All Levels of Providers Can Effectively and Efficiently Teach Pelvic Floor Strength Assessment at Time of Pelvic Examination.
In women who undergo provider-guided vaginal biofeedback of pelvic floor muscle strength, we sought to determine whether the level of the provider correlates with the patient's ability to achieve adequate pelvic floor muscle contractions (PFMCs). From August 2017 to April 2018, patients from 2 urogynecology clinics were recruited to participate in an institutional review board-approved, prospective study examining PFMCs. Pelvic examination and teaching session were done by providers who had specific training on how to assess pelvic floor muscle strength using the validated, modified Oxford scale. Patients were asked to perform a baseline PFMC during a 2-digit pelvic examination. Thereafter, patients were counseled to relax their muscles, identify the levator ani muscles during provider teaching, and perform 3 consecutive provider-guided PFMCs. The strength of each PFMC was measured, and the time-to-teach (TTT) was recorded. The level of provider and TTT were correlated with PFMC1 to PFMC3 using Spearman correlation coefficient. One hundred women participated. Obstetrics/gynecology (OB/GYN) residents (post-graduate years 1-4) evaluated 20 patients; female pelvic medicine and reconstructive surgery fellowship trainees (post-graduate years 5-7), 38 patients; OB/GYN nurse practitioners, 18 patients; generalist OB/GYN faculty, 9 patients; and female pelvic medicine and reconstructive surgery faculty, 15 patients. There was no correlation between level of provider and TTT or between level of provider and strength of PFMC1, PFMC2, or PFMC3. At the time of pelvic floor muscle assessment, the level of provider does not impact teaching time or PFMC1 to PFMC3. Teaching pelvic floor muscle exercise is a cost-effective, low-resource tool to improve patient care, and providers of any level should be encouraged to teach pelvic floor muscle exercise to patients at the time of office examination.


Effect of continuous positive airway pressure applied by face mask on right ventricular function after cardiac surgery.
The effect of respiratory therapy with continuous positive airway pressure (CPAP) on right ventricular function 24 hours after elective cardiac surgery was evaluated in patients with or without severe coronary artery disease. The first group included 10 patients following coronary artery bypass graft (CABG) surgery, and the second group included 10 patients following aortic valve replacement (AVR) without preexisting coronary artery disease. Patients of both groups had preoperative left ventricular ejection fractions above 40%. CPAP was applied by face mask at a flow rate of 20 L/min with 40% oxygen in nitrogen and with a positive end-expiratory pressure of 12 cmH2O. Right ventricular function was estimated at end-expiration by a fast-response thermodilution cardiac output catheter. The results demonstrate that in both groups of patients, CPAP did not significantly modify right ventricular indices, ejection fraction, end-systolic and end-diastolic volume indices, and stroke volume index, indicating that CPAP can safely be applied after elective cardiac surgery in patients with or without severe coronary artery disease and preoperative left ventricular ejection fractions above 40%. Furthermore, the concomitant postoperative intravenous infusion of nitroglycerin (to all 10 patients of the CABG group and to 4 patients of the AVR group) counteracted the expected beneficial effect of CPAP therapy on arterial oxygenation.


The electron impact induced fragmentation of Aspergillus amstelodami alkaloids and derivatives.
The mass spectral data of four isoprenylated indole alkaloids containing a piperazinedione group, neoechinuline, cryptoechinuline C, and A and echinuline, isolated from Aspergillus amstelodami cultures, and of two derivatives obtained by catalytic hydrogenation of neoechinuline and echinuline, are reported and discussed. Their fragmentation patterns are strongly dependent upon the presence of a single or a double bond betueen C-8 and C-9.


Skin infections and infestations in prison inmates.
Skin infections and infestations are common in a prison environment. The prison is in dynamic equilibrium with the larger society. Hence, it serves as a reservoir of infections which can spread to the larger society. The study sets out to find out how rampant these infections might be in the prison and the factors responsible. Inmates at a Nigerian prison in Ilesha, Osun State, were examined for skin infections. Personal hygiene and living conditions were critically examined. The overall prevalent rate of infectious dermatoses was 49.2% (150/305). There were 178 infections. Dermatophytes accounted for 64%, pityriasis versicolor 27%, bacterial infections 3.4%, and others 5.6%. Only frequency of soap use and accommodation arrangement significantly contributed to the overall prevalence. However, infectious dermatoses were significantly affected by prison status (PP = 0.04), frequency of bath (PP = 0.025), changing of clothing (PP = 0.05), accommodation arrangement (P = 0.0001), frequency of soap usage (P = 0.005), and toilet facility (P = 0.001). The HIV status of the inmates was unknown. Hence, effect of HIV infection cannot be ascertained. Skin infections and infestations are common in prison. A change in living conditions and personal hygiene will definitely help in reducing these infections.


Temporary keratoprosthesis for transscleral fixation of posterior chamber intraocular lenses with penetrating keratoplasty.
In the absence of zonular and capsular support, cataract surgeons increasingly prefer suture-fixated posterior chamber intraocular lenses (IOLs) to angle-supported anterior chamber lenses as a secondary IOL. Various suturing techniques have been proposed for fixating the posterior chamber IOL. Transscleral suture fixation appears advantageous but problematic when performed on an open globe. Moreover, excision of the vitreous base is impeded by the iris and the dark, unstable image. This article describes a technique that takes advantage of a temporary keratoprosthesis (TKP). When sutured onto the trephination opening, the TKP provides a bright, stable image and permits peripheral indentation of the globe, allowing for controlled, thorough vitrectomy. With the infusion pressure supplying adequate eye tone, ab externo transfixation, and thus a targeted passage of the sulcus, is possible. If the cornea permits transfixation, TKP may be used to tamponade after trephination and as a lens rest while the surgeon ties the sutures to the haptics.


[Prediction of pancreatitis following endoscopic retrograde cholangiopancreatography].
The aim of this study was to determine if the difference in serum amylase levels prior to, and two hours following, an endoscopic retrograde cholangiopancreatography (ERCP), or the ratio of the two-hour post-ERCP amylase level to the pre-ERCP amylase level was a better predictor of post-ERCP pancreatitis (PEP). This was a retrospective, single-center study of consecutive patients, who underwent ERCP between April 2015 and August 2018. Serum amylase was measured before and two hours following ERCP. We compared the difference and the ratio of the two levels in predicting PEP using a receiver operating characteristic (ROC) curve analysis. A total of 1029 patients underwent ERCP, with PEP occurring in 118 (11.5%). Multivariate analysis revealed that an elevated two-hour post-ERCP serum amylase level was a significant predictor of PEP. ROC analysis of the difference and the ratio of the two levels found good performance for both parameters, with an area under the curve (AUC) of 0.861 (95% confidence interval [CI], 0.823-0.900) and 0.847 (95% CI, 0.809-0.886), respectively. The difference between the values was a significantly more effective predictor of PEP, based on the AUC analysis (P = 0.011). The difference between pre and two-hour post-ERCP amylase levels is a better predictor of PEP than the ratio of the two.


Transcriptional analysis reveals a high impact of conjugated linoleic acid on stearoyl-Coenzyme A desaturase 1 mRNA expression in mice gastrocnemius muscle.
We examined the potential implication of skeletal muscle in the fat-lowering effect observed in mice treated with moderate doses of CLA. In experiment 1, mice fed with a standard-fat diet were orally treated with sunflower oil (control) and 3 or 10 mg CLA mixture/day for 37 days. In experiment 2, mice were fed with a high-fat diet for 65 days. For the first 30 days, they received the same doses as in experiment 1 and, from that time onwards, animals received double doses. Gene expression of key proteins involved in fatty acid transport, oxidation, regulation of lipid and carbohydrate utilization, composition of muscle fiber, and thermogenesis were determined and, in most of them, no major impact of CLA was seen. Therefore, enhancement of fatty acid oxidation in muscle did not seem to contribute to the antiobesity effect of CLA as seen in other studies with higher CLA doses. However, a strong induction of classically associated lipogenic genes such as Fasn (up to twofold) and, particularly, Scd1 (up to ninefold) was found. This activation could contribute to a protective role in muscle cells, since expression of ER stress markers was decreased and inversely correlated with the induction of Scd1.


Salmonella in free-living exotic and native turtles and in pet exotic turtles from SW Spain.
We screened 78 native and 94 exotic turtles from natural ponds and 39 exotic pet turtles for presence of Salmonella, resulting with infection rates of 6.61%, 6.4%, and 5.1%, respectively. Concurrent shedding of multiple serotypes of the bacteria was only detected in one pet turtle. Eleven isolates were obtained in free-living turtles, including serotypes commonly found in reptiles and also the serotype Typhimurium, which is commonly related to human infections. In pet turtles, the five serotypes isolated were different to those isolated in free-living turtles and had been reported to cause reptile-associated salmonellosis in humans. These results confirm the risk of transmission of Salmonella from free-living and pet turtles to humans, demanding the necessity of regulation of pet turtle trade in Europe.


Size Does Matter: The Influence of Bulb Size on the Phytochemical and Nutritional Profile of the Sweet Onion Landrace "Premanturska Kapula" (Allium cepa L.).
The Mediterranean area is especially rich in old, both sweet and pungent, varieties of onion. The synthesis of phytochemicals takes place concurrently with the overall development and maturation of vegetables; however, it is unclear whether there is a correlation between onion bulb size and antioxidant compound content, antioxidant capacity, and nutritional parameters and what the origin of these variations is. The aim of this work was to investigate the biochemical and nutritional aspects of the sweet onion landrace "Premanturska kapula", as well as to investigate the influence of onion bulb size on onion phytochemical and nutritional profile. The sweet onion landrace "Premanturska kapula" has a high soluble sugar content, a high antioxidant capacity, and a high phenolic compound content. Quercetin-3,4'-diglucoside and quercetin-4'-glucoside were the major flavonols, while protocatehuic acid was the major phenolic acid detected. The choice of onion bulb size can impact the profile of the sugars present, with large bulb sizes favoring higher sucrose and fructooligosaccharides content compared to small bulb sizes which were more abundant in glucose. The total sugars or bulb dry matter were not affected by bulb size. Phenolic compounds were more abundant in smaller bulb sizes, thus indicating a link between bulb development and phenolic compound allocation within the plant. This link possibly derived from agronomic practices such as bare-root transplants, or even open pollination which causes a broader genetic variability. From a consumer perspective, it can be a choice between the small and medium bulb sizes on one hand, which are more abundant in polyphenolics and simple sugars, or on the other hand, the larger bulbs which are more abundant in fructooligosaccharides known to carry excellent health benefits.


