatory to diagnose it.


Conserved T-cell receptor beta chain CDR3 sequences in IgA nephropathy biopsies.
We have previously reported that both alpha beta and gamma delta T cells are involved in the progression of IgA nephropathy (IgAN) to renal failure. To determine whether the T-cells seen in the interstitium represent a generalized inflammatory response or whether they are proliferating oligoclonally in response to a particular antigen, we analyzed the TCR Vbeta gene usage by T cells infiltrating renal biopsies from patients with IgAN. Fourteen IgAN patients were divided by clinical criteria into stable and progressive groups (7 in each group). Reverse transcription-polymerase chain reaction (RT-PCR) and cloning were used to characterize the expression of TCR Vbeta families in renal biopsies and in peripheral blood lymphocytes. TCR Vbeta8 was significantly and preferentially expressed in most IgAN kidney biopsies compared with peripheral blood lymphocytes from both IgAN patients and healthy controls (P < 0.001). TCR Vbeta8 expression was more marked in progressive biopsies than in stable biopsies (P < 0.05). Spectratyping of Vbeta8 RT-PCR products from T cells infiltrating the kidney showed an intense spectratype band at the shortest range of amplified CDR3s in the renal biopsies of four patients. Analysis of nucleotide and deduced amino acid sequences of Vbeta8 PCR products derived from intense spectratype bands from these renal biopsies revealed a high concordance across the CDR3 region. A conserved amino acid (leucine) at the first position of the nongermline-encoded nucleotides and diversity (ND) junction of Vbeta8 was found at a frequency of 95% in multiple sequences obtained from the renal biopsies of all four patients examined. The preferential use of Vbeta8 with marked similarities in the CDR3 region by some renal infiltrating T cells suggests clonal expansion of T cells in the kidneys of some IgAN patients. Conserved amino acids in the TCR CDR3 hypervariable region may contribute to the recognition of a particular antigen or set of antigens.


Maternal and neonatal outcomes in women with preeclampsia.
Preeclampsia is a pregnancy-specific hypertensive syndrome associated with significant morbidity and mortality in mother and neonate. We compared neonatal and maternal complications in preeclamptic women with healthy pregnant women. All 125 consecutive women with preeclampsia at Bandarabbas Shariati Hospital were assessed between July 2005 and July 2006. Parity, type of delivery, common causes of cesarean section, gestational age, birth weight, and neonatal complications and mortality were included as study variables and compared with the control group. Cesarean section rates were significantly higher in the group with preeclampsia than in the control group (p < 0.05). The mean parity was higher in the normotensive group than in the preeclamptic patients (2.3 +/- 0.65 vs. 3.6 +/- 0.74; p < 0.05). In the preeclamptic women undergoing vaginal delivery, 31% of them underwent induction of labor. The most common indication for induction of labor was severity of preeclampsia (77.8%). Birth weight was statistically significantly lower in women with preeclampsia (p < 0.0001). Among the patients, 5.6% of them were admitted with intrauterine fetal demise, while 111 neonates survived for the remaining patients. The most common causes of neonatal mortality were congenital abnormalities and respiratory distress syndrome. Gestational age, parity, cesarean section rate, the rate of induced labor, and low birth weight neonates were more frequent in preeclamptic women than in healthy pregnant women.


Irradiation-induced motor disorder of the oesophagus.
This case report describes the late development of an achalasia-like disturbance of oesophageal motility following irradiation to the neck for a pharyngeal lymphosarcoma. The radiological, manometric and endoscopic findings are recorded as well as laboratory investigations showing evidence of complete vagal denervation.


Salivary microbial profiles associate with responsiveness to warning oral sensations and dietary intakes.
Oral microbiota-host interactions are gaining recognition as potential factors contributing to interindividual variations in taste perception. However, whether such possible links imply specific bacterial co-occurrence networks remains unknown. To address this issue, we used 16 s rRNA gene sequencing to profile the salivary microbiota of 100 healthy individuals (52 % women; 18-30 y/o), who provided hedonic and psychophysical responses to 5 liquid and 5 solid commercially-available foods, each chosen to elicit a target sensation (sweet, sour, bitter, salty, pungent). The same cohort also completed several psychometric measures and a 4-day food diary. Unsupervised data-driven clustering of genus-level Aitchison distances supported the existence of two salivary microbial profiles (CL-1, CL-2). While CL-1 (n = 57; 49.1 % women) exhibited higher α-diversity metrics and was enriched in microbial genera assigned to the class Clostridia (e.g., Lachnospiraceae_[G-3]), CL-2 (n = 43; 55.8 % women) harbored greater amounts of taxa with potential cariogenic effects (e.g., genus Lactobacillus) and significantly lower abundances of inferred MetaCyc pathways related to the metabolic fate of acetate. Intriguingly, CL-2 showed enhanced responsiveness to warning oral sensations (bitter, sour, astringent) and a higher propensity to crave sweet foods or engage in prosocial behaviors. Further, the same cluster reported habitually consuming more simple carbohydrates and fewer beneficial nutrients (vegetable proteins, monounsaturated fatty acids). In summary, while the mediating role of participants' baseline diet on findings can not be definitively excluded, this work provides evidence suggesting that microbe-microbe and microbe-taste interactions may exert an influence on dietary habits and motivates further research to uncover a potential "core" taste-related salivary microbiota.


Assessment of heavy metal impact on sediment quality of the Xiaoqinghe estuary in the coastal Laizhou Bay, Bohai Sea: inconsistency between two commonly used criteria.
Surface sediments in the Xiaoqinghe estuary, southwestern coastal Laizhou Bay, were examined to assess the bio-toxic risk of heavy metals (Cd, Cu, Ni, Pb and Zn) with the effects range-low and effects range-median guidelines (ERL-ERMs) and the concentration ratio of simultaneously extractable metals to acid volatile sulfides ([SEM]/[AVS]). Based on the ERL-ERM guidelines, bio-toxic effect caused by Cu, Ni, Pb and Zn could be expected in the riverine surface sediments of the Xiaoqinghe estuary; and the surface sediments in the marine area were in good quality and only Ni might cause bio-toxic effect occasionally. The AVS-SEM guidelines revealed that no bio-toxic effect could be caused by any of the studied metals in both the riverine and marine sediments, since there were excess sulfides in surface sediments which could form water-insoluble substances with free metal ions and reduce the bioavailability of heavy metals.


