Anatomy education of medical and dental students during COVID-19 pandemic: a reality check.
During this forced down-time of COVID-19 pandemic, shift to virtual anatomy education is the solitary solution to support the learning of students. The purpose of this study was to understand the visible and invisible potential challenges being faced by the 1st year medical and dental students while attending digital anatomy classes. The present study was conducted on 81st year medical and dental students who were admitted to their respective college in August 2019 and were willing to participate in the study. A multiple choice close-ended questionnaire regarding their opinion on virtual classes was designed and feedback was taken from the students. Majority (65%) of the students agreed that they missed their traditional anatomy learning i.e., dissection courses, face to face lectures and interaction with mentors. The students strongly felt the lack of confidence and difficulty in the topics completed without dissections, models, microscopic slides and other modalities. 83% felt lack of proper gadgets, high-band width and strong internet connections, a potential barrier in their digital learning. Lack of self-motivation was felt by 69% students. The current situation of anatomy education is not intentional, and is not the long term silver bullet solution for a visual subject like anatomy. Though learners face a lot of challenges, however, a shift to online must be supported at this time of health crisis. As the digital learning may go for indefinite period, the feedback of students may be helpful for relevant and timely modifications in digital anatomy education.


The phenol red thread tear test in large Psittaciformes.
To develop a standard method for measuring tear production in large Psittaciformes using the phenol red thread (PRT) tear test. To establish mean PRT tear test values in clinically normal pet birds and to assess the reproducibility of the test. Two geographically distinct populations of healthy, large Psittaciformes (pilot study and study population). Species groups include: cockatoo (17), macaw (22), Amazon (10), African gray (1), eclectus (1) and pionus (1). The PRT was placed under the upper eyelid and both eyelids were held closed throughout the test. The PRT tear test was repeated after 2 months in the pilot study and after approximately 5 min in the study population. The mean PRT tear test values for the pilot study were OD=28.2 mm/15 s (+/- 6.3 mm), OS=24.1 mm/15 s (+/- 6.6 mm) and OD=25.4 mm/15 s (+/- 3.3 mm), OS=25.5 mm/15 s (+/- 5.2 mm), for the first and second visits respectively. The mean PRT tear test value for the study population was: OD=19.8 mm/15 s (+/- 4.3 mm), OS=20.1 (+/- 3.9 mm) and OD=20.0 mm/15 s (+/- 4.5 mm), OS=19.1 mm/15 s (+/- 3.3 mm), for the first and second tests respectively. There was poor repeatability between tests. Results suggest that the PRT tear test is a practical method for measuring tear production in large Psittaciformes, although adaptations to the established diagnostic method are necessary to overcome some anatomical differences present in birds. Good reproducibility of the PRT tear test could not be demonstrated in a clinically normal population of birds but geographic location appears to significantly influence results.


Isolation of cDNAs for mouse phenol and bilirubin UDP-glucuronosyltransferases and mapping of the mouse gene for phenol UDP-glucuronosyltransferase (Ugtla1) to chromosome 1 by restriction fragment length variations.
The mouse gene for phenol UDP-glucuronosyltransferase (UDPGT; Ugtla1) was mapped at 42 cM on chromosome 1, a position identical to that of the gene for bilirubin UDPGT (Ugtla1), from linkage analysis of a three-point cross test with Idh-1, En-1, and Ugtla1 as marker genes. The cDNAs for mouse phenol and bilirubin UDPGTs, isolated after amplification by PCR, shared an identical 3'-half region. Our results strongly suggest that mouse bilirubin and phenol UDPGTs are expressed from a single gene and involve alternative splicing events. We also detected duplication of the gene for phenol UDPGT in all mouse strains examined with the exception of MOL-MIT and SUB-SHH.


Specialized metabolites of the fungal genus Phomopsis: Structures, bioactivities and biosynthesis.
Fungi are important resources of novel bioactive compounds which have a high potential to be drug leads or candidates for further pharmacological applications. Phomopsis, a genus widely distributed in the environment, can produce various types of compounds including polyketides, alkaloids, terpenoids, cytochalasins, steroids and flavonoids. The metabolites of Phomopsis sp. showed diverse bioactivities such as antibacterial, anti-inflammatory, antimalarial, and so on, many of which may influence the physiological behaviour of the host plants. In this review, we focus on the chemical structures and biological activities of 183 specialized metabolites isolated from Phomopsis sp. in the decade (2013-2022). Moreover, the biosynthetic pathways of some typical components are summarized.


Salt sensitivity and systemic hypertension in the elderly.
Aging in industrialized societies is accompanied by increases in the incidence and prevalence of hypertension, with a disproportionately greater increase occurring among aging blacks than among aging whites. This geriatric hypertension is generally of a salt-sensitive nature with a disproportionate frequency of isolated systolic hypertension. Although salt-taste acuity declines with age, salt sensitivity among the elderly does not appear to result from a compensatory increase in salt intake. Rather, age-related increases in salt sensitivity result, in part, from a reduced ability to appropriately excrete a salt load, which is due to a decline in renal function and to a reduced generation of natriuretic substances such as prostaglandin E2 and dopamine. Age-associated declines in the activity of membrane sodium/potassium-adenosine triphosphatase (Na/K-ATPase) may also contribute to geriatric hypertension because this results in increased intracellular sodium that may cause reduced sodium-calcium exchange and thereby increase intracellular calcium and vascular resistance. Reductions in cellular calcium efflux due to reduced calcium-ATPase activity may similarly cause an increase in intracellular calcium and vascular resistance. Increasing dietary calcium intake may represent an effective nonpharmacologic treatment for some salt-sensitive persons because it appears to reduce intracellular calcium by (1) suppressing parathyroid hormone-mediated calcium influx, (2) increasing Na/K-ATPase activity, and (3) reducing intravascular volume due to calcium-induced natriuresis.


Tamsulosin MR and OCAS (modified release and oral controlled absorption system): current therapeutic uses.
Although tamsulosin is mainly used to treat lower urinary tract symptoms secondary to benign prostatic hyperplasia, with better understanding of functional anatomy and distribution of alpha(1) receptors, it is also indicated in other conditions of genito-urinary tract in both men and women. To detail the therapeutic use and clinical effects of tamsulosin. The scope of the review was related to tamsulosin and its therapeutic application in conditions of genitourinary tract. Publications were searched from Pubmed and Medline from 1975 to 2007 using the search words tamsulosin, lower urinary tract symptoms, alpha receptors and blockers. The management of benign prostatic hyperplasia was transurethral resection of prostate until simpler and alternative treatments were tried in the last two decades, particularly alpha(1) adrenoceptor-blocking agents. Tamsulosin is a potent, third-generation selective alpha(1A) adrenoceptor-blocking agent.


Occurrence of plasmid-mediated fosfomycin resistance (fos genes) among Escherichia coli isolates, Portugal.
To evaluate the occurrence of plasmid-mediated fos genes among fosfomycin-resistant Escherichia coli isolates collected from patients in Lisbon, Portugal, and characterize the fos-positive strains. A total of 19 186 E. coli isolates were prospectively collected between April 2022 and January 2023 from inpatients and outpatients at a private laboratory in Lisbon. Fosfomycin resistance was initially assessed by semi-automated systems and further confirmed by the disc diffusion method. Resistant isolates were investigated for plasmid-mediated fos genes (fosA1-fosA10, fosC and fosL1-fosL2) and extended-spectrum beta-lactamases (ESBLs) by PCR and sequencing. Multilocus sequence typing was performed to evaluate the clonal relationship among fos-carrying isolates. Out of the 19 186 E. coli isolates, 100 were fosfomycin-resistant (0.5%), out of which 15 carried a fosA-like gene (15%). The most prevalent fosfomycin-resistant determinant was fosA3 (n = 11), followed by fosA4 (n = 4). Among the 15 FosA-producing isolates, 10 co-produced an ESBL (67%), being either of CTX-M-15 (n = 8) or CTX-M-14 (n = 2) types. The fosA3 gene was carried on IncFIIA-, IncFIB-, and IncY-type plasmids, whereas fosA4 was always located on IncFIB-type plasmids. Most FosA4-producing isolates belonged to a single sequence type ST2161, whereas isolates carrying the fosA3 gene were distributed into nine distinct genetic backgrounds. The prevalence of fosfomycin-resistant E. coli isolates is still low in Portugal. Notably, 15% of fosfomycin-resistant isolates harbour a transferable fosA gene, among which there is a high rate of ESBL producers, turning traditional empirical therapeutical options used in Portugal (fosfomycin and amoxicillin-clavulanic acid) ineffective.


Effect of the Mediterranean diet with and without weight loss on markers of inflammation in men with metabolic syndrome.
Intervention studies on the Mediterranean Diet (MedDiet) have often led to weight loss, which may have contributed to the purported anti-inflammatory effects of the MedDiet. To investigate the impact of the MedDiet consumed under controlled feeding conditions before (-WL) and after weight loss (+WL) on markers of inflammation in men with metabolic syndrome (MetS). Subjects (N = 26, male, 24-65 years) with MetS first consumed a North American control diet for 5 weeks followed by a MedDiet for 5 weeks both in isocaloric feeding conditions. After a 20-week weight loss period in free-living conditions (10 ± 3% reduction in body weight, P < 0.01), participants consumed the MedDiet again under isocaloric-controlled feeding condition for 5 weeks. MedDiet - WL significantly reduced plasma C-reactive protein (CRP) concentrations (-26.1%, P = 0.02) and an arbitrary inflammatory score (-9.9%, P = 0.01) that included CRP, interleukin-6 (IL-6), IL-18, and tumor necrosis factor-α (TNF-α) compared with the control diet. The MedDiet + WL significantly reduced plasma IL-6 (-20.7%) and IL-18 (-15.6%, both P ≤ 0.02) concentrations compared with the control diet but had no further significant impact on plasma CRP concentration. Participants with a reduction in waist circumference ≥8.5 cm after MedDiet + WL showed significantly greater reductions in inflammation markers than those with a change in waist circumference <8.5 cm. Thus, consuming MedDiet even in the absence of weight loss significantly reduces inflammation. However, the degree of waist circumference reduction with weight loss magnifies the impact of the MedDiet on other markers of inflammation associated with MetS in men.