Characterization of a heat-stable protein with antimicrobial activity from Arabidopsis thaliana.
A heat-stable protein with antimicrobial activity was isolated from Arabidopsis thaliana plants by buffer-soluble extraction and two chromatographic procedures. The results of MALDI-TOF analysis revealed that the isolated protein shares high sequence identity with aspen SP1. To determine the exact antimicrobial properties of this protein, a cDNA encoding the protein was isolated from an A. thaliana leaf cDNA library and named AtHS1. AtHS1 mRNA was induced by exposure to external stresses, such as salicylic acid and jasmonic acid. We also analyzed the antimicrobial activity of recombinant AtHS1 expressed in Escherichia coli. This protein inhibited pathogenic fungal strains, except for Phytophthora infestans and Phytophthora nicotianae, and it exhibited antibacterial activity against E. coli and Staphylococcus aureus. These results suggest that AtHS1 shows good potential for use as a natural material in the study of antimicrobial agents.


Another look at the role of empty categories in sentence processing (and grammar).
The gap/gapless processing debate in the psycholinguistics literature contrasts two processing models: one that assumes the trace-based Government and Binding (or Principles and Parameters) Grammar and the (augmented) Active Filler Strategy and one that assumes the traceless Dependency Categorial Grammar and the Principle of Dependency Formation. This paper reports on an experiment that found new evidence against the gapless/traceless model, considers why such evidence was not found in previous studies, and explores whether a parser that combines a (partially) traceless grammar and the augmented Active Filler Strategy can explain the current finding.


Proteome analysis of the dystrophin-deficient MDX diaphragm reveals a drastic increase in the heat shock protein cvHSP.
Duchenne muscular dystrophy is the most commonly inherited neuromuscular disorder in humans. Although the primary genetic deficiency of dystrophin in X-linked muscular dystrophy is established, it is not well-known how pathophysiological events trigger the actual fibre degeneration. We have therefore performed a DIGE analysis of normal diaphragm muscle versus the severely affected x-linked muscular dystrophy (MDX) diaphragm, which represents an established animal model of dystrophinopathy. Out of 2398 detectable 2-D protein spots, 35 proteins showed a drastic differential expression pattern, with 21 proteins being decreased, including Fbxo11-protein, adenylate kinase, beta-haemoglobin and dihydrolipoamide dehydrogenase, and 14 proteins being increased, including cvHSP, aldehyde reductase, desmin, vimentin, chaperonin, cardiac and muscle myosin heavy chain. This suggests that lack of sarcolemmal integrity triggers a generally perturbed protein expression pattern in dystrophin-deficient fibres. However, the most significant finding was the dramatic increase in the small heat shock protein cvHSP, which was confirmed by 2-D immunoblotting. Confocal fluorescence microscopy revealed elevated levels of cvHSP in MDX fibres. An immunoblotting survey of other key heat shock proteins showed a differential expression pattern in MDX diaphragm. Stress response appears to be an important cellular mechanism in dystrophic muscle and may be exploitable as a new approach to counteract muscle degeneration.


The significance of chromosomal findings for the differentiation between lymphoma and lymphoblastoid cell lines.
Cytogenetic studies have been performed from four Burkitt's lymphoma cell lines, one cell line obtained after successful xenotransplantation of a Burkitt's lymphoma cell line into athymic nude mice, and from ten lymphoblastoid cell lines (three derived from umbilical cord blood cells, one from acute myelogenous leukemia and six from Hodgkin's disease specimens). Our findings indicate the non-neoplastic nature of lymphoblastoid cell lines in spite of their high proliferative activity in vitro and their aneuploidy after long-term cultivation. In contrast, cell lines of Burkitt's lymphoma origin apparently are truly malignant lymphoma cells, characterized by aneuploidy and by the presence of a 14q+-marker chromosome even in the EBV-negative cell lines. The 14q+-marker chromosome, observed in Burkitt's lymphoma as well as in other malignant lymphomas, seems to be related to neoplasia, independent on the presence of EBV. The significance of the aneuploidy for the differentiation between lymphoma and lymphoblastoid cell lines is discussed.


Cadherin-10 is a novel blood-brain barrier adhesion molecule in human and mouse.
Maintenance of the specialised environment of the central nervous system requires barriers provided by the endothelium of brain microvessels (the blood-brain barrier (BBB)) or the epithelium lining the ventricles (CSF-brain barrier) or the choroid plexus (blood-CSF barrier). Inter-endothelial junctions are more extensive in the BBB than in other tissues, with elaborate tight junctions. However, few differences in the molecular composition of these junctions have been described. Here, we show, in both human and mouse brain, that the type II classical cadherin, cadherin-10, is expressed in BBB and retinal endothelia, but not in the leaky microvessels of brain circumventricular organs (CVO), or in those of non-CNS tissues. This expression pattern is distinct from, and reciprocal to, VE-cadherin, which is reduced or absent in tight cortical microvessels, but present in leaky CVO vessels. In CVO, the barrier function is switched from the microvasculature to the adjacent ventricular epithelium, which we also find to express cadherin-10. In the vessels of gliobastoma multiforme tumours, where BBB is lost, cadherin-10 is not detected. This demonstration of a distinctive expression pattern of cadherin-10 suggests that it has a pivotal role in the development and maintenance of brain barriers.


Pseudotumor cerebri.
The authors evaluate the case of a 20-year-old, four-month-pregnant woman who presented with papilledema and visual field loss, and developed headache, intermittent diplopia and impairment of color vision over the next month. The procedures and considerations leading to the diagnosis of pseudotumor cerebri are discussed, as are the various modes of therapy and their indications.


Is bone marrow biopsy always indicated in patients with primary cutaneous marginal zone B-cell lymphoma?
Bone marrow involvement at the time of diagnosis is uncommon in patients with primary cutaneous marginal zone B-cell lymphoma (PCMZL). Moreover, in these patients such involvement is rarely found in isolation on diagnosis. Typically the few patients with PCMZL who have early bone marrow involvement also present secondary nodal or visceral involvement, which is detected by other staging studies (usually computed tomography). In recent years, this has given rise to some debate about whether a bone marrow biopsy should be routinely performed in patients diagnosed with PCMZL in view of the good prognosis and low incidence of bone marrow infiltration and/or extracutaneous involvement in this type of lymphoma.


Mr. G And The Revolving Door: Breaking The Readmission Cycle At A Safety-Net Hospital.
A patient with complex needs returns to the hospital again and again, despite his care team's efforts to reduce readmissions.


Strontium doped poly-ε-caprolactone composite scaffolds made by reactive foaming.
In the reconstruction and regeneration of bone tissue, a primary goal is to initiate bone growth and to stabilize the surrounding bone. In this regard, a potentially useful component in biomaterials for bone tissue engineering is strontium, which acts as cationic active agent, triggering certain intracellular pathways and acting as so called dual action bone agent which inhibits bone resorption while stimulating bone regeneration. In this study we established a novel processing for the foaming of a polymer (poly-ε-caprolactone) and simultaneous chemical reaction of a mixture of calcium and strontium hydroxides to the respective carbonates using supercritical carbon dioxide. The resultant porous composite scaffold was optimized in composition and strontium content and was characterized via different spectroscopic (infrared and Raman spectroscopy, energy dispersive X-ray spectroscopy), imaging (SEM, μCT), mechanical testing and in vitro methods (fluorescence vital staining, MTT-assay). As a result, the composite scaffold showed good in vitro biocompatibility with partly open pore structure and the expected chemistry. First mechanical testing results indicate sufficient mechanical stability to support future in vivo applications.


Cholesterol lowering effects of nuts compared with a Canola oil enriched cereal of similar fat composition.
Small quantities of nuts protect against subsequent cardiovascular risk. There is speculation that the cholesterol lowering effect associated with nut consumption arises primarily from the fatty acid composition of nuts but may be caused by some other component. To evaluate this possibility we compared the effect of various nuts, against a Canola oil based cereal with a comparable fatty acid profile, on lipids, lipoproteins and fatty acids to determine whether the fatty acid profile of nuts explains their cholesterol lowering effects. Twenty-eight men and women with mean (s.d.) levels of total and low density lipoprotein cholesterol of 6.0 (1.1) mmol/L, and 4.1 (1.0) mmol/L, respectively and a mean body mass index (BMI) of 26.9 (3.2) kg/m2 took part in a randomised cross over trial. For two periods of six weeks, separated by a four-week washout, participants were asked to consume a low saturated fat diet, which included either 30 g/d nuts (nut diet) or one serving of a cereal containing Canola oil (cereal diet). There were no significant differences in the lipids, lipoproteins, plasma fatty acids or other variables between the two diets at the end of the study. Total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were lower on both experimental diets than at baseline, 0.51 mmol/L and 0.40 mmol/L (p<0.001, p<0.01), respectively on the nut diet and 0.42 mmol/L and 0.37 mmol/L (p<0.001, p<0.01), respectively on the cereal diet. A 30 g serving of nuts, or a serving of a Canola oil enriched cereal with a similar fatty acid composition reduced total and LDL cholesterol to a similar extent when consumed as part of a lipid lowering diet. Results suggest that foods with a similar fatty acid composition to nuts can produce comparable decreases in lipoprotein mediated cardiovascular risk.


Evaluation of antibiotic efficacy against infections caused by planktonic or biofilm cultures of Pseudomonas aeruginosa and Klebsiella pneumoniae in Galleria mellonella.
The lack of novel antibiotics for more than a decade has placed increased pressure on existing therapies to combat the emergence of multidrug-resistant (MDR) bacterial pathogens. This study evaluated the Galleria mellonella insect model in determining the efficacy of available antibiotics against planktonic and biofilm infections of MDR Pseudomonas aeruginosa and Klebsiella pneumoniae strains in comparison with in vitro minimum inhibitory concentration (MIC) determination. In general, in vitro analysis agreed with the G. mellonella studies, and susceptibility in Galleria identified different drug resistance mechanisms. However, the carbapenems tested appeared to perform better in vivo than in vitro, with meropenem and imipenem able to clear K. pneumoniae and P. aeruginosa infections with strains that had bla(NDM-1) and bla(VIM) carbapenemases. This study also established an implant model in G. mellonella to allow testing of antibiotic efficacy against biofilm-derived infections. A reduction in antibiotic efficacy of amikacin against K. pneumoniae and P. aeruginosa biofilms was observed compared with a planktonic infection. Ciprofloxacin was found to be less effective at clearing a P. aeruginosa biofilm infection compared with a planktonic infection, but no statistical difference was seen between K. pneumoniae biofilm and planktonic infections treated with this antibiotic (P>0.05). This study provides important information regarding the suitability of Galleria as a model for antibiotic efficacy testing both against planktonic and biofilm-derived MDR infections.