Students' perceptions on shadowing during COVID-19 and an exploration of innovative solutions for clinical exposure.
The objective of this project was to evaluate the perceptions of predental students' shadowing experiences during a pandemic and further, explore innovative solutions that can be implemented to ensure that shadowing opportunities are equitable and accessible. Data was collected via the Web 2.0 social media platform, Instagram (owned by Meta Platforms, Inc.) from 122 participants attending college in North America and are on the predental track: freshman (N = 11), sophomores (N = 25), juniors (N = 30), seniors (N = 34) and recent college graduates (N = 22). Participants completed a survey consisting of 20 questions. Results showed that the pandemic disrupted traditional shadowing methods; students turned to various virtual platforms, such as YouTube and Zoom, to obtain shadowing experiences. There was an increase in the number of students who shadowed virtually during the pandemic versus pre-COVID-19. The majority of the respondents (80%) agreed that dental schools have not provided sufficient guidance on how to approach shadowing during a pandemic. Innovative shadowing platforms should be implemented in order to help college students explore careers within dentistry and beyond. The development of a standardized virtual shadowing program with clear guidelines can increase equity and accessibility.


Fossil Shell Flour in Livestock Production: A Review.
Fossil shell flour (FSF), also known as Diatomaceous earth, or diatomite, consists of amorphous silicates with important physical and chemical characteristics, including porosity and permeability, low density and thermal conductivity, tiny particle size, high surface area, solubility, hydrophobia, and absorption capabilities, which are molecular filter actors, substituting their integral cations without physical changes. The substance is nontoxic, cheap, and readily available in large quantity in many countries. Recently, FSF has been modified as additives for several uses. Recent studies have supported its use as animal growth promoter, vaccine adjuvant in livestock, water purifier, mycotoxin binder, inert dust applications in stored-pest management, pesticide, animal feed additive, as a natural source of silicon in livestock and as natural anthelmintic. Numerous advantages of FSF include its low-cost and availability, its nontoxic characteristics, and the fact that food grade diatomaceous earth is safe for human consumption. In this paper, we review the main uses of FSF in the livestock industry, with reference to similar works earlier published that elucidate their important roles.


Non-Hodgkin's lymphoma in a woman with adult-onset Still's disease: a case report.
Adult onset Still's disease is a chronic multisystemic inflammatory disorder characterized by high spiking fever, polyarthralgia and rash. Lymphadenopathy is a prominent feature of adult onset Still's disease and is seen in about 65% of patients. Searching the medical literature using the MEDLINE database from January 1966 through November 2007 we could only find two reported cases of adult onset Still's disease that had progressed to lymphoma. We describe a woman who was diagnosed with adult onset Still's disease and developed lymphoma 10 months after the onset of her symptoms. She initially presented with fever and arthritis of the knees, ankles and shoulders, along with a nonpruritic skin rash, myalgia and weight loss. On physical examination she was found to have several enlarged anterior cervical lymph nodes and left posterior auricular lymph nodes all of which were non-tender, immobile and rubbery. Excisional biopsy of the cervical lymph nodes was negative for malignancy. Bone marrow biopsy was also negative for malignancy. She was treated with prednisone. She remained in good health until she presented 10 months later with low back pain, dyspnea and weight loss. Work up revealed malignant lymphoma. She was treated with chemotherapy and was doing well until she presented with abdominal pain. Work up revealed a cirrhotic liver and ascites. She then passed away from hepatorenal syndrome 13 years after the diagnosis of lymphoma. To our knowledge, this is the third reported case of such an occurrence. Although the association between adult onset Still's disease and lymphoma has been rarely reported, careful screening for this malignancy in patients suspected to have adult onset Still's disease is warranted.


Highly Efficient Multiphoton Absorption of Zinc-AIEgen Metal-Organic Frameworks.
A series of luminescent frameworks was synthesized from the selective combination of aggregation induced emission (AIE)-linker tetra-(4-carboxylphenyl)ethylene (H4 TCPE) and Zn2+ . Complex 1 was formed by the close packing of Zn-TCPE hinge, and isostructural complexes 2-5 were constructed by the linkage of Zn-TCPE layer and pillar ligands. These complexes exhibit highly efficient multiphoton excited photoluminescence (MEPL) and concomitant third-harmonic generation (THG). The multiphoton absorption (MPA) parameters of 1 are superior to other multiphoton emission materials including the perovskite nanocrystals. The incorporation of pillar linkers slows down the charge transfer between layers of Zn-TCPE, and the aromatic core of pillar linkers has a great influence on the MPA performance of the corresponding frameworks.


The impact of the COVID-19 pandemic on child protective services caseworkers and administrators.
The COVID-19 pandemic has impacted children and young people experiencing child abuse and neglect. Child Protective Services (CPS) has played an important role in supporting children and families during the COVID-19 pandemic. Few studies to-date have evaluated the impact of the pandemic on CPS caseworkers and administrators in the United States. We conducted interviews to explore CPS caseworkers' and administrators' experiences working and serving families during the pandemic. Participants were U.S.-based CPS caseworkers and administrators. We conducted semi-structured virtual interviews with participants and used an inductive thematic analysis approach. We conducted 37 interviews. Participants discussed how the COVID-19 pandemic has changed the way they conduct investigations and provide services to families in the CPS system. Several services were adapted to occur virtually, providing challenges and unique opportunities. Participants also described the personal barriers they faced during the pandemic, including working remotely, experiencing burnout, and challenges obtaining personal protective equipment. Finally, participants shared creative solutions they engaged in to support children and families during the COVID-19 pandemic, including expanding collaborations with other community-based organizations. This study suggests the important role that CPS has played during the pandemic and challenges individual CPS workers felt, in terms of both experiencing burnout and difficulty obtaining personalized protective equipment. Inclusion of the CPS system in emergency preparedness planning for future pandemics or natural disasters will ensure continuation of these vital services.


Radical hysterectomy: a critical review of twenty-two years' experience.
One hundred seventy-eight patients who had radical hysterectomy performed for management of invasive carcinoma of the cervix over 22 year period at the Medical University of South Carolina were critically analyzed. The degree of differentiation of the malignancy appeared to be of more significance than tumor size in Stage 1 lesions. With proper patient selection and excellent operative technique, survival rates well over 90% with minimal complications can be obtained. The radical hysterectomy should never be used in association with irradiation.


