The binding of snake venom cardiotoxins to heart cell membranes.
Cobra venom cardiotoxins have the effect, inter alia, of causing systolic arrest of the heart. We have observed significant binding in vitro of 35S-labelled cardiotoxins to mouse heart cell membranes. Part of the binding was saturable and could be displaced with homologous unlabelled cardiotoxins but not by neurotoxins or cardiotoxins inactivated by chemical modification. The specifically bound component represented more than 70% of total binding at saturation. Inclusion of Triton X-100 and NaCl in the phosphate-buffered incubation medium prevented nonspecific adsorption to centrifuge tube walls, and gave lower but more reproducible specific binding results, respectively. An apparent dissociation constant of 5 . 10(-7) M and a binding density of 500 pmol toxin/mg membrane protein were derived from the saturation isotherms.


Electromechanical noise in atrial muscle cells of the carp: a possible ionic feed-back mechanism.
1. Spontaneous electrical fluctuations (+/- 0.2-0.4 mV) were recorded in 'quiescent' atrial fibres of the carp. 2. The noise decreased in acetylcholine, small hyperpolarization and EGTA. 3. The noise increased (to +/- 1-2 mV) and became more synchronous in K+-free Ringer and in ouabain. 4. Large voltage fluctuations (+/- 1-2 mV) were accompanied by a fine mechanical tremor, indicating intracellular [Ca2+] fluctuations. 5. Spectral analysis showed a clear resonant frequency at about 1 Hz, indicating that the noise cannot result from the random switching of independent ionic channels. 6. We propose that the intracellular [Ca2+] and the membrane K+-conductance are involved in a feed-back loop which can oscillate and produce the electromechanical noise. The frequency of oscillation is determined by the relatively slow diffusion of Ca2+ from the intracellular reservoir to the surface membrane.


Sex and COVID-19: A Protective Role for Reproductive Steroids.
Evidence shows coronavirus disease 2019 (COVID-19)-induced symptom severity and mortality is more frequent in men than in women, suggesting sex steroids may play a protective role. Female reproductive steroids, estrogen and progesterone, and its metabolite allopregnanolone, are anti-inflammatory, reshape competence of immune cells, stimulate antibody production, and promote proliferation and repair of respiratory epithelial cells, suggesting they may protect against COVID-19 symptoms.


Dopaminergic receptor D5 mRNA expression is increased in circulating lymphocytes of Tourette syndrome patients.
Tourette syndrome (TS) is a neuropsychiatric disorder in which dopaminergic dysfunction and immune system abnormalities seem to coexist. Using real-time PCR, we determined mRNA expression of dopamine receptors (DRs) D1-5 in peripheral blood lymphocytes (PBLs) from 15 TS patients and 15 sex- and age-matched healthy controls (HCs). DRD5 mRNA levels in cells from TS were higher than in cells from HCs. In TS patients with obsessive-compulsive disorder, DRD5 mRNA levels in PBLs showed a highly positive correlation with the severity of compulsive symptoms. DRD5 mRNA upregulation in PBLs from TS patients may represent a peripheral marker of dopaminergic dysfunction and supports the involvement of the immune system in TS.


Inhalation of 1-bromopropane causes excitation in the central nervous system of male F344 rats.
The present study investigates the effects of 1-bromopropane (1BP) on animal behavior to determine the extent of toxicity to the central nervous system (CNS). We measured the spontaneous locomotor activity (SLA) of rats before and after 3 weeks of exposure to 1BP for 8 h per day. In control and 10 ppm groups, the SLA values were similar to pre-exposure levels on post-exposure Day 1 and thereafter. However, the SLA values in the 50 and 200 ppm groups were higher than pre-exposure levels. Open-field behavior was evaluated after exposure and freezing time decreased with exposure to increasing concentrations of 1BP. Ambulation and rearing scores in the exposed groups were higher than control values, particularly in the 50 and 200 ppm groups. The frequency of defecation and urination decreased almost dose-dependently. Exposure to 50-1000 ppm of 1BP did not affect passive avoidance behavior examined using a step-through type apparatus. The amount of time swimming in the water maze test was not affected in the controls, or groups exposed to 50 and 200 ppm 1BP, but that in the 1000 ppm group was increased compared with control. Exposure at 50-1000 ppm dose-dependently decreased the traction performance of rats, indicating decreased muscle strength. We found that 10-200 ppm of 1BP exposure did not affect motor coordination determined by rota-rod performance. The increased SLA values and open-field activity support the notion that 1BP has excitatory effects on the CNS of F344 male rats. In addition, 1BP reduced the grip or muscle strength of the rats. Memory function was not disordered and the motor coordination of all four limbs remained normal.


Interleukin-1β-Activated Microvascular Endothelial Cells Promote DC-SIGN-Positive Alternatively Activated Macrophages as a Mechanism of Skin Fibrosis in Systemic Sclerosis.
To characterize the role of interleukin-1β (IL-1β) and microvascular endothelial cells (MVECs) in the generation of alternatively activated macrophages in the skin, and to explore their role in the development of skin fibrosis in patients with systemic sclerosis (SSc; scleroderma). Conditioned medium prepared with MVECs purified from the skin of healthy donors and the skin of SSc patients was used to generate monocyte-derived macrophages. Flow cytometry, multiplex protein assessment, real-time quantitative polymerase chain reaction, and tissue immunofluorescence were used to characterize MVEC-induced polarization of alternatively activated macrophages. Coculture experiments were conducted to assess the role of MVEC-induced alternatively activated macrophages in fibroblast activation. Alternatively activated macrophages were characterized in the skin of healthy donors and SSc patients using multiparametric immunofluorescence and multiplex immunostaining for gene expression. Based on our in vitro data, we defined a supervised macrophage gene signature score to assess correlation between the macrophage score and clinical features in patients with SSc, using the Spearman's test. IL-1β-activated MVECs from SSc patients induced monocytes to differentiate into DC-SIGN+ alternatively activated macrophages producing high levels of CCL18, CCL2, and CXCL8 but low levels of IL-10. DC-SIGN+ alternatively activated macrophages showed significant enhancing effects in promoting the production of proinflammatory fibroblasts and were found to be enriched in perivascular regions of the skin of SSc patients who had a high fibrosis severity score. A novel skin transcriptomic macrophage signature, defined from our in vitro findings, correlated with the extent of skin fibrosis (Spearman's r = 0.6, P = 0.0018) and was associated with early disease manifestations and lung involvement in patients with SSc. Our findings shed new light on the vicious circle implicating unabated IL-1β secretion, MVEC activation, and the generation of DC-SIGN+ alternatively activated macrophages in the development of skin fibrosis in patients with SSc.


Competition between rotifers and cladocerans of different body sizes.
We conducted laboratory experiments to test the hypothesis that rotifers could coexist with small (<1.2 mm) but not large (>1.2 mm) cladocerans. Keratella cochlearis was excluded in <8 days by the large cladocerans Daphnia pulex and D. magna, probably through both interference and exploitative competition. On the other hand, K. cochlearis persisted for 8 weeks with two small cladocerans (Bosmina longirostris and Ceriodaphnia dubia) and excluded a third small cladoceran (D. ambigua). Similarly, Synchaeta oblonga coexisted with B. longirostris for >7 weeks, and K. testudo coexisted with D. ambigua for >4 weeks. Coexistence of small cladocerans and rotifers was always accompanied by suppression of one or both populations, probably primarily if not exclusively by exploitative competition for limiting food resources. These results indicate that the competitive dominance of cladocerans over rotifers decreases markedly with cladoceran body size and that factors other than body size may determine the competitive outcome between rotifers and small cladocerans. Our study provides a mechanistic explanation for a commonly observed pattern in natural zooplankton communities: planktonic rotifers often are abundant when only small cladocerans occur but typically are rare when large cladocerans are present.


Insights into the correlations between the size of starch at nano- to microscale and its functional properties based on asymmetrical flow field-flow fractionation.
In this study, the starches were isolated from three botanical sources (i.e., rice, sweet potato, and lotus seed). The size distributions of starch granules and molecules were determined by asymmetrical flow field-flow fractionation (AF4), and compared with those measured from optical microscopy (OM) and dynamic light scattering (DLS). Furthermore, the starches were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). AF4 coupled online with UV-visible, multiangle light scattering (MALS), and differential refractive index (dRI) detectors (AF4-UV-MALS-dRI) was employed for the investigation of the digestion and retrogradation properties of starches. Meanwhile, the relationships between the size of starch at nano- to microscale and its functional properties (i.e., digestibility, retrogradation, and thermal properties) were studied by Pearson correlation analysis. AF4-UV-MALS-dRI was proved to be a rapid and gentle method for the separation and size characterization of starches at both micro- and nano-molecule levels. Moreover, it was demonstrated that AF4-UV-MALS-dRI is a useful tool for the monitoring of the digestion and retrogradation properties of starches. The results suggested that the sizes of starch granules and molecules were to some extent correlated with their thermal properties and digestibility, but not with retrogradation property.


Metabolic syndrome clusters and the risk of incident stroke: the atherosclerosis risk in communities (ARIC) study.
Little is known about the metabolic syndrome (MetS) and the risk of incident stroke. This study is designed to identify particular clusters of MetS components that carry the highest risk of incident stroke. We analyzed the public use data from the population-based Atherosclerosis Risk in Communities study. At baseline, 14 993 stroke-free middle-aged individuals were followed-up over 9 years for incident stroke. MetS components were defined according to the National Heart, Lung, and Blood Institute/American Heart Association criteria. Incident stroke was identified using a standardized incident events identification and classification protocol. Proportional hazard models were used to assess the RRs and 95% CIs of ischemic stroke associated with MetS and its different clusters. At baseline, the prevalence of MetS was 39%. The mean age was 54, with 26% blacks and 55% females. The hazard ratio of incident ischemic stroke associated with MetS among women (hazard ratio, 2.41; 95% CI, 1.69 to 3.49) and men (hazard ratio, 2.11; 95% CI, 1.56-2.85) was similar. There was a dose-response relationship between the numbers of MetS components and the risk of incidence stroke. Persons with either elevated blood pressure or elevated fasting glucose in the clusters to form a MetS had the highest risk for incident stroke (hazard ratio, 2.74-4.16 comparing to the reference group) than MetS without these 2 components (hazard ratio, </=2.00 comparing to the reference group). The data support the need to target MetS, especially MetS, with these 2 highest risk components (elevated blood pressure or elevated fasting glucose) in the clusters.