Usefulness of arrival time parametric imaging in evaluating the degree of liver disease progression in chronic hepatitis C infection.
To determine whether the degree of liver disease progression in chronic hepatitis C infection can be evaluated by arrival time parametric imaging using contrast-enhanced sonography with Sonazoid (perfluorobutane; GE Healthcare, Oslo, Norway). In this study, 60 patients with liver disease in chronic hepatitis C infection were examined and compared with 10 healthy volunteers who served as controls. A recommended dose of the sonographic contrast agent Sonazoid was intravenously infused, and the S5 or S6 region of the liver and right kidney were observed concurrently while movies of the procedure were saved. Arrival time parametric images of liver parenchymal blood flow were created, with red pixels to indicate an arrival time of 0 to 5 seconds and yellow pixels to indicate an arrival time of 5 to 10 seconds. From the obtained images, the ratio of the red area to the entire enhanced area of the liver was calculated using image-processing software. Each participant was subsequently subjected to liver biopsy for liver fibrosis staging according to Metavir scores, and the determined fibrosis stage was compared with the ratio of red. The serum albumin level, platelet count, and prothrombin time were also compared with the ratio of red for each participant. The ratio of red increased significantly as liver fibrosis stage advanced (P < .01 for F1 versus F2; P < .01 for F1 versus F3; P < .01 for F1 versus F4; and P < .01 for F2 versus F4). As the ratio of red increased, significant decreases were observed in the serum albumin level (r = -0.29; P = .027), platelet count (r = -0.46; P = .0003), and prothrombin time (r = -0.46; P = .0002). Arrival time parametric imaging using Sonazoid-enhanced sonography enables noninvasive evaluation of the degree of progression of liver disease in chronic hepatitis C infection and is thus considered clinically useful.


Infusion of apomorphine into the dorsocentral striatum produces acute drug-induced recovery from neglect produced by unilateral medial agranular cortex lesions in rats.
Previous studies have shown that systemic administration of apomorphine is effective in producing acute drug-induced recovery from neglect induced by unilateral medial agranular cortex (AGm) lesions. More recent studies have demonstrated that recovery from neglect may be due to plastic changes occurring in the dorsal central striatum (DCS). Further, lesions of the DCS produce neglect that does not respond to systemic administration of apomorphine, suggesting that this area may be crucial for the therapeutic effects of apomorphine. In the present study, the behavioral effects of apomorphine infused into the DCS of animals with AGm lesion-induced neglect were examined to determine whether the DCS is a site of drug action. An infusion of 0.375 micro g of apomorphine into the DCS, but not a lateral striatal control area, was effective in producing acute recovery from neglect. The results of this study support the crucial role of the DCS in recovery from neglect induced by unilateral AGm lesions and suggest that the DCS may be an important site of action for the therapeutic effects of apomorphine. Because dopamine agonist therapy has been shown to be effective in humans with neglect, the results of the current study may represent an important step in the development of future pharmacotherapies.


Outcome in six children with mucopolysaccharidosis type IH, Hurler syndrome, after haematopoietic stem cell transplantation (HSCT).
To follow-up six children with severe mucopolysaccharidosis type IH, Hurler syndrome, who were treated before 24 months of age with haematopoietic stem cell transplantation. In Sweden, during the last 10-year period, six consecutive children born with severe mucopolysaccharidoses type IH have been successfully transplanted using matched unrelated donors between the ages of 11 and 24 months (mean age 18 months). Three children received intravenous enzyme replacement therapy once a week, from diagnosis until engraftment of their bone marrow. Two children developed chimerism and a progressive increase in recipient cells and later received a successful re-transplantation. One to two years after transplantation the children demonstrated some developmental delays in cognitive function. Latterly this was followed by normalization. Orthopaedic operations on the spine and hips and carpal tunnel syndrome were still required following transplantation. Cardiac valve involvement remained progressive in the children. The outcome of six children in this study confirms that early haematopoietic stem cell transplantation in mucopolysaccharidosis type I, Hurler syndrome, preserves an affected child's mental ability. Consequently, it is essential that clinical recognition and early diagnosis take place, providing an additional challenge to paediatricians treating this condition.


Influence of purinergic signaling on glucose transporters: A possible mechanism against insulin resistance?
Metabolic disorders, such as insulin resistance, affect many people worldwide due to the prevalence of obesity and type 2 diabetes, which are pathologies that impair glycemic metabolism. Glucose is the primary energetic substrate of the body and is essential for cellular function. As the cell membrane is not permeable to glucose molecules, there are two distinct groups of glucose transporters: sodium-glucose-linked transporters (SGLTs) and the glucose transporter (GLUT) family. These transporters facilitate the entry of glucose into the bloodstream or cytoplasm where it functions in the production of adenosine 5 ́-triphosphate (ATP). This nucleotide acts in several cellular mechanisms, such as protein phosphorylation and cellular immune processes. ATP directly and indirectly acts as an agonist for purinergic receptors in high concentrations in the extracellular environment. Composed by P1 and P2 groups, the purinoreceptors cover several cellular mechanisms involving cytokines, tumors, and metabolic signaling pathways. Previous publications have indicated that the purinergic signaling activity in insulin resistance and glucose transporters modulates relevant actions on the deregulations that can affect glycemic homeostasis. Thus, this review focuses on the pharmacological influence of purinergic signaling on the modulation of glucose transporters, aiming for a new way to combat insulin resistance and other metabolic disorders.


Transcriptomic analysis of maize uncovers putative genes involved in metabolic detoxification under four safeners treatment.
Isoxadifen-ethyl (IDF) and cyprosulfamide (CSA) can effectively protect maize from nicosulfuron (NIC) injury, while mefenpyr-diethyl (MPR) and fenchlorazole-ethyl (FCO) did not. Their chemical diversity and requirement to use them in combination with the corresponding herbicides suggest that their elicitation of gene expression are complex and whether it is associated with the safening activity remains elusive. In this study, our first objective was to determine whether or not the ability of four safeners to enhance the metabolic rate of nicosulfuron. It was found that nicosulfuron degradation in maize was accelerated by IDF and CSA, but not by FCO and MPR. Transcriptomic analysis showed that the number of genes induced by IDF and CSA were larger than that induced by FCO and MPR. Overall, 34 genes associated with detoxification were identified, including glutathione S-transferase (GST), cytochrome P450 (CYP450), UDP-glucosyltransferase (UGT), transporter and serine. Moreover, 14 detoxification genes were screened for further verification by real-time PCR in two maize inbred lines. Two maize inbred lines exhibited high expression levels of four genes (GST31, GST39, AGXT2 and ADH) after IDF treatment. GST6, GST19, MATE, SCPL18 and UF3GT were specifically up-regulated in telerant maize inbred line under IDF and IDF + NIC treatments. Seven genes, namely GST31, GST6, GST19, UF3GT, MATE, ADH and SCPL18, are induced by IDF and CSA to play a vital role in regulating the detoxification process of NIC. Accordingly, the GST activity in maize was accelerated by IDF and CSA, but not by FCO and MPR. This result is consistent with transcriptome and metabolic data.These results indicate that the mitigation of NIC damage is associated with enhanced herbicide metabolism. IDF and CSA were more effective in protecting maize from NIC injury due to their ability to enhance the detoxification of specific types of herbicides, compared to FCO and MPR. The chemical specificity of four safeners is attributed to the up-regulated genes related to the detoxification pathway.


Global perspective on microplastics in landfill leachate; Occurrence, abundance, characteristics, and environmental impact.
Plastic wastes deposited in landfills eventually break down and degrade into microplastics by physical, chemical, and biological forces. Though microplastics in leachate pose significant threats to the environment, the leachate generated from landfills has not received much attention as a possible source of environmental microplastics. A descriptive and systematic investigationof the global distribution of microplastics in landfill leachate does not exist to date. Therefore, this attempt is to provide a concise scientometric review of the studies on the presence of microplastics in landfill leachate. The present review revealed that the global trend in research on microplastics in leachate has increased exponentially after 2018 and China is the leading country. Different geographical regions have reported different microplastic abundances with the highest of 291.0 ± 91.0 items/L from a landfill in Shanghai. The use of novel sampling techniques to detect small microplastics (20-100 µm) has led to the high abundance of microplastics in landfill leachate in Shanghai. Due to its widespread usage, polyethylene is the most typically encountered polymer type in landfill leachate around the world. However, it is quite challengingto compare the results among studies due to the use of different size categories and extraction techniques. The removal of microplastics by the current leachate treatment facilities is still mostly unexplored, thus it is crucial to develop novel technologies to treat the microplastics in landfill leachate. Further investigations on the transport of microplastics in landfill leachate are urgently required to have a better understanding of potential human exposure and health implications.


Molecular mechanism of age-specific hepatic lipid accumulation in PPARalpha (+/-):LDLR (+/-) mice, an obese mouse model.
This study aimed to clarify the molecular mechanisms of age-specific hepatic lipid accumulation accompanying hyperinsulinemia in a peroxisome proliferator-activated receptor alpha (PPARalpha) (+/-):low-density lipoprotein receptor (LDLR) (+/-) mouse line. The hepatic fat content, protein amounts, and mRNA levels of genes involved in hepatic lipid metabolism were analyzed in 25-, 50-, 75- and 100-week-old mice. Severe fatty liver was confirmed only in 50- and 75-week-old mice. The hepatic expression of proteins that function in lipid transport and catabolism did not differ among the groups. In contrast, the mRNA levels and protein amounts of lipogenic enzymes, including acetyl-coenzyme A carboxylase-1, fatty acid synthase, and glycerol-3-phosphate acyltransferase, enhanced in the mice with fatty liver. Elevated mRNA and protein levels of lipoprotein lipase and fatty acid translocase, which are involved in hepatic lipid uptake, were also detected in mice with fatty liver. Moreover, both protein and mRNA levels of sterol regulatory element-binding protein-1 (SREBP-1), a transcription factor regulating lipid synthesis, had age-specific patterns similar to those of the proteins described above. Therefore, the age-specific fatty liver found in the PPARalpha (+/-):LDLR (+/-) mouse line is probably caused by age-specific expression of SREBP-1 and its downstream lipogenic genes, coordinated by the increased uptake of lipids. All of these factors might be affected by age-specific changes in serum insulin concentration.


