Indocyanine green angiographic features of traumatic choroidal ruptures.
To investigate the indocyanine green (ICG) angiographic findings of healed traumatic choroidal ruptures. Three eyes of two patients with choroidal ruptures underwent both fluorescein angiography and ICG angiography with a digital high-resolution system. Fundus examination showed healed choroidal ruptures in all three eyes. Two of the eyes had old macular scars and one eye had a recent choroidal neovascular membrane with serous detachment of the macula. On fluorescein angiography, the choroidal ruptures showed hypofluorescence at very early stages followed by late hyperfluorescence. On ICG angiography, the choroidal ruptures were hypofluorescent in early, mid and late phases. ICG angiography provided a clear delineation of the choroidal ruptures. In all eyes, the lesion was better defined on the ICG angiogram than on the fluorescein angiogram. ICG angiography can be helpful in the clinical evaluation of choroidal ruptures and can be used together with fluorescein angiography for the diagnosis and follow-up of choroidal ruptures.


Direct evidence for intra- and intermolecular disulfide bond formation in the human glucocorticoid receptor. Inhibition of DNA binding and identification of a new receptor-associated protein.
We have investigated the potential for the steroid affinity-labeled human glucocorticoid receptor to form both intramolecular and intermolecular disulfide bonds. Glucocorticoid receptors labeled in intact HeLa S3 cells with the covalent affinity label [3H]dexamethasone mesylate ([3H]DM) were analyzed on denaturing 5-12% polyacrylamide gels under both nonreducing and reducing conditions. Under nonreducing conditions the affinity-labeled receptor migrated as a heterogeneous species having an average molecular mass of approximately 96 kDa whereas, under reducing conditions, the receptor migrated as a more discrete form. These data suggest that a reducing environment can influence the structure of the glucocorticoid receptor monomer and further imply that sulfhydryl groups within the affinity-labeled receptor are available for modification. To pursue this observation in greater detail, we tested the effect of oxidizing conditions on the structure of the glucocorticoid receptor. The presence of low concentrations (0.125-0.5 mM) of three oxidizing reagents (sodium tetrathionate, disulfiram, and iodosobenzoate) altered the migration of the affinity-labeled receptor resulting in forms of apparent lower molecular mass (as low as 78 kDa). This altered migration, not seen with most other cytosolic proteins, is consistent with the formation of intramolecular disulfide bonds within the receptor which presumably cause it to assume a folded conformation and migrate faster through the gel. At higher concentrations of these reagents (up to 5.0 mM), we also detect a saturably labeled [3H]DM band which has a higher molecular mass (approximately 140 kDa), indicating the formation of intermolecular disulfide bonds between the [3H]DM-labeled receptor and another closely associated protein(s) having a molecular mass of approximately 40 kDa. The effects which these oxidizing reagents have on glucocorticoid receptor structure are completely reversed upon the addition of dithiothreitol, indicating that the observed changes in migration do not reflect receptor proteolysis but rather a folding and unfolding within the receptor monomeric protein. We have also analyzed the effect of this oxidation/reduction on the function of the glucocorticoid receptor. Oxidation of the [3H]DM-labeled receptor complex with 0.5 mM sodium tetrathionate inhibited activation of receptor to a form capable of binding to DNA-cellulose. This inhibition can be reversed with dithiothreitol at 25 degrees C but not at 0 degrees C, suggesting that these oxidizing reagents are inhibitory at the transformation and/or activation steps.(ABSTRACT TRUNCATED AT 400 WORDS)


The "parasite detoxification hypothesis": lead exposure potentially changes the ecological interaction from parasitism to mutualism.
In urban areas, organisms are exposed to high pollutant levels, especially element trace metals that may impact host-parasite interactions. Indeed, parasites have been reported to reduce the negative effects of pollutants on their hosts. The fitness of parasitized organisms in polluted environments may therefore be greater than that of unparasitized organisms. In our study, we used an experimental approach to test this hypothesis on feral pigeons (Columba livia), which are endemically parasitized by nematodes and exposed to high levels of lead in urban areas. We tested the combined effects of lead exposure and helminth parasitism on different pigeon fitness components: preening, immunocompetence, abundance of lice (Columbicola columbae) and haemosporidian parasites (Heamoproteus spp., Plasmodium spp.), reproduction investment, and oxidative stress. Our results show that among pigeons exposed to lead treatment, individuals harboring nematode parasites exhibit more preening activity and have fewer ectoparasites lice than nematode-free individuals. Benefits for nematode-parasitized individuals exposed to lead were not detected for other fitness parameters. Further studies are required to confirm the "parasite detoxification hypothesis" in pigeons and to identify the mechanisms by which this detoxification occurs.


Antibodies against oxidized LDL and atherosclerosis in rheumatoid arthritis patients treated with biological agents: a prospective controlled study.
The aim of this study was to investigate the relation among atherosclerosis, antibodies against oxidized LDL (anti-oxLDL), and inflammation in rheumatoid arthritis (RA) patients treated with biological (b) disease-modifying anti-rheumatic drugs (DMARDs). Fifty-nine patients who were receiving conventional synthetic DMARDs and were eligible for treatment with a biological agent were included in the study. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and IgG antibodies against oxidized LDL (anti-oxLDL) as well as carotid intima-media thickness (cIMT) were determined before and after 6 months of treatment. Thirty-one healthy individuals were used as a control group. At baseline, RA patients had lower TC and HDL-C levels and increased cIMT compared to controls. After a 6-month follow-up, the re-evaluation of carotids revealed a statistically important decrease of cIMT values. This observation was accompanied by a statistically important elevation of HDL-C levels and a reduction of the titer of anti-oxLDL antibodies regardless of the bDMARD that was administered. No statistically significant association was found between the cIMT and anti-oxLDL, HDL-C, CRP, or DAS28 score neither before nor 6 months after treatment using linear regression analyses adjusted for age and gender. We provide evidence that atherogenic lipid profile and ongoing atherosclerosis which characterize RA patients appear to improve after biological therapy, and we also suggest a possible atherogenic effect of IgG anti-ox LDL antibodies.


Purification of saikosaponins a, c and d. Application of large-scale reversed high-performance liquid chromatography.
The preparative separation of saikosaponins a, c, and d from Bupleurum falcatum was performed by high-performance liquid chromatography on a 100 X 11 cm I.D. axially compressed column, packed with 20-micron ODS silica gel using a step gradient with mixtures of acetonitrile and water as the mobile phase. Gram quantities of pure compounds were obtained in a single run.


Effect of potassium deficiency and gossypol on urinary N-acetyl-beta-glucosaminidase excretion in the rat.
Some men receiving gossypol in China developed elevated urinary N-acetyl-beta-glucosaminidase (NAG) levels and hypokalemia. Since idiopathic hypokalemia occurs in China, hypokalemic nephropathy may have caused the elevated NAG levels. To learn if gossypol is directly nephrotoxic, we treated rats with a normal or low potassium diet with or without gossypol. The low potassium diet produced high NAG levels rather than the gossypol. This indicates the importance of differentiating hypokalemic nephropathy from drug nephrotoxicity in regions where idiopathic hypokalemia occurs.


A new mitochondria-related disease showing myopathy with episodic hyper-creatine kinase-emia.
To elucidate the relationship between mitochondrial DNA (mtDNA) alterations and a mitochondrial disease with a distinct combination of characteristic symptoms, namely episodic hyper-creatine kinase (CK)-emia and mild myopathy. We selected 9 patients with mtDNA np8291 alteration from 586 patients suspected to have a mitochondrial disease, and assessed them clinically, pathologically, and genetically. These 9 patients had undiagnosed mitochondrial myopathy with episodic hyper-CK-emia, all showing similar symptoms and progression. Patients had mild muscle weakness and episodic hyper-CK-emia triggered by infections or drugs. Five of 9 patients were initially diagnosed with other conditions, such as myasthenia gravis, polymyositis, viral myositis, and drug-induced myopathy, because these conditions were acute or subacute, and 9 patients showed the same 16 mtDNA alterations, which have been reported to be nonpathological polymorphisms. Muscle biopsy revealed ragged-red fibers, highly expressed succinate dehydrogenase staining fibers, and cytochrome c oxidase-deficient fibers. Because their mitochondrial sequence data was almost the same, and 9 patients live in widely separated cities in Japan, the alterations may have arisen from a single source. These findings suggest that mild myopathy with episodic hyper-CK-emia associated with some of the 16 mtDNA alterations or at least with their mitochondria, could be a novel mitochondrial disease. Therefore, we propose that this disease be named as "mitochondrial myopathy with episodic hyper-CK-emia (MIMECK)." These alterations could work concomitantly and probably modify the impact of medications or other environmental factors. We believe these findings provide an insight into a novel aspect of mitochondrial disease pathogenesis.


TFE3-renal carcinoma in an adult patient: a case with strong expression of phosphorylated hepatocyte growth factor (HGFR)/Met.
TFE3-renal carcinoma is rare in adults. Patients with this disease often have a poor prognosis, because it has reached an advanced stage at presentation, and there is lack of an effective therapy. The exact mechanism of its malignant behavior is still unclear. In recent years, a significant relationship between TFE3 fusion protein and hepatocyte growth factor receptor (HGFR)/Met tyrosine kinase activity was reported in several malignancies. We previously reported that phosphorylation of HGFR/Met was associated with malignant aggressiveness and survival in patients with conventional RCC. Here, using immunohistochemical techniques, we examined two types of phosphorylated HGFR/Met (pY1234/1235 and pY1349) in a specimen of a 29-year-old man with TFE3-renal carcinoma. Strong expression of both proteins was detected in carcinoma cells, but not in normal kidney tissues. In addition, they were expressed more strongly in TFE3-renal carcinoma than in conventional RCC. Although tumor was diagnosed at T1N0M0 and the patient received radical nephrectomy, the tumor metastasized to multiple organs, and he died 2 years after surgery. We speculate that upregulated phosphorylation of HGFR/Met could be partly associated with the malignant aggressiveness and poor survival of this patient.


