Methodological issues in the use of the concurrent activities paradigm.
This paper presents a critical analysis of one type of dual-task procedure, the lateralized concurrent activities paradigm. Extrinsic and intrinsic factors that may influence the interpretation of results obtained with this paradigm are isolated and methodological refinements in experimental design and analysis are suggested.


Effect of non-saponin fraction from Panax ginseng on cGMP and thromboxane A2 in human platelet aggregation.
The non-saponin fraction (NSF; lipophilic fraction) from the roots of Panax ginseng inhibited the aggregation of human platelets induced by thrombin (0.1 units/ml) in a dose-dependent manner. NSF induced the elevation of cGMP concentration in human platelets in a similar manner to molsidomine, a known vasodilator. NSF also inhibited Ca(2+)-influx into platelets. While verapamil, a Ca(2+)-antagonist, increased the cAMP level in platelets stimulated by thrombin, NSF had little effect on cAMP formation. Instead, NSF potently inhibited the thromboxane A2 (TXA2) production. The results suggest that NSF may regulate the levels of cGMP and TXA2 to inhibit platelet aggregation induced by thrombin.


B1 transmit phase gradient coil for single-axis TRASE RF encoding.
TRASE (Transmit Array Spatial Encoding) MRI uses RF transmit phase gradients instead of B0 field gradients for k-space traversal and high-resolution MR image formation. Transmit coil performance is a key determinant of TRASE image quality. The purpose of this work is to design an optimized RF transmit phase gradient array for spatial encoding in a transverse direction (x- or y- axis) for a 0.2T vertical B0 field MRI system, using a single transmitter channel. This requires the generation of two transmit B1 RF fields with uniform amplitude and positive and negative linear phase gradients respectively over the imaging volume. A two-element array consisting of a double Maxwell-type coil and a Helmholtz-type coil was designed using 3D field simulations. The phase gradient polarity is set by the relative phase of the RF signals driving the simultaneously energized elements. Field mapping and 1D TRASE imaging experiments confirmed that the constructed coil produced the fields and operated as designed. A substantially larger imaging volume relative to that obtainable from a non-optimized Maxwell-Helmholtz design was achieved. The Maxwell (sine)-Helmholtz (cosine) approach has proven successful for a horizontal phase gradient coil. A similar approach may be useful for other phase-gradient coil designs.


Spermine reduces infarction and neurological deficit following a rat model of middle cerebral artery occlusion: a magnetic resonance imaging study.
The role of nitric oxide (NO) in post-ischemic cerebral infarction has been extensively examined, but few studies have investigated its role on the neurological deficit. In the present study, we investigated the effect of spermine on the temporal evolution of infarct volume, NO production and neurological deficit using magnetic resonance imaging in a model of permanent focal cerebral ischemia in rats. Spermine given at 10 mg/kg 2 h after ischemia reduced the infarct volume by 40% and abolished brain NO production and improved the neurological score 24 h, 48 h and 72 h after ischemia. Spermine also reduced the neurological deficit as evaluated by rotamex, grip strength and neurological severity score tests.


Postoperative vomiting following strabismus surgery in paediatric outpatients: spontaneous versus controlled ventilation.
The study was designed to compare the frequency and severity of postoperative vomiting in paediatric out-patients receiving controlled ventilation (IPPV) or breathing spontaneously (SV) during anaesthesia for strabismus repair. One hundred and twenty unpremedicated children (ages 2-12 years) were studied in a randomized fashion. After intravenous induction of anaesthesia and tracheal intubation, patients breathed halothane 1-1.5 per cent inspired and N2O 66 per cent in O2 spontaneously (n = 60), or received IPPV, halothane 0.5-1 per cent, N2O 66 per cent, and pancuronium 0.05 mg.kg-1, which was reversed with neostigmine and atropine (n = 60). The incidence of vomiting with SV was 50 per cent (95 per cent confidence limits: 34.5-65.5 per cent) compared with 40 per cent (24.5-55.5 per cent) with IPPV (p greater than 0.25). Patients in the SV group experiencing emesis had longer operations than those not vomiting (mean +/- SEM = 1.5 +/- 0.1 vs 1.2 +/- 0.1 hours, p less than 0.005). This was not the case with IPPV. There was no correlation between age, sex, duration of surgery, or number of extraocular muscles repaired, and frequency or severity of vomiting or time to discharge. No significant advantage was afforded by IPPV over SV in the present study.


[Continuous positive airway pressure therapy affects the recurrence of atrial fibrillation in patients with obstructive sleep apnea: a systematic review and meta-analysis].
Objective: A higher incidence of atrial fibrillation is associated with obstructive sleep apnea. The effects of continuous positive airway pressure on atrial fibrillation have been studied in observational studies and randomized controlled trials. We therefore conducted this meta-analysis to assess the effect of continuous positive airway pressure on the recurrence of atrial fibrillation after radiofrequency ablation. Methods: A comprehensive search was conducted in Pubmed, Embase, Cochrane, Web of Science, Wanfang Data and CNKI databases from inception to October 2022. We included cohort studies and randomized controlled trials containing atrial fibrillation situation after catheter ablation with and without continuous positive airway pressure therapy. The random effects model was used to assess odds ratios (OR) and confidence intervals (CI). I2 was used to assess the heterogeneity. Results: Eight studies with a total of 1 395 patients with obstructive sleep apnea met the inclusion criteria. Continuous positive airway pressure therapy decreased atrial fibrillation recurrence by 61% (OR=0.392, 95%CI: 0.267-0.576, I2=37.6%). Subgroup analysis showed that the protective effect was more significant in groups with more hypertension patients (OR=0.272 vs. 0.550, 95%CI: 0.165-0.449 vs. 0.329-0.922). Conclusions: Continuous positive airway pressure therapy reduces the recurrence rate of atrial fibrillation. Patients with hypertension are more likely to benefit from it.


Synthesis and in vitro evaluation of vanillin derivatives as multi-target therapeutics for the treatment of Alzheimer's disease.
A number of novel naphthalimido and phthalimido vanillin derivatives were synthesised, and evaluated as antioxidants and cholinesterase inhibitors in vitro. Antioxidant activity was assessed using DPPH, FRAP, and ORAC assays. All compounds demonstrated enhanced activity compared to the parent compound, vanillin. They also exhibited BuChE selectivity in Ellman's assay. A lead compound, 2a (2-(3-(bis(4-hydroxy-3-methoxybenzyl)amino)propyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione), was identified and displayed strong antioxidant activity (IC50 of 16.67 µM in the DPPH assay, a 25-fold increase in activity compared to vanillin in the FRAP assay, and 9.43 TE in the ORAC assay). Furthermore, 2a exhibited potent BuChE selectivity, with an IC50 of 0.27 µM which was around 53-fold greater than the corresponding AChE inhibitory activity. Molecular modelling studies showed that molecules with bulkier groups, as in 2a, exhibited better BuChE selectivity. This work provides a promising basis for the development of multi-target hybrid compounds based on vanillin as potential AD therapeutics.


Phylogenetic analysis of basidiomycetous yeasts by means of 18S ribosomal RNA sequences: relationship of Erythrobasidium hasegawianum and other basidiomycetous yeast taxa.
The basidiomycetous yeast genus Erythrobasidium Hamamoto, Sugiyama & Komagata, based on the type species E. hasegawianum Hamamoto et al., is characterized by filobasidiaceous basidia and the Q-10 (H2) system as its major ubiquinone. It is tentatively placed in the Filobasidiaceae. The molecular characterization is based on 18S ribosomal RNA sequence comparisons among the basidiomycetous yeasts, and the ultrastructural characterization on the cell wall and hyphal septal pores in E. hasegawianum clearly indicate a close relationship with the teliospore-forming yeasts Rhodosporidium toruloides and Leucosporidium scottii. Our molecular phylogeny with statistical analysis suggests that the existing taxonomic system of basidiomycetous yeasts, based primarily on the morphology of basidia including the teliospores (probasidia), should be revised.


Differential Functional Connectivity Correlates of Cerebrospinal Fluid Biomarkers in Dementia of the Alzheimer's Type.
Alzheimer's disease (AD) is characterized by two cardinal pathologies, which have different topological distributions. The differential anatomical distributions of these pathologies raise the possibility that they exert differential effects on brain networks. To investigate whether cerebrospinal fluid (CSF) biomarkers of the cardinal pathologies have differential relationships with functional connectivity networks in patients with dementia of the Alzheimer's type (DAT). Thirty-nine participants underwent CSF sampling and resting-state functional magnetic resonance imaging. Functional connectivity networks were computed for each participant. CSF biomarker levels of p-tau and amyloid-β (Aβ) were regressed onto these networks to identify subnetworks associated with each biomarker. A subnetwork associated with tau-related pathology was identified with its hub in the right anterior entorhinal cortex. A separate subnetwork associated with Aβ with its hub in the right dorsal anterior cingulate cortex was identified. These results demonstrate the differential effects of AD biomarkers on functional connectivity networks, supporting a possible division of labour between the cardinal pathologies.


Effect of pectin on serum cholesterol, fecal bile acids and biliary lipids in normolipidemic and hyperlipidemic individuals.
Pectin, 40-50 g/day for two weeks administered to nine normolipidemic and hyperlipidemic patients, had no effect on serum triglycerides but did cause a significant decrease in the serum total and unesterified cholesterol of hypercholesterolemic subjects in particular. This was associated with increased excretion of fecal bile acids and total steroids and increased concentration of plasma methyl sterols. Thus, the serum cholesterol reduction by pectin appears to be caused by increased cholesterol elimination into stools as bile acids which is then balanced by enhanced cholesterol synthesis. The composition of biliary bile acids and lipids was not changed and secondary bile acids and sterols decreased inconsistently in feces. The measurement of fecal dry weight suggested that the bulk of the pectin was degraded by bacteria during passage through the intestine. Consequently fecal mass and dry weight were not consistently increased, suggesting that pectin may not be an ideal fibre for increasing fecal bulk in functional colonic disorders.