Regional Arterial Infusion Chemotherapy improves the Pathological Response rate for advanced gastric cancer with Short-term Neoadjuvant Chemotherapy.
To identify clinicopathologic and treatment variables that could predict pathologic tumor response to short-term neoadjuvant chemotherapy (NAC) for patients with locally advanced gastric cancer. A retrospective analysis was conducted of 178 patients who underwent short-term NAC with EOX regimen followed by surgery from January 2008 to December 2010. Neoadjuvant treatment response was evaluated using tumor regression grade. Relationships between pathologic tumor response and clinicopathological factors were evaluated using logistic regression analysis. The benefits of regional arterial infusion chemotherapy were investigated separately. The postoperative pathological response rate was 46.1% (82/178) and 4 patients (2.2%) had complete pathological remission. Pathological response was significantly associated with tumor differentiation (P = 0.008), abnormal a-fetoprotein levels (P = 0.01) and administration approach to chemotherapy (intravenous versus regional arterial infusion chemotherapy) (P = 0.018). Most bone marrow toxicities, vomiting, nausea, alopecia, and fatigue were acceptable. Grade 3/4 toxicities were not commonly observed. The 3-year overall survival (OS) and recurrence free survival (RFS) were 67.0% and 53.0%, respectively. Regional arterial infusion NAC group had significantly better median RFS (48.0 versus 34.0 months) than the intravenous NAC group (P = 0.049). In conclusion, regional arterial infusion NAC can improve the pathological response rate of advanced gastric cancer treated with EOX regimen.


Both type I and type II interferons down-regulate human tumor necrosis factor receptors in human hepatocellular carcinoma cell line Hep G2. Role of protein kinase C.
It is well known that interferon-gamma (IFN-gamma; type II) potentiates various responses of human tumor necrosis factor (TNF) in a wide variety of cells and that this potentiation is accompanied by the up-regulation of TNF receptor synthesis. In the present studies we examined the regulation of TNF receptors by type I and type II IFNs in a hepatocellular carcinoma cell line, HEP G2. Exposure of these cells to IFN-gamma led to a decrease in TNF receptor number (4029 vs. 2719 sites/cell) without any change in the receptor affinity (0.96 nM vs. 1.1 nM). The effect was time and dose-dependent. Like IFN-gamma, IFN-alpha and IFN-beta (type I) down-modulated the TNF receptors on these cells. The effect of IFNs on the TNF receptors was inhibited by staurosporin, a protein kinase C (PK-C) inhibitor. Furthermore, by the use of receptor-specific antibodies, we found that the IFN-dependent decrease was primarily due to the p60 form of the TNF receptor. Our results presented are the first to demonstrate that IFNs can also down-modulate TNF receptors in certain cells and that this effect is mediated through PK-C.


Self-organized spreading of droplets to fluid toroids.
Mixing of a chemical trigger of lower surface tension into a microdroplet with relatively higher surface tension can cause a rapid spreading of the droplet on a liquid-sublayer to form a host of metastable liquid morphologies such as sheets, toroids, threads, or droplets. Subsequently, such metastable fluidic objects break into a collection of droplets to form microemulsions. Introduction of surfactant loaded water or long-chain alcohols into an oleic acid microdroplet stimulate a rapid spreading of the same on a water sublayer, which helps in the formation of a metastable liquid sheet connected to a liquid toroid. Much like slipping films, the liquid sheet dewets the water underlayer through the formation of holes before they grow and coalesce to form liquid ribbons. While such liquid structures eventually break into an array of microdroplets, the liquid toroid expands before undergoing a Plateau-Rayleigh instability to form microdroplets. A single step self-organization process in which a chemical trigger can convert a microdroplet into a liquid-toroid on a water surface, in absence of any rotational influence. A symmetric to asymmetric transition in toroid morphology is observed due to the changeover of laminar to turbulent flow regimes with the reduction in viscosity of fluid-sublayer or variation in chemical triggers. The toroid cross-section and droplet spacing after the toroid breakup follow a length scale evaluated from a linear stability analysis.


HO-1 induction ameliorates experimental murine membranous nephropathy: anti-oxidative, anti-apoptotic and immunomodulatory effects.
Therapeutic agents for membranous nephropathy (MN) remain ill-defined. Haeme oxygenase (HO)-1 is considered to play a protective role in various disorders. Here, we assessed the efficacy of HO-1 induction therapy for MN. MN was induced in BALB/c mice with intravenous injections of cationic bovine serum albumin. Three groups of mice were administered 100 micromol/kg Cobalt protoporphyrin (CoPP, a potent HO-1 inducer), Tin protoporphyrin (SnPP, a potent HO-1 inhibitor) or phosphate-buffered saline via intra-peritoneal injections once a week starting from the induction of MN. Disease severity was verified by serum and urine metabolic profiles and by renal histopathology. Cytokine profiles, immunoglobulin production, the expression of oxidative stress markers (thiobarbituric acid reactive substances, TBARS) and apoptosis, as measured by TUNEL, were also determined. Mice treated with CoPP displayed a significant reduction in proteinuria and a marked amelioration of glomerular lesions, accompanied by attenuated immune-complex deposition. The production of immunoglobulins in MN mice treated with CoPP was significantly reduced compared with that of mice in the other two groups. TBARS in the serum and kidneys, as well as apoptosis, were also significantly reduced in CoPP-treated mice. Cytokine mRNA expression in the renal cortex indicated that CoPP not only decreased the expression of proinflammatory cytokines, but also increased the expression of anti-inflammatory cytokines (interleukin-10). HO-1 induction therapy may ameliorate experimental MN via multiple pathways, including anti-oxidative, anti-apoptotic and immunomodulatory effects. HO-1 inducing regimens should be considered as a potential therapeutic intervention in MN in the future.


Effects of short term water immersion on peripheral reflex excitability in hemiplegic and healthy individuals: A preliminary study.
Reflex excitability is increased in hemiplegic patients compared to healthy controls. One challenge of stroke rehabilitation is to decrease the effects of hyperreflexia, which may be possible with water immersion. Methods/Aims: The present study examined the effects of acute water immersion on electrically-evoked Hmax:Mmax ratios (a measure of reflex excitability) in 7 hyperreflexive hemiplegic patients and 7 age-matched healthy people. Hmax:Mmax ratios were measured from soleus on dry land (L1), immediately after (W1) and 5 minutes after immersion (W5), and again after five minutes on land (L5). Water immersion led to an acute increase in Hmax:Mmax ratio in both groups. However, after returning to dry land, there was a non-significant decrease in the Hmax:Mmax ratio of 8% in the hemiplegic group and 10% in healthy controls compared to pre-immersion values. A short period of water immersion can decrease peripheral reflex excitability after returning to dry land in both healthy controls and post-stroke patients, although longer immersion periods may be required for sustainable effects. Water immersion may offer promise as a low-risk, non-invasive and non-pharmaceutical method of decreasing hyperreflexivity, and could thus support aquatic rehabilitation following stroke.


History of the terrestrial isopod genus Ligidium in Japan based on phylogeographic analysis.
Phylogeographical approaches explain the genetic diversity of local organisms in the context of their geological and geographic environments. Thus, genetic diversity can be a proxy for geological history. Here we propose a genus of woodland isopod, Ligidium, as a marker of geological history in relation to orogeny and the Quaternary glacial cycle. Mitochondrial analysis of 721 individuals from 97 sites across Japan revealed phylogenetic divergence between the northeastern and southwestern Japan arcs. It also showed repeated population expansions in northeastern Japan in response to Quaternary glacial and interglacial cycles. Genome-wide analysis of 83 selected individuals revealed multiple genetic nuclear clusters. The genomic groupings were consistent with the local geographic distribution, indicating that the Ligidium phylogeny reflects its regional history. Ligidium DNA sequence analysis can provide insight into the geological, geographical, and paleoenvironmental history of the studied region.


Organization and development of the perivascular space system in the neurohypophysis of the laboratory mouse.
The organization of the system of perivascular space around the capillaries in the neurohypophysis was studied in the adult and developing laboratory mouse by the use of histological silver impregnation and electron microscopical techniques. In the median eminence short and long extensions, arising mainly from the shallow space around capillary loops of the primary plexus of the portal system, formed radiations into the adjacent neural tissue of the external zone. The tissue of the neural lobe was separable into non-vascular regions dominated by undilated portions of neurosecretory nerve fibres and pituicytes, and neurovascular regions with perivascular space extensions forming an extensive system of connections between neighbouring capillaries. In the median eminence, the system of extensions of the perivascular space was estimated to increase the neurovascular contact surface area by at least 50%, implying an increased efficiency of the organ without a notable increase of its volume. The possibility that the ramifications of the perivascular space imply an enhanced uptake rate into the bloodstream and a subsequent increased concentration of the neurohormones in the portal blood, was discussed. During development of the median eminence, differentiation of perivascular space extensions of the adult type started in the juvenile of about three weeks of age, when shallow capillary loops had been formed. In the neural lobe, perivascular space ramifications were already present when the internal capillaries were formed and were fairly frequent in ten-day young. At the age of three to four weeks the organization of the system was similar to that of the adult animal.


Embryonic and adult neurons interact to allow Purkinje cell replacement in mutant cerebellum.
It has often been proposed that one way of replacing degenerating neurons in the brain is to implant embryonic neurons of the same type. However, in the case of so-called 'point-to-point' systems, as opposed to the 'paracrine' systems which mainly involve local release of neurotransmitter, functional recovery requires a precise re-establishment of the missing circuitry. We recently showed that in one point-to-point system, the cerebellum of adult mice homozygous for the mutation Purkinje cell degeneration (pcd)2, missing Purkinje cells can be replaced by grafting cerebellar primordia from normal mouse embryos. Here, we present studies of the cellular mechanisms underlying this successful replacement. Grafted Purkinje cells leave the graft to migrate along stereotyped pathways to their final position in the deficient molecular layer, where they receive synaptic contacts from adult host neurons. Both the detailed timetable and the precise cellular interactions observed are remarkably similar to those occurring during normal development. Our results suggest that the deficient molecular layer exerts a selective neurotropic effect on neurons of the missing category, and that the embryonic neurons are able to respond to this signal during a period defined by their own internal clock. We also raise the possibility that embryonic Purkinje cells can induce in adult neural cells a new type of plasticity, that of recreating a permissive microenvironment for the integration of embryonic neurons.