Tracheostomy in childhood: review of the literature on complications and mortality over the last three decades.
Tracheostomy is a procedure with unique characteristics when used on pediatric patients due to the greater technical difficulty and higher morbidity and mortality rates relative to the procedure in adults. In recent decades, there have been significant changes in the medical care available to children, particularly for those who need intensive care. Surgical conditions have also improved, and there has been an advent of new equipment and medications. These advances have brought changes to both tracheostomy indications and tracheostomy complications. To perform a review of the articles published over the last three decades on the complications and mortality associated with tracheostomies in children. Articles were selected from the Cochrane, Latin American and Caribbean Health Sciences Literature, SciELO, National Library of Medicine (Medline Plus), and PubMed online databases. The articles selected had been published between January 1985 and December 2014, and the data was compared using the Chi-square test. A total of 3797 articles were chosen, 47 of which were used as the basis for this review. When the three decades were evaluated as a whole, an increase in tracheostomies in male children under one year of age was found. The most common complications during the period analyzed in descending order of frequency were granuloma, infection, and obstruction of the cannula, accidental decannulation, and post-decannulation tracheocutaneous fistula. In the second and third decades of the review, granulomas represented the most common complication; in the first decade of the review, pneumothoraces were the most common. Mortality associated with tracheostomy ranged from 0% to 5.9%, while overall mortality ranged from 2.2% to 59%. In addition, the review included four studies on premature and/or very underweight infants who had undergone tracheostomies; the studies reported evidence of higher mortality in this age group to be largely associated with underlying diseases. Improved surgical techniques and intensive care, the creation of new medications, and vaccines have all redefined the main complications and the mortality rates of tracheostomy in children. It is a safe procedure that increases chances of survival in those who require the prolonged use of mechanical ventilation.


Can a family medicine rotation improve medical students' knowledge, skills and attitude towards primary care in Vietnam? A pre-test-post-test comparison and qualitative survey.
Well-designed studies on the impact of a family medicine rotation on medical students are rare, and very few studies include a qualitative component. This study aimed to determine the improvement of medical students' knowledge, communication skills and attitude towards primary care and explore their perceptions after rotations, in comparison with a control group. We used a mixed-methods design, comprising a pre-test-post-test comparison between a sample of trained students who took family medicine rotations and a control group and a qualitative survey. The measurement of improvement included (i) multiple choice question testing, (ii) objective structured checklist examinations, (iii) self-reporting and (iv) interviews and focus group discussions. Data were collected from August 2017 to June 2018. There were 696 students in the trained group and 617 controls. The two groups' baseline scores in knowledge, communication skills and attitude were not significantly different. Knowledge covering five domains of family medicine (Pearson's r from 0.6 to 0.9) improved significantly, as did attitudes towards primary care in the trained group. There were no differences in communication and counselling skills between the two groups for four situations, but for two-health check-ups and mental health care-skills were significantly improved (Pearson's r from 0.28 to 0.43). The qualitative survey showed highly positive feedback from trained students. The family medicine rotation significantly improved students' knowledge and attitude towards primary care and some communication skills. Further studies should investigate students' interest in and career choice for this discipline.


Subcellular localization of aldehyde dehydrogenase isozymes in human liver.
The subcellular distribution of aldehyde dehydrogenase (ALDH) isozymes in human liver was studied by isoelectric focusing and biochemical procedures in biopsied liver specimens obtained during surgical procedures. Four types of ALDH isozymes (ALDH I, II, III and IV) were identified in human liver by isoelectric focusing. In 6 of the 13 livers examined, ALDH I was not detected, indicating that about half of the Japanese people may be classified as the unusual type. ALDH I, which exhibits a low Km with respect to acetaldehyde (Ac-CHO), was located mainly in the mitochondrial and cytosolic fractions. ALDH II (high Km for Ac-CHO) was found to be localized mainly in the microsomal and cytosolic fractions. ALDH III and IV (very high Km for Ac-CHO) were localized in all fractions, except for ALDH III in the microsomal fraction. Biochemical analysis indicates that low Km ALDH activity was localized in the mitochondrial and cytosolic fractions, while high Km and whole ALDH activities were detected in all 3 fractions. More than 80% of the low Km, high Km and whole ALDH activity was found in the cytosolic fraction. These distribution patterns were quite different from those in rats. These results indicate that the results obtained in animal experiments cannot be directly applied to humans and that the main site of Ac-CHO oxidation in the human liver is in the cytosol.


[Acute mesenteric ischemia].
Acute vascular occlusion within the mesenteric circulation leads to ischemic damage of the corresponding bowel segment, which starts on the mucosal level and progresses transmurally. Report on pathogenesis, clinical picture and treatment of various forms of intestinal ischemia. Analysis of the available literature taking into consideration our own experience. Frequently, predisposing diseases and risk factors are present (e.g., cardiac diseases, hypercoagulability, status post cardiac surgery, circulatory failure, or administration of vasoconstrictive drugs). Acute small bowel ischemia-caused by either mesenteric embolism, mesenteric artery thrombosis, nonocclusive mesenteric ischemia (NOMI) or mesenteric venous thrombosis-represents an acute emergency. If this condition is suspected clinically, the diagnosis must be established immediately by computed tomography of the abdomen with intravenous administration of contrast medium in order to prevent irreversible damage to the small bowel. Medical treatment is supportive. If possible, occluded vessels may be re-opened either by radiologic intervention or surgically. Irreversibly damaged bowel segments must be surgically removed. Ischemic colitis has a benign course in most cases if limited to reversible mucosal damage. The diagnosis is based mainly on colonoscopy and computed tomography findings, and treatment is symptom oriented. Rarely, severe manifestations with a worse prognosis due to considerable comorbidities occur. In such cases, surgical removal of the ischemic bowel is frequently required. Even today, acute mesenteric ischemia is associated with a poor prognosis. To improve survival and to reduce long-term morbidity, a rapid and systematic diagnostic workup is mandatory.


Primary open angle glaucoma: an overview on medical therapy.
The purpose of this review is to discuss the topics relevant to the use of intraocular pressure-lowering strategies, which remains the first line in the management of glaucoma. Estimates of blindness from glaucoma and identification of risk factors remain of interest for all ophthalmologists. New functional tests offer promise for better detection and more accurate diagnosis of glaucoma. We finally discuss the impact of various glaucoma therapies, the principles of monotherapy and fixed combinations, which offer benefits of convenience, cost, and safety.


Improving lupeol production in yeast by recruiting pathway genes from different organisms.
Lupeol is a pentacyclic triterpene that shows a variety of pharmacological properties. Compared to engineering the production of sesquiterpenes and diterpenes, it is much more challenging to engineer the biosynthesis of triterpenes in microbial platforms. This study showed our efforts on engineering the triterpene pathway in Escherichia coli and Saccharomyces cerevisiae cells by recruiting the codon-optimized three lupeol pathway genes from different organisms. By comparing their activities with their respective counterparts, the squalene synthase from Thermosynechococcus elongates (tSQS), the squalene epoxidase from Rattus norvegicus (rSE) and the lupeol synthase from Olea europaea (OeLUP) were introduced into E. coli BL21(DE3), a break-through from zero was observed for lupeol biosynthesis in a prokaryotic host. We also assessed the lupeol pathway under two different yeast backgrounds-WAT11 and EPY300, and have found that the engineered strains based on EPY300, named ECHHOe, processed the best lupeol-producing ability with the maximum lupeol titer being 200.1 mg l-1 at 30 °C in a 72 h-flask culture, which so far was the highest amount of lupeol obtained by a microbial system and provides a basis for further industrial application of lupeol in the future.


A thermoplastic elastomer patch matrix for traditional Chinese medicine: design and evaluation.
To design and evaluate a novel pressure sensitive adhesive (PSA) patch containing traditional Chinese medicine (TCM) using styrene-isoprene-styrene (SIS) copolymer. A mixture D-optimal design with ternary response surface diagram was employed in the optimization process. The proportions of SIS copolymer, tackifying resin and plasticizer were selected as the independent variables while tack force, peel strength of the patch and skin penetrability of methyl salicylate were selected as the dependent variables. The optimized patch was then evaluated including in vivo absorption, pharmacological activities and skin irritation, by comparing with a commercial patch based on natural rubber. The optimized patch, which comprised 30.0% SIS copolymer, 26.6% tackifying resin and 43.4% plasticizer, was superior to commercial patch in skin permeation, pharmacological activities and skin biocompatibility. SIS copolymer was a suitable substitute to natural rubber in producing patches containing TCM formula.


Potential hazards of the dental ultrasonic descaler.
The use of a dental ultrasonic descaler may be associated with biological hazards to structures within the oral cavity. Thermal hazards may result from either frictional contact between the oscillating probe and tooth or from absorption of acoustic energy within the tooth. Transmission of ultrasound along the tooth may result in thrombogenic damage to nearby blood vessels. The vibrating probe tip may produce scratching of the tooth surface, and incorporation of oral bacteria within the aerosol generated by the instrument which may result in transmission of infected material. Damage to the ear may arise from the coupling of ultrasound to the bones of the skull via the tooth. Furthermore the electro-magnetic field produced by these devices may interfere with cardiac pacemakers. It is the patient receiving treatment who is mainly exposed to these potential hazards. However, the clinician and his supporting staff may also be at risk.


A rapid microdetermination of phosphoserine, phosphothreonine, and phosphotyrosine in proteins by automatic cation exchange on a conventional amino acid analyzer.
A cation-exchange chromatographic method for the separation and determination of phosphoserine, phosphothreonine, and phosphotyrosine in proteins after partial acid hydrolysis is described. The short column (0.6 X 8 cm) of an automatic amino acid analyzer was used and elution was carried out isocratically with 10 mM trifluoroacetic acid. The method is highly sensitive and each of the three O-phosphoamino acids can be accurately determined down to the 50-pmol level. Higher sensitivity may be obtained by the use of [32P]phosphate-labeled proteins. A correction factor for the decomposition of phosphoserine or phosphothreonine during acid hydrolysis can be deduced from the amount of inorganic phosphate recovered at the column void volume. The method is sensitive enough to be used for 32P-labeled proteins isolated by two-dimensional gel electrophoresis.


Avoidable mortality for causes amenable to medical care and suicide in physicians in Spain.
To compare avoidable mortality for causes amenable to medical care and suicide in physicians versus other professionals with similar university studies and socioeconomic position in Spain. All people aged 25-64 years who were employed on 1 November 2001 (8,697,387 men and 5,282,611 women) were included. Their vital status was followed for 10 years and the cause of death of deceased was recorded. Using a Poisson regression to estimate the mortality rate ratio (MRR), we compared mortality due to causes of death amenable to medical care, all other causes, and suicide in physicians versus other professionals. Mortality in physicians was used as a reference. The lowest MRR for causes amenable to medical care was observed in engineers/architects (men: 0.84, 95% confidence interval [CI] 0.72, 0.97; women: 0.93, 95% CI 0.64, 1.35) and healthcare professions other than physicians/pharmacists/nurses (men: 0.86, 95% CI 0.56, 1.34; women: 0.69, 95% CI 0.32, 1.46). Regarding mortality for all other causes of death, professionals from these and other occupations presented lower mortality than physicians. Other healthcare professions, entrepreneurs, and managers/executives completed suicide at a higher rate than physicians. Although the accessibility to the healthcare system and to the pharmacological drugs could suggest that physicians would present low rates for causes amenable to medical care and high rates of suicide, our results show that this is not the case in Spain.