Genetic determinants of exceptional human longevity: insights from the Okinawa Centenarian Study.
Centenarians represent a rare phenotype appearing in roughly 10-20 per 100,000 persons in most industrialized countries but as high as 40-50 per 100,000 persons in Okinawa, Japan. Siblings of centenarians in Okinawa have been found to have cumulative survival advantages such that female centenarian siblings have a 2.58-fold likelihood and male siblings a 5.43-fold likelihood (versus their birth cohorts) of reaching the age of 90 years. This is indicative of a strong familial component to longevity. Centenarians may live such extraordinarily long lives in large part due to genetic variations that either affect the rate of aging and/or have genes that result in decreased susceptibility to age-associated diseases. Some of the most promising candidate genes appear to be those involved in regulatory pathways such as insulin signaling, immunoinflammatory response, stress resistance or cardiovascular function. Although gene variants with large beneficial effects have been suggested to exist, only APOE, an important regulator of lipoproteins has been consistently associated with a longer human lifespan across numerous populations. As longevity is a very complex trait, several issues challenge our ability to identify its genetic influences, such as control for environmental confounders across time, the lack of precise phenotypes of aging and longevity, statistical power, study design and availability of appropriate study populations. Genetic studies on the Okinawan population suggest that Okinawans are a genetically distinct group that has several characteristics of a founder population, including less genetic diversity, and clustering of specific gene variants, some of which may be related to longevity. Further work on this population and other genetic isolates would be of significant interest to the genetics of human longevity.


The relationship between contralateral prophylactic mastectomy and breast reconstruction, complications, breast-related procedures, and costs: A population-based study of health insurance data.
Increasingly, women are undergoing contralateral prophylactic mastectomy for the treatment of unilateral breast cancer. The relationship between contralateral prophylactic mastectomy and breast reconstruction, postsurgical complications, additional breast-related procedures, and cost has not received the attention it deserves. Data from the New York comprehensive, all-age, all-payer, Statewide Planning and Research Cooperative System were queried to identify patients undergoing unilateral mastectomy or contralateral prophylactic mastectomy from 2008 to 2010. We identified the complications and breast-related procedures within a 2-y follow-up period. Costs of the index operation and subsequent follow-up were estimated. Univariate and multivariate analyses were conducted. Of 12,959 women identified, 10.7% underwent contralateral prophylactic mastectomy. On univariate analysis, contralateral prophylactic mastectomy was positively associated with breast reconstruction, complications, and additional breast-related procedures. Rates of complications were greater for women who had contralateral prophylactic mastectomy (29.5% vs 20.8% for unilateral mastectomy group; P < .001), but not after stratifying by breast reconstruction. Additional breast-related procedures were more common in the contralateral prophylactic mastectomy group than in the unilateral mastectomy group, but only for those who underwent breast reconstruction (82.8% vs 72.1%; P < .001). Unadjusted costs were greater for women with contralateral prophylactic mastectomy than with unilateral mastectomy but did not differ between the groups after adjusting for breast reconstruction and additional breast-related procedures. Women who elected contralateral prophylactic mastectomy in this population-based study were more likely to have both breast reconstruction and additional breast-related procedures than women with unilateral mastectomy. The greater rates of complications and costs associated with contralateral prophylactic mastectomy were explained by breast reconstruction and additional breast-related procedures. Surgeons should counsel patients regarding the increased cost and likelihood of undergoing additional, non-complication-related procedures after contralateral prophylactic mastectomy with breast reconstruction.


Identification of genes and variants associated with quantitative traits using Bayesian factor screening.
We propose a factor-screening method based on a Bayesian model selection framework and apply it to Genetic Analysis Workshop 17 simulated data with unrelated individuals to identify genes and SNP variants associated with the quantitative trait Q1. A Metropolis-Hasting algorithm is implemented to generate a posterior distribution in a restricted model space and thus the marginal posterior distribution of each variant. Our framework provides flexibility to make inferences on either individual variants or genes. We obtained results for 10 simulated data sets. Our methods are able to identify FTP1 and KDR, two genes that are associated with Q1 in a majority of replicates.


Impaired trial-by-trial adjustment of cognitive control in obsessive compulsive disorder improves after deep repetitive transcranial magnetic stimulation.
Adaptive decision making requires the adjustment of behaviour following an error. Some theories suggest that repetitive thoughts and behaviours in obsessive compulsive disorder (OCD) are driven by malfunctioning error monitoring. This malfunction may relate to demonstrated hyperactivity in the medial prefrontal cortex (mPFC), including the dorsal anterior cingulate cortex. In this study, we measured aspects of error monitoring in individuals with OCD and administered deep low frequency repetitive transcranial magnetic stimulation (rTMS) in an attempt to modulate error monitoring capacity. For this pilot study, ten OCD patients and 10 aged-matched healthy controls completed modified versions of the Eriksen Flanker task before and after one session of deep 1 Hz rTMS (1200 pulses) over the mPFC (Brodmann areas 24 and 32). OCD patients received nine additional sessions of daily rTMS to assess their clinical response. Flanker tasks were repeated with patients post-treatment. Overall error rates were higher for patients compared to controls. When subjects were asked to report their errors, OCD patients were able to report fewer of their errors than the control group. In contrast to controls, patients did not demonstrate a normal post-error slowing (PES) phenomenon. This abnormal PES was mainly driven by abnormally slow response times (RTs) following correct responses rather than a failure to slow down after errors. Patients' symptoms and slowed RTs following correct responses improved after ten sessions of rTMS. Certain aspects of error monitoring, namely conscious error report and post error slowing, are impaired in OCD. These impairments can at least be partly corrected by 1 Hz deep rTMS over the mPFC. Simultaneous improvement of OCD symptoms by this method might suggest a correlation between error monitoring impairment and OCD pathophysiology. ClinicalTrials.gov NCT02541812; 09/02/2015.


Selective removal of retinoids and palmitic acid from microsomes by fatty acid binding protein and cellular retinol binding protein.
Studies were conducted to explore the effect of mouse liver cytosolic proteins enriched in fatty acid binding protein or cellular retinol binding protein on the removal of palmitic acid and retinoids from microsomal membranes. When the soluble proteins were incubated with mouse liver microsomes containing (14C)palmitic acid or (3H)retinoids, it was observed that fatty acid binding protein removed selectively the fatty acid and retinyl ester, whereas the retinol was mainly removed by cellular retinol binding protein.


Rationale for Timely Insulin Therapy in Type 2 Diabetes Within the Framework of Individualised Treatment: 2020 Update.
Type 2 diabetes is characterised by chronic hyperglycaemia and variable degrees of insulin deficiency and resistance. Hyperglycaemia and elevated fatty acids exert harmful effects on β-cell function, regeneration and apoptosis (gluco-lipotoxicity). Furthermore, chronic hyperglycaemia triggers a vicious cycle of insulin resistance, low-grade inflammation and a cascade of pro-atherogenic processes. Thus, timely near to normal glucose control is of utmost importance in the management of type 2 diabetes and prevention of micro- and macroangiopathy. The majority of patients are multimorbid and obese, with critical comorbidities such as cardiovascular disease, heart failure and chronic kidney disease. Recently published guidelines therefore recommend patient-centred risk/benefit-balanced use of oral glucose-lowering drugs or a glucagon-like peptide 1 (GLP-1) receptor agonist, or switching to insulin with glycated haemoglobin (HbA1c) out of target. This article covers the indications of early insulin treatment to prevent diabetes-related complications, particularly in subgroups with severe insulin deficit, and to achieve recovery of residual β-cell function. Furthermore, the individualised, risk/benefit-balanced, timely initiation of insulin as second and third option is analysed. Timely insulin initiation may prevent diabetes progression, reduce diabetes-related complications and has less serious adverse effects. Basal insulin is the preferred option in most clinical situations with consequences of undertreatment of chronic hyperglycaemia.


Treatment of CHO cells with Taxol and reversine improves micronucleation and microcell-mediated chromosome transfer efficiency.
Microcell-mediated chromosome transfer is an attractive technique for transferring chromosomes from donor cells to recipient cells and has enabled the generation of cell lines and humanized animal models that contain megabase-sized gene(s). However, improvements in chromosomal transfer efficiency are still needed to accelerate the production of these cells and animals. The chromosomal transfer protocol consists of micronucleation, microcell formation, and fusion of donor cells with recipient cells. We found that the combination of Taxol (paclitaxel) and reversine rather than the conventional reagent colcemid resulted in highly efficient micronucleation and substantially improved chromosomal transfer efficiency from Chinese hamster ovary donor cells to HT1080 and NIH3T3 recipient cells by up to 18.3- and 4.9-fold, respectively. Furthermore, chromosome transfer efficiency to human induced pluripotent stem cells, which rarely occurred with colcemid, was also clearly improved after Taxol and reversine treatment. These results might be related to Taxol increasing the number of spindle poles, leading to multinucleation and delaying mitosis, and reversine inducing mitotic slippage and decreasing the duration of mitosis. Here, we demonstrated that an alternative optimized protocol improved chromosome transfer efficiency into various cell lines. These data advance chromosomal engineering technology and the use of human artificial chromosomes in genetic and regenerative medical research.


Magnetic resonance imaging of the heart for determination of ejection fraction.
In 28 patients with various cardiac diseases we compared ejection fractions obtained by magnetic resonance imaging in a single oblique slice with monoplane ventriculography in the right anterior oblique projection, the latter serving as the standard. Also, results were evaluated for clinical relevance and relation to image quality. The correlation between the two techniques was moderate (r = 0.65). According to our standardized limits for clinical relevance, insufficiently correlating ejection fractions were obtained in 14 patients. In 8 of these patients this was attributed to poor endocardial edge detection. Edge detection problems were more frequently encountered by imaging with echo-time 20 msec than with echo-time 32 msec. Other causes for mismatching of the obtained ejection fractions are discussed. It is concluded that determination of ejection fraction by single slice magnetic resonance imaging should not be used for clinical application. Improvement can be expected by using a contiguous slicing technique, a longer echo-time in the spin-echo pulse sequence, or in due course by application of newly developed fast-imaging pulse sequences.


(Nano)platforms in breast cancer therapy: Drug/gene delivery, advanced nanocarriers and immunotherapy.
Breast cancer is the most malignant tumor in women, and there is no absolute cure for it. Although treatment modalities including surgery, chemotherapy, and radiotherapy are utilized for breast cancer, it is still a life-threatening disease for humans. Nanomedicine has provided a new opportunity in breast cancer treatment, which is the focus of the current study. The nanocarriers deliver chemotherapeutic agents and natural products, both of which increase cytotoxicity against breast tumor cells and prevent the development of drug resistance. The efficacy of gene therapy is boosted by nanoparticles and the delivery of CRISPR/Cas9, Noncoding RNAs, and RNAi, promoting their potential for gene expression regulation. The drug and gene codelivery by nanoparticles can exert a synergistic impact on breast tumors and enhance cellular uptake via endocytosis. Nanostructures are able to induce photothermal and photodynamic therapy for breast tumor ablation via cell death induction. The nanoparticles can provide tumor microenvironment remodeling and repolarization of macrophages for antitumor immunity. The stimuli-responsive nanocarriers, including pH-, redox-, and light-sensitive, can mediate targeted suppression of breast tumors. Besides, nanoparticles can provide a diagnosis of breast cancer and detect biomarkers. Various kinds of nanoparticles have been employed for breast cancer therapy, including carbon-, lipid-, polymeric- and metal-based nanostructures, which are different in terms of biocompatibility and delivery efficiency.


