Lack of Baseline Intracranial Aneurysm Wall Enhancement Predicts Future Stability: A Systematic Review and Meta-Analysis of Longitudinal Studies.
The utility of vessel wall MR imaging in identifying unstable intracranial aneurysms has been suggested but remains controversial. Our aim was to provide further insight into the potential relationship between aneurysm wall enhancement on initial vessel wall imaging and aneurysm instability at follow-up. Our sources were PubMed, Scopus, the Web of Science, and the Cochrane Central Register of Controlled Trials. We searched for English language studies that reported the presence of vessel wall enhancement of unruptured intracranial aneurysms on baseline vessel wall imaging studies with longitudinal follow-up of aneurysm status. Aneurysms were grouped into "stable" and "unstable" groups at follow-up on the basis of growth, symptomatic manifestation, or rupture. The association of each group with aneurysm wall enhancement on initial vessel wall imaging was determined. Three studies constituting 407 aneurysms were included. Aneurysms with wall enhancement were at higher risk of being unstable at follow-up (risk ratio = 3.6; 95% confidence interval, 1.7-7.5). The sensitivity of aneurysm wall enhancement on vessel wall imaging was 74.3% (95% CI, 56.7%-87.5%), specificity was 58.3% (95% CI, 53.1%-63.4%), positive predictive value was 14.4% (95% CI, 11.8%-17.4%), negative predictive value was 96.0% (95% CI, 93.2%-97.7%), and the overall accuracy of the test was 59.7% (95% CI, 54.8%-64.5%). Only 3 studies were identified for inclusion in this analysis. More longitudinal studies of vessel wall imaging and aneurysm progression are needed. The lack of wall enhancement may be a predictor of aneurysm stability. The utility of vessel wall imaging in detecting unstable aneurysms requires more data.


Hallucial convergence in early hominids.
There is a richly documented fossil record of the evolutionary transition from ape-sized brains that are less that one-third the size of modern humans through a series of intermediate-sized brains up to the modern range. The first report on the discovery of the foot of the Stw 573 skeleton emphasized the apparent transitional nature of its great toe [Clarke, R.J., Tobias, P.V., 1995. Sterkfontein Member 2 foot bones of the oldest South African hominid. Science 269, pp. 521-524]. The hallux appeared to be intermediate in its divergence between human-like adduction and ape-like abduction. A major part of this evidence is the medial encroachment of the metatarsal I facet on the medial cuneiform. This study quantifies the variability of this feature in extant hominoids and fossil hominids. The results are consistent with the view that all currently known hominids were specialized for bipedality and lacked the ape-like ability to oppose the great toe.


2D/2D Biochar/Bi2WO6 Hybrid Nanosheets with Enhanced Visible-Light-Driven Photocatalytic Activities for Organic Pollutants Degradation.
In this work, a novel two-dimensional/two-dimensional (2D/2D) hybrid photocatalyst consisting of Bi2WO6 (BWO) nanosheets and cotton fibers biochar (CFB) nanosheets was successfully prepared via a facile hydrothermal process. The as-prepared photocatalysts were characterized by a variety of techniques, including X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and UV-vis diffuse reflectance spectroscopy. It was revealed that amorphous CFB nanosheets were uniformly immobilized on the surface of crystalline BWO nanosheets, and an intimate contact between CFB and BWO was constructed. The photocatalytic activities of the prepared BWO and CFB-BWO photocatalysts were evaluated by photocatalytic degradation of rhodamine B (RhB) and tetracycline hydrochloride (TC-HCl) in aqueous solutions under visible-light irradiation. Compared to the pristine BWO, the CFB-BWO composite photocatalysts exhibited significant enhancement in photocatalytic activities. Among all CFB-BWO samples, the 9CFB-BWO sample with the CFB mass ratio of 9% exhibited optimal photocatalytic activities for RhB or TC-HCl degradation, which was ca. 1.8 times or 2.4 times that of the pristine BWO, respectively. The improvement in photocatalytic activities of the CFB-BWO photocatalysts could be ascribed to the enhanced migration and separation of photogenerated charge carriers due to the formation of a 2D/2D interfacial heterostructure between CFB and BWO. Meanwhile, the possible mechanism of CFB-BWO for enhanced photocatalytic performance was also discussed. This work may provide a new approach to designing and developing novel BWO-based photocatalysts for the highly efficient removal of organic pollutants.


Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer's disease.
We examined whether cortical microvascular blood volume and hemodynamics in Alzheimer's disease (AD) are consistent with tissue hypoxia and whether they correlate with cognitive performance and the degree of cortical thinning. Thirty-two AD patients underwent cognitive testing, structural magnetic resonance imaging (MRI), and perfusion MRI at baseline and after 6 months. We measured cortical thickness, microvascular cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and capillary transit time heterogeneity (CTH) and estimated tissue oxygen tension (PtO2). At baseline, poor cognitive performance and regional cortical thinning correlated with lower CBF and CBV, with higher MTT and CTH and with low PtO2 across the cortex. Cognitive decline over time was associated with increasing whole brain relative transit time heterogeneity (RTH = CTH/MTT). Our results confirm the importance of microvascular pathology in AD. Deteriorating microvascular hemodynamics may cause hypoxia, which is known to precipitate amyloid retention.


Restoration of cholinomimetic activity by clonidine in cholinergic plus noradrenergic lesioned rats.
The effects of combined lesions of forebrain cholinergic and noradrenergic systems on memory and responsivity to the memory enhancing effects of cholinomimetics were investigated in rats. Forebrain noradrenergic deficits produced by the injection of 6-hydroxydopamine into the ascending noradrenergic bundle (ANB) blocked the ability of cholinomimetics such as physostigmine and oxotremorine to enhance retention test performance in nucleus basalis of Meynert lesioned rats. Low doses of the noradrenergic receptor agonist clonidine, when administered in conjunction with cholinomimetics reversed this blockade. These results suggest that combined cholinergic/noradrenergic therapy may be of value in the treatment of some Alzheimer's disease patients.


Incidence rate drive the multiple wave in the COVID-19 pandemic.
The last three years have been the most challenging for humanity due to the COVID-19 pandemic. The novel viral infection has eventually been able to infect most of the human population. It is now considered to be in the endemic stage, meaning it will remain in our world throughout our lifetime. There will be an intermittent outbreak of the COVID infection from time to time. Therefore, it is necessary to formulate a robust Mathematical model to study the dynamics of disease to have a control mechanism in place. In this article, we suggest a modified MSEIR model to explain the dynamics of COVID-19 infection. We assume that a susceptible person contracting the coronavirus develops a transient immunity to the illness. Further, infectives comprise asymptomatic, symptomatic, hospitalized and quarantined individuals. We assume that the incidence rate is of standard type, and susceptible can only become infective if they come in contact with either asymptomatic or symptomatic individuals. This basic and simple model effectively models the various waves every country has seen during the Pandemic. The simple analysis shows that the model could suggest various waves in future if we carefully select the incidence rate for the infection. In summary, we have discussed the following major points in this article. •We have analysed for local behavior infection-free equilibrium solution. Further, a thorough numerical exploration with various parameter settings has been performed to obtain the different cases of infection dynamics of the coronavirus epidemic.•We have found some interesting scenarios which explain the emergence of multiple waves observed in many countries.


Tuberculosis control in a highly endemic indigenous community in Brazil.
In Latin America, indigenous populations have high rates of non-completion of TB treatment and case fatality and have been defined as a priority group for investments. To evaluate TB control, a retrospective cohort study was performed to identify factors predictive of non-completion of treatment and mortality in an indigenous and non-indigenous population between 2002 and 2008 in Dourados, Brazil. A 90% reduction in non-completion of TB treatment was observed in the indigenous population after DOTS (directly observed treatment, short course) implementation (20% vs 2%). In the non-indigenous population, the number of patients not completing TB treatment continued to increase. Non-indigenous TB patients had 4.5 times higher mortality than indigenous TB patients (9% vs 2%). In multivariate analysis, non-indigenous race [odds ratio (OR) 2.33, 95% CI 1.32-4.10] was associated with non-completion of TB treatment, and HIV-positive status (OR 5.58, 95% CI 2.38-13.07) was associated with mortality. Implementation of DOTS in the indigenous populations in Dourados showed a significant reduction in non-completion of TB treatment. Nevertheless, a high rate of TB in children and young adults indicates the continuous transmission and maintenance of the epidemic in this community. Among the non-indigenous population, the TB case fatality rate is closely linked to the HIV prevalence.


Surfactant Nebulization to Prevent Intubation in Preterm Infants: A Systematic Review and Meta-analysis.
Surfactant nebulization (SN) may offer a safe alternative for surfactant administration in respiratory distress syndrome of preterm infants. To evaluate the efficacy of SN for the prevention of early intubation. Medline, Embase, The Cochrane Library, clinicaltrials.gov, published abstracts, and references of relevant articles were searched through March 23, 2021. Randomized clinical trials of preterm infants <37 weeks' gestation comparing SN with noninvasive respiratory support or intratracheal surfactant application. Two reviewers extracted data and assessed risk of bias from included studies separately and blinded. Data were pooled by using a fixed-effects model. Subgroups (gestational age, type of nebulizer, surfactant type, and dosage) were evaluated. Primary outcome was intubation rate at 72 hours after birth. Nine studies recruiting 1095 infants met inclusion criteria. SN compared with standard care significantly reduced intubation rate at 72 hours after birth (226 of 565 infants [40.0%] vs 231 of 434 infants [53.2%]; risk ratio [RR]: 0.73, 95% confidence interval [CI]: 0.63-0.84; number needed to treat: 8; 95% CI: 5-14]). Prespecified subgroup analysis identified important heterogeneity: SN was most effective in infants ≥28 weeks' gestation (RR: 0.70, 95% CI: 0.60-0.82), with a pneumatically driven nebulizer (RR: 0.52, 95% CI: 0.40-0.68) and in infants receiving ≥200 mg/kg and animal-derived surfactant (RR: 0.63, 95% CI: 0.52-0.75). No differences in neonatal morbidities or mortality were identified. Quality of evidence was low owing to risk of bias and imprecision. SN reduced the intubation rate in preterm infants with a higher efficacy for specific subgroups. There was no difference in relevant neonatal morbidities or mortality.