Non-target screening reveals the mechanisms responsible for the antagonistic inhibiting effect of the biocides DBNPA and glutaraldehyde on benzoic acid biodegradation.
The desalination and reuse of discharged cooling tower water (CTW) as feed water for the cooling tower could lower the industrial fresh water withdrawal. A potential pre-treatment method before CTW desalination is the use of constructed wetlands (CWs). Biodegradation is an important removal mechanism in CWs. In the present study, the impact of the biocides 2,2-dibromo-2-cyanoacetamide (DBNPA) and glutaraldehyde on the biodegradation process by CW microorganisms was quantified in batch experiments in which benzoic acid was incubated with realistic CTW biocide concentrations. DBNPA had a stronger negative impact on the biodegradation than glutaraldehyde. The combination of DBNPA and glutaraldehyde had a lower impact on the biodegradation than DBNPA alone. UHPLC-qTOF-MS/MS non-target screening combined with data-analysis script 'patRoon' revealed two mechanisms behind this low impact. Firstly, the presence of glutaraldehyde resulted in increased DBNPA transformation to the less toxic transformation product 2-bromo-2-cyanoacetamide (MBNPA) and newly discovered 2,2-dibromopropanediamide. Secondly, the interaction between glutaraldehyde and DBNPA resulted in the formation of new products that were less toxic than DBNPA. The environmental fate and toxicity of these products are still unknown. Nevertheless, their formation can have important implications for the simultaneous use of the biocides DBNPA and glutaraldehyde for a wide array of applications.


Serum IgA1 and IgA2 in normal adults and patients with systemic lupus erythematosus and hepatic disease.
As an early step in examining the factors that regulate synthesis of the IgA subclasses, IgA1 and IgA2, we determined the serum levels of IgA1, IgA2 and total IgA in 50 normal adults, 20 patients with systemic lupus erythematosus (SLE), and 11 patients with liver disease. A quantitative solid phase radioimmunoassay using subclass specific monoclonal hybridoma antibodies was used. Within the normal population there were large variations in the concentrations of IgA1 and IgA2. The levels of IgA1 and IgA2 in samples from males were not significantly different from those from females. However, the mean concentration of IgA1 in samples from Blacks was significantly lower than that from Caucasians, P less than 0.005. In the control population IgA2 constituted from 6 to 35% of the total serum IgA and the levels of IgA1 did not correlate with the levels of IgA2. The mean IgA1 and total IgA in samples obtained from patients with SLE were significantly higher than those from the normal population (P less than 0.0001) although there was no significant difference in the levels of IgA2 in the two groups. In the samples obtained from patients with liver disease both IgA1 and IgA2 were markedly elevated and the levels of IgA1 did correlate with the levels of IgA2. These results indicate that the serum levels of IgA1 and IgA2 are controlled by factors that influence each subclass independently as well as factors that affect each subclass equivalently.


A Very Early Rehabilitation Trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial.
Mobilising patients early after stroke [early mobilisation (EM)] is thought to contribute to the beneficial effects of stroke unit care but it is poorly defined and lacks direct evidence of benefit. We assessed the effectiveness of frequent higher dose very early mobilisation (VEM) after stroke. We conducted a parallel-group, single-blind, prospective randomised controlled trial with blinded end-point assessment using a web-based computer-generated stratified randomisation. The trial took place in 56 acute stroke units in five countries. We included adult patients with a first or recurrent stroke who met physiological inclusion criteria. Patients received either usual stroke unit care (UC) or UC plus VEM commencing within 24 hours of stroke. The primary outcome was good recovery [modified Rankin scale (mRS) score of 0-2] 3 months after stroke. Secondary outcomes at 3 months were the mRS, time to achieve walking 50 m, serious adverse events, quality of life (QoL) and costs at 12 months. Tertiary outcomes included a dose-response analysis. Patients, outcome assessors and investigators involved in the trial were blinded to treatment allocation. We recruited 2104 (UK, n = 610; Australasia, n = 1494) patients: 1054 allocated to VEM and 1050 to UC. Intervention protocol targets were achieved. Compared with UC, VEM patients mobilised 4.8 hours [95% confidence interval (CI) 4.1 to 5.7 hours; p < 0.0001] earlier, with an additional three (95% CI 3.0 to 3.5; p < 0.0001) mobilisation sessions per day. Fewer patients in the VEM group (n = 480, 46%) had a favourable outcome than in the UC group (n = 525, 50%) (adjusted odds ratio 0.73, 95% CI 0.59 to 0.90; p = 0.004). Results were consistent between Australasian and UK settings. There were no statistically significant differences in secondary outcomes at 3 months and QoL at 12 months. Dose-response analysis found a consistent pattern of an improved odds of efficacy and safety outcomes in association with increased daily frequency of out-of-bed sessions but a reduced odds with an increased amount of mobilisation (minutes per day). UC clinicians started mobilisation earlier each year altering the context of the trial. Other potential confounding factors included staff patient interaction. Patients in the VEM group were mobilised earlier and with a higher dose of therapy than those in the UC group, which was already early. This VEM protocol was associated with reduced odds of favourable outcome at 3 months cautioning against very early high-dose mobilisation. At 12 months, health-related QoL was similar regardless of group. Shorter, more frequent mobilisation early after stroke may be associated with a more favourable outcome. These results informed a new trial proposal [A Very Early Rehabilitation Trial - DOSE (AVERT-DOSE)] aiming to determine the optimal frequency and dose of EM. The trial is registered with the Australian New Zealand Clinical Trials Registry number ACTRN12606000185561, Current Controlled Trials ISRCTN98129255 and ISRCTN98129255. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 54. See the NIHR Journals Library website for further project information. Funding was also received from the National Health and Medical Research Council Australia, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, and the Stroke Association. In addition, National Health and Medical Research Council fellowship funding was provided to Julie Bernhardt (1058635), who also received fellowship funding from the Australia Research Council (0991086) and the National Heart Foundation (G04M1571). The Florey Institute of Neuroscience and Mental Health, which hosted the trial, acknowledges the support received from the Victorian Government via the Operational Infrastructure Support Scheme.


What your eyes tell me: Theory of mind in bipolar disorder.
The aim of this study was to assess social- perceptual Theory of Mind in bipolar disorder (BD). 112 euthymic participants with BD I or BD II (65 with BD I and 47 with BD II) were compared to a group of 112 persons with no psychiatric diagnosis and 43 with unipolar depression (UD). They completed the task of the "Reading the Mind in the Eyes" (RMET). The results show that participants with BD, I and II, as well as the group with UD performed significantly more poorly than the control group. As for the wrong answers, BDs mostly chose positive valence stimuli, while the UD group chose negative valence items. The main limitation of this research is related to the characteristics of the cross-sectional study. It cannot detect at what time of the disorder these differences in emotion processing will appear with more intensity. As for future research, we suggest interventions to improve the deficits in ToM in bipolar persons. The use of the RMET in the first stages of BD II could help to facilitate a correct diagnosis.


Transmembrane signalling at the epidermal growth factor receptor.
The EGF receptor, which is homologous to the v-erb-B oncogene product, has intrinsic tyrosine kinase activity, and mediates an increase in polyphosphoinositide turnover and [Ca2+]i. Recently, great progress has been made in understanding the mechanism of signal transduction at this receptor. Jacopo Meldolesi and colleagues discuss how this knowledge may lead to a better understanding of the control of cell proliferation.


Pulmonary response to cadmium and nickel coated fly ash.
Pulmonary reaction to fly ash coated with cadmium (Cd) or nickel (Ni) and to native fly ash was studied in rats after intratracheal inoculation of dust suspensions. The histopathological alterations and changes in biochemical and cellular constituents of the bronchoalveolar lavage were correlated with the metal content in lungs and kidneys. More Ni was adsorbed than Cd on fly ash particulates. Metal-coated fly ash was more toxic than uncoated fly ash. Cd-coated fly ash produced significantly more histopathological and biochemical changes than Ni-coated fly ash. A high concentration of Cd was detected in the kidneys of rats exposed to Cd-coated fly ash.


Review of cardiovascular imaging in The Journal of Nuclear Cardiology in 2014: Part 2 of 2: Myocardial perfusion imaging.
In this new feature of The Journal of Nuclear Cardiology we will summarize key articles that were published in the Journal in the previous year. In the first article of this 2-part series we concentrated on publications dealing with cardiac positron emission tomography, computed tomography, and neuronal imaging. This review will focus on myocardial perfusion imaging summarizing advances in the field including in diagnosis, prognosis, appropriateness, and safety of testing.


Rheumatoid and seronegative arthropathies of the foot.
The foot is often involved in rheumatoid arthritis and its seronegative variants. This article presents an overview of the subject and highlights the various distinguishing features of these arthritic disorders in the foot.


Secondary lens implantation in aphakia: visual results and complications.
We reviewed 70 cases that had undergone secondary lens implantation. The lenses used included 34 Medallion and 36 Choyce Mark VIII lenses. A 20/40 or better vision was present in 74.3% of the cases before implantation, and could be achieved postoperatively in 95.7% of the cases. Corneal changes, i.e. endothelial corneal dystrophy and induced astigmatism, were not noted in cases where Choyce Mark VIII lenses were used. Cystoid macular edema occurred in three cases where surgery followed an intracapsular cataract extraction (5.3%).


The management of penile zip entrapment in children.
Thirty boys, aged 2-12 years, presented with penile zip entrapment to one Paediatric Accident and Emergency Department over a 7 year period. The rate of presentation was one zip entrapment per 4068 new patient attendances. In contrast to previous reports, injuries occurred most commonly whilst the zip was being done up and whilst underpants were being worn. Two types of entrapment were seen, determining the way in which release was achieved. Contrary to previous suggestions, most children (26 out of 30) were easily managed in the Accident and Emergency Department without general anaesthetic. No patient required circumcision or suffered any sequelae. An algorithm for treatment based upon the experience of this study is presented.