A controlled trial of dapsone versus pyrimethamine-sulfadoxine for primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis in patients with AIDS.
Pneumocystis carinii pneumonia (PCP) is the most common opportunistic human immunodeficiency virus (HIV)-related infection, occurring in 85% of HIV infected patients without prophylaxis. Preventive treatment is required when CD4 cell count falls below 200 cells per cubic millimeter. Cotrimoxazole has been shown to be highly effective but alternative drug regimens are often necessary because of the frequent drug hypersensitivity exhibited by HIV infected patients. The aim of this prospective, open, randomized, one-site study, involving HIV-infected patients with a CD4 cell count below 200/mm3, or a percentage under 20%, randomly assigned to receive either dapsone 50 mg daily or Fansidar one tablet weekly, was to compare the efficacy and safety of these drugs in the primary prophylaxis of PCP. Both dapsone and Fansidar appear to be safe and effective alternative agents for the prevention of PCP. Their role in Toxoplasma gondii prophylaxis requires further evaluation.


Novel naphthoquinone derivatives: synthesis and activity against human African trypanosomiasis.
A series of naphthoquinone derivatives has been synthesized and tested for its biological activity against human African trypanosomiasis. The use of reverse micellar medium not only enhanced the conversion rate, but also showed selectivity towards mono-coupled product in aryl chloride-aniline coupling reactions. Two derivatives of naphthoquinone (9b and 9c) exhibited potent activity against Trypanosoma brucei in vitro with low cytotoxicity.


Modification of a Kowa RC-2 fundus camera for self-photography without the use of mydriatics.
Research on retinal circulation during space flight required the development of a simple technique to provide self monitoring of blood vessel changes in the fundus without the use of mydriatics. A Kowa RC-2 fundus camera was modified for self-photography by the use of a bite plate for positioning and cross hairs for focusing the subject's retina relative to the film plane. Dilation of the pupils without the use of mydriatics was accomplished by dark adaption of the subject. Pictures were obtained without pupil constriction by the use of a high speed strobe light. This method also has applications for clinical medicine.


Isozyme variation and phylogenetic relationships in Vicia subgenus Cracca (Fabaceae).
The phylogenetic relationships among 27 vetch species belonging to the subgenus Cracca of the genus Vicia were studied in comparison with three species of Lathyrus section Lathyrus on the basis of isozyme variation. Isozymes encoded by 15 putative loci of ten enzymes were resolved by polyacrylamide gel electrophoresis and isozyme variation was analysed by using parsimony and neighbour-joining methods. The analyses revealed 63 parsimony-informative and 36 species-specific orthozymes. Of the latter, 23 are monomophic and are suitable for identification of V. benghalensis, V. palaestina, V. dumetorum, V. pisiformis, V. sylvatica, V. onobrychioides, V. cappadocica, V. cretica, V. articulata, V. tetrasperma, V. ervilia, V. hirsuta and V. loiseleurii. Polymorphism with heterozygous and homozygous isozyme genotypes was found for V. cracca, V. tenuifolia, V. ochroleuca, V. villosa, V. sylvatica, V. cassubica, V. sparsiflora, V. megalotropis, V. altissima, V. onobrychioides, V. cassia, V. cretica and L. heterophyllus, reflecting outcrossing in these species. By contrast, V. benghalensis, V. palaestina, V. disperma, V. dumetorum, V. pisiformis, V. orobus, V. pauciflora, V. tetrasperma and V. loiseleurii had only homozygous isozyme genotypes at polymorphic loci. Isozyme-based phylogenetic trees are presented. Sections Cracca, Ervum, Pedunculatae and Lenticula of traditional taxonomy are monophyletic groups, whereas sections Oroboideae (= Vicilla) and Panduratae appear polyphyletic and section Cassubicae is split into two species-couples linked at a low level of support. Treatment of ervoid species in a separate subgenus Ervum is not supported because of its polyphyly.


Influence of culture medium pH on growth, aggregation, and biofilm formation of Xylella fastidiosa.
The major feature of Xylella fastidiosa growing in its hosts, as well as in culture media, is its cellular aggregation and biofilm formation, leading to partial obstruction of the xylem causing water stress in the plant. We report that growth, aggregation, and biofilm formation of X. fastidiosa are influenced by the medium pH. We have verified that X. fastidiosa cell aggregation is reversibly inhibited by decreasing the medium pH from 6.6 to 6.4. Biofilm formation on glass walls was affected as well, and a concomitant decrease in cell multiplication was observed below pH 6.4. The manipulation of culture medium pH can be used as a tool for the cloning of X. fastidiosa strains isolated from plant hosts, because different strains can inhabit the same plant. Also, X. fastidiosa mutants produced by gene manipulation can be isolated from cell aggregates containing transformed and untransformed cells.


Adropin regulates hepatic glucose production via PP2A/AMPK pathway in insulin-resistant hepatocytes.
Adropin as a secretory peptide has shown a protective role on the disorders of glucose and lipid metabolism. However, the role and mechanism of this peptide on the hepatic glucose production has remained unclear. Adropin knockout (KO) mice were generated to explore its effects on the enhanced hepatic glucose production in obesity. We found that compared to wild-type (WT) mice, adropin-KO mice developed the unbalanced enhanced hepatic glucose production in advance of the whole-body insulin resistance (IR) by high-fat diet (HFD). Mechanistically, adropin dissociated CREB-CRTC2 and FoxO1-PGC1α complex and reduced their binding to the promoters of G6Pase and PEPCK to decrease glucose production in IR. However, these effects were not observed in insulin-sensitive hepatocytes. Furthermore, in IR hepatocytes, dampened AMPK signaling was re-activated by adropin treatment via inhibition of PP2A. To further authenticate AMPK role in vivo, we administrated HFD-fed mice with AAV8-CA AMPKα and found that AMPK activation functionally restored the aberrant glucose production and IR induced by adropin-deficiency. This study provides evidence that adropin activates the AMPK pathway via inhibition of PP2A and decreases the liver glucose production in IR context. Therefore, adropin may represent a novel target for the prevention and treatment of diabetes.


Nanogels fabricated from bovine serum albumin and chitosan via self-assembly for delivery of anticancer drug.
In this study, bovine serum albumin (BSA) and chitosan (CS) were used to prepare BSA-CS nanogels by a simple green self-assembly technique. Then the nanogels were successfully used to entrap doxorubicin hydrochloride (DOX) with an entrapment ratio of 46.3%, aiming to realize the slow-release effect and lower the cytotoxicity of DOX. The IC50 values of DOX-loaded BSA-CS (DOX-BSA-CS) and free DOX obtained by MTT assay in SGC7901 cells were 0.22 and 0.05μg/mL, respectively. The cytotoxicity of DOX significantly decreased within 24h after encapsulation by the nanogels, indicating that the loaded drug could slowly release within 24h and the BSA-CS was a good slow release system. The cellular uptake experiments indicated DOX-BSA-CS diffused faster into the cancer cell than the bare drug. The flow cytometry and TUNEL assay proved DOX-BSA-CS could induce a larger apoptosis proportion of gastric cancer cells 7901 than the bare drug and it is promising to be used for curing gastric cancer.


Supraspinatus tendon tears: comparison of US and MR arthrography with surgical correlation.
The aim of this study was to compare the diagnostic reliability of US with MR arthrography in diagnosing supraspinatus tendon tears. Surgical findings were used as the gold standard in detecting tears. A total of 44 patients were assessed with transverse and longitudinal US scans with respect to the long axis of the rotator cuff tendons and then examined with MR arthrography. This technique involved free-hand injection of contrast medium into the shoulder joint. At surgery 20 incomplete and 24 complete tears were observed. Ultrasound offered good results for the large tears, but its sensitivity decreased proportionally with the size of the tears. Magnetic resonance arthrography correctly diagnosed 43 tears, whereas only one false-negative diagnosis of tendinosis was made for a partial tear on the bursal side. Since it improves the diagnosis of small tears, MR arthrography must be performed on all patients for whom surgical repair is necessary in order to restore normal functions.


Evolving views of involution.
The developmental preparation of the mammary gland for milk production that occurs during pregnancy is followed by an equally dramatic process of involution as the gland returns to its prepregnancy state. Two detailed, microarray-based surveys reported in this issue extend our understanding of the nature and timing of molecular and cellular events in involution that underlie these developmental changes.


Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model.
Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m(2)/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing.


Colonization of the gut microbiota of honey bee (Apis mellifera) workers at different developmental stages.
The role of the gut microbiome in animal health has become increasingly evident. Although the structure of the gut microbiome of A. mellifera is well known, little is known about the dynamic change across different developmental stages. In this study, we explored the dynamic changes of the gut microbiota of A. mellifera at different developmental stages covering the whole life cycle using high-throughput 16S rRNA gene sequencing. The results indicated that the core (shared) gut microbiota changes significantly among different developmental stages. The diversity of the bacterial community in workers among different ages was significantly different. In addition, by comparing the core gut microbiota among different-aged workers, we found that newly emerged workers had fewer core microbiota. Three genera, Gilliamella, Frischella, and Snodgrassella, were significantly colonized at 1 day poste mergence (dpe); Lactobacillus, Bifidobacterium, Commensalibacter were significantly colonized at 3 dpe and significantly reduced with Gilliamella. Lactobacillus kunkeei and Bartonella were significantly colonized at 12 dpe and were significantly decreased with Lactobacillus helsingborgensis. Commensalibacter and Bifidobacterium were significantly decreased at 25 dpe, and Bacteroides, Escherichia-Shigella, and Porphyromonadaceae were significantly decreased between 19 and 25 dpe. Our results reveal the succession of the gut microbiota of workers from birth to senescence, which provides a theoretical basis for further exploring the roles of gut microbiota during different developmental stages.