Wear of bulk-fill resin composites.
Bulk-fill resin composites are a special group of restorative materials designed to reduce chair time needed to insert a direct composite restoration. However, other factors determine the clinical success of a restorative material. Clinically the major reasons for failure of direct restorations are secondary caries and fracture of the restoration or the tooth itself. In the long-term composite resin restorations in posterior teeth may be prone to wear. As bulk-fill materials have their own composition that will determine their mechanical properties, the wear resistance may be affected as well. The aim of this in vitro study was to evaluate the wear of bulk-fill composites in comparison with a conventional hybrid composite. The null hypothesis was that there are no differences between the four bulk-fill materials and one traditional highly filled nanohybrid composite for posterior use when subjected to a two-body wear rate test and hardness measurement. Four bulk-fill composites SDR Smart Dentin Replacement (SDR), X-tra base (XBA), FiltekBulk Fill (FUP), Dual-Curing Bulk Composite (FBFL) and conventional nanohybrid resin composite Grandio (GDO) subjected to a two-body wear test against a stainless steel (SS) antagonist wheel. Scanning Electron Microscopy analysis was performed to detect the surface alterations. Microhardness of all samples was tested (n = 5) with a Vickers diamond indenter (5 indentations in each specimen). One-way ANOVA and Tukey's post hoc test (P < 0.01) were used to analyze differences in wear values. The hardness data were submitted to one-way ANOVA test, followed by the Tukey post hoc test (α = 0.05). T-test was applied to compare wear rate in time interval between one day and one month. The highest wear rate values were recorded for SDR and the lowest wear rate values were for GDO. Hardness was the highest for GDO and the lowest for FBFL. The bulk-fill composites have a higher wear rate and lower hardness than the conventional nanohybrid composite, making them less suitable for stress-bearing restorations.


Addition of CT to Improve the Diagnostic Confidence for the Detection of Sacroiliac Joint Erosions in Patients with Equivocal MRI Findings.
To determine if CT can improve the diagnostic confidence for the detection of sacroiliac joint (SIJ) erosions in patients with equivocal MRI findings. A retrospective analysis of adult patients who had an SIJ MRI and a subsequent SIJ CT within 12 months was conducted. Using a 5-point Likert scale, two reviewers evaluated the de-identified MRI and CT images in randomized order and in separate sessions to answer the question: "Does the patient have SIJ erosions?". A Fisher's exact test was used to analyze the difference in diagnostic confidence, and intraclass correlation coefficient (ICC) was used to determine interrater reliability. 54 patients were included in the analysis (average age, 43.9 years). The average time interval between initial SIJ MRI and subsequent CT was 14.4 weeks (range, 5.6-50.3 weeks). CT resulted in significantly more cases with definitive diagnostic confidence than cases with probable or equivocal confidence compared to MRI (P < .001). Amongst cases with equivocal findings on MRI, 73.2% of cases had definitive diagnoses on CT. There was moderate interrater agreement for MRI, with an ICC of .490 [95% CI, .258-.669], and excellent agreement for CT, with an ICC of .832 [95% CI, .728-.899]. Overall, CT led to significantly increased diagnostic confidence and higher interrater reliability for the detection of SIJ erosions compared to MRI. Judicious use of CT may be useful in detecting SIJ erosions in patients with equivocal MRI findings.


The effect of glucagon on rat cardiac cyclic AMP, phosphorylase a and force of contraction.
Glucagon produced dose-dependent increases in cyclic AMP, contractile force and % phosphorylase a when injected into isolated perfused rat hearts. Time-response experiments demonstrated that the increase in cyclic AMP occurred prior to changes in the other two parameters. All glucagon effects were enhanced by perfusion of the hearts with 1.0 mM theophylline although contractile force was affected less than the other 2 events. The data lend support to the concept that increases in cyclic AMP may be involved in the inotropic effect of glucagon. It should be noted, however, that the cyclic AMP increases produced by glucagon were considerably less than those previously noted with either the catecholamines or histamine.


Identification of 4-quinolone derivatives as inhibitors of reactive oxygen species production from human umbilical vein endothelial cells.
Oxidative stress is widely recognized as being associated with a number of disorders, including metabolic dysfunction and atherosclerosis. A series of substituted 4-quinolone derivatives were prepared and evaluated as inhibitors of reactive oxygen species (ROS) production from human umbilical vein endothelial cells (HUVECs). One compound in particular, 2-({[4-(3-hydroxy-3-methylbutoxy)pyridin-2-yl]oxy}methyl)-3-methylquinolin-4(1H)-one (25b), inhibited ROS production from HUVECs with an IC(50) of 140 nM. This compound also exhibited low CYP2D6 inhibitory activity, high aqueous solubility, and good in vitro metabolic stability. An in vivo pharmacokinetic study of this compound in SD rats revealed high oral bioavailability and a long plasma half-life.


An uncommon ankle sprain.
Ankle sprain is the most frequently occurring acute injury in tennis, accounting for 20-25% of all injuries. In the current paper, we assess the cause of ankle sprain and suggest possibilities to be considered during diagnosis. We assessed a professional tennis player with a partial tear of the long peroneal tendon after an ankle sprain by physical exam, X-ray and MRI. Conservative treatment by means of soft cast and propriocepsis training led to full recovery. Peroneal tendon disorders must be part of the differential diagnosis after ankle sprain in the professional athlete.


Identification of Y-Chromosome Sequences in Turner Syndrome.
To investigate the presence of Y-chromosome sequences and determine their frequency in patients with Turner syndrome. The study included 23 patients with Turner syndrome from Brazil, who gave written informed consent for participating in the study. Cytogenetic analyses were performed in peripheral blood lymphocytes, with 100 metaphases per patient. Genomic DNA was also extracted from peripheral blood lymphocytes, and gene sequences DYZ1, DYZ3, ZFY and SRY were amplified by Polymerase Chain Reaction. The cytogenetic analysis showed a 45,X karyotype in 9 patients (39.2 %) and a mosaic pattern in 14 (60.8 %). In 8.7 % (2 out of 23) of the patients, Y-chromosome sequences were found. This prevalence is very similar to those reported previously. The initial karyotype analysis of these patients did not reveal Y-chromosome material, but they were found positive for Y-specific sequences in the lymphocyte DNA analysis. The PCR technique showed that 2 (8.7 %) of the patients with Turner syndrome had Y-chromosome sequences, both presenting marker chromosomes on cytogenetic analysis.


deepBioWSD: effective deep neural word sense disambiguation of biomedical text data.
In biomedicine, there is a wealth of information hidden in unstructured narratives such as research articles and clinical reports. To exploit these data properly, a word sense disambiguation (WSD) algorithm prevents downstream difficulties in the natural language processing applications pipeline. Supervised WSD algorithms largely outperform un- or semisupervised and knowledge-based methods; however, they train 1 separate classifier for each ambiguous term, necessitating a large number of expert-labeled training data, an unattainable goal in medical informatics. To alleviate this need, a single model that shares statistical strength across all instances and scales well with the vocabulary size is desirable. Built on recent advances in deep learning, our deepBioWSD model leverages 1 single bidirectional long short-term memory network that makes sense prediction for any ambiguous term. In the model, first, the Unified Medical Language System sense embeddings will be computed using their text definitions; and then, after initializing the network with these embeddings, it will be trained on all (available) training data collectively. This method also considers a novel technique for automatic collection of training data from PubMed to (pre)train the network in an unsupervised manner. We use the MSH WSD dataset to compare WSD algorithms, with macro and micro accuracies employed as evaluation metrics. deepBioWSD outperforms existing models in biomedical text WSD by achieving the state-of-the-art performance of 96.82% for macro accuracy. Apart from the disambiguation improvement and unsupervised training, deepBioWSD depends on considerably less number of expert-labeled data as it learns the target and the context terms jointly. These merit deepBioWSD to be conveniently deployable in real-time biomedical applications.


Resolvin D1 via prevention of ROS-mediated SHP2 inactivation protects endothelial adherens junction integrity and barrier function.
Resolvins are a novel class of lipid mediators that play an important role in the resolution of inflammation, although the underlying mechanisms are not very clear. To explore the anti-inflammatory mechanisms of resolvins, we have studied the effects of resolvin D1 (RvD1) on lipopolysaccharide (LPS)-induced endothelial barrier disruption as it is linked to propagation of inflammation. We found that LPS induces endothelial cell (EC) barrier disruption via xanthine oxidase (XO)-mediated reactive oxygen species (ROS) production, protein tyrosine phosphatase SHP2 inactivation and Fyn-related kinase (Frk) activation leading to tyrosine phosphorylation of α-catenin and VE-cadherin and their dissociation from each other affecting adherens junction (AJ) integrity and thereby increasing endothelial barrier permeability. RvD1 attenuated LPS-induced AJ disassembly and endothelial barrier permeability by arresting tyrosine phosphorylation of α-catenin and VE-cadherin and their dislocation from AJ via blockade of XO-mediated ROS production and thereby suppression of SHP2 inhibition and Frk activation. We have also found that the protective effects of RvD1 on EC barrier function involve ALX/FPR2 and GPR32 as inhibition or neutralization of these receptors negates its protective effects. LPS also increased XO activity, SHP2 cysteine oxidation and its inactivation, Frk activation, α-catenin and VE-cadherin tyrosine phosphorylation and their dissociation from each other leading to AJ disruption with increased vascular permeability in mice arteries and RvD1 blocked all these effects. Thus, RvD1 protects endothelial AJ and its barrier function from disruption by inflammatory mediators such as LPS via a mechanism involving the suppression of XO-mediated ROS production and blocking SHP2 inactivation.


Expression and characterization of the human alpha 2B-adrenoceptor in a vascular smooth muscle cell line.
A vascular smooth muscle cell line stably expressing the human alpha 2B-adrenoceptor at a density of 1.5 pmol/mg membrane protein was generated by transfection of rat A7r5 cells. [35S]GTPgammaS binding experiments and [3H]thymidine incorporation experiments indicated that the expressed receptors were functional, had the expected pharmacological characteristics and efficiently stimulated smooth muscle cell proliferation. Confocal fluorescence microscopy was used to visualize alpha2B-adrenoceptors in A7r5-alpha 2B cells and indicated that the receptors were mainly localized in the plasma membrane. The expression of the smooth muscle-specific marker alpha-actin was similar in transfected A7r5-alpha 2B cells and in non-transfected A7r5 wild-type cells. The generated A7r5-alpha 2B cell line will be a useful tool for studying the function and regulation of alpha 2B-adrenoceptors in vascular smooth muscle cells.


Effect of implanted bisphosphonate-enriched cement on the trabecular microarchitecture of bone in a rat model using micro-computed tomography.
Bisphosphonates (BPs) are antiresorptive drugs typically used to inhibit bone resorption. The latest reports show that BPs play an important role in not only achieving better bone mineral density but also in improving bone microarchitecture. The mechanism of action of the BPs is complex and multifactorial. We tried to determine whether there are any changes in the microarchitectural bone structure during local use of BP (Pamifos 60). The aim of this study was to see if BP-enriched cement used in rat models had positive effects on bone formation. Research was performed on 40 adult male Wistar rats that were divided into four groups: two control groups and two experimental groups. Rats in the experimental groups were implanted with BP-enriched cement into the bone, while the control group rats were implanted with clean bone cement (without BP). Micro-computed tomography was applied for the investigation of trabecular microarchitecture of the proximal physis of the tibial bone in all animals three and six weeks after surgery. In all microCT images variables such as bone volume density (BV/TV), trabecular thickness (TbTh), trabecular separation (TbSp) and trabecular number (TbN) were used to describe trabecular bone morphometry. The major finding of this study is that using BP-enriched cement results in distinct changes in bone microarchitecture. We showed that local use of pamidronate (Pamifos 60) in orthopaedic cement had a positive effect on bone formation. It significantly changed three variables. We noticed increasing bone volume fraction and trabecular thickness together with decreasing trabecular separation. In this paper we demonstrate the efficacy of using BP-enriched cement in vitro in the tibiae of rats. Our most significant finding based on micro-CT picture analysis allows us to start further work on more suitable applications of BP-enriched cement in humans. We believe that future successful experiments will facilitate potential use of BP-enriched cement in clinical applications.