Gas-solid chromatographic procedures for determining acrylonitrile monomer in acrylonitrile-containing polymers and food simulating solvents.
A gas chromatographic method is described for acrylonitrile monometer (AN), using a nitrogen/phosphorus detector. Procedure for the analysis of AN in 5 food simulants (water, 3% acetic acid, heptane, 50% ethanol, and 8% ethanol) as well as in the polymer matrix are included. The quantitation limit for direct injection of AN/food simulant solution is 0.04 ng AN/microliter. AN-based polymers are dissolved in N,N-dimethylacetamide and injected directly. Residual AN in the polymer can be quantitated at the 0.5 ng/microliter level. Results of migration studies are also presented.


Significant postoperative refractive errors in vivo with the Mentor Memorylens intraocular lens.
To determine the difference between the predicted and postoperative refraction in eyes after implantation of the Mentor MemoryLens intraocular lens (IOL) and compare these results with those of 2 other types of foldable IOLs implanted by the same surgeons. Community-based group practice ophthalmology clinic. All operated eyes (341) of all patients who had routine phacoemulsification with implantation of a MemoryLens IOL performed by 1 of 2 surgeons were evaluated retrospectively. The predicted refractive error and actual postoperative refractive error were compared in each eye in the MemoryLens group and in 2 smaller control groups with an AcrySof acrylic (Alcon) or SI-40 silicone (Allergan Medical Optics) IOL implanted by the same surgeons using identical technique and IOL calculation parameters. Patients in whom the difference between the predicted and actual postoperative refraction fell significantly outside expected parameters were rechecked with repeat axial length and keratometric readings, and these measurements were used to back-calculate the effective in vivo IOL power. The MemoryLens group had significantly greater variability in postoperative refractive results from those predicted by the Hoffer program than the 2 control groups. The postoperative refractive error in the MemoryLens group differed from +1.50 to -5.50 diopters (D) from that predicted by the IOL calculation formulas. When the outlier groups (ie, greater than +0.50 D or less than -1.00 D from predicted refractive error) were evaluated and compared to the rest of the MemoryLens group and the 2 control groups, no significant difference in axial length, keratometric measurements, operative surgeon, surgical technique, or patient age was found. Repeat axial length and keratometric measurements in the outlier group were not significantly different from those in the same eyes preoperatively. Back-calculation using postoperative axial length and keratometric measurements in the highly myopic outlier group showed that the mean difference between the labeled IOL power and actual in vivo IOL power in the outlier group was -3.08 D (range -1.98 to -7.54 D). The best corrected visual acuity was not affected in patients in the outlier groups despite the refractive variability. The variation in postoperative refractive results in the MemoryLens group was significantly greater than in the 2 other foldable IOL groups.


Both scanning plane and observer affect measurements of scaphoid deformity.
The influence of angular deformity of the scaphoid on wrist function and arthrosis is debated and the reliability of the described quantitative measurements of deformity has been questioned. We hypothesized that the inherent imprecision with which computed tomography scanning planes are selected introduces another source of variability in measurements of scaphoid deformity, further diminishing their reliability. Sagittal plane images of 15 computed tomograms of normal scaphoids were evaluated in 3 different reconstruction planes. Four observers measured the lateral intrascaphoid angle, the dorsal cortical angle, and the height-to-length ratio of the 45 images in random order and then measured them again in a distinct random order 2 weeks later. The variability of each observer's measurements (intraobserver reliability) was evaluated with Pearson correlation coefficients. The agreement of the measurements made by the 4 observers (interobserver reliability) and the agreement of the measurements of the same bone in different reconstruction planes (interplane reliability) were evaluated using interclass correlation coefficients. The intraobserver reliability was poor for 27 of 36 comparisons. The interobserver reliability of the dorsal cortical angle and the intrascaphoid angle was poor for all reconstruction planes. The interobserver reliability of the height-to-length ratio was good for 2 planes and poor for the third plane. The interplane reliability was poor for 7 of 12 comparisons, with no single measurement technique remaining consistent for all observers across reconstruction planes. Quantitative measurements of scaphoid deformity have very limited reliability for individual observers, between different observers, and depending on the plane in which the image of the scaphoid is produced. Even the most reliable measure of deformity (height-to-length ratio) was not consistent between reconstruction planes. Unless more reliable scanning and measurement techniques are developed ideas about the effect of scaphoid deformity on wrist function will remain to a large degree speculative.


Serum amylase isozymes in patients with chronic pancreatitis with hyperamylasemia.
In order to clarify the relationship between hyperamylasemia and clinical states in chronic pancreatitis, serum amylase isozymes were studied in 39 cases of chronic pancreatitis including 13 cases of alcoholic pancreatitis. Hyperamylasemia in chronic pancreatitis is generally due to high pancreatic type isoamylase (P-amylase) activity in acute exacerbation, sometimes accompanied by a transient elevation in salivary type isoamylase (S-amylase). On remission, however, hyperamylasemia due to high S-amylase activity has been found. These were cases of advanced alcoholic pancreatitis, which exhibited a characteristic pattern of low serum P-amylase and high serum S-amylase activities while the clearance ratio (Cam/Ccr) was normal despite high S-amylase activity. It should be noted that hyperamylasemia in chronic pancreatitis may be caused by high S-amylase activity in addition to high P-amylase activity, especially in alcoholic pancreatitis.


The use of human albumin millimicrospheres tagged with 99mTc in the evaluation of the removal capacity of the reticuloendothelial system.
Liver uptake kinetics of 99mTc labelled millimicrospheres of human serum albumin (MM) was studied in 16 subjects. Every subject received four doses of MM intravenously. The uptake constant decreased progressively with increasing dose. The maximum liver removal capacity, a parameter which is independent of liver blood flow, was calculated according to the method of Iio and Wagner (1963). From these data we conclude that MM are taken up by the reticuloendothelial system (RES) with saturable kinetics, and they are suitable for clinical use to evaluate RES function in man.


Trametinib and Hydroxychloroquine (HCQ) Combination Treatment in KRAS-Mutated Advanced Pancreatic Adenocarcinoma: Detailed Description of Two Cases.
Over the last decades, cytotoxic chemotherapy has been the cornerstone of metastatic pancreatic adenocarcinoma treatment. In late-stage disease, a range of treatment regimens still offers minor benefits. Molecular profiling studies have shown that pancreatic adenocarcinoma (PDAC) is a mutation-driven tumor type, with KRAS mutations found in approximately 90% of cases, which could partially explain the resistance to chemotherapy. Preclinical data on selective targeting of a downstream point of the RAF-MEK-ERK pathway with a MEK inhibitor along with the concurrent use of an autophagy inhibitor such as hydroxychloroquine appears to be one alternative approach to overcome resistance and inhibit cell proliferation. We herein aim to investigate the rationale of autophagy inhibitors use and describe the outcomes of patients who received this experimental treatment. Two patients have received this experimental regimen from January 2020 to the present date, achieving disease stabilization that is clinically meaningful, considering the chemoresistance scenario of the included patients. Our real-life data regarding KRAS-mutated PDAC patients who received treatment with the MEK inhibitor trametinib combined with hydroxychloroquine after experiencing disease progression are consistent with the preclinical data, pointing to the clinical benefits of this regimen.


[Eosinophilic gastritis].
Two case studies of eosinophilic gastritis studied by the Pathology Department of the Hospital Central de San Luis Potosi are presented. Based on these cases, the clinical pathological forms of the entity are analized together with the classification and etiopathology, from which it is considered a late allergic or hipersensitive reaction to foreign proteins. Therefore, it is essentially different from the neoplastic, histiocitic, eosinophilic granuloma of the bone.


Tissue distribution and warfarin sensitivity of vitamin K epoxide reductase.
The distribution of vitamin K epoxide reductase activity and its sensitivity to warfarin have been examined in whole microsomes from tissues of both control and warfarin-resistant strain rats. The distribution of activity roughly paralleled that previously shown for the vitamin K-dependent carboxylase. Activity on a per gram tissue basis was highest in kidney, adrenal, spleen, lung, testes, and epididymis at a level about 1/20th of that present in liver microsomes. Vitamin K quinone formation by microsomes from warfarin-resistant rats was approximately half that of control strain samples. In addition, hydroxy vitamin K was formed by warfarin-resistant strain microsomes to about the same extent as vitamin K quinone in all tissues. The Km values for dithiothreitol (DTT) and vitamin K epoxide were similar in all tissues (range = 0.1-0.2 mM DTT at 40 microM vitamin K epoxide, and 10-30 microM vitamin K epoxide at 2 mM DTT). The sensitivities to warfarin were similar for all control strain rat tissues (I50 = 10-20 microM at 2 mM DTT and 40 microM vitamin K epoxide) and similarly elevated for all warfarin-resistant rat tissues (I50 = 30 to greater than 80 microM). These results suggest that the identical enzyme is expressed in all tissues and that tissue specific isozymes do not occur.


Endosomal trafficking of the ligated FcvarepsilonRI receptor.
In addition to initiating signaling cascades leading to mast cell mediator release, aggregation of the high affinity IgE receptor (FcvarepsilonRI) leads to rapid internalization of the cross-linked receptor. However, little is known about the trafficking of the internalized FcvarepsilonRI. Here we demonstrate that in RBL-2H3 cells, aggregated FcvarepsilonRI appears in the early endosomal antigen 1 (EEA1(+)) domains of the early endosomes within 15min after ligation. Minimal co-localization of FcvarepsilonRI with Rab5 was observed by 30min, followed by its appearance in the Rab7(+) late endosomes and lysosomes at later time points. During endosomal sorting, FcvarepsilonRIalpha and gamma subunits remain associated. In Syk-deficient RBL-2H3 cells, the rate of transport to lysosomes is markedly increased. Taken together, our data demonstrate time-dependent sorting of aggregated FcvarepsilonRI within the endosomal-lysosomal network, and that Syk may play an essential role in regulating the trafficking and retention of FcvarepsilonRI in endosomes.