Encephalopathy with combined lithium-risperidone administration.
Lithium-neuroleptics induced encephalopathy is a rare drug interaction. Here I am reporting a patient who developed reversible encepatholopathy with lithium-risperidone combination. A single case report. A patient of bipolar disorder, who presented with manic symptoms with psychotic feature, started with a combination of lithium and risperidone. Within few days, the patient developed encepatholopathy, which reversed upon discontinuation of lithium and risperidone. Combining lithium and neuroleptic is useful in treatment of bipolar disorder. However, encepatholapthy can be anticipated to result when lithium is used with high potency anti-psychotic such as haloperidol and risperidone and there are baseline EEG abnormalities.


Is there any potential management against COVID-19? A systematic review and meta-analysis.
A recent survey has shown that the COVID-19 pandemic has culminated in dramatical and critical treatment particularly in acute infected patients. In fact, this systematic review-meta-analysis was directly pertained to estimation at the efficient value of some clinical managements to confront the COVID-19 infection. Pubmed, Embase, Scopus, Cochrane, and Scholar databases were searched from inception to July 1, 2020, to identify studies reporting the current treatment process and medications (e.g. hydroxychloroquine, antiviral therapy, convalescent plasma, and immunomodulatory agents) for COVID-19. A random-effects model meta-analysis was performed to calculate the relative risk (RR) with 95% confidence intervals (CI). The outcomes of this study were the frequency of negative conversion cases, clinical improvements, mechanical ventilation demand, intensive care unit (ICU) entry, and mortality. The standard treatment refers to the published guidelines and specialist experience which varies in different articles, and the proposed treatment refers to the kind of interest suggested in the included studies. A number of 45 articles met the eligibility criteria (out of 6793 articles). Among them, 26 articles involving 3263 patients were included in quantitative analysis. Anti-COVID-19 interventions could significantly increase clinical improvement (RR 1.17, 95% CI 1.08-1.27; I2 = 49.8%) and reduce the mortality rate (RR 0.58, 95% CI 0.35-0.95; I2 = 74.8%). Although in terms of negative conversion, ICU entry, and mechanical ventilation demand, clinical intervention had no beneficial effect. The clinical effect of immunomodulatory agents (especially tocilizumab and anakinra) was noticeable compared to other medications with RR of 0.22 (95% CI 0.09-0.53; I2 = 40.9%) for mortality and 1.25 (95% CI 1.07-1.46; I2 = 45.4%) for clinical improvement. Moreover, Antivirals (RR 1.13, 95% CI 1.01-1.26; I2 = 47.0%) and convalescent plasma therapy (RR 1.41, 95% CI 1.01-1.98; I2 = 66.6%) had significant beneficial effects on clinical improvement. Based on our findings, all the included interventions significantly declined the mortality and enhanced clinical improvements with no effect on negative conversion and mechanical ventilation demand. Especially, immunomodulators and plasma therapy showed favorable outcomes. An evaluation on the efficacy of proposed treatment against COVID-19.


Polypyrrole nanowire as an excellent solid phase microextraction fiber for bisphenol A analysis in food samples followed by ion mobility spectrometry.
A polypyrrole nanowire coated fiber was prepared and used in head-space solid phase microextraction coupled with ion mobility spectrometry (HS-SPME-IMS) to the analysis of bisphenol A (BPA) in canned food samples, for the first time. This fiber was synthesized by electrochemical oxidation of the monomer in aqueous solution. The fiber characterization by scanning electron microscopy (SEM) revealed that the new fiber exhibited two-dimensional structures with a nanowire morphology. The effects of important extraction parameters on the efficiency of HS-SPME were investigated and optimized. Under the optimum conditions, the linearity of 10-150ngg(-1) and limit of detection (based on S/N=3) of 1ngg(-1) were obtained in BPA analysis. The repeatability (n=5) expressed as the relative standard deviation (RSD%) was 5.8%. At the end, the proposed method was successfully applied to determine BPA in various canned food samples (peas, corns, beans). Relative recoveries were obtained 93-96%. Method validation was conducted by comparing our results with those obtained through HPLC with fluorescence detection (FLD). Compatible results indicate that the proposed method can be successfully used in BPA analysis. This method is simple and cheaper than chromatographic methods, with no need of extra organic solvent consumption and derivatization prior to sample introduction.


Glaucoma electronic patient record--design, experience and study of high-risk patients.
To set-up a glaucoma electronic patient record (GEPR) and study referral details to a new glaucoma service, concentrating on high-risk patients. A GEPR was designed using the pre-existing hospital information technology (IT) infrastructure. Referral details of all new patients to the glaucoma service were completely electronically entered and analysed. A GEPR was successfully established. A total of 402 referrals were studied. In all, 43% (40) of high-risk clinic patients (IOP>29 mmHg, or C/D ratio >0.8 or moderate to advanced visual field defects) had to wait longer than 8 weeks from GP referral to be seen at the glaucoma service. Of these, nine patients lost more than one line of Snellen's visual acuity attributable to glaucoma. The optometrist failed to document IOP in 17%, fundoscopy in 30%, and visual fields in 45% of all referrals. A GEPR can be introduced in an NHS setting without disruption of clinical care and ophthalmic training, and facilitates detailed, accurate and rapid audit. Study of high-risk glaucoma referrals showed inadequate optometric referral details and poor prioritisation of urgent cases. This information is being utilised with the cooperation of local optometrists to refine the pattern of glaucoma referrals.


Acute gouty arthritis following percutaneous cryoablation of renal cell carcinoma.
We report a case of acute gouty monoarthritis of the left ankle in a 58-year-old female with chronic renal insufficiency after cryoablation of a 3.8 cm left renal cell carcinoma. The patient's symptoms resolved after intravenous Solumedrol and did not recur at her 1-month follow-up visit. To the best of our knowledge, this is the first reported case of acute gouty monoarthritis after cryoablation of a renal cell carcinoma lesion in a patient with underlying chronic renal insufficiency. Clinicians should be vigilant of the potential for this complication in at-risk patient populations.


IgA and the intestinal microbiota: the importance of being specific.
Secretory IgA has long been a divisive molecule. Some immunologists point to the mild phenotype of IgA deficiency to justify ignoring it, while some consider its abundance and evolutionary history as grounds for its importance. Further, there is extensive and growing disagreement over the relative importance of affinity-matured, T cell-dependent IgA vs. "natural" and T cell-independent IgA in both microbiota and infection control. As with all good arguments, there is good data supporting different opinions. Here we revisit longstanding questions in IgA biology. We start the discussion from the question of intestinal IgA antigen specificity and critical definitions regarding IgA induction, specificity, and function. These definitions must then be tessellated with the cellular and molecular pathways shaping IgA responses, and the mechanisms by which IgA functions. On this basis we propose how IgA may contribute to the establishment and maintenance of beneficial interactions with the microbiota.


Piezo1 in Digestive System Function and Dysfunction.
Piezo1, a non-selective cation channel directly activated by mechanical forces, is widely expressed in the digestive system and participates in biological functions physiologically and pathologically. In this review, we summarized the latest insights on Piezo1's cellular effect across the entire digestive system, and discussed the role of Piezo1 in various aspects including ingestion and digestion, material metabolism, enteric nervous system, intestinal barrier, and inflammatory response within digestive system. The goal of this comprehensive review is to provide a solid foundation for future research about Piezo1 in digestive system physiologically and pathologically.


Receptor-mediated interaction of ricin with the lipid bilayer of ganglioside GM1-liposomes.
The interaction of ricin with ganglioside GM1 or glycoprotein containing liposomes was investigated. At neutral pH, ricin bound to galactose moieties on the surface of the liposomes to form ricin-liposomes complexes, but did not associate with their lipid bilayers. When these ricin-liposomes complexes were exposed to a pH below 5, ricin bound to GM1-liposomes became associated with the lipid bilayer, whereas ricin bound to glycoprotein-liposomes (containing human erythrocyte Band 3) was only rarely associated. Association of ricin with the lipid bilayer of GM1-liposomes did not occur in the presence of lactose, which inhibits the binding of ricin to ganglioside GM1. Using a hydrophobic probe, 8-amino-1-naphthalene sulfonic acid (ANS), it was revealed that an acidity below pH 5 resulted in exposure of hydrophobic regions on the ricin molecule. These results strongly suggest that association of ricin with the lipid bilayer of GM1-liposomes at acidic pH is mediated by the binding of ricin to ganglioside GM1 at neutral pH and occurs through interaction between the exposed hydrophobic region on the ricin molecule and the lipid bilayer of GM1-liposomes at low pH.


A high-resolution reference map for cytoplasmic and membrane-associated proteins of Corynebacterium glutamicum.
We present a high-resolution reference map for soluble proteins obtained from Corynebacterium glutamicum cells grown in glucose minimal medium. The analysis window covers the pl range from 4-6 and the molecular mass range from 5-100 kDa. Using overlapping narrow immobilized pH gradients for isoelectric focusing, 970 protein spots were detected after second-dimensional separation on SDS-polyacrylamide gels and colloidal Coomassie-staining. By tryptic peptide mass fingerprinting 169 protein spots were identified, representing 152 different proteins including many enzymes involved in central metabolism (18), amino acid biosynthesis (24) and nucleotide biosynthesis (11). Thirty-five of the identified proteins have no known function. A comparison of the observed and the expected physicochemical properties of the identified proteins indicated that nine proteins were covalently modified, since variants with apparently identical molecular mass, but differing pl were detected. The N-termini of eight proteins were determined by post-source decay (PSD) analysis of selected peptides. In addition to the soluble proteins, a map of the membrane-bound proteins within the pl range 4-7 is presented, which contains 660 protein spots, 22 of which were identified, representing 13 different proteins.


Faster and more efficient swimming: energy consumption of murine spermatozoa under sperm competition†.
ATP supply is essential for sperm performance and increases in ATP content coevolve with enhanced sperm swimming velocity as a response to sperm competition in rodents. ATP content is the balance between production and consumption but, although ATP production has received much attention, little is known about ATP consumption. The rate of ATP consumption is crucial for the propagation of the flagellar wave, becoming a main determinant of the time and distance sperm could move before exhausting their reserves. A high yield in distance per unit of ATP consumed (efficiency) could provide advantages in sperm competition. We characterized sperm ATP consumption rate in a group of mouse species with different sperm competition levels to understand its impact on swimming velocity, duration, and yield of sperm ATP reserves. Interspecific comparisons revealed that sperm of species with higher sperm competition levels had high ATP consumption rates and faster swimming velocity. Moreover, sperm that consumed ATP at a faster rate swam more efficiently, since they were able to cover more distance per unit of ATP consumed. Our results suggest that by coupling the advantages of higher ATP turnover rates to increased efficiency of ATP expenditure, sperm would respond to increasingly competitive environments while maintaining a positive ATP balance.