Syndromes, disorders and maternal risk factors associated with neural tube defects (V).
Fetuses with neural tube defects (NTDs) may suffer from associated syndromes and disorders. This article provides a comprehensive review of the syndromes and disorders associated with NTDs, including Pallister-Hall syndrome, Walker-Warburg syndrome and Fukuyama congenital muscular dystrophy, MURCS association, Roberts syndrome, cerebro-costo-mandibular syndrome, laterality sequences, hydrolethalus syndrome, Knobloch syndrome, oculoauriculovertebral spectrum (hemifacial microsomia), cervico-oculo-acoustic syndrome, Fanconi anemia, Miller-Dieker lissencephaly syndrome, Fraser syndrome, frontonasal dysplasia, Adams-Oliver syndrome, CHILD syndrome, dyssegmental dysplasia, and monozygotic twinning. NTDs associated with these syndromes and disorders are a rare but important cause of NTDs. The risk of NTDs in subsequent fetuses and the preventive effect of maternal folic acid intake in NTDs associated with syndromes and disorders may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes and disorders associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.


Impact of management practices on the tallgrass prairie.
The ELM ecosystem-level grassland model simulates the flow of water, heat, nitrogen, and phosphorus through the ecosystem and the biomass dynamics of plants, consumers, and the decomposers. This model was adapted to a tallgrass prairie site in northeastern Oklahoma, USA, the Osage Site of the U.S. International Biological Program Grassland Biome. Several range management manipulations were simulated by the model and the results compared to field data and literature information: (1) altering the grazing intensity, grazing system, and grazing time period; (2) adding nitrogen and phosphorus to the grassland; (3) adding water during the growing season; and (4) spring burning of the prairie.The model showed that cattle weight gain per head, above-ground and belowground plant production, transpiration water loss, standing dead biomass, and the net nitrogen balance decrease with increasing grazing intensity, while soil water content and bare soil water loss increase. A moderately stocked year-round cow-calf grazing system is more beneficial to the grassland than a more highly stocked seasonal steer grazing system because the former increases the aboveground and belowground primary production and the plant nutrient uptake rates. Range manipulations, such as fire, which stimulate uniform grazing of a pasture, increase primary production, cattle weight gains, and nutrient uptake of plants and animals. Model results indicated that adding fertilizer was the best strategy for increasing cattle weight gains per head, while adding water would produce the greatest increase in primary production. Simulation of yearly and triennial spring burns suggests that these treatments increase primary production, plant nutrient uptake, and cattle weight gain per head. Burning increases the nitrogen losses from the systems; however, these losses are greater with annual burns. The model results also suggest the spatial grazing pattern of cattle must be considered to correctly represent the impact of grazing on the prairie.The model is used to describe the behavior of the tallgrass prairie ecosystem, evaluate alternative management strategies, and identify future scientific research and management studies.


Experimental arterial lesions after narrow-beam gamma irradiation used in stereotactic radiosurgery.
An experimental study on rats showing the arterial lesions caused by the beams of gamma irradiation used in stereotactic radiosurgery is presented. The common carotid artery of the rat was irradiated with a single narrow-beam of gamma radiation with a maximum dose of 30 and 60 Gy. The results were evaluated at 4, 12 and 24 weeks after irradiation. Several focal changes in the arterial walls were observed in all periods of study with a predominance of hyperplastic (proliferative) alterations at doses of 30 Gy, and hyaline degeneration at doses of 60 Gy. Total occlusion was not observed in any case. In conclusion, vascular hyperplasia is more prominent with the lower doses evaluated.


[Syphilis epidemic and an increase of the number of HIV infections among homosexual men attending the Amsterdam venereal disease clinic].
The registered number of cases of early infectious syphilis and of (ano)genital gonorrhoea among the attendees of the outpatient clinic for sexually transmitted diseases of the Amsterdam municipal health service shows a strong increase for both diagnoses in the period 1990-2001, notably in the last few years. Nearly all of this increase is accounted for by homosexual men. Syphilis increased mostly among men aged 35 years and over, gonorrhoea mostly among younger men. The population of older men also showed a distinct increase since 1997 in HIV incidence.


Protein tyrosine kinase inhibitors reduce high-voltage activating calcium currents in CA1 pyramidal neurones from rat hippocampal slices.
We have investigated the effects of protein tyrosine kinases (PTKs) inhibitors on high-threshold voltage activating (HVA) calcium currents in CA1 pyramidal neurones, whole-cell patch-clamp recorded from rat hippocampal slices. Genistein (100 microM) and tyrphostin B42 (100 microM), two PTKs inhibitors, reduced the steady-state barium current (IBa). On the other hand, daidzein and genistin (100 microM), two inactive analogues of genistein, had no effect on IBa amplitude. The inhibition induced by genistein was more pronounced at negative potentials. In order to characterize the calcium channels subtypes inhibited by PTKs inhibitors, we examined the effect of genistein in the presence of different calcium channel blockers. When L-type calcium channels were blocked by nifedipine, genistein induced a strong inhibition of the nifedipine-resistant IBa, suggesting an effect on non-L-type channels. Genistein did not antagonize the depressant effect of omega-Conotoxin-GVIA, a selective N-type calcium channel blocker, suggesting that N-type channels were not blocked by genistein. omega-Conotoxin-MVIIC (3-10 microM), a selective P/Q-type calcium channel blocker, greatly antagonized the depressant effect of genistein. Our results suggest that PTKs inhibitors reduce P-/Q-type, but not L- or N-types calcium currents in neurones of the CNS. The possible modulation of calcium channels by endogenous PTKs is discussed.


Levels of cyclic GMP in dormant, germinated, and outgrowing spores and growing and sporulating cells of Bacillus megaterium.
The level of cyclic GMP was less than one molecule per organism in dormant, germinated, and outgrowing spores of Bacillus megaterium. A significant level (approximately 8 pmol/g, dry weight) of cyclic GMP was found in early to mid-log phase cells, but the level fell to below 0.2 pmol/g, dry weight, in late-log phase and only rose slightly to approximately 0.9 pmol/g, dry weight, in stationary phare. No significant amount of cyclic GMP was detected in the growth medium at any time.


Insect signalling: components of giant hornet alarm pheromone.
Up to 74 people die each year in Japan after being stung by Hymenopteran insects, with hornets (Vespa spp.) being among the worst offenders. Here we identify a volatile, multi-component alarm pheromone in the venom of the world's largest hornet, V. mandarinia, and use field bioassays to show that 2-pentanol is its principal active component, and that 3-methyl-1-butanol and 1-methylbutyl 3-methylbutanoate act synergistically with it. The compound 1-methylbutyl 3-methylbutanoate, which may also be a foraging-site-marking pheromone, elicits a strong defensive reaction in the sympatric prey hornet V. simillima xanthoptera. As these chemicals are sometimes used in food flavourings and as fragrances in cosmetics, it is possible that they might provoke a seemingly unwarranted hornet attack on humans.


Bunchgrass architecture, light interception, and water-use efficiency: assessment by fiber optic point quadrats and gas exchange.
The bunchgrass growth form, which is very prominent in water-limited environments, can result in considerable self-shading of photosynthetically active foliage. The consequences of this growth form for light interception and water-use efficiency (photosynthesis/transpiration, P/T) were investigated for two Agropyron species which differ in tussock density and degree of self-shading. During the period of most active gas exchange, the tussocks were very compact and photosynthesis of shaded foliage was markedly light-limited. Stomatal control of older shaded foliage was poorly attuned for water-use efficiency. At low light, P/T decreased and intercellular CO2 concentrations increased. Despite differences in architecture and amount of shaded foliage, P/T of whole tussocks under ambient field conditions did not differ between these species. Partial defoliation decreased, rather than increased, P/T, primarily as a result of the poor photosynthetic light harvesting by the remaining foliage. Despite self-shading, the architecture of widely-spaced bunchgrasses provides for interception of as much direct beam solar radiation as is calculated for a rhizomatous grass occupying an area six-fold greater than the ground area underneath the canopy of these bunchgrasses.


Designing bifunctional NOP receptor-mu opioid receptor ligands from NOP receptor-selective scaffolds. Part I.
The nociceptin receptor (NOP) and its endogenous agonist, nociceptin/orphanin FQ (N/OFQ), members of the opioid receptor and peptide families respectively, modulate the pharmacological effects of classical opioids, particularly opioid-induced reward and nociception. We hypothesized that compounds containing both NOP and opioid receptor activity in a single molecule may have useful pharmacological profiles as non-addicting analgesics or as drug abuse medications. We report here our forays into the structure-activity relationships for discovering 'bifunctional' NOP-mu opioid receptor (MOP) ligands, starting from our NOP-selective scaffolds. This initial SAR suggests pharmacophoric elements that may be modified to modulate/increase opioid affinity, while maintaining high affinity for the NOP receptor, to result in potent bifunctional small-molecule NOP/MOP ligands.


Off pump coronary artery bypass grafting in a patient with tracheopathia osteoplastica.
Tracheopathia osteoplastica is a rare disease of the tracheobronchial tree, which is often misdiagnosed and recognised only at post-mortem. We report the case of a 66-year-old man with this condition, mistakenly thought to be suffering from chronic bronchiectasis. He underwent successful coronary artery bypass grafting for unstable angina using an off-pump technique. A case report and brief literature review is presented.


HLA antigens in lyophilised corneal lenticules.
To investigate the presence of Human Leukocyte Antigens (HLA) in organ cultured corneas, in lyophilised epikeratophakia lenticules prepared by dry state lathing, and in lenticules subjected to prolonged rehydration in Balanced Salt Solution (BSS). Twelve lenticules and 3 organ cultured corneas were studied for the presence of HLA-ABC (class I), and HLA-DR, -DQ, and -DP (class II), antigens using the immunoperoxidase technique. HLA-ABC antigens were detected in all lenticules. HLA-DR antigen was also detected in low concentrations in 6 out of 12 lenticules. HLA-DQ and -DP antigens were generally absent. Incubation in BSS for 24 and 48 hours did not change the expression of antigens. HLA-class I, and to some degree HLA-class II antigens, are present in the stroma of both organ cultured corneas, and in lyophilised lenticules. Incubation in BSS for up to 48 hours did not reduce the expression of antigens.


Geriatric tuberculosis in India-challenges and solutions.
India has the highest burden of tuberculosis (TB) in the world. Despite a national program for control and elimination of TB, there is a lot to achieve to effectively diagnose and treat TB. One important aspect that often remains ignored is geriatric TB. This article focuses on the challenges in clinical presentation, diagnosis and treatment of geriatric TB along with some suggested solutions.


