The transcription regulator Lmo3 is required for the development of medial ganglionic eminence derived neurons in the external globus pallidus.
The external globus pallidus (GPe) is an essential component of the basal ganglia, a group of subcortical nuclei that are involved in control of action. Changes in the firing of GPe neurons are associated with both passive and active body movements. Aberrant activity of GPe neurons has been linked to motor symptoms of a variety of movement disorders, such as Parkinson's Disease, Huntington's disease and dystonia. Recent studies have helped delineate functionally distinct subtypes of GABAergic GPe projection neurons. However, not much is known about specific molecular mechanisms underlying the development of GPe neuronal subtypes. We show that the transcriptional regulator Lmo3 is required for the development of medial ganglionic eminence derived Nkx2.1+ and PV+ GPe neurons, but not lateral ganglionic eminence derived FoxP2+ neurons. As a consequence of the reduction in PV+ neurons, Lmo3-null mice have a reduced GPe input to the subthalamic nucleus.


Women Urologists: Changing Trends in the Workforce.
To characterize the current workforce of women urologists in the United States. An anonymous electronic survey was sent to all members of the Society of Women in Urology and all female non-Society of Women in Urology members of the American Urologic Association. The survey was distributed in January of 2015. Demographic, work, and personal life data were collected. Of 1563 e-mails with a link to our survey sent to women urologists in the United States, 365 surveys were completed for a 23% response rate. The average age of all participants was 39 years (range 25-73 years). Practicing women urologists had an average age of 44 years (range 32-65 years) compared to the average age (53 years) of all practicing urologists reported in the 2014 American Urologic Association Census. The majority of practicing female urologists live and work in a population of >1 million whereas a few live and work in rural areas. Practicing women urologists are most likely to work academic or group practice. Twenty percent of practicing women urologists reported working part-time, but almost 70% report working >50 hours/week. Women urologists in the United States are younger than their male counterparts and most work full-time in urban academic centers.


Brief Myocardial Ischemia Produces Cardiac Troponin I Release and Focal Myocyte Apoptosis in the Absence of Pathological Infarction in Swine.
In a porcine model of brief ischemia leading to reversible stunning in the absence of tissue necrosis, we demonstrated delayed release of cTnI that exceeded the 99th percentile for normals 60-minutes after reperfusion and rose to readily detectable levels 24-hours later. While tissue analysis at 60-minutes showed no evidence of infarction, TUNEL staining demonstrated isolated myocytes undergoing apoptosis, which was absent after 24-hours. These results demonstrate that cTnI elevations occur after ischemia of a duration that is insufficient to produce myocyte necrosis and reflect myocyte injury associated with delayed apoptosis in the absence of pathological evidence of infarction.


A giant cystic mesenchymal hamartoma of the liver: diagnosis, management, and study of cyst fluid.
A 21-yr-old West Indian woman with a giant hepatic cyst is reported. Preoperative investigations revealed that it was not a simple congenital cyst but that it was highly vascular. Studies of the cyst fluid obtained by percutaneous catheter drainage suggested that the epithelial lining was of bile duct origin. Fluid output was increased by secretin administration, but remained unchanged after amiloride. Bromsulphthalein did not enter the cyst fluid after intravenous injection. A hemihepatectomy was performed and the histologic appearances of the lesion were consistent with cystic mesenchymal hamartoma, a rare lesion in this age group. The patient is well 4.5 yr later.


Morphological effect of BiVO4 catalysts on degradation of aqueous paracetamol under visible light irradiation.
Morphological effect of bismuth vanadate (BiVO4) on visible light-driven catalytic degradation of aqueous paracetamol was carefully investigated using four monoclinic BiVO4 catalysts. The catalysts with different morphologies were controllably prepared by a hydrothermal method without any additions. The prepared catalysts were fully characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and UV-Vis diffuse reflectance spectroscopy (DRS). Under the visible light irradiation, these catalysts with different morphology were investigated to degrade aqueous paracetamol contaminant. The degradation effects were evaluated based on the catalyst morphology, solution pH, initial paracetamol concentration, and catalyst dosage. Cube-like BiVO4 powders exhibited excellent photocatalytic performance. The optimal photocatalytic performance of the cube-like BiVO4 in degrading paracetamol was achieved.


The Rendezvous Technique for Common Bile Duct Stones: A Meta-Analysis.
This article aimed to clarify the effectiveness and the efficiency of the rendezvous technique for patients with common bile duct stones. Four databases were searched on associations with rendezvous treatment. Six randomized controlled trials were evaluated for their success rate, stone clearance, morbidity, mortality, conversions, hospital stay, operating time, and hospitalization charges. This meta-analysis suggested no significant difference between the rendezvous group and the sequence group in the success rate and the stone clearance, but showed significant differences in the morbidity [odds ratio (OR)=0.54; 95% confidence intervals (CI), 0.30, 0.96], conversions (OR=0.40; 95% CI, 0.16, 0.97), the length of hospital stay (OR=-1.97; 95% CI, -2.29, -1.66), and the operating time (OR=12.95; 95% CI, 7.66, 18.24). The rendezvous technique is as effective as sequential endoscopic management for patients with common bile duct stones in its success rate and stone clearance, but the former is preferred in terms of morbidity, hospital stay, and hospitalization charges.


Disulfiram-loaded hollow copper sulfide nanoparticles show anti-tumor effects in preclinical models of colorectal cancer.
Colorectal cancer is one of the most common malignancies causing the majority of cancer-related deaths. There is an urgent need to develop new anticancer modalities. Recently, efforts have been made to turn clinically approved drugs into anticancer agents in specific tumor microenvironments via NPs. Disulfiram (DSF) as an effective copper (Cu2+)-dependent anti-tumour drug, which has been more widely used in antitumor research. Here, we constructed a novel therapeutic nanoplatforms, DSF@CuS, by encapsulating DSF in hollow CuS NPs to enable in situ chemoselective activation of DSF and hyperthermal amplified chemotherapy. The anticancer effect of DSF was enhanced by the thermal energy generated under NIR irradiation through the intrinsic photothermal conversion of CuS. As a result, significant apoptosis was induced in vitro, and tumor elimination was achieved in vivo. Collectively, DSF@CuS combined with photothermal therapy can significantly promote the apoptosis of CT26 colorectal cancer cells both in vitro and in vivo, providing a potential theoretical agent for the treatment of colorectal cancer.


Collagenases from human and rat skin fibroblasts purified on a zinc chelating column reveal marked differences in latency as a result of serum culture conditions.
1. Fibroblasts from both human and rat skin were grown in the presence or absence of serum and the collagenase activity in the medium was partially purified on zinc-Sepharose. 2. During chromatography, using a discontinuous elution gradient, the rat collagenase elutes at different pH and ionic strength than the human collagenase. Both latent and active collagenases of both species are retarded by the affinity matrix. 3. Latency of collagenase in media obtained from fibroblast cultures appears to be influenced by the presence of a serum component in the culture medium. 4. The results demonstrate that collagenases secreted by fibroblast cultures established from the same tissue but obtained from different species are biochemically diverse and that, within one species, the amount of active enzyme depends on the presence of a serum factor.


Quantification of PCR products by phosphate measurement.
Various techniques for quantification of PCR are available. Most frequently, the densitometric intensities of ethidium bromide-stained PCR products separated in gels are compared after normalizing to the levels of housekeeping gene products such as beta-actin. More precise, but extremely time consuming, is the technique of competitive PCR. Newer methods, such as tracking amplification in real-time, have high start-up and maintenance costs (e.g., TaqMan, Applied Biosystems; LightCycler, Roche; I-Cycler, Bio-Rad). Here, I describe an alternative, simple technique to quantify PCR products by determining the entire phosphate released during PCR. The method can be performed using common laboratory equipment, and the reagents needed are extremely cheap. The method is validated by measuring the induction of inducible nitric oxide synthase gene expression in cell culture and comparing the results with data obtained by LightCycler experiments and RNase protection assays.


Association between azathioprine therapy and lymphoma in rheumatoid disease.
Three out of 41 patients treated with azathioprine and low-dose corticosteroids from 1976 to 1983 developed non-Hodgkin's lymphoma. This strikingly high incidence of lymphoma may be a reflection of long-term use of azathioprine.


Association Between CT Angiogram Collaterals and CT Perfusion in Delayed Time Windows for Large Vessel Occlusion Ischemic Strokes.
Recent endovascular trials have established the use of CT perfusion (CTP) in endovascular treatment selection for patients with large vessel occlusions (LVO). However, the relationship between CTP and collateral circulation is unclear in delayed time windows. We explored the relationship between CT Angiogram (CTA) collaterals and CTP parameters in delayed time windows (6-24 hours). We utilized a single institutional, retrospective stroke registry of consecutive patients between May 2016 and May 2018 with anterior LVO with CTA and CTP imaging within 6-24 hours of stroke onset. We graded baseline collaterals on single phase CTA using modified Tan collateral score (0-3) and dichotomized into good (2-3) and poor (0-1) collaterals. We recorded automated CTP parameters, including estimated ischemic core (cerebral blood flow (CBF)<30%), penumbra (Tmax>6 s), and mismatch ratio. We used Mann-Whitney test and linear regression to assess associations. We included 48 patients with median age of 62 years (IQR= 52-72), median core of 17.5 mL (IQR=0-47), and median penumbra of 117.5 mL (IQR= 62-163.5). Patients with good collaterals had smaller median core (0 mL, IQR=0-12 mL vs. 40.5 mL, IQR=15-60 mL) (p < 0.001), smaller median penumbra (83.5 mL, IQR=43-135 mL vs. 142.5 mL, IQR=77-190 mL) (p = 0.04), larger median mismatch ratio (13.7, IQR=5.7-58.0 vs. 3.1, IQR=2.1-5.0) (p < 0.001), and lower median hypoperfusion intensity ratio (0.23, IQR=0-0.44 vs. 0.52, IQR=0.45-0.63) (p < 0.001) than patients with poor collaterals. In delayed time window LVO patients, good CTA collaterals are significantly associated with smaller CTP core, smaller penumbra, larger mismatch ratio, and lower hypoperfusion intensity ratio. CTA collateral assessment could be a potential valuable surrogate to perfusion imaging, particularly in stroke centers where CTP is unavailable.