The mental health and biosocial context of help-seeking in longitudinal perspective: the Midtown Longitudinal Study, 1954 to 1974.
This study of a representative community survivor sample of 695 respondents from the 1954 Midtown Manhattan Study found that parental socioeconomic status unequivocally predicted help-seeking. Age, gender, adult SES, and impaired mental health in 1954 predicted help-seeking interactively. The mental health of help-seekers continued to be unfavorable, or was worsening, from 1954 to 1974.


Adult hippocampal neurogenesis: an actor in the antidepressant-like action.
Depression and anxiety are psychiatric illnesses that are major burdens in society and affect as much as 7% of the world's population. The heterogeneous nature of depression suggests an involvement of multiple distinct brain regions including amygdala, prefrontal cortex and the hippocampus, which may be responsible for the diversity of the symptoms. Besides its critical role in learning and memory, the hippocampus is one of only two areas in mammalian brain where adult neurogenesis occurs. Of the current leading hypotheses of the pathophysiology and treatment of depression, the neurogenesis hypothesis of depression deserves particular attention because changes in neurogenesis are only seen after chronic, but not acute, antidepressant treatment. This review revisits the role of adult hippocampal neurogenesis in the pathophysiology of mood disorders, especially anxiety/depression, and also in the antidepressant-like responses, especially in stressed rodents.


Alexithymia is not a stable personality trait in patients with substance use disorders.
The construct of alexithymia as a vulnerability factor for substance use disorders (SUD) is under debate, because of conflicting research results regarding alexithymia as a state or trait phenomenon. The absolute and relative stability of alexithymia were evaluated in a pre-post design as part of a randomised controlled trial, controlling for several co-variates. Assessments were done with the Toronto Alexithymia Scale (TAS-20) and the Addiction Severity Index (EuropASI) at baseline and follow-up of a 3-month trial of inpatient Cognitive Behavioural Therapy (CBT) with or without a Shared Decision Making intervention for 187 SUD patients. Paired sample t-tests and analyses of variance were performed to assess absolute stability, intraclass correlation coefficients were calculated for relative stability and multivariate linear regression models were used to evaluate the relation between co-variates and change in alexithymia. Mean level reduction of total TAS-20 and two subfactors demonstrated no absolute stability, but change in alexithymia differed for patients with low, moderate and high alexithymia scores. Relative stability of alexithymia was moderate to high for the total population, but differed according to low, moderate and high alexithymia scores. The EuropASI "psychiatry" domain, covering anxiety and depression, was related to alexithymia, but CBT-related variables were not. In conclusion, alexithymia is partly a state-dependent phenomenon, but not a stable personality trait in this SUD population.


Stimulation of the Neurovascular Bundle Results in Rhabdosphincter Contraction in a Proportion of Men Undergoing Radical Prostatectomy.
To use nerve conduction studies to clarify the functional innervation of the male urethral rhabdosphincter (RS). In particular, to test the hypothesis that in some men, fibers of the neurovascular bundle supply the RS. These fibers may be at risk during radical prostatectomy. Men undergoing robot-assisted radical prostatectomy for clinically localized prostate cancer were included. Men with a history of pelvic surgery and/or radiation and/or trauma, obesity, or neurological diseases were excluded. Nerve conduction studies were performed before and after prostate removal. The St. Mark's pudendal electrode was used for pudendal (control) stimulation. The ProPep Nerve-Monitoring System (ProPep Surgical, Austin, TX) was used to stimulate the neurovascular bundle at the level of the prostate base, mid, and apex. ProPep needle electrodes inserted into the RS were used to measure evoked compound motor action potential response. Results were only included if a valid pudendal control was elicited. Seventeen men in total underwent investigation. Valid measurements were obtained after initial quality control in seven. In two cases, evidence of sphincteric activation was observed, providing evidence to support neurovascular bundle innervation of the RS. In the other five patients, no intrapelvic nerve supply was demonstrated. Somatic nerve supply to the RS is variable. Direct intrapelvic supply to the RS may exist in some men. This may be one explanation as to why some patients unexpectedly develop severe urinary incontinence postoperatively despite technically satisfactory surgery. Further research is required to validate our findings.


Cardioprotective effects of different flavonoids against myocardial ischaemia/reperfusion injury in Langendorff-perfused rat hearts.
Flavonoids are important components of 'functional foods', with beneficial effects on the cardiovascular function, mainly due to their antioxidant activity. Many flavonoids exert antihypertensive, anti-atherosclerotic and antiplatelet activity and positive effects against endothelial dysfunction. Recent evidence indicates that they exert cardioprotective effects against myocardial ischaemia/reperfusion (I/R) injury. The aim of this work was to investigate these properties for flavonoids with different structural characteristics. In this work, the cardioprotective effects of eight flavonoids endowed with different structural characteristics were tested on Langendorff-perfused rat hearts submitted to 30 min of global ischaemia followed by 120 min of reperfusion (I/R). Only the 5-hydroxy-substituted derivatives, such as 5-hydroxy flavone, apigenin, chrysin and naringenin, conferred on the hearts an improved post-ischaemic functional recovery associated with lower extension of tissue injury. A similar pharmacological profile was exhibited by 5-methoxy flavone. In contrast, 6-hydroxy flavone, 7-hydroxy flavone and 4'-hydroxy flavanone did not confer significant protection against the injury induced by I/R. Some flavonoids exhibit direct cardioprotective effects against the injury induced by drastic I/R and this pharmacological property seems to be related to their structural characteristics. Such an influence of structural requirements seems to indicate that the cardioprotective effects may be due to the interaction with specific pharmacological targets.


Production of carbonyl reductase by Metschnikowia koreensis.
A new strain of the yeast Metschnikowia koreensis was grown in shake flasks and a stirred bioreactor for the production of carbonyl reductase. The optimal conditions in the bioreactor for maximizing the biomass specific activity of the enzyme were found to be: a medium composed of glucose (20 g/L), peptone (5 g/L), yeast extract (5 g/L) and zinc sulfate (0.3g/L); the pH controlled at 7; the temperature controlled at 25 °C; an agitation speed of 500 rpm; and an aeration rate of 0.25 vvm. In the bioreactor, a biomass specific enzyme activity of 115.6 U/gDCW was obtained and the maximum biomass concentration was 15.3 gDCW/L. The biomass specific enzyme activity obtained in the optimized bioreactor culture was 11-fold higher than the best result achieved in shake flasks. The bioreactor culture afforded a 2.7-fold higher biomass concentration than could be attained in shake flasks.


Reasoning about conditional sentences: development of understanding of cues to quantification.
The previous literature has reported that when children are asked to judge the truth or falsity of universally quantified conditional sentences of the form If a thing is P then it is Q they typically give responses, e.g., responding "true" whenever there is a case of P and Q even if there are also cases of P and not-Q. Three experiments are reported that address possible sources of this error. Experiment 1 shows that the error survives on sentences that refer to particular things as well as to things of a particular kind, and further shows that articulating the necessity of the consequent (... then it has to be Q) eliminates the error for adults and reduces it for fifth graders, although it does not affect second grade performance. Experiment 2 shows that for second and fifth graders the error survives to problems that are not universally quantified and for second graders to problems that are not conditionals although are otherwise structurally similar. Experiment 3 compares various verbal formulations of such universally quantified conditionals: Second and fifth graders do not make the error when the quantification is expressed with the surface structure that makes its universality most explicit (all things ...); the error tendency is greatest when the indefinite article is used (if a thing ...); and formulations using any fall in between. We argue that such erroneous evaluations of universally quantified conditionals have more to do with the quantificational aspect than the conditional aspect of the problems; children interpret the indefinite article as existential, although they resist the error when the cue to universal quantification is completely clear. The error appears to result more from the surface-structure form of the stimuli than from an inability of children to appreciate the logic of universally quantified conditionals.


Spatiotemporal changes and driving factors of vegetation in 14 different climatic regions in the global from 1981 to 2018.
Climate change affects the change of vegetation, and the analysis of vegetation change and its drivers in different globe climate zones is important for ecological conservation, energy balances, and climate change in different global climate zones. Based on the vegetation leaf area index (LAI) and climate factor datasets, this paper uses an integrated empirical model decomposition, sensitivity rate, contribution rate, and geographic detector analysis method to study the vegetation drivers and their changes in 14 different climate zones around the globe from 1981 to 2018. The results showed that (1) Vegetation changes were sensitive to precipitation and evapotranspiration in arid climate zones and to temperature and soil temperature in cold climate zones. In the tundra climate zone, the sensitivity of vegetation change to temperature was higher than that to precipitation and evapotranspiration. (2) Soil moisture has the highest contribution to vegetation change, and the areas with absolute contribution rates over 60% account for 50.26% of the total area of global vegetation cover. The areas with high contributions of temperature and soil temperature to the LAI are mainly distributed in the Northern Hemisphere, which indicates that temperature has a high contribution to vegetation change in low-temperature environments. (3) The areas with significant increasing trends for the global vegetation LAIs accounted for approximately 15.32% of the total global vegetation cover (slope ≥ 0.01), which are mainly located in equatorial savannahs with dry winters, warm temperate climates with dry winters, and warm temperate climates with fully humid climatic zones. (4) The LAIs were dominated by medium-high fluctuations and sustainable increasing changes, which accounted for 61.27% and 69.34% of the total global vegetation cover area, respectively. (5) Globally, the driving factors influencing LAI changes are specific humidity, temperature, soil temperature, evapotranspiration, precipitation, and soil moisture in descending order, with the largest interaction effect of specific humidity and soil moisture on LAI changes. This research provides a scientific basis for vegetation change monitoring, driving mechanisms, and ecological protection in different climate regions around the globe.


Formation of Heterotypic Amyloids: α-Synuclein in Co-Aggregation.
Protein misfolding resulting in the formation of ordered amyloid aggregates is associated with a number of devastating human diseases. Intrinsically disordered proteins (IDPs) do not autonomously fold up into a unique stable conformation and remain as an ensemble of rapidly fluctuating conformers. Many IDPs are prone to convert into the β-rich amyloid state. One such amyloidogenic IDP is α-synuclein that is involved in Parkinson's disease. Recent studies have indicated that other neuronal proteins, especially IDPs, can co-aggregate with α-synuclein in many pathological ailments. This article describes several such observations highlighting the role of heterotypic protein-protein interactions in the formation of hetero-amyloids. It is believed that the characterizations of molecular cross talks between amyloidogenic proteins as well as the mechanistic studies of heterotypic protein aggregation will allow us to decipher the role of the interacting proteins in amyloid proteomics.