Allergic rhinitis and rhinosinusitis.
A relationship between allergic rhinitis and acute and chronic rhinosinusitis has been postulated for many years. Epidemiologic evidence suggests that such a relationship is likely. In addition, evidence of a common pathophysiologic mechanism linking these diseases is compelling and continues to evolve. Although a clear and definitive causal relationship remains to be elucidated, an increasing number of studies support the plausibility of this link. The current paradigm of the "unified airway" and evidence to support this model further strengthen this link. This article reviews the literature relating allergic rhinitis and acute and chronic rhinosinusitis.


Incidence and prevalence of hepatitis C in prisons and other closed settings: results of a systematic review and meta-analysis.
People detained in prisons and other closed settings are at elevated risk of infection with hepatitis C virus (HCV). We undertook a systematic review and meta-analysis with the aim of determining the rate of incident HCV infection and the prevalence of anti-HCV among detainees in closed settings. We systematically searched databases of peer-reviewed literature and widely distributed a call for unpublished data. We calculated summary estimates of incidence and prevalence among general population detainees and detainees with a history of injection drug use (IDU), and explored heterogeneity through stratification and meta-regression. The summary prevalence estimates were used to estimate the number of anti-HCV positive prisoners globally. HCV incidence among general detainees was 1.4 per 100 person-years (py; 95% confidence interval [CI]: 0.1, 2.7; k = 4), and 16.4 per 100 py (95% CI: 0.8, 32.1; k = 3) among detainees with a history of IDU. The summary prevalence estimate of anti-HCV in general detainees was 26% (95% CI: 23%, 29%; k = 93), and in detainees with a history of IDU, 64% (95% CI: 58%, 70%; k = 51). The regions of highest prevalence were Central Asia (38%; 95% CI 32%, 43%; k = 1) and Australasia (35%; 95% CI: 28%, 43%; k = 9). We estimate that 2.2 million (range: 1.4-2.9 million) detainees globally are anti-HCV positive, with the largest populations in North America (668,500; range: 553,500-784,000) and East and Southeast Asia (638,000; range: 332,000-970,000). HCV is a significant concern in detained populations, with one in four detainees anti-HCV-positive. Epidemiological data on the extent of HCV infection in detained populations is lacking in many countries. Greater attention towards prevention, diagnosis, and treatment of HCV infection among detained populations is urgently required.


Behavioral and life-history evidence for interspecific competition in the larvae of two heliconian butterflies.
Interspecific competition in herbivorous insects remains a controversial issue. To date, many studied systems have not met assumptions of the traditional competition theory, and a new paradigm has been emerging. We examined the behavioral and life-history consequences of common host plant use of Heliconius erato and Dryas iulia (Nymphalidae) in relation to Passiflora suberosa (Passifloraceae). Larvae of the former use the apical portion of this host; the latter is presumably able to explore all plant parts. We assessed host use pattern in relation to leaf age, when reared either alone (D. iulia) or together (D. iulia and H. erato). Larval feeding choice tests with respect to leaf age were performed, and performance was recorded. Observations were made to assess antagonistic behavior of H. erato and D. iulia towards each other, if any. Similarly to H. erato, D. iulia fed on the young leaves significantly more than the mature ones; larvae were not induced to prefer mature leaves. First instars of H. erato used only the apical parts of P. suberosa and displayed aggressive behavior towards D. iulia, which moved to the lower shoot portions. Larval mortality and development time of both species significantly increased when reared together; such performance costs were more pronounced in D. iulia than H. erato. Our study gathers evidences that use of P. suberosa by these heliconian butterflies represent a case of competitive exclusion resulting in niche differentiation, where costs are higher for D. iulia than H. erato.


Does the law matter? An empirical study on the accessibility of Finnish higher education institutions' web pages.
Information and communication technology (ICT) has made higher education available to many students in a new way. The role of online learning in higher education institutions (HEIs) has grown to an unprecedented scale due to the COVID-19 pandemic. The diversity of higher education students has increased, and accessible solutions are needed. New European and national regulations support these trends. The research reported in this paper was conducted in Finland, which is one of the leading European countries in terms of high technology and digitalisation. The aim of this research is to explore the accessibility of all Finnish HEIs' (N = 38) landing pages based on Web Content Accessibility Guidelines (WCAG 2.1). The situations before and after recent legislation are compared. Previous studies have shown that HEIs' landing pages typically have many accessibility errors. Unlike previous studies, this study considered the types of accessibility errors at a detailed level to support HEIs' development and implementation of accessibility standards. A combination of two automated accessibility testing tools was used, and the performance of individual tools was analysed. The results show that HEIs' landing pages are not accessible and there are enormous differences between institutions. Two clusters of HEIs were found: one with good accessibility in terms of WCAG 2.1's four principles (perceivable, operable, understandable, and robust), and one with poor accessibility. On half of the HEIs' landing pages with poor accessibility, the number of errors increased even given the binding nature of the law. Obviously, there is still work to be done. Implications for practice are also discussed.


[Haemophilia A and intracranial bleedings in infants].
Haemophilia is a well-known X-linked recessive bleeding disorder related to a deficiency of factor VIII. The aim of the paper is to point out the role of an early diagnosis in cases of intracranial bleeding, especially in neonates and to highlight the bad prognosis. Three patients were included in the study from our prospective data. All had severe factor VIII deficiency (less than 1%). The first of them was a newborn without familial history of haemophilia which presented with hypotonia and seizures after a delivery with vacuum. CT showed a subdural haematoma and MRI multiple ischemic lesions. Two months later, he died from a new intracranial haemorrhagic episode resistent to infusion of factor VIII related to development of an anti-factor VIII antiboby. The second neonate had no familial history more and experienced hypothermia and areactive mydriasis because of an acute subdural haematoma. He died eight days later of ischemic lesions in spite of a craniotomy. The third was a 5-month-old boy with a familial history. Physical examination revealed lethargy, seizure and a recent cranial perimeter increase. He underwent a craniotomy with a good result. The authors stress the need for immediate factor VIII infusion and appropriate neurosurgical work-up. The rapid medical management is mandatory if morbidity and mortality are to be minimized.


Bile immunoglobulins and blockage of biliary endoprosthesis: an immunohistochemical study.
Endoscopic biliary stenting for pancreaticobiliary malignancy is often limited by recurrent stent occlusion as a result of bacterial biofilm formation and sludge deposition. Bile immunoglobulins are thought to be important in combating biliary sepsis. To investigate whether bile immunoglobulins are involved in the pathogenesis of stent blockage. Immunohistochemical technique was used to study the distribution of bile immunoglobulins, bacteria and sludge in blocked biliary stents. Patients with malignant obstructive jaundice were palliated by endoscopic insertion of a 10-FG polyethylene stent into the biliary tract. Blocked stents were retrieved from those who presented with recurrent jaundice and fever. The stents were cross-sectionally cut into slices and fixed in formalin. Immunoglobulins were demonstrated by the peroxidase-anti-peroxidase staining procedure using rabbit anti-serum. The central bulk of the stent deposits appeared as an amorphous, structureless material. IgA was found as a rim of dark brown discoloration at the periphery. IgG showed similar distribution and intensity to that of IgA whereas little IgM was detected. Bile immunoglobulins may facilitate bacterial adhesion, clumping, and hence biofilm formation on the stent surface.


Angiolymphoid hyperplasia involving large arteries.
Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare vascular proliferative disorder, which most commonly involves the skin of the head and neck regions. Noncutaneous localization of this pathology is unusual, and its primary localization in large arteries presenting as a pulsatile mass is extremely rare. We report here two cases of ALHE manifested as masses of the occipital and brachial artery. ALHE should be considered in the differential diagnosis of localized peripheral arterial masses in young patients.


[A cohort study on risk factors of lung cancer in Yunnan tin miners].
Smoking is a major cause of lung cancer. Studies of lung cancer among miners have shown that occupational exposure also played an important role. The aim of this study is to investigate radon, cigarette use and other risk factors of lung cancer in Yunnan tin miners and to provide a scientific basis for the prevention and control of occupational lung cancer. A prospective cohort study was conducted among Yunnan tin miners, the associations between potential risk factors for lung cancer were analyzed by multivariate Cox regression model. Effects of age at first radon exposure and radon exposure rate on lung cancer risk were analyzed. The relationship between cumulative working level month and lung cancer was analyzed according to smoking status. The joint effect of tobacco use and cumulative radon exposure was analyzed based on additive and multiplicative models. Increased risk of lung cancer was associated with age at enrollment, tobacco use, prior bronchitis, and cumulative arsenic and radon exposure, while higher education level was associated with decreased lung cancer risk. An inverse effect of radon exposure rate was observed. There was no significant association between lung cancer risk and first radon exposure age. There was a significant additive interaction between tobacco use and radon exposure on lung cancer risk. Several risk factors may contribute to the high incidence of lung cancer in Yunnan tin miners. Further studies are warranted to evaluate joint effect of different risk factors.


The impact of early-life environment on absence epilepsy and neuropsychiatric comorbidities.
This review discusses the long-term effects of early-life environment on epileptogenesis, epilepsy, and neuropsychiatric comorbidities with an emphasis on the absence epilepsy. The WAG/Rij rat strain is a well-validated genetic model of absence epilepsy with mild depression-like (dysthymia) comorbidity. Although pathologic phenotype in WAG/Rij rats is genetically determined, convincing evidence presented in this review suggests that the absence epilepsy and depression-like comorbidity in WAG/Rij rats may be governed by early-life events, such as prenatal drug exposure, early-life stress, neonatal maternal separation, neonatal handling, maternal care, environmental enrichment, neonatal sensory impairments, neonatal tactile stimulation, and maternal diet. The data, as presented here, indicate that some early environmental events can promote and accelerate the development of absence seizures and their neuropsychiatric comorbidities, while others may exert anti-epileptogenic and disease-modifying effects. The early environment can lead to phenotypic alterations in offspring due to epigenetic modifications of gene expression, which may have maladaptive consequences or represent a therapeutic value. Targeting DNA methylation with a maternal methyl-enriched diet during the perinatal period appears to be a new preventive epigenetic anti-absence therapy. A number of caveats related to the maternal methyl-enriched diet and prospects for future research are discussed.