The spasticity-related quality of life 6-dimensions instrument in upper-limb spasticity: Part II A first psychometric evaluation.
Psychometric evaluation of the Spasticity-related Quality of Life 6-Dimensions instrument (SQoL-6D). A clinimetric evaluation conducted in a multicentre, prospective, longitudinal cohort study at 8 UK sites. Adult patients (n=104) undergoing focal treatment of upper-limb spasticity. The SQoL-6D was administered in the clinic at enrolment and at 8 weeks, then 1-4 days later at home to assess test-retest reliability. The SQoL-6D demonstrated adequate construct validity and unidimensionality of the scale, allowing the calculation of a Total score. Cronbach's alpha (0.74) supported the internal consistency reliability, while the intraclass correlation coefficient supported test-retest reliability (0.82). Correlation coefficients with established instruments supported convergent validity, while significant differences between known-groups (of differing clinical severity) in SQoL-6D Total score confirmed its sensitivity to both cross-sectional and longitudinal differences. The SQoL-6D is a promising new measure to assess health status for patients with upper-limb spasticity of any aetiology. Further investigation and exploration of the allocation of weights to convert the SQoL-6D to a health-related quality of life utility index, are required.


Bioelectrical osteogenesis: acceleration of fracture repair and bone growth. An alternative to bone grafting in nonunions.
Electrical stimulation of fracture nonunions has become a viable alternative to bone grafting. The success rate is comparable but the morbidity rate is significantly lower. Individual fracture healing problems must be thoroughly assessed and the treatment designed for the individual patient.


Modulation of CD39 and Exogenous APT102 Correct Immune Dysfunction in Experimental Colitis and Crohn's Disease.
CD39/ENTPD1 scavenges pro-inflammatory nucleotides, to ultimately generate immunosuppressive adenosine, which has a central role in immune homeostasis. Global deletion of Cd39 increases susceptibility to experimental colitis while single nucleotide polymorphisms within the human CD39 promoter, and aberrant patterns of expression during experimental hypoxia, predispose to Crohn's disease. We aimed to define the impact of transgenic human CD39 [hTG] overexpression in experimental colitis and to model therapeutic effects using the recombinant apyrase APT102 in vivo. We also determined the in vitro effects of APT102 on phenotypic and functional properties of regulatory T-lymphocytes derived from patients with Crohn's disease. Colitis was induced by administration of dextran sulfate sodium in wild-type [WT] or hTG mice, and, in another model, by adoptive transfer of CD45RBhigh cells with or without WT or hTG regulatory T cells [Treg]. In additional experiments, mice were treated with APT102. The effects of APT102 on phenotype and function of Treg and type-1 regulatory T [Tr1] cells were also evaluated, after purification from peripheral blood and lamina propria of Crohn's disease patients [n = 38]. Overexpression of human CD39 attenuated experimental colitis and protected from the deleterious effects of systemic hypoxia, pharmacologically induced by deferoxamine. Administration of APT102 in vivo enhanced the beneficial effects of endogenous Cd39 boosted by the administration of the aryl hydrocarbon receptor [AhR] ligand unconjugated bilirubin [UCB]. Importantly, supplemental APT102 restored responsiveness to AhR stimulation by UCB in Treg and Tr1 cells, obtained from Crohn's disease patients. hCD39 overexpression ameliorated experimental colitis and prevented hypoxia-related damage in vivo. Exogenous administration of APT102 boosted AhR-mediated regulatory effects in vivo while enhancing Treg functions in Crohn's disease in vitro.


[Experimental studies on the pathophysiology of knee ligament lesions (author's transl)].
The cruciates and the collateral ligaments of the knee compare well with a crossed four-joint chain. In surgery of the ligamentous lesions of the knee it is essential to reinsert the ligaments exactly at their anatomic position. Studies of cadaver knees have demonstrated that the medial collateral ligament ensures medial rotational stability to a greater degree than the meniscofemoral and meniscotibial bands. In every stage of medial and anterior ligamentous lesions, external rotation in 90 degrees of flexion shows the same amount of anterior laxity of the medial tibial condyle as the test of Slocum. In contrast to Nicholas the pivot point in anteromedial complex instability is situated posterolaterally.


Deoxycholic acid degradation by a Pseudomonas sp. Acidic intermediates with A-ring unsaturation.
The microbial catabolism of deoxycholic acid by a Pseudomonas sp. was studied, and six further acidic intermediates were isolated, as their methyl esters. Evidence is presented that the compounds are methyl 12 alpha-hydroxy-3-oxochol-4-en-24-oate, methyl 12 alpha-hydroxy-3-oxo-23,24-dinorchol-4-en-22-oate, methyl 12 alpha-hydroxy-3-oxochola-1,4-dien-24-oate, methyl 12 alpha-hydroxy-3-oxo-23,24-dinorchola-1,4-dien-22-oate, methyl 12 alpha-hydroxy-3-oxochola-1,4,22E-trien-24-oate and methyl 12 alpha-hydroxy-3-oxo-23,24-dinorchola-1,4,17(20)-trien-22-oate. On the basis of these compounds, together with the seven intermediates previously reported, a catabolic pathway is proposed.


Head size and schizophrenia.
There is a small but intriguing body of literature which suggests that head size may be reduced in patients with schizophrenia. This literature sits alongside more substantial and compelling evidence that there is a reduction in cerebral volume in schizophrenia. As an extension of earlier work, measures of extracranial head size derived from standard anthropometric approaches were assessed in 44 patients and 46 control subjects. Head size was found to be normal in schizophrenia. The relationship of brain size to head size is elaborated.


Reduction of bovine pulmonary hypertension by normoxia, verapamil and hexoprenaline.
In calves with hypoxic pulmonary hypertension, resistance was reduced by 40 +/- 3% with normoxia, 19 +/- 4% with verapamil, and 60 +/- 1% with hexoprenaline. It is possible that the increased resistance during normoxia is due to partly to vasoconstriction rather than solely to vascular thickening, and that the vasoconstriction is due to an abnormality in calcium metabolism by the hypertensive vasculature.


Anti-Di(b) as a red cell autoantibody.
It is known that some "warm"-reactive autoantibodies are directed against epitopes on the red cell anion exchanger, protein band 3. Some such antibodies (but not all) recognize Wrb. It is also known that Dia and Dib represent an amino acid polymorphism of band 3. Autoantibodies from 119 patients were tested against Di(b-) red cells. Seventy-four of these autoantibodies were subsequently absorbed with Di(b-) red cells. All 119 autoantibodies initially reacted with the Di(b-) red cells, which showed that none contained only anti-Dib. Among the 74 adsorbed with Di(b-) red cells, two were found to contain an unadsorbed anti-Dib component. No example of autoanti-Dib as the only autoantibody present was found among the 119 samples tested. However, 2 (2.7%) of 74 autoantibodies subjected to adsorption with Di(b-) red cells were seen to contain an anti-Dib component. This low incidence of autoanti-Dib is in marked contrast to the high incidence of autoanti-Wrb, although both antibodies define epitopes associated with the red cell anion exchanger, band 3.


Socio-economic status and COVID-19-related cases and fatalities.
The United States has the highest number of coronavirus disease 2019 (COVID-19) in the world, with high variability in cases and mortality between communities. We aimed to quantify the associations between socio-economic status and COVID-19-related cases and mortality in the U.S. The study design includes nationwide COVID-19 data at the county level that were paired with the Distressed Communities Index (DCI) and its component metrics of socio-economic status. Severely distressed communities were classified by DCI>75 for univariate analyses. Adjusted rate ratios were calculated for cases and fatalities per 100,000 persons using hierarchical linear mixed models. This cohort included 1,089,999 cases and 62,298 deaths in 3127 counties for a case fatality rate of 5.7%. Severely distressed counties had significantly fewer deaths from COVID-19 but higher number of deaths per 100,000 persons. In risk-adjusted analysis, the two socio-economic determinants of health with the strongest association with both higher cases per 100,000 persons and higher fatalities per 100,000 persons were the percentage of adults without a high school degree (cases: RR 1.10; fatalities: RR 1.08) and proportion of black residents (cases and fatalities: Relative risk(RR) 1.03). The percentage of the population aged older than 65 years was also highly predictive for fatalities per 100,000 persons (RR 1.07). Lower education levels and greater percentages of black residents are strongly associated with higher rates of both COVID-19 cases and fatalities. Socio-economic factors should be considered when implementing public health interventions to ameliorate the disparities in the impact of COVID-19 on distressed communities.


A novel multifaceted physical therapy approach for stress incontinence secondary to prostatectomy: Randomized controlled trial.
40 men with stress urinary incontinence (SUI) secondary to radical prostatectomy were randomly assigned to two groups (control = 20, treatment = 20). The treatment group received a novel multifaceted approach (including interferential therapy, a combination of exercise therapy approaches, and manual therapy) and the control group received sham electrotherapy. Both groups received 12 sessions of treatment in one month. Outcome measures include SF12 form to assess the quality of life and bladder diary to assess incontinence parameters including urination amount, fluid intake, urinary frequency, and incontinence frequency. treatment group shows significant improvement in comparison with the control group in quality of life (control group from 29.6 ± 4.5 to 31.0 ± 4.9 and the treatment group from 30.6 ± 4.4 to 42.2 ± 2.4, P = 0.003), urinary frequency (control group from 10.1 ± 2.0 to 9.2 ± 1.8 and treatment group from 9.7 ± 1.91 to 7.1 ± 1.1, P = 0.038), and incontinence frequency (control group from 7.0 ± 2.2 to 6.4 ± 2.0 and treatment group from 7.8 ± 2.4 to 1.2 ± 1.1, P = 0.003). Also, urination amount (control group from 1621.50 ± 403.7 to 1507.2 ± 402.3 and treatment group from 1638.3 ± 356.1 to 1360.55 ± 360.9, P = 0.503) and fluid intake (control group from 2024.0 ± 595.5 to 1865.2 ± 596.5 and treatment group from 2184.4 ± 484.5 to 1724.2 ± 596.6, P = 0.987) showed no significant difference between the two groups after the treatment sessions. the multifaceted approach presented here, consists of electrotherapy (interferential therapy), exercise therapy, and manual therapy that can improve incontinence and quality of life in patients with stress incontinence secondary to prostatectomy. To determine the long-term efficacy of this approach, studies with long-term evaluation are required.