The gut microbiome in human immunodeficiency virus infection.
HIV/AIDS causes severe dysfunction of the immune system through CD4+ T cell depletion, leading to dysregulation of both the adaptive and innate immune arms. A primary target for viral infection is the gastrointestinal tract, which is a reservoir of CD4+ T cells. In addition to being a major immune hub, the human gastrointestinal tract harbors trillions of commensal microorganisms, the microbiota, which have recently been shown to play critical roles in health. Alterations in the composition and function of microbiota have been implicated in a variety of 'multi-factorial' disorders, including infectious, autoimmune, metabolic, and neoplastic disorders. It is widely accepted that, in addition to its direct role in altering the gastrointestinal CD4+ T cell compartment, HIV infection is characterized by gut microbiota compositional and functional changes. Herein, we review such alterations and discuss their potential local and systemic effects on the HIV-positive host, as well as potential roles of novel microbiota-targeting treatments in modulating HIV progression and associated adverse systemic manifestations.


Role of monkey superior colliculus in saccade averaging.
We have investigated the involvement of collicular movement cells in the monkey in the execution of averaging saccades, elicited by a visual double-step stimulus. We found that, qualitatively, most (12/14) movement cells were recruited during averaging saccades in roughly the same way as for comparable visually-elicited saccades to single targets (V-saccades). However, movement-cell responses during averaging saccades in trials where the target suddenly changed direction were often less intense than for a comparable V-saccade. In these cases, the averaging responses were observed to be also slower than V-saccades of the same amplitude. Firing rate and double-step saccade dynamics were found to be significantly correlated in 9/14 cells tested. Several hypotheses for the collicular role in the generation of averaging saccades are discussed.


Organocatalytic One-Pot Asymmetric Synthesis of Thiolated Spiro-γ-lactam Oxindoles Bearing Three Stereocenters.
The first asymmetric synthesis of spiro-γ-lactam oxindoles bearing three stereocenters is reported. One-pot thiol-Michael/Mannich/lactamization reactions promoted by a recyclable fluorous bifunctional cinchona alkaloid/thiourea organocatalyst afford products in moderate to good yields with up to 95% ee and 6:1 dr.


Genome Sequence of Salipaludibacillus sp. Strain CUR1, Isolated from an Alkaline-Saline Lake in Rajasthan, India.
We report the complete genome sequence of Salipaludibacillus sp. strain CUR1, which was isolated from Sambhar Lake (a soda lake) in Rajasthan, India. The whole-genome sequencing of this strain has been done to explore the industrially important hydrolytic and extracellular enzymes that can be active under high-salt and high-pH conditions.


Analysis of the impact of liver transplantation as a condition of health.
To analyse the impact that liver transplantation has had on the patient as a condition of their health. A prospective study was carried out, the sample of which was made up of liver transplant patients at the Gregorio Marañón General University Hospital from November 2019 to August 2021. The hospital anxiety and depression scale, the Model for End-stage liver disease sodium and liver fragility index and the Transplant Effects Questionnaire Spanish were used. The data were analysed using descriptive statistics. The student's t-test was used for continuous variables and the chi-square test for categorical variables. For non-parametric samples, the Wilcoxon, Mann-Whitney U test and Kruskal-Wallis's sign were used. The sample was made up of 60 patients with a mean age of 55.68 years, 70% being men. The mean anxiety and depression scores of the patients improved significantly after liver transplantation. The impact of physical health resulted that those patients with a higher Model for End-stage liver disease sodium were correlated with a greater feeling of guilt after transplantation. Furthermore, greater adherence to immunosuppressive treatment was directly correlated with greater disclosure and inversely with guilt, after transplantation. Liver transplantation is a process that impacts the health of patients. Those patients who arrive at the transplant with a more deteriorated physical situation present a greater guilt after the transplant. This impact is inversely correlated with adherence to immunosuppressive treatment. Nurses should intervene in such patients to reduce the impact on adherence to treatment.


Receipt of COVID-19 vaccine in preterm-born children aged 3-7 in China.
To determine the COVID-19 vaccination rate in preterm-born children aged 3-7 in China and influential factors, identify vaccination-related adverse reactions, and clarify reasons behind parental refusal of vaccination to their children. This cross-sectional study was conducted in parents of preterm-born children aged 3-7 in different regions of China through WeChat. Of 1,924 Chinese preterm-born children aged 3-7 included in this study, 1,552 (80.7%) had been vaccinated against COVID-19, with a higher vaccination rate in eastern China. Children older than 4 years, kids in kindergartens and primary schools, children living in eastern or western China, and children whose fathers had received at least one dose of a COVID-19 vaccine tended to be vaccinated against COVID-19 after adjusting for other covariates. Conversely, children living in urban areas, children whose annual family income was < 50,000 CNY or more than 300,000 CNY, premature children who underwent hospital transfers, and children with underlying diseases were less likely to get vaccinated. Adverse reactions occurred in 59/1,552 (3.8%) vaccinated children. Parents of 118/372 (31.7%) children expressed their concerns over adverse reactions to COVID-19 vaccination. Other reasons like the absence of information about the place where they could get vaccination were mentioned as well. COVID-19 vaccination-related adverse reactions rarely occurred and most of them were mild among preterm-born children aged 3-7. Higher vaccination coverage can be achieved as parents are provided with more scientific data about benefits of vaccination, vaccination contraindications and precautions, and more information about vaccination sites.


Efficacy and immunological actions of FAHF-2 in a murine model of multiple food allergies.
Food Allergy Herbal Formula-2 (FAHF-2) prevents anaphylaxis in a murine model of peanut allergy. Multiple food allergies (MFA) are common and associated with a higher risk of anaphylaxis. No well-characterized murine model of sensitization to multiple food allergens exists, and no satisfactory therapy for MFA is currently available. To determine the effect of FAHF-2 in a murine model of MFA. C3H/HeJ mice were orally sensitized to peanut, codfish, and egg concurrently. Oral FAHF-2 treatment commenced 1 day after completing sensitization and continued daily for 7 weeks. Mice were subsequently orally challenged with each allergen. Antibodies in sera from mice simultaneously sensitized with peanut, codfish, and egg recognized major allergens of all 3 foods, demonstrating sensitization to multiple unrelated food allergens (MFA mice). Sham-treated MFA mice exhibited anaphylactic symptoms accompanied by elevation of plasma histamine and hypothermia. In contrast, FAHF-2-treated MFA mice showed no anaphylactic symptoms, normal body temperature, and histamine levels after challenge with each allergen. Protection was accompanied by reduction in allergen-specific immunoglobulin E levels. Allergen-stimulated Th2 cytokine interleukin-4 and interleukin-13 production levels decreased, whereas the Th1 cytokine interferon-γ levels were elevated in cultured splenocytes and mesenteric lymph node cells in FAHF-2-treated mice. We established the first murine model of MFA. FAHF-2 prevents peanut, egg, and fish-induced anaphylactic reactions in this model, suggesting that FAHF-2 may have potential for treating human MFA.


Characterization of demethylation of methylmercury in cultured astrocytes.
Mercury (Hg) is a well-known neurotoxicant but its toxicity depends on the species present. A steady emergence of inorganic Hg in the brain following chronic and accidental exposure to methylmercury (MeHg) has suggested that MeHg can undergo demethylation. The objective of this study is to develop an in vitro model to study factors affecting Hg demethylation in the central nervous system. Astrocytes obtained from neonatal rat pups were cultured for 24h with 1 microM MeHg in the presence of two pro-oxidants, buthionine sulphoximine (BSO) and rotenone. The BSO treatment produced a 21% increase in reactive oxygen species (ROS) content compared to the control (control vs. BSO; 100+/-1.35 vs. 121+/-1.52 relative fluorescence units (RFU)mg(-1) protein, p<0.001) but did not affect total Hg accumulation (control vs. BSO=86.5+/-4.14 ng mg(-1) vs. 95.7+/-9.26 ng mg(-1)). Rotenone increased ROS levels 107% (control vs. rotenone; 100%+/-1.35 vs. 207%+/-6.78RFU mg(-1)protein, p<0.001) and significantly increased the accumulation of total Hg (control vs. rotenone=86.5+/-4.14 ng mg(-1) vs. 124+/-3.80 ng mg(-1), p<0.001). There was no detectable demethylation in the control or BSO treated group, however, the rotenone treatment significantly increased the demethylation (control vs. rotenone=-1.86+/-5.57% vs. 16.3+/-2.68%, p<0.05). For the first time, we have demonstrated in an in vitro primary astrocyte culture model that MeHg can be converted to inorganic Hg and demethylation increases with oxidative stress. Our results provide a useful model to study demethylation of Hg in astrocytes and to explore potential ways to protect against Hg toxicity.


"Tianeptine abuse via novel, extended-release, star-shaped, drug delivery device".
We report a rare domestic case of exposure to tianeptine and use of a novel, extended-release, six-armed, star-shaped, drug delivery capsule. A 40-year-old male with a history of depression, anxiety, ethanol, opioid, cannabis, and tobacco use disorders presented to the emergency department (ED) from a substance abuse residential recovery treatment program after developing hypertension, tachycardia, and tremor for two day. He used an extended-release, six-armed, star-shaped, drug delivery device he purchased online, filling each arm with 15 mg of tianeptine (90 mg total). His intention was to mitigate the symptoms of kratom/opioid withdrawal through this extended-release method while simultaneously undergoing formal treatment for ethanol withdrawal. Tianeptine is an atypical tricyclic antidepressant that exerts complex mechanisms of action including serotonin (5-HT) neuromodulation as well as full μ-opioid and ∂-opioid receptor agonism. The capsule itself is made of caprolactone, which is a bioabsorbable material similar to absorbable sutures, initially developed as a long-term enteral antimalarial delivery method and is not FDA approved for human use. Over the course of the patients two day hospitalization course he developed symptoms consistent with uncomplicated ethanol withdrawal, which were treated with as-needed phenobarbital. No clinical manifestations of opioid or serotonin toxicity developed. Serial EKGs and telemetry monitoring remained unchanged. The patient was then medically cleared and discharged back to the residential recovery treatment program.