Population structure inhibits evolutionary diversification under competition for resources.
A model is presented that explores how population structure affects the evolutionary outcome of ecological competition for resources. The model assumes that competition for resources occurs within groups of a finite number of individuals (interaction groups), and that limited dispersal of individuals between groups (according to Wright's island model of population structure) results in genetic structuring of the population. It is found that both finite-sized interaction groups and limited dispersal can have substantial effects on the evolution of resource exploitation strategies as compared to models with a single, infinitely large, well-mixed interaction group. Both effects, in general, tend to select for less aggressive competitive strategies. Moreover, both effects also tend to reduce the likelihood of the evolutionary diversification of resource exploitation strategies that often occurs in models of resource competition with infinite populations. The results are discussed in the context of theories of the evolutionary diversification of resource exploitation strategies and speciation.


Device profile of the Ambicor two-piece inflatable penile prosthesis for treatment of erectile dysfunction: overview of its safety and efficacy.
Introduction: Erectile dysfunction is one of the most common forms of male sexual dysfunction worldwide. Over the past several decades, the inflatable penile prosthesis has emerged as the gold standard surgical treatment for refractory erectile dysfunction. The vast majority of current penile implants are three-piece inflatable penile prostheses. However, the design of the two-piece inflatable penile prosthesis offers certain advantages for both the patient and surgeon, and may be the preferred penile implant for certain patient populations.Areas covered: The Ambicor two-piece inflatable penile prosthesis (Men's Health Division, Boston Scientific, Marlborough, MA, USA) was introduced in 1994 by American Medical Systems (Minnetonka, MN, USA, now a subsidiary of Boston Scientific) and received further design improvements in 1998 to address early mechanical issues with the device. Currently, the Ambicor is the only two-piece inflatable penile prosthesis available in the United States. This review article aims to provide an overview of the Ambicor device and summarize the best available clinical data regarding outcomes and safety.Expert opinion: While two-piece devices account for a small minority of current penile implants, the Ambicor should be considered a safe, reliable, and effective option for appropriately selected patients with the advantage of avoiding blind reservoir placement.


Antirestriction Protein ArdB (R64) Interacts with DNA.
The antirestriction ArdB protein inhibits the endonuclease activity of type I restriction/modification (RM) systems in vivo; however, the mechanism of inhibition remains unknown. In this study, we showed that recombinant ArdB from Escherichia coli cells co-purified with DNA. When overexpressed in E. coli cells, a portion of ArdB protein formed insoluble DNA-free aggregates. Only native ArdB, but not the ArdBΔD141 mutant lacking the antirestriction activity, co-purified with DNA upon anion-exchange and affinity chromatography or total DNA isolation from formaldehyde-treated cells. These observations confirm the hypothesis that ArdB blocks DNA translocation via the R subunits of the R2M2S complex of type I RM enzymes.


Defective assembly of the mitochondrial ribosomes in yeast cells grown in the presence of mitochondrial protein synthesis inhibitors.
The involvement of mitochondrial protein synthesis in the assembly of the mitochondrial ribosomes was investigated by studying the extent to which the assembly process can proceed in the presence of mitochondrial protein synthesis inhibitors erythromycin and chloramphenicol. Yeast cells grown in the presence of erythromycin (2 mg/ml) do not appear to contain any detectable amounts of the mitochondrial small (37 S) ribosomal subunit. Instead, a ribonucleoparticle with a sedimentation coefficient of 30 S was observed; this particle could be shown to be related to the mitochondrial small ribosomal subunit by two-dimensional gel electrophoretic analysis of its protein components. Since the var1 protein is the only mitochondrial translation product known to be associated with the mitochondrial ribosome, our results suggest that this protein is essential for the assembly of the mature small subunit, and that the var1 protein enters the pathway for the assembly of the small subunit at a late step. In at least one strain of yeast the accumulation of the 30-S particle appears to be very sensitive to catabolite repression. When yeast cells are grown in the presence of chloramphenicol instead of erythromycin, assembly of the small subunit appears to be only partially inhibited, and the presence of the 30-S particle could not be clearly demonstrated. This observation is consistent with the fact that in yeast, chloramphenicol inhibits mitochondrial protein synthesis by about 95% only and that the synthesis of the var1 protein appears to be the least sensitive to this inhibition.


Oxidative stress and status of antioxidant enzymes in children with Kashin-Beck disease.
To clarify whether there is oxidative stress in Kashin-Beck disease (KBD) and if cartilage damage from reactive oxygen species (ROS) and oxidative stress mediate the chondral necrosis in articular cartilage of KBD. We recruited 64 KBD patients, 46 healthy children from severely affected KBD regions, 81 healthy children from a non-severely affected KBD endemic regions, and 91 healthy control children from a non-KBD region. Ten patients with KBD from the non-severely affected KBD regions were included in the experiment. The 2,3-DAN fluorescence technique was used to test selenium in the hair and blood. The biochemical techniques used to test the indicators of oxidative stress included thiobarbituric acid reactive substances (TBARS) levels, and antioxidant enzyme activities in serum samples. Histochemical staining was used to detect proteoglycans in cartilage sections. The 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxydeoxyguanisine (8-OHdG) were localized by immunohistochemistry. The levels of TBARS in serum were significantly increased in KBD children. The levels of antioxidants in serum were significantly higher in both KBD and normal children from KBD regions than in the normal children from non-KBD regions. The percentage of chondrocytes staining for 4-HNE and 8-OHdG in KBD patients was significantly higher than in controls. Staining for 4-HNE and 8-OHdG in KBD patients was prominent in all zones of articular cartilage, especially in the necrotic chondrocytes of the deep zone. KBD is an oxidative stress-related disease, and the oxidative stress in cartilage contributes to the pathology of cartilage damage in KBD.


Involvement of spinal opioid systems in footshock-induced analgesia: antagonism by naloxone is possible only before induction of analgesia.
Footshock reliably produces analgesia in rats which is mediated either by opiate or non-opiate systems. It has recently been demonstrated that a critical factor determining the involvement of endogenous opioids is the body region shocked; front paw shock produces a naloxone-reversible analgesia and hind paw shock produces an analgesia which fails to be attenuated by this opiate antagonist. The present study demonstrated that a crucial opiate site for the production of front paw footshock-induced analgesia (FSIA) exists within the spinal cord. One microgram of naloxone delivered directly to the lumbosacral cord immediately prior to shock significantly attenuated this analgesia. However, the efficacy of naloxone antagonism was order-dependent in that naloxone failed to antagonize fron paw FSIA if delivered immediately after shock; naloxone could prevent but could not reverse the analgesic state. The body region shocked was again observed to be a critical factor determining the involvement of endogenous opioids since 1 microgram of spinal naloxone failed to antagonize hind paw FSIA. These results were discussed in light of recent evidence proposing a neuromodulatory role of opioids within the spinal cord.


Pretreatment C-reactive protein is a predictor for outcomes after reduced-intensity allogeneic hematopoietic cell transplantation.
We tested the independent prognostic impact of 2 commonly used biomarkers, C-reactive protein (CRP) and interleukin (IL)-6, on the outcomes of allogeneic hematopoietic cell transplantation (HCT). Consecutive patients who underwent a uniform reduced-intensity conditioning (RIC) regimen of fludarabine (Flu), melphalan (Mel), and alemtuzumab were evaluated retrospectively. Cryopreserved serum samples drawn before the RIC were available to measure CRP levels in 81 patients and IL-6 levels in 79 patients. Patients with CRP levels above the median of 18.5 mg/L had significantly more grade 3-4 hepatic toxicity (P=.01), longer HCT hospital stay (P=.005), more acute graft-versus-host disease (aGVHD) (P=.003), greater nonrelapse mortality (NRM) (P=.01), and inferior overall survival (OS; P=.02). Higher baseline CRP showed no significant correlation with grade 3-4 infectious toxicity (P=.09). In contrast to CRP, pre-HCT IL-6 levels above the median of 78.3 pg/mL did not confer a statistically significant increased risk of toxicity or mortality. An elevated HCT comorbidity index (HCT-CI) did not predict for any measure of HCT morbidity. After adjustment for disease status, comorbidity, performance status, and age, elevated CRP concentration remained predictive of NRM. These data require confirmation in non-T cell-depleted conditioning regimens. If validated, they suggest that preconditioning CRP holds promise for enhancing estimates of transplantation tolerance.


Synergistic effects of 1,25(OH)2D3 and 24,25(OH)2D3 on duodenal CaBP in rachitic chicks and on eggshell weight in Japanese quails.
The role of 24,25(OH)2D3 in calcium homeostasis is still controversial. In the present study the administration of low doses of 1,25(OH)2D3 and of higher doses of 24,25(OH)2D3 either alone or in conjunction with each other, were studied in rachitic chicks and in Japanese quails. Whereas 24,25(OH)2D3 alone had no significant effect on duodenal CaBP and on alkaline phosphatase in chick serum, it increased the influence of 1,25(OH)2D3 on these two parameters strongly. Also, when 1,25(OH)2D3 and 24,25(OH)2D3 were given simultaneously to Japanese quails, calcium excretion via the egg shell was clearly higher than when either metabolite had been administered alone. These results indicate that 1,25(OH)2D3 and 24,25(OH)2D3 exert a strong synergistic effect in rachitic animals.