PLasma glucagon levels during rapid exsanguination with and without adrenergic blockade.
In eleven dogs made hypotensive by means of rapid exsanguination over a period of forty to seventy minutes, mean glucagon rose to a peak of 516 plus or minus (S.E.) 150 pg/ml. and mean glucose to a peak of 341 plus or minus 27 mg. per 100 ml. The hyperglucagonemia induced by exsanguination was substantially reduced, although not abolished, by propranolol infusion, but was not diminished by phentolamine, suggesting that it was largely a beta-adrenergic effect. Its possible contribution to survival during shock is considered.


[A critical review of abdominal version in the terminal phase in breech presentation (author's transl)].
Attention is drawn to the possible risks of abdominal version in the terminal phase (prolapse of the cord, fetomaternal transfusion, premature liberation) on the basis of a prospective study. The author's experience points to restricted indication. In this connection, it is particularly important to pay attention to the seat of the placenta.


Multiple melt bodies fed the AD 2011 eruption of Puyehue-Cordón Caulle, Chile.
Within the volcanological community there is a growing awareness that many large- to small-scale, point-source eruptive events can be fed by multiple melt bodies rather than from a single magma reservoir. In this study, glass shard major- and trace-element compositions were determined from tephra systematically sampled from the outset of the Puyehue-Cordón Caulle (PCC) eruption (~1 km(3)) in southern Chile which commenced on June 4(th), 2011. Three distinct but cogenetic magma bodies were simultaneously tapped during the paroxysmal phase of this eruption. These are readily identified by clear compositional gaps in CaO, and by Sr/Zr and Sr/Y ratios, resulting from dominantly plagioclase extraction at slightly different pressures, with incompatible elements controlled by zircon crystallisation. Our results clearly demonstrate the utility of glass shard major- and trace-element data in defining the contribution of multiple magma bodies to an explosive eruption. The complex spatial association of the PCC fissure zone with the Liquiñe-Ofqui Fault zone was likely an influential factor that impeded the ascent of the parent magma and allowed the formation of discrete melt bodies within the sub-volcanic system that continued to independently fractionate.


Development of a Water-Soluble Fluorescent Probe Based on Natural Flavylium for Mercury(II) Ion Detection and Clinical Antidote Evaluation.
The health hazard posed by Hg2+ makes it imperative to develop a fast and convenient means for detecting Hg2+ in water samples and living objects. While fluorescence sensing technology is considered a promising candidate, the poor water solubility and fluorescence quenching in aqueous solutions of most existing probes limit their practical application. To overcome this, we developed a natural flavylium-inspired fluorescent probe with excellent water solubility. Our probe demonstrated outstanding performance of high sensitivity (LOD = 0.47 nM), fast response (<10 min), and great selectivity for Hg2+. Notably, we validated its applicability in real water, urine samples, and living cells. Furthermore, the probe was successfully applied to evaluate the effectiveness of antidotes for clinical Hg2+ poisoning.


Reconstruction of microtia with laser hair removal before transplantation of costal cartilage.
When scalp skin is contained in reconstruction of microtia, the hair growth on the reconstructed auricle causes aesthetic problems. Several techniques to deal with hairline, such as skin graft, skin flap, tissue expander and electroepilation, have been reported, but there are few reports using laser hair removal for microtia patients. We performed presurgical laser therapy in five patients. The low regions of hairlines in unilateral microtia children were irradiated by two kinds of laser systems for 1 year before the transplantation of costal cartilage. When hair growth was seen after the surgery, laser irradiations were performed. Video-microscopic and histological studies were examined to check the rates of epilation and skin injuries. There were no conspicuous hairs on the reconstructed ears and no side effects such as skin injury, folliculitis and deformity of cartilage. Video-microscopic examination revealed that terminal hair was rarely observed after irradiation, although the amount of vellus hair after irradiation was the same as that before irradiation. Histological examination showed that atrophy or hyperplasia of epidermis and dermis were not observed. Although patients had to undergo laser epilation from four to seven times because of a hair cycle, the laser epilation is less invasive and safer than other surgical procedures to reconstruct non-haired helix.


The utility and financial implications of obtaining routine lead levels for child psychiatric inpatients.
This study attempted to challenge the CDC recommendations regarding routine screening blood lead levels in children. The purpose was to determine the efficacy of obtaining routine lead levels on all patients admitted to a child psychiatric inpatient unit. A retrospective chart review of children admitted to a psychiatric inpatient unit during a 12 month period. The audit determined average lead levels and costs associated with the screening program. 1 of 61 admitted children was found to have an elevated lead level. Number needed to treat was determined to be 98. The cost per case detected was determined to be over $8,600. Routine screening for blood lead levels in all children admitted to a psychiatric inpatient unit does not appear efficacious or cost effective.


Melanoma skews dendritic cells to facilitate a T helper 2 profile.
Patients with progressing melanoma have a circulating cytokine profile reflecting a T helper cell type 2 (Th2) imbalance, while patients responding to therapy favor a Th1 profile. The aim of this study was to determine the role of circulating dendritic cells (DCs) in mediating this imbalance. Isolated human peripheral blood mononuclear cells (PBMCs) were exposed to cell-free melanoma-conditioned medium (MCM) or control fibroblast-conditioned medium before stimulation. In separate experiments, isolated circulating DCs were exposed to MCM before addition of T cells. DC maturation and function were determined. Mixed leukocyte response T-cell proliferation was quantified and supernatants were assayed for Th1 (interleukin [IL]-2 and interferon gamma) and Th2 (IL-4, IL-5, and IL-10) cytokines. PBMCs exposed to MCM produced significantly more Th2-type cytokines (IL-4, IL-5, and IL-10) over time than those exposed to control medium. DCs exposed to MCM before addition of T cells, produced a similar pattern of a sustained longer term Th2 response after an initial burst of IL-2. Exposure to MCM did not significantly affect DC maturation or IL-12 production. T-cell proliferation did not change significantly in the mixed leukocyte response, however, the percentage of viable CD4+ T cells in the MCM-treated group was significantly less than control (37 vs 50%, P < .05). Exposure of PBMCs to melanoma produces a Th2-type cytokine profile, which may be, in part, facilitated by DCs.


Automatic lexeme acquisition for a multilingual medical subword thesaurus.
We present a method for the automated acquisition of a multilingual medical lexicon (for Spanish, French and Swedish) to be used within the framework of a medical cross-language text retrieval system. For the lexical acquisition process, we incorporate seed lexicons and lists of trusted term translations derived from the UMLS Metathesaurus. The seed lexicons for Spanish, French and Swedish are automatically generated from (previously manually constructed) Portuguese, German and English sources by simple string transformations. Lexical and semantic hypotheses are then validated by processing pairs of term translations. In a last step, we use the cleaned list of "approved" translations in order to augment, step by step, the target dictionaries by processing the parallel corpora in terms of co-occurrence patterns of hypothesized translation equivalents which cannot be derived by simple character substitutions. An existing multilingual lexicon for the medical domain with about 60,000 entries for English, German, and Portuguese was automatically augmented by more then 17,000 new lexemes for Spanish, French, and Swedish. Our approach constitutes a promising method for the automated creation of new lexicon entries and their linkage to semantic identifiers.


Electron affinities from gas chromatography electron capture detector and negative ion mass spectrometry responses and complementary methods.
The use of the electron-capture detector, ECD, to measure molecular electron affinities and kinetic parameters for reactions of thermal electrons with molecules at atmospheric pressure separated by chromatography and the sensitive and selective quantitative analysis of certain classes molecules are reviewed. The evaluated ground state electron affinities of the main group elements and diatomic molecules from slightly positive, 0+, to 3.6 eV are summarized. The electron affinities of twenty-seven superoxide states determined from pulsed discharge ECD and other methods are used to calculate one dimensional potential energy curves in agreement with theory. Advances in literature searches have uncovered ECD data in dissertations and theses and in the Russian and Japanese literature. These data, unpublished radioactive and pulsed discharge ECD thermal data from the University of Houston laboratories are used to report and evaluate electron affinities. The accuracy and precision of ECD electron affinities of organic molecules are identified and tabulated so that they can be added to compilations. A procedure for calculating the temperature dependence of electron molecule reactions is presented using kinetic and thermodynamic data. These are used toselect the most appropriate equipment and conditions for ECD analyses and physical determinations.


Charcot salvage of the foot and ankle using external fixation.
This article details the advantages of external fixation for salvage of the Charcot foot and ankle. Preoperative evaluation, postoperative care, and surgical technique for external fixation are described. The literature on the effectiveness of this technique in the Charcot foot and ankle is reviewed.


The effects of genetic variation in N-acetyltransferases on 4-aminobiphenyl genotoxicity in mouse liver.
Inbred, congenic and transgenic strains of mice were characterized for acetylation of p-aminobenzoic (PABA) and the carcinogen 4-aminobiphenyl (4ABP). C57Bl/6 mice have the NAT2*8 allele, A/J mice have NAT2*9 and congenic B6.A mice have NAT2*9 on the C57Bl/6 background. The first transgenic strain with human NAT1, the functional equivalent of murine NAT2, was also tested. The murine NAT2*9 allele correlated with a slow phenotype measured with the murine NAT2 selective substrate PABA. The two strains having this allele also had a lower capacity to acetylate 4ABP. A line with five copies of the human NAT1 transgene was bred for at least five generations with either C57Bl/6 or A/J mice. There was no significant change in PABA NAT activity on the C57Bl/6 background but a 2.5-fold increase was seen in hNAT1:A/J compared with A/J. The effect of variation in NATs on 4ABP genotoxicity was assessed in these strains. Twenty-four hours after exposure to a single oral dose of 120 mg 4ABP/kg, hepatic 4ABP-DNA adducts were detected by immunofluoresence in all strains. Nuclear fluorescence intensities (mean+/-S.D.) were 41.1+/-3.6 for C57Bl/6, 37.9+/-1.11 for A/J and 36.3+/-2.44 for B6.A. There was no correlation between murine NAT2 alleles and 4ABP-DNA adduct levels. Similar results were seen with the transgenic strains. The data indicate that the range of variation present in these strains of mice was insufficient to alter susceptibility to 4ABP genotoxicity. The impact of these relatively modest differences in the acetylation of the activation of 4ABP may be masked by other competing biotransformation reactions since 4ABP is a substrate for both NAT1 and NAT2. Mouse models with variation in both isoforms are needed to adequately assess the role of variation in NATs in susceptibility to 4ABP genotoxicity.