Reduction of antigen-induced respiratory abnormalities and airway inflammation in sensitized guinea pigs by a superoxide dismutase mimetic.
Reactive oxygen species have been implicated in the pathogenesis of asthma and, in atopic asthmatics, endogenous superoxide dismutase (SOD) enzyme levels are known to decrease. This suggests that replacing a failed endogenous SOD enzyme system with a mimetic of the endogenous enzyme would be beneficial and protective. In this study we demonstrate that removal of superoxide by the SOD mimetic (SODm) M40403 reduces the respiratory and histopathological lung abnormalities due to ovalbumin (OA) aerosol in a model of allergic asthma-like reaction in sensitized guinea pigs. Both respiratory abnormalities and bronchoconstriction in response to OA challenge are nearly absent in naïve animals, while they sharply became severe in sensitized animals. In addition, OA aerosol induced a reduction of MnSOD activity which was paralleled with bronchiolar lumen reduction, pulmonary air space hyperinflation, mast cell degranulation, eosinophil infiltration, bronchial epithelial cell apoptosis, increase in myeloperoxidase activity, malonyldialdehyde production and 8-hydroxy-2'-deoxyguanosine formation in the lung tissue, as well as elevation of PGD2 in the bronchoalveolar lavage fluid. Treatment with M40403 restored the levels of MnSOD activity and significantly reduced all the above parameters. In summary, our findings support the potential therapeutic use of SOD mimetics in asthma and anaphylactic reactions and account for a critical role for superoxide in acute allergic asthma-like reaction in actively sensitized guinea pig.


Biotechnology and bone graft substitutes.
Trauma, disease, developmental deformities, and tumor resection frequently cause bone defects that seriously challenge the skills of orthopedic and maxillofacial surgeons. Currently, repairing osseous deficiencies involves various medical surgical techniques, including autogenous grafts, allografts, internal and external fixation devices, electrical stimulation, and alloplastic implants. The existing technology, though effective in many cases, still is beset with numerous difficulties and disadvantages. A critical need for improved treatment methods exists today. Biotechnology now provides access to new bone repair concepts via administration of protein growth and morphogenic factors. Implantable device and drug delivery system technologies also have advanced. The converging biopharmaceutical, device, and delivery technologies represent an opportunity to improve the quality of health care for individuals with orthopedic and maxillofacial deficiencies. This report reviews current concepts in fracture healing and bone repair and examines existing treatment modalities. It also addresses novel protein drugs that stimulate osseous regeneration and delivery systems for these drugs.


A case of PANDAS with Kleine-Levin type periodic hypersomnia.
We report on an 11-year-old girl, presenting with clinical features suggesting both pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and Kleine-Levin syndrome (KLS), who was successfully treated with penicillin prophylaxis. KLS is a sleep disorder characterized by recurrent episodes of hypersomnia and at least one of the following symptoms: (1) cognitive or mood disturbances, (2) megaphagia with compulsive eating; (3) hypersexuality with inappropriate behaviors; and (4) abnormal behavior. The etiopathogenesis is still unclear and there is no effective treatment other than symptomatic therapies. This intriguing case report suggests novel insight into the pathogenesis of this rare and enigmatic syndrome.


Chromosome-level genome assembly of Nibea coibor using PacBio HiFi reads and Hi-C technologies.
Nibea coibor belongs to Sciaenidae and is distributed in the South China Sea, East China Sea, India and the Philippines. In this study, we sequenced the DNA of a male Nibea coibor using PacBio long-read sequencing and generated chromatin interaction data. The genome size of Nibea coibor was estimated to be 611.85~633.88 Mb based on k-mer counts generated with Jellyfish. PacBio sequencing produced 29.26 Gb of HiFi reads, and Hifiasm was used to assemble a 627.60 Mb genome with a contig N50 of 10.66 Mb. We further found the canonical telomeric repeats "TTAGGG" to be present at the telomeres of all 24 chromosomes. The completeness of the assembly was estimated to be 98.9% and 97.8% using BUSCO and Merqury, respectively. Using the combination of ab initio prediction, protein homology and RNAseq annotation, we identified a total of 21,433 protein-coding genes. Phylogenetic analyses showed that Nibea coibor and Nibea albiflora are closely related. The results provide an important basis for research on the genetic breeding and genome evolution of Nibea coibor.


Broadband WET: a novel technique for quantitative characterization of minor components in foods.
NMR analysis of foods frequently suffers from a problem of dynamic range, which limits the detection of minor components due to the huge signals of water and major components such as sugars. In the present study, we propose a new method named as 'broadband WET'. This pulse scheme was applied to persimmon fruit juice for saturating the resonances of water and sugars, which covered a broad bandwidth. In comparison with the conventional solvent suppression methods such as WET and DPFGSE-WATERGATE, it was shown that broadband WET provided highly selective suppression of resonances covering an extensive bandwidth and quantitative signals of minor components without distortion. The proposed method is suitable to detect quantitative signals of the minor components with a high sensitivity.


New inhibitors of dihydroorotate dehydrogenase (DHODH) based on the 4-hydroxy-1,2,5-oxadiazol-3-yl (hydroxyfurazanyl) scaffold.
Based on some structural analogies with leflunomide and brequinar, two well-known inhibitors of dihydroorotate dehydrogenase (DHODH), a new series of products was designed, by joining the substituted biphenyl moiety to the 4-hydroxy-1,2,5-oxadiazol-3-yl scaffold through an amide bridge. The compounds were studied for their DHODH inhibitory activity on rat liver mitochondrial/microsomal membranes. The activity was found to be closely dependent on the substitution pattern at the biphenyl system; the most potent products were those bearing two or four fluorine atoms at the phenyl adjacent to the oxadiazole ring. A molecular modeling study suggested that these structures might have a brequinar-like binding mode. The greater potency of fluorinated analogs may depend partly on enhanced interactions with the hydrophobic ubiquinone channel, and partly on the role of fluorine in stabilizing the putative bioactive conformation.


Comprehensive guava fruit data set: Digital and thermal images for analysis and classification.
Guava (Psidium guajava) is a nutritious fruit known for its origin in Mexico, Central or South America, and the Caribbean. Its production faces declining levels, infections, and disease outbreaks. This dataset focuses on the early identification of guava diseases using image processing and computer vision. Farmers can detect and address diseases promptly by developing an expert system, increasing yields and reducing economic losses. The technology behind this dataset enables sustainable guava farming and disease prevention. This dataset consists of digital and thermal images of guava fruits, including healthy, damaged, and various diseased conditions such as wilt, Anthracnose, canker, and rot. The images are categorized based on the fruit's maturity level (mature, half-mature, and mature) and captured under different drop heights. The dataset also includes information on the damage-inducing methods, storage conditions, image capture schedule, and specific diseases present. The thermal images were acquired using hot air with controlled temperature and velocity.


Spatiotemporal localization of proteins in mycobacteria.
Although prokaryotic organisms lack traditional organelles, they must still organize cellular structures in space and time, challenges that different species solve differently. To systematically define the subcellular architecture of mycobacteria, we perform high-throughput imaging of a library of fluorescently tagged proteins expressed in Mycobacterium smegmatis and develop a customized computational pipeline, MOMIA and GEMATRIA, to analyze these data. Our results establish a spatial organization network of over 700 conserved mycobacterial proteins and reveal a coherent localization pattern for many proteins of known function, including those in translation, energy metabolism, cell growth and division, as well as proteins of unknown function. Furthermore, our pipeline exploits morphologic proxies to enable a pseudo-temporal approximation of protein localization and identifies previously uncharacterized cell-cycle-dependent dynamics of essential mycobacterial proteins. Collectively, these data provide a systems perspective on the subcellular organization of mycobacteria and provide tools for the analysis of bacteria with non-standard growth characteristics.


Benefits of active participation of family physicians in geriatric consultations.
Geriatric consultation services are generally beneficial in improving the health and well-being of the elderly. We prospectively studied whether the active participation of family physicians (FPs) in the process of geriatric consultation would improve implementation rates and benefit the health care of the elderly. We carried out a comparative prospective intervention study in three urban academic family medicine clinics. Patients in the control clinics were evaluated by the consultant geriatrician, and a summary of the findings and recommendations were presented to the FP in a brief meeting. In the intervention clinic, the referring FP joined the geriatrician throughout the geriatric assessment. The percentage of implementation of suggested recommendations was evaluated. Information regarding the utilization of health services was provided from computerized data. Of the 212 patients included in the study, 107 were in the intervention group and 105 were controls. The overall rate of implementation was significantly higher for patients in the intervention group (329/445; 73.9%) than for patients in the control group (232/387; 59.9%), P < 0.0001. In the year after the geriatric assessment, those in the intervention group visited the FP less often. A model co-consultation actively involving the FP in the process of assessment of the older patient by the geriatrician improves the degree of implementation of recommendations without an increase in related heath care utilization and costs. This model should be further developed and studied.


Limitations of detection of malignancy in pleural effusions using ELISA-based TRAP assay: comparison with cytological examination.
Telomerase is active in almost all cancers from various organs but is not detectable in most normal cells. Thus, telomerase activity might be a universal and specific marker for diagnosing malignancy. The aim was to evaluate the potential use of the ELISA-based TRAP assay to detect malignancy in pleural effusion, and to compare it with conventional cytological examination. Using the ELISA-based TRAP assay, telomerase activity was examined in 94 consecutive pleural effusions submitted for cytological examination. According to the results of cytology, the 94 samples were divided into two groups: group I, 79 non-malignant pleural effusions, including group IA, no association with a malignant tumour, a control group (n = 63), and group IB, associated with a malignant tumour (n = 16); and group II, 15 malignant pleural effusions. Telomerase activity was detected in five of 63 samples in group IA (7.9%), four of 16 samples in group IB (25%), and six of 15 samples in group II (40%). All five false-positive effusions were from patients with tuberculosis. Comparing group II with group IA, the TRAP assay showed 40% sensitivity, 92.1% specificity, 54.5% positive and 86.6% negative predictive value, and 82.1% accuracy. However, the detection rate of the TRAP assay (88.9%) was higher than that of the cytological examination (66.7%) in lung cancer-inflicted pleural effusions. The ELISA-based TRAP assay is relatively insensitive; therefore, it is unsuitable as a routine diagnostic tool for pleural effusion. False-positive telomerase activity due to lymphocytic contamination may weaken its diagnostic value for malignant effusions in a tuberculosis-endemic area.