PD-1/PD-L1 Blockade Therapy in Advanced Non-Small-Cell Lung Cancer: Current Status and Future Directions.
The use of immune checkpoint inhibitors (ICIs) has become one of the most promising approaches in the field of cancer therapy. Unlike the current therapies that target tumor cells, such as chemotherapy, radiotherapy, or targeted therapy, ICIs directly restore the exhausted host antitumor immune responses mediated by the tumors. Among multiple immune modulators identified, the programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) axis leading to the exhaustion of T-cell immunity in chronic infections and tumors has been widely investigated. Therefore, blocking antibodies targeting PD-1 or PD-L1 have been developed and approved for the treatment of various advanced cancers, including non-small-cell lung cancer (NSCLC), making them the most successful ICIs. Compared with chemotherapy or radiotherapy, PD-1/PD-L1 blockade therapy significantly improves the durable response rate and prolongs long-term survival with limited adverse effects in both monotherapy and combination therapy for advanced NSCLC. However, extensive challenges exist for further clinical applications, such as a small fraction of benefit population, primary and acquired resistance, the lack of predictive and prognostic biomarkers, and treatment-related adverse effects. In this article, we summarize the latest clinical applications of PD-1/PD-L1 blockade therapy in advanced NSCLC worldwide, as well as in China, and discuss the bottlenecks related to the use of this therapy in clinical practice. An exploration of the underlying mechanism of PD-1/PD-L1 blockade therapy and biomarker identification will maximize the application of ICIs in advanced NSCLC and facilitate bedside-to-bench studies in cancer immunotherapy as well. IMPLICATIONS FOR PRACTICE: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) display apparent benefits for the treatment of advanced non-small-cell lung cancer (NSCLC). However, the clinical applications of these therapies are challenged by the limited benefit population with additional high economic burden and adverse events. This review discusses the bottlenecks of ICI therapy in clinical practice and provides appropriate guidance in the development of predictive biomarkers, the establishment of the criteria for combining PD-1/PD-L1 blockade therapy with the existing therapies, and the management of adverse events observed both in monotherapy and combination therapy, which will help maximize the applications of ICIs in advanced NSCLC.


Vitamin B12 and bile acid metabolism in patients with partial iieal resection.
The vitamin B12 and bile acid metabolism was studied in 20 patients in whom a standardized Bricker procedure without irradiation was performed. No significant vitamin B12 malabsorption, steatorrhea, fecal bile acid loss or bile acid deconjugation was found. Therefore, no long-term adverse metabolic consequences of segmental preterminal ileal resection are to be expected in these patients.


Communication and its disorders.
This article defines communication and describes its various disorders. Some of these disorders are associated with other DSM-IV conditions, such as mental retardation or pervasive developmental disorder. Others are specific to the language-learning process. The interactions between communication and psychiatric disorders are discussed. Suggestions for integrating treating approaches among communication disorders and mental health professionals are presented.


Sphingosine 1-phosphate induced synthesis of glycocalyx on endothelial cells.
Sphingosine 1-phosphate (S1P) protects glycocalyx against shedding, playing important roles in endothelial functions. We previously found that glycocalyx on endothelial cells (ECs) was shed after plasma protein depletion. In the present study, we investigated the role of S1P on the recovery of glycocalyx, and tested whether it is mediated by phosphoinositide 3-kinase (PI3K) pathway. After depletion of plasma protein, ECs were treated with S1P for another 6h. And then, the major components of glycocalyx including syndecan-1 with attached heparan sulfate (HS) and chondroitin sulfate (CS) on endothelial cells were detected using confocal fluorescence microscopy. Role of PI3K in the S1P-induced synthesis of glycocalyx was confirmed by using the PI3K inhibitor (LY294002). Syndecan-1 with attached HS and CS were degraded with duration of plasma protein depletion. S1P induced recovery of syndecan-1 with attached HS and CS. The PI3K inhibitor LY294002 abolished the effect of S1P on recovery of glycocalyx. Thus, S1P induced synthesis of glycocalyx on endothelial cells and it is mediated by PI3K pathway.


Proestrous compared to diestrous wildtype, but not estrogen receptor beta knockout, mice have better performance in the spontaneous alternation and object recognition tasks and reduced anxiety-like behavior in the elevated plus and mirror maze.
17beta-Estradiol (E(2)) may influence cognitive and/or affective behavior in part via the beta isoform of the estrogen receptor (ERbeta). Endocrine status and behavior in cognitive (object recognition, T-maze), anxiety (open field, elevated plus maze, mirror maze, emergence), and motor/coordination (rotarod, activity chamber) tasks of proestrous and diestrous wildtype (WT) and ERbeta knockout (betaERKO) mice was examined. Proestrous (WT or betaERKO), versus diestrous, mice had higher E(2) and progestin levels in plasma, hippocampus, and cortex. The only effect of genotype on hormone levels was for corticosterone, such that betaERKO mice had higher concentrations of corticosterone than did WT mice. Proestrous WT, but not betaERKO, mice had improved performance in the object recognition (greater percentage of time with novel object) and T-maze tasks (greater percentage of spontaneous alternations) and less anxiety-like behavior in the plus maze (increased duration on open arms) and mirror chamber task (increased duration in mirror) than did diestrous mice. This pattern was not seen in the rotarod, open field, or activity monitor, suggesting effects may be specific to affective and cognitive behavior, rather than motor behavior/coordination. Thus, enhanced performance in cognitive tasks and anti-anxiety-like behavior of proestrous mice may require actions of ERbeta in the hippocampus and/or cortex.


An agent-based lattice model for the emergence of anti-microbial resistance.
This work introduces a new probabilistic agent-based lattice model for studying the emergence of anti-microbial resistance (AMR) and proposes a new proxy to measure it: the average death probability of the population under the action of the AMD. Both analytical studies and computer simulations of the microscopic behaviour of a bacterial culture interacting with anti-microbial drugs on a discrete lattice are carried out by focusing on the dynamics of this quantity. A unique genotype-phenotype map and classes of AMDs follow as emergent properties and their effects on the possible reversal of resistance are analysed. We also discuss briefly the possibility of using machine learning techniques to learn the model parameters.


Prospective evaluation of anticoagulant reversal with oral vitamin K1 while continuing warfarin therapy unchanged.
To study the efficacy and safety of partially correcting therapeutic anticoagulation by administering oral vitamin K1. Prospective interventional trial. Outpatient anticoagulation clinic. Patients who required reversal of their normal or excessive therapy with oral anticoagulant drugs were recruited. All patients received a single oral dose of vitamin K1. The dose was calculated using a regression formula and was intended to decrease the international normalized ratio (INR) to a predetermined value. Patient follow-up continued for 8 weeks. We compared the actual change of the INR to the predicted change. Sixty-five reversals of anticoagulant therapy were initiated in the study group. Sixty-four of the 65 reversals were successful. The mean (+/-SEM) initial INR was 2.6+/-0.1 for the preprocedure patients and 8.4+/-0.5 for the excessively anticoagulated patients. The predicted change in the INR correlated with the actual change (r = 0.92, p < 0.0001). There were no thromboembolic events and only one hemorrhagic complication. The mean (+/-SEM) dose of oral vitamin K1 was 5.0+/-0.3 mg for the preprocedure patients and 10.0+/-1.0 mg for the excessively anticoagulated patients. The administration of a single oral dose of vitamin K1 is a safe and effective method for partially reversing anticoagulant therapy without disrupting the daily maintenance dose of warfarin. A reliable regression formula was developed to predict the dose of vitamin K1 needed to achieve the desired INR.


Regulation of the relative abundances of mRNAs in hepatoma and liver.
Comparison of the polysomal poly(A)+ RNAs of normal rat liver and hepatoma (HTC) cells have shown that, while few sequences are specific to either hepatocytes or hepatoma cells, some of the abundant liver mRNAs (perhaps 20% by weight) are much rarer in the polysomal RNA from HTC cells. In contrast, these mRNA sequences are at quite similar abundances in nuclear poly(A)+ RNA from hepatocytes and hepatoma cells. The use of cloned cDNAs to measure the relative abundances of individual liver mRNA sequences in hepatocytes and HTC cells has shown that these changes occur in both directions, and indicated that post-transcriptional modulations, which are cell-type-specific and sequence-specific, play a significant role in establishing steady-state levels of polysomal poly(A)+ mRNAs. To investigate post-transcriptional regulation of mRNA abundance, a cell-free system consisting of isolated HTC-cell nuclei has been developed. This system supports the in vitro processing and/or transport of rRNA and a complex mixture of poly(A)+ RNA sequences which resembles polysomal poly(A)+ RNA from HTC cells. The pattern of relative abundances of the sequences in released poly(A)+ RNA is intermediate between that of polysomal and nuclear poly(A)+ RNAs, and indicates that some degree of sequence-specific selection of processing and/or transport is maintained in isolated nuclei. Sequence-specific selection of individual poly(A)+ RNA sequences in vitro has been detected with cloned cDNAs.


A previously unreported variation related to the insertion of the tibialis anterior muscle and the superficial fibular (peroneal) nerve.
During dissection classes in 2003 in the Department of Anatomy at Ege University Faculty of Medicine, an unexpected variation of the insertion of the tibialis anterior tendon was determined on the right side of a formalin-fixed cadaver of a 40-year-old man without any trace of scars, adhesions or signs of trauma or operation. The insertion of the tibialis anterior tendon was very abnormal, not on the medial side of the foot but on the lateral side. The tibialis anterior is an important muscle because of its function and use in tendon transfer as a treatment of recurrent congenital clubfoot and paralytic equinovarus foot deformities in cerebral palsy and arthroscopy, as discussed herein.


SARS-CoV-2 RNA and antibody dynamics in a Dutch household study with dense sampling frame.
This study investigated the dynamics of SARS-CoV-2 infection and diagnostics in 242 household members of different ages and with different symptom severity after SARS-CoV-2 exposure early in the pandemic (March-April 2020). Households with a SARS-CoV-2 confirmed positive case and at least one child in the Netherlands were followed for 6 weeks. Naso (NP)- and oropharyngeal (OP) swabs, oral fluid and feces specimens were analyzed for SARS-CoV-2 RNA and serum for SARS-CoV-2-specific antibodies. The dynamics of the presence of viral RNA and the serological response was modeled to determine the sampling time-frame and sample type with the highest sensitivity to confirm or reject a SARS-CoV-2 diagnosis. In children higher viral loads compared to adults were detected at symptom onset. Early in infection, higher viral loads were detected in NP and OP specimens, while RNA in especially feces were longer detectable. SARS-CoV-2-specific antibodies have 90% probability of detection from 7 days (total Ig) and 18 days (IgG) since symptom onset. For highest probability of detection in SARS-CoV-2 diagnostics early in infection, RT-PCR on NP and OP specimens are more sensitive than on oral fluid and feces. For SARS-CoV-2 diagnostics late after infection, RT-PCR on feces specimens and serology are more valuable.