Item response analysis on an examination in anesthesiology for medical students in Taiwan: a comparison of one- and two-parameter logistic models.
Student examinations are an essential component of medical education and item analyses are important to assess test quality. Among miscellaneous psychometric theories used for test analyses, item response theory is more flexible and versatile than other theories. This study aimed to apply item response models to analyze an anesthesiology examination for medical and dental students. This examination included 50 items that were administered to 170 5(th)- and 6(th)-year medical and dental students. One- and two-parameter logistic (1-PL and 2-PL) item response models were used to conduct item analyses of the examination. Fit statistics were examined to exclude misfit items and evaluate test reliability. Goodness-of-fit analyses were used to select the model having the better fit to data. Examinee's ability and item difficulty were estimated and then expressed on the common scale. Potentially differential items were detected using logistic regression. The goodness-of-fit analysis revealed that, in our case, the 1-PL model was more suitable for item response analyses. No misfit item was noted and the test reliability was 0.81 (1-PL model). The mean examinee's ability was set at 0 by definition [standard deviation (SD) = 0.61] and the mean item difficulty was -2.08 (SD = 1.93). There were 24 items with a difficulty level lower than the least able examinee, and three items had a difficulty level higher than the most able examinee. Four potentially differential items were identified. Item response models are useful for medical test analyses and provide valuable information about model comparisons and identification of differential items other than test reliability, item difficulty, and examinee's ability.


Rotational thrombelastometry (ROTEM) improves hemostasis assessment compared to conventional coagulation test in ACLF and Non-ACLF patients.
Patients with liver cirrhosis typically exhibit abnormal coagulation parameters in conventional coagulation tests (CCTs). Rotational thromboelastometry (ROTEM) is a holistic blood coagulation assay. This method provides an insight into the global hemostatic capabilities and has been suggested to provide a better overview of the coagulation system in liver cirrhosis. The goal of this study was to examine hemostasis in patients with stable liver cirrhosis (Non-ACLF) and in acute-on-chronic liver failure (ACLF) by CCT and ROTEM including agreement of both tests and the prospective assessment of test performance based on clinical outcomes in ACLF patients. Therefore, ACLF patients were additionally subgrouped by bleeding events. Fifty-five Non-ACLF patients and twenty-two patients with ACLF were analysed in this prospective cohort study. Coagulation parameters analysed by CCT were outside the normal range in Non-ACLF and ACLF patients, but were significantly more aberrant in ACLF patients. Non-ACLF patients analysed by ROTEM revealed parameters largely within the normal limits, while significantly more ROTEM parameters in ACLF patients were affected. Maximum clot firmness (MCF) was significantly divergent between both patient groups and correlated well with levels of fibrinogen and platelet count. Using Cohen's Kappa coefficient κ, the strength of agreement between CCT and ROTEM analyses was determined to be fair for Non-ACLF patients and moderate for ACLF patients. Bleeding events occurred significantly more often in ACLF group with significantly reduced A10 and MCF. For assessing hemostasis in Non-ACLF and ACLF patients the underlying dataset shows advantages of ROTEM over CCT. A10 and MCF represent suitable prognostic parameters in predicting bleeding events in ACLF group.


Comparison of Access Route for Endovascular Treatment by Time-Spatial Labeling Inversion Pulse (Time-SLIP) MRA and Contrast-Enhanced MRA.
In endovascular treatment, it is important to evaluate the access route for placing a catheter into the common carotid artery (CCA) promptly and safely prior to the procedure. We examined whether non-contrast MRA using time-spatial labeling inversion pulse (Time-SLIP) can be used in patients prior to endovascular thrombectomy for acute ischemic stroke. We compared Time-SLIP MRA to contrast-enhanced (CE) MRA and evaluated the efficacy in the evaluation of access routes. We retrospectively reviewed 31 patients admitted between October 2018 and December 2018 for cerebral infarction at our hospital. Blood vessels were imaged from the aortic arch to the CCA. A radiologist blindly evaluated quality score, stenosis, shape of the aorta, and degree of tortuosity. There were no "non-diagnostic" images. The sensitivity, specificity, positive predictive value, and negative predictive value for stenosis were 83%, 96%, 83%, and 96%, respectively. The sensitivity for the aorta type classification was 100%. The sensitivity for mild tortuosity was 93%, for moderate was 100%, and for severe was 100%. Time-SLIP MRA can be an alternative to CE MRA in access route assessment for patients with cerebral infarction who are not eligible for acute thrombectomy therapy.


AI-2 biosynthesis module in a magnetic nanofactory alters bacterial response via localized synthesis and delivery.
Nanofactories are nano-dimensioned and comprised of modules serving various functions that alter the response of targeted cells when deployed by locally synthesizing and delivering cargo to the surfaces of the targeted cells. In its basic form, a nanofactory consists of a minimum of two functional modules: a cell capture module and a synthesis module. In this work, magnetic nanofactories that alter the response of targeted bacteria by the localized synthesis and delivery of the "universal" bacterial quorum sensing signal molecule autoinducer AI-2 are demonstrated. The magnetic nanofactories consist of a cell capture module (chitosan-mag nanoparticles) and an AI-2 biosynthesis module that contains both AI-2 biosynthetic enzymes Pfs and LuxS on a fusion protein (His-LuxS-Pfs-Tyr, HLPT) assembled together. HLPT is hypothesized to be more efficient than its constituent enzymes (used separately) at conversion of the substrate SAH to product AI-2 on account of the proximity of the two enzymes within the fusion protein. HLPT is demonstrated to be more active than the constituent enzymes, Pfs and LuxS, over a wide range of experimental conditions. The magnetic nanofactories (containing bound HLPT) are also demonstrated to be more active than free, unbound HLPT. They are also shown to elicit an increased response in targeted Escherichia coli cells, due to the localized synthesis and delivery of AI-2, when compared to the response produced by the addition of AI-2 directly to the cells. Studies investigating the universality of AI-2 and unraveling AI-2 based quorum sensing in bacteria using magnetic nanofactories are envisioned. The prospects of using such multi-modular nanofactories in developing the next generation of antimicrobials based on intercepting and interrupting quorum sensing based signaling are discussed.


Detection of bovine papillomavirus DNA on the normal skin and in the habitual surroundings of horses with and without equine sarcoids.
The purpose of the present study was to examine whether bovine papillomavirus (BPV) DNA can be detected on the normal skin and in the habitual surroundings of horses with and without equine sarcoids by means of superficially taken swabs. In affected horses, no significant difference in presence of BPV-DNA could be observed between samples obtained from the equine sarcoid surface, from normal skin close to the tumour and from a normal skin site in direct contact with the tumour. From the group of healthy horses living in contact with affected horses, 44% were BPV-DNA positive. The surroundings of affected and non-affected horses are probably not a major source of BPV-DNA contamination. It can be concluded that BPV-DNA is present on the normal skin of horses affected by equine sarcoid and to a lesser degree, on the normal skin of horses living in contact with affected horses.


Every fifth patient suffered a high nutritional risk-Results of a prospective patient survey in an oncological outpatient center.
Malnutrition in cancer patients often remains undetected and underestimated in clinical practice despite studies revealing prevalences from 20 to 70%. Therefore, this study aimed to identify patient groups exposed to an increased nutritional risk in a university oncological outpatient center. Between May 2017 and January 2018 we screened oncological patients there using the malnutrition universal screening tool (MUST). Qualitative data were collected by a questionnaire to learn about patients' individual information needs and changes in patients' diets and stressful personal nutrition restrictions. We included 311 patients with various cancers. 20.3% (n = 63) were found to be at high risk of malnutrition, 16.4% (n = 51) at moderate risk despite a mean body mass index (BMI) of 26.5 ± 4.7 kg/m2. The average age was 62.7 (± 11.8) with equal gender distribution (52% women, n = 162). In 94.8% (n = 295) unintended weight loss led to MUST scoring. Patients with gastrointestinal tumors (25%, n = 78) and patients >65 years (22%, n = 68) were at higher risk. Furthermore, there was a significant association between surgery or chemotherapy within six months before survey and a MUST score ≥2 (OR = 3.6). Taste changes, dysphagia, and appetite loss were also particular risk factors (OR = 2.3-3.2). Young, female and normal-weight patients showed most interest in nutrition in cancer. However, only 38% (n = 118) had a nutritional counseling. This study confirms that using the MUST score is a valid screening procedure to identify outpatients at risk of developing malnutrition. Here one in five was at high risk, but only 1% would have been detected by BMI alone. Therefore, an ongoing screening procedure with meaningful parameters should be urgently implemented into the clinical routine of cancer outpatients as recommended in international guidelines.


Association among kidney function, frailty, and oral function in patients with chronic kidney disease: a cross-sectional study.
Chronic kidney disease (CKD) involves many factors that can cause frailty and oral hypofunction. We aimed to investigate the prevalence of frailty and oral hypofunction and to examine the associations among kidney function, frailty, and oral function in adults with CKD in Japan. This cross-sectional study was conducted at two institutions. The participants included 109 patients with CKD stages 3-5 who visited outpatient clinics or were admitted for inpatient treatment. Frailty was evaluated using the Japanese version of the Cardiovascular Health Study frailty criteria. Oral function was evaluated by assessing oral motor skills [oral diadochokinesis (ODK) rate], masticatory ability, and the repetitive saliva swallowing test. The estimated glomerular filtration rate (eGFR) was used to indicate kidney function. We examined the associations among kidney function, frailty, and oral function using binomial logistic regression analysis. In total, 31 participants (28.4%) were classified as being frail. Univariate analysis showed that age, body mass index, eGFR, and haemoglobin level were significantly associated with frailty. ODK and swallowing function were significantly associated with frailty. Multivariate analysis revealed that frailty was significantly associated with eGFR [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.92-1.00, p = 0.048] and ODK rate (OR 0.68, CI 0.47-0.98, p = 0.038). However, no significant association was found between CKD severity and masticatory or swallowing function. We found a high prevalence of frailty in patients with CKD and a significant association between frailty and oral motor skills, affecting the swallowing function of patients with nondialysis CKD. The high prevalence of frailty among patients with CKD suggests that routine assessment of frailty is necessary to prevent the development of severe complications. In addition, oral and kidney function should be carefully evaluated, and oral health education and interventions should be performed for patients with CKD.