LncRNA DSCAM-AS1 acts as a sponge of miR-137 to enhance Tamoxifen resistance in breast cancer.
To investigate the influence of long noncoding RNA (lncRNA) DSCAM-AS1 on the propagation and apoptosis of Tamoxifen-resistant (TR) breast cancer cells via regulation of mircoRNA (miR)-137 and epidermal growth factor receptor pathway substrate 8 (EPS8). Data of GSE5840 downloaded from the Gene Expression Omnibus database were utilized to screen out aberrantly expressed lncRNA and messenger RNA in breast cancer tissue samples. The expressions of DSCAM-AS1, miR-137, and EPS8 were determined by quantitative real time polymerase chain reaction (qRT-PCR). Cell lines were screened by half maximal inhibitory concentration (IC 50 ). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and the flow cytometry assay were used to detect cell proliferation, apoptosis, and cell cycle. The relationship among DSCAM-AS1, miR-137, and EPS8 was studied by miRcode, TargetScan, and Pearson correlation coefficient. A xenograft mouse model experiment was performed to demonstrate the effect of DSCAM-AS1 and EPS8 on tumor growth in vivo. LncRNA DSCAM-AS1 and EPS8 were significantly upregulated, whereas miR-137 was downregulated in TR tissues. DSCAM-AS1 could promote the Tamoxifen resistance of breast cancer, and it was negatively correlated with miR-137, whereas positively correlated with the expression of EPS8 in TR breast cancer tissues. Furthermore, miR-137 could inhibit tumor development and arrest cell cycle at the G0/G1 phase by targeting the 3'-UTR of EPS8. DSCAM-AS1 targeted miR-137 and EPS8 to promote propagation of TR breast cancer cells and inhibit cell apoptosis. LncRNA DSCAM-AS1 acts as a competing endogenous RNA of miR-137 and regulates EPS8 to promote cell reproduction and suppresses cell apoptosis in TR breast cancer.


Evaluation of sugar-cane vinasse treated with Pleurotus sajor-caju utilizing aquatic organisms as toxicological indicators.
Toxicity tests with aquatic organisms constitute an effective tool in the evaluation, prediction and detection of the potential effect of pollutants from environmental samples in living organisms. Vinasse, a highly colored effluent, is a sub-product rich in nutrients, mainly organic matter, with high pollutant potential when disposed in the environment. Assays for vinasse decolorization were performed using the fungus Pleurotus sajor-caju CCB020 in vinasse biodegradation study, were occurred reductions of 82.8% in COD, 75.3% in BOD, 99.2% in the coloration and 99.7% in turbidity. The vinasse toxicity reduction was determined by the exposition to the following organisms: Pseudokirchneriella subcapitata, Daphnia magna, Daphnia similis and Hydra attenuata. This work concluded that the systematic combination of P. sajor-caju and vinasse can be applied in the bioprocess of color reduction and degradation of complex vinasse compounds, with reduction in the toxicity and improving its physical-chemical properties.


Stereospecific effects of (+)- and (-)-catechin on glycogen metabolism in isolated rat hepatocytes.
(+)- and (-)-catechin showed opposite effects on glycogen metabolism in isolated rat hepatocytes. Addition of 0.5 mM catechin to hepatocytes from fasted rats resulted in the case of the (+)-isomer in a 90% stimulation and the case of the (-)-isomer in a 90% inhibition of net glycogen production. When 0.5 mM of the two isomers were added to hepatocytes from fed rats, (+)-catechin inhibited glycogenolysis by 33%, whereas the (-)-isomer stimulated the same process by 42%. At equal concentrations, the effects of (-)-catechin were stronger than those of the (+)-isomer. (-)-Epicatechin acted in a manner similar to (+)-catechin; however, the effect was less pronounced. (+)-Catechin antagonized the inhibitory action of suboptimal doses of glucagon on glycogen production whereby no change in basal or glucagon-elevated cyclic AMP level was observed. The activities of glycogen synthase a and glycogen phosphorylase a were changed by (+)- and (-)-catechin in a way corresponding to the changes in glycogen production and breakdown. (-)-Catechin, however, stimulated the activities of both glycogen synthase a and glycogen phosphorylase a in hepatocytes from fed rats. A possible interaction of the flavonoids or of their metabolites with glycogen phosphorylase is discussed.


The natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination.
The lymphatic vascular system represents a major route for dissemination of several solid tumors, including melanoma. Even though the members of the Vascular Endothelial Growth Factor family VEGF-C and VEGF-A have been shown to drive tumor lymphangiogenesis, experimental evidence indicates that also the pro-angiogenic factor Fibroblast Growth Factor-2 (FGF2) may play a role in the lymphangiogenic switch by triggering the activation of lymphatic endothelial cells (LECs) in cooperation with VEGFs.The soluble pattern recognition receptor Long Pentraxin 3 (PTX3) acts as a natural FGF trap, thus exerting an oncosuppressive role in FGF-dependent tumors. Here, the capacity of PTX3 to modulate lymphangiogenesis was assessed in vitro and in vivo. The results demonstrate that recombinant human PTX3 inhibits the lymphangiogenic activity exerted by the VEGF-A/FGF2/sphingosine-1-phosphate (VFS) cocktail on human and murine LECs. In keeping with in vitro data, a reduced lymphangiogenic response was observed in a lymphangiogenic Matrigel plug assay following the subcutaneous injection of the VFS cocktail in PTX3-overexpressing transgenic TgN(Tie2-hPTX3) mice when compared to wild-type or Ptx3 null animals. Accordingly, the capacity of B16F10-VEGFC-luc melanoma cells to colonize the primary tumor-draining lymph node after grafting into the foot pad was dramatically impaired in PTX3-overexpressing mice.Together with the observation that both the VFS cocktail and melanoma cell conditioned media caused a significant downregulation of PTX3 expression in LECs, these data indicate that the FGF trap activity of PTX3 may exert a key effect in the modulation of lymphangiogenesis and tumor metastatic dissemination.


Clinicopathological spectrum of biopsy-proven renal diseases of patients at a single center in Sri Lanka: a cross sectional retrospective review.
The clinical presentation of renal diseases can vary widely. The lack of a comprehensive national registry for Sri Lanka makes it difficult to provide a detailed record of the various clinical presentations and histopathology of renal disorders in the nation. Therefore, this study aims to provide a record of the spectrum of renal diseases in Sri Lanka. Renal biopsies performed at the nephrology unit in Colombo South Teaching Hospital (CSTH), Sri Lanka from March 2018 to October 2019 was retrospectively studied. Indications for renal biopsy were nephrotic range proteinuria, sub nephrotic range proteinuria, acute kidney injury without obvious etiology, chronic renal disease without obvious etiology and haematuria. A total of 140 native kidney biopsies were analyzed in which majority were females (55.7%). The mean age of the population was 46 ± 15.3 years. The most common indications for renal biopsy were nephrotic range proteinuria (54.3%), followed by sub-nephrotic range proteinuria (14.3%), nephrotic range proteinuria with haematuria (14.3%), sub-nephrotic range proteinuria with haematuria (9.3%), AKI without known cause (4.3%), and CKD without known cause (3.6%). The leading histopathological diagnoses were FSGS (22.1%), lupus nephritis (20%), PSGN (17.1%), DN (12.1%), HTN (9.3%), MCD (6.4%), IgA nephropathy (5.7%), IN (4.3%), vasculitis (2.1%), and MGN (0.7%). The most common indication for renal biopsy was nephrotic range proteinuria in our population. FSGS was the most prevalent histopathological diagnosis and the least frequent diagnosis reported was MGN. The spectrum of renal diseases could differ according to the study location and it changes over time. Therefore, a renal biopsy registry is needed for documenting the changing disease pattern in Sri Lanka.


Case study: The influence of Achilles tendon rupture on knee joint stress during counter-movement jump - Combining musculoskeletal modeling and finite element analysis.
Presently, the current research concerning Achilles tendon rupture repair (ATR) is predominantly centered on the ankle joint, with a paucity of evidence regarding its impact on the knee joint. ATR has the potential to significantly impede athletic performance and increase tibiofemoral contact forces in athletes. The purpose of this study was to prognosticate the distribution of stress within the knee joint during a countermovement jump through the use of a simulation method that amalgamated a musculoskeletal model of a patient who underwent Achilles tendon rupture repair with a finite element model of the knee joint. A male elite badminton player who had suffered an acute Achilles tendon rupture in his right leg one year prior was selected as our study subject. In order to analyze his biomechanical data, we employed both the OpenSim musculoskeletal model and finite element model to compute various parameters such as joint angles, joint moments, joint contact forces, and the distribution of knee joint stress. During the jumping phase, a significantly lower knee extension angle (p < 0.001), ankle dorsiflexion angle (p = 0.002), peak vertical ground reaction force (p < 0.001), and peak tibiofemoral contact force (p = 0.009) were observed on the injured side than on the uninjured side. During the landing phase, the ankle range of motion (ROM) was significantly lower on the injured side than on the uninjured side (p = 0.009), and higher peak vertical ground reaction forces were observed (p = 0.012). Additionally, it is logical that an injured person will put higher load on the uninjured limb, but the finite element analysis indicated that the stresses on the injured side of medial meniscus and medial cartilage were significantly greater than the uninjured side. An Achilles tendon rupture can limit ankle range of motion and lead to greater joint stress on the affected area during countermovement jumps, especially during the landing phase. This increased joint stress may also transfer more stress to the soft tissues of the medial knee, thereby increasing the risk of knee injury. It is worth noting that this study only involves the average knee flexion angle and load after ATR in one athlete. Caution should be exercised when applying the conclusions, and in the future, more participants should be recruited to establish personalized knee finite element models to validate the results.


Amniotic fluid concentration of 5-hydroxyeicosatetraenoic acid is increased in human parturition at term.
5-hydroxyeicosatetraenoic acid (5-HETE) is an arachidonate lipoxygenase product capable of stimulating uterine contractility in a dose-dependent manner in vitro. The purpose of this study was to determine if spontaneous human labor at term is associated with changes in the concentration of this metabolite in amniotic fluid. Fluid was retrieved from 36 women not in labor and from 30 women in active labor at term. 5-HETE was determined by radioimmunoassay. The median amniotic fluid concentration of 5-HETE of women in labor was significantly greater than that of women not in labor (3538 pg/ml vs. 1977 pg/ml, respectively; p = 0.05). This observation is consistent with activation of the lipoxygenase pathway of arachidonic acid metabolism during spontaneous human parturition at term.