Distribution pattern of mercury in northern Barents Sea and Eurasian Basin surface sediment.
Marine sediment is a significant sink for the global pollutant mercury. In a rapidly changing Arctic region, mercury (Hg) bioaccumulation in the marine ecosystem remains a prominent environmental issue. Here, we report surface sediment (0-2 cm) concentrations of Hg and other toxic elements of interest (Cr, Ni, Zn, Cu, As, Cd, Pb) in the northern Barents Sea and Eurasian Basin. We observed average Hg concentrations of 65 ± 23 ng/g with the highest concentration of 116 ng/g in the Eurasian Basin. Our calculated enrichment factors suggest low anthropogenic enrichment for mercury, chromium, nickel, and copper. Mercury and trace element geographic patterns are best explained by the origin and transportation of fine grain sediment towards the Eurasian Basin, with scavenging by both particulate organic carbon and metal oxides as significant delivery mechanisms.


Effect of hydrocortisone on interleukin-6 production in human ,peripheral blood rnononuclear ceils.
The effect of hydrocortisone on the production of interleukin-6 (IL-6) in human peripheral blood mononuclear cells was studied. Using our newly developed radioimmunoassay system for IL-6 of which specificity, reproducibility, sensitivity and usefulness have been demonstrated. IL-6 production in peripheral blood mononuclear cells of ten normal subjects revealed that in lipopolysaccharide (LPS, 10mug/ml)-stimulation, the mean +/- SD of IL-6 was 2.71 +/- 0.85 ng/ml. No detectable amount of IL-6 was observed in the absence of LPS and in the presence of hydrocortisone alone. Hydrocortisone (10(-10) M to 10(-3) M) inhibited LPS-stimulated IL-6 production in a dose-dependent manner. However, there was a wide variation in the response to hydrocortisone, namely, ranging from steroid-sensitive to steroid-resistant. Based on the concentration required to inhibit 50% of LPS-stimulated IL-6 production, three of ten subjects were at 10(-6) M, three at 10(-5) M and the rest at 10(-4) M, respectively. The dramatic anti-inflammatory and immunosuppressive effects of glucocorticosteroids can be life-saving in autoimmune diseases. The present findings suggested that there existed the differences in susceptibility to glucocorticosteroids even among normal subjects, providing some implications for the drug treatment, and also gave further evidence that there may exist an immunoregulatory feedback circuit between the immune and neuroendocrine systems.


Appendiceal involvement in pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a diagnostic challenge in the coronavirus disease (COVID) era.
Many studies on pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS) have described abdominal findings as part of multisystem involvement, with limited descriptions of abdominal imaging findings specific to PIMS-TS. To perform a detailed evaluation of abdominal imaging findings in children with PIMS-TS. We performed a single-center retrospective study of children admitted to our institution between April 2020 and January 2021 who fulfilled Royal College of Paediatrics and Child Health criteria for PIMS-TS and who had cross-sectional abdominal imaging. We studied clinical data, abdominal imaging, laboratory markers, echocardiography findings, treatment and outcomes for these children. We also reviewed the literature on similar studies. During the study period, 60 PIMS-TS cases were admitted, of whom 23 required abdominal imaging. Most (74%) were from a Black, Asian or minority ethnic background and they had an average age of 7 years (range 2-14 years). All children had fever and gastrointestinal symptoms on presentation with elevated C-reactive protein, D-dimer and fibrinogen. Most had lymphopenia, raised ferritin and hypoalbuminemia, with positive severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibodies in 65%. Free fluid (78%), right iliac fossa mesenteric inflammation (52%), and significantly enlarged mesenteric lymph nodes (52%) were the most common imaging findings. Appendiceal inflammation (30%) and abnormal distal ileum and cecum/ascending colon wall thickening (35%) were also common. All children responded well to medical management alone, with no mortality. In addition to free fluid, prominent lymphadenopathy, and inflammatory changes in the right iliac fossa, we found abnormal long-segment ileal thickening and appendicitis to be frequent findings. Recognition of appendiceal involvement as a component of the PIMS-TS spectrum should help clinicians avoid unnecessary surgical intervention as part of a multidisciplinary team approach.


Ilex Paraguariensis exposition to As and Cd in a closed soilless system.
The exposition of mate (Ilex Paraguariensis A. St.-Hil.) to As and Cd was investigated in plants derived from young mini-cuttings. Mate plants were cultivated in a closed soilless system, composed of coarse sand as substrate and flood fertirrigation. Plantlets were fertirrigated with nutritive solution and As and Cd solutions were added to the nutritive solution in the final concentration of 8 and 17 mg L-1 (As) and of 17 and 33 mg L-1 (Cd) during 14 days. Results show that stem diameter and Dickson quality index (DQI) variables could not be used as a potential indicator of accumulation of As and Cd. The shoot height, number of leaves and chlorophyll index are variables easy and quick to measure and they can be used as parameters to evaluate the stress caused in mate plants cultivation in a closed soilless system. The highest concentration of As and Cd was in roots of plants. Beyond the roots, As and Cd also can be translocated to the leaves achieving high concentrations. In addition, leaves from the treated mate plants were submitted to a hot infusion extraction in order to simulate the traditional beverage and As and Cd were determined in the infusion. Regarding to the infusion procedure, considerable As and Cd amounts were extracted from the leaves leading to conclude that this way of consumption can be an important source of toxic elements for the human diet.


Association between FAS 1377G>A polymorphism and breast cancer susceptibility: a meta-analysis.
Published studies on the association between FAS 1377G>A polymorphism and breast cancer susceptibility were inconclusive. To derive a more precise assessment of the association, a meta-analysis of published studies was performed. PubMed, Embase, and Web of Science were searched for eligible studies on the association between FAS 1377G>A polymorphism and breast cancer susceptibility. Five studies with a total of 2,905 cases and 3,090 controls were included into the meta-analysis. Overall, FAS 1377G>A polymorphism was significantly associated with increased susceptibility to breast cancer (for AA versus GG: odds ratio (OR) = 1.39, 95% confidence interval (95% CI) 1.12-1.72, P = 0.003; for AA/GA versus GG: OR = 1.18, 95% CI 1.06-1.32, P = 0.004; for AA versus GG/GA: OR = 1.28, 95% CI 1.05-1.56, P = 0.015). Subgroup analysis by ethnicity found that FAS 1377G>A polymorphism was significantly associated with increased susceptibility to breast cancer in Asians (for AA versus GG: OR = 1.48, 95% CI 1.16-1.89, P = 0.001; for AA/GA versus GG: OR = 1.24, 95% CI 1.06-1.46, P = 0.008; for AA versus GG/GA: OR = 1.35, 95% CI 1.08-1.69, P = 0.008), but the association was not found in Caucasians. Therefore, the findings of the meta-analysis suggest that FAS 1377G>A polymorphism is significantly associated with increased susceptibility to breast cancer in Asians.


The effect of dietary phosphorus on heat shock protein mRNAs during acute heat stress in male broiler chickens (Gallus gallus).
A 2 x 2 factorially arranged completely randomized experimental design was used to study the relationship between inorganic phosphorus (Pi) and heat shock protein (HSP) mRNA expression in different organs of commercial broiler cockerels during acute heat stress (HS). Brain, heart, liver and spleen were assayed for hsp70, hsp90alpha and hsp90beta mRNA. At 1 day of age, chickens were assigned randomly to two dietary Pi treatment groups (Pi-: 0.16%; Pi+: 0.5%). At 3 weeks of age, half of the chickens in each Pi group were subjected to HS (Ta=41 degrees C, 60 min) while the other half was maintained in a thermoneutral environment (CN, Ta=25 degrees C). The results showed inter-organ variation in the expression of HSP mRNAs. Brain expressed the most HSP mRNAs while spleen expressed the least. When broilers were subjected to HS, the expression of HSP mRNAs was influenced positively by the consumption of the Pi+ diet. However, analysis of variance revealed that Ta influenced HSP transcription more than phosphorus availability. Thermal stress caused induction of hsp90alpha and hsp90beta in heart, liver and spleen, but hsp90alpha and hsp9beta mRNA levels were stable in brain. Transcription of hsp70 increased (P< or =0.05) in all organs from chickens in HS groups when compared to chickens in CN groups. Although Pi+ did not show any significant increases in the expression of hsp mRNAs, there were consistently larger HSP mRNA values in liver and spleen tissues. The high expression of hsp90alpha and hsp90beta in brain of chicks in both CN and HS conditions could be due to the involvement of hsp90 in steroid hormone receptors or the high metabolic activity of neurons in the central nervous system.


Endoscopic resection of pleomorphic adenoma arising in the nasopharynx.
Pleomorphic adenoma is the commonest benign tumor of the salivary glands. It has rarely been reported arising in the nasopharynx. A pleomorphic adenoma originating from the left lateral wall of the nasopharynx was found in a 61-year-old female who presented with nasal obstruction and intermittent epistaxis. It was successfully removed by combined transnasal and transoral surgery under endoscopic visualization. Endoscope-guided surgery may be helpful for the complete resection of benign nasopharyngeal tumors whilst minimizing injury to the Eustachian tube openings or velopharynx.


A Weaving Rip-Stop Technique Leads to a Significantly Increased Load to Failure and Reduction in Suture-Tendon Cut-Through in a Biomechanical Model of Rotator Cuff Repair.
To present an alternative arthroscopic rip-stop technique with a single suture tape weaved through the tendon from anterior to posterior and to biomechanically test its strength against a control technique consisting of a single-row repair with simple sutures. This was a controlled biomechanical study. Dissection and harvesting of the supraspinatus muscle-tendon unit were performed along the cable in 9 matched-pair cadaveric shoulders. Samples were divided into 2 groups: simple suture repair only (SSR) and simple suture repair with rip-stop (SSPR). Biomechanical testing was performed with an initial preload, followed by cyclic loading and then ramp to failure. Peak-to-peak displacement, stiffness (in newtons per millimeter), load at failure (in newtons), and failure mechanism were recorded. Data were compared using the paired-sample t test. The average peak-to-peak displacement for SSR samples was not significantly different from that of SSPR samples (P = .96). Similarly, elongation in the SSR and SSPR groups was not significantly different (P = .82). Stiffness was significantly different between the SSR and SSPR groups (P = .0054): SSR samples were less stiff than SSPR samples. Moreover, SSR samples failed at significantly lower forces than did SSPR samples (P = .028). A larger percentage of failures occurred due to tendon cut-through among SSR samples versus suture breakage among SSPR samples. An alternative rip-stop technique is presented in this biomechanical model that may assist surgeons to better deal with difficult rotator cuff repairs. Weaving a suture tape as a rip-stop can increase stiffness, achieve higher failure loads when compared with simple suture repair with no rip-stop, and reduce tendon cut-through. This study provides insight into a variation of rip-stop stitch techniques that may help solve the clinical problem of failure occurring at the suture-tendon interface, specifically tendon cut-through.