A comparison of the complication rates following unilateral and bilateral varicose vein surgery.
To compare the complication rates of unilateral and bilateral varicose vein surgery. Observational clinical study with prospective data collection. Southport and Ormskirk Hospital NHS Trust. 1090 patients undergoing varicose vein surgery during the period January 2002-June 2005. 695 (64%) of these had unilateral surgery and 395 (36%) had bilateral surgery giving a total of 1485 legs operated on (47% as a unilateral operation and 53% as a bilateral operation). 43/695 (6.2%) of patients who underwent unilateral surgery and 34/395 (8.6%) of patients who underwent bilateral surgery developed a wound infection. 77/695 (11%) of patients who underwent unilateral surgery developed paraesthesia compared to 81/395 (21%) for bilateral surgery. 2/695 (0.13%) unilateral surgery patients and no bilateral surgery patients developed neuralgia. Residual varicose veins were present in 30/695 (4.3%) of unilateral group and 32/395 (8.1%) of the bilateral group. 1/695 (0.14%) of unilateral surgery patients and 3/395 (0.75%) of bilateral surgery patients developed DVTs. Comparing limbs, a complication of any type was seen in 153/695 (22%) limbs treated by unilateral surgery and 150/790 (19% N.S., Chi squared) limbs treated by bilateral surgery. Complications following varicose vein surgery appear to be more common following bilateral procedures. However, the complication rate per limb is similar for unilateral and bilateral operations.


An avirulent Brachyspira hyodysenteriae strain elicits intestinal IgA and slows down spread of swine dysentery.
Swine dysentery caused by Brachyspira hyodysenteriae, results in substantial economic losses in swine producing countries worldwide. Although a number of different vaccine approaches have been explored with regard to this disease, they show limitations and none of them have reached the market. We here determine the vaccine potential of a weakly haemolytic B. hyodysenteriae strain. The virulence of this strain was assessed in experimental infection trials and its protection against swine dysentery was quantified in a vaccination-challenge experiment using a seeder infection model. Systemic IgG production and local IgA production were monitored in serum and faeces respectively. Across all trials, pigs that were colonized by virulent, strongly haemolytic B. hyodysenteriae strains consistently developed swine dysentery, in contrast to none of the pigs colonized by the weakly haemolytic B. hyodysenteriae vaccine strain. In the seeder vaccination trial nearly all immunised animals developed swine dysentery on subsequent challenge with a virulent strain, but the speed of spread of swine dysentery and faecal score were significantly reduced in animals immunised with the weakly haemolytic strain compared to sham-immunised animals. The IgA response of immunised animals upon challenge with a virulent B. hyodysenteriae strain significantly correlated to a later onset of disease. The correlation between local IgA production and protection induced by a weakly haemolytic B. hyodysenteriae strain provides leads for future vaccine development against swine dysentery.


A simple instrument for surgical tattooing and skin marking.
We describe here a reliable and inexpensive surgical marking instrument utilizing materials that are readily available. It can be used preoperatively or intraoperatively for tattooing points of reference in spite of vigorous preps.


Correction to 'Mathematical modelling of oxygen transport in a muscle-on-chip device' (2022) by Hardman et al.
[This corrects the article DOI: 10.1098/rsfs.2022.0020.][This corrects the article DOI: 10.1098/rsfs.2022.0020.].


Influence of the Ag concentration on the medium-range order in a CuZrAlAg bulk metallic glass.
Fluctuation electron microscopy of bulk metallic glasses of CuZrAl(Ag) demonstrates that medium-range order is sensitive to minor compositional changes. By analyzing nanodiffraction patterns medium-range order is detected with crystal-like motifs based on the B2 CuZr structure and its distorted structures resembling the martensitic ones. This result demonstrates some structural homology between the metallic glass and its high temperature crystalline phase. The amount of medium-range order seems slightly affected with increasing Ag concentration (0, 2, 5 at.%) but the structural motifs of the medium-range ordered clusters become more diverse at the highest Ag concentration. The decrease of dominant clusters is consistent with the destabilization of the B2 structure measured by calorimetry and accounts for the increased glass-forming ability.


Glial fibrillary acidic polypeptides in peripheral glia. Molecular weight, heterogeneity and distribution.
Glial fibrillary acidic (GFA) polypeptides are present in major categories of rat peripheral glia including non-myelin-forming Schwann cells, enteric glia and some satellite cells. They can be detected both immunochemically and immunohistochemically. The immunoreactivity is associated with a polypeptide which has an MW of 49 000, indistinguishable from that of glial fibrillary acidic protein (GFAP) from rat brain. In spite of this, the GFA polypeptides found in the peripheral nervous system and central nervous system are not identical since they can be distinguished both immunohistochemically and immunochemically by a monoclonal GFAP antibody which recognizes GFAP in astrocytes and some enteric glia, but not GFAP in non-myelin-forming Schwann cells, satellite cells and many enteric glia. GFA-related molecules can also be detected in human Schwann cells by immunofluorescence. The results suggest, however, that the glial filament polypeptides of peripheral glia and astrocytes are less closely related in the human than in the rat. The glial distribution of GFAP is closely paralleled by 2 cell surface proteins, Ran-2 and A5E3 antigen. Although GFAP, Ran-2 and A5E3 are individually expressed by diverse cell types, the phenotype GFAP+, Ran-2+, A5E3+ defines a narrow group including only non-myelin-forming Schwann cells, enteric glia and astrocytes. These observations suggest that the non-myelin-forming cells of the central and peripheral nervous system may share some common functions.


Son preference and child replacement in Bangladesh: a new look at the child survival hypothesis.
Birth history data from women in the 1975-76 Bangladesh Fertility Survey were used to search for intentions to replace dead children. The median intervals between successive births of orders (i) and (i + 1) were not shorter when some siblings of orders below (i) had died. Nor was the median duration between the death of a child and the first posthumous birth shorter when the dead child was a boy or when it was survived by fewer than two brothers. The median intervals were generally shorter when the mother lived in an urban rather than a rural area but this difference was attributable only to the shorter duration of breast-feeding by urban women. These results disputed the notions that the timing of births was deliberately quicker to replace a dead child, that attempts at replacement were sex-selective, or that child replacement intentions were stronger in urban than in rural populations.


Diagnostic Testing for SARS-CoV-2 Infection.
Given the rapid development of diagnostic approaches to test for and diagnose infection with SARS-CoV-2, many options are available to assess infection. Multiple established diagnostic companies are now providing testing platforms whereas initially, testing was being performed with simple PCR-based tests using standard laboratory reagents. Additional testing platforms continue to be developed but challenges with testing, including obtaining testing reagents and other related supplies, are frequently encountered. With time, the testing supply chain will improve and more companies will be providing materials to support these testing efforts. In the USA, the need for rapid assay development and subsequent approval through attainment of emergency use authorization (EUA) has superseded the traditional arduous diagnostic testing approval workflow mandated by the FDA. It is anticipated that the USA will be able to continue to significantly increase its testing capabilities to address this pandemic; however, challenges remain due to the diversity of the performance characteristics of tests being utilized. This review provides an overview of the current diagnostic testing landscape, with pertinent information related to SARS-CoV-2 virology and antibody responses, that is available to diagnose infection.


Zinc deficiency alters responsiveness to antidepressant drugs in mice.
There is some evidence coming from preclinical and clinical studies suggesting a relationship between dietary zinc intake and depressive symptoms. The aim of the study was to determine whether zinc deficiency alters the response to antidepressants with a different mechanism of action. We examine also whether these changes are related to activity of the hypothalamic-pituitary-adrenal HPA axis. Male CD-1 mice were assigned to groups according to diet and antidepressant administration. To evaluate animal behavior, the immobility time in the forced swim test (FST) and locomotor activity were measured. To determine serum zinc levels the flame atomic absorption spectroscopy (FAAS) was used. The serum corticosterone was determined by radioimmunoassay (RIA). Antidepressants administered to zinc-deprived mice induced an altered response in the FST when compared to animals fed with an adequate diet. There were no changes in locomotor activity. Animals subjected to a zinc-deficient diet showed a significant reduction in serum zinc levels, which was normalized by antidepressant treatment. An increase in serum corticosterone concentrations in mice fed with a zinc-deficient diet and treated with antidepressants was observed, so it can be concluded that reduced levels of zinc contribute hyperactivation of the HPA axis. The results of this study suggest that a diet with a reduced zinc level alters antidepressant action, which is associated with a reduction in the serum zinc level and rise in the corticosterone level. The results of this study may indicate the involvement of zinc deficiency in the pathogenesis of depression.


Emergent Gene Expression Responses to Drug Combinations Predict Higher-Order Drug Interactions.
Effective design of combination therapies requires understanding the changes in cell physiology that result from drug interactions. Here, we show that the genome-wide transcriptional response to combinations of two drugs, measured at a rigorously controlled growth rate, can predict higher-order antagonism with a third drug in Saccharomyces cerevisiae. Using isogrowth profiling, over 90% of the variation in cellular response can be decomposed into three principal components (PCs) that have clear biological interpretations. We demonstrate that the third PC captures emergent transcriptional programs that are dependent on both drugs and can predict antagonism with a third drug targeting the emergent pathway. We further show that emergent gene expression patterns are most pronounced at a drug ratio where the drug interaction is strongest, providing a guideline for future measurements. Our results provide a readily applicable recipe for uncovering emergent responses in other systems and for higher-order drug combinations. A record of this paper's transparent peer review process is included in the Supplemental Information.


Susceptibility of Dermanyssus gallinae from China to acaricides and functional analysis of glutathione S-transferases associated with beta-cypermethrin resistance.
Dermanyssus gallinae poses a significant threat to poultry production, and the resistance to pyrethroids has been identified worldwide. Periodic monitoring of acaricide resistance in D. gallinae is very important for its control, and molecular mechanism associated with beta-cypermethrin resistance in D. gallinae is not fully clear. Results showed, four field isolates of CBP-1, CBP-2, CBP-5 and CBY-1 from China remained either susceptible or with decreased susceptibility (resistance ratio < 5.0) to phoxim, amitraz, propoxur and carbaryl. Four field isolates of CBP-1, CBP-3, CBY-2 and CBH-1 had developed high or extremely high level of resistance (resistance ratio ≥ 40.0) to beta-cypermethrin or permethrin. Detoxification enzyme activity of GSTs was significantly higher in beta-cypermethrin resistant (RS) than susceptible strain (SS), indicating that GSTs are probably involved in beta-cypermethrin resistance in D. gallinae. The recombinant GSTs (rGST-1, 2, 3) showed a pronounced activity toward the conjugates of 1-chloro-2, 4 dinitrobenzene (CDNB) and glutathione (GSH), with rGST-1 presenting the highest enzymatic activity. Constitutive over-expression of Deg-GST-2 was detected in RS strain, and GSTs genes were all inducible with the treatment of beta-cypermethrin in SS and RS strains. More importantly, knocking down Deg-GST-2 gene expression by RNAi increased the susceptibility of RS strain to beta-cypermethrin. HPLC analysis indicated that rGST-1 protein could metabolize phoxim directly, but rGSTs could not directly metabolize beta-cypermethrin. Our results indicated that some field isolates of D. gallinae from China had developed high level of resistance to pyrethroids, and elevated GSTs activity as well as increased GSTs expression levels were involved in beta-cypermethrin resistance, but the three evaluated GSTs did not play a direct role in the metabolism of beta-cypermethrin.