Antioxidant and prooxidant properties of a polyphenol-rich extract from Geranium sanguineum L. in vitro and in vivo.
A polyphenol-rich extract from Geranium sanguineum L. (PC) protected biological membranes due to its antioxidant capacity. PC caused a dose-dependent decrease of the osmotic hemolysis of human erythrocytes and increased their resistance against the toxic effect of H(2)O(2); no effect on catalase activity was observed. While PC reduced the accumulation of TBA-reactive products in rat liver microsomes in inducible lipid peroxidation (LPO), the non-induced LPO was not affected. Further the effect of PC on the products of LPO was investigated in the lungs, livers and sera of intact and influenza virus-infected mice (VIM). The infection enhanced LPO in the lungs and livers. In the group of PC-treated VIM, malondialdehyde (MDA) in the lungs and livers was brought to control levels. PC-treatment caused a significant increase of MDA in the lungs of intact mice, a slight one in the livers and did not affect MDA in the sera. Thus the extract exhibited prooxidant characteristics in intact animals as well as antioxidant properties in VIM. The reducing ability of PC on LPO could be an alternative mechanism of its protective effect in experimental influenza infection.


Effect of cytochalasin D on secretion by rat pancreatic acini.
Using the model of isolated acini the effect of cytochalasin D (CD) on rat pancreatic secretion in vitro was studied. The influence of CD (0.01-10 micrograms/ml = 0.02-19.7 microM) on amylase secretion and 3H-pulse-labelled protein release was measured under two sets of conditions: (a) basal, and (b) stimulated by 77pM caerulein. Basal secretion was not altered, but stimulated secretion of amylase and 3H-labelled proteins were similarly inhibited by up to 45%. It is concluded that CD affects only exocytosis of zymogen granules and not intracellular transport.


Electronic, optical and spectroscopic properties of N-dialkyl-imidazolium hexafluorophosphate (CNMIM.PF6) ionic liquid crystal molecules investigated by computational methods.
In this present work, we calculate the electronic, spectroscopic and nonlinear optical properties (NLO) of N-dialkyl-imidazolium hexafluorophosphate (CNMIM.PF6, where N = 10, 12, 14, 16, 18, 20) ionic liquid crystal molecules under the effect of alkyl chain length variation in cation moiety [CNMIM]+ with fixed anion [PF6]-. CONTEXT: The majority of research on ionic liquid crystal to date has been focused on experiments, while theoretical studies on the optical properties of ionic liquid crystal have been extremely rare. Nonlinear phenomena in optical devices have attracted many researchers. Therefore, results of NLO properties may favor facile synthesis and fabrication of novel-type of materials as well as optoelectronic devices. Spectroscopic studies elucidate further insight into ionic liquid crystal behavior. The results demonstrate that variations in alkyl chain length have an impact on the conformers' electrical, spectroscopic, and NLO properties as well as their stability. The stability of ionic liquid crystal molecules increases with increase in the alkyl chain length and the energy band gap range is 6.64-6.29 eV. Understanding ionic liquid crystal's physical behavior requires an understanding of their dipole moments and NLO features, which are covered in this article. The results of NLO characteristics for all ionic liquid crystal molecules show that their first-order hyperpolarizabilities are higher than the reference molecule (urea). METHODS: The electronic (molecular energy band gap, electrostatic potential map, as well as HOMO-LUMO orbitals) and spectroscopic (IR-RAMAN, UV) properties were evaluated with the help of theoretical model at B3LYP/6-31G(d) while the NLO study has been performed using B3LYP and M06-2X with different basis sets 6-31G(d) and 6-311++G(d,p), as implemented in Gaussian09 software.


Randomized clinical trial to assess the impact of oral intervention with cetylpyridinium chloride to reduce salivary SARS-CoV-2 viral load.
Aerosols released from the oral cavity help spread the SARS-CoV-2 virus. The use of a mouthwash formulated with an antiviral agent could reduce the viral load in saliva, helping to lower the spread of the virus. The aim of this study was to assess the efficacy of a mouthwash with 0.07% cetylpyridinium chloride (CPC) to reduce the viral load in the saliva of Coronavirus disease 2019 (COVID-19) patients. In this multi-centre, single-blind, randomized, parallel group clinical trial, 80 COVID-19 patients were enrolled and randomized to two groups, namely test (n = 40) and placebo (n = 40). Saliva samples were collected at baseline and 2 h after rinsing. The samples were analysed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and an enzyme-linked immunosorbent assay test specific for the nucleocapsid (N) protein of SARS-CoV-2. With RT-qPCR, no significant differences were observed between the placebo group and the test group. However, 2 h after a single rinse, N protein concentration in saliva was significantly higher in the test group, indicating an increase in lysed virus. The use of 0.07% CPC mouthwash induced a significant increase in N protein detection in the saliva of COVID-19 patients. Lysis of the virus in the mouth could help reduce the transmission of SARS-CoV-2. However, more studies are required to prove this.


Assessing the Impact of the COVID-19 Pandemic on Training at the MD Anderson Cancer Center Anatomical Pathology Fellowship Program.
To provide high-quality, safe training during the COVID-19 pandemic, our anatomic pathology fellowship program implemented a hybrid virtual/in-person training model with supplemental digital material. To evaluate the impact of this model. We examined Accreditation Council for Graduate Medical Education survey results and board pass rates for fellows before the pandemic (group 1); during the pandemic peak (group 2); and early and late after the pandemic peak (groups 3 and 4). Additionally, we distributed an online survey including questions related to performance as attending physicians and fellowship experience to recent graduates. Information loss during handover, supervision and teaching by faculty, and having at least 4 free days a month exhibited the greatest score declines between group 1 and groups 2, 3, and 4 on the Accreditation Council for Graduate Medical Education surveys. No differences were seen in board passing rates between groups. The groups did not differ in responses regarding preparation for role as attending, confidence in role as attending, or overall impression of the fellowship program. The pandemic-affected groups responded more positively on the perceived utility of supplemental digital material, impact of digital pathology on quality of education, and impact of supplemental digital material on familiarity with digital pathology. The difference was particularly large between group 1 and combined groups 3 and 4. Despite the limitations noted, the hybrid training model was effective and successfully prepared fellows for their role as attending physicians. Similar studies can be informative for the implementation of similar programs or for the meaningful integration of digital pathology into training curricula.


A comparative study of the cardiac troponin inhibitory factor (TNI) from mammalians.
Troponin inhibitory factor, TNI, was prepared by affinity chromatography from different mammalian hearts. (i) Structure. These different TNI have the same M.W. (28000), which is higher than that found in rabbit skeletal muscle (23000). Nevertheless they differ with respect of their charge as shown by alkaline urea polyacrylamide gel electrophoresis using cardiac TNI which has previously been bound to an excess of skeletal troponin Ca2+-binding factor. These changes do not correlate with the PO4 content of TNI. They are associated with structural differences demonstrated by peptide mapping of the unfolded molecule after papain treatment. The structure of cardiac TNI from rat and rabbit differs clearly from that of crow and pig. (ii) Biological activity. These different TNI have the same inhibitory effect on skeletal actomyosin. ATPase, the same content of PO4 and the same ability to be phosphorylated in-vitro by a bovine heart c-AMP-dependent protein kinase.


Hyper-Eosinophilic Syndrome Masquerading as Myocardial Infarction, Stroke and Cancer.
Hyper-eosinophilic syndrome (HES) can be fatal if left untreated; and it is difficult to make a diagnosis early on due to the symptoms overlapping with many other conditions. For patients presenting with eosinophilia and end-organ damage, clinicians should have a high degree of suspicion for HES. Treatment with steroids can prevent further progression or can lead to complete resolution of the symptoms.


[Hemorheologic changes in patients with chronic hepatitis B].
To study the variation of the hemorheology in patients with chronic hepatitis B and study its relations with HBV DNA, liver function and oxidative stress markers. Indices for hemorheology, oxidative stress markers, liver function, and HBV DNA were measured in 55 patients with chronic hepatitis B and correlative analysis was made. The low-shear whole blood viscosity (BV), RBC aggregation index were significantly higher in hepatitis B group than those in the control group (P < 0.05), Hematocrit (HCT), the low-shear BV, RBC aggregation index were significantly higher in the patients whose ALT was higher than the patients whose ALT was normal and the controls. No significant difference was found in HBV DNA and indices of hemorheology (P > 0.05), nor in indices of hemorheology and oxidative stress markers (P > 0.05). There is disturbance of microcirculation and oxidative stress in the body of patients with chronic hepatitis B. The hemorheology and oxidative stress markers should be regarded as useful indexes in patients with chronic hepatitis B in addition to HBV markers.


[The role of the vesical imaging-reporting and data system (VI-RADS) for bladder cancer diagnostics-status quo].
Initial clinical and pathological diagnostic workup of urinary bladder cancer is based on cystoscopy, transurethral resection of suspicious lesions, and computed tomography when indicated. Accurate staging is necessary for further therapeutic decision-making. This review summarizes the current status of multiparametric magnetic resonance imaging (mpMRI) and the vesical imaging-reporting and data system (VI-RADS) classification. MpMRI may improve the accuracy of assessment of local tumor invasion compared to conventional imaging alone. VI-RADS standardizes reporting of MRI staging and classifies the likelihood of muscle-invasive bladder cancer into five categories. Preliminary data suggest low interobserver variability. However, prospective multicenter studies are necessary to validate the VI-RADS classification. Progress in functional, molecular, and hybrid imaging may further improve the accuracy of clinical tumor and nodal staging for bladder cancer.


[Radiolabeling and biodistribution studies of polymeric nanoparticles as adjuvants for ocular vaccination against brucellosis].
To optimize radiolabeling with (99m)Tc of mannosylated Gantrez(®) nanoparticles loaded with the Brucella Ovis antigen (Man-NP-HS) and to carry out biodistribution studies in mice after ocular administration of the nanoparticles. Man-NP-HS nanoparticles were prepared by the solvent displacement method. They were purified, lyophilized and characterized. Following this, they were radiolabeled with 74 MBq of (99m)TcO4(-) previously reduced with an acidic stannous chloride solution, working in absence of oxygen and at a final pH of 4. Radiolabeling yield was evaluated by TLC. Biodistribution studies were carried out in mice after ocular administration of the formulation and control of free (99m)TcO4(-). To do so, the animals were humanely killed at 2 and 24hours after the ocular administration and activity in organs was measured in a Gamma counter. Radiolabeling yield obtained was greater than 90%. Biodistribution studies of (99m)Tc-Man-NP-HS showed radioactivity accumulated at 2 and 24hours in nasal and ocular mucosa and gastrointestinal tract, in contrast to biodistribution of free (99m)TcO4(-) that remained concentrated in the skin around the eye and gastrointestinal tract. Biodistribution studies of (99m)Tc-Man-NP-HS after ocular instillation have made it possible to demonstrate its biodistribution in nasal mucosa and gastrointestinal tract. This characteristic is essential as an antigenic delivery system throughout the ocular mucosa. This, together with its elevated immune response, effective protection and intrinsic avirulence make them a suitable anti-Brucella vaccine candidate.