Ontogeny and estrogen responsiveness of creatine kinase and glycolytic enzymes in brain and uterus of rat.
We have studied the postnatal ontogeny of creatine kinase (CK) and the glycolytic enzymes phosphoglycerate kinase (PGK), phosphoglycerate mutase (PGM), enolase (En), and pyruvate kinase (PK) in rat brain and uterus. In 30-day-old rat, brain and uterus express the fetal isoforms CK-B, PGK-A, PGM-B, En-alpha and PK-M2, and the differentiated isoforms En-gamma and PK-M1. The activity of glycolytic enzymes in uterus of two-day-old rat is as in brain, while CK activity is 3 times higher in brain. The activity of the glycolytic enzymes in brain began to increase (3-4-fold) 10 days after birth, in a coordinated manner. CK activity began to increase 5 days after birth in both brain (4.2-fold) and uterus (4.5-fold), suggesting the dissociation of glycolytic enzyme ontogeny from CK. In contrast to brain, the levels of glycolytic enzymes in uterus were highest at birth, suggesting the action of a tissue-specific mechanism for regulation of the constitutive levels of glycolytic isozymes. Except for PGM, all enzymes showed an increase in total activity, in response to estrogen, in uterus but not in whole brain.


A venom protein of ectoparasitoid Pachycrepoideus vindemiae, PvG6PDH, contributes to parasitism by inhibiting host glucose-6-phosphate metabolism.
To achieve successful development, female parasitoids, while laying eggs, introduce various virulence factors, mainly venoms, into host insects to manipulate their physiology. Although numerous studies have been conducted to characterize the components of venoms that regulate host immune responses, few systematic investigations have been conducted on the roles of venom proteins in host metabolic regulation. In this investigation, we characterized a novel venom protein in Pachycrepoideus vindemiae called glucose-6-phosphate dehydrogenase (PvG6PDH) and showed it has a vital role in regulating host carbohydrate metabolism. PvG6PDH encodes 510 amino acids and features a signal peptide and two conserved "G6PDH" domains. Multiple sequence alignment showed it has high amino acid identity with G6PDH from other pteromalids, and quantitative polymerase chain reaction analysis and immunofluorescent staining demonstrated a significantly higher expression of PvG6PDH in the venom apparatus compared with the carcass. We report that PvG6PDH contributes to parasitism by inhibiting the glucose-6-phosphate (G6P) metabolism of host Drosophila melanogaster, as demonstrated by PvG6PDH injection and RNA interference analysis. Further tests revealed that the accumulation of host G6P was caused by the transcriptional inhibition of G6P-metabolism-related genes. These findings greatly contribute to our understanding of venom-mediated host metabolic regulation, further laying the foundation for the development of venom proteins as biological agents for pest control.


The onset of faba bean farming in the Southern Levant.
Even though the faba bean (Vicia faba L.) is among the most ubiquitously cultivated crops, very little is known about its origins. Here, we report discoveries of charred faba beans from three adjacent Neolithic sites in the lower Galilee region, in the southern Levant, that offer new insights into the early history of this species. Biometric measurements, radiocarbon dating and stable carbon isotope analyses of the archaeological remains, supported by experiments on modern material, date the earliest farming of this crop to ~10,200 cal BP. The large quantity of faba beans found in these adjacent sites indicates intensive production of faba beans in the region that can only have been achieved by planting non-dormant seeds. Selection of mutant-non-dormant stock suggests that the domestication of the crop occurred as early as the 11(th) millennium cal BP. Plant domestication| Vicia faba L.| Pre-Pottery Neolithic B| radiocarbon dating| Δ(13)C analysis.


5-Lipoxygenase pharmacological blockade decreases tau phosphorylation in vivo: involvement of the cyclin-dependent kinase-5.
The 5-lipoxygenase (5LO) enzyme is widely distributed within the central nervous system. Previous works showed that this protein is upregulated in Alzheimer's disease, and that its genetic absence results in a reduction of amyloid beta levels in Tg2576 mice. However, its contribution to tau pathology remains to be investigated. To this end we studied the effect of 5LO chronic pharmacologic inhibition on endogenous tau level and metabolism in the same mice. The phosphorylation of tau at S396 and S396/404 in the brains of mice receiving zileuton, a selective and specific 5LO inhibitor, was significantly reduced when compared with their controls, while there was no significant change of tau phosphorylation at S202/T205, T231/S235, and T181 epitopes. The 5LO-dependent reduction of tau phosphorylation resulted from a significant decrease in the level and activity of the cyclin-dependent kinase-5 but not other kinases. Our findings highlight the novel functional role that neuronal 5LO plays in modulating tau phosphorylation, and suggest that pharmacologic inhibition of 5LO could provide a novel therapeutic opportunity also for Alzheimer's disease-related tau pathology.


Platelet aggregation and platelet-inhibiting drugs.
Platelet function may cause a progression of central gray matter damage after cerebrospinal hemorrhage or trauma because of the thrombotic occlusion of injured vessels or a vasospasm induced by extravasated blood. It has therefore been suggested that antiplatelet drugs could limit the extent of the neurological lesions produced by a spinal trauma. In view of this possibility, the hemostatic functions of platelets and the mechanism of action of antiplatelet drugs are briefly reviewed.


Malpositioned posterior chamber lenses: etiology, prevention, and management.
The various types of posterior chamber intraocular lens malpositions, in increasing degrees of severity, are described. These include pupillary capture, optic decentration, malpositioned loop, windshield wiper, sunrise, sunset and lost lens syndromes. The etiologies, management, and prevention of these complications are discussed.


Inorganic and Organic Carbon Uptake Processes and Their Connection to Microbial Diversity in Meso- and Bathypelagic Arctic Waters (Eastern Fram Strait).
The deep Arctic Ocean is increasingly vulnerable to climate change effects, yet our understanding of its microbial processes is limited. We collected samples from shelf waters, mesopelagic Atlantic Waters (AW) and bathypelagic Norwegian Sea Deep Waters (NSDW) in the eastern Fram Strait, along coast-to-offshore transects off Svalbard during boreal summer. We measured community respiration, heterotrophic carbon production (HCP), and dissolved inorganic carbon utilization (DICu) together with prokaryotic abundance, diversity, and metagenomic predictions. In deep samples, HCP was significantly faster in AW than in NSDW, while we observed no differences in DICu rates. Organic carbon uptake was higher than its inorganic counterpart, suggesting a major reliance of deep microbial Arctic communities on heterotrophic metabolism. Community structure and spatial distribution followed the hydrography of water masses. Distinct from other oceans, the most abundant OTU in our deep samples was represented by the archaeal MG-II. To address the potential biogeochemical role of each water mass-specific microbial community, as well as their link with the measured rates, PICRUSt-based predicted metagenomes were built. The results showed that pathways of auto- and heterotrophic carbon utilization differed between the deep water masses, although this was not reflected in measured DICu rates. Our findings provide new insights to understand microbial processes and diversity in the dark Arctic Ocean and to progress toward a better comprehension of the biogeochemical cycles and their trends in light of climate changes.


In-vivo rat striatal 5-HT4 receptor occupancy using non-radiolabelled SB207145.
The objective of the current investigation was to develop a simple, rapid method for determining in-vivo 5-hydroxytryptamine type 4 receptor (5-HT4 R) occupancy in rat brain using non-radiolabelled SB207145 as a tracer for accelerating the drug discovery process. In-vivo tracer optimization studies for tracer dose, survival intervals and brain distribution profile were carried out in rats. The tracer was pharmacologically validated using potent well-characterized 5-HT4 R ligands. The brain regional concentrations of tracer (SB207145); plasma and brain concentrations of 5-HT4 R ligands were quantified using high-performance liquid chromatography coupled with a tandem mass spectrometric detector (LC-MS/MS). SB207145 showed a higher specific binding in striatum (1.96 ng/g) and lower binding in cerebellum (0.66 ng/g), which is consistent with findings of other published 5-HT4 R expression studies. Pretreatment with potent 5-HT4 ligands dose-dependently reduced striatal SB207145 concentration and the effective dose to achieve 50% receptor occupancy (ED50 ) values were 4.8, 2.0, 7.4, 9.9, 3.8 and 0.02 mg/kg for GR113808, piboserod, prucalopride, RS67333, TD8954 and PF04995274, respectively. Results from the mass spectrometry approach to determine 5-HT4 R occupancy in rat brain are comparable with those reported using radiolabelled scintillation spectroscopy methods. In conclusion, the LC-MS/MS characterization permits use of tracer at a preclinical stage in high-throughput fashion as well as characterization of target expression.


Nonspecific inflammatory monoarthritis in the vicinity of bony metastases.
We describe a patient that presented with arthritis of a knee joint unresponsive to conventional treatment and who was found to have bony metastases of the distal femur from lung carcinoma. The presence of malignant cells could not be demonstrated in the synovial fluid or in the synovium. Our case illustrates the fact that malignant metastatic deposits in bone adjacent to a joint may cause a nonspecific synovial inflammation.


Immunological experimental arthritis in pigs. IV. Reaction of the synovial membrane of the non-immunized and immunized pigs after intraarticular administration of the virus of Aujeszky's disease.
7 days after intramuscular administration of the attenuated virus of Aujeszky's disease, strain TK 300 L, it was found: in non-immunized animals--immunological arthritis with fibrinoid necrosis and abundant infiltrations from lymphoid cells; in animals of low antibodies titer--only few infiltrations from lymphoid and plasmic cells round the sub-synovial vessels; in animals of high antibodies titer--vast areas of fibrinoid necrosis, abundant infiltrations from lymphoid cells and presence of gigantic cells.


Shifts in Social Determinants of Vitamin A Supplementation Among Children Under Five in Kenya, 2003-2014.
In Africa and Asia, 190 million preschoolers are vitamin A deficient. This study examined the social determinants of intake of vitamin A supplementation (VAS) among children aged 6-59 months during three different time periods in Kenya to identify those most vulnerable to vitamin A deficiency and highlight the varied targeting and outreach efforts; before the onset of a national restructuring and targeted distribution of VAS in children below 5 years through a twice-yearly door-to-door campaign called Child Health Weeks, during the implementation period, and several years later. The cross-sectional, national Demographic and Health Surveys were administered in Kenya in 2003, 2008-09, and 2014. Bivariate and multivariable logistic regression analyses were used to assess variables associated with VAS among children (n = 28,239). An overall two-fold increase in VAS was recorded between 2003 (31.8%) and 2014 (67.5%). In 2008-09, children aged 6-11 months were the most likely to receive VAS. In 2003 and 2014, geographical regions and settings, birth order of the child, educational level of the mother, religion, wealth index, number of antenatal visits, and access to a radio were identified as being significantly associated with VAS, in at least one of the years. These determinants were not significant in 2008-09 during the initial Child Health Weeks promotion campaign. The determinants of VAS varied during the three study periods, particularly in 2008-09 when the Child Health Weeks was first implemented. As efforts to increase VAS continue, addressing child-specific determinants will be essential to reduce health disparities.