Arylamine based cathepsin K inhibitors: investigating P3 heterocyclic substituents.
A modification of novel cathepsin K inhibitors I was carried out. The structural design was aimed at reducing the lipophilic character of compounds I for obtaining better pharmacokinetic profiles. This modification afforded several less lipophilic compounds with good inhibitory activities and pharmacokinetic profiles, although the enzyme selectivity over cathepsin S was left at issue.


Effects of Different Limb Remote Ischaemic Preconditioning on Ischaemia Reperfusion Injury in an Acute Left Anterior Descending Artery Occlusion Rat Model.
The aim is to compare effects of three different protocols of limb remote ischaemic preconditioning (LRIP) on ischaemia reperfusion injury in an acute left anterior descending artery (LAD) occlusion model rat. Forty adult male Wistar rats were randomly assigned into four groups: group A, control; group B, LRIP in bilateral upper-limb (BUL) IP; group C, LRIP in bilateral lower-limb (BLL) IP; group D, LRIP in bilateral upper and lower limbs (ULL) IP. The 60min ligation and 180min reperfusion in LAD were applied to all rats. Limb remote ischaemic preconditioning was performed using 5min occlusion and 15min reperfusion (six cycles). Heart rate, blood pressure and electrogastrography (EGG) were recorded. Creatine kinase isoenzyme (CK-MB) level and infarct size were measured. Limb remote ischaemic preconditioning did not significantly affect heart rate, systolic blood pressure and arrhythmia score. However, LRIP significantly increased DBP value and decreased CK-MB levels and infarct size in group B, C, and D. Moreover, LRIP in ULL had a significantly better effect on reducing infarct size than LRIP in BUL and BLL. Limb remote ischaemic preconditioning at limbs could significantly reduce reperfusion injury in the heart. Moreover, LRIP in ULL indicated a better effect in reducing infarct size than LRIP in BUL and BLL.


Participation of NO-Dependent Mechanisms in the Effects of Increased Systemic Level of Interleukin-1β on Pial Microvessels under Conditions of Acute Hypoxia.
We studied the effect of increased systemic levels of the proinflammatory cytokine IL-1β on the vasomotor reactions of pial microvessels in anesthetized rats under conditions of experimentally simulated progressively increasing acute normobaric hypoxia. Vital microscopy showed that more pronounced dilatation of pial vessels in response to IL-1β under hypoxic conditions was almost completely prevented by pretreatment with non-specific NO synthase blocker L-NAME. These findings indicate the involvement of NO-dependent mechanisms in the vasodilator effect of proinflammatory cytokines under conditions of acute hypoxic exposure.


Induction of PGHS-2 mRNA in response to cerebral hypoperfusion in late-gestation fetal sheep.
Previous studies have demonstrated that cerebral ischemia stimulated the increased abundance of immunoreactive PGHS-2, but not PGHS-1, in brain tissue homogenates in late-gestation fetal sheep. The goal of the present study was to detect PGHS-1 and PGHS-2 mRNA in specific fetal brain regions, and to semi-quantitatively detect changes in the abundance of the respective mRNA's in response to cerebral hypoperfusion. Fetal brain tissues were collected from control fetuses and from fetuses 30 min and 2 h after cerebral hypoperfusion (produced by brachiocephalic occlusion). Messenger RNA was studied by RT-PCR, and expressed semiquantitatively as a ratio of PGHS-1 or PGHS-2 mRNA abundance to beta-actin mRNA abundance. PGHS-2 mRNA was only detected in the fetal hippocampus, hypothalamus, and brain stem and it was induced by cerebral hypoperfusion. In contrast, PGHS-1 mRNA was detected in all fetal brain tissues but was not induced. We conclude that cerebral hypoperfusion induced PGHS-2 gene expression in hippocampus, hypothalamus, and brainstem, and we speculate that the increased abundance of the enzyme is likely to be important for control of reflex responses to hypotension in the fetus.


Chest wall mesenchymoma (hamartoma) in infancy. CT and MR findings.
A case of a chest wall mesenchymoma in a five month old infant is presented, and the role of CT and MR are emphasized. There have been no prior reports of the CT or MR findings in this entity.


Differences in COVID-19 Risk by Race and County-Level Social Determinants of Health among Veterans.
COVID-19 disparities by area-level social determinants of health (SDH) have been a significant public health concern and may also be impacting U.S. Veterans. This retrospective analysis was designed to inform optimal care and prevention strategies at the U.S. Department of Veterans Affairs (VA) and utilized COVID-19 data from the VAs EHR and geographically linked county-level data from 18 area-based socioeconomic measures. The risk of testing positive with Veterans' county-level SDHs, adjusting for demographics, comorbidities, and facility characteristics, was calculated using generalized linear models. We found an exposure-response relationship whereby individual COVID-19 infection risk increased with each increasing quartile of adverse county-level SDH, such as the percentage of residents in a county without a college degree, eligible for Medicaid, and living in crowded housing.


Signaling peptides direct the art of rebirth.
Signaling peptide-mediated cell-cell communication is crucial for plant growth, development, and adaptive responses to environmental stimuli. Given the prominent roles signaling peptides play in stem cell homeostasis, we propose investigating their impact on plant regeneration, which requires cellular reprogramming of differentiated cells to stem cells and establishment of nascent meristems.


The breastfeeding surgical patient.
In the United States, more than 10 million women are either pregnant or breastfeeding at any given time. Of the women currently pregnant, over 70% will initially choose to breastfeed. The needs of a breastfeeding surgical patient are unique and are best met by a supportive surgical team using evidenced-based practice. The outcomes of such care will have long-term effects on both the breastfeeding surgical patient and her infant. Evidenced-based practice resources for care of the breastfeeding surgical patient are scarce. This article applies available resources to the perioperative care of the breastfeeding surgical patient.


Soft Gasket Seal Reconstruction After Endoscopic Endonasal Transtuberculum Resection of Craniopharyngiomas.
The expanded endoscopic endonasal approach (EEA) is currently well accepted for a variety of ventral skull base tumors. Such an approach often results in a transdural defect and intraoperative cerebrospinal fluid (CSF) leak, and adequate reconstruction is necessary to prevent postoperative CSF leak and its complications. Reconstruction is usually performed using a variety of materials along with the nasoseptal flap. This work's aim is to describe a new reconstructive technique called the "soft gasket seal" (SGS) in detail and compare it with the standard reconstructive technique at our institution for craniopharyngiomas operated via transtuberculum EEA. A retrospective chart review was achieved to identify patients who underwent transtubercular EEA for craniopharyngioma between 2010 and 2018, by the same neurosurgical and otolaryngology team using either the SGS or standard reconstructive technique. Of 36 patients who met criteria and were considered for analysis, 15 of them underwent SGS reconstruction and 21 had standard reconstruction. There were 16 female (44%) and 20 male (56%) patients. The median age was 42.2 ± 20.9 years. The rate of postoperative CSF leak in the group of patients treated with the standard technique was 14.2% and 6.6% in the SGS group (odds ratio 0.43 [confidence interval 95% 0.007-6.15], P = 0.62). The SGS technique provides a simple reconstructive technique in conjunction with the nasoseptal flap, showing a tendency of lower complications when compared with our standard technique while avoiding donor site morbidity. Such results are encouraging, but further studies are necessary to confirm these findings.


Assembly of M13 and M13am8H1R1 procoat protein into microsomes is stimulated by rabbit reticulocyte lysate and ATP.
Processing of M13 procoat protein to transmembrane coat protein by dog pancreas microsomes is stimulated by a component of rabbit reticulocyte lysate and ATP. We asked whether this ATP-dependent reaction, involved in membrane assembly of procoat protein in the eukaryotic system, is related to the membrane potential dependent reaction observed for the membrane assembly of procoat protein in E. coli. Specifically, we asked if a mutant procoat protein which had been previously shown to be independent of the membrane potential with respect to its assembly in E. coli (M13am8H1R1 procoat protein) shows a stimulation by reticulocyte lysate and ATP in its assembly into microsomes. Since the mutant procoat protein behaved exactly as the wild type procoat protein in the eukaryotic in vitro system, we propose that the ATP-dependent reaction observed for the eukaryotic system does not substitute for the membrane potential dependent reaction in the prokaryotic system.


The health and cost consequences of obesity among the future elderly.
Obesity could have serious consequences for older cohorts. We used a microsimulation to estimate lifetime costs, life expectancy, disease, and disability for seventy-year-olds based on body mass. Obese seventy-year-olds will live about as long as those of normal weight but will spend more than 39,000 dollars more on health care. Moreover, they will enjoy fewer disability-free life years and experience higher rates of diabetes, hypertension, and heart disease. Medicare will spend about 34 percent more on an obese person than on someone of normal weight. Obesity might cost Medicare more than other diseases, because higher costs are not offset by reduced longevity.


Inhibition of Henipavirus fusion and infection by heptad-derived peptides of the Nipah virus fusion glycoprotein.
The recent emergence of four new members of the paramyxovirus family has heightened the awareness of and re-energized research on new and emerging diseases. In particular, the high mortality and person to person transmission associated with the most recent Nipah virus outbreaks, as well as the very recent re-emergence of Hendra virus, has confirmed the importance of developing effective therapeutic interventions. We have previously shown that peptides corresponding to the C-terminal heptad repeat (HR-2) of the fusion envelope glycoprotein of Hendra virus and Nipah virus were potent inhibitors of both Hendra virus and Nipah virus-mediated membrane fusion using recombinant expression systems. In the current study, we have developed shorter, second generation HR-2 peptides which include a capped peptide via amidation and acetylation and two poly(ethylene glycol)-linked (PEGylated) peptides, one with the PEG moity at the C-terminus and the other at the N-terminus. Here, we have evaluated these peptides as well as the corresponding scrambled peptide controls in Nipah virus and Hendra virus-mediated membrane fusion and against infection by live virus in vitro. Unlike their predecessors, the second generation HR-2 peptides exhibited high solubility and improved synthesis yields. Importantly, both Nipah virus and Hendra virus-mediated fusion as well as live virus infection were potently inhibited by both capped and PEGylated peptides with IC50 concentrations similar to the original HR-2 peptides, whereas the scrambled modified peptides had no inhibitory effect. These data also indicate that these chemical modifications did not alter the functional properties of the peptides as inhibitors. Nipah virus and Hendra virus infection in vitro can be potently blocked by specific HR-2 peptides. The improved synthesis and solubility characteristics of the second generation HR-2 peptides will facilitate peptide synthesis for pre-clinical trial application in an animal model of Henipavirus infection. The applied chemical modifications are also predicted to increase the serum half-life in vivo and should increase the chance of success in the development of an effective antiviral therapy.