Pemphigus vulgaris-IgG causes a rapid depletion of desmoglein 3 (Dsg3) from the Triton X-100 soluble pools, leading to the formation of Dsg3-depleted desmosomes in a human squamous carcinoma cell line, DJM-1 cells.
In this study, we examined desmoglein (Dsg) 3 and other desmosomal molecules after pemphigus vulgaris (PV)-immunoglobulin G (IgG) binding to the Dsg3 on the cell surface in DJM-1 cells, a human squamous cell carcinoma cell line. After cells were incubated with PV-IgG for various time periods (0, 5, 10, 20, 30, 60 min, or 30 h), cells were fractionated into phosphate-buffered saline soluble (cytosol), phosphate-buffered saline insoluble-Triton X-100 soluble (membrane), and Triton X-100 insoluble (cytoskeleton) fractions, and subjected to immunoblotting and immunofluorescence microscopy using antibodies against Dsgl, Dsg3, plakoglobin, desmoplakin 1, and cytokeratins. Immunoblot analysis with PV-IgG revealed that Dsg3 was already dramatically depleted from the membrane fraction 20 min after PV-IgG treatment, whereas no reduction of Dsg3 was detected in the cytoskeleton fraction as examined by immunoblotting. A 30 h incubation with PV-IgG, however, caused a marked disappearance of Dsg3, but not other desmosomal molecules, from cytoskeleton fractions. Furthermore, double-staining immunofluorescence microscopy revealed that Dsg3 was depleted from the desmosomes whereas Dsg1, desmoplakin 1, plakoglobin, and keratin filaments were bound to desmosomes. These results provide a novel interpretation for a better understanding of mechanisms for blistering in PV; i.e., a possibility that PV-IgG generates the formation of aberrant desmosomes, which are lacking in Dsg3, but not other desmosomal constituents.


Down's syndrome and myocardial reperfusion injury.
Down syndrome is known to be an independent risk factor for mortality after surgical repair of congenital heart anomalies. It is also associated with neurodegenerative disease and accelerated aging. The mechanism of the latter features has been attributed to abnormal handling of oxygen-free radicals as well as mitochondrial dysfunction. These properties also place the child with Down syndrome at a risk of an exaggerated myocardial ischemia/reperfusion injury. A 6 month old child with Down syndrome is reported who suffered from obvious clinical ischemia/reperfusion injury following an uncomplicated repair of complete AV canal. Both intraoperative as well as postoperative echocardiography documented a satisfactory technical repair. After resting the heart on ECMO the child's myocardial function returned to normal. The mechanisms by which patients with Down syndrome are at risk of ischemia/reperfusion injury are reviewed. Future studies should focus on specific approaches for myocardial protection in the child with Down syndrome undergoing cardiac surgery.


Cerebellar abnormalities following hypoxia alone compared to hypoxic-ischemic forebrain injury in the developing rat brain.
Two-day-old (P2) rat pups were subjected to either a global hypoxia or to electrocoagulation of the right carotid artery followed by 2.5 h hypoxia. Cellular and regional injury in the cerebellum (CB) was studied at 1, 2 and 19 days using immunohistology. Following hypoxia and hypoxia-ischemia, all neuronal populations of the CB were damaged in a subset of Purkinje cells. The decrease in the number of interneurons, as well as the thickness of molecular and granular layers was significant following hypoxia. Diffuse white matter damage, with loss of preoligodendrocytes was more severe following hypoxia than hypoxia-ischemia. Global hypoxia in the rat at P2 produces extensive damage to many cell types in different areas of the CB. The addition of unilateral forebrain ischemia does not increase the severity of these changes. Our data provide insight into the mechanisms of the changes observed in the CB of premature newborns.


Developmental patterns of sexual identity, romantic attraction, and sexual behavior among adolescents over three years.
Adolescents are heterogeneous in how they define and experience their sexual orientation, which can include specific identity labels, romantic attractions, and other- and/or same-sex sexual behavior. These three components of sexual orientation are not always concordant, and studies suggest adolescents-particularly girls-are fluid in these dimensions of orientation over time. The current study examined: 1) fluidity in adolescent girls' and boys' self-labeled identities and romantic attractions over time, and 2) patterns of adolescent girls' and boys' self-labeled identities and romantic attractions as they coincide with sexual behavior. Surveys were administered to adolescents in three low-income high schools in the rural Southeastern U.S. at three yearly intervals (n = 744; Mage = 15.0; 54.3% girls; 48% White, 24% Hispanic/Latinx, 21% Black/African American). Participants reported their self-labeled sexual identity and romantic attraction at each time point and their lifetime sexual behavior with girls and boys at year 3. Results revealed 26% of girls and 11% of boys reported fluidity in identity and 31% of girls and 10% of boys reported fluidity in attractions. At each time point, up to 20% of girls and 6% of boys reported a sexual minority identity label with concurrent same-sex attraction; the majority of these participants also reported same-sex behavior. Among heterosexual-identified participants reporting some degree of same-sex attraction at year 3, approximately 66% of girls and 10% of boys reported same-sex behavior. The findings suggest that many adolescents are nuanced and dynamic in how they identify and experience their developing sexualities.


How air influences radiation dose deposition in multiwell culture plates: a Monte Carlo simulation of radiation geometry.
Radiation of experimental culture cells on plates with various wells can cause a risk of underdosage as a result of the existence of multiple air-water interfaces. The objective of our study was to quantify this error in culture plates with multiple wells. Radiation conditions were simulated with the GAMOS code, based on the GEANT4 code, and this was compared with a simulation performed with PENELOPE and measured data. We observed a slight underdosage of ∼ 4% on the most superficial half of the culture medium. We believe that this underdosage does not have a significant effect on the dose received by culture cells deposited in a monolayer and adhered to the base of the wells.


Food selection based on total antioxidant capacity can modify antioxidant intake, systemic inflammation, and liver function without altering markers of oxidative stress.
It is unknown whether diets with a high dietary total antioxidant capacity (TAC) can modify oxidative stress, low-grade inflammation, or liver dysfunction, all of which are risk factors for type 2 diabetes and cardiovascular disease. We studied the effect of high- and low-TAC (HT and LT, respectively) diets on markers of antioxidant status, systemic inflammation, and liver dysfunction. In a crossover intervention, 33 healthy adults (19 men, 14 women) received the HT and LT diets for 2 wk each. Dietary habits were checked with a 3-d food record during both diet periods and the washout period. Fruit and vegetable, macronutrient, dietary fiber, and alcohol intakes did not differ significantly between the 2 diets, whereas dietary TAC, alpha-tocopherol, and ascorbic acid were significantly (P < 0.001) higher during the HT diet. Plasma alpha-tocopherol rose during the HT and decreased during the LT diet (P < 0.02 for difference) without changes in markers of oxidative stress except plasma malondialdehyde, which decreased unexpectedly during the LT diet (P < 0.05). Plasma high-sensitivity C-reactive protein, alanine aminotransferase, gamma-glutamyltranspeptidase, and alkaline phosphatase concentrations decreased during the HT compared with the LT diet (mean +/- SEM for pre-post changes: -0.72 +/- 0.37 compared with 1.05 +/- 0.60 mg/L, P < 0.01; -1.73 +/- 1.02 compared with 2.33 +/- 2.58 U/L, P < 0.01; -2.12 +/- 1.45 compared with 5.15 +/- 2.98 U/L, P < 0.05; and 1.36 +/- 1.34 compared with 5.06 +/- 2.00 U/L, P < 0.01, respectively). Selecting foods according to their TAC markedly affects antioxidant intake and modulates hepatic contribution to systemic inflammation without affecting traditional markers of antioxidant status.


Effects of palm olein and palm stearin on cecal and fecal microbiota of C57BL/6J mice under low and high fat intakes.
This work aimed to study the effects of dietary lipid composition and content on cecal and fecal microbiota of mice fed the following diets for 8 weeks: palm olein (PO)-based low-fat diet, PO-based high-fat diet, palm stearin (PS)-based low-fat diet, and PS-based high-fat diet. Increasing the dietary PS level favored the growth of Firmicutes over Bacteroidetes in the cecum and feces. In addition, it significantly elevated the total lipid (p < 0.01) and bile acid content (p < 0.01) in feces, resulting in the enrichment of fat-degrading and bile-acid tolerant genera within the families Ruminococcaceae and Lachnospiraceae. Although increasing the PO intake also caused obesity in mice, it did not affect the microbial structure. When fat intake is constant, only at a high-fat level can PS (vs PO) induce the above-mentioned microbial shifts. These results highlighted the combined roles of lipid quality and quantity on the gut microbiota.


A family of repeated DNA sequences, one of which resides in the second intervening sequence of the mouse dihydrofolate reductase gene.
One member of a repeated sequence family has been found in the second intron of the mouse dihydrofolate reductase gene. The family consists of approximately 20 members/haploid genome, two of which have been sequenced and found to contain a 480-base pair region of homology with a significant amount of sequence divergence. Rat, Chinese hamster, Syrian hamster, and human DNAs contain homologous repetitious elements, and the four rodent species have a member of this family associated with the dihydrofolate reductase gene.


Effects of ultrasound-assisted slightly acidic electrolyzed water thawing on myofibrillar protein conformation and gel properties of chicken breasts.
The effects of air thawing, water thawing, slightly acidic electrolyzed water thawing, ultrasound-assisted water thawing (WUT) and ultrasound-assisted slightly acidic electrolyzed water thawing (EUT) on the myofibrillar protein conformation and gel quality of chicken breasts were investigated. In the EUT group, protein solubility was higher (52.43%) than other thawing groups, and particle size was 24.57% smaller than the control group. Gel of EUT and WUT groups had stronger elasticities than the control group. Gel whiteness level was not significantly different between the EUT and control group. Gel water holding capacity of the EUT group was 9.07% greater than the control group. Gel water distributions and mobilities of the EUT and WUT groups were closer to the control group. The gel of the EUT group had a compact and homogeneous network. In conclusion, EUT treatment effectively reduced conformation disruption and improved gel properties, which was conducive to producing gel products.