What are students' needs and preferences for academic feedback in higher education? A systematic review.
Feedback is a fundamental factor within the learning process for students. However, it is widely known that students generally report that feedback is done sub-optimally in higher education. Therefore, this systematic review aims to identify students' needs and preferences for academic feedback in higher education. Design, data sources, review methods. A systematic review was conducted according to the PRISMA Statement Guidelines. Electronic databases were searched using a range of keywords and the findings were integrated in a narrative synthesis. Quality appraisal was undertaken. 5884 articles were retrieved, and 36 papers included. Three themes emerged across a wide range of academic disciplines which included: 1) preferences for feedback, 2) multimodality feedback and 3) emotional impact. Overall, quality feedback was related to the timeliness of feedback; balance between positive and constructive comments; direct feedback on content; linguistic clarity and legibility; grade justification and feeding forward. This review has informed several important implications for practice uniquely from the students' perspectives. Educators are encouraged to implement the evidence-based preferences for student feedback in their daily practice. Students value multimodality feedback which is personalised to enable students to feed forward in their own individual learning journeys. Future research should explore whether demographic variables influence student feedback needs over time. We would recommend that future studies need to employ a rigorous methodology to avoid the shortcomings in the studies already conducted in this area.


Machine learning-based protein signatures for differentiating hypertensive disorders of pregnancy.
Hypertensive disorders of pregnancy (HDP) result in major maternal and fetal complications. Our study aimed to find a panel of protein markers to identify HDP by applying machine-learning models. The study was conducted on a total of 133 samples, divided into four groups, healthy pregnancy (HP, n = 42), gestational hypertension (GH, n = 67), preeclampsia (PE, n = 9), and ante-partum eclampsia (APE, n = 15). Thirty circulatory protein markers were measured using Luminex multiplex immunoassay and ELISA. Significant markers were screened for potential predictive markers by both statistical and machine-learning approaches. Statistical analysis found seven markers such as sFlt-1, PlGF, endothelin-1(ET-1), basic-FGF, IL-4, eotaxin and RANTES to be altered significantly in disease groups compared to healthy pregnant. Support vector machine (SVM) learning model classified GH and HP with 11 markers (eotaxin, GM-CSF, IL-4, IL-6, IL-13, MCP-1, MIP-1α, MIP-1β, RANTES, ET-1, sFlt-1) and HDP with 13 markers (eotaxin, G-CSF, GM-CSF, IFN-gamma, IL-4, IL-5, IL-6, IL-13, MCP-1, MIP-1β, RANTES, ET-1, sFlt-1). While logistic regression (LR) model classified PE with 13 markers (basic FGF, IL-1β, IL-1ra, IL-7, IL-9, MIP-1β, RANTES, TNF-alpha, nitric oxide, superoxide dismutase, ET-1, PlGF, sFlt-1) and APE by 12 markers (eotaxin, basic-FGF, G-CSF, GM-CSF, IL-1β, IL-5, IL-8, IL-13, IL-17, PDGF-BB, RANTES, PlGF). These markers may be used to diagnose the progression of healthy pregnant to a hypertensive state. Future longitudinal studies with large number of samples are needed to validate these findings.


No Reliable Evidence That Emotional Disorders Are Proximal Antecedents, Concomitants, or Short-Term Consequences of First Episode Alcohol Use Disorders in a Representative Community Sample.
Emotional disorders and alcohol use disorders (AUDs) frequently demonstrate significant 12-month and lifetime comorbid associations. This comorbidity has been incorporated into influential theories of addiction processes that posit direct or indirect causal associations between these disorder categories. There is currently no consensus, however, about the sequencing of these disorders. In this research, longitudinal data from a regionally representative community sample were used to evaluate whether emotional disorders constitute a proximal antecedent, concomitant, or short-term consequence of first episode (or index) AUDs. Participants were 131 persons with index AUD episodes lasting 12 months or more and 131 matched controls. For each participant with an AUD, the presence or absence of an emotional disorder was coded for three time intervals: (a) the 12 months preceding full syndrome AUD episode onset; (b) the last 12 months of the AUD episode; and (c) the 12 months following complete symptom AUD episode offset. These intervals, referenced to participant age, were matched to those of control participants, and emotional disorder rate comparisons subsequently performed both within and between groups. Findings indicated an absence of significant within- or between-subject differences in emotional disorder rates, suggesting that the association between AUDs and emotional disorders is neither directional nor systematic. There was also no indication that the length of the AUD episode increased risk for an emotional disorder in the year following AUD offset. Overall, this research suggests that emotional disorders are generally independent events in relation to the index AUD episode.


Syntheses and characterization of copper complexes with the ligand 2-aminoethyl(2-pyridylmethyl)-1,2-ethanediamine (apme).
Copper(I)/(II) complexes with the ligand 2-aminoethyl(2-pyridylmethyl)1,2-ethanediamine (apme, abbreviated as PDT in the literature as well) were prepared and characterized. Crystal structures of the copper(I) complexes, [Cu2(apme)2]X2 (1, 2; X=ClO4, CF3SO3), showed that they are dinuclear, in contrast to the trigonal bipyramidal copper(II) complexes [Cu(apme)Cl]BPh4 (3) and [Cu(apme)(DMF)](BPh4)2 (4). 1 and 2 could be investigated in solution by NMR spectroscopy and 3 and 4 by cyclovoltammetry. From the results of these studies it is clear that in solution equilibria between the dinuclear complexes 1/2 and another species exist, most likely the monomeric [Cu(apme)CH3CN]+. Time-resolved UV/vis spectra at low temperatures allowed the spectroscopic detection of dioxygen adduct complexes as reactive intermediates during the oxidation of 1/2 with dioxygen that seem to play an important role in copper enzymes such as peptidylglycine-alpha-hydroxylating monooxygenase (PHM).


Biomechanical Comparison of Intramedullary Fibular Nail Versus Plate and Screw Fixation.
Clinical evidence has shown that percutaneous ankle fracture fixation using an intramedullary fibular nail results in good outcomes at 1 year and reduces postoperative wound complications in patients with vulnerable soft tissues. Confirmatory biomechanical evidence of its strength when used to secure a supination external rotation (SER) IV (AO/OTA 44B-type) fracture, compared with traditional plates and screws, is currently lacking. Twenty cadaveric lower limbs (10 cadavers) had a SER IV injury surgically created. One leg was randomly allocated to fixation with a fibular nail and the other a lag screw and neutralization plate. A mechanical testing apparatus subjected all lower limbs to an axially loaded supination external rotation force to failure. Superior ultimate torque to failure was demonstrated with a trend toward increased energy absorption in the nail group ( P = .28 and .07, respectively). No difference was demonstrated in angle at failure. All specimens in the plate group lost reduction at the bone-metal interface as a result of screw pullout. In contrast, all specimens in the nail group failed because of disruption of the lateral ligaments. This study demonstrated greater torque to failure and better maintenance of the fibular construct for the intramedullary fibular nail compared to standard plating. These results suggest that the previously documented clinical benefits of the fibular nail are complemented by biomechanical properties that compare favorably to standard techniques.


Fatty acid metabolism in fasting elephant seal pups.
The turnover of two plasma free fatty acids (FFA) were measured in 5 northern elephant seal pups (Mirounga angustirostris) after approximately 2 months of post-weaning fasting. Turnover was determined using simultaneous bolus injections of 14C-palmitate, 3H-oleate and Evans blue (EB) administered via an indwelling extradural intravertebral catheter. At this time in their natural fast, the seals exhibited plasma FFA levels and turnover values higher than reported for other marine mammals and most terrestrial carnivores. There was no consistent difference between plasma FFA turnover measured by palmitate or oleate tracers. The results imply that FFA metabolism is the primary source of energy during fasting. This is interesting in light of previous observations of minimal ketoacid accumulation and low levels of glucose and protein energy production during fasting in these juvenile seals.


A simple technique for multigraft cardioplegic infusion during coronary artery bypass.
The use of a Silastic four-armed cardioplegic infusion device during coronary artery bypass grafting, which has facilitated multidose cardioplegic infusion through the aorta and vein grafts, is described. The device also permits transaortic needle sump suction for decompression of the left ventricle. This device has been used effectively in more than 250 patients.


Synthesis of Highly Fluorinated Arene Complexes of [Rh(Chelating Phosphine)]+ Cations, and their use in Synthesis and Catalysis.
The synthesis of rhodium complexes with weakly binding highly fluorinated benzene ligands is described: 1,2,3-F3 C6 H3 , 1,2,3,4-F4 C6 H2 and 1,2,3,4,5-F5 C6 H are shown to bind with cationic [Rh(Cy2 P(CH2 )x PCy2 )]+ fragments (x=1, 2). Their structures and reactivity with alkenes, and use in catalysis for promoting the Tishchenko reaction of a simple aldehyde, are demonstrated. Key to the synthesis of these complexes is the highly concentrated reaction conditions and use of the [Al{OC(CF3 )3 }4 ]- anion.


Flat-Panel CT Imaging for Individualized Pitch Mapping in Cochlear Implant Users.
This study aims to identify electrode contact location and to assess frequency deviation between predicted and actual frequency allocation maps in cochlear implant (CI) users. This is a retrospective clinical study. Flat-panel computed tomography (FPCT) scans were collected for 17 CI users. Cochlear length was measured using three-dimensional curved multiplanar reconstruction on high-resolution secondary reconstructions. Each electrode's percentage of distance from the base of the helicotrema was measured, and a modified Greenwood's function was applied. The patients' frequency allocation maps were retrieved from electronic medical records and compared with their calculated characteristic frequencies. Our results revealed that reprogramming based on FPCT imaging findings might improve 83% (n = 216) of 260 electrode contacts. The most basal and apical electrodes (12, 11, 10, 5, 4, 3, 2, and 1) most consistently deviated (>83% of the time) from their theoretical characteristic frequencies; the basal electrodes undershot and the apical electrodes overshot their theoretical values. Frequency mismatch between the characteristic frequencies of auditory neurons and programmed center frequencies ranges from 0.41 to 1.51 in octave bands. Using FPCT imaging and a modified Greenwood's function, we identify a mathematical discrepancy between theoretical and actual CI placement with respect to frequency-place mapping. We demonstrate a clinically reproducible and direct assessment of frequency-place mismatch. Our individualized calculations account for inter-individual variability in cochlear lengths, operative differences in insertion depths, and electrode array kinking within the cochlea. The benefits of allocating electrode contact frequencies to their tonotopy-derived locations in the cochlea were not investigated in this study, and future prospective trials are needed to demonstrate the consequences of personalized pitch mapping for CI users with respect to speech and pitch perception.