Intervention mechanism of self-degradation of ready-to-eat sea cucumber by adding green tea extract and gallic acid.
Gallic acid (GA) and green tea extract (GT) could retard the self-degradation of ready-to-eat sea cucumber (RSC). The physical and chemical properties of RSC were changed after cross-linking. Cross-linkers could retard the conversion of α-helix like structure to random coil. Besides, the peptides of cross-linked RSC were easily broken at the sites of G, E, A, L, S, H, Y, V and I after stored for 30 d. The self-degradation rate of RSC before and after cross-linking was determined by synthetic typical peptides. After cross-linked by GA, the relative peak heights of NQ, NL and GLQ increased by 20.59%, 11.14% and 31.49%, indicating that GA could effectively retard the degradation of the peptides during storage. Moreover, hydrogen bond was confirmed as the main force to maintain the stability of RSC body wall before and after cross-linking.


Cataract surgery in neovascular AMD: impact on visual acuity and disease activity.
Cataract and neovascular age-related macular degeneration (nAMD) often co-exist and both contribute to impaired vision. It has been debated whether cataract surgery can increase nAMD activity. The purpose of this retrospective study was to investigate the impact of cataract surgery on visual acuity, treatment intensity for nAMD and macular morphology in patients with on-going treatment for nAMD. Data was obtained from the Swedish Macular Register, the Swedish National Cataract Register, optical coherence tomography (OCT) images and patient charts. All eyes were treated at the Department of Ophthalmology at the County Hospital of Västmanland, Västerås, Sweden. Follow-up was 6 months after surgery. The study was approved by the Swedish Ethical Review Authority. In total, 156 patients (168 eyes) were included. The mean age at cataract surgery was 82 (standard deviation, SD 6) years. Both distance and near visual acuity improved after surgery. Distance visual acuity increased from 59 (SD 12) to 66 (SD 15) letters ETDRS (P < 0.001). Proportion of eyes with normal near visual acuity increased from 12 to 41%. The anti-vascular endothelial growth factor (VEGF) treatment intensity remained unchanged: mean of 3.4 (SD 1.9) and 3.3 (SD 1.7) treatments were given 6 months pre- and postoperatively, respectively. The prevalence of intraretinal fluid (IRF) in the macula increased from 22 to 31% postoperatively, while subretinal fluid, fluid under the pigment epithelium (sub-RPE fluid) and central retinal thickness were unaltered. In eyes with new IRF, improvement in visual acuity and number of anti-VEGF treatments were similar to eyes without new IRF. Cataract surgery improved visual acuity in patients with on-going treatment for nAMD and did not affect anti-VEGF treatment intensity. Macular morphology remained unchanged. The slight increase in intraretinal fluid after surgery was not found to affect visual acuity or anti-VEGF treatment intensity. It is hypothesized that this might indicate that it represents degenerative intraretinal cystic fluid.


The effect of methadone treatment on the quantity and quality of human fetal movement.
To evaluate the effect of daily maternal methadone maintenance treatment on the quality and quantity of fetal movement. At 34-37 weeks gestation, real-time ultrasound recordings were obtained from 17 methadone treated and 17 non-opioid-dependent mothers at two time points relative to the methadone mothers' daily dose of methadone. The first observation was just prior to the mother taking her daily dose (Time A) and the second was 1-h postdose (Time B). The incidence and pattern of fetal breathing movements (FBMs), fetal trunk movements (FTMs) and total fetal activity (TFA) were obtained from these ultrasounds. A time by group effect was found for measures of FBM and TFA, Fs(1,32)=6.06 and 4.94, P<0.05. At Time A and Time B for these measures t-tests showed no difference in the incidence of FBM (47.9% vs. 55.4%) and TFA (56% vs. 64%) at Time A between the methadone and comparison groups; however, at Time B the incidence of FBM (16.6% vs. 53.5%) and TFA (27% vs. 65%) was decreased for the methadone group. In addition, there was a between-group difference for two qualitative measures of fetal breathing. A slower rate of fetal breathing (40.3 vs. 47.2 breaths/min) and fewer FBMs per breathing episode (51.7 vs. 92.4) were found for the methadone group regardless of time since the mothers' daily dose. Taken together these results suggest that daily maternal methadone maintenance treatment altered both quantitative and qualitative measures of fetal activity that have been found to be related to normal fetal development.


The use of novel Therakos™ Cellex® for extracorporeal photopheresis in treatment of graft-versus-host disease in paediatric patients.
Extracorporeal photopheresis (ECP) is an established second line treatment option for graft-versus-host disease (GVHD) post-haematopoietic progenitor cell transplant. At our centre, the Therakos™ Cellex(®) has replaced the Therakos™ UVAR-XTS™ machine for ECP since 2009. We reviewed the records of 385 procedures using the Therakos™ Cellex(®) for safety and tolerability. Nine patients underwent ECP for GVHD. The median age was 13·5 years (range 3·7-24) and weight was 49·2 kg (range 18·5-86·3). The mean duration per procedure was 106 min (range 60-205). Fifteen (3·9%) procedures were cancelled and 10 (2·6%) were delayed, with central venous line (CVL) issues being the most frequent problem. With the use of prophylactic tissue plasminogen activator, fewer CVL-related occlusions were observed (4·7% vs. 2·3%). There was one episode of a CVL-associated thrombosis and one episode of delayed bleeding. There were four episodes of viral reactivation, four CVL-associated infections (1142 catheter days) and one episode of systemic inflammatory response syndrome. No patient experienced symptomatic hypotension. This is the first report outlining the safety and tolerability of the Therakos™ Cellex(®) device for ECP in children and young adults.