Hierarchical Porous Metallic V2O3@C for Advanced Aqueous Zinc-Ion Batteries.
Aqueous Zn-ion batteries (ZIBs) are a potential electrochemical energy storage device because of their highly intrinsic safety, low cost, and large capacity. However, it is still in the primary stage because of the limited selection of cathode materials with high rate and long-life cycling stability. In addition, the energy storage mechanisms of ZIBs have not been well established. In this work, we report the synthesis of porous V2O3@C materials with high conductivity and further illustrate its application as the intercalation cathode for aqueous zinc-ion batteries. The unique channel and appropriate pore size distribution of corundum-type V2O3 are beneficial to the rapid zinc ion intercalation and removal, leading to a high rate capability. Also, the carbon framework structure achieves a high cyclic stability. The porous V2O3@C cathode delivers high capacities of 350 mA h g-1 at 100 mA g-1, an excellent rate capability (250 mA h g-1 at 2 A g-1), and an impressive long-life cycling stability with 90% capacity retention over 4000 cycles at 5 A g-1. The storage mechanism of zinc ions in the Zn/V2O3 system was studied by various analytical methods and first-principles calculation.


Prevalence of skin and genital mucous membrane irritations in patients confined to bed.
A comparative and prospective study of the skin and genital mucous membrane conditions of 50 intensive care patients, who were entirely confined to bed, was conducted. Skin and/or genital mucous membrane irritations were developed by 31 patients during their stay in the ICU. These patients had a significantly longer stay in bed in the ICU than those who did not develop such changes. Patients with lesions were significantly washed more often using the pH 8.5 soap than those without lesions. Erythematous was the most commonly observed symptom and the area between the buttocks and saccrum was the most affected.


Outcome of endovascular treatment in postthrombotic syndrome.
The postthrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT) that is characterized by leg swelling and ulceration. Sixty-seven cases of PTS underwent attempted endovascular treatment with success in 63 between June 2005 and June 2012. Thirty-six cases underwent endovascular treatment only and 18 cases combined with temporary femoral arteriovenous fistula, 5 cases great saphenous vein ligation and stripping whereas 4 cases with communicating branch ligation around ulcers. Stenting was successfully performed in 63 of 67 patients. The technical success rate was 94% with no mortality. Fifty-eight cases were followed up from 1 to 84 months. Stent occlusion or restenosis occurred in 17 patients. The primary and secondary patency rates were 87.9% and 93.1%, respectively, at 12 months and 70.7% and 82.8%, respectively, at 36 months. Endovascular treatment of PTS is safe and effective. It can alleviate symptoms and prevent further deterioration of patients with PTS.


Pharmacokinetics and pharmacodynamics of pravastatin alone and with cholestyramine in hypercholesterolemia.
The pharmacokinetics, pharmacodynamics, and safety of pravastatin, a new selective 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, were evaluated during monotherapy and with subsequent concomitant cholestyramine therapy in 33 patients with primary hypercholesterolemia in this randomized study. After 4 weeks, pravastatin monotherapy (5 mg, 10 mg, and 20 mg twice daily) significantly decreased total cholesterol by 17% to 24% (p less than 0.001 versus baseline) and low-density lipoprotein cholesterol by 23% to 35% (p less than 0.001). High-density lipoprotein cholesterol increased by 8% to 9%, and triglycerides decreased by 6% to 9%. The area under the serum concentration-time curve and maximum serum concentration of pravastatin showed dose-proportionality; time to maximum serum concentration and serum elimination half-life were independent of dose. When added to pravastatin therapy, cholestyramine enhanced the lipid-lowering effects of pravastatin. After 4 weeks of combination therapy, total cholesterol was reduced by 32% to 38% (p less than 0.001 versus baseline), and low-density lipoprotein cholesterol was reduced by 47% to 56% (p less than 0.001). High-density lipoprotein cholesterol increased by 11% to 18% (p less than 0.05). Pravastatin was well tolerated; no clinical adverse events directly attributable to the drug were reported.


Cisplatin-induced peripheral neurotoxicity in rats reduces the circulating levels of nerve growth factor.
The pathogenesis of the neurotoxicity of most antineoplastic drugs is unknown. Recent reports suggest that changes in the circulating levels of nerve growth factor (NGF) might be related to the dorsal root ganglia sensory neuron damage induced by cisplatin (CDDP), the first member of a family of widely used and very effective platinum-derived anticancer agents. Using a well-characterized model of CDDP neurotoxicity, we demonstrated that the NGF circulating level decreased during chronic CDDP administration in close accordance with the clinical course and returned to normal levels after recovery from the neurotoxic damage. Moreover, these changes were restricted to NGF and did not involve other trophic factors of the same neurotrophin family. Our findings are in agreement with previous in vitro and in vivo results and further suggest that NGF plays a specific role in the course of CDDP-induced primary sensory neuron damage.


Allergen Extraction and Purification from Natural Products: Main Chromatographic Techniques.
The development of techniques and methods for allergen purification is essential for diagnosis and the development of safe immunotherapeutic agents. The most common purification techniques include chromatographic methodologies. In this chapter, we review and describe the details of the methodologies of using ion-exchange, gel-filtration, and affinity chromatography to purify two well-known panallergens, profilin and parvalbumin.


The Kuwait University Anxiety Scale: reliability and criterion-related validity in Syrian college students.
The Kuwait University Anxiety Scale was administered to 51 male and 56 female undergraduates in Syria. Respectively, the coefficients alpha for men, women, and the whole group were .91, .92, and .92; the test-retest rs after 14 to 21 days .88, .81, and .84; and the criterion-related validities .64, .62, and .64 against scores on Spielberger, et al.'s Trait Anxiety scale.


Effect of delays in initiation of adjuvant endocrine therapy on survival among women with breast cancer.
Delays in initiating adjuvant endocrine therapy (AET) are a cause for concern among women with breast cancer and clinicians, but the impact of delayed AET on overall survival (OS) is unclear. This study seeks to describe the relationship between delayed AET and OS. Retrospective cohort study of women with stage II and III hormone receptor positive, human epidermal receptor 2 negative, invasive breast cancer, identified from the National Cancer Database. The primary exposure delayed AET, was defined as initiation of AET more than 12 months after breast cancer diagnosis. Using logistic regression, we examined predictors of delayed AET. The survival analysis with Cox proportional hazards regression adjusted for patient, tumor, and treatment characteristics. Among the 391,594 included women, 12,162 (3.1%) had delayed AET. Predictors of delayed AET included Black race (adjusted odds ratio [aOR] = 1.61, 95% confidence interval [CI] 1.52-1.70) or Hispanic ethnicity (aOR = 1.25, 95% CI 1.16-1.35) vs white race, Medicare (aOR = 1.13, 95% CI 1.06-1.20) or Medicaid (aOR = 1.41, 95% CI 1.32-1.50) versus private insurance, and cancer stage III (aOR = 1.24, 95% CI 1.19-1.30) vs stage II. With median follow-up of 67.4 months, 67,335 (17.2%) patients died. Delayed AET had no statistically significant effect on the hazard of death (adjusted hazards ratio = 1.01; 95% CI 0.96-1.06) compared to initiation within 12 months of diagnosis. This study suggests that there may be no adverse impact on survival if initiation of AET occurs 12 to 24 months after initial diagnosis compared to within 12 months of diagnosis as currently recommended.


Evaluation of timolol maleate combination therapy in chronic open-angle glaucoma.
In an eight-week study, timolol maleate ophthalmic solution 0.25% was administered twice daily with either pilocarpine 2% four times a day, epinephrine 2% twice a day, carbachol 1.5% four times a day, or 250 mg of acetazolamide twice a day to 44 patients with chronic open-angle glaucoma. Compared to baseline readings on standard therapy alone, mean intraocular pressure was significantly reduced after addition of timolol maleate to each of the regimens. Mean facility of outflow was unaffected. No clinically significant ocular irritation or changes in visual acuity, pupil size, or vital signs were observed in any patient. Timolol maleate appears to be effective and well tolerated when administered with other antiglaucoma medications in patients with open-angle glaucoma.


Developing and validating nomograms for predicting the survival in patients with clinical local-advanced gastric cancer.
Many patients with gastric cancer are at a locally advanced stage during initial diagnosis. TNM staging is inaccurate in predicting survival. This study aims to develop two more accurate survival prediction models for patients with locally advanced gastric cancer (LAGC) and guide clinical decision-making. We recruited 2794 patients diagnosed with LAGC (2010-2015) from the Surveillance, Epidemiology, and End Results (SEER) database and performed external validation using data from 115 patients with LAGC at Yantai Affiliated Hospital of Binzhou Medical University. Univariate and multifactorial survival analyses were screened for meaningful independent prognostic factors and were used to build survival prediction models. Concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were evaluated for nomograms. Finally, the differences and relationships of survival and prognosis between the three different risk groups were described using the Kaplan-Meier method. Cox proportional risk regression model analysis identified independent prognostic factors for patients with LAGC, and variables associated with overall survival (OS) included age, race, marital status, T-stage, N-stage, grade, histologic type, surgery, and chemotherapy. Variables associated with cancer-specific survival (CSS) included age, race, T-stage, N-stage, grade, histological type, surgery, and chemotherapy. In the training cohort, C-index of nomogram for predicting OS was 0.722 (95% confidence interval [95% CI]: 0.708-0.736] and CSS was 0.728 (95% CI: 0.713-0.743). In the external validation cohort, C-index of nomogram for predicted OS was 0.728 (95% CI:0.672-0.784) and CSS was 0.727 (95% CI:0.668-0.786). The calibration curves showed good concordance between the predicted and actual results. C-index, ROC, and DCA results indicated that our nomograms could more accurately predict OS and CSS than TNM staging and had a higher clinical benefit. Finally, to facilitate clinical use, we set up two web servers based on nomograms. The nomograms established in this study have better risk assessment ability than the clinical staging system, which can help clinicians predict the individual survival of LAGC patients more accurately and thus develop appropriate treatment strategies.