Pentraxin 3 deficiency ameliorates the severity of osteoarthritis and alleviates inflammation.
Osteoarthritis is one of the most common degenerative joint disorders, characterized by articular cartilage breakdown, synovitis, osteophytes generation and subchondral bone sclerosis. Pentraxin 3 (PTX3) is a long pentraxin protein, secreted by immune cells, and PTX3 is identified to play a critical role in inflammation and macrophage polarization. However, the underlying mechanism of PTX3 in osteoarthritis under the circumstance of Ptx3-knockout (KO) mice model is still unknown. Murine destabilization of the medial meniscus (DMM) OA model was created in Ptx3-knockout (KO) and wildtype mice, respectively. The degenerative status of cartilage was detected by Safranin O, H&E staining, immunohistochemistry (IHC) and micro-CT. OARSI scoring was employed to assess the proteoglycan of cartilage. Serum inflammatory cytokines were examined by ELISA and systematic macrophage polarization in spleen was analyzed by flow cytometry. Safranin O and H&E staining confirmed that the joint cartilage was mostly with reduced degeneration in both the senior KO mice and the DMM model generated from the KO mice, compared to the WT group. This is also supported by micro-CT examination and OARSI scoring. Immunohistochemistry illustrated an up-regulation of Aggrecan and Collagen 2 and down-regulation of ADAMTS-5 and MMP13 in KO mice in comparison with the WT mice. ELISA indicated a dramatical decrease in the serum levels of TNF-α and IL-6 in KO mice. Polarization of M2-like macrophages was observed in the KO group. Pentraxin 3 deficiency significantly ameliorated the severity of osteoarthritis by preventing cartilage degeneration and alleviated systematic inflammation by inducing M2 polarization.


Isolation and gene expression analysis of a papain-type cysteine protease in thermogenic skunk cabbage (Symplocarpus renifolius).
Skunk cabbage (Symplocarpus renifolius) spadices contain abundant transcripts for cysteine protease (CP). From thermogenic spadices, we isolated SrCPA, a highly expressed CP gene that encoded a papain-type CP. SrCPA is structurally similar to other plant CPs, including the senescence-associated CPs found in aroids. The expression of SrCPA increased during floral development, and was observed in all floral tissues except for the stamens.


Stress orientations in subduction zones and the strength of subduction megathrust faults.
Subduction zone megathrust faults produce most of the world's largest earthquakes. Although the physical properties of these faults are difficult to observe directly, their frictional strength can be estimated indirectly by constraining the orientations of the stresses that act on them. A global investigation of stress orientations in subduction zones finds that the maximum compressive stress axis plunges systematically trenchward, consistently making an angle of 45° to 60° with respect to the subduction megathrust fault. These angles indicate that the megathrust fault is not substantially weaker than its surroundings. Together with several other lines of evidence, this implies that subduction zone megathrusts are weak faults in a low-stress environment. The deforming outer accretionary wedge may decouple the stress state along the megathrust from the constraints of the free surface.


Single nucleotide polymorphisms and type of steroid impact the functional response of the human glucocorticoid receptor.
Clinical trials evaluating the use of steroids in septic shock have shown variable outcomes. Our previous studies have implicated human glucocorticoid receptor (hGR) polymorphisms as a possible cause of altered steroid response. To further evaluate this variability, we hypothesized that hGR polymorphisms along with type of steroid influence the functional response. Total RNA was isolated from healthy human blood samples and surveyed for the hGR gene. The National Center for Biotechnology Information hGRα sequence was used as a reference, and two unique single nucleotide polymorphisms (SNPs) (A214G and T962C) were selected for evaluation. Functional response was measured using a luciferase reporting assay after transfecting hGR isoforms into tsA201 cells and stimulation with graded concentrations of hydrocortisone (HYD), methylprednisolone (MPS), and dexamethasone (DEX). Each isoform had a unique dose-response curve with the optimal activity depending on concentration and type of steroid. The presence of either SNP A214G or T962C resulted in a decreased response when compared with hGRα when stimulated with HYD (P < 0.01). The same decreased response occurred for the SNPs with DEX stimulation, but at a much lower concentration range than HYD (P < 0.01). However, in the presence of MPS, SNP A214G resulted in greater activity when compared with hGRα (P < 0.01), whereas the presence of T962C resulted in activity equivalent to hGRα. SNPs, type of steroid, and concentration range impact the functional response of the hGR. A greater understanding of hGR polymorphisms and steroid response may further elucidate mechanisms explaining the variable response seen with patient treatment.


Induction of tolerance in experimental autoimmune myasthenia gravis with solubilized MHC class II:acetylcholine receptor peptide complexes.
Stimulation of T lymphocytes through the T cell receptor in the absence of costimulatory signal(s) induces a state of unresponsiveness to subsequent antigen presentation. We have employed solubilized complexes consisting of rat class II MHC molecules containing an immunodominant peptide of the acetylcholine receptor (AChR alpha 100-116) to induce unresponsiveness in the autoreactive T lymphocytes mediating an animal model of myasthenia gravis. In vitro incubation of rat T cell lines specific for peptide AChR alpha 100-116 with solubilized complexes of MHC II and AChR alpha 100-116 (MHC II:AChR alpha 100-116) rendered the T cells unresponsive to subsequent stimulation by antigen presenting cells and the peptide. T cell lines with a broader specificity to the entire AChR protein pentamer had an 81% reduction in proliferation to AChR following a preincubation with solubilized MHC II:AChR alpha 100-116. Treatment with the solubilized MHC II:AChR alpha 100-116 induced phosphatidylinositol 4,5-bisphosphate hydrolysis, an early signalling event associated with binding to the TCR. Rats primed with AChR and injected intravenously with MHC II:AChR alpha 100-116 had reduced in vitro T cell proliferation to the AChR alpha 100-116 peptide and to whole AChR. Solubilized MHC II:AChR alpha 100-116 injected i.v. into rats exhibiting serological clinical symptoms of experimental autoimmune myasthenia gravis (EAMG) prevented death in 67% of the treated animals, compared to a 0-20% survival rate in all other control groups. These results demonstrate that solubilized MHC II complexed with an immunodominant autoantigenic peptide is tolerogenic and improves the survival rate of rats with EAMG, suggesting the basis for an antigen-specific therapy in autoimmune diseases such as MG.


Medical error theory.
Some errors in health care are inevitable because of human fallibility and system complexity. To improve patient safety we must develop three strategies. First, prevent errors with forcing functions, reducing complexity and providing reminders at the point of care. Second, everyone working in health care should be alert to identify and eliminate latent (potential) errors before patients are harmed. Finally, we must establish defensive barriers that will intercept those errors that still occur and prevent them from causing patient injury. Only in this way can health care fulfill its potential and significantly reduce iatrogenic harm.


Reversible CSF cyst related to a functioning ventriculo-peritoneal shunt.
Although the occurrence of CSF oedema and cyst has been described in presence of a blocked ventriculoperitoneal shunt, especially distal end block, its occurrence in presence of a well functioning shunt has not been described so far. We report a case where a 51-year old lady developed an insidious onset and gradually progressive CSF cyst without any clinical or radiological feature of shunt block over a period of about 2 years. The changes started about 6 months after a course of radiation therapy for an extensive residual supra and infratentorial meningioma. Following surgery, where the cyst was punctured and a new ventricular catheter was inserted, despite well functioning upper and lower end, the cyst gradually disappeared. We review the literature and hypothesize that the radiation-induced changes were responsible for initiation and progression of the cyst.


Educational diagnosis of patients under oral anticoagulant therapy: Development of a 4-category patient profiling score based on a retrospective study and prospective analysis.
Oral anticoagulants are used in numerous pathologies and their consumption is growing. However, to prevent their occurrence, their use should be supervised and the patients educated. Patients vary in understanding and compliance. Therefore, it seems necessary to standardize educational diagnosis with a patient profiling score to adapt therapeutic education to the individual patient profile. A retrospective study based on observation of consecutive patients treated by an oral anticoagulant therapy and involved in a therapeutic education program conducted between October 2014 and December 2015. A 12-item questionnaire distinguished 4 profiles based on the educational diagnosis. In a prospective double-blind study including consecutive patients with an indication to anticoagulants and admitted to the Internal Medicine department of the Louis-Mourier Hospital (AP-HP, University of Paris), the patient's profile defined by a clinician using the questionnaire was compared to the one defined by the Therapeutic Education Leader after standardized educational diagnosis. The questionnaire was tested prospectively in 53 patients, 26 of which had also a complete therapeutic education by the TEP leader. In any case, the assessment assisted by the questionnaire succeeded in identifying the patient profile, as determined by the therapeutic education specialist. The present questionnaire helps identify different patient profiles and therefore standardize educational diagnosis. The perspective is to adapt therapeutic education to individual patient profile, with the objective to improve compliance.


Coagulation testing in green iguanas (Iguana iguana) with development of prothrombin time assays using reptile and avian thromboplastin.
Captive reptiles often present with clinical signs suggestive of a clotting disorder or severe illness that can induce or exacerbate a coagulopathy. However, coagulopathies in reptiles are difficult to characterize due to lack of species-appropriate reagents to perform coagulation tests. The objective of this study was to develop screening tests to evaluate the extrinsic and common pathways of coagulation in green iguanas (Iguana iguana). Reptile and avian thromboplastin, extracted from reptile and avian brains, respectively, were used to initiate coagulation in prothrombin time (PT) assays and commercially available reagents were used to determine Russell's viper venom time, thrombin time, and fibrinogen using the Clauss method. Coagulation assays were performed on citrate-anticoagulated plasma from 18 healthy green iguanas. Results were summarized as median (minimum-maximum): PT (reptile thromboplastin), 34.8 seconds (27.1-42.1 s), PT (avian thromboplastin), 78.5 seconds (51.6-114.23 s), Russell's viper venom time, 56.15 seconds (18.4-79.7 s), thrombin time, 10 seconds (7.0-36.5 s), and fibrinogen, 258 mg/dl (89-563.0) (2.58 [0.89-5.63 g/L]). Commercial reagents can be used to evaluate the common pathway and fibrinogen; however, avian- or reptile-sourced thromboplastin is preferred for a reliable coagulation trigger to perform the PT assay and evaluate the extrinsic pathway.