Optimal strategy of systemic treatment for unresectable pancreatic neuroendocrine tumors based upon opinion of Japanese experts.
A number of therapeutic agents have been reported to be clinically useful for the management of the patients with unresectable pancreatic neuroendocrine tumors (PanNETs) including somatostatin analogues, molecular-targeted agents and cytotoxic agents. However, the optimal strategy for selection among those treatment modalities above in these patients has remained unexplored. Japanese experts for PanNET discussed and determined the optimal treatment strategies according to the results of previously reported studies. The tumor volume of liver metastases and the Ki-67 labeling index were unanimously accepted as indicators of the tumor burden and tumor aggressiveness, respectively, which are two most clinically pivotal factors for determining the strategy of systemic treatment for unresectable PanNETs. In addition, for those with a relatively small tumor burden and slow disease progression, somatostatin analogues were selected as the first-line treatment agents. For those with a relatively large tumor burden and rapid tumor progression, cytotoxic agents were selected, possibly aiming at tumor shrinkage. For those of intermediate tumor volume and/or growth rate, molecular-targeted agents were selected as the first choice. Based on this strategy discussed among the experts, we tentatively prepared a MAP for proposing optimal treatment strategy and examined its validity in some patients with unresectable PanNETs. Results validated the usefulness of this MAP proposed for patients harbouring unresectable PanNETs. We herein propose a tentative MAP for optimal treatment selection for the patients harbouring unresectable PanNETs. Further large scale studies are, however, warranted to validate the usefulness of this MAP proposed in this study.


Combination of plasma tumor necrosis factor receptors signaling proteins, beta-amyloid and apolipoprotein E for the detection of Alzheimer's disease.
Activation of inflammatory processes has been observed within the brain as well as periphery of subjects with Alzheimer's disease (AD). Among several putative neuroinflammatory mechanisms, the tumor necrosis factor-α (TNF-α) signaling system plays a central role. TNF-α converting enzyme (TACE) does not only cleave pro-TNF-α but also TNF receptors, however, whether the TACE activity and soluble TNF receptors (sTNFRs) were changed in the plasma were not clear. The aim of this study was to determine whether the levels of TACE activity and sTNFRs are sufficiently altered in the plasma of AD patients to be helpful in AD diagnosis. We examined TACE levels in the plasma of 153 patients with AD, 98 patients with amnestic mild cognitive impairment (aMCI), 53 patients with vascular dementia (VaD), and 120 age-matched healthy control subjects, and found TACE activity and sTNFRs were significantly higher in patients with AD and aMCI compared with control subjects (TACE: P<0.001, P<0.01; sTNFR1: P<0.001, P<0.001; sTNFR2: P<0.001, P<0.01, respectively). The TACE activity and sTNFRs levels in VaD patients were significantly higher than the levels observed in AD patients (TACE activity: P<0.001, sTNFR1: P<0.01, sTNFR2: P<0.01). In the plasma of AD patients, the levels of both TACE activity and sTNFRs positively correlated with the levels of Aβ40 and negatively correlated with the ratio of Aβ42/Aβ40. AD patients with at least one copy of the ApoEε4 allele showed higher TACE activity and sTNFR plasma levels compared with patients without the ApoEε4 allele. We then combined the data on plasma TACE activity, sTNFRs, and Aβ with the presence of the APOEε4 allele and found that this biomarker panel exhibited a high sensitivity and specificity for discriminating AD patients from non-demented control subjects and VaD patients.


Applying leadership skills in conflict management. Synopsis of the AAP program presentation at the 49th annual assembly of the American Academy of Physical Medicine and Rehabilitation, Orlando, Florida, October 1987.
This brief paper has reviewed a few of the basic concepts related to the understanding of leadership styles. The unavoidable nature of conflict in organizations has been described. One of the best ways a person can make conflict more manageable is to become increasingly aware of his or her own fundamental leadership style as well as that of others. Without such an effort, people run the risk of moving apart rather than toward a closer working relationship. Regardless of whether an organization is a rehabilitation team, a university faculty or any other group in society, improvements in organizational functioning cannot be made without an awareness of conditions that create conflict.


Behavioral Health Integration in a Medicaid Accountable Care Organization: Management Lessons from a Health Center.
Behavioral health integration, including as used in Medicaid Accountable Care Organizations, can improve care and decrease costs. Our model strives to integrate fully its medical, behavioral health, and substance use disorder services into one primary care clinic. Merged management has decreased wait times, improved billing, and enabled several promising innovations.


Prey processing in the Siamese fighting fish (Betta splendens).
We studied prey processing in the Siamese fighting fish (Betta splendens), involving slow, easily observed head-bobbing movements, which were compared with prey processing in other aquatic feeding vertebrates. We hypothesized that head-bobbing is a unique prey-processing behaviour, which alternatively could be structurally and functionally analogous with raking in basal teleosts, or with pharyngognathy in neoteleosts. Modulation of head-bobbing was elicited by prey with different motility and toughness. Head-bobbing involved sustained mouth occlusion and pronounced cranial elevation, similar to raking. However, the hyoid and pectoral girdle were protracted, and not retracted as in both raking and pharyngognathy. High-speed videofluoroscopy of hyoid movements confirmed that head-bobbing differs from other known aquatic prey-processing behaviours. Nevertheless, head-bobbing and other prey-processing behaviours converge on a recurrent functional theme in the trophic ecology of aquatic feeding vertebrates; the use of intraoral and oropharyngeal dentition surfaces to immobilize, reduce and process relatively large, tough or motile prey. Prey processing outside the pharyngeal region has not been described for neoteleosts previously, but morphological evidence suggests that relatives of Betta might use similar processing behaviours. Thus, our results suggest that pharyngognathy did not out-compete ancestral prey-processing mechanisms completely during the evolution of neoteleosts.


Energetics and kinetics of cooperative cofilin-actin filament interactions.
We have evaluated the thermodynamic parameters associated with cooperative cofilin binding to actin filaments, accounting for contributions of ion-linked equilibria, and determined the kinetic basis of cooperative cofilin binding. Ions weaken non-contiguous (isolated, non-cooperative) cofilin binding to an actin filament without affecting cooperative filament interactions. Non-contiguous cofilin binding is coupled to the dissociation of approximately 1.7 thermodynamically bound counterions. Counterion dissociation contributes approximately 40% of the total cofilin binding free energy (in the presence of 50 mM KCl). The non-contiguous and cooperative binding free energies are driven entirely by large, positive entropy changes, consistent with a cofilin-mediated increase in actin filament structural dynamics. The rate constant for cofilin binding to an isolated site on an actin filament is slow and likely to be limited by filament breathing. Cooperative cofilin binding arises from an approximately tenfold more rapid association rate constant and an approximately twofold slower dissociation rate constant. The more rapid association rate constant is presumably a consequence of cofilin-dependent changes in the average orientation of subdomain 2, subunit angular disorder and filament twist, which increase the accessibility of a neighboring cofilin-binding site on an actin filament. Cooperative association is more rapid than binding to an isolated site, but still slow for a second-order reaction, suggesting that cooperative binding is limited also by binding site accessibility. We suggest that the dissociation of actin-associated ions weakens intersubunit interactions in the actin filament lattice that enhance cofilin-binding site accessibility, favor cooperative binding and promote filament severing.