Nifedipine, a calcium-channel blocker, attenuated glucose intolerance and white adipose tissue dysfunction in type 2 diabetic KK-A(y) mice.
To explore the metabolic actions of nifedipine on diabetes, we examined glucose intolerance and white adipose tissue changes in type 2 diabetic KK-A(y) mice. Male KK-A(y) mice were treated with nifedipine (1.5 mg/kg/day in lab chow) for 5 weeks, which did not affect blood pressure or feeding of KK-A(y) mice. After treatment with nifedipine, body weight tended to decrease and the weight of white adipose tissue was reduced. Without food restriction, nifedipine decreased plasma insulin level, while plasma glucose level tended to decrease. In oral glucose tolerance test, nifedipine suppressed the increase in glucose level after a glucose load without affecting plasma insulin concentration. Nifedipine also improved the result of insulin tolerance test. In white adipose tissue, nifedipine increased adipocyte number and the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and adipocyte fatty acid-binding protein related to adipocyte differentiation. In addition, expression of adiponectin, insulin receptor, insulin receptor substrate-1, and glucose transporter type-4 was also increased by nifedipine. Nifedipine also increased the expression of NO synthase in white adipose tissue. Nifedipine did not affect expression of angiotensin II type 1 (AT₁) and type 2 (AT₂) receptors in white adipose tissue. Such changes in white adipose tissue were apparent in retroperitoneal adipose tissue. Nifedipine did not change the expression of angiotensin receptors, renin receptor, and angiotensinogen in white adipose tissue. Moreover, nifedipine attenuated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and increased superoxide dismutase (SOD) activity in white adipose tissue. These results suggest that nifedipine can enhance insulin sensitivity and reduce white adipose tissue, possibly related to stimulation of adipocyte differentiation.


Suppressing ion migration in metal halide perovskite via interstitial doping with a trace amount of multivalent cations.
Cations with suitable sizes to occupy an interstitial site of perovskite crystals have been widely used to inhibit ion migration and promote the performance and stability of perovskite optoelectronics. However, such interstitial doping inevitably leads to lattice microstrain that impairs the long-range ordering and stability of the crystals, causing a sacrificial trade-off. Here, we unravel the evident influence of the valence states of the interstitial cations on their efficacy to suppress the ion migration. Incorporation of a trivalent neodymium cation (Nd3+) effectively mitigates the ion migration in the perovskite lattice with a reduced dosage (0.08%) compared to a widely used monovalent cation dopant (Na+, 0.45%). The photovoltaic performances and operational stability of the prototypical perovskite solar cells are enhanced with a trace amount of Nd3+ doping while minimizing the sacrificial trade-off.


[Fear and beliefs about vaccination in compulsory education teachers during the covid-19 pandemic.]
Schools can help to restore confidence in vaccines by providing reliable information to their students. To do this, teachers must be willing to convey a pro-vaccination message. In this context, know the fear and beliefs about vaccination of the teachers may be appropriate. An online cross-sectional study was carried out, in December 2020, on active teachers from the autonomous community of Catalonia (Spain). The sample included 1507 subjects, men (23.4%) and women (76.6%), aged 21 to 66 years, from preschool (21.1%), primary (41.9%) and secondary (37%) levels. A sociodemographic questionnaire, the Vaccination Fear Scale VFS-6, and a questionnaire on vaccines and vaccination beliefs were administered. Univariate and descriptive data analysis was performed. In this study, only 45.3% of the teachers did not show vaccination fear; data consistent with a high proportion of teachers who did not believe they should be vaccinated (27.3%) or who hesitate about the need to do so (24.4%), regardless of the high perception of the disease severity or belonging to a risk group. With high percentages (>50%) of teachers who did not believe, or doubt, about the safety and usefulness of vaccines; and less significant but important percentages that indicated distrust in pharmaceutical companies and in the government. Being a woman, young and a preschool education teacher, followed by primary education, were risk factors for vaccination refusal. The study shows high rates of fear and mistrust towards vaccines in teachers.


Vitamin D transport - the nature of the interaction between plasma DBP and tissue protein.
The plasma-binding protein for vitamin D and its metabolites (DBP) is bound with high affinity (KA approximately 10(7) M-1) and specificity by a 40,000-dalton protein which is a proven constituent of all tissue cytosols examined. This association may be important for in vivo sterol transfer, but its role is currently not defined.


Peripheral blood lymphocyte responses to cytomegalovirus seropositivity after allogeneic-hematopoietic stem cell transplantation.
The main purpose of this study was to investigate the relationship among cytomegalovirus (CMV) viremia, peripheral immune cells alternations, and leukemia prognosis. We studied 90 leukemia patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from 2008 to 2015. Their complete clinical laboratory data were collected until 1 year after transplantation. All patients were serum CMV negative before allo-HSCT. After transplantation, the CMV reactivation group showed increased peripheral CD8+ T cells and decreased CD4+ T cells and B cells. However, CD8/CD4 ratio and B cells restored by control of CMV infection due to 2 months maximum course of ganciclovir treatment. CMV seropositivity was positively related to leukemia-free survival (LFS) of all recruited leukemia types. In summary, CMV drives immune cell post-transplantation fluctuation, which also favors LFS of leukemia partly resulted from CD8+ T cells.


Factors related to SARS-CoV-2 infection in healthcare professionals in Spain. The SANICOVI project.
To describe the factors related to the situation of SARS-CoV-2 transmission identified by health professionals in Spain and to propose prevention strategies. Cross-sectional descriptive study. The population were healthcare professionals working in institutions caring for COVID-19 patients and also confirmed cases of SARS-CoV-2 infection. A questionnaire with sociodemographic, occupational and epidemiological variables was used. Descriptive and bivariate analysis was performed according to the nature of the variables. A total of 2.230 questionnaires were analysed on a potential population of 41,239 (5.47%). The diagnosis was made based on a suspicious case (63.4%) and a probable case (12.3%). A study of contacts was carried out at 50.3%. The perception about the availability of protective measures as «always/frequently» were: FPP1 mask 57.3%, gloves 89.5%, soap 95% and hydroalcoholic solution 91.5%. In PPE, FPP2, FPP3 mask, goggles and disposable gowns at around 50%. The availability of protective measures, by field of work, presented significant differences. The average number of patients attended related to the performance of hand hygiene at moment4 and the perception of performing it correctly at moments4 and5. Preliminary data are presented, with variability in the response rate by Autonomous Region. Healthcare professionals infected by SARS-CoV-2 identified the management of the chain of infection transmission, the use and adequacy of protective equipment, as well as the effectiveness of handwashing as factors related to the transmission of the virus among professionals.


[INTRAVENOUS IMMUNOGLOBULIN TREATMENT TO PREVENT BK NEPHROPATHY IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS WITH BK VIRUS].
In this retrospective study we examined the safety and efficacy of high-dose intravenous immunoglobulin (HD-IVIG) therapy in preventing BKVN in pediatric renal transplant recipients with BK-viremia/viruria. BK virus nephropathy (BKVN) is diagnosed in 5-16% of pediatric renal transplant recipients and is preceded by BK viremia/viruria. Despite irreversible renal damage associated with BKVN, there is a lack of evidence-based guidelines for preventive measures in patients with BK viremia/viruria. All pediatric renal transplant recipients under our care underwent routine testing for urine and blood BK virus, using the polymerase chain reaction (PCR) technique. Patients exhibiting BK-viruria < 107 copies/milliliter (ml) and/or BK-viremia<103 copies/ml without any evidence of BKVN, were managed with 50% dose reduction of the immunosuppressive drug mycophenolate mofetil (MMF). Absence of BK viral load decline within two months from MMF dose reduction was managed with HD-IVIG (at 2 grams/kg body weight). The study included 62 patients over a 6-year period; 31 patients (50%) showed BK-viremia/viruria; 13/31 patients (42%) suffered from significant and persistent BK-viremia/viruria, unresponsive to MMF dose reduction, and were managed with HD-IVIG; 12/13 (92%) showed significant BK viral load reduction within 6 months from HD-IVIG therapy. Except for transient headache, no patient exhibited major adverse effects to HD-IVIG therapy, and none developed overt BKVN during the study period. Preventive HD-IVIG therapy in pediatric renal transplant recipients with BK viremia/viruria unresponsive to MMF dose reduction is safe and effective in preventing the development of BKVN. Additional large-scale studies are necessary to establish our findings.


SARS-CoV-2 wastewater surveillance in Germany: Long-term RT-digital droplet PCR monitoring, suitability of primer/probe combinations and biomarker stability.
In recent months, wastewater-based epidemiology (WBE) has been shown to be an important tool for early detection of SARS-CoV-2 circulation in the population. In this study, a detection methodology for SARS-CoV-2 RNA (wildtype and variants of concern) in wastewater was developed based on the detection of different target genes (E and ORF1ab) by polyethylene glycol (PEG) precipitation and digital droplet PCR. This methodology was used to determine the SARS-CoV-2 concentration and the proportion of N501Y mutation in raw sewage of the wastewater treatment plant of the city of Karlsruhe in south-western Germany over a period of 1 year (June 2020 to July 2021). Comparison of SARS-CoV-2 concentrations with reported COVID-19 cases in the catchment area showed a significant correlation. As the clinical SARS-CoV-2 official case report chain takes time, viral RNA titre trends appeared more than 12 days earlier than clinical data, demonstrating the potential of wastewater-based epidemiology as an early warning system. Parallel PCR analysis using seven primer and probe systems revealed similar gene copy numbers with E, ORF, RdRP2 and NSP9 assays. RdPP1 and NSP3 generally resulted in lower copy numbers, and in particular for N1 there was low correlation with the other assays. The occurrence of the N501Y mutation in the wastewater of Karlsruhe was consistent with the occurrence of the alpha-variant (B.1.1.7) in the corresponding individual clinical tests. In batch experiments SARS-CoV-2 RNA was stable for several days under anaerobic conditions, but the copy numbers decreased rapidly in the presence of dissolved oxygen. Overall, this study shows that wastewater-based epidemiology is a sensitive and robust approach to detect trends in the spread of SARS-CoV-2 at an early stage, contributing to successful pandemic management.


Task-Specific Fatigue Among Older Primary Care Patients.
Fatigue is a common condition contributing to disability among older patients. We studied self-reported task-specific fatigue and its relation with mobility task performance among community-dwelling primary care patients. Cross-sectional analysis of baseline demographic and health data from a prospective cohort study of 430 primary care patients aged 65 years or older. Fatigue was measured using the Avlund Mobility-Tiredness Scale. Performance tasks included rising from a chair, walking 4 m, and climbing two flights of stairs. Among demographic and health factors, pain was the only attribute consistently predictive of fatigue status. Self-reported chair rise fatigue and walking fatigue were associated with specific task performance. Stair climb fatigue was not associated with stair climb time. Pain is strongly associated with fatigue while rising from a chair, walking indoors, and climbing stairs. This study supports the validity of self-reported chair rise fatigue and walking fatigue as individual test items.


