Evaluation of a gender synchronized family planning intervention for married couples in rural India: The CHARM2 cluster randomized control trial.
Despite calls for gender transformative family planning interventions to increase male engagement and female reproductive agency, there is limited research involving rigorous evaluation of the integration of these approaches. CHARM2 (counseling Husbands and wives to Achieve Reproductive Health and Marital Equity) builds upon a prior three-session male engagement intervention by integrating female-focused sessions emphasizing women's choice and agency (i.e., gender synchronization). We hypothesized that CHARM2 participants will be more likely to report marital contraceptive use and communication and women's contraceptive agency, and less likely to report unintended pregnancy, relative to participants in the control condition. We conducted a two-armed cluster randomized controlled trial evaluating the effects of CHARM2 on marital contraceptive use, communication, decision-making; women's contraceptive agency, and pregnancy among young married couples in rural Maharashtra, India (ClinicalTrials.gov #NCT03514914, complete). 40 geographic clusters, defined based on the catchment areas of subcenter health facilities (the most proximal level of community health care within India's public health system) were randomized to control (n = 20) and intervention (n = 20). We assigned all participants within that geographic cluster to the corresponding cluster treatment condition; participants, investigators, and study staff were not masked to treatment assignment. Eligibility criteria included wife aged 18-29, couple residing together for at least six months with no plan for migration, and neither spouse sterilized or infertile. The CHARM2 intervention included five provider-delivered sessions on gender equity and family planning, two delivered in parallel to husbands and wives separately by gender-matched providers, and one final joint session, delivered within the four months subsequent to baseline survey. We conducted surveys and pregnancy testing at baseline and 9-month and 18-month follow-up. We used difference-in-differences multilevel mixed effects logistic regressions to assess CHARM2 effects on marital contraceptive use and communication, and women's contraceptive agency; we used single time point mixed effects logistic regressions for pregnancy outcomes. All analyses used an intention-to-treat approach. 1201 couples were recruited between September 2018 and June 2019; 600 intervention and 601 control. All couples were included in outcome analyses. Full couple retention was 90·2% (n = 1083) at 9-month follow-up and 90·5% (n = 1087) at 18-month follow-up. Modern contraceptive use was higher among intervention participants at 9-month but not 18-month follow-up (9-month adjusted ratio of odds ratio [AROR] 1·5, 95% CI 1·03-2·3; 18-month AROR 0·8, 95% CI 0·4-1·4). Communication (9-month AROR 1·9, 95% CI 1·0-3·6; 18-month AROR 2·7, 95% CI 1·5-4·8) and agency (9-month AROR 5·1, 95% CI 1·2-22·4; 18-month AROR 8·1, 95% CI 1·4-48·2) both improved at both time points. There was no significant difference in pregnancy between groups over the 18-month period (AOR 0·8, 95% CI 0·7-1.1) However, for women who expressed fertility ambivalence at baseline, unintended pregnancy was marginally less likely among intervention participants (47% vs 19%) (p = 0·07). There were no reported adverse events. The CHARM2 intervention offers a scalable model to improve contraceptive use, communication, and agency and possibly decrease unplanned pregnancies for couples in rural India.


[Asthma is an epidemic].
Asthma is a frequent illness in young adults and is characterized by airway hyper responsiveness (AHR) and airway inflammation. Asthma is a complex disease and AHR as well as inflammation may be limited, although characteristic symptoms are present. The clinical experience in asthma treatment is that not all asthmatics have a satisfactory effect of the different drugs. Asthma has been found to develop from one disease to a multifaceted disease with numerous different possibilities. More research is needed in strategic asthma management in the search for tailored treatment strategy.


Light and electron microscope study in allergic rhinitis patients (ARP) with or without bronchial hyperreactivity (BHR).
Little is known about the pathogenesis of bronchial hyperreactivity associated with allergic rhinitis. For this purpose, bronchial biopsies and bronchoalveolar lavage from 6 allergic rhinitis patients with bronchial hyperreactivity, 5 allergic rhinitis patients without bronchial hyperreactivity and 3 healthy, normoreactive control subjects were obtained by fiberoptic bronchoscope and investigated with light and transmission electron microscope. Varying degrees of morphological alterations were observed in all groups; however, the intensity of the epithelial shedding, goblet cells, basement membrane thickness, stromal collagenous fibers and smooth muscle cells appeared to be increased in allergic rhinitis patients with bronchial hyperreactivity. In the mucosa and submucosa, the numbers and activation of lymphocytes, neutrophils and macrophages were lower in allergic rhinitis patients with bronchial hyperreactivity than in the control group and in allergic rhinitis patients without bronchial hyperreactivity. In accordance with these findings, bronchoalveolar lavage showed increased numbers of lymphocytes and surface alterations of phagocytic cells in allergic rhinitis patients without bronchial hyperreactivity. As a result, we could not find evidence of inflammation accompanying bronchial hyperreactivity in allergic rhinitis patients.