The development of novel and selective p56lck tyrosine kinase inhibitors.
Early T-cell receptor mediated signal transduction involves the activation of several tyrosine protein kinases. One of these tyrosine kinases, p56lck, is expressed primarily in T-cells and Natural Killer (NK) cells and has been shown to be critical for their proliferative and effector functions. Indandiones have been identified as a potent and selective chemical class that inhibits p56lck.


Physiological and biochemical roles of ascorbic acid on mitigation of abiotic stresses in plants.
Under conditions of abiotic stress several physiological and biochemical processes in plants can be modified. The production of reactive oxygen species (ROS) is toxic at high concentrations and promotes RNA, DNA and plant cell membrane degradation. Plants have enzymatic and non-enzymatic adaptation mechanisms to act against ROS detoxification. Ascorbic acid (AsA) is the non-enzymatic compound essential for several biological functions, which acts in the elimination and balance of ROS production and with the potential to promote several physiological functions in plants, such as the photosynthetic process. For plant development, AsA plays an important role in cell division, osmotic adjustment, hormone biosynthesis, and as an enzymatic cofactor. In this review, the redox reactions, biosynthetic pathways, and the physiological and biochemical functions of AsA against abiotic stress in plants are discussed. The concentration of AsA in plants can vary between species and depend on the biosynthetic pathways d-mannose/l-galactose, d-galacturonate, euglenids, and d-glucuronate. Although the endogenous levels of AsA in plants are used in large amounts in cell metabolism, the exogenous application of AsA further increases these endogenous levels to promote the antioxidant system and ameliorate the effects produced by abiotic stress. Foliar application of AsA promotes antioxidant metabolism in plants subjected to climate change conditions, also allowing the production of foods with higher nutritional quality and food safety, given the fact that AsA is biologically essential in the human diet.


Fatal measles encephalopathy with retinopathy during cytotoxic chemotherapy.
A 14-year-old boy receiving post-operative cytotoxic chemotherapy for a testicular rhabdomyosarcoma developed a fatal encephalopathy associated with retinal changes 2 months after an episode of acute measles. Post-mortem histological examination showed intranuclear inclusion bodies in the neurons and glial cells, but inflammatory cell infiltrations were absent. Electron-microscopic and immunofluorescent studies revealed intracellular masses of paramyxovirus nucleocapsid-like structures, which had the morphological and antigenic properties of measles virus. Recent reports have emphasized the possibility of occurrence of a similar encephalopathy in treated childhood leukemia. It is evident, however, that this potentially fatal complication must be borne in mind when measles is contracted during any form of cytotoxic treatment or immunosuppression. Retinal changes may be of value for the diagnosis during life. We propose the designation "measles encephalopathy during immunosuppression" (MEI) for this condition.


Effects of vasectomy and antisperm antibodies on human seminal fluid deoxyribonucleic acid polymerase activity.
DNA-synthesizing complexes possessing a sucrose buoyant density of 1.24 to 1.25 gm/ml were identified in cell-free human seminal fluids prior to and 1 to 3 months following division of the vasa deferentia, performed for fertility control in otherwise normal males. After vasectomy, there was a 3.5-fold decrease in endogenous DNA polymerase activity per ejaculate. Partial purification of the seminal fluid DNA polymerase by gel filtration revealed a similar 3.5-fold decrease in dT12--18-poly (rA)-templated DNA polymerase activity postvasectomy. Immunoglobulin G, isolated from a rabbit immunized with nuclei derived from detergent-treated ejaculated human spermatozoa, inhibited both sperm- and seminal fluid-derived DNA polymerase activity. The decrease in seminal fluid enzyme activity following vasectomy might be due to its inhibition by sperm autoantibodies induced after vas division.


Tamm-Horsfall protein: unusual, large perinephric deposits.
A case in which unusually large deposits of Tamm-Horsfall protein were identified in perinephric adipose tissue is presented. The deposition around the kidney in this case was most likely due to calyceal rupture, secondary to distal ureteric obstruction. The peculiar gross and microscopic appearance of these deposits, their intense staining with the periodic acid--Schiff technique, and their association microscopically with epithelial fragments raised the possibility of infiltration by mucin-producing adenocarcinoma. The localization of Tamm-Horsfall protein in the deposits by the immunoperoxidase technique helped to confirm their true nature.


Dry reforming of methane to syngas: a potential alternative process for value added chemicals-a techno-economic perspective.
During the past decade, there has been increasing global concern over the rise of anthropogenic CO2 emission into the Earth's atmosphere (J Air Waste Manage Assoc 53:645-715, 2003). The utilization of CO2 to produce any valuable product is need of the hour. The production of syngas from CO2 and CH4 seems to be one of the promising alternatives in terms of industrial utilization, as it offers several advantages: (a) mitigation of CO2, (b) transformation of natural gas and CO2 into valuable syngas, and (c) producing syngas with H2/CO ratio 1 which may further be used for the production of valuable petrochemicals (J Air Waste Manage Assoc 53:645-715, 2003). A conceptual design for the production of synthesis gas by dry reforming of methane is presented here. An economic assessment of this process with an integrated methanol production section as a case was conceptualized and compared with the conventional steam methane reforming route to produce methanol. The economic study indicated that dry reforming of natural gas/methane is a competitive process with lower operating and capital costs in comparison with steam reforming assuming negligible cost of CO2 import.