Mast cells and angiogenesis in multiple sclerosis.
Multiple sclerosis (MS) is an autoimmune disease, characterized by multiple demyelination of axons in both white and gray matter in the Central Nervous System (CNS). There is increasing evidence to support the notion that angiogenesis and chronic inflammation are mutually related. Different immune cells, including monocytes-macrophages, lymphocytes, neutrophils, mast cells (MCs) and dendritic cells are able to secrete an array of angiogenic cytokines, which promote growth, migration, and activation of endothelial cells. MCs play various roles in MS pathogenesis, influencing the innate immune response in peripheral tissues and in CNS. The aim of this review article is to discuss the role of MCs in MS pathogenesis with particular reference to the involvement of these inflammatory cells in the angiogenic processes occurring during MS.


The KROX-20 transcription factor in the rat central and peripheral nervous systems: novel expression pattern of an immediate early gene-encoded protein.
The KROX-20 protein (also termed EGR-2) is encoded by an immediate early gene cloned by cross-hybridization to the Drosophila melanogaster Krüppel gene. It belongs to a class of transcription factors with zinc finger motifs and binding activity to a transcriptional regulatory DNA element termed the early growth response consensus sequence. In the present study the temporospatial expression of KROX-20 was investigated in the central and peripheral nervous systems of normal rats and after various stimuli known to induce immediate early genes, including epileptic seizures, axotomy, pharmacological treatment with glutamate and alpha-adrenergic receptor antagonists, and peripheral noxious stimulation. Immunocytochemistry was performed with a specific polyclonal antiserum generated against a fusion protein containing KROX-20 sequences. In the central nervous system, KROX-20 protein demonstrated distinct constitutive nuclear expression in specific neuronal subpopulations of the cortex, septum, amygdala, olfactory bulb and hypothalamus. In addition, distinct cytoplasmic immunoreactivity was present in spinal and medullary motoneurons, dorsal root ganglion neurons and a few neuronal cell populations of midbrain and forebrain. In the CNS, KROX-20 was only induced by bicuculline-induced epileptic seizures. Topographically, the postictal increase of KROX-20 levels was restricted to areas with constitutive expression, such as cerebral cortex, fornix and amygdala. Induction of KROX-20 peaked at 4-8 h after onset of seizure activity. No increase in immunoreactivity was observed in the hippocampus, the brain region most severely affected by bicuculline-induced seizures. Transection of central and peripheral nerve fibers did not result in KROX-20 induction in axotomized neurons. However, KROX-20 was induced in Schwann-like cells after transection of the sciatic nerve. In contrast to KROX-20, KROX-24, a related transcription factor of the zinc finger family, was markedly induced in hippocampal and spinal neurons following seizures and peripheral noxious stimulation, respectively, as well as in CNS neurons following axotomy. Our data indicate that KROX-20 represents an immediately early gene product with basal expression in selected neuronal populations of the nervous system and a restricted inducibility after intentional stimuli.


Development and validation of the food allergy severity score.
The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10-6 -1.23 × 10-3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.


Hematological, biochemical, and biometric changes in Clarias gariepinus exposed to antipsychotic drug chlorpromazine.
Chlorpromazine (CPZ) is a neuroleptic and antipsychotic medication for individuals suffering from schizophrenia and other medical conditions. This study investigated the effects of CPZ on the hematological, biochemical, and biometric characteristics in juvenile Clarias gariepinus. The fish were exposed to 0.53, 1.06, and 2.11 mgL-1 CPZ for 15 days after which they were withdrawn from the toxicant and allowed to recover for 5 days. Blood were sampled from the fish on days 1, 5, 10, 15, and during the 5-day recovery for hematological and biochemical analysis, and thereafter, the fish were sacrificed for the morphometric analysis. While the values of the white blood cells significantly increased in the exposed fish, the hemoglobin, red blood cells, and packed cell volume decreased. Compared with the control, there were no significant differences in the values of the blood derivatives in the exposed fish. The values of protein and glucose reduced, but those of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly elevated. Though there was no significant difference in the condition factor, a significant increase in hepatosomatic index occurred on day 15 at 5.28 mg/L CPZ. After the 5-day withdrawal from the drug, most of the studied parameters returned to the control values. The present study indicated that CPZ is toxic to fish and should be used with utmost care to guard against toxicological effect on non-target organisms.


Does land use and land cover affect adult communities of Ephemeroptera, Plecoptera and Trichoptera (EPT)? A systematic review with meta-analysis.
We conducted a systematic review to better understand this gap and analyzed i) in which global regions are studies usually conducted, ii) the taxon studied, iii) sampling methods and iv) how authors collaborated in these studies. We also tested the relationship between different types of land use and land cover and adult EPT communities using a meta-analysis. We searched for relevant articles on the website Web of Science, using specific words related to the subject. We found 454 papers and selected 31 of them for the scientometric analysis, as they were in accordance with our objectives, and eight for the meta-analysis. Among this subset, we observed that study areas and collaborations among authors were largely restricted to a few countries in Europe and North America. Most studies used the group Trichoptera, probably due to its diversity and the longevity of the adults compared to other groups. Light traps were the most common sampling method, most likely due to their efficiency in capturing flying insects with nocturnal habits. The greatest differences in adult EPT communities were found between open areas (moorland and prairie) and forest areas. This result indicated that the conversion of forest habitats into open areas negatively impacts adult EPT communities. Our systematic review can be an important tool to help researchers choose appropriate collection methods and taxonomic groups to work with in studies on impacts of land use change on adult EPT communities.


The association between periodontal disease and peritonsillar infection: a prospective study.
To study the relationship between periodontal status and peritonsillar disease/recurrent tonsillitis. A total of 158 patients presenting over a 3-year period with peritonsillar abscess (PTA) confirmed by needle aspiration and a control group of 112 patients booked for elective tonsillectomy for recurrent tonsillitis (RT) were examined in terms of their periodontal status using the WHO Community Periodontal Index of Treatment Needs (CPITN). The mean CPITN index was 2.81 (Standard Deviation [SD], 1.10) in patients with PTA and 1.41 (SD, 0.92) in patients with RT. One hundred seven of 158 patients with PTA had significant periodontal pathology (CPITN, 3 or 4) compared with 12 of 112 patients with RT. These differences were statistically significant. Patients with peritonsillar abscess had an increased prevalence of periodontal disease as compared with patients with recurrent tonsillitis. There is a need to further explore this correlation and determine its nature, although it could be the result of common pathogenic factors, a causal relation cannot be excluded.


[Follow-up and evaluation of non-neurogenic OAB treatments].
The purpose of monitoring a patient treated for overactive bladder (OAB) is to ensure the effectiveness of the treatment and to detect any side effects. To synthesize current knowledge on the follow-up and the evaluation of non-neurogenic OAB treatments. A systematic literature review based on Pubmed, Embase, Google Scholar was conducted in June 2020. The definition of success of OAB treatments is not consensual. Definitions of success in clinical trials usually use bladder diary data. However, they cannot always be transposed into clinical practice because they do not measure the overall effectiveness of a treatment, reported by the patient, or the satisfaction with the treatment. It is then necessary to have symptom questionnaires with an assessment of quality of life. Indeed, the concept of therapeutic success is different depending on the view of the physician or the patient. It is therefore important to carefully assess with the patient, and before initiating any treatment, the objectives and expected results of the treatment. The definition of "refractory" OAB is heterogeneous but important to select candidates for second-line treatments. Monitoring a patient with OAB is essential to adapt the treatment to efficacy and tolerance, but also to detect any change in symptoms that may reveal another urological disease. The success or failure of OAB treatments depends on the interaction of many factors, including objective criteria measured by the clinician, and subjective criteria of perception of the treatment effectiveness by the patient.


Evidence for a cytochrome f-Rieske protein subcomplex in the cytochrome b6f system from spinach chloroplasts.
The cytochrome b6f complex of spinach chloroplasts was prepared with minor modification according to the method of E. Hurt and G. Hauska (1981) Eur. J. Biochem. 117, 591-599) replacing, however, the final ultracentrifugation step by hydroxyapatite chromatography as suggested by M. F. Doyle and C.-A Yu (1985) Biochem. Biophys. Res. Commun. 131, 700-706). The purified complex was partially dissociated by treatment with 4 M urea or 0.1% sodium dodecyl sulfate (SDS) in the absence of reducing agents. A binary subcomplex consisting of cytochrome f and the Rieske iron-sulfur protein was observed under these conditions by three different methods: (a) hydroxyapatite chromatography; (b) extraction with an isopropanol/water/trifluoroacetic acid mixture; and (c) gel filtration in the presence of low SDS concentrations. The subcomplex dissociated into its components by treatment with mercaptoethanol. These results suggest a close interaction of the cytochrome f with the Rieske protein involving SH groups which under reducing conditions leads to complete dissociation of the subcomplex.


One new species of Ptomaphaminus Perreau, 2000 (Coleoptera: Leiodidae: Cholevinae: Ptomaphagini) from a granitic subterranean environment in Vietnam.
Ptomaphaminus granophilus n. sp. from Vietnam is described and illustrated. The special subterranean biotope of this species, deep interstices in a granitic blockfield, is emphasized.


Synthesis and antiproliferative activity of 6BrCaQ-TPP conjugates for targeting the mitochondrial heat shock protein TRAP1.
A series of 6BrCaQ-Cn-TPP conjugates 3a-f and 5 was designed and synthesized as a novel class of TRAP1 inhibitors. Compound 3a displayed an excellent anti-proliferative activity with mean GI50 values at a nanomolar level in a diverse set of human cancer cells (GI50 = 0.008-0.30 μM) including MDA-MB231, HT-29, HCT-116, K562, and PC-3 cancer cell lines. Moreover, the best lead compound 6BrCaQ-C10-TPP induces a significant mitochondrial membrane disturbance combined to a regulation of HSP and partner protein levels as a first evidence that his mechanism of action involves the TRAP-1 mitochondrial Hsp90 machinery.


Unveiling the potential for an efficient use of nitrogen along the food supply and consumption chain.
Ensuring global food security is one of the challenges of our society. Nitrogen availability is key for food production, while contributing to different environmental impacts. This paper aims firstly to assess nitrogen flows and to highlight hotspots of inefficient use of nitrogen along the European food chain, excluding primary production. Secondly, it aims to analyse the potential for reducing the identified inefficiencies and increase nitrogen circularity. A baseline and three scenarios-reflecting waste targets reported in EU legislation and technological improvements- are analysed. Results highlighted a potential to reduce reactive nitrogen emissions up to more than 45%. However, this would imply the conversion of reactive nitrogen in molecular nitrogen, such as urea, before re-entering in the food chain. Techniques to harvest reactive nitrogen directly from urine and wastewater are considered promising to increase nitrogen use efficiency along the food chain.