Studies on the translocation characteristics of 13C-photoassimilates to fruit during the fruit development stage in 'Fuji' apple.
In order to define translocation characteristics of 13C-photoassimilates to fruit during the fruit development stage in 'Fuji' apple, the 13C labeled tracer method was used in whole five-year-old 'Fuji'3/M26/Malus hupehensis (Pamp.) Rehder apple trees at different days after flowering (DAF). The changes in 13C translocation to the fruit, source strength of the leaves, and sink strength of the fruits were assessed. The results indicated that the δ13C value and 13C distribution rate of the fruit increased first and then decreased with the increase in the fruit development period, being higher from 120 to 135 DAF. The leaves appeared to moderately senesce in an attempt to maintain high photosynthesis during 120-135 DAF, which promoted the outward transport of photoassimilates. The single fruit weight and longitudinal and transverse diameter of the fruit increased rapidly during 120-150 DAF, which increased the sink zone for the unloading of photoassimilates in the fruit. The activity of sorbitol dehydrogenase (SDH) and amylase (AM), the content of indole-3-acetic acid (IAA), the gibberellin (GA3) and abscisic acid (ABA) in the fruit flesh, and the gene expression levels of MdSOT1, MdSOT2, MdSOT3, MdSUT1, and MdSUT4 in the fruit stalk tissue were higher during 120-135 DAF. At this point, the difference in the sorbitol content between the fruit stalk and fruit flesh was also at the highest level of the entire year. These factors together increased the sink activity of the fruit, thus improving the photoassimilate transport efficiency to the fruit.


Effects of electrical stimulation of different frequencies on the myonuclei and fiber size in human muscle.
Male physical education students were subjected to electrical stimulation for a period of 21 days. The stimulation was performed with alternating currents of rectangular wave form. Group I was stimulated with a frequency of 50 Hz, group II with a frequency of 2000 Hz. Before and after the experimental period, biopsies were taken from the m. gastrocnemius. The muscle fiber size and the number and size of nuclei was estimated at the light microscopic level using stereological methods. The fiber size was significantly increased only in group I. The nuclear number and the nuclear size increased significantly in both groups leading to a higher nuclear volume per unit tissue volume. It was assumed that the proliferation of nuclei is correlated to satellite cell proliferation resulting probably in hypertrophy or hyperplasia of electrostimulated skeletal muscle.


Digital Phenotyping to Quantify Psychosocial Well-Being Trajectories After Spinal Cord Injury.
The aim of the study was to explore feasibility of smartphone-based digital phenotyping methods to examine depression and its relation to psychosocial well-being indicators after spinal cord injury. Smartphone research platform obtained smartphone sensor and survey data among community-living adult wheelchair users with spinal cord injury. Weekly measurements for 4 mos included Patient Health Questionnaire 8, Spinal Cord Injury-Quality of Life Satisfaction with and ability to participate in social roles and activities, global positioning system-derived community mobility metrics, health conditions, and physical activity. Forty-three individuals were enrolled. Study retention was higher among individuals offered financial incentives (78%) compared with participants enrolled before incentives (50%). Participants who dropped out more commonly had nontraumatic or acute spinal cord injury, were older, and had less satisfaction and lower participation in social roles and activities. Among 15 individuals with complete data, half had 1 wk or more of mild depression. Those with depression had frequent health issues, less satisfaction, and lower participation in social roles and activities. Those without depression experienced increased social engagement over time. Average community mobility was similar across depression groups. Relationships were typically in-phase but also varied by individual. Smartphone-based digital phenotyping of psychosocial well-being after spinal cord injury is feasible but not without attrition challenges. Individual differences in depression patterns highlight clinical utility of scaling these methods.


Genetic structure of a population of the fungus Leptosphaeria maculans in a disease nursery of Brassica napus in Australia.
Microsatellite, minisatellite and mating type markers were used to determine the genetic structure of the fungus Leptosphaeria maculans within a disease nursery, where Brassica napus lines were screened for resistance to blackleg disease under high inoculum pressure. Fungal isolates were collected from pseudothecia in infected stubble and pycnidia within cotyledon lesions on seedlings within the nursery. Genetic diversity was high with gene diversity at H=0.700 across four polymorphic loci, and genotypic diversity at D=0.993. Among the 159 isolates analysed, 102 multilocus genotypes were identified. The even distribution of mating type idiomorphs MAT1-1 and MAT1-2 and gametic equilibrium within the population provided further evidence of random mating. Genetic diversity was distributed on a very fine scale in the disease nursery. The majority of genetic diversity (67%) was distributed among conidia within a lesion or among ascospores from a piece of stubble, while the remainder (33%) was distributed within lesions on seedlings or different stubble pieces. There were no among-group differences between samples from stubble and seedlings. This is consistent with the low level of genetic differentiation between the ascospore and conidia samples (F (ST)=0.017) indicating that all isolates of L. maculans from the disease nursery most likely belong to one population, and that ascospores form the primary inoculum in the disease nursery.


HLA antigen distribution in different clinical subgroups demonstrates genetic heterogeneity in lichen planus.
HLA-A, B, Cw, DR and DQ antigens were serologically determined in 105 patients suffering from lichen planus (LP). Of these patients, 87 had idiopathic LP and 18 had secondary LP. In the first group, 43 had cutaneous LP without mucosal lesions, 17 had cutaneous LP with mucosal lesions and 27 had purely mucosal LP. No HLA antigen was found to be significantly associated with secondary LP or with mucosal idiopathic LP. In cutaneous idiopathic LP with or without mucosal lesions, the HLA-DR1 and DQ1 antigen frequency was significantly increased, and that of HLA-DQ3 significantly decreased. Among the HLA-DR1 cutaneous idiopathic LP patients, 78.5% carried the DRB1*0101 allele, and 21.4% the DRB1*0102 allele, compared with 35.7 and 67.8%, respectively, of the HLA-DR1 controls. Our data demonstrate that idiopathic LP is influenced by HLA-associated genetic susceptibility and resistance factors not involved in secondary LP, and that cutaneous idiopathic LP is a genetically and therefore pathogenetically different condition from purely mucosal idiopathic LP.


The endocrine pancreas of the fetus from diabetic pregnant rat.
Diabetes was induced in female rats by streptozotocin administration prior to mating. Pregnant rats were divided into "severe diabetics" (blood glucose concentration above 300 mg/100 ml) and "mild diabetics" (blood glucose ranging from 100 to 200 mg/100 ml). When compared to control fetuses, fetuses from severely diabetic mothers showed a slight decrease of body weight on days 20.5 and 21.5. Fetal pancreatic insulin stores and plasma insulin concentrations were decreased at 19.5, 20.5 and 21.5 days. The insulin response to glucose was impaired both in vivo and in vitro. In contrast, fetuses from mildly diabetic females showed no change in body weight. Pancreatic and plasma insulin concentrations were increased at 19.5, 20.5 and 21.5 days. The response of the beta cells of term fetuses of mild diabetics to glucose stimulation was enhanced in vitro. These results are consistent with the hyperglycaemia-hyperinsulinaemia theory with regard to the fetuses from mildly diabetic rats and with an impairment of insulin biosynthesis and release in fetuses from severely diabetic females.


Postpartum evaluation of stress urinary incontinence among primiparas.
To assess the prevalence of postpartum stress urinary incontinence (SUI); the relationship between postpartum SUI and mode of delivery; and the association between SUI and other obstetric factors. In this prospective study, 1000 primiparas with no history of UI were recruited and followed up for 4 months after delivery. The chi(2) and Fisher's Exact tests were used to calculate the effects of the nominal variables. The prevalence of postpartum SUI was 14.1%, and the mode of delivery was significantly associated with SUI. The prevalence rates were 15.9% after vaginal delivery, 10.7% after elective cesarean section (CS), and 25% after CS performed for obstructed labor. The prevalence of postpartum SUI was similar following spontaneous vaginal delivery and CS performed for obstructed labor (P=.21). Meanwhile, elective CS with no trial of labor was found to be associated with a significantly lower prevalence of postpartum SUI (P=.01; chi(2)=12.42). A maternal body mass index greater than 30 before pregnancy and fetal weight higher than 3000 g appeared to be associated with an increased rate of SUI (P=.001; chi(2)=17.6 and P=.000; chi(2)=22.5, respectively). Elective CS significantly reduced the rate of postpartum SUI.


An analysis of DPV and DIVE registry patients with chronic kidney disease according to the finerenone phase III clinical trial selection criteria.
The FIDELIO-DKD and FIGARO-DKD randomized clinical trials (RCTs) showed finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (MRA), reduced the risk of renal and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Using RCT inclusion and exclusion criteria, we analyzed the RCT coverage for patients with T2DM and CKD in routine clinical practice in Germany. German patients from the DPV/DIVE registries who were ≥ 18 years, had T2DM and CKD (an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 OR eGFR ≥ 60 mL/min/1.73m2 and albuminuria [≥ 30 mg/g]) were included. RCT inclusion and exclusion criteria were then applied, and the characteristics of the two populations compared. Overall, 65,168 patients with T2DM and CKD were identified from DPV/DIVE. Key findings were (1) Registry patients with CKD were older, less often male, and had a lower eGFR, but more were normoalbuminuric vs the RCTs. Cardiovascular disease burden was higher in the RCTs; diabetic neuropathy, lipid metabolism disorders, and peripheral arterial disease were more frequent in the registry. CKD-specific drugs (e.g., angiotensin-converting enzyme inhibitors [ACEi] and angiotensin receptor blocker [ARBs]) were used less often in clinical practice; (2) Due to the RCT's albuminuric G1/2 to G4 CKD focus, they did not cover 28,147 (43.2%) normoalbuminuric registry patients, 4,519 (6.9%) albuminuric patients with eGFR < 25, and 6,565 (10.1%) patients with microalbuminuria but normal GFR (≥ 90 ml/min); 3) As RCTs required baseline ACEi or ARB treatment, the number of comparable registry patients was reduced to 28,359. Of these, only 12,322 (43.5%) registry patients fulfilled all trial inclusion and exclusion criteria. Registry patients that would have been eligible for the RCTs were more often male, had higher eGFR values, higher rates of albuminuria, more received metformin, and more SGLT-2 inhibitors than patients that would not be eligible. Certain patient subgroups, especially non-albuminuric CKD-patients, were not included in the RCTs. Although recommended by guidelines, there was an undertreatment of CKD-patients with renin-angiotensin system (RAS) blockers. Further research into patients with normoalbuminuric CKD and a wider prescription of RAS blocking agents for CKD patients in clinical practice appears warranted.