Behavior genetic differences within and between defined human populations.
The small populations of the Caucasus offer a unique opportunity to consider concepts, such as heritability, which are often considered properties of a trait but which are really properties of a population. A comprehensive strategy is outlined for studying intra- and interpopulation genetic structure across a wide range of traits and environments. A three-way association is demonstrated between 12 of 16 psychophysiological traits, attitude, and the t allele for PTC sensitivity. Differences between populations and traits are evaluated in theoretical terms for morphological, physiological, and psychological measures. While decreases in performance with inbreeding are often predicted, in these small, isolated populations the effects are minimal.


Single-dose cephalosporin prophylaxis of 929 surgical procedures in a prepaid group practice: a prospective, randomized comparison of cefoperazone and cefotaxime.
In this report, we summarize 929 surgical cases (812 evaluable) receiving preoperatively prophylaxis with either cefoperazone (1 g), or cefotaxime (1 g). The patients were randomized to one of the two single-dose cephalosporin regimens and by operative procedure groups that included hysterectomies, genitourinary procedures, gastrointestinal operations, and the "other procedures" category that was dominated by orthopedic cases, such as total joint replacements and open fracture reductions. The postoperative wound infectious morbidity rates were: cefoperazone 2.2% and cefotaxime 3.0% (overall rate, 2.6%). Most wound infections were superficial, with more than half discovered after patient discharge and unrelated to the surgical prophylaxis. The wound infections associated with colorectal surgery cases given a single-dose of cefoperazone were twofold higher than the control regimen. Non-wound infectious morbidity was 5.8% (p greater than 0.05) for cefoperazone, mostly urinary tract infections causes by Escherichia coli, Streptococcus faecalis, and Staphylococcus spp. Side effects were not considered severe and occurred at a very low rate. Abnormally elevated prothrombin times of patients receiving cefoperazone were not any more frequent than the control regimens. The two prophylaxis regimens were not different statistically (p greater than 0.05) as to the infectious morbidity or adverse reactions. By using either studied single-dose schedule in our prepaid group practice setting, compared with the previously used multi-dose schedules, we could predict an annualized cost savings of $50,000 (cefazolin) and greater than $200,000 (cefoxitin). We propose a single 1-g dose of cefoperazone or cefotaxime (FDA approved) as a cost-effective prophylaxis alternative.


Effect of olive ripening degree on the antidiabetic potential of biophenols-rich extracts of Brava Gallega virgin olive oils.
The diet management is imperative to anticipate risk factors that favour the development of diseases; indeed, the intake of virgin olive oil could be an alternative natural source of α-glucosidase enzyme inhibitors, which delay the digestion rate of carbohydrates. Consequently, the impact of diabetes mellitus (DM) could be diminished. Extra Virgin Olive Oils (EVOO) were elaborated from Galician autochthonous variety 'Brava Gallega' with olives selected at three different degree of ripeness (ripening index, RI: 1.4, 3.0, 5.5) in order to assess the effect of maturation on overall chemical composition, sensory quality, and enzyme inhibition. The phenolic profile of the EVOOs determined by LC-ESI-IT-MS exhibited quantitative differences as ripening advanced; for example oleocanthal, tyrosol, luteolin and apigenin concentrations were higher in the overripe olive oil (RI 5.5). Anyway, the phenolic extracts (from every tested RI) were more active than acarbose. In particular, those obtained from the most mature olives displayed the most powerful inhibitory activity (IC50 value of 143 µg of dry extract/mL). In addition, the significant effect of these compounds (i.e. luteolin, apigenin, tyrosol and oleocanthal) on the inhibitory activity of the olive oil extracts was demonstrated. Our results suggest that, regardless of RI, the inhibitory activity of 'Brava Gallega' olive oils could represent a valuable strategy for reinforcing the health claim of olive oil for phenolic compounds.


Translation and Validation of the Dizziness Handicap Inventory into Thai Language.
To translate and evaluate psychometric properties of Thai version of the Dizziness Handicap Inventory (DHI-TH). A cross-sectional study. Ambulatory. Fifty patients with dizziness at a vestibular clinic. Translation and cross-cultural adaptation of the original English version of the DHI was performed according to published guidelines. Psychometric evaluation included internal consistency, content validity, test-retest reliability, convergent validity, discriminant ability, and responsiveness. Responsiveness was examined in 28 patients with vestibular dysfunction who received vestibular rehabilitation for 6 to 8 weeks. There were no floor and ceiling effects. The Cronbach's alpha was good for the total score (0.87) and subscale scores (0.70 physical, 0.73 emotional, and 0.71 functional). Excellent test-retest reliability was demonstrated for the total and subscales (ICC ranged from 0.91 to 0.97, p < 0.001). The SEM was 3.50 and the MDC was 9.68. The total and subscales of DHI-TH were moderately correlated with the SF-36-TH scores (r ranged from -0.40 to -0.63). An optimal cut-off point for detection of dizziness was 21 points (98% sensitivity, 94% specificity). Responsiveness of the DHI-TH was excellent. The ES and SRM were large (1.25 and 1.59, respectively). The DHI-TH discriminated well between patients with self-perceived improved dizziness versus unchanged dizziness (AUC = 0.87). The MCID was 17 points (82.0% sensitivity, 82.0% specificity). The DHI-TH demonstrated good psychometric properties for patients with dizziness. The DHI-TH is a valid and reliable instrument recommended as a measure of disability and quality of life in Thai patients with dizziness.


Virological and serological studies on poliomyelitis in Karachi, Pakistan. I. Outbreaks in 1990-91.
Between October 1989 and September 1991, 124 cases of poliomyelitis visited the Department of Paediatrics, Civil Hospital Karachi, Pakistan. The majority of them were between 6 months and 2 years of age and the epidemics occurred during the hot seasons. The dominant serotype was poliovirus type 1 during the epidemic season in 1990 and type 2 in 1991. All the polioviruses isolated from the patients were wild-type. Virological studies also disclosed that enteroviruses other than polioviruses were prevalent among healthy children as well as among diarrheal and polio patients. A serological survey to elucidate the serological efficacy of oral polio vaccine (OPV) showed that: (i) in 112 unimmunized children, after disappearance of transplacental maternal antibody during early infancy, antibody prevalence increased gradually and > 80% of the children were seropositive against all three types of polioviruses at 5 years of age; (ii) in 201 children immunized with full doses of OPV in their infancy, the decrease in antibody titer during infancy was less and seroprevalence rose sharply afterwards: at 2 years of age, > 80% of them were seropositive against all three types of the virus. The rapid increase of seroprevalence might be the effect of OPV administration. However, the prevalence was lower than that in developed countries.


Effect of Haemaphysalis punctata infestation on growing lambs and rabbits.
Lambs infected with adult Haemaphysalis punctata and rabbits infected with nymphs developed a macrocytic normochromic anaemia during seven and six successive infestations, respectively. The anaemia was directly proportional to the degree of infestation but disappeared several days after the termination of infestation. A leucocytosis, due to neutrophilia, was seen in both lambs and rabbits. Rabbits developed a thrombocytosis and reticulocytosis. Infested lambs grew less rapidly than uninfested animals. Signs of tick toxicosis and several other clinical manifestations appeared in both infested sheep and rabbits. Circulating antibodies against salivary antigen of adult H punctata were demonstrated in the sera of infested lambs by the micro-ELISA test. Titres were first detected on day 3 after infestation and increased gradually as infestation progressed. No precipitating antibodies in either infested sheep or rabbits were detected.


Family structure differences in health care utilization among U.S. children.
This study explores the relationship between family structure and children's access to health care using data from the 2001-2003 waves of the child sample files from the U.S. National Health Interview Survey. Specifically, we investigate the extent to which family structure types predict children's utilization of preventive health care, and barriers to care. We then explore whether observed differences across family structures can be attributed to differences in demographic characteristics, socioeconomic status (SES), and child health status. Using logistic regression models, we document substantial variation in health care usage and barriers to health care across a variety of family structures. Of note is the finding that the children of single mothers demonstrate extremely different patterns of health care access than do the children of single fathers, and the importance of SES as a risk factor for diminished levels of access to health care varies by family type. SES plays a major role in mediating the relationship between access to care for children in single mother and cohabiting families (when contrasted against children in two married parent families), but less of a role for children living with stepparents, a single father, or with parents and other relatives.


HOMECAT: consensus homologs mapping for interspecific knowledge transfer and functional genomic data integration.
Comparative studies are encouraged by the fast increase of data availability from the latest high-throughput techniques, in particular from functional genomic studies. Yet, the size of datasets, the challenge of complete orthologs findings and not last, the variety of identification formats, make information integration challenging. With HOMECAT, we aim to facilitate cross-species relationship identification and data mapping, by combining orthology predictions from several publicly available sources, a convenient interface for high-throughput data download and automatic identifier conversion into a Cytoscape plug-in, that provides both an integration with a large set of bioinformatics tools, as well as a user-friendly interface. HOMECAT and the Supplementary Materials are freely available at http://www.cbmc.it/homecat/.


Evaluation of Breast Cancer Tumor-Infiltrating Lymphocytes on Ultrasound Images Based on a Novel Multi-Cascade Residual U-Shaped Network.
Breast cancer has become the leading cancer of the 21st century. Tumor-infiltrating lymphocytes (TILs) have emerged as effective biomarkers for predicting treatment response and prognosis in breast cancer. The work described here was aimed at designing a novel deep learning network to assess the levels of TILs in breast ultrasound images. We propose the Multi-Cascade Residual U-Shaped Network (MCRUNet), which incorporates a gray feature enhancement (GFE) module for image reconstruction and normalization to achieve data synergy. Additionally, multiple residual U-shaped (RSU) modules are cascaded as the backbone network to maximize the fusion of global and local features, with a focus on the tumor's location and surrounding regions. The development of MCRUNet is based on data from two hospitals and uses a publicly available ultrasound data set for transfer learning. MCRUNet exhibits excellent performance in assessing TILs levels, achieving an area under the receiver operating characteristic curve of 0.8931, an accuracy of 85.71%, a sensitivity of 83.33%, a specificity of 88.64% and an F1 score of 86.54% in the test group. It outperforms six state-of-the-art networks in terms of performance. The MCRUNet network based on breast ultrasound images of breast cancer patients holds promise for non-invasively predicting TILs levels and aiding personalized treatment decisions.