Dilatation of the entire thoracic aorta in patients with bicuspid aortic valve: a magnetic resonance angiography study.
The presence of a bicuspid aortic valve (BAV) might be associated with a progressive dilatation of the aortic root and ascending aorta. However, involvement of the aortic arch and descending aorta has not yet been elucidated. Magnetic resonance angiography (MRA) was used to assess the diameter of the ascending aorta, aortic arch, and descending aorta in 28 patients with bicuspid aortic valves (mean age 30 +/- 9 years). Patients with BAV, but without significant aortic stenosis or regurgitation (n = 10, mean age 27 +/- 8 years, n.s. versus control) were compared with controls (n = 13, mean age 33 +/- 10 years). In the BAV-patients, aortic root diameter was 35.1 +/- 4.9 mm versus 28.9 +/- 4.8 mm in the control group (p < 0.01). The diameter of the ascending aorta was also significantly increased at the level of the pulmonary artery (35.5 +/-5.6 mm versus 27.0 +/- 4.8 mm, p < 0.001). BAV-patients with moderate or severe aortic regurgitation (n = 18, mean age 32 +/- 9 years, n.s. versus control) had a significant dilatation of the aortic root, ascending aorta at the level of the pulmonary artery (41.7 +/- 4.8 mm versus 27.0 +/- 4.8 mm in control patients, p < 0.001) and, furthermore, significantly increased diameters of the aortic arch (27.1 +/- 5.6 mm versus 21.5 +/- 1.8 mm, p < 0.01) and descending aorta (21.8 +/- 5.6 mm versus 17.0 +/- 5.6 mm, p < 0.01). The whole thoracic aorta is abnormally dilated in patients with BAV, particularly in patients with moderate/severe aortic regurgitation. The maximum dilatation occurs in the ascending aorta at the level of the pulmonary artery. Thus, we suggest evaluation of the entire thoracic aorta in patients with BAV.


Defining hypoxaemia from pulse oximeter measurements of oxygen saturation in well children at low altitude in Bangladesh: an observational study.
WHO defines hypoxaemia, a low peripheral arterial oxyhaemoglobin saturation (SpO2), as <90%. Although hypoxaemia is an important risk factor for mortality of children with respiratory infections, the optimal SpO2 threshold for defining hypoxaemia is uncertain in low-income and middle-income countries (LMICs). We derived a SpO2 threshold for hypoxaemia from well children in Bangladesh residing at low altitude. We prospectively enrolled well, children aged 3-35 months participating in a pneumococcal vaccine evaluation in Sylhet district, Bangladesh between June and August 2017. Trained health workers conducting community surveillance measured the SpO2 of children using a Masimo Rad-5 pulse oximeter with a wrap sensor. We used standard summary statistics to evaluate the SpO2 distribution, including whether the distribution differed by age or sex. We considered the 2.5th, 5th and 10th percentiles of SpO2 as possible lower thresholds for hypoxaemia. Our primary analytical sample included 1470 children (mean age 18.6±9.5 months). Median SpO2 was 98% (IQR 96%-99%), and the 2.5th, 5th and 10th percentile SpO2 was 91%, 92% and 94%. No child had a SpO2 <90%. Children 3-11 months had a lower median SpO2 (97%) than 12-23 months (98%) and 24-35 months (98%) (p=0.039). The SpO2 distribution did not differ by sex (p=0.959). A SpO2 threshold for hypoxaemia derived from the 2.5th, 5th or 10th percentile of well children is higher than <90%. If a higher threshold than <90% is adopted into LMIC care algorithms then decision-making using SpO2 must also consider the child's clinical status to minimise misclassification of well children as hypoxaemic. Younger children in lower altitude LMICs may require a different threshold for hypoxaemia than older children. Evaluating the mortality risk of sick children using higher SpO2 thresholds for hypoxaemia is a key next step.


A phase 1 trial of PfCP2.9: an AMA1/MSP1 chimeric recombinant protein vaccine for Plasmodium falciparum malaria.
Apical Membrane Antigen 1 (AMA1) and Merozoite Surface Protein 1 (MSP1) were produced as a recombinant fusion protein and formulated with the adjuvant Montanide ISA 720 with the aim of replicating the structure present in the parasite protein. A previous trial with this construct demonstrated the vaccine was safe and immunogenic but was associated with injection site reactogenicity. This Phase 1a dose-escalating, double blind, randomized, controlled trial of PfCP2.9/Montanide ISA 720 was conducted to evaluate alternative dose levels and vaccination schedules, with a pre-formulated vaccine that had undergone more in-depth and frequent quality control and stability analysis. The trial was conducted in seventy healthy Chinese malaria-naïve volunteers between January 2006 and January 2007. The objective was to assess the safety, reactogenicity and immunogenicity of 5, 20 and 50microg of PfCP2.9/ISA 720 under 2 different schedules. The most common adverse event was injection site tenderness (53%). The frequency and severity of adverse events was similar in both vaccination schedules. Antibody responses were induced and remained elevated throughout the study in volunteers receiving vaccine (p<0.001). Although high antibody titers as measured by ELISA to the PfCP2.9 immunogen were observed, biological function of these antibodies was not reflected by the in vitro inhibition of parasite growth, and there was limited recognition of fixed parasites in an immunofluorescence assay. At all three dose levels and both schedules, this formulation of PfCP2.9/ISA 720 is well tolerated, safe and immunogenic; however no functional activity against the parasite was observed.


Cross-sectional survey on Toxoplasma gondii infection in cattle, sheep and pigs in Serbia: seroprevalence and risk factors.
Toxoplasmosis is a globally distributed zoonosis with a clinical impact in the unborn fetus and in the immunosuppressed individual. In Serbia, studies of risk factors for Toxoplasma gondii infection in humans have shown that the relatively high prevalence is associated mainly with consumption of undercooked meat and/or meat products. However, data on T. gondii infection in domestic animals mostly used for human consumption are scarce. We thus conducted a cross-sectional survey on the seroprevalence of T. gondii infection in a representative sample of cattle, sheep and pigs from different regions of Serbia between June 2002 and June 2003, and analyzed the main risk factors associated with the infection. Sera from 611 cattle (yearlings and adults of both sexes), 511 ewes, and 605 pigs (market-weight and sows), were examined for T. gondii antibodies by the modified agglutination test. The seroprevalences determined were 76.3% in cattle, 84.5% in sheep and 28.9% in pigs. The antibody levels ranged from 1:25 to 1:400 in cattle, and up to 1:25,600 in sheep and to 1:12,800 in pigs. Among the seropositive, the proportion of high antibody levels (> or =1:1600), suggestive of acute infection, was 10% in sheep, and 4% in pigs. Possible association of the infection with biologically plausible risk factors including gender, age, herd size/farm type, type of housing, feeding practices and region, was analyzed by univariate analysis, and variables significant at P< or =0.1 were included in multivariate logistic regression models. The results showed that risk factors for cattle were small herd size (odds ratio, OR=2.19, 95% confidence interval, CI=1.28-3.75, P=0.004) and farm location in Western Serbia (OR=2.04, 95% CI=1.10-3.79, P=0.024), while housing in stables with access to outside pens was protective (OR=0.37, 95% CI=0.21-0.67, P=0.001). In sheep, an increased risk of infection was found in ewes from state-owned flocks (OR=4.18, 95% CI=2.18-8.00, P<0.001) vs. private flocks, and, interestingly, also in those from Western Serbia (OR=4.66, 95% CI=1.18-18.32, P=0.028). In pigs, the risk of infection was highly increased in adult animals (OR=3.87, 95% CI=2.6-5.76, P<0.001), as well as in those from finishing type farms (OR=3.96, 95% CI=1.97-7.94, P<0.001). In addition to providing data on the current T. gondii seroprevalence in meat animals in Serbia, the results of this study show the main risk factors associated with infection, thereby pointing to the type of preventive measures to reduce T. gondii infection.


Prognostic and biological function value of OSBPL3 in colorectal cancer analyzed by multi-omic data analysis.
Colorectal cancer (CRC) is one of the most common malignancies in the world. This study proposes to reveal prognostic biomarkers for the prognosis and treatment of CRC patients. Differential analysis of OSBPL3 was performed in pan-cancer, and the correlation between clinical stage and OSBPL3 was analyzed. Multiple omics analysis was used to compare the relationship between survival of patients and copy number variation, single nucleotide variant, and methylation status. Survival differences between high and low OSBPL3 expression groups were analyzed. Differentially expressed genes (DEGs) between high and low OSBPL3 expression groups were obtained, and functional enrichment analysis was implemented. Correlations between immune cells and OSBPL3 was analyzed. Drug sensitivity between the two OSBPL3 expression groups was compared. Moreover, the expression of OSBPL3 was verified by immunohistochemistry and real-time quantitative PCR. OSBPL3 was differentially expressed in 13 tumors and had some correlations with T and N stages. OSBPL3 expression was regulated by methylation and higher OSBPL3 expression was associated with poorer prognosis in CRC. 128 DEGs were obtained and they were mainly involved in signaling receptor activator activity, aspartate and glutamate metabolism. T cell gamma delta and T cell follicular helper were significantly different in the high and low OSBPL3 expression groups. Moreover, OSBPL3 showed negative correlations with multiple drugs. OSBPL3 was significantly upregulated in CRC samples compared to normal samples. A comprehensive analysis demonstrated that OSBPL3 had potential prognostic value, and guiding significance for CRC chemotherapeutic.


The Landscape of Tumor Fusion Neoantigens: A Pan-Cancer Analysis.
Compared with SNV&indel-based neoantigens, fusion-based neoantigens are not well characterized. In the present study, we performed a comprehensive analysis of the landscape of tumor fusion neoantigens in cancer and proposed a score scheme to quantitatively assess their immunogenic potentials. By analyzing three large-scale tumor datasets, we demonstrated that (1) the tumor fusion candidate neoantigen burden is not related to the immunotherapy outcome; (2) fusion neoantigens tend to have notably higher immunogenic potentials than SNV&indel-based candidate neoantigens, making them better candidates for cancer vaccines; (3) fusion candidate neoantigens distribute sparsely between individual patients. Although several recurrent candidate neoantigens exist, they usually have extremely low immunogenic potentials, suggesting that vaccination-based cancer immunotherapy must be personalized; (4) compared with fusion mutations involving tumor passenger genes, fusion mutations involving oncogenic genes have remarkably low immunogenic potentials, indicating that they undergo selection pressure during tumorigenesis.