Effect of exogenously administered glucagon on plasma glucose levels in totally depancreatized dogs.
Glucagon was administered exogenously via a subcutaneous route to totally depancreatized adult mongrel dogs and studies were made with major emphasis on glucagon effect on the plasma glucose levels. 1. In the totally depancreatized dogs, the plasma glucose levels determined 90 minutes after glucagon injection (40 micrograms/kg s.c.). were compared with the pretreatment fasting plasma glucose levels. The rate of increase in the plasma glucose levels was 5.13 +/- 0.48 times (M +/- SEM) in dogs with low pretreatment level (lower than 100 mg/dl). In dogs with higher pretreatment levels (100-400 mg/dl), the increase was 1.62 +/- 0.40 times. And in dogs with the pretreatment levels higher than 400 mg/dl, the value was 0.90 +/- .07 times. 2. Ninety minutes after regular insulin injection (0.25 U/kg i.v.), glucagon was administered (40 micrograms/kg s.c.), and the changes in the plasma glucose levels were determined. 3. In totally depancreatized dogs, a transient increase in the plasma insulin level was noted when glucagon was administered (40 micrograms/kg s.c.) under infusion of a mixture of glucose and insulin. 4. There was no significant difference in the rate of disappearance of glucagon from the blood between normal and totally depancreatized dogs. 5. It is considered that glucagon would be useful for the treatment of hypoglycemia encountered after total pancreatectomy.


Comparison of adult somatic and excretory-secretory antigens in enzyme-linked immunosorbent assay for serodiagnosis of human infection with Paragonimus heterotremus.
Adult somatic antigen extract of Paragonimus heterotremus was compared with excretory-secretory (ES) antigen in an enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of human paragonimiasis. The absorbence values in ELISA using the adult somatic antigen were not significantly different from the values obtained using ES antigens (P greater than 0.05). The sensitivity of the ELISA using either antigen was 100%, but the specificity was 96% with somatic and 98% with ES antigens due to a cross reaction with fascioliasis sera. It appears that both somatic and ES antigens are effective antigens for use in serodiagnosis of human paragonimiasis heterotremus.


A fluoride-insensitive inorganic pyrophosphatase isolated from Methanothrix soehngenii.
An inorganic pyrophosphatase [E.C. 18.104.22.168] was isolated from Methanothrix soehngenii. In three steps the enzyme was purified 400-fold to apparent homogeneity. The molecular mass estimated by gelfiltration was 139 +/- 7 kDa. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis indicated that the enzyme is composed of subunits with molecular masses of 35 and 33 kDa in an alpha 2 beta 2 oligomeric structure. The enzyme catalyzed the hydrolysis of inorganic pyrophosphate, tri- and tetrapolyphosphate, but no activity was observed with a variety of other phosphate esters. The cation Mg2+ was required for activity. The pH optimum was 8 at 1 mM PPi and 5 mM Mg2+. The enzyme was heat-stable, insensitive to molecular oxygen and not inhibited by fluoride. Analysis of the kinetic properties revealed an apparent Km for PPi of 0.1 mM in the presence of 5 mM Mg2+. The Vmax was 590 mumol of pyrophosphate hydrolyzed per min per mg protein, which corresponds to a Kcat of 1400 per second. The enzyme was found in the soluble enzyme fraction after ultracentrifugation, when cells were disrupted by French Press. Upto 5% of the pyrophosphatase was associated with the membrane fraction, when gentle lysis procedure were applied.


Short epitope-based synthetic peptides for serodiagnosis of human strongyloidiasis.
Strongyloidiasis is one of the major intestinal infections in humans, and a neglected tropical disease whose diagnosis still poses a challenge. We hypothesized that diagnostic tests based on short peptides containing major epitopes may represent a promising strategy to improve strongyloidiasis detection due to reduced cross-reactivity and higher sensitivity. Our aim was to evaluate two synthetic peptides selected by phage display (C10 and D3) as potential tools for serodiagnosis of strongyloidiasis, and to predict their putative antigen target. To investigate their diagnostic potential, we have tested different panels of serum samples (n=120) by enzyme linked immunosorbent assay (ELISA) to detect specific IgG, and their diagnostic parameters were calculated. Similarities with proteins from Strongyloides stercoralis were searched and conformational epitopes were predicted and aligned to known protein structures. Both C10 and D3 achieved sensitivity of 95%, and specificities were 89.2% and 92.5%, respectively. D3 presented the highest diagnostic efficiency (93.3%). Epitope prediction for both C10 and D3 led to the alignment with the cytochrome c oxidase subunit 1 structure. In brief, we propose two synthetic peptides as new biomarkers for serodiagnosis of strongyloidiasis, which can be promptly used for ELISA and in future field sensor platforms.


[Evaluation of the cytogenetic effect of the herbicide treflan and of a number of its metabolites on mammalian somatic cells].
Investigation of the cytogenetic effect of two samples of trifluralin, a herbicide, (chemically pure active ingredient and 25% emulsion concentrate) and its eight metabolites in the culture of human peripheral lymphocytes in vitro and in the bone marrow cells of mice in vivo has revealed that trifluralin itself does not induce chromosome aberrations both in vitro and in vivo, but some of its derivatives possess moderate (metabolites III and VII) or weak (metabolites II and XI) clastogenic activity. The results obtained should be taken into account for the hygienic regulation of trifluralin use allowing for the reality of entrance of its mutagenic derivatives into the human organism and for the degree of its genetic danger.


Disability in people with epilepsy: A nationally representative cross-sectional study.
The objective of this study was to explore the prevalence and predictors of limitations causing disability in patients treated for seizures or epilepsy compared with patients without epilepsy. This was a retrospective cross-sectional study using the National Health and Nutrition Examination Survey (NHANES). We included all participants ≥20 years old for 2013-2018. We classified patients as having epilepsy if they reported taking at least one prescription medication to treat seizures or epilepsy. Physical, mental, and social limitations were determined from interview questions. We report the prevalence of any limitation and total number of limitations for participants without vs. with epilepsy using serial negative binomial regressions and severity of individual limitations according to epilepsy status. We included 17,057 participants, of whom 148 (0.8%) had epilepsy. Overall, 80% (95% confidence interval [CI]: 73%-86%) with epilepsy vs. 38% (95% CI: 36%-39%) without epilepsy reported at least 1 limitation (p < 0.01). The mean number of limitations was 7.5 (95% CI: 6.2-8.8) for those with epilepsy vs. 2.4 (95% CI: 2.3-2.6) for those without epilepsy (p < 0.01). Epilepsy was associated with an incidence rate ratio (IRR) of 3.1 (95% CI: 2.6-3.7) in an unadjusted negative binomial regression. After adjusting for demographics and comorbidities, this association was no longer significant (IRR: 1.2, 95% CI: 0.9-1.7). Limitations cited by 40-50% of participants with epilepsy included stooping/kneeling/crouching, standing for long periods of time, and pushing/pulling objects. Limitation severity was consistently higher in patients with epilepsy. Patients with epilepsy had 3.1 times as many physical, mental, or social limitations compared with those without epilepsy, and disability severity was consistently higher. This effect was attenuated after considering baseline variables such as smoking and depression severity. Our work implies the importance of structured mental health screening and self-management programs targeting mood, weight, and lifestyle as potential leverage points towards alleviating epilepsy-related disability.


PDK1 in NF-κB signaling is a target of Xanthium strumarium methanolic extract-mediated anti-inflammatory activities.
Xanthium strumarium L. (Asteraceae) has traditionally been used to treat bacterial infections, nasal sinusitis, urticaria, arthritis, chronic bronchitis and rhinitis, allergic rhinitis, edema, lumbago, and other ailments. However, the molecular mechanisms by which this plant exerts its anti-inflammatory effects are poorly characterized. Here we studied the immunopharmacological activities of the methanolic extract of the aerial parts of this plant (Xs-ME) and validated its pharmacological targets. To evaluate the anti-inflammatory activity of Xs-ME, we employed lipopolysaccharide (LPS)-treated macrophages and an HCl/EtOH-induced mouse model of gastritis. We also used HPLC to identify the potentially active anti-inflammatory components of this extract. The molecular mechanisms of its anti-inflammatory activity were studied by kinase assays, reporter gene assays, immunoprecipitation analysis, and overexpression of target enzymes. The production of nitric oxide (NO) and prostaglandin E2 (PGE2) were both suppressed by Xs-ME. Moreover, orally administered Xs-ME ameliorated HCl/EtOH-induced gastric lesions. Furthermore, this extract downregulated the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and reduced the nuclear levels of NF-κB. Signaling events upstream of NF-κB translocation, such as phosphorylation of AKT and the formation of PDK1-AKT signaling complexes, were also inhibited by Xs-ME. Moreover, Xs-ME suppressed the enzymatic activity of PDK1. Additionally, PDK1-induced luciferase activity and Akt phosphorylation were both inhibited by Xs-ME. We also identified the polyphenol resveratrol as a likely active anti-inflammatory component in Xs-ME that targets PDK1. Xs-ME exerts anti-inflammatory activity in vitro and in vivo by inhibiting PDK1 kinase activity and blocking signaling to its downstream transcription factor, NF-κB.


Factors influencing the success of conservative treatment of interstitial pregnancy.
To identify demographic, morphological and biochemical characteristics of interstitial pregnancies that are associated with a successful outcome of conservative treatment (expectant management or medical treatment with methotrexate). Over a period of 6 years all clinically stable women with a certain ultrasound diagnosis of interstitial ectopic pregnancy were managed either expectantly (no interventions) or medically (systemic or local methotrexate injection). The outcome of conservative treatment was compared to a number of diagnostic parameters, which were recorded at the initial visit. The treatment was classified as successful if serum human chorionic gonadotropin (hCG) level declined below 20 IU/L without the need for any additional interventions, such as the administration of methotrexate or surgery. A total of 42 interstitial pregnancies were diagnosed during the study period. Out of 35 women included in the final analysis 7 (20%) were managed expectantly and 28 (80%) received either local (n = 23) or systemic methotrexate (n = 5). There were no significant differences in the success rates of expectant treatment and treatment with either systemic or local methotrexate. The initial median serum hCG was significantly lower in women with successful conservative management (3216 IU/L vs. 15 900 IU/L; P < 0.05) but there were no other significant differences between cases with successful and failed treatment. The measurement of serum hCG at the initial visit may be used to predict the likelihood of successful conservative treatment of interstitial pregnancy.


THN 102 for Excessive Daytime Sleepiness Associated with Parkinson's Disease: A Phase 2a Trial.
Excessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's disease (PD) without approved treatment. THN102 is a novel combination drug of modafinil and low-dose flecainide. The aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS. The method involved a randomized, double-blind, placebo-controlled, crossover trial testing two doses of THN102 (200 mg/d modafinil with 2 mg/d [200/2] or 18 mg/d flecainide [200/18]) versus placebo; 75 patients were exposed to treatment. The primary endpoint was safety. The primary efficacy outcome was the change in Epworth Sleepiness Scale (ESS) score. Both doses of THN102 were well tolerated. ESS significantly improved with THN102 200/2 (least square means vs. placebo [95% confidence interval, CI]: -1.4 [-2.49; -0.31], P = 0.012) but did not change significantly with the 200/18 dosage. THN102 was well tolerated and showed a signal of efficacy at the 200/2 dose, supporting further development for the treatment of EDS in PD. © 2021 International Parkinson and Movement Disorder Society.