Potential of Eichhornia crassipes for biomass refining.
Here we explore the utilization of Eichhornia crassipes, commonly known as water hyacinth, as a competitive source of biomass for conversion to fuel. Ecologically, E. crassipes is the most undesirable of a class of noxious and invasive aquatic vegetation. Water hyacinth grows rapidly on the surface of waterways, forming a dense mat which depletes the surrounding environment of essential nutrients. These properties, rarely encountered in other plant systems, are features of an ideal feedstock for renewable biomass. The high characteristic water content limits the range over which the material can be transported; however it also makes E. crassipes a natural substrate for rapid microbial metabolism that can be employed as a potentially effective biological pretreatment technology. We show through a life cycle analysis that water hyacinth is a competitive feedstock with the potential to be produced at a cost of approximately 40 dollars per ton of dry mass.


Long-term aeration management for improved N-removal via SND in a sequencing batch reactor.
Management of the aeration length in a sequencing batch reactor (SBR) can improve N-removal by minimising the amount of organic substrate that is oxidised aerobically. This study investigates the long-term effect of aeration control on N-removal via simultaneous nitrification and denitrification (SND) by a mixed culture in a 2L acetate-fed SBR, using PHB as the electron donor for denitrification. The reactor was operated continuously with automated termination of the aerobic phase after ammonium depletion, using the specific oxygen uptake rate (SOUR) as the control parameter. This resulted in an increase of the organic loading rate (OLR) from 0.33 to 0.59 g BOD g(-1)d(-1). Over the first 12 cycles of operation, the PHB content of the biomass increased three-fold and resulted in a progressively increasing SOUR, which allowed an increased amount of nitrogen removal via SND from 34% to 52%. After one month of continuous operation with controlled aeration, the settling efficiency of the biomass had significantly improved (SVI 70 mL g(-1) X). Long-term oxygen management resulted in biomass with a higher capacity for N-removal via SND and improved settling characteristics. Our results may help to explain long-term historical effects of N-removal capabilities in WWTPs and assist design engineers in choosing an appropriate aeration length and OLR.


Prevalence of factor V Leiden and prothrombin G20210A mutations in unselected patients with venous thromboembolism.
We determined the prevalence of factor V Leiden and of prothrombin G20210A mutations in a cohort of unselected outpatients (n = 748) referred for suspected deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and a pooled analysis of similar studies was also performed. Based on the clinical presentation, the prevalence of factor V Leiden was 15.7% in the 83 patients with DVT and 14.1% in the 99 patients with PE compared with 5.3% in patients without DVT and/or PE (control group). The prevalence of the prothrombin G20210A mutation did not differ among the three groups (3.9% for controls, 4. 8% for DVT and 3.9% for PE patients). We then divided the 99 patients with PE by separately analysing those with PE but without DVT (n = 57) and those with PE and DVT (n = 42). Compared with the control group, the prevalence of factor V Leiden was 10.5%, odds ratio (OR) 2.10 [95% confidence interval (95% CI) 0.68-5.45] in patients with primary PE and 19.1%, OR 4.20 (95% CI 1.54-10.30) in patients with DVT and PE. For the prothrombin G20210A mutation, no statistically significant differences were found between the control group and the three other groups. In conclusion, our data and the pooled analysis indicate that patients with primary PE are less often affected by the factor V Leiden mutation. No statistically significant differences were observed between patients and controls for the prothrombin G20210A mutation.


Regulation of the MLH1-MLH3 endonuclease in meiosis.
During prophase of the first meiotic division, cells deliberately break their DNA1. These DNA breaks are repaired by homologous recombination, which facilitates proper chromosome segregation and enables the reciprocal exchange of DNA segments between homologous chromosomes2. A pathway that depends on the MLH1-MLH3 (MutLγ) nuclease has been implicated in the biased processing of meiotic recombination intermediates into crossovers by an unknown mechanism3-7. Here we have biochemically reconstituted key elements of this pro-crossover pathway. We show that human MSH4-MSH5 (MutSγ), which supports crossing over8, binds branched recombination intermediates and associates with MutLγ, stabilizing the ensemble at joint molecule structures and adjacent double-stranded DNA. MutSγ directly stimulates DNA cleavage by the MutLγ endonuclease. MutLγ activity is further stimulated by EXO1, but only when MutSγ is present. Replication factor C (RFC) and the proliferating cell nuclear antigen (PCNA) are additional components of the nuclease ensemble, thereby triggering crossing-over. Saccharomyces cerevisiae strains in which MutLγ cannot interact with PCNA present defects in forming crossovers. Finally, the MutLγ-MutSγ-EXO1-RFC-PCNA nuclease ensemble preferentially cleaves DNA with Holliday junctions, but shows no canonical resolvase activity. Instead, it probably processes meiotic recombination intermediates by nicking double-stranded DNA adjacent to the junction points9. As DNA nicking by MutLγ depends on its co-factors, the asymmetric distribution of MutSγ and RFC-PCNA on meiotic recombination intermediates may drive biased DNA cleavage. This mode of MutLγ nuclease activation might explain crossover-specific processing of Holliday junctions or their precursors in meiotic chromosomes4.


[Pathological gambling in adolescence].
Today's juveniles are the first generation to be raised in an environment where gambling is very accessible and socially acceptable. The recent legalization of Internet gambling has increased this accessibility. With 28,8 millions of gamblers in France in 2010, many believe that gambling is an innocent leisure activity. The first results of the national survey on the prevalence of gambling practices conducted in France show that in 2010, 1.3% of the population had a gambling problem. Also, despite the prohibition of gambling to minors, the mean age of onset of gambling behavior in the world is 11.5 years. Gambling (even non-problematic) in adolescence is associated with poor school performance, criminal behavior and family conflict. Recreational gambling shares with pathological gambling high rates of psychiatric comorbidities in adults, and risk behaviors among adolescents. Similarly, international studies show prevalence of problem gambling 2 to 4 times higher among adolescents than among adult, 3.5% to 8% of adolescents between 12 and 17 are pathological gamblers. The validity of the screening instruments and the frequency of spontaneous recovery in adulthood are discussed to explain the high prevalence in adolescence. This article proposes a focus on the practice of gambling in adolescence and its characteristics when the practice becomes pathological. We discuss the epidemiological, diagnostic, etiologic and therapeutic aspects of this problem. Three major types of risk factors implicated in gambling problems are identified: some of them are related to the subject (individual factors), others are related to the object of the addiction, here the gambling activity by itself (structural factors) like Internet with the recent legalization of gambling online, and the last are related to environment (contextual or situational factors). Thus, the development and maintenance of pathological gambling in youth seems to be conditioned by the interaction of a person and a gambling activity, in a particular context. This conceptual model is based on the well-known theory of Olivenstein on toxicomania, which was proposed in the seventies. In France, very few is known about problem gambling in this age and its implications in terms of treatment, prevention and research. There is little in the way of specific treatments for adolescent pathological gamblers so we briefly reviewed possibilities and limits. We discuss the importance to develop prevention, in particular to delay the initiation, and the necessity of research to develop screening instruments and news studies to have a better knowledge of this population.


Materials and methods for cleaning dentures.
Proper hygienic care of removable dentures is an important means of maintaining a healthy oral mucosa in denture wearers. Denture cleanliness is often poor due to improper mechanical cleansing and the relative inefficiency of most commercial products for chemical cleansing of dentures. Dentists and patients should realize that microbial plaque on dentures may be harmful to both the oral mucosa and the patient's general health. It is the responsibility of the patient to maintain oral hygiene through a daily home care routine. It is the obligation of the dentist to motivate and instruct the patient and provide the means and methods for plaque control. Future research should be directed to developing solution cleansers which can maintain plaque-free dentures with a daily soaking period of 15 to 30 minutes and not affect the color and surface luster of the denture acrylic resin.


Erratum: (4Z)-4-Benzyl-idene-2-phenyl-1,3-oxazol-5(4H)-one. Corrigendum.
In the paper by Asiri et al. [Acta Cryst. (2012), E68, o1154], the title and the chemical name of one of the reagents used in the synthesis are corrected.[This corrects the article DOI: 10.1107/S1600536812011579.].


Use of proper statistical techniques for research studies with small samples.
In this review I discuss the appropriateness of various statistical methods for use with small sample sizes. I review the assumptions and limitations of these methods and provide recommendations for figures and statistical tests.


Protein tyrosine phosphatase 1B: a potential leptin resistance factor of obesity.
Indirect evidence implicates leptin resistance in the pathogenesis of the lipotoxicity that complicates obesity and results in the metabolic syndrome. In this issue of Developmental Cell, two groups identify protein tyrosine phosphatase 1B (PTP1B) as a cause of leptin resistance through dephosphorylation of Jak2.


A simple and sensitive nonradioactive method for the detection of urinary human chorionic gonadotropin and diagnosis of early human pregnancy. II. Single-unit test.
A simple, sensitive, and reliable single-unit nonradioactive method for the detection of human chorionic gonadotropin (hCG) in concentrated urine and the diagnosis of early pregnancy is reported. This unit, presently termed the Ayerst pregnancy test kit (APTK), consists of four components: a sampler-filter paper cone, an ultrafilter-concentrator to which a vial holder is attached, a support stand with a mirror, and an immunologic reagent vial. In the APTK, 5 to 6 ml of urine were sampled, filtered, and concentrated, and the hCG in the retentate was detected by Ayerst immunologic reagents [APTK(AY)] and by the Pregnosticon "All In" [APTK(P)]. Some of the unconcentrated urine samples (0.1 ml) were also tested in hemagglutination inhibition tests (HIT) using Ayerst [HIG(AY)] and Pregnosticon "All In" [HIT(P)] reagents. Urine samples from pregnant, nonpregnant (ovulating and nonovulating), perimenopausal, and menopausal women were tested. It was found that the APTK(AY) and APTK(P) were significantly more sensitive and reliable than the HIT(AY) and HIT(P) in detecting low levels of urinary hCG for early diagnosis of pregnancy. The sensitivity and specificity of the APTK(AY) were better than those of the APTK(P). The APTK(AY) give significantly more correct positive and negative results than the other tests performed simultaneously. The APTK(AY) is simpler and safer than the serum radioimmunoassays and radioreceptor assay presently used to detect low levels of hCG for the early diagnosis of pregnancy and other hCG-producing states.