Efficacy of perineural versus intravenous dexamethasone in prolonging the duration of analgesia when administered with peripheral nerve blocks: a systematic review and meta-analysis.
Perineural dexamethasone has been regarded as a promising adjunct for prolonging the duration of nerve blocks. However, it is uncertain whether its effects are due to local effects on the nerves or from systemic absorption. This systematic review aimed to compare the duration of postoperative analgesia associated with perineural versus intravenous dexamethasone as an adjunct to peripheral nerve blocks. A total of 2,216 relevant academic articles were identified after a comprehensive search of PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from 1967 until 2020. All randomized controlled trials that compared perineural and intravenous dexamethasone as adjuncts to peripheral nerve limb blocks were included. Fifteen randomized controlled trials (1,467 cases; 738 perineural dexamethasone, 729 intravenous dexamethasone) were eligible. The primary outcome (duration of analgesia) was significantly longer in the perineural than in the intravenous dexamethasone group (mean difference [MD]: 2.72 h, 95% CI [1.42, 4.01], P < 0.001). Perineural dexamethasone was also found to prolong the sensory block (MD: 3.45 h, 95% CI [1.36, 5.54], P = 0.001) and lower 24 h postoperative pain scores (MD: -0.74 h, 95% CI [-1.40, -0.07], P = 0.03). This review confirms the greater efficacy of perineural compared to intravenous dexamethasone in prolonging the analgesic duration of peripheral nerve blocks. However, the extent of prolongation was small and may not represent a clinically meaningful difference.


Comparison of two methods for the detection of hepatitis A virus in clam samples (Tapes spp.) by reverse transcription-nested PCR.
The detection of hepatitis A virus in shellfish by reverse transcription-nested polymerase chain reaction (RT-nested PCR) is hampered mainly by low levels of virus contamination and PCR inhibitors in shellfish. In this study, we focused on getting a rapid and sensitive processing procedure for the detection of HAV by RT-nested PCR in clam samples (Tapes spp.). Two previously developed processing methods for virus concentration in shellfish have been improved upon and compared. The first method involves acid adsorption, elution, polyethylene glycol (PEG) precipitation, chloroform extraction and PEG precipitation. The second method is based on elution with a glycine buffer at pH 10, chloroform extraction and concentration by ultracentrifugation. Final clam concentrates were processed by RNA extraction or immunomagnetic capture of viruses (IMC) before the RT-nested PCR reaction. Both methods of sample processing combined with the RNA extraction from the concentrates were very efficient when they were assayed in seeded and naturally contaminated samples. The results show that the first method was more effective in removal inhibitors and the second was simpler and faster. The IMC of HAV from clam concentrates processed by method 1 was revealed to be a very effective method of simultaneously removing residual PCR inhibitors and of concentrating the virus.


Fluorescence resonance energy transfer (FRET) spatiotemporal mapping of atypical P38 reveals an endosomal and cytosolic spatial bias.
Mitogen-activated protein kinase (MAPK) p38 is a central regulator of intracellular signaling, driving physiological and pathological pathways. With over 150 downstream targets, it is predicted that spatial positioning and the availability of cofactors and substrates determines kinase signaling specificity. The subcellular localization of p38 is highly dynamic to facilitate the selective activation of spatially restricted substrates. However, the spatial dynamics of atypical p38 inflammatory signaling are understudied. We utilized subcellular targeted fluorescence resonance energy transfer (FRET) p38 activity biosensors to map the spatial profile of kinase activity. Through comparative analysis of plasma membrane, cytosolic, nuclear, and endosomal compartments, we confirm a characteristic profile of nuclear bias for mitogen-activated kinase kinase 3/6 (MKK3/6) dependent p38 activation. Conversely, atypical p38 activation via thrombin-mediated protease-activated receptor 1 (PAR1) activity led to enhanced p38 activity at the endosome and cytosol, limiting nuclear p38 activity, a profile conserved for prostaglandin E2 activation of p38. Conversely, perturbation of receptor endocytosis led to spatiotemporal switching of thrombin signaling, reducing endosomal and cytosolic p38 activity and increasing nuclear activity. The data presented reveal the spatiotemporal dynamics of p38 activity and provide critical insight into how atypical p38 signaling drives differential signaling responses through spatial sequestration of kinase activity.


Avoidance of the use of vomerine mucosa in primary surgical management of velopalatine clefts.
A brief review of normal maxillary growth and the dysfunctional pathoanatomy of velopalatine clefts is presented. A plan of management for patients with these deformities is proposed; this is based on the degree to which the deformity departs from normal. The authors stress the importance of early, complete reconstitution of the soft palate and avoidance of the use of vomer flaps in the closure of the hard palate. The influence of the vomer, nasal septum, and labionasal musculature on postnatal facial development is discussed.


Multiple cutaneous plexiform schwannomas as initial presentation of neurofibromatosis 2 in a 9-year-old.
Neurofibromatosis 2 (NF2) is an autosomal-dominant disease caused by genetic mutations of the NF2 gene on chromosome 22. Patients are often diagnosed according to the presence of bilateral vestibular schwannomas and other tumors in the brain and spinal cord. In children, NF2 can present early with ocular findings and cutaneous tumors. We report here a 9-year-old girl who presented with multiple pigmented, slightly tender plaques on her scalp, face, and back that were revealed by histopathology to be plexiform schwannomas. We suspected NF2 and sent the patient's blood for genetic testing, which confirmed our diagnosis.


Management and outcomes of patients for non-functioning pancreatic neuroendocrine tumours: a multi-institutional analysis.
To analysed the short- and long-term outcomes of patients who underwent surgical resection for non-functioning pancreatic neuroendocrine tumours (NF-PNETs) to gain insights into treatment approaches for this rare and heterogeneous entity. All patients who underwent surgical resection for NF-PNETs at The Second Affiliated Hospital of Guangzhou Medical University, and West China Hospital, Sichuan University, from 2009 to 2019 were retrospectively reviewed. The data of patients was including perioperative management, pathologic analysis and follow-up. A total of 119 cases with histologically or cytologically confirmed NF-PNETs, The mean age of the patients was 52, and 56.3% were female. Twenty-three patients received post-operative adjuvant therapy, and five of nine (55.6%) patients with distant metastasis showed recurrence 14(60.9%) G2/G3 patients without distant metastasis received post-operative therapy with octreotide. Of these 14 patients, 3 (21.4%) revealed recurrence. Univariate analysis indicated that symptoms (P = 0.03), tumour size >4 cm (P = 0.029), ENETS stages III-IV (P < 0.001), positive lymph nodes (P < 0.001), vascular/perineural invasion (P < 0.001), and pathology grade G2 were associated with significantly higher risks of recurrence; age, gender, surgery type, and tumour location were not. Multivariate analysis revealed that positive lymph nodes (P < 0.001), vascular/peripheral invasion (P < 0.001), and pathology grade G3 (P = 0.03) are significant prognostic factors of tumour recurrence. Positive lymph nodes, vascular/peripheral invasion and pathology grade G3 were related to recurrence of NF-PNETs. Lymph node resection is recommend when FNA biopsy indicates pathology grade G3 for patients with NF-PNETs.