Formation of imine derivatives between tris(hydroxymethyl)-aminomethane and saturated 3-oxo steroids during conventional work up of biological samples dissolved in Tris-HCl buffers.
Extraction with organic solvents of Tris-HCl buffer solutions containing microgram amounts of saturated 3-oxo-steroids, followed by evaporation of the organic solvent, produce a condensation product identified as the Tris-3-imino-derivative of the steroid. The yields range between 20-40%. The conditions governing the formation of the derivatives have been explored.


Quinidine-induced hemolytic anemia: immunohematologic characterization.
A 40-year-old white male with quinidine induced hemolytic anemia but no thrombocytopenia is described. Hemolysis was extravascular in nature and via the immune-complex mechanism. The quinidine antibody was an IgG immunoglobulin that did not activate complement.


Prediction of the distribution volumes of cefazolin and tobramycin in obese children based on physiological pharmacokinetic concepts.
So as to estimate the appropriate dose of antibacterial drugs in obese children, prediction of the volume of distribution in these children was attempted based on physiological pharmacokinetic concepts which had been constructed from results in normal-weight children. Serum concentration-time data after intravenous drip infusions of tobramycin and cefazolin were analyzed using noncompartmental analysis of obese children in whom the degree of obesity ranged from 30 to 80%. Volume of distribution at steady state (Vss) per total body weight of tobramycin was significantly less than that for normal-weight children (P less than 0.05), whereas the value of cefazolin was almost equal to that for normal-weight children. The equation to express the difference of Vss between cefazolin and tobramycin obtained in normal-weight children failed in obese children, suggesting that there is a large decrease in the extracellular space in obese children exceeding the interindividual variations in normal-weight children. The Vss value (liter) for tobramycin was predicted by using the equation 0.261 . (ideal body weight (kg) + 0.4 . [total body weight (kg) - ideal body weight (kg)]). The Vss value of cefazolin was predicted to be 0.3 . (predicted Vss of tobramycin) + 0.052 . total body weight (kg). A good correlation between the predicted and the observed Vss values was obtained.


Abnormal glucose metabolism in Hispanic parents of children with acanthosis nigricans.
Objective. Assess the prevalence of abnormal glucose metabolism among Hispanic parents of children with acanthosis nigricans (AN). Methods. Hispanic families (n = 258) were evaluated for metabolic and anthropometric parameters including fasting glucose levels and AN status. Results. Mothers with AN+ children had IFG (17.3%) and 4% had glucose levels ≥126 mg/dL (P = 0.028) compared to 7.1% and 1.8% of mothers with AN- children, respectively. Mothers of AN+ children also had greater odds of having impaired fasting glucose levels (OR: 3.917, 95% CI: 1.475-10.404; P < 0.004) but this was not the case for fathers (OR: 1.125, 95% CI: 0.489-2.586; P = 0.781). Mothers of AN+ children were also more likely to be AN+ (OR: 5.76, 95% CI: 2.98-11.13, P < 0.001). Screening discovered glucose levels >126 mg/dL in 9% of fathers with AN+ children. Conclusions. Hispanic mothers of AN+ children are at higher risk of carbohydrate metabolism abnormalities. AN in children can be a marker for prevention and delay programs aimed at identifying adults at risk for diabetes.


The christian religious education teachers' attitudes toward the five-stage lesson plan framework in Kenya: A gender-based analysis.
New approaches have emerged in teaching Christian Religious Education (CRE). Five-stage lesson plan framework (FSLP) is one of the innovative approaches applicable in all learning areas. Even though the framework is learner-oriented, understanding teachers' attitudes towards the framework are essential. Developing a positive attitude among the stakeholders remains crucial in implementing any teaching approach. Therefore, this study assessed gender differences in the attitude toward the five-stage lesson plan framework among CRE teachers in Meru County, Kenya. A multi-stage sampling technique randomly selected 143 and 83 female and male CRE teachers. Using a semi-structured questionnaire, quantitative data were collected in a cross-sectional survey. Chi-square and t-test statistics were applied to test the statistical significance of the dummy and mean value of continuous variables using sex-disaggregated data. The study revealed that teachers' attitudes towards the FSLP framework did not significantly differ between male and female teachers. The study employed multiple linear regression modeling to assess the determinants of the attitudes towards the five-stage lesson plan framework for male, female, and pooled teachers. Similar determinants influenced teachers' attitudes towards the FSLP framework: academic qualification, teaching experience, utilization, and awareness. Researchers established that educational qualification was a negative and significant determinant of attitudes towards the FSLP framework among the participants. Teaching experience, awareness, and utilization of the FSLP framework among CRE teachers were positive and significant determinants of the attitudes towards the FSLP framework. The study findings implied development of policies inclined to the attitudes supporting the proper implementation of newly emerged teaching strategies among the stakeholders. The supplement schemes should be restructured and shaped to meet teachers' specific needs and preferences regarding the utilization of educational innovations to enable CRE teachers to select and practice the FSLP framework.


Cell kinetics and immunoegenicity of lymphoma cells treated with 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DIC) in vivo.
A cycle of treatment with antineoplastic compounds may alter the immunologic properties of experimental tumors leading to an increased survival of syngeneic hosts as compared to that observed with the original parental tumors. However, a loss of growth potential in drug-treated tumors might account for this preferential rejection by syngeneic or by allogeneic animals. In the present study the cell cycle kinetics of parental (L1210 and L5178Y) and DIC-altered leukemic cells (L1210/DIC; L5178Y/DIC) has been evaluated by the establishment of labelled mitosis curves. The in vitro DNA synthesis and cell loss were also investigated. The experimental results indicate that no significant differences in the above properties were present for parental and corresponding drug-treated leukemic sublines. Immuno-depressed allogeneic mice were more resistant to lymphoma challenge when inoculated with the DIC-sublines than with the parental lines. On adoptive transfer of immune lymphocytes there was increased survival of allogeneic animals challenged with DIC cells, attributable to an additional immune response to DIC-induced antigens. Thus, parental or DIC-tumors showed similar tumorigenic characteristics, and the increased allogeneic host survival to DIC-cell challenge may be attributed to an additional immune response of the animal DIC-induced antigens.


Global trends and prospects in microplastics research: A bibliometric analysis.
Microplastic pollution is a global enviromental issues. This is the first time in recent decades that quantitative and qualitative evidence from bibliometrics and Altmetric has been used to conduct an in-depth statistical analysis of global microplastics research knowledge and demonstrate research progress, trends and hotspots. We comprehensively searched the Web of Science Core Collection scientific database from its inception (1986) to September 21, 2019. The study shown that the number of papers on microplastics has increased significantly since 2011. Worldwide, researchers in the field come mostly from Western Europe, mainly spread in the UK, Netherlands and Belgium. With the exception of China, the contribution of developing countries was very limited. Moreover, this study systematically elaborated the hotspots in this field (especially in ecological toxicity and human health risks). The results shown that research on marine systems and marine plankton is still dominant. Since human beings are the ultimate consumers of the food chain, microplastics may have potential effects on the human respiratory system and gastrointestinal tract. Towards that end, some topics and perspectives are noted that could indicate the current scientific hotspots and guide future research directions.


Low level of c-kit expression marks deeply quiescent murine hematopoietic stem cells.
Although c-kit is expressed highly on murine hematopoietic stem cells (HSCs) and essential for bone marrow (BM) hematopoiesis, the significance of the high level of expression of c-kit on HSCs was not well determined. We show here that CD150(+) CD48(-) Lineage(-) Sca-1(+) c-kit(+) HSCs in adult BM are distributed within the range of roughly a 20-fold difference in the expression level of c-kit, and that c-kit density correlates with the cycling status of the HSC population. This predisposition is more evident in the BM of mice older than 30 weeks. The HSCs in G(0) phase express a lower level of c-kit both on the cell surface and inside the cells, which cannot be explained by ligand receptor binding and internalization. It is more likely that the low level of c-kit expression is a unique property of HSCs in G(0). Despite functional differences in the c-kit gradient, the HSCs are uniformly hypoxic and accessible to blood perfusion. Therefore, our data indicate the possibility that the hypoxic state of the HSCs is actively regulated, rather than them being passively hypoxic through a simple anatomical isolation from the circulation.


Overexpression of cyclin D1 and cdk4 in tumorigenesis of sporadic hepatoblastomas.
Abnormality of the cyclin D1/cdk4/p16INK4a/pRb pathway during tumorigenesis has recently been reported. Hepatoblastoma is a rare malignant liver tumor of childhood, but underlying abnormalities of cell-cycle regulating protein remain to be elucidated. The expression of cyclin D1, cdk4, p16 and retinoblastoma gene product (pRb) was studied by immunohistochemistry in 17 paraffin-embedded tissues consisting of both tumor and corresponding non-neoplastic tissues. Tumor tissues showed overexpression of cyclin D1 (13/17, 76%) and cdk4 (15/17, 88%). Eleven cases showed co-overexpression of both cyclin D1 and cdk4. No abnormal p16 or pRb expression was noted. In the group with a high score (+4) for cyclin D1 expression, a positive correlation with tumor recurrence was noted (P = 0.043). These data suggest that overexpressed cyclin D1 and cdk4 protein might play an important role in the tumorigenesis of hepatoblastoma and that in the group with high cyclin D1 expression, tumor recurrence may be more frequent.


ADPGK-AS1 long noncoding RNA switches macrophage metabolic and phenotypic state to promote lung cancer growth.
Long noncoding RNAs (lncRNAs) influence the transcription of gene networks in many cell types, but their role in tumor-associated macrophages (TAMs) is still largely unknown. We found that the lncRNA ADPGK-AS1 was substantially upregulated in artificially induced M2-like human macrophages, macrophages exposed to lung cancer cells in vitro, and TAMs from human lung cancer tissue. ADPGK-AS1 is partly located within mitochondria and binds to the mitochondrial ribosomal protein MRPL35. Overexpression of ADPGK-AS1 in macrophages upregulates the tricarboxylic acid cycle and promotes mitochondrial fission, suggesting a phenotypic switch toward an M2-like, tumor-promoting cytokine release profile. Macrophage-specific knockdown of ADPGK-AS1 induces a metabolic and phenotypic switch (as judged by cytokine profile and production of reactive oxygen species) to a pro-inflammatory tumor-suppressive M1-like state, inhibiting lung tumor growth in vitro in tumor cell-macrophage cocultures, ex vivo in human tumor precision-cut lung slices, and in vivo in mice. Silencing ADPGK-AS1 in TAMs may thus offer a novel therapeutic strategy for lung cancer.


Lower incidence of biliary carcinoma in patients with primary sclerosing cholangitis and high serum levels of immunoglobulin E.
High serum levels of immunoglobulin (Ig)E often are detected in patients with primary sclerosing cholangitis (PSC), but the clinical significance is not known. We analyzed data from 44 patients with PSC and known serum levels of IgE. They were divided into groups called high IgE (>170 IU/mL; n = 17) or normal IgE (n = 27). We compared occurrence of biliary carcinoma including cholangiocellular and gallbladder carcinoma, liver transplantation, and death between groups. The high IgE group had a later age of onset of PSC than the normal IgE group (54 ± 20 y vs 39 ± 16 y; P = .010); they also had a higher serum level of IgG (2078 ± 638 vs 1517 ± 475 mg/dL; P = .002) and IgG4 (104 ± 102 vs 38 ± 16 mg/dL; P = .002). Association with inflammatory bowel disease did not differ significantly between groups (5 of 17 vs 11 of 27; P = .661). No patient had biliary carcinoma in the high IgE group, but biliary carcinoma was observed during the follow-up period in 8 patients in the normal IgE group (0 of 17 vs 8 of 27; P = .016). The occurrence of biliary carcinoma, liver transplantation, or death did not differ between groups (4 of 17 vs 13 of 27; P = .124). High serum levels of IgE often are observed in older patients with PSC and are associated with a reduced incidence of biliary carcinoma.


Threshold vision under full-field stimulation: Revisiting the minimum number of quanta necessary to evoke a visual sensation.
At the absolute threshold of vision, Hecht, Shlaer and Pirenne estimate that 5-14 photons are absorbed within a retinal area containing ~500 rods. Other estimates of scotopic threshold vision based on stimuli with different durations and focal areas range up to ~100,000 photons. Given that rod density varies with retinal eccentricity and the magnitude of the intrinsic noise increases with increasing stimulus area and duration, here we determine whether the scotopic threshold estimates with focal stimuli can be extended to full-field stimulation and whether summation explains inter-study differences. We show that full-field threshold vision (~1018 mm2, 10 ms duration) is more sensitive than at absolute threshold, requiring the absorption of ~1000 photons across ~91.96 million rods. A summation model is presented integrating our and published data and using a nominal exposure duration, criterion frequency of seeing, rod density, and retinal area that largely explains the inter-study differences and allows estimation of rods per photon ratio for any stimulus size and duration. The highest signal to noise ratio is defined by a peak rod convergence estimated at 53:4:1:2 (rods:rod bipolar cells:AII amacrine cells:retinal ganglion cells), in line with macaque anatomical estimates that show AII amacrine cells form the bottleneck in the rod pathway to set the scotopic visual limit. Our model estimations that the rods per photon ratio under full-field stimulation is ~3000X higher than at absolute threshold are in accordance with visual summation effects and provide an alternative approach for understanding the limits of scotopic vision.


Pseudoprogression prediction in high grade primary CNS tumors by use of radiomics.
Our aim is to define the capabilities of radiomics and machine learning in predicting pseudoprogression development from pre-treatment MR images in a patient cohort diagnosed with high grade gliomas. In this retrospective analysis, we analysed 131 patients with high grade gliomas. Segmentation of the contrast enhancing parts of the tumor before administration of radio-chemotherapy was semi-automatically performed using the 3D Slicer open-source software platform (version 4.10) on T1 post contrast MR images. Imaging data was split into training data, test data and an independent validation sample at random. We extracted a total of 107 radiomic features by hand-delineated regions of interest (ROI). Feature selection and model construction were performed using Generalized Boosted Regression Models (GBM). 131 patients were included, of which 64 patients had a histopathologically proven progressive disease and 67 were diagnosed with mixed or pure pseudoprogression after initial treatment. Our Radiomics approach is able to predict the occurrence of pseudoprogression with an AUC, mean sensitivity, mean specificity and mean accuracy of 91.49% [86.27%, 95.89%], 79.92% [73.08%, 87.55%], 88.61% [85.19%, 94.44%] and 84.35% [80.19%, 90.57%] in the full development group, 78.51% [75.27%, 82.46%], 66.26% [57.95%, 73.02%], 78.31% [70.48%, 84.19%] and 72.40% [68.06%, 76.85%] in the testing group and finally 72.87% [70.18%, 76.28%], 71.75% [62.29%, 75.00%], 80.00% [69.23%, 84.62%] and 76.04% [69.90%, 80.00%] in the independent validation sample, respectively. Our results indicate that radiomics is a promising tool to predict pseudo-progression, thus potentially allowing to reduce the use of biopsies and invasive histopathology.


Measuring school health center impact on access to and quality of primary care.
School health centers (SHC) that provide comprehensive health care may improve access and quality of care for students; however, published impact data are limited. We evaluated access and quality of health services at an urban high school with a SHC compared with a school without a SHC, using a quasiexperimental research design. Data were collected at the beginning of the school year, using a paper and pencil classroom questionnaire (n = 2,076 students). We measured SHC impact in several ways including grade by school interaction terms. Students at the SHC school were more likely to report having a regular healthcare provider, awareness of confidential services, support for health services in their school, and willingness to utilize those services. Students in the SHC school reported higher quality of care as measured by: respect for their health concerns, adequate time with the healthcare provider, understandable provider communications, and greater provider discussion at their last visit on topics such as sexual activity, birth control, emotions, future plans, diet, and exercise. Users of the SHC were also more likely to report higher quality of care, compared with either nonusers or students in the comparison school. Access to comprehensive health services via a SHC led to improved access to health care and improved quality of care. Impact was measureable on a school-wide basis but was greater among SHC users.


Effects of dissolved oxygen level on rapamycin production by pellet-form of Streptomyces hygroscopicus.
Rapamycin was known to have the functions of being an antibiotic and immunosuppressant; recently it was also recognized as being able to retard the aging process. The effects of dissolved oxygen (DO) level on rapamycin production by pellet-form of Streptomyces hygroscopicus were investigated in this study. The results suggest that a high DO level is required to enhance rapamycin production. However, the premise for getting a high rapamycin concentration by using DO control was keeping the intact of pellet-form of S. hygroscopicus. What if the high DO level achieved was coming from the increase of agitation; it might break down the morphology of pellets-form in the fermentation tank and result in the decrease of rapamycin production. The maximum rapamycin obtained in this study was about 780 mg/L in the 5 L fermentor batch with DO controlled over 30%, with the supplement of pure oxygen in the inlet gas, and the agitation speed limited to less than 200 rpm. Conclusively, a high DO level and the morphology of pellets form both were detrimental to achieving a high rapamycin production by S. hygroscopicus in the agitation fermentor.


The transition of the thick ascending limb of Henle's loop into the distal convoluted tubule in the nephron of the rat kidney.
Examination of serial semithin sections of rat kidney cortex and a subsequent electron microscopic study of selected areas revealed that the characteristic epithelium of the cortical part of the thick ascending limb of Henle extends for a varying distance beyond the macula densa. The transition from the relatively thin epithelium of the thick ascending limb at this site to the three--or even four--fold thicker epithelium of the convoluted part of the distal tubule is sharply defined and occurs without the interposition of an intermediate cell type. The position of the macula densa at the end but still clearly within the ascending limb of Henle's loop is functionally interpreted to guarantee the separation of the sensor point macula densa from disturbing influences which might arise from the secretory activity of the subsequent tubular portion.


Assessment of sagittal spinopelvic alignment in asymptomatic Chinese juveniles and adolescents: a large cohort study and comparative meta-analysis.
Retrospective study and comparative meta-analysis. To document the sagittal spinopelvic alignment in a large cohort study in asymptomatic Chinese juveniles and adolescents, and to explore whether these parameters were different from various regions using meta-analysis. Medical records of 656 asymptomatic Chinese juveniles and adolescents were reviewed, whose mean age was 13.14 ± 3.41 years old, including 254 male and 402 female volunteers. Demographic and lateral radiological parameters were evaluated. Furthermore, a systematic online search was performed to identify eligible studies. Weight mean difference (WMD) with 95% confidence interval (CI) were used to evaluate whether these sagittal parameters were different from various regions. The mean value of sagittal spinopelvic alignment in this study was calculated and analyzed respectively. Significant differences of PI (34.20 ± 4.00 vs. 43.18 ± 7.12, P < 0.001) and PT (3.99 ± 6.04 vs. 8.42 ± 7.08, P < 0.001) were found between juveniles and adolescents. A total of 17 studies were recruited for meta-analysis. For juvenile populations, TK, PI and SS of Caucasians were significantly larger than those of our study (all P < 0.001). As for adolescent populations, PI (P = 0.017), TK (P = 0.017) and SS (P < 0.001) of Caucasians was found to be greater when compared with that of our study. All in all, TK, PI and SS in Chinese pre-adult populations were significantly smaller than those populations in Caucasian regions (all P < 0.001). Our study was the first large-scale study that reported the mean values of sagittal parameters in asymptomatic Chinese juveniles and adolescents. There were significant differences in TK, PI and SS between our study and other previous reported populations, which reminded us for using specific mean values in different populations when restoring a relatively normal sagittal spinopelvic balance in spinal deformity.


Rapid titration of retroviral vectors using a β-lactamase protein fragment complementation assay.
The availability of rapid and quantitative titration assays for retroviral vectors is important, especially in the context of clinical applications. In this report, we describe a novel assay to titrate lentiviral and gamma retroviral vectors. This rapid assay is based on protein fragment complementation involving the N-terminal (Bla1) and the C-terminal (Bla2) fragments of TEM-1 β-lactamase (BLAK). The Bla1 protein fragment is incorporated in the vector's envelope during vector production. Bla1-bearing vectors are titrated on Bla2-expressing cells. Upon transduction, Bla1 and Bla2 heterodimerize and restore BLAK's enzymatic function. The enzymatic activity of BLAK is quantified by flow cytometry using the green fluorescent CCF2/AM substrate, which is converted into a blue fluorescent product. The enzymatic conversion of the CCF2/AM substrate was found to be directly related to vector entry, as a neutralizing antibody completely blocked the conversion. The titers obtained using this rapid assay correlated well with the titers measured by functional transduction assays. The whole assay can be finished within 8 h. Thus, it is considerably less time consuming compared with other transduction-based titration assays for lentiviral and gamma retroviral vectors.