Prolongation of QTc interval: relationship with etiology and severity of liver disease, mortality and liver transplantation.
A prolonged QTc interval has been reported in patients with liver disease. The objectives of our study were to determine whether a prolonged QTc interval was an independent predictor of mortality in patients with cirrhosis and to examine the effect of liver transplantation (LT) on QTc interval. We retrospectively studied two cohorts of patients - QTc interval was measured in 409 patients (pre-transplant group), and in 162 patients (transplant group) before and 6 months after LT. QT interval (mean) corrected (QTc) for ventricular rate was read from a 12-lead EKG. Patients with known cardiovascular disease or other risk factors that are known to cause a prolonged QTc interval were excluded. Pre-transplant group. One hundred and sixty-two patients (40%) had a prolonged QTc interval (>440 ms). By binary logistic regression, age (P=0.005), alcoholic cirrhosis (P=0.007) and Child-Pugh scores (P=0.007) were independent predictors of prolonged QTc interval. Sixty-six patients died during a mean follow-up of 8.9 years. Although the Kaplan-Meier survival curve showed a lower survival in patients with a prolonged QTc interval (P=0.03 by log rank test), when survival was adjusted for the Child-Pugh score by Cox regression survival analysis, there were no survival differences in patients with and without prolonged QTc interval. Cox regression analysis showed that the Child-Pugh score (hazard ratio 1.5, CI 1.3-1.6, s<0.001) was the only independent predictor of survival. Transplant group. In this cohort, 91 patients (56%) had prolonged QTc (>440 ms) before LT. Mean QTc improved significantly after LT (429 +/- 29 ms vs. 450 +/- 39 ms P<0.002). Of the 91 patients with prolonged QTc, 50 (55%) normalized, three (3.3%) remained unchanged, 12 (13.3%) showed further prolongation, and 26 (28%) showed improvement but remained above normal limits. An additional nine patients who had normal QTc before LT developed prolonged QTc (>440 ms) after LT. A prolonged QTc interval was common in patients with cirrhosis, but its presence had no independent effect on mortality. Prolonged QTc returns to normal values in about half of the patients after LT, suggesting that liver disease plays a role, but may not be the only factor in the pathogenesis of prolonged QTc.


The impact of advancing age on postoperative outcomes in plastic surgery.
Age has been shown to be an independent predictor of complications in general surgery patients. In contrast, the effect of age on outcomes after plastic surgery has yet to be confirmed or refuted. The objective of the current investigation was to evaluate a possible association between age and postoperative outcomes after plastic surgery. The 2005-2012 NSQIP database was retrospectively reviewed for all patients undergoing plastic surgery. Patients ≥60 years with procedures under the category of plastic surgery in NSQIP were selected for analysis. The primary outcome of interest was 30-day overall complication rates. Multivariate regression models were constructed to control for potential perioperative confounders. Of the 2,320,920 patients captured in the NSQIP database, 36,819 patients underwent plastic surgery and met inclusion criteria. The incidence of unadjusted overall complications increased with age with an overall complication rate of 9.0% in patients <60 years, 11.6% in patients 60-69 years, 13.2% in patients 70-79 years, and 15.9% in patients 80 or more years (p < 0.001). After adjusting for potential confounders, age was not independently associated with increased overall complications rates in patients 60-69 years (OR = 1.026; 95% CI = 0.927-1.135; p = 0.619) and 70-79 years (OR = 0.933; 95% CI = 0.797-0.919; p = 0.393), although patients 80 years and older experienced more medical complications (OR = 1.626; 95% CI = 1.218-2.172; p = 0.001). Age is not independently associated with overall worse outcomes in patients undergoing plastic surgery. Medical complications and mortality were more likely in extremes of age (>80 years). Age alone should not be included as a decisional factor in patients <80 years old considering plastic surgery.


Does Personality Moderate Reaction and Adaptation to Major Life Events? Evidence from the British Household Panel Survey.
A nationally representative panel study of British households was used to examine the extent to which Big Five personality traits interact with the experience of major life events (marriage, childbirth, unemployment, and widowhood) to predict increases and decreases in life satisfaction following the event. Results show that major life events are associated with changes in life satisfaction, and some of these changes are very long lasting. Personality traits did not have consistent moderating effects on the association between stressful life events and life satisfaction over time.


Dimensions of uncertainty communication: What is conveyed by verbal terms and numeric ranges.
The paper reviews two strands of research on communication of uncertainty that usually have been investigated separately: (1) Probabilities attached to specific outcomes, and (2) Range judgments. Probabilities are sometimes expressed by verbal phrases ("rain is likely") and at other times in a numeric format ("70% chance of rain"), whereas range judgments describe the potential amounts expected ("1-4 mm of rain"). Examination of previous research shows that both descriptions convey, in addition to the strength of expectations, pragmatic information about the communicative situation. For instance, so-called verbal probability expressions (VPE), as likely, unlikely, a chance, or not certain give some, albeit vague, probabilistic information, but carry in addition an implicit message about the sources of uncertainty, the outcome's valence and severity, along with information about the speakers' attitudes and their communicative intentions. VPEs are directional by drawing attention either to an outcome's occurrence ("it is possible") or to its non-occurrence ("it is doubtful"). In this sense they may be more informative than numbers. Uncertainties about outcomes in a distribution (continuous quantities) are alternatively expressed as interval estimates. The width of such intervals can function as a cue to credibility and expertise. Incomplete, one-sided intervals, where only one boundary is stated, imply directionality. "More than 100 people" suggests a crowd, while "less than 200" implies a shortfall. As with VPEs, directionally positive intervals are more frequent, and perhaps more neutral than negative ones. To convey expectancies and uncertainty in a balanced way, communicators may have to alternate between complementary frames.


[Behavior of plasma amino acids in alcohol-induced chronic liver diseases].
In chronic liver diseases of alcoholic and non-alcoholic origin there are strikine differences of aspartate, glutamate and prolin. Where as plasma levels of aspartate and prolin are in most cases higher than in non-alcoholics, glutamate shows a contrary behaviour except in hepatic coma. The plasma ratio of alpha-amino-butyric acid to leucin allows no distinction of alcoholic from non-alcoholic liver lesion.


Computer-interactive stereotactic resection of deep-seated and centrally located intraaxial brain lesions.
The carbon dioxide laser has been incorporated into a computer-interactive stereotactic system for precision resection of deep-seated intraaxial neoplasma defined by stereotactic computed tomography and magnetic resonance imaging. One hundred and ninety-seven procedures were performed on 191 patients having deep-seated lesions. Postoperative results have been satisfactory as regards the postoperative condition of the patient in consideration of the completeness of tumor removal achieved.


Labor law violations in Japanese public hospitals from March 2002 to March 2011.
According to the Japan Pediatric Society, the mean extra work hours of hospital pediatricians in 2010 was approximately 80 h per month, which is the certification criterion for Karoshi (death from overwork), but there is no precise picture of personnel management at hospitals because the labor authorities do not disclose detailed statistics concerning labor law violations to the public. Most local governments have a disclosure system, and the local governments that operate public hospitals were requested to disclose warning documents issued by the labor authorities from March 2002 to March 2011. A total of 208/369 public hospitals (56.4%) with ≥200 beds in Japan were warned of labor law violations. Offenses included exceeding the limit of working hours (177 hospitals) and non-payment of increased wages for night and holiday work (98 hospitals). Many public hospitals in Japan did not always pay workers including physicians for increased workload because they do not regard night and holiday duties as work hours.


Molecular Dynamics Methods for Antibody Design.
Complex and coordinated dynamics are closely connected with protein functions, including the binding of antibodies to antigens. Knowledge of such dynamics could improve the design of antibodies. Molecular dynamics (MD) simulations provide a "computational microscope" that can resolve atomic motions and inform antibody design efforts.


The role of the plasma glycosylated hemoglobin A1c/Apolipoprotein A-l ratio in predicting cardiovascular outcomes in acute coronary syndrome.
Glucose and lipid metabolism are major prognostic indicators of coronary heart disease. The ratio of plasma glycosylated hemoglobin A1c (HbA1c) to apolipoprotein A-l (ApoA-l) is an indirect measure of insulin resistance. The study aimed to evaluate whether the HbA1c/ApoA-1 ratio can predict the prognosis in patients with the acute coronary syndrome (ACS). A total of 476 ACS patients diagnosed by coronary angiography were enrolled in this longitudinal, observational, retrospective study. Plasma HbA1c, fasting blood glucose and lipid profile were measured. Patients were stratified according to the tertiles of HbA1c/ApoA-l levels. Cox proportional hazard model was used to examine the predictive value of HbA1c/ApoA-l for study endpoints. The association between the Log HbA1c/ApoA-l ratio and major adverse cardiovascular events (MACEs) was estimated using multiple logistic regression. Baseline characteristics showed a mean age of 66 ± 8 years, and 52.5% were hypertensive, 26.8% diabetic, and 54.5% current or prior smokers. During a mean follow-up period of 22.3 ± 1.7 months, 59 deaths occurred. After adjusting for age, gender, smoking, hypertension, diabetes, and coronary artery disease severity, patients in the highest HbA1c/ApoA-l ratio tertile had a 4.36-fold increased risk of mortality compared with those in the lowest tertile. The multivariate logistic regression showed that the Log HbA1c/ApoA-l ratio was associated with MACEs (Odds ratio 2.95, p = 0.013). After adjusting for traditional cardiovascular risk factors and ACS severity scores, the HbA1c/ApoA-1 ratio remained an independent predictor of all-cause mortality and MACEs in the ACS patients undergoing angiography.


What is the impact, prevalence, disability, and quality of life of pediatric headache?
Pediatric headache is a common health problem in children, with a significant headache reported in more than 75% by the age of 15 years. Pediatric migraine occurs in up to 10.6% of children between the ages of 5 and 15 years and in up to 28% of adolescents between the ages of 15 and 19 years. Given this high frequency, the impact of this disease on the lives of these children and their parents can be quite significant. This impact can be assessed with disease-specific disability and impairment as well as disease non-specific effects on quality of life. The goal of evaluation should be recognition of this impact, whereas the goal of management should be effective treatment that minimizes the impact of this disorder in the short term and for the life of the patient.


Crystal structure of the Al20Mn5.37Ni1.31 phase in the Al-Mn-Ni system.
The inter-metallic phase with composition Al20Mn5.37Ni1.31 (icosa-aluminium penta-manganese nickel) was synthesized by high-temperature sinter-ing of a mixture with initial chemical composition Al60Mn7Ni3. Al20Mn5.37Ni1.31 adopts the Co2Al5 structure type in space-group type P63/mmc, replacing the Co atoms with the transition-metal atoms Mn and Ni. Structure analysis revealed that one of the two transition-metal sites is partially occupied by Ni [refined occupancy 0.342 (2)] and the other is co-occupied by Mn and Ni with a ratio of 0.895 (14):0.105 (14). The present refined chemical composition is supported by complementary energy-dispersive X-ray fluorescence (EDX) analysis and is in agreement with the previously determined Al-Mn-Ni phase diagram [Balanetskyy et al. (2011 ▸). J. Alloys Compd, 509, 3795-3805].