Geochemical processes of phosphorus‑iron on sediment-water interface during discharge of groundwater to freshwater lakes: Kinetic and mechanistic insights.
Groundwater is widely recognized as a source of lake materials. When it discharges into lakes, phosphorus(P)‑iron(Fe) geochemical reactions occur due to environmental changes, affecting P discharge from groundwater. However, redox kinetics of Fe and associated P geochemical processes at the sediment-water interface are not fully understood. Taking Dongting Lake as an example, this study explored Fe and P geochemical processes at the sediment-water interface under groundwater discharge with high Fe and P concentrations. We incubated sediments from Dongting Lake under anoxic-oxic conditions with different initial aqueous P/Fe ratios and pH. Aqueous PO43--P and Fe2+, and solid P and Fe phases in sediments were analyzed, and experimental data were further simulated using numerical reactive models. At the beginning of the experiment, aqueous P and Fe were adsorbed rapidly on sediments. Under anoxic conditions, the Fe reduction rate decreased with decreasing content of poorly crystalline ferric (oxyhydr)oxides, and the addition of aqueous P and Fe at neutral pH enhanced the reduction rate. The increased aqueous P was dominated by desorption caused by sediment Fe reduction and then fixed by gibbsite adsorption and hydroxyapatite precipitation. Under oxic conditions, Fe(II) oxidation under was pH- and (P:Fe)ini-independent, with a sharp rate decline. Furthermore, the final sediment Fe(II) content was higher than the initial content, indicating the formation of a low-oxidizability Fe(II) phase. The P dynamics were dominated by adsorption on the produced Fe-oxides. The numerical models also suggested that heterogeneity in natural sediments promotes hydroxyapatite formation at low pH, but restricts it at high pH. The findings reveal that although aqueous P concentration decreased during groundwater discharge to lakes, PO43--P concentration remained much higher than that in natural lake water, increasing the risk of lake eutrophication. The paper provides references for further understanding of P loading from groundwater discharge into lakes.


Mesenchymal stem cell-derived extracellular vesicle-based therapies protect against coupled degeneration of the central nervous and vascular systems in stroke.
Stem cell-based treatments have been suggested as promising candidates for stroke. Recently, mesenchymal stem cells (MSCs) have been reported as potential therapeutics for a wide range of diseases. In particular, clinical trial studies have suggested MSCs for stroke therapy. The focus of MSC treatments has been directed towards cell replacement. However, recent research has lately highlighted their paracrine actions. The secretion of extracellular vesicles (EVs) is offered to be the main therapeutic mechanism of MSC therapy. However, EV-based treatments may provide a wider therapeutic window compared to tissue plasminogen activator (tPA), the traditional treatment for stroke. Exosomes are nano-sized EVs secreted by most cell types, and can be isolated from conditioned cell media or body fluids such as plasma, urine, and cerebrospinal fluid (CSF). Exosomes apply their effects through targeting their cargos such as microRNAs (miRs), DNAs, messenger RNAs, and proteins at the host cells, which leads to a shift in the behavior of the recipient cells. It has been indicated that exosomes, in particular their functional cargoes, play a significant role in the coupled pathogenesis and recovery of stroke through affecting the neurovascular unit (NVU). Therefore, it seems that exosomes could be utilized as diagnostic and therapeutic tools in stroke treatment. The miRs are small endogenous non-coding RNA molecules which serve as the main functional cargo of exosomes, and apply their effects as epigenetic regulators. These versatile non-coding RNA molecules are involved in various stages of stroke and affect stroke-related factors. Moreover, the involvement of aging-induced changes to specific miRs profile in stroke further highlights the role of miRs. Thus, miRs could be utilized as diagnostic, prognostic, and therapeutic tools in stroke. In this review, we discuss the roles of stem cells, exosomes, and their application in stroke therapy. We also highlight the usage of miRs as a therapeutic choice in stroke therapy.


[Rhythmic electrical activity of the isolated spinal cord of the chick embryo].
Experiments on the isolated spinal cord have shown that even in early chicken embryogenesis, when first signs of the locomotor activity appeared, modulation of the presynaptic inhibition by the locomotor generator was present. Only few spinal cord segments are able to generate the locomotor rhythm.


Minimizing misclassification bias with a model to identify acetabular fractures using health administrative data: A cohort study.
Acetabular fractures (AFs) are relatively uncommon thereby limiting their study. Analyses using population-based health administrative data can return erroneous results if case identification is inaccurate ('misclassification bias'). This study measured the impact of an AF prediction model based exclusively on administrative data upon misclassification bias.We applied text analytical methods to all radiology reports over 11 years at a large, tertiary care teaching hospital to identify all AFs. Using clinically-based variable selection techniques, a logistic regression model was created.We identified 728 AFs in 438,098 hospitalizations (15.1 cases/10,000 admissions). The International Classification of Disease, 10th revision (ICD-10) code for AF (S32.4) missed almost half of cases and misclassified more than a quarter (sensitivity 51.2%, positive predictive value 73.0%). The AF model was very accurate (optimism adjusted R2 0.618, c-statistic 0.988, calibration slope 1.06). When model-based expected probabilities were used to determine AF status using bootstrap imputation methods, misclassification bias for AF prevalence and its association with other variables was much lower than with International Classification of Disease, 10th revision S32.4 (median [range] relative difference 1.0% [0%-9.0%] vs 18.0% [5.4%-75.0%]).Lone administrative database diagnostic codes are inadequate to create AF cohorts. The probability of AF can be accurately determined using health administrative data. This probability can be used in bootstrap imputation methods to importantly reduce misclassification bias.


Synthesis of 2,3-di-O-phytanyl-1-O-(alpha-D-glucopyranosyl)-sn-glycerol derivatives, analogues of polar lipids isolated from a halophilic bacterial strain.
2,3-Di-O-phytanyl-1-O-glucopyranosylglycerol and polar derivatives of its 6'-glucose moiety have been synthesized. The target molecule contains the diphytanyl-sn-glycerol moiety which is alpha-linked to glucose. The key step in its synthesis involves the coupling of phytanyl bromide and isopropylidene threitol. We also demonstrated that the 6'-hydroxyl group of glycolipids can be functionalized without protection of the sugar moiety.


DRESS syndrome in the setting of oxacillin therapy-a call for better patient preparedness: a case report.
Drug reaction with eosinophilia and systemic symptoms syndrome is a rare but severe and potentially life-threatening hypersensitivity reaction, with significant morbidity and mortality. The clinical presentation of drug reaction with eosinophilia and systemic symptoms may include extensive skin rash, fever, lymphadenopathy, internal organ involvement, eosinophilia, and atypical lymphocytosis, most commonly due to drug-induced reaction. Our case is a rare occurrence of drug reaction with eosinophilia and systemic symptoms syndrome in the setting of oxacillin therapy. A 55-year-old Caucasian male presented to the emergency department on account of acute onset, 2-day history of generalized pruritic rash with associated fever, occurring 3 weeks after commencing therapy with intravenous oxacillin for methicillin-sensitive Staphylococcus aureus bacteremia. He had no known drug allergies. Two days prior to hospitalization, he had a telehealth visit with the infectious diseases specialist on account of his rash, and was recommended to use oral diphenhydramine. However, with the onset of fever and persistence of his rash, he was advised to discontinue the oxacillin and present to the emergency department. On examination, he was febrile at 101.2 °F and had a generalized blanchable maculopapular and morbilliform rash involving the face, trunk, upper and lower extremities, but sparing the palms, soles, and oral mucosa. He had palpable nontender lymph nodes in the cervical and inguinal regions bilaterally. Laboratory studies revealed atypical lymphocytosis, eosinophilia, neutrophilia, and elevated serum transaminases. He was started on intravenous diphenhydramine and admitted to the in-patient medical service. On the second day of hospitalization, his fever resolved. However, his rash was persistent and generalized, as well as elevated transaminases and an abnormal cell count on the second day of hospitalization. To complete his 6-week course of antibiotics for methicillin-sensitive Staphylococcus aureus bacteremia, he was switched to an alternative therapy with cefazolin, and he was scheduled for weekly follow-up assessments following hospital discharge. Healthcare providers should increasingly be aware of the significant morbidity and mortality attributable to drug reaction with eosinophilia and systemic symptoms syndrome and the potential medications which may incite such life-threatening reactions. Early recognition of drug reaction with eosinophilia and systemic symptoms syndrome and prompt institution of management strategies can promote improved clinical outcomes. Enhanced patient-provider communication strategies should be implemented to better prepare patients for the likelihood of such drug reactions, with the goal of improving patient-centered care and adherence with treatment strategies.


Abomasal impaction in Holstein-Friesian cows: 80 cases (1980-2003).
To determine clinical examination findings, clinicopathologic abnormalities, and outcome of treatment in dairy cattle with abomasal impaction. Retrospective study. 80 lactating Holstein-Friesian cows > or = 2 years old. Medical records of cattle with abomasal impaction admitted between 1980 and 2003 were retrieved, and data were extracted. All cows were reported to have decreased food intake; concurrent diseases were identified in 54 (68%). Seventeen cows did not have detectable ruminal motility, but physical examination findings were nonspecific and variable. In general, cattle had mild hypocalcemia, hyperbilirubinemia, and hyperglycemia, but serum potassium and chloride concentrations were typically within reference limits. Fifty-five (69%) cattle had impaction of the pyloric antrum alone, and 25 (31%) had impaction of the abomasal body and pyloric antrum. Right flank laparotomy and abomasal massage were performed in 73 cattle. After surgery, 54 (74%) cattle received 3 to 4 L of mineral oil, PO, daily for 1 to 5 days. Short-term (ie, discharged from the hospital) survival rate was significantly higher for cows with impaction of the pyloric antrum alone (42/45 [93%]) than for cows with impaction of the body and antrum (12/24 [50%]). Results suggest that physical examination findings and results of serum biochemical analyses do not facilitate the diagnosis of abomasal impaction in lactating Holstein cows and that exploratory right flank laparotomy is necessary to make the diagnosis. Abomasal impaction should be considered as a differential diagnosis for inappetence and poor milk production in lactating dairy cows.


Characterization of a double avirulent mutant of rabies virus and its potency as a vaccine, live or inactivated.
A strain bearing two mutations which abolish the virulence for adult animals after intracerebral or intramuscular inoculation has been constructed from the CVS strain of rabies virus. This apathogenic phenotype is stable after three successive passages of the double mutant in suckling mice brain. Trials of vaccination performed on mice in parallel with the double mutant and CVS both inactivated with beta-propiolactone indicate that the mutant is at least as efficient as CVS. This strain has also been found to be efficient as a live virus vaccine.