COVID-19 pandemic and the changing views of mobility: the case of Nepal-Malaysia migration corridor.
For decades, Malaysia has been heavily dependent on unskilled and temporarily contracted migrant workers to fulfil labour gaps in the country. While Malaysia's economy continues to rely on migrant workers, the COVID-19 pandemic has further aggravated their precarious working and living conditions. In-depth interviews with Nepali migrant workers and community leaders in Malaysia and Nepal in 2021 revealed the incidence of labour rights violations, compounded by the lack of access to justice and effective remedies. Besides, workers are allegedly no longer benefiting from the competitive wages, subsequently limiting the value of their remittance to Nepal. We argue that these incidents serve as the drivers of the changing views of mobility, eventually influencing the emigration environment in which the social construction of migration exists in Nepal. This study examines the migratory realities in the Nepal-Malaysia migration corridor during the pandemic, subsequently contributing to current debate on the aspiration-ability model as a class of research.


[Application of photodynamic therapy combined with compound betamethasone in treatment of hypertrophic scar].
To investigate the effect of photodynamic therapy combined with compound betamethasone in the treatment of hypertrophic scar. 37 cases of keloid were divided into two groups, 19 cases in the treatment group, 18 cases in the control group. The patients in treatment group were treated with photodynamic therapy combined with compound betamethasone injection therapy. The patients in the control group were treated by compound betamethasone injection. The effect and recurrence rate were compared before and after treatment. The effective rate was 89.5% in the treatment group, 55. 6% in the control group, showing significant difference between the two groups (P = 0.029) The relapse rate in treatment group was significantly lower than that in the control group (P = 0.047) CONCLUSIONS: Photodynamic therapy combined with compound betamethasone has good effect and safety for the treatment of hypertrophic scar. The combined treatment can reduce the treatment period and side effects


Epidemiologic studies of glyphosate and non-Hodgkin's lymphoma: A review with consideration of exposure frequency, systemic dose, and study quality.
I reviewed the epidemiologic literature for glyphosate and non-Hodgkin's lymphoma (NHL) in the context of the frequency of exposure in each epidemiologic study, systemic dose from biomonitoring studies of applicators, and aspects of study quality. Nine studies were identified, 7 case control and 2 cohort, by a literature search and a review of reference lists from published studies and recent regulatory evaluations. All but one study involved exposure scenarios that were so infrequent that they are not credible for cancer causation. Most studies failed to address potential confounding from other pesticides. Only one study - the US Agricultural Health Study (AHS) - included individuals with relatively frequent exposure to glyphosate and involved comprehensive statistical analyses to address potential confounding by personal factors and other pesticide exposures. The AHS did not find an association between glyphosate and NHL, even among the most frequently exposed participants (≥ 109 days of use) (RR = 0.80, 95% CI 0.60, 1.06). These findings are consistent with observations that glyphosate systemic doses from agricultural applications are many orders of magnitude less than daily lifetime doses considered by regulatory agencies to impart no excess risk of deleterious health effects, even for sensitive subpopulations.


Inhibition of mouse liver sialidase by the root of Scutellaria baicalensis.
Of 266 Chinese crude drugs, the hot water extract from the root of Scutellaria baicalensis showed potent mouse liver sialidase inhibitory activity; in addition, wogonin, wogonin glucuronide, baicalein, and baicalin were identified as the inhibitors. These flavonoids showed almost the same inhibitory activity when 50-125 micrograms/ml doses of the samples were used for the assay, while wogonin and baicalein showed a more potent activity than wogonin glucuronide and baicalin at the lower concentration (10 micrograms/ml). However, these flavonoids, except wogonin, showed negligible inhibitory activity against Arthrobacter ureafaciens sialidase. These results indicated that S. baicalensis extract contains the sialidase inhibitors which are specific to mouse liver sialidase.


Robotic versus Open Pancreatoduodenectomy for Pancreatic and Periampullary Tumors (PORTAL): a study protocol for a multicenter phase III non-inferiority randomized controlled trial.
Pancreatoduodenectomy is a complex and challenging procedure that requires meticulous tissue dissection and proficient suturing skills. Minimally invasive surgery with the utilization of robotic platforms has demonstrated advantages in perioperative patient outcomes in retrospective studies. The development of robotic pancreatoduodenectomy (RPD) in specific has progressed significantly, since first reported in 2003, and high-volume centers in pancreatic surgery are reporting large patient series with improved pain management and reduced length of stay. However, prospective studies to assess objectively the feasibility and safety of RPD compared to open pancreatoduodenectomy (OPD) are currently lacking. The PORTAL trial is a multicenter randomized controlled, patient-blinded, parallel-group, phase III non-inferiority trial performed in seven high-volume centers for pancreatic and robotic surgery in China (> 20 RPD and > 100 OPD annually in each participating center). The trial is designed to enroll and randomly assign 244 patients with an indication for elective pancreatoduodenectomy for malignant periampullary and pancreatic lesions, as well as premalignant and symptomatic benign periampullary and pancreatic disease. The primary outcome is time to functional recovery postoperatively, measured in days. Secondary outcomes include postoperative morbidity and mortality, as well as perioperative costs. A sub-cohort of 128 patients with pancreatic adenocarcinoma (PDAC) will also be compared to assess the percentage of patients who undergo postoperative adjuvant chemotherapy within 8 weeks, in each arm. Secondary outcomes in this cohort will include patterns of disease recurrence, recurrence-free survival, and overall survival. The PORTAL trial is designed to assess the feasibility and safety of RPD compared to OPD, in terms of functional recovery as described previously. Additionally, this trial will explore whether RPD allows increased access to postoperative adjuvant chemotherapy, in a sub-cohort of patients with PDAC. ClinicalTrials.gov NCT04400357 . Registered on May 22, 2020.


Lactic acid and lactate: revisiting the physiological roles in the tumor microenvironment.
Lactic acid production has been regarded as a mechanism by which malignant cells escape immunosurveillance. Recent technological advances in mass spectrometry and the use of cell culture media with a physiological nutrient composition have shed new light on the role of lactic acid and its conjugate lactate in the tumor microenvironment. Here, we review novel work identifying lactate as a physiological carbon source for mammalian tumors and immune cells. We highlight evidence that its use as a substrate is distinct from the immunosuppressive acidification of the extracellular milieu by lactic acid protons. Together, data suggest that neutralizing the effects of intratumoral acidity while maintaining physiological lactate metabolism in cytotoxic CD8+ T cells should be pursued to boost anti-tumor immunity.


The preparedness assessment for the transition home after stroke predicts key domains of caregiver health.
Caregivers of stroke survivors often experience adverse health effects due to poor preparation. We evaluate the concurrent and predictive validity of the Preparedness Assessment for the Transition Home after Stroke (PATH-s) family caregiver assessment tool relative to important domains of caregiver health and stroke survivor outcomes. A convenience sample of caregivers (N = 183) was assessed on several health-related quality of life instruments prior to stroke survivor discharge (T1), and at 30-days (T2) and 90-days (T3) post-discharge. Caregivers completed assessments at T1 (N = 183), T2 (N = 116, 63%), and T3 (N = 97, 53%). At T1, the PATH-s demonstrated concurrent validity with depressive symptoms (r = -0.26, p < .001), global health (r = 0.45 p < .001) and activation (r = 0.34, p < .001). The PATH-s also has predicted improvements in T2 outcomes including depressive symptoms (radj = -0.21, p < .05), global health (radj = 0.30, p < .01), perceived stress (radj = -0.30, p < .01), activation (radj = 0.21, p < .05), caregiving-specific health-related quality of life (r = 0.23, p < .05), and caregiver strain (r = -0.36, p < .001). At T3, higher scores on the PATH-s were a significant predictor for improvements in activation (radj = 0.24, p < .05). The PATH-s demonstrates good concurrent and predictive validity and predicts important domains relevant to caregiver well-being. This can be used to identify gaps in caregiver preparedness so interventions can be tailored to optimize the transition home and mitigate adverse effects of caregiving.


Comparison of survival of black and white patients in each stage of Hodgkin's disease during 1970-1980.
A survival and mortality study of all the patients referred to the radiotherapy department between 1970 and 1980 with a diagnosis of Hodgkin's disease was performed. Generally, black patients with cancer have a poorer survival rate compared with that of white patients with cancer, as reported by the U.S. Department of Health and Human Services. In this series, no difference in survival and mortality was found between patients of the two races when they were compared in each stage of Hodgkin's disease.


Molecular evidence that the opportunistic fungal pathogen Trichosporon asahii is part of the normal fungal microbiota of the human gut based on rRNA genotyping.
The fungus Trichosporon asahii is distributed widely in the environment and is frequently isolated from clinical specimens. It can cause life-threatening disseminated infections, including breakthrough infection after the administration of candin antifungal drugs. However, the definitive infection route is still unclear. In this study, 43 T. asahii genotypes were detected in 72 fecal samples from healthy subjects. The rRNA genotypes of the species were determined using a culture-independent method. The genotypes of T. asahii were almost identical to those of reported clinical isolates. Therefore, T. asahii colonizing the gastrointestinal tract might be associated with the development of trichosporonosis, and not environmental isolates.


Development and characterization of chitosan/polyvinyl alcohol polymer material with elastolytic and collagenolytic activities.
The biologically active polymeric material with entrapped peptidase Bacillus thuringiensis var. israelensis with caseinolytic, collagenase and elastase activities was developed as a promising product for medical use. We have evaluated and reported here the following physical-chemical and biochemical characteristics of entrapped enzyme: peptidase/polymer interaction and morphology analyses, film thickness, water content, time of dissolution in water and physiological saline, kinetic of casein hydrolysis and pH- and thermoprofiles of proteolytic activity. Scanning electron microscopy images shows the relative uniformity of the film surface with entrapped peptidase. The released peptidase was characterized by increased proteolytic activity in the acidic (14%-35%) and alkaline (7%-32%) regions. After nine months of storage, peptidase in chitosan/polyvinyl alcohol films retains more than 95% of its initial proteolytic activity. We consider this film as a perspective biotechnological agent in medicine.