A Pituitary cell type coexpressing messenger ribonucleic acid of proopiomelanocortin and the glycoprotein hormone alpha-subunit in neonatal rat and chicken: rapid decline with age and reappearance in vitro under regulatory pressure of corticotropin-releasing hormone in the rat.
Promiscuous hormone mRNA expression in the pituitary remains poorly understood. We examined by means of RT-PCR and immunostaining whether glycoprotein hormone alpha-subunit (alphaGSU) could be coexpressed with proopiomelanocortin (POMC) in vivo and under pressure of CRH in vitro. Cells coexpressing alphaGSU and POMC mRNA amounted to 2.6% of the cells in ex vivo rat pituitary at birth [postnatal d 1 (P1)], fell to much lower level at P14, and were undetectable in adulthood. In cultured pituitary aggregates of P14 rats, alphaGSU/POMC cells remained scarce but represented up to 6.6% after chronic treatment with CRH but not leukemia inhibitory factor. CRH was less effective in aggregates from P1 and adult rats. The total alphaGSU population ex vivo at P1 was two times smaller than at P14, but in culture it expanded 2.5 times, concomitantly with a reciprocal change in POMC cell abundance. Tpit transcripts were detected in POMC-only and alphaGSU/POMC cells but not in alphaGSU-only cells. Cells coexpressing alphaGSU and POMC mRNA were relatively abundant in P14 chicken pituitary and aggregate cultures, but occurrence was not affected by CRH. Immunostaining showed alphaGSU and POMC colocalization in sporadic cells in intact rat pituitary and CRH-treated cultures at P1 but not at P14 and adult age. The data demonstrate the occurrence of cells coexpressing alphaGSU and POMC in rat and chicken pituitary. The developmental dynamics of this cell population and its response to CRH in vitro in the rat suggest a relationship of these cells with the embryonic branching of the POMC and alphaGSU cell lineages and their mutually opposite developmental course during early postnatal life.


B-cell O-galactosyltransferase activity, and expression of O-glycosylation genes in bone marrow in IgA nephropathy.
In IgA nephropathy (IgAN), pathogenic IgA1 is likely derived from bone marrow (BM) cells and exhibits reduced O-galactosylation. Defective O-galactosylation may arise from the compromised expression or function of the enzyme beta-galactosyltransferase and/or its molecular chaperone (Cosmc). We measured B-cell O-galactosylation activity and the relative gene expression of beta-galactosyltransferase and Cosmc in peripheral blood and BM taken from patients with IgAN and controls. O-galactosylation activity was measured in peripheral and BM B cells by the incorporation of radiolabeled galactose into an asialo-mucin acceptor. Gene expression of beta-galactosyltransferase and Cosmc was measured by real-time PCR and related to that of the enzyme GalNAc-T2 (UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-2), which synthesizes the core O-glycan. Neither the B-cell O-galactosylation activity nor the gene expression of the enzyme or chaperone was different between patients and controls. However, the relationships between the O-glycosylation of serum IgA1, galactosylation activity, and beta-galactosyltransferase gene expression showed different patterns in IgAN and controls. In IgAN, O-galactosylation activity correlated with beta-galactosyltransferase gene expression, but not with IgA1 O-glycosylation, suggesting that factors other than the availability of beta-galactosyltransferase or Cosmc are responsible for altered IgA1 O-glycosylation.


Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk.
The genetic aspects of AAT deficiency and the variable manifestations of lung disease in PI Z individuals are reviewed. The role of modifying genetic factors which may interact with environmental factors (such as cigarette smoking) is discussed, and directions for future research are presented.


Short-term effects of air pollution on respiratory morbidity at Rio de Janeiro--PART I: Air pollution assessment.
Exposure to air pollution has been related with the most varied adverse health outcomes. This study aims to assess the impact of air pollution on the emergency hospitalization for respiratory disease in Rio de Janeiro, Brazil. The study was divided in two parts: Part I specifically addressing the air pollution assessment and Part II addressing the health assessment. Accordingly, this Part I aims to: i) evaluate the concentrations of PM(10), SO(2) and CO at two sites in Rio de Janeiro and compare them; ii) analyse the concentrations observed according to the national and international standards; and iii) analyse the air pollutants behaviour, namely, annually, seasonally, daily and considering weekdays/weekends variations. The pollutant concentrations were measured at two different sites in Rio de Janeiro and the analysis was performed for the period between September 2000 and December 2005. Results showed that PM(10) concentrations in Rio de Janeiro exceeded the daily and annual standards imposed by the European Union, the Brazilian legislation and WHO guidelines. Regarding SO(2) and CO, concentrations were, generally, below both European and Brazilian standards. Nevertheless, considering WHO guidelines, SO(2) threshold for daily concentrations (20 μg m(-3)) was exceeded around 150 times. Behaviour assessment showed that the influence of traffic is a major factor affecting the air pollution in Rio de Janeiro. Considering the results achieved and the proven health effects of air pollution, strategies should be defined for its reduction, particularly concerning particulate matter, and consequently contribute to the protection of public health.


The contribution of more sensitive hepatitis B surface antigen assays to detecting and monitoring hepatitis B infection.
Hepatitis B surface antigen (HBsAg) remains the main viral marker for screening and monitoring hepatitis B virus (HBV) infection. The quantification limit of most current HBsAg assays is around 0.05 IU/mL. The Lumipulse-G-HBsAg-Quant assay (Fujirebio) claims to obtain a tenfold improvement in sensitivity. This study aimed to assess the performance of this assay in detecting low HBsAg levels in clinical samples. Three panels of stored frozen samples were selected on the basis of HBV-DNA and HBsAg values obtained previously with routine techniques. Panels 1 (n=13) and 2 (n=52) consisted of DNA-positive/HBsAg-negative samples from individuals in the window period and with occult HBV infection respectively. Panel 3 comprised 23 samples with low or discrepant HBsAg screening results. All these samples were tested retrospectively with the DiaSorin and Fujirebio HBsAg assays. Sixteen out of 65 samples (25 %), initially screened HBsAg negative, were reactive only with the Fujirebio assay (median value= 0.015 IU/mL; IQR= 0.012): three (23 %) samples from panel 1 and 13 (25 %) from panel 2. Thirteen of these 16 (81 %) had HBsAg values below 0.03 IU/mL with the DiaSorin assay. In panel 3, 22 (96 %) samples were quantified successfully with the Fujirebio assay (median: 0.32 IU/mL; IQR: 1.20) and 19 (83 %) with the DiaSorin assay (median: 0.31 IU/mL; IQR: 0.65). Concentrations obtained with the two assays showed good correlations (r=0.893, Spearman). HBsAg assays with enhanced analytical sensitivity could improve HBV serological profile interpretation with possible consequences on clinical management of infected patients, and on blood transfusion safety.


RNA-dependent RNA polymerase activity in two morphologically different white clover cryptic viruses.
RNA-dependent RNA polymerase activities were detected in purified particles of white clover cryptic viruses 1 and 2. The polymerases of the two viruses had different requirements for optimum activity. Enzyme activity was dependent upon the presence of virus particles, Mg2+, and the four ribonucleoside triphosphates, and was insensitive to actinomycin D, alpha-amanitin, and rifampicin. The labeled reaction products were dsRNAs as indicated by CF 11 column chromatography and by their ionic-strength-dependent sensitivity to hydrolysis by RNase A and resistance to S1 nuclease. The dsRNAs synthesized in vitro had the same electrophoretic mobilities as the corresponding viral templates.


Precipitation of (Mg/Fe-CTAB) - Layered double hydroxide nanoparticles onto sewage sludge for producing novel sorbent to remove Congo red and methylene blue dyes from aqueous environment.
Preparation of new sorbent from precipitation of nano-sized (Mg/Fe-CTAB)- layered double hydroxide (LDH) on the surfaces of sewage sludge byproduct to remove the anionic and cationic dyes was the focal point of this work. The presence of nanoparticles and enlarged of interlayers by CTAB intercalation have increased the sludge surface area from 5.34 to 10.32 m2/g. The CTAB mass 0.03 g/50 mL, sludge dosage 1 g/50 mL and (Mg/Fe) molar ratio 2 were the best preparation conditions required to obtain effective sorbent with efficiencies exceeded 93% for MB and CR dyes. These efficiencies were obtained under operational conditions for batch study of 0.5 g coated sludge per 50 mL colored dye solution, initial pH 3 (for CR) and 12 (for MB), and time 3 h for 10 mg/L dyes at 200 rpm. Models of Langmuir and pseudo second-order have a high capability in the representation of sorption records with maximum capacities of adsorption 163.6 and 132.6 mg/g for CR and MB dye, respectively. The X-ray diffraction analysis proved that the calcite occurred mainly at 2θ = 29.8° while quartz corresponded to the 21, 26.6, 36.4, 36.9, 50.1, 60.01 and 68.4°. Characterization tests showed that nano-sized particles of magnesium/iron were precipitated on the sludge due to the formation of hydrotalcite-like compounds with an increase in the percentages of Mg and Fe from 0.87 and 1.36 to 4.25 and 3.03%, respectively. The results showed that the electrostatic attraction, intra-particle diffusion and hydrogen bonding were predominant mechanisms for removal of CR and MB onto coated sludge.


Synergistic effect of tumor necrosis factor-alpha and hydrogen peroxide on the induction of IL-8 production in human intestinal Caco-2 cells.
Oxidative stress and inflammatory cytokines such as TNF-α are thought to be involved in mucosal inflammation. The intestinal epithelium may be concurrently stimulated by both oxidative stress and inflammatory cytokines during the inflammation process in the intestines. However, experimental models for intestinal inflammation still employ single stimulation, either by an oxidative stress or inflammatory cytokine. We therefore examined an in vitro inflammation study using human intestinal epithelial Caco-2 cells, in which the cells were stimulated both by hydrogen peroxide and TNF-α, and measured the IL-8 production as an index of inflammation. The IL-8 production (secretion, mRNA expression, and transcriptional activity) induced by both TNF-α and H(2)O(2) was significantly higher than that by single stimulation. The synergistic effect of TNF-α and H(2)O(2) on the NF-κB signaling pathway (transcriptional activity and p65 nuclear translocation) was also observed. Oxidative stress and TNF-α may cooperatively enhance IL-8 production via NF-κB in Caco-2 cells.