[Effects of antithrombin-III on cytokines in rats with multiple organ dysfunction syndrome].
To observe the effect of the antithrombin-III (AT-III) on cytokine levels in multiple organ dysfunction syndrome (MODS) in rats. Seventy Wistar rats were randomly divided into three groups: normal control group, MODS group, and AT-III treatment group. The rats in MODS group and the treatment group were given lipopolysaccharide (LPS) two times to replicate systemic inflammatory response syndrome (SIRS)/MODS model. One hour after the injections of LPS, the rats in the treatment group were given AT-III (25 U/kg, 0.5 ml/100 g) intravenously. Four hours after treatment, blood samples were collected in rats. The tissue samples were collected and preserved in formalin. By use of radioimmunoassay and histopathology, the effect of the AT-III was observed in rats with SIRS/MODS. Endotoxin (ET), interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels were all increased significantly in MODS animals (all P<0.01), and they were decreased after AT-III treatment (all P<0.01), though still higher than those of the normal controls (all P<0.01). The pathologic changes in lung, kidney and liver in the treatment group were milder than in the MODS group. These data suggest that AT-III could inhibit systemic inflammatory response and it might be used in the treatment of SIRS/MODS.


Colorectal Cancer Screening in the Elderly: Is Age Just a Number?
Colorectal cancer screening improved outcomes for patients diagnosed between the age of 45-75. Present life expectancy is beyond this limit, yet there are no guidelines for these ages. We aim to identify outcomes after screening and intervention in patients ≥75 years and correlate with frailty. Records between 2011 and 2019 were queried. Patients ≥75 screened and treated for colorectal cancer were included. Patient demographics, perioperative mortality, age at last colonoscopy and frailty score were calculated. A Modified Frailty Index from the Canadian Study of Health and Aging Frailty Index was used. A score of 1 to 11 was calculated based on patient comorbidities. The MFI was assigned from 0 to 11: 0 signified absence of frailty and 11 indicated maximum frailty. Of 179 patients were identified, 46.3% males. 171(95%) had elective and 8 (5%) had emergent surgery. The average age was 81.8 years. All colonoscopies were performed for symptoms. A modified frailty index was retrospectively calculated; 75% of patients scored between 0 and 2 and 1% scored >6. Older patients who underwent colonoscopy and surgery for symptomatic colon cancer had a low mortality, 2%. The average age was 6.8 years older than the recommended cutoff for colonoscopy screening. Most patients scored 0 to 2 on the modified frailty index, suggesting that not only are older patients more fit than previously thought, but also able to tolerate colorectal interventions more liberally. Utilizing frailty indices to identify screening patterns beyond 75 years of age might prove beneficial for this patient population. Further studies are recommended.


Fine needle aspiration in the diagnosis and classification of hepatoblastoma: Analysis of 21 New Cases.
Diagnosis of hepatoblastoma (HBL) is based on characteristic clinical and radiological presentation, young age and marked elevation of serum α-fetoprotein (aFP). Fine needle aspiration (FNA) technique is successfully used in the diagnosis of hepatoblastoma. To evaluate the value of FNA in the diagnosis and subtyping of HBL, we report our experience correlated to histological sections (core needle biopsy, CNB). From 1991 to 2015, 21 cases from 20 patients were cytologically diagnosed as HBL. The patients were 15 males and 5 females, mean age being 3 years, and median age being 2 years and 4 months. Serum aFP levels ranged from negative to 1,285,000 ng/ml. We defined cytological criteria to diagnose fetal, embryonal, mesenchymal, and small cell undifferentiated components. The accurate cytological diagnosis of HBL was made in all cases; 8 cases exhibited a single component and 13 cases exhibited two or more components. Fetal and embryonal components were seen in 18 and 13 cases, respectively, and small cell undifferentiated component was seen in one case. Mesenchymal component was seen in 12 cases. Comparing cytology and histology, identical components were identified on both, FNA and CNB in 14 cases. When analyzing only the presence of epithelial components, 17 cases were concordant in both techniques. FNA allows to accurately diagnose HBL and recognize its histological subtypes. On the basis of high concordance between cytological and histological diagnosis, FNA is validated as an alternative diagnostic method to CNB. Diagn. Cytopathol. 2017;45:91-100. © 2016 Wiley Periodicals, Inc.


Classification of human chronotype based on fMRI network-based statistics.
Chronotype-the relationship between the internal circadian physiology of an individual and the external 24-h light-dark cycle-is increasingly implicated in mental health and cognition. Individuals presenting with a late chronotype have an increased likelihood of developing depression, and can display reduced cognitive performance during the societal 9-5 day. However, the interplay between physiological rhythms and the brain networks that underpin cognition and mental health is not well-understood. To address this issue, we use rs-fMRI collected from 16 people with an early chronotype and 22 people with a late chronotype over three scanning sessions. We develop a classification framework utilizing the Network Based-Statistic methodology, to understand if differentiable information about chronotype is embedded in functional brain networks and how this changes throughout the day. We find evidence of subnetworks throughout the day that differ between extreme chronotypes such that high accuracy can occur, describe rigorous threshold criteria for achieving 97.3% accuracy in the Evening and investigate how the same conditions hinder accuracy for other scanning sessions. Revealing differences in functional brain networks based on extreme chronotype suggests future avenues of research that may ultimately better characterize the relationship between internal physiology, external perturbations, brain networks, and disease.


Functional relationship of AtABCG21 and AtABCG22 in stomatal regulation.
Stomatal regulation is important for water transpiration from plants. Stomatal opening and closing are controlled by many transporter proteins in guard cells. AtABCG22 is a member of the ATP-binding cassette (ABC) transporters and is a stomatal regulator; however, the function of AtABCG22 has not yet been determined fully, although a mutant phenotype included a significant effect on stomatal status. Here, we further investigated the function of the AtABCG22 gene and its functional relationships with other subfamily genes. Among close family members, we found a functional relationship of stomatal phenotypes with AtABCG21, which is also expressed specifically in guard cells. Based on an analysis of double mutants, adding the atabcg21 mutation to atabcg22 mutant partially suppressed the open-stomata phenotype of atabcg22. Multiple-mutant analyses indicated that this suppression was independent of abscisic acid signaling in guard cells. We also found that atabcg22 mutant showed a unique time course-dependent phenotype, being defective in maintenance of stomatal status after initial stomatal opening elicited by light signaling. The function of AtABCG22 and its relationship with AtABCG21 in stomatal regulation are considered.