National in-hospital morbidity and mortality trends after lumbar fusion surgery between 1998 and 2008.
Increasing numbers of posterior lumbar fusions are being performed. The purpose of this study was to identify trends in demographics, mortality and major complications in patients undergoing primary posterior lumbar fusion. We accessed data collected for the Nationwide Inpatient Sample for each year between 1998 and 2008 and analysed trends in the number of lumbar fusions, mean patient age, comorbidity burden, length of hospital stay, discharge status, major peri-operative complications and mortality. An estimated 1 288 496 primary posterior lumbar fusion operations were performed between 1998 and 2008 in the United States. The total number of procedures, mean patient age and comorbidity burden increased over time. Hospital length of stay decreased, although the in-hospital mortality (adjusted and unadjusted for changes in length of hospital stay) remained stable. However, a significant increase was observed in peri-operative septic, pulmonary and cardiac complications. Although in-hospital mortality rates did not change over time in the setting of increases in mean patient age and comorbidity burden, some major peri-operative complications increased. These trends highlight the need for appropriate peri-operative services to optimise outcomes in an increasingly morbid and older population of patients undergoing lumbar fusion.


Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.
Using the marrow canal of a tubular bone as a holding compartment for implant stems has been the paradigm in total joint arthroplasty for more than a century, and for direct skeletal attachment of limb prostheses for about forty years. Both interventions rely on the osteogenesis in the inner walls of the marrow canal in a direction radially inwards. It so remains despite the frequent aseptic loosening of the implant stems caused by the resorption of the marrow canal's inner walls which increases the canal's diameter and reduces its capacity to hold the implant. To improve the bone-device bond, we suggest an implantation methodology that activates positive osteogenic remodeling in the circular direction rather than radially inwards. The rationale is that circular osteogenesis is a component of natural healing of bone fractures and its activating may mitigate the consequences of resorption caused by stress shielding, bone developmental growth and other factors. Circular osteogenesis occurs in response to the distraction of slots precut into the bone tube. We call this methodology distraction implantation (DI) because of its debt to Ilizarov type distraction osteogenesis (DO). The methodology is accompanied by a design of an implant stem, and has been investigated in a previous pilot animal study. Distraction implantation is based on a component of natural healing of bone fractures and therefore has merit to be investigated further.


Genetic and experiential influences on behavior: Twins reunited at seventy-eight years.
Twins living in different countries offer opportunities to explore associations between observed differences and experiential effects. This report compared the life histories, cognitive abilities, personality traits, psychomotor skills, medical characteristics, job satisfaction, social support and social relations of dizygotic (DZ) female twins reunited at 78, the world's longest separated set. The twins' advanced age also enabled a study of how co-twin differences in aging may be associated with current behavioral and social differences. Consistent with previous studies, these dizygotic reared apart (DZA) twins showed discordance across some, but not all, traits. Their different rearing situations and life histories may explain current differences in their responses to meeting their twin. This case highlights the importance of both genetic and rearing factors on behavior, but does not allow firm conclusions regarding the extent to which these sources explain individual developmental differences. However, such data contribute to the growing number of cross-culturally separated twins, generating novel hypotheses that may be assessed using larger samples.


Ultrastructural organisation of the projection from the superior colliculus to the ventral lateral geniculate nucleus of the rat.
Retinorecipient regions of the ventral lateral geniculate nucleus of the thalamus and the superior colliculus of the midbrain are linked by reciprocal axonal projections. In this study we have investigated the ultrastructural characteristics, the distribution, and the postsynaptic targets of the terminals of axons projecting to the ventral lateral geniculate nucleus from the superior colliculus. Horseradish peroxidase was injected into the superior colliculi of adult albino rats, and the Hanker-Yates method was used to visualize anterogradely and retrogradely transported peroxidase in the ventral lateral geniculate nuclei 24 hours following the injection. Labelled terminals were found in the lateral and ventrolateral parts of the external division of the ipsilateral ventral lateral geniculate nucleus. The labelled terminals were confined to areas of simple, nonglomerular neuropil. They were 0.45-1.5 micron in diameter; contained small, dark mitochondria and spherical synaptic vesicles; and established Gray type I (asymmetrical) synaptic contacts with the dendritic shafts, dendritic spines, and occasionally cell bodies of cells with the ultrastructural characteristics of projection cells. A few labelled terminals established synaptic contact with retrogradely labelled cells. Thus, in the rat, the projection from the superior colliculus gives rise to a uniform population of axon terminals in the nonglomerular neuropil of the lateral portion of the ventral lateral geniculate nucleus, which synapse with, and are probably excitatory to, geniculocollicular and other projection cells.


Photocontact allergy to 6-methylcoumarin.
A proprietary sunscreen-induced photosensitivity reactions in a small number of users. Laboratory study revealed that the reactions were of the photoallergic type and were due to the presence of a synthetic fragrance, 6-methylcoumarin. By photomaximization testing 6-methylcoumarin was found to be a potent photocontact allergen.


Malignant duodenocolic fistula diagnosed by endoscopy.
A case of duodenocolic fistula secondary to carcinoma of the hepatic flexure is reported that was diagnosed by gastroduodenoscopy. The clinical, endoscopic, and radiographic features of this entity are discussed. Treatment options are reviewed.


Indoleamine 2,3-dioxygenase 1 regulates breast cancer tamoxifen resistance through interleukin-6/signal transducer and activator of transcription.
Breast cancer is the primary cause of cancer-related deaths in women. Tamoxifen (TAM) is the preferred drug for treating premenopausal luminal-type breast cancer, but TAM resistance restricts its ability to benefit patients. To date, the mechanism of this resistance remains unclear, and there is currently no effective treatment for reversing it. The expression of indoleamine 2,3-dioxygenase 1 (IDO1) has been shown to be elevated in various malignancies. Here, we aimed to investigate the role of IDO1 in TAM-resistant breast cancer. We confirmed that IDO1 is strongly expressed in TAM-resistant breast cancer, and it mediates drug-resistant cell proliferation, metastasis, and TAM resistance in vivo and in vitro through interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3). We also found that the mechanism by which TAM upregulates IDO1 is dependent on STAT1 activation. In summary, IDO1 regulates TAM resistance and can serve as a novel target for treatment of TAM-resistant breast cancer.


Nephrolithiasis.
The management of the patient presenting to the Emergency Department with nephrolithiasis or renal colic should include evaluation of the patient for concurrent diseases, risk factors for stone formation, and possible etiologies for stones. Suspicion of ureterolithiasis is based on a cogent history and physical examination and reinforced by a finding of hematuria. Diagnosis should be based upon a promptly performed intravenous pyelogram, unless the patient is truly allergic to contrast media or has substantial risk of a contrast-induced renal failure. A solitary flat plate of the abdomen adds no useful information and is an unnecessary expense to the patient. Essential laboratory data include a urinalysis, CBC, and electrolyte, BUN, creatinine, and serum calcium levels. A urine culture should be obtained in all patients because urinalysis alone may not be sufficient to exlude a urinary tract infection. Initial treatment of the patient with an uncomplicated renal colic should include hydration, relief of pain, and reassurance. Evaluation by a consultant may be done as an outpatient on a nonemergent basis. If the colic has not resolved after 72 hours, hospitalization generally is recommended. If the patient has vomiting, dehydration, a complete obstruction, or a solitary kidney, hospitalization in indicated and urgent consultation recommended. If the patient has fever or other signs of infection, emergent consultation and immediate hospitalization are essential. Retained obstructing stones are generally managed by urologic consultants. It is in the care of the patient with the retained stone that greatest advances have been made in the past 10 years. Patients should be counseled that the retained stone no longer calls for extended hospitalization and convalescence.


Chemical characterization of decomposition products of pyrazolidinedione-3,5 derivatives. Part 2: Chemical transformations of 4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (prenazone) and its main decomposition product N,N'-diphenylhydrazide-2-carboxy-5-methyl-4-hexenoic acid in sulphuric acid concentrated.
4-Prenyl-1,2-diphenyl-3,5-pyrazolidinedione (prenazone) in the medium of sulphuric acid concentrated (92-98%) undergoes an intramolecular rearrangement to 6',6'-dimethyl-4',5'-dihydropyrane-[2',3'-d]-1,2-diphenyl-3-pyrazolinone. The main decomposition product of prenazone, formed due to the hydrolytic process in the above conditions, undergoes changes according to two parallel reactions. First, it is hydrolyzed to prenylmalonic acid and hydrazobenzene which is subsequently transformed to benzidine. The second reaction proceeds via cyclization to form prenazone as well as 6',6-dimethyl-4',5'-dihydropyrane [2',3'-d]-1,2-diphenyl-3-pyrazolinone.


The consequences of predation in the population biology of the monocarpic species Cirsium palustre and Cirsium vulgare.
Predation by rabbits, Cheilosia grossa and especially Epiblema scutulana considerably reduces achene production in Cirsium palustre and Cirsium vulgare. In both species larger plants in a population are more frequently attacked, however the effect of predation is greater in medium sized plants. As a result the contribution of larger plants to the total achene production of the population is increased.In Cirsium vulgare larger populations are more susceptible to attack. The pattern and consequences of predation are discussed in relation to the occurrence in temporary habitats and to selectional processes. Predation intensifies existing developments in the population biology of these species. To compare the effect of predation for both species, detailed information of their population biology is necessary. At the moment the outcome of the comparison can only be indicated.