Risk Burden of Coronary Perforation in Chronic Total Occlusion Recanalization: Latin American CTO Registry Analysis.
Background Coronary perforation is a life-threatening complication of acute percutaneous coronary intervention (PCI) for chronic total occlusions (CTO), but data on midterm outcomes are limited. Methods and Results Data from LATAM (Latin American)-CTO Registry (57 centers; 9 countries) were analyzed. We assessed the risk of 30-day, 1-year major adverse cardiac events of coronary perforation using time-to-event and weighted composite end point analysis having CTO PCI without perforation as comparators. Additionally, we studied the independent predictors of perforation in these patients. Of 2054 patients who underwent CTO PCI between 2015 and 2018, the median Multicenter CTO Registry in Japan and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention-Chronic total occlusions scores were 2.0 (1.0-3.0) and 1.0 (0.0-2.0), respectively. The perforation rate was 3.7%, of which 55% were Ellis class 1. After 1-year coronary perforation had higher major adverse cardiac events rates (24.9% versus 13.3%; P<0.01). Using weighted composite end point, perforation was associated with increased bleeding and ischemic events at 6 months (P=0.04) and 1 year (P<0.01). We found as independent predictors associated with coronary perforation during CTO PCI: maximum activated clotting time (P<0.01), Multicenter CTO Registry in Japan score ≥2 (P=0.05), antegrade knuckle wire (P=0.04), and right coronary artery CTO PCI (P=0.05). Conclusions Coronary perforation was infrequent and associated with anatomical and procedural complexity, resulting in higher risk of hemorrhagic and ischemic events. Landmark and weighted analysis showed a sustained burden of major events between 6 months and 1 year follow-up.


[Evaluation with the computer of infrared photos of the optic fundus. I. Technical basis (author's transl)].
The importance of spectral analysis for the ophthalmology is explained by means of the optical properties of hamoglobin and pigment. Basic technical provisions for the applied infraredfundusphotography as well as methods of computer aided image analysis are explained.


Aspirin and cancer risk: an updated quantitative review to 2005.
Aspirin has been associated to a reduced risk of colorectal, and possibly of a few other common cancers. Epidemiological studies on aspirin and cancer risk published up to December 2005 have been reviewed, and pooled relative risks (RR) for several cancers have been provided. Besides a reduction in the risk of cancer of the colorectum (RR = 0.71, 95% confidence interval, CI: 0.67-0.75), there is evidence-although more limited, and mainly from case-control studies-that aspirin has a favourable effect on cancers of the esophagus (RR = 0.72, 95% CI: 0.62-0.84), stomach (RR = 0.84, 95% CI: 0.76-0.93), breast (RR = 0.91, 95% CI: 0.88-0.95), ovary (RR = 0.89, 95% CI: 0.78-1.02) and lung (RR = 0.94, 95% CI: 0.89-1.00). The role of aspirin on other cancers, such as pancreatic, prostate, bladder cancer, and non-Hodgkins' lymphomas is less clear, and an increase of risk has been suggested for kidney cancer. For most cancer sites, however, significant heterogeneity between studies, and particularly across study design, was found, with a reduction in risk generally stronger in case-control than in cohort studies. Further, notwithstanding the large amount of epidemiological evidence, substantial uncertainties remain about the proper aspirin dose and duration of treatment.


The effect of reflective writing interventions on the critical thinking skills and dispositions of baccalaureate nursing students.
The importance of critical thinking is well-documented by the American Association of Colleges of Nursing and the National League for Nursing. Reflective writing is often used to increase understanding and analytical ability. The lack of empirical evidence about the effect of reflective writing interventions on critical thinking supports the examination of this concept. Study objectives were: This study used an experimental, pretest-posttest design. The setting was two schools of nursing at universities in the southern United States. The convenience sample included 70 fourth-semester students in baccalaureate nursing programs. Randomly assigned control and experimental groups completed the California Critical Thinking Skills Test (CCTST) and the California Critical Thinking Dispositions Inventory Test (CCTDI). The experimental group completed six reflective writing assignments. Both groups completed the two tests again. Results showed that the experimental group had a significant increase (p=0.03) on the truthseeking subscale of the CCTDI when compared to the control group. The experimental group's scores increased on four CCTST subscales and were higher than the control group's on three CCTST subscales. The results of this study make it imperative for nursing schools to consider including reflective writing-especially assignments based on Paul's (1993) model-in nursing courses. If future studies, testing over longer periods of time, show significant increases in critical thinking, those interventions could be incorporated into nursing curriculum and change the way nurse educators evaluate students.


Effects of D-penicillamine on lymphocyte modulation of synovial collagenase production.
While D-Penicillamine is effective in the treatment of rheumatoid arthritis, its mechanism of action is unknown. In this study, effects of D-Penicillamine on collagenase production by adherent rheumatoid synovial cells were investigated. D-Penicillamine did not directly affect the synovial collagenase production. However, lymphocyte-free-supernatant (LFS) recovered from lymphocytes exposed to D-Penicillamine in vivo and in vitro significantly reduced collagenase production by adherent synovial cells. LFS from lymphocytes of normal subjects and from non-D-Penicillamine treated rheumatoid patients stimulated collagenase production. These investigations indicate that D-Pencillamine indirectly affects collagenase production by cultured synovial cells and suggests beneficial effects on controlling the primary disease process.


Growth of various bacteria and yeast in a peptide and an element diet.
Solutions of a peptide and an elemental diet were artificially contaminated with several bacterial and yeast strains. Their growth was measured after eight and 24 h incubation at 4 degrees and 22 degrees C. At 4 degrees C no increase in colony count could be observed in either diet within 24 h. At 22 degrees a significant increase of all but the campylobacter strains was obtained after 24 h in the peptide diet. In the elemental diet only the pseudomonas and the yeast strains showed a small increase, the campylobacters were reduced and the colony count of all the other test strains remained constant. As such diets are administered continuously for up to 24 h via a tube into the duodenum for severe intestinal disorders it is suggested (i) that they should be prepared under sterile conditions (ii) that peptide diets should be given for no longer than 8 h and (iii) that solutions of both diets should not be stored for longer than 24 h in the refrigerator.


Flow-independent improvement by diltiazem of ischemia-induced conduction delay in porcine hearts.
The calcium channel blocking agent, diltiazem, improves ischemia-induced conduction delays in the canine heart. It is not known, however, if the improvement of myocardial blood flow caused by diltiazem participates in this response. Accordingly, ischemia-induced conduction delay was measured during brief coronary artery occlusion before and after administration of diltiazem in nine anesthetized pigs with fixed heart rate. Acute coronary occlusion prolonged subendocardial (mean +/- standard error of the mean, 39.9 +/- 3.9 ms) and subepicardial (41.6 +/- 4.1 ms) conduction times (time to peak of the bipolar electrogram in each region) by 51 +/- 4 and 58 +/- 5%, respectively. Regional myocardial blood flow at the ischemic electrode sites was 0.006 +/- 0.002 ml/min per g and was unaffected by diltiazem. Intravenous diltiazem pretreatment (0.01, 0.1, 0.3 and 1.0 mg/kg) 5 minutes before coronary occlusion significantly reduced the ischemia-induced conduction delay in both subendocardial and subepicardial regions during coronary occlusion. The pigs in which ventricular fibrillation occurred within 10 minutes showed a significantly longer conduction delay than that observed in pigs in which ventricular fibrillation occurred later (greater than 10 minutes). Thus, the data suggest that the reduction of ischemia-induced conduction delay produced by diltiazem is independent of blood flow changes and, therefore, that diltiazem may have a beneficial antiarrhythmic action.


Assessment of age-specific safety of laparoscopic surgery in elderly patients with ovarian tumors.
We assessed the age-specific safety of laparoscopic surgery in elderly patients with ovarian tumors. We performed a retrospective analysis of 55 elderly patients treated by laparoscopic salpingo-oophorectomy under the diagnosis of an ovarian tumor between January 2009 and December 2014. We divided patients into three groups: "young-elderly" (aged 65-74), "old-elderly" (aged 75-84), and "super-elderly" (aged 85-105) and assessed clinical characteristics, surgical results and postoperative course. Statistical significance of categorical variables was examined by the Student's t-test, Mann-Whitney U test, or Fisher's exact test. Multiple regression analysis was used for multivariate analysis. Of a total of 55 patients who underwent laparoscopic surgery, there were 36 patients in the young-elderly group, 17 in the old-elderly group, and two in the super-elderly group. Statistical analysis was performed between the young-elderly and the old-elderly groups because of the small number in the super-elderly group. More frequent comorbidities were found in the patients in the old-elderly than in the young-elderly group (Fisher's exact test, P = 0.007). There were no significant differences in operative time, estimated blood loss and postoperative hospital stay between the young-elderly and old-elderly groups. Intraoperative complications only occurred in the young-elderly group. Postoperative complications occurred in all groups. Although patients in the old-elderly group had a significantly higher risk for surgery, they had equivalent surgical results to the young-elderly group for laparoscopic salpingo-oophorectomy.


The area of the neuroretinal rim of the optic nerve in normal eyes.
We randomly photographed 113 eyes in 113 people without ocular disease. The area of the disk and its neuroretinal rim as well as the width of the disk and cup were measured. The measurements were corrected for magnification of each eye by measuring its refraction and axial length. A linear correlation between disk area and neuroretinal rim area was found (r = .75) as well as a correlation between the disk area and the cup area (r = .83). There was no correlation between age and disk area or rim area.


'I'm still here, I'm alive and breathing': The experience of Black Americans with long COVID.
In this study, we aimed to characterize the impact of long COVID on quality of life and approaches to symptom management among Black American adults. As a novel condition, qualitative evidence concerning long COVID symptoms and their impact on quality of life can inform the refinement of diagnostic criteria and care plans. However, the underrepresentation of Black Americans in long COVID research is a barrier to achieving equitable care for all long COVID patients. We employed an interpretive description study design. We recruited a convenience sample of 15 Black American adults with long COVID. We analysed the anonymized transcripts from race-concordant, semi-structured interviews using an inductive, thematic analysis approach. We followed the SRQR reporting guidelines. We identified four themes: (1) The impact of long COVID symptoms on personal identity and pre-existing conditions; (2) Self-management strategies for long COVID symptoms; (3) Social determinants of health and symptom management; and (4) Effects on interpersonal relationships. Findings demonstrate the comprehensive ramifications of long COVID on the lives of Black American adults. Results also articulate how pre-existing conditions, social risk factors, distrust due to systemic racism, and the nature of interpersonal relationships can complicate symptom management. Care approaches that support access to and implementation of integrative therapies may be best suited to meet the needs of long COVID patients. Clinicians should also prioritize eliminating patient exposure to discrimination, implicit bias, and microaggressions. This is of particular concern for long COVID patients who have symptoms that are difficult to objectively quantify, such as pain and fatigue. While patient perspectives and experiences were the focus of this study, patients were not involved with the design or conduct of the study, data analysis or interpretation, or writing the manuscript.