Isolation and partial characterization of rhoptries and micronemes from Eimeria nieschulzi zoites (Sporozoa, Coccidia).
Homogenization and subcellular fractionation of sporozoites of Eimeria nieschulzi have allowed the recovery of highly enriched fractions of rhoptries and micronemes. The isolated organelles kept their in situ morphological characteristics. Their apparent densities in sucrose solutions were approximately 1.18 g/cm3 for rhoptries and 1.14 g/cm3 for micronemes. When subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the microneme fraction showed two major polypeptides at 220 and 94 kDa. The rhoptry fraction contained at least three predominant peptides at 200, 150, and 63 kDa. Micronemes were also isolated from third-generation merozoites of the same species; their characteristics were identical to those of the organelles isolated from sporozoites.


The influence of surface-active media on the mechanical properties of materials.
This survey summarizes studies dealing with the influence of surface-active media on the mechanical behavior of materials that have been carried out at the Institute of Physical Chemistry of the Russian Academy of Sciences, at the Department of Chemistry of Moscow State University and at the Department of Geography and Environmental Engineering of the Johns Hopkins University, and presented partially at the SIS Symposia. The phenomena of the environment-sensitive mechanical behavior take place for all kinds of solids under the effect of adsorption layers and due to the contact with liquid phases containing some specific components which are physically-chemically akin with respect to a given solid and cause lowering of the surface energy of the solid and weakening of the cohesive forces in the surface (interfacial) layer. Studies of these effects and their atomic-molecular mechanisms provide basis for control, prevention or utilization of these phenomena.


Long-term efficacy of anti-IL-4 receptor antibody in a patient with aspirin-exacerbated respiratory disease and IgG4-related disease.
Aspirin-exacerbated respiratory disease (AERD) and IgG4-related disease (IgG4RD) share a common pathway of Th2-mediated immune mechanism; there have been several cases of IgG4RD developed in patients with asthma, especially in those comorbid with chronic rhinosinusitis (CRS). IgG4RD has often been treated with systemic corticosteroids, rituximab, or immune-suppressive agents, but frequently failed with relapse. Here, we present a case of a 64-year-old male patient with severe AERD with CRS complicated with IgG4RD, who has been successfully treated and maintained with anti-IL-4 receptor antibody, dupilumab after achieving unsatisfactory responses with previous treatments including steroids, rituximab, omalizumab, and reslizumab. The patient's symptoms (periorbital swelling and asthmatic/nasal symptoms) were remarkably improved; serum levels of IgG4/IgE as well as plasmablast/eosinophil counts progressively decreased without any recurrence sign for over 2 years of dupilumab treatment. These findings demonstrate that blocking the IL-4/IL-13 pathway with dupilumab can be an effective treatment with long-term safety in patients with severe AERD with CRS complicated by IgG4RD.


Influence of pectin and glucose on growth and polygalacturonase production by Aspergillus niger in solid-state cultivation.
The solid-state production of endo- and exo-polygalacturonases (PG) by Aspergillus niger was studied in a media containing wheat bran, salts, and different citric pectin and/or glucose concentrations. Kinetic analysis of the process indicated that the formation of PG and the growth of A. niger are associated processes. By increasing citric pectin from 0 to 16% (w/w), the maximum A. niger concentration (X (m)) was raised from 94 to 121 mg/g dry medium suggesting that pectin can be used by A. niger as a growth substrate besides its role as an inducer. With 16% (w/w) pectin, 281 U exo-PG/gdm and 152 U endo-PG/gdm were obtained. Otherwise, pectin concentrations from 20 to 30% (w/w) hindered both production and growth. A. niger concentrations of 108-113 mg/gdm were achieved in runs with glucose from 5 to 12% (w/w), whereas at 16 and 20% (w/w) glucose, lower X (m) values (ca. 100 mg/gdm) were measured. The addition of glucose to the wheat bran medium, up to 10% (w/w) led to maximum endo-PG titers slightly lower than those found in the absence of glucose. Nevertheless, exo-PG formation in these media was strongly increased and activities over 370 U/gdm were achieved. The results suggest that in experiments with pectin concentrations until 16% (w/w), exo-PG production was repressed by pectin-degradation products although these same substances had favored biomass growth. When glucose concentrations over 10% (w/w) were added to the media, the maximum activities of both enzymes decreased drastically, suggesting that glucose at high concentrations also exerts a repressive effect on PG production.


The risk of overall mortality in patients with Type 2 diabetes receiving different combinations of sulfonylureas and metformin: a retrospective analysis.
Sulfonylureas have been shown to increase mortality when used in combination with metformin. This may not be a class effect of sulfonylureas, but rather secondary to differences in properties inherent to the individual sulfonylureas (hypoglycaemic risk, sulfonylurea receptor selectivity and effects on myocardial ischemic preconditioning). The purpose of this study was to assess the risk of overall mortality in patients with Type 2 diabetes treated with different combinations of sulfonylureas and metformin. A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record system to identify 7320 patients with Type 2 diabetes (3768 initiators of glyburide (glibenclamide) and metformin, 2277 initiators of glipizide and metformin and 1275 initiators of glimepiride and metformin), ≥ 18 years of age and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the electronic health record and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts. No statistically significant difference in overall mortality risk was observed among the different combinations of sulfonylureas and metformin: glimepiride and metformin vs. glipizide and metformin (HR 1.03; 95% CI 0.89-1.20), glimepiride and metformin vs. glyburide (glibenclamide) and metformin (HR 1.08; 95% CI 0.90-1.30), or with glipizide and metformin vs. glyburide (glibenclamide) and metformin (HR 1.05; 95% CI 0.95-1.15). Our results did not identify an increased mortality risk among the different combinations of sulfonylureas and metformin, suggesting that overall mortality is not substantially influenced by the choice of sulfonylurea.