Adenosine triphosphatase activity in few tissues of a fresh water teleost, Channa gachua following in vivo exposure to endosulfan.
Fresh water teleost fish, Channa gachua, were chronically exposed to various sublethal concentrations of endosulfan (0.00534, 0.00355, 0.00213 and 0.00174 mg/1) at 25 +/- 4 degrees C for 30 and 60 days respectively. The study shows enzyme inhibitions, greatest in oligomycin-insensitive Mg2+ ATPase in brain, gill and liver tissues, with pronounced effects at highest endosulfan concentration for 60 days exposure. However, in kidney the highest inhibition was of oligomycin-sensitive (mitochondrial) Mg2+ ATPase. The study indicates that endosulfan interferes with energy metabolism in vivo. The marked sensitivity of mitochondrial Mg2+ ATPase to endosulfan is suggestive of the potential for endosulfan to interfere markedly with various energy requiring processes in the fish body.


Impact of sleep opportunity on asthma outcomes in adolescents.
Insufficient sleep is associated with a number of negative health outcomes; as most adolescents obtain <7 h of sleep per night, it is important to understand how sleep impacts asthma among adolescents. To examine the impact of sleep opportunity on asthma in adolescents. In this study, 54 adolescents with asthma (12-17 years, 69% female, 65% Caucasian) participated in a randomized, cross-over sleep manipulation trial, including a sleep stabilization week, five nights of a "Short" sleep opportunity (time in bed: 6.5 h/night), and five nights of a "Long" sleep opportunity (time in bed: 9.5 h/night). Wake times were consistent across all three study weeks. Primary outcomes were lung function (daily peak expiratory flow rate, weekly spirometry) and functional asthma outcomes (daily asthma symptoms, Asthma Control Questionnaire, PROMIS Asthma Impact Scale). Markers of inflammation were also explored. Compared to the Long sleep week, during the Short sleep week, morning FEV1 was lower (p = 0.006), while asthma symptoms and albuterol use was higher (p < 0.05), and asthma showed a trend towards greater negative impact on daily life (p = 0.07). No differences were found for weekly measures of lung function or inflammation. An insufficient sleep opportunity negatively impacts objective and subjective daily symptoms of asthma in adolescents, as well as health related quality of life. As most adolescents are significantly sleep deprived, it is important to target sleep health in the treatment of asthma.


Complexity generation in fungal peptidyl alkaloid biosynthesis: a two-enzyme pathway to the hexacyclic MDR export pump inhibitor ardeemin.
Ardeemins are hexacyclic peptidyl alkaloids isolated from Aspergillus fischeri as agents that block efflux of anticancer drugs by MultiDrug Resistance (MDR) export pumps. To evaluate the biosynthetic logic and enzymatic machinery for ardeemin framework assembly, we sequenced the A. fischeri genome and identified the ardABC gene cluster. Through both genetic deletions and biochemical characterizations of purified ArdA and ArdB we show this ArdAB enzyme pair is sufficient to convert anthranilate (Ant), L-Ala, and L-Trp to ardeemin. ArdA is a 430 kDa trimodular nonribosomal peptide synthase (NRPS) that converts the three building blocks into a fumiquinazoline (FQ) regioisomer termed ardeemin FQ. ArdB is a prenyltransferase that takes tricyclic ardeemin FQ and dimethylallyl diphosphate to the hexacyclic ardeemin scaffold via prenylation at C2 of the Trp-derived indole moiety with intramolecular capture by an amide NH of the fumiquinazoline ring. The two-enzyme ArdAB pathway reveals remarkable efficiency in construction of the hexacyclic peptidyl alkaloid scaffold.


Communicative trust in therapeutic encounters: users' experiences in public healthcare facilities and community pharmacies in Maputo, Mozambique.
Interactions between healthcare users and providers are an essential but often problematic element in therapeutic processes. In many settings worldwide, there has been a general recognition of the importance of adopting care approaches that understand patients as active agents, moving away from traditional paternalistic forms of interaction. Research shows that improving the quality of communication in therapeutic encounters fosters mutual understanding and cooperation in healthcare processes, helping to create the grounding conditions for building trusting relationships. But what are the communicative mechanisms through which trust in healthcare providers is cultivated? Going beyond the traditional 'doctor-patient' dyad analysis, and using data from a mixed-method study on medicine use in Maputo, Mozambique, this paper explores healthcare users' experiences and interpretations of their interactions with public healthcare professionals (medical doctors and prescribing nurses) and community pharmacy workers (pharmacists, technicians and other attendants). The analysis evolves around various communicative and relational aspects, emphasised by users as meaningful and underpinning different qualities of care, competence, integrity and trustworthiness. These attributes were assessed based on a combination of verbal conversation and information exchange, together with the use of other (non-verbal) situationally valued artefacts such as biomedical tools and communicative rituals performed by providers. This study shows that despite healthcare providers' different attributes of competence and authority, it is mainly their communicative performances during interactions that influence whether (symbolic) trust has the space to evolve or crystallise. Moreover, while performing certain rituals may be an effective form of communication, the lack of other (verbal and non-verbal) communicative elements during the interaction may compromise patient trust in what is being prescribed or advised. Efforts to improve the quality and responsiveness of healthcare services centred around citizens' needs should take users' perspectives into account and pay particular attention to these communicative and relational dimensions.


Lacrimal sac tumors.
Tumors of the lacrimal sac are a rare entity in ophthalmology, but represent a potentially life-threatening situation that can easily be overlooked. This paper will review the literature and describe clinically and pathologically the more common types of lacrimal sac tumors, and give a description of the less common types of primary and secondary tumors of the lacrimal sac and a case presentation.


Impairment of the hemostatic potential of platelets during storage as evaluated by flow cytometry, thrombin generation, and thrombelastography under conditions promoting formation of coated platelets.
The increasing demand for platelet (PLT) transfusions has focused attention on appropriate use. Coated PLTs are a subpopulation of highly procoagulant PLTs formed by simultaneous stimulation by the agonist's collagen and thrombin hypothesized to drive clot formation at the site of vascular injury. Prolonged storage of PLTs may reduce their ability to support optimal hemostasis upon transfusion. PLT concentrates (PCs) stored for 1, 4, 6, and 8 days were costimulated with thrombin and the collagen glycoprotein VI (GPVI) receptor agonist convulxin, and their ability to form coated PLTs was determined by flow cytometry. Further, a plasma-based thrombin generation assay and thrombelastography were used to evaluate the aged PCs' capacity to support thrombin generation and clot formation, respectively. The stored PCs were additionally tested by standard quality control methods. PLT quality as measured by standard analyses was acceptable according to current practice. The hemostatic potential, however, was impaired with increasing storage time. The formation of coated PLTs decreased significantly from approximately 85 to 55 percent with increasing storage time (p<0.05). The velocity of clot formation was significantly increased from Day 4 (p<0.05). The velocity of thrombin generation and resistance against fibrinolysis were significantly reduced on Day 8 compared to Day 1 of storage (p<0.05). Data in the present study suggest that storage significantly reduced the stored PLTs' ability to respond to conditions expected to exist at the site of vascular injury and that storage-induced reduction in PLT activation sensitivity correlated with a loss of hemostatic potential.


Myeloid-derived suppressor cells support remyelination in a murine model of multiple sclerosis by promoting oligodendrocyte precursor cell survival, proliferation, and differentiation.
The most frequent variant of multiple sclerosis (MS) is the relapsing-remitting form, characterized by symptomatic phases followed by periods of total/partial recovery. Hence, it is possible that these patients can benefit from endogenous agents that control the inflammatory process and favor spontaneous remyelination. In this context, there is increasing interest in the role of myeloid-derived suppressor cells (MDSCs) during the clinical course of experimental autoimmune encephalomyelitis (EAE). MDSCs speed up infiltrated T-cell anergy and apoptosis. In different animal models of MS, a milder disease course is related to higher presence/density of MDSCs in the periphery, and smaller demyelinated lesions in the central nervous system (CNS). These observations lead us to wonder whether MDSCs might not only exert an anti-inflammatory effect but might also have direct influence on oligodendrocyte precursor cells (OPCs) and remyelination. In the present work, we reveal for the first time the relationship between OPCs and MDSCs in EAE, relationship that is guided by the distance from the inflammatory core. We describe the effects of MDSCs on survival, proliferation, as well as potent promoters of OPC differentiation toward mature phenotypes. We show for the first time that osteopontin is remarkably present in the analyzed secretome of MDSCs. The ablation of this cue from MDSCs-secretome demonstrates that osteopontin is the main MDSC effector on these oligodendroglial cells. These data highlight a crucial pathogenic interaction between innate immunity and the CNS, opening ways to develop MDSC- and/or osteopontin-based therapies to promote effective myelin preservation and repair in MS patients.


Symbolic extensions applied to multiscale structure of genomes.
A genome of a living organism consists of a long string of symbols over a finite alphabet carrying critical information for the organism. This includes its ability to control post natal growth, homeostasis, adaptation to changes in the surrounding environment, or to biochemically respond at the cellular level to various specific regulatory signals. In this sense, a genome represents a symbolic encoding of a highly organized system of information whose functioning may be revealed as a natural multilayer structure in terms of complexity and prominence. In this paper we use the mathematical theory of symbolic extensions as a framework to shed light onto how this multilayer organization is reflected in the symbolic coding of the genome. The distribution of data in an element of a standard symbolic extension of a dynamical system has a specific form: the symbolic sequence is divided into several subsequences (which we call layers) encoding the dynamics on various "scales". We propose that a similar structure resides within the genomes, building our analogy on some of the most recent findings in the field of regulation of genomic DNA functioning.