Internet-based cognitive behavioural therapy (iCBT) for posttraumatic stress disorder versus waitlist control: study protocol for a randomised controlled trial.
This randomised controlled trial (RCT) with two parallel arms will evaluate the efficacy of an internet-delivered six-lesson 10-week cognitive behavioural therapy (iCBT) intervention for posttraumatic stress disorder (PTSD). It will also investigate the association between changes in PTSD symptoms, intolerance of uncertainty (IU) and emotion regulation. Patients with PTSD will be recruited via the research arm of a not-for-profit clinical and research unit in Australia and randomised to a treatment group or waitlist control group. The minimum sample size for each group (alpha 0.05, power 0.80 for a g of 0.47) was identified as 72, but 10 % more will be recruited to hedge against expected attrition. PTSD diagnosis will be determined using the PTSD module from the Mini International Neuropsychiatric Interview version 5.0.0. The PTSD Checklist - Civilian version (PCL-C) will be used to measure PTSD symptoms (the primary outcome measure), with the Intolerance of Uncertainty Scale 12-item version (IUS-12) and the Emotion Regulation Questionnaire (ERQ) used to measure intolerance of uncertainty and emotion regulation, respectively. The PCL-C will be administered to the treatment group before each lesson of the PTSD program and at 3-month follow-up. The IUS-12 and ERQ will be administered before lessons 1 and 4, at post-treatment and at 3-month follow-up. The waitlist control group will complete these measures at week 1, week 5 and week 11 of the waitlist period. PTSD program efficacy will be determined using intent-to-treat mixed models. Maintenance of gains will be assessed at 3-month follow-up. Mediation analyses using PROCESS will be used to examine the association between change in PTSD symptoms over treatment and change in each of IU and emotion regulation ability in separate analyses. The current RCT seeks to replicate previous efficacy findings of iCBT for PTSD in a formally assessed PTSD sample from the general population. Findings may point to future lines of enquiry for the role of IU and emotion regulation in the mechanism of PTSD symptom change during CBT. Australian New Zealand Clinical Trials Registry: ACTRN12614001213639 , registered 18 November 2014. This trial protocol is written in compliance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.


Associations between physical activity and mental health among bariatric surgical candidates.
To examine associations between physical activity (PA) and mental health among adults undergoing bariatric surgery. Cross sectional analysis was conducted on pre-operative data of 850 adults with ≥class 2 obesity. PA was measured with a step activity monitor; mean daily steps, active minutes, and high-cadence minutes (proxy for moderate-vigorous intensity PA) were determined. Mental health functioning, depressive symptoms and treatment for depression or anxiety were measured with the medical outcomes study 36-item short form, Beck depression inventory, and a study-specific questionnaire, respectively. Logistic regression analyses tested associations between PA and mental health indicators, controlling for potential confounders. Receiver operative characteristic analysis determined PA thresholds that best differentiated odds of each mental health indicator. Each PA parameter was significantly (p<.05) associated with a decreased odds of depressive symptoms and/or treatment for depression or anxiety, but not with impaired mental health functioning. After controlling for sociodemographics and physical health, only associations with treatment for depression and anxiety remained statistically significant. PA thresholds that best differentiated those who had vs. had not recently received treatment for depression or anxiety were <191 active minutes/day, <4750 steps/day, and <8 high-cadence minutes/day. Utilizing high-cadence minutes, compared to active minutes or steps, yielded the highest classification accuracy. Adults undergoing bariatric surgery who meet relatively low thresholds of PA (e.g., ≥8 high-cadence minutes/day, representative of approximately 1h/week of moderate-vigorous intensity PA) are less likely to have recently received treatment for depression or anxiety compared to less active counterparts.


Highly sensitive electrochemical sensing platform for lead ion based on synergetic catalysis of DNAzyme and Au-Pd porous bimetallic nanostructures.
In this work, a sensitive and specific electrochemical biosensor for lead ion (Pb(2+)) detection was developed by coupling with synergetic catalysis of porous Au-Pd bimetallic nanoparticles and hemin/G-quadruplex-based DNAzyme. In the presence of target Pb(2+), the substrate strand was cleaved and the enzyme strand was released. Subsequently, G-rich DNA-labeled Au-Pd bimetallic nanoparticle was linked with the released enzyme strand through the helper DNA. Upon addition of hemin, a large number of hemin/G-quadruplex-based DNAzyme molecules were formed on the electrode to serve as nicotinamide adenine dinucleotide hydrogen (NADH) oxidase and peroxidase mimics. DNAzyme could catalyzed the reduction of H2O2, generated from NADH in the presence of O2, to produce an electrochemical signal when using thionine as the electron mediator. Introduction of porors Au-Pd bimetallic nanoparticles could enhance the detectable signal and cause the increase in the sensitivity. Experimental results showed that the variations (∆I) in the cathodic peak currents of the biosensor were linearly dependent on target Pb(2+) concentrations from 1.0 pM to 100 nM with a detection limit (LOD) of 0.34 pM. The excellent performance of the sensing platform indicated its promising prospect as a valuable tool for simple and cost-effective Pb(2+) detection in practical application.


Meta-analysis and construction of simple-to-use nomograms for approximating testosterone levels gained from weight loss in obese men.
Obesity-induced hypogonadism, which manifests as erectile dysfunction and a lack of libido, is a less visible and under-recognized obesity-related disorder in men. We examined the impact of weight loss on total (TT) and free testosterone (FT) levels, and constructed nomograms to provide an easy-to-use visual aid for clinicians. Meta-analysis was conducted using RevMan (v5.3) and expressed in standardized mean differences (SMD) for testosterone. Parallel-scale nomograms were constructed from baseline and target body mass index values to estimate the gain in testosterone. In total, 44 studies were included, comprising 1,774 participants and 2,159 datasets, as some studies included several datasets at different time points. Weight loss was controlled by low calorie diet (LCD) in 19 studies (735 participants, 988 datasets), by bariatric surgery (BS) in 26 studies (1,039 participants, 1,171 datasets), and by both in one study. The median follow-up was 26 weeks (interquartile range = 12-52). The range of baseline mean age was 21-68 yr, BMI: 26.2-71.2 kg/m2 , TT: 7-20.2 nmol/L and FT: 140-583 pmol/L. TT levels increased after weight loss by LCD: SMD (95%CI) = 2.5 nmol/L (1.9-3.1) and by BS: SMD = 7.2 nmol/L (6.0-8.4); the combined TT gain was 4.8 nmol/L (3.9-5.6). FT levels increased after weight reduction by LCD: SMD = 19.9 pmol/L (7.3-32.5) and by BS: SMD = 58.0 pmol/L (44.3-71.7); the combined gain was 42.2 pmol/L (31.4-52.9). Greater amounts of total and free testosterone could be gained by weight loss in men with higher baseline BMI, or lower levels of SHBG, TT and FT, while gain in TT was relatively greater in older and FT in younger age. Age-stratified nomograms revealed that compared to older men (> 40 yr), younger men (≤ 40 yr) gained less TT but more FT for a given weight loss. Both TT and FT levels increased after weight loss, relatively greater with higher baseline BMI, or lower levels of SHBG, TT and FT. Nomograms constructed from a large number of participants with a wide range of BMI and testosterone values provide an evidence-based and simple-to-use tool in clinical practice.


Implantation of Autologous Cartilage Chips Improves Cartilage Repair Tissue Quality in Osteochondral Defects: A Study in Göttingen Minipigs.
Osteochondral injuries have poor endogenous healing potential, and no standard treatment has been established. The use of combined layered autologous bone and cartilage chips for treatment of osteochondral defects has shown promising short-term clinical results. This study aimed to investigate the role of cartilage chips by comparing combined layered autologous bone and cartilage chips with autologous bone implantation alone in a Göttingen minipig model. The hypothesis was that the presence of cartilage chips would improve the quality of the repair tissue. Controlled laboratory study. Twelve Göttingen minipigs received 2 osteochondral defects in each knee. The defects were randomized to autologous bone graft (ABG) combined with autologous cartilage chips (autologous dual-tissue transplantation [ADTT]) or ABG alone. Six animals were euthanized at 6 months and 6 animals were euthanized at 12 months. Follow-up evaluation consisted of histomorphometry, immunohistochemistry, semiquantitative scoring (International Cartilage Repair Society II), and computed tomography. There was significantly more hyaline cartilage in the ADTT group (25.8%) compared with the ABG group (12.8%) at 6 months after treatment. At 12 months, the fraction of hyaline cartilage in the ABG group had significantly decreased to 4.8%, whereas the fraction of hyaline cartilage in the ADTT group was unchanged (20.1%). At 6 and 12 months, there was significantly more fibrocartilage in the ADTT group (44% and 60.8%) compared with the ABG group (24.5% and 41%). The fraction of fibrous tissue was significantly lower in the ADTT group compared with the ABG group at both 6 and 12 months. The implanted cartilage chips stained >75% positive for collagen type 4 and laminin at both 6 and 12 months. Significant differences were found in a number of International Cartilage Repair Society II subcategories. The volume of the remaining bone defect significantly decreased from 6 to 12 months in both treatment groups; however, no difference in volume was found between the groups at either 6 or 12 months. The presence of cartilage chips in an osteochondral defect facilitated the formation of fibrocartilage as opposed to fibrous tissue at both 6 and 12 months posttreatment. The implanted chips were present in the defect and viable after 12 months. This study substantiates the chondrogenic role of cartilage chips in osteochondral defects.


New-Onset Stutter After Electrode Insertion in the Ventrocaudalis Nucleus for Face Pain.
Deep brain stimulation (DBS) of the ventrocaudalis nucleus of the thalamus is a last resort treatment for chronic refractory pain. DBS is generally a safe procedure, although it can result in functional disturbances depending on the site of stimulation. There has been 1 previous report of stuttering induced by microlesioning of the thalamus, as well as several reports of stuttering induced by stimulation of the thalamus and other related structures in the brain. We describe the case of a patient with trigeminal deafferentation face pain who was treated with DBS of the ventrocaudalis nucleus thalamus and developed a reversible stutter immediately on insertion of the electrode. The stutter improved significantly over 12 days after implant; however, the device was not effective in relieving the patient's pain and was removed. Stuttering is a rare complication of deep brain exploration of the sensory thalamus. Our coordinates are near to but in a distinct anatomic region compared with cases previously described as having similar effects on speech.


Dietary Intervention With α-Amylase Inhibitor in White Kidney Beans Added Yogurt Modulated Gut Microbiota to Adjust Blood Glucose in Mice.
White kidney beans contain α-amylase inhibitors that can be used in diet for weight reduction. In this study, we investigated the potential of white kidney bean (phaseolus vulgaris L.) extract enriched in α-amylase inhibitor as a food additive in yogurt to regulate blood glucose in hyperglycemic animals. Five groups of C57BL/6J mice were fed for 8 weeks with standard chow diets, high-fat diets (HFD), or high-fat diets with supplement of α-amylase inhibitor in white kidney beans (P. vulgaris extract, PVE), yogurt (Y), and PVE added yogurt (YPVE), respectively. The HFD weakened glucose tolerance and caused insulin resistance in mice, and changed the characteristics of intestinal flora. The intervention of Y, PVE, and YPVE decreased blood glucose, insulin, hyperlipidemia, and inflammatory cytokine levels in mice fed with HFD. Moreover, the YPVE could regulate the components of host intestinal microbiota toward a healthy pattern, significantly increased the metabolic-related flora Corynebacterium, Granulicatella, and Streptococcus, while it decreased Paraprevotella and Allobaculum. Thus, YPVE markedly increased functions of "Amino Acid Metabolism," "Energy Metabolism," "Nucleotide Metabolism," and declined functions of "Glycan Biosynthesis and Metabolism." Consequently, YPVE could be developed as a new functional food because of its beneficial prebiotic properties in the metabolic syndrome.


The greasy response to virus infections.
Virus replication requires lipid metabolism, but how lipids mediate virus infection remains obscure. In this issue, Amini-Bavil-Olyaee et al. (2013) reveal that IFITM proteins disturb cholesterol homeostasis to block virus entry. Previously, in Cell, Morita and colleagues (2013) showed the antiviral potency of the lipid mediator protectin D1.


Single Nucleotide Polymorphisms as Genomic Markers for High-Throughput Pharmacogenomic Studies.
Genetic variations in patients have strong impact on their drug therapies and responses because the variations may contribute to the efficacy and/or produce undesirable side effects for any given drug. The Drug Metabolizing Enzymes and Transporters (DMET) assay is a high-throughput technology by Affymetrix that is able to simultaneously genotype variants in multiple genes involved in absorption, distribution, metabolism, and excretion of drugs for subsequent clinical applications, i.e., the assay allows for a precise genetic map that can guide therapeutic interventions and avoid side effects.


An in vivo method for studying afferent fibre activity from cervical paravertebral tissue during vertebral motion in anaesthetised cats.
We describe a method for characterizing and studying afferent input to the central nervous system arising from deep axial structures of the neck during defined cervical vertebral movement. Multiple or single unit recordings of afferent activity arising from identified receptive fields in these tissues can now be studied in situ while simultaneously inducing 'natural' stimulation of mechanoreceptors during well defined movements of the intact vertebral column. When combined with existing strategies for extracellular and intracellular recordings of neurones, the methods described here will allow in vivo investigation of the central effects of functionally identified afferents innervating identified receptive fields located in deep paravertebral tissues during a variety of discrete movements of individual vertebra. This has particular importance in determining the relative role that afferents innervating specific axial tissues have on identified neurones in the central nervous system. It will allow determination of the 'bias' of input to projection cells, such as 'hyperconvergent' neurones, during natural movement. Furthermore, it will allow investigation of their role in the control of somatic and autonomic reflex behaviour.


Further Delineation of the ALG9-CDG Phenotype.
ALG9-CDG is one of the less frequently reported types of CDG. Here, we summarize the features of six patients with ALG9-CDG reported in the literature and report the features of four additional patients. The patients presented with drug-resistant infantile epilepsy, hypotonia, dysmorphic features, failure to thrive, global developmental disability, and skeletal dysplasia. One patient presented with nonimmune hydrops fetalis. A brain MRI revealed global atrophy with delayed myelination. Exome sequencing identified a novel homozygous mutation c.1075G>A, p.E359K of the ALG9 gene. The results of our analysis of these patients expand the knowledge of ALG9-CDG phenotype.


Development of a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS) method for the quantification of bioactive substances present in olive oil mill wastewaters.
A novel liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI MS/MS) method was developed and validated for the simultaneous determination of the bioactive substances hydroxytyrosol, tyrosol and 2-(5-ethylidene-2-oxo-tetrahydro-2H-pyran-4-yl)acetic acid in olive oil mill wastewater samples (OMW). The chromatographic separation was performed on a RP-C8 column using a water-acetonitrile gradient program and the detection was achieved by tandem MS in the negative ion mode. Calibration curves were linear for all bioactive compounds over the range of 1-100 ng injected, while the method exhibited good accuracy, intra- and inter-day precision. The limit of detection and the limit of quantification were in the low to mid pg range and the method was simple and rapid. Because the disposal of OMW is an environmental problem and on the other hand OMW are rich in biologically active compounds that could be recovered and exploited in various applications, the developed method was applied to the monitoring of OMW samples and the quantitative determination of the aforementioned substances. In this way, the original content in bioactive compounds could be assigned in the raw matrix, and the enrichment of the samples by various pretreatment methods could be assessed. Also, full-scan ESI MS was applied to OMW samples for the identification of several compounds known to be present in OMW.


MDR1 gene C3435T polymorphism and cancer risk: a meta-analysis of 34 case-control studies.
P-glycoprotein, the product of the MDR1 gene, is a transmembrane active efflux pump for a variety of environmental toxins and xenobiotics. Epidemiological studies have evaluated the association between MDR1 C3435T polymorphism and cancer susceptibility. However, published data are still inconclusive. To derive a more precise assessment of this relevance, we performed a meta-analysis, up to September 2010, of 5,196 cases with different cancer types and 6,827 controls from 34 published case-control studies. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for MDR1 C3435T polymorphism and cancer were estimated using fixed- and random-effects models when appropriate. The overall results suggested that the variant was associated with a moderately increased cancer risk in all comparison models tested (OR = 1.26, 95% CI: 1.06-1.50 for TT vs. CC; OR = 1.19, 95% CI: 1.04-1.37 for CT vs. CC; OR = 1.15, 95% CI: 1.01-1.32 for recessive model; OR = 1.21, 95% CI: 1.06-1.38 for domain model, and OR = 1.14, 95% CI: 1.04-1.26 for allele contrast). In the subgroup analysis by cancer types, significant associations were found in breast cancer (OR = 1.66, 95% CI: 1.24-2.21 for TT vs. CC; OR = 1.44, 95% CI: 1.14-1.82 for recessive model; OR = 1.41, 95% CI: 1.10-1.81 for domain model; and OR = 1.31, 95% CI: 1.13-1.52 for allele contrast) and renal cancer (OR = 1.99, 95% CI: 1.37-2.90 for TT vs. CC; OR = 1.74, 95% CI: 1.25-2.42 for domain model; OR = 1.43, 95% CI: 1.09-1.88 for recessive model; and OR = 1.40, 95% CI: 1.17-1.68 for allele contrast). However, no significant associations were found in colorectal cancer, gastric cancer, and acute lymphoblastic leukemia for all genetic models. In the ethnicity subgroup analysis, a significant association with cancer among Caucasians was found under the dominant model, homozygote comparison, CT versus CC comparison, and allele comparison. In summary, this meta-analysis suggests that the MDR1 C3435T polymorphism is associated with cancer susceptibility, increasing the risk of breast and renal cancer.


Non-linear kinetics of ethanol elimination in man: medico-legal applications of the terminal concentration-time data analysis.
Research regarding parameters suitable for reporting on the activity of enzymatic systems responsible for ethanol metabolism is of obvious interest in medico-legal practice. Blood ethanol concentration-time curves, following oral administration of ethanol, have been developed for ethylic and non-ethylic subjects. This study has confirmed the non-linear kinetics of ethanol elimination; however, existing non-linear models appear to be inadequate for usual medico-legal practice, because of their complexity. We observed three phases during the elimination of ethanol. The first order terminal phase is characterized by its half-life. This parameter seems adequate as a basis for determining the activity of enzyme systems responsible for the metabolism of ethanol.


The single-cell transcriptome and chromatin accessibility datasets of peripheral blood mononuclear cells in Chinese holstein cattle.
This study was performed in the frame of a more extensive study dedicated to the integrated analysis of the single-cell transcriptome and chromatin accessibility datasets of peripheral blood mononuclear cells (PBMCs) with a large-scale GWAS of 45 complex traits in Chinese Holstein cattle. Lipopolysaccharide (LPS) is a crucial mediator of chronic inflammation to modulate immune responses. PBMCs include primary T and B cells, natural killer (NK) cells, monocytes (Mono), and dendritic cells (DC). How LPS stimulates PBMCs at the single-cell level in dairy cattle remains largely unknown. We sequenced 30,756 estimated single cells and mapped 26,141 of them (96.05%) with approximately 60,075 mapped reads per cell after quality control for four whole-blood treatments (no, 2 h, 4 h, and 8 h LPS) by single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq). Finally, 7,107 (no), 9,174 (2 h), 6,741 (4 h), and 3,119 (8 h) cells were generated with ~ 15,000 total genes in the whole population. Therefore, the single-cell transcriptome and chromatin accessibility datasets in this study enable a further understanding of the cell types and functions of PBMCs and their responses to LPS stimulation in vitro.


Cancer Screening in Older Adults.
Cancer screening is an important tool for reducing morbidity and mortality in the elderly. In this article, performance characteristics of commonly used screening tests for colorectal, lung, prostate, breast, and cervical cancers are discussed. Guidelines are emphasized and key issues to consider in screening older adults are highlighted.


Success Through Simplicity: What Other Artificial Intelligence Applications in Medicine Should Learn from History and ChatGPT.
Many artificial intelligence (AI) algorithms have been developed for medical practice, but few have led to clinically used products. The recent hype of ChatGPT shows us that simple, user-friendly interfaces are one major factor in the applications' popularity. The majority of AI-based applications in clinical practice are still far from simple-to-use applications with user-friendly interfaces. Therefore, simplifying operations is one key to AI-based medical applications' success.


IMMUNOREACT 0: Biopsy-based immune biomarkers as predictors of response to neoadjuvant therapy for rectal cancer-A systematic review and meta-analysis.
The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to NT. We performed a meta-analysis to estimate their predictive significance. A systematic literature search of PubMed, Ovid MEDLINE and EMBASE databases was performed to identify eligible studies. Studies on patients with rectal cancer undergoing NT in which the predictive significance of at least one of the immunological markers of interest was assessed by immunohistochemistry (IHC) in pretreatment biopsies were included. Seventeen studies reporting sufficient data met the inclusion criteria for meta-analysis. High levels of total CD3+, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs), as well as stromal and intraepithelial CD8+ compartments, significantly predicted good pathological response to NT. Moreover, high levels of total (tumoral and immune cell expression) PD-L1 resulted associated to a good pathological response. On the contrary, high levels of intraepithelial CD4+ TILs were correlated with poor pathological response. FoxP3+ TILs, tumoral PD-L1 and CTLA-4 were not correlated to the treatment response. This meta-analysis indicated that high-density TILs might be predictive biomarkers of pathological response in patients that underwent NT for rectal cancer.


Transcriptome of pituitary function changes in rat model of high altitude cerebral edema.
High altitude cerebral edema (HACE) is a serious subtype of acute mountain sickness (AMS). Studies have suggested that increased expression of corticotropin releasing hormone receptor 1 (CRFR1) in pituitary is related to the development of HACE, but no study has revealed the molecular landscape of pituitary function changes in this process. Rat model of HACE was established by simulating the high-altitude hypobaric hypoxia environment. Then RNA-sequencing was performed of rat pituitary gland (PG) in HACE and non-HACE groups. The function annotations, enrichment analysis, protein-protein interaction (PPI) network, chromosome location and drug repositioning of differentially expressed genes (DEGs) were explored based on the transcriptomic data. And we found pituitary secretion function was disordered in HACE, which was partly due to activated inflammation and oxidative stress. In addition, we identified potential biomarkers for early recognition of pituitary dysfunction and potential protective drugs for pituitary function in HACE.


Utility and diagnostic test properties of pulmonary and cardiovascular point of care ultra-sonography (POCUS) in COVID-19 patients admitted to critical care unit.
We conducted this study to assess the diagnostic test properties of point of care ultrasonography (POCUS) of lung and cardiovascular system in prediction of mortality in COVID-19 patients. This is a cross-sectional study of 178 Covid-19 patients; POCUS was performed within one hour of admission to the ICU. We estimated sensitivity, specificity, positive predictive value, negative predictive value for prediction of mortality. The mean (SD) age of these patients was 57.3 (12.8) years. The findings were on cardiac ultrasonography were: mild pericardial effusion (45%), chamber dilatation (15%), hypokinesia (11%), and low ejection fraction (8%). In our study, 30 patients (17%) had died. A cut-off score of > to 13 (for lung ultrasound score [LUS]) had high sensitivity for mortality (93.3%, 95% CI: 77.9-99.2%). However, low ejection fraction (92.3%, 95% CI: 86,6-96.1%), and thrombosis in either vein (96.5%, 95% CI: 92.0-98.9%) were specific for mortality. A combination of LUS > =13 or low ejection fraction or thrombosis or spontaneous echo contrast (slow flow) improved sensitivity for mortality to 96.7% (95% CI: 82.8-99.9%). The agreement between LUS of > =13 and CT score of moderate/severe was 85.7% (95% CI: 62.8-100%). The interrater agreement between these two parameters was 0.82 (95% CI: 0.68, 0.97). Multi-organ POCUS is effective in diagnosis, prognosis, and management of COVID-19 patients. Rather than just lung ultrasound, clinicians should use multiorgan POCUS for early identification of severe lung involvement and thrombotic changes; it may help reduce mortality in these patients.


Flavonoid-induced reduction of ENaC expression in the kidney of Dahl salt-sensitive hypertensive rat.
Flavonoid, a plant extract, exhibits various biological actions. Dietary flavonoid intake is reported to reduce an elevated blood pressure, however the mechanism is unknown. The epithelial Na+ channel (ENaC) in the kidney plays a key role in the regulation of blood pressure by contributing to the Na+ reabsorption in renal tubules. Thus, we investigated the effect of quercetin, a flavonoid, on ENaC mRNA expression in the kidney of hypertensive Dahl salt-sensitive rats. Dahl salt-sensitive rats of 8 weeks were acclimated for 1 week in a metabolic cage and were subsequently kept for 4 weeks under four different conditions: (1) normal salt diet (0.3% NaCl), (2) normal salt diet with quercetin (10 mg/kg/day), (3) high-salt diet (8% NaCl), and (4) high-salt diet with quercetin. Quercetin diminished the alphaENaC mRNA expression in the kidney associated with reduction of the systolic blood pressure elevated by high-salt diet, suggesting that one of the mechanisms of the flavonoid's antihypertensive effect on salt-sensitive hypertension would be mediated through downregulation of ENaC expression in the kidney.


Selection of a derivative of the antiviral agent 9-[(1,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) with improved oral absorption.
Various diesters of 9-[(1,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) were screened in order to identify a derivative with improved oral absorption. The solubilities and dissolution rates decreased with increasing chain length and branching of the ester group. However, the dipropionate ester showed an anomalously faster dissolution rate. The rates of hydrolysis to DHPG in the presence of intestinal homogenates were found to increase with increasing carbon number for the straight-chain alkyl esters and decreased with branching. The shorter-chain alkyl esters were relatively more stable in intestinal homogenates than in liver homogenates. Therefore they may have a better membrane permeability than DHPG due to their intact ester group. The hydrolysis rates in human blood increased with increasing carbon number for the straight-chain alkyl esters. The dipropionate ester appeared to be the most promising derivative because of its rapid dissolution rate, slower hydrolysis in the intestine, and rapid conversion to DHPG in liver and blood.


Benign mass lesions deep inside the temporal bone: imaging diagnosis for proper management.
Among mass lesions inside the temporal bone, benign tumors and cholesteatomas can be differentiated by contrast enhancement in T1-weighted images (T1WI) and by diffusion-weighted images (DWI). Moreover, DWI will also facilitate discrimination between cholesteatomas accompanied by granulation and other non-neoplastic lesions such as mucoceles and cholesterol granulomas. To review the imaging characteristics of mass lesions inside the temporal bone and to investigate pertinent imaging modalities for differential diagnosis, which is crucial for appropriate treatment planning. This was a retrospective case series study of six patients seen between 2002 and 2005 with mass lesions deep inside the temporal bone. One patient had facial schwannoma, two had glomus jugulare tumor, and three had cholesteatoma. Plain high resolution CT gave few clues to the nature of the mass lesions. MRI study provided us with better clues: contrast enhancement on T1WI was observed only in benign tumors and only cholesteatomas showed high intensity on DWI. With the assistance of neurosurgeons, surgery was successfully performed in all cases.


Association of the human semen DNA virome with successful in vitro fertilization.
To comprehensively characterize the DNA virome in semen samples collected for in vitro fertilization (IVF). A descriptive clinical study. Single academic fertility center. Twenty-four male partners from couples undergoing IVF. Couples were randomized to receive 1 g of azithromycin (standard of care) or no azithromycin at the time of baseline IVF assessment. Semen samples were collected at the time of the female partners' egg retrieval, and 100 μL of the sample was used for the virome analysis. Detection of viruses by ViroCap enrichment of viral nucleic acid and sequencing. Association between the virome, semen parameters, and pregnancy outcomes. We detected viruses in 58% of the participants. Viruses included polyomaviruses, papillomaviruses, herpesviruses, and anelloviruses. Viromes detected in semen had little overlap with the viromes detected in vaginal samples from their female partners collected at the time of embryo transfer, which were analyzed in a previous study. A lower viral diversity in semen samples was positively associated with pregnancy (Hodges-Lehmann estimate of difference, 1; 95% confidence interval, 2-0.00003). There was no association between viral diversity and sperm concentration, motility, or fertilization rates. This comprehensive characterization of the DNA virome in semen reveals an association between virome diversity and pregnancy in couples undergoing IVF. However, no association was found with specific semen parameters or fertilization rates, suggesting that viral exposure may negatively affect pregnancy after fertilization. Future studies should be undertaken to evaluate the associations between the semen virome with IVF outcomes in larger cohorts.


Comparison of the efficacy and safety of statin and statin/ezetimibe therapy after coronary stent implantation in patients with stable angina.
Little is known about the efficacy and safety of intensive lowering of low-density lipoprotein cholesterol (LDL-C) with statin/ezetimibe therapy after coronary stent implantation in patients with stable angina. Fifty patients with stable angina were randomly divided into an atorvastatin (10 mg/day) (A) group and an atorvastatin (10 mg/day)/ezetimibe (10 mg/day) (A+E) group after stent implantation. Follow-up coronary angiography was performed at 6-9 months after stenting. The A and A+E groups showed significant reductions in LDL-C. The levels of LDL-C in the A+E group were significantly lower than those in the A group at follow-up, whereas there were no differences in major adverse cardiac events, in-stent restenosis, or in-stent % diameter stenosis (DS) between the groups. Only the A+E group showed a significant decrease in the levels of highly sensitive C-reactive protein. In a sub-analysis, %DS in the non-target vessel significantly decreased in both groups. Moreover, Δ%DS (Δ=the value at baseline minus that at follow-up) in the A+E group was more closely associated with LDL-C levels at follow-up than that in the A group. There were no significant differences in adverse effects between the A and A+E groups. In conclusion, although statin/ezetimibe therapy was effective and safe for intensive lipid-lowering in patients with stable angina after successful coronary stent implantation, improvement in clinical outcomes with the combination therapy remains unclear.


Evaluation of the patient with otitis externa.
This article considers the history, physical examination, cytologic evaluation of smears and fungal and bacterial culture and sensitivity testing, clinical interpretation of information obtained from a biopsy of the external ear canal, and ancillary aids for the evaluation of the patient with otitis externa.


DNA-targeted 2-nitroimidazoles: in vitro and in vivo studies.
A series of compounds in which a 2-nitroimidazole is linked to a DNA intercalating phenanthridine moiety has been synthesised. Previously, three such compounds, termed nitroimidazole-linked phenanthridines or NLPs, were tested in vitro and showed a greatly enhanced molar efficiency as hypoxic cell radiosensitisers and cytotoxins compared with the untargeted 2-nitroimidazole, misonidazole. Since the cytoxicity of these compounds was shown to be inversely proportional to linker chain length while radiosensitising ability was dependent of it, compounds with five and six carbons in the chain were synthesised in an attempt to lower the toxicity of the drugs while increasing their ability to 'scan' DNA for target radicals. These compounds and a comparison series of n-alkylated phenathridinium ions have been characterised and evaluated in vitro using Chinese hamster ovary and V79 cells and their effects compared with misonidazole. Based on in vitro results, one member of the series was selected and evaluated in vitro using a V79 spheroid tumour model and in vivo using an SCCVII transplantable tumour system. These studies have demonstrated the potential utility of this class of compound.


Determination of residual ethylene dibromide in cereals by glass capillary gas chromatography.
This study describes two methods for the quantitative determination of residual ethylene dibromide (1,2-dibromoethane) in cereals, especially wheat, and in dried fruit. The first method is based on a solvent-extraction technique; in the second a continuous micro steam-distillation--solvent-extraction apparatus is used. The quantitative determination of ethylene dibromide is performed by electron-capture gas chromatography using a glass capillary column coated with CPwax 51. The absolute detection limit for EDB is 0.5 pg and recoveries of 82 and 98% resp. are obtained for samples with EDB added in the range of 10 to 50 micrograms/kg. 75 samples of cereal products and 19 samples of dried fruit have been analysed with the solvent extraction method. For 22 samples the micro steam-distillation-solvent-extraction technique has been used.