Identification and purification of EBP1: a HeLa cell protein that binds to a region overlapping the 'core' of the SV40 enhancer.
The SV40 enhancer consists of multiple DNA sequence motifs that are recognized by a variety of trans-acting factors. Using DNase I protection and a gel electrophoresis DNA-binding assay, we identified a HeLa cell protein (EBP1) that binds to the 'core' region of the SV40 enhancer. A short double-stranded synthetic oligonucleotide containing the binding site for EBP1 was used to assay for EBP1 activity and to purify a 57,000-m.w. polypeptide by recognition site affinity chromatography. Bromodeoxyuracil cross-linking identified a 60,000-m.w. species as the polypeptide responsible for the DNA-binding activity. Analysis of the DNA sequences required for EBP1 binding indicated that EBP1 could be distinguished from a number of recently characterized proteins (EBP20, AP-2, and AP-3) by its binding to a variety of mutant templates. Correlation of the in vivo transcriptional activity of wild-type and mutated enhancers with EBP1 binding indicates that this protein may be important for SV40 enhancer activity because mutations that abolish EBP1 binding also have a severe deleterious effect on transcription.


Confocal Raman Microscopy for the Analysis of the Three-Dimensional Shape of Polymeric Microsphere Layers.
The reconstruction of the three-dimensional (3D) morphology of polymeric microsphere layers based on confocal Raman microscopy was studied. Refraction of the Raman laser beam at the curved surface of the spheres broadens the focus volume inside the sphere. Compared to planar layers, the focus gets trapped inside the spheres such that the measured depth profiles are shifted and broadened. Additionally, the Raman signal of the underlying substrate is already observed for nominal focus positions above the microsphere layer. The results are successfully modeled with ray-optical simulations that allow for a clear understanding of the relevant mechanisms that lead to the generation of the Raman signals in the complex three-dimensional structures.


Multistage designs for vaccine safety studies.
In a placebo-controlled vaccine safety trial, the primary interest is to demonstrate that the vaccine is sufficiently safe, rejecting the null hypothesis that the relative risk of an adverse event attributable to the vaccine is above a prespecified value, greater than one. We develop sequential as well as multistage designs for such trials where the interim analyses are conducted not after a given number of subjects but rather after a given number of events observed. We show that these designs achieve significant improvement over single-stage conditional test in terms of both the required number of events to be observed and the required number of subjects to be enrolled.


Physiological monitoring in firefighter ensembles: wearable plethysmographic sensor vest versus standard equipment.
We evaluated the accuracy of a wearable sensor vest for real-time monitoring of physiological responses to treadmill exercise. Ten subjects in standard firefighter ensembles, treadmill exercising at 50% VO(2) max, had heart rate (HR), respiratory rate (RR), skin temperature (T(sk)), oxygen saturation (SaO(2)), tidal volume (V(T)), and minute ventilation (V(E)) recorded concurrently by a wearable plethysmographic sensor vest and standard laboratory physiological monitoring equipment for comparison. A high degree of correlation was noted for most of the measured variables [HR (r = 0.99), RR (r = 0.98), T(sk) (r = 0.98), V(E) (r = 0.88), and SaO(2) (r = 0.79)]. V(T) (r = 0.60) had a moderate correlation, although a paired differences analysis showed a mean paired difference of -0.03 L. This mean paired difference represents a 1.92% variation for V(T). Data from the wearable sensor vest is comparable to data captured from standard laboratory physiological monitoring equipment on subjects wearing standard firefighter ensembles while exercising at a moderate work rate. This study demonstrates the accuracy of the wearable sensor technology for these physiological parameters under these conditions and suggests that it could be useful for actual field studies of firefighters in traditional firefighting gear.


Single-Pixel Densitometry Revealed the Presence of Peptidoglycan in the Intermembrane Space of the Moss Chloroplast Envelope in Conventional Electron Micrographs.
Chloroplasts are believed to be descendants of ancestral cyanobacteria that have a peptidoglycan layer between the outer and the inner membranes. In particular, cyanelles having peptidoglycan in Cyanophora paradoxa are considered as evidence for the endosymbiotic origin of chloroplasts. The moss Physcomitrella patens has a complete set of genes involved in the synthesis of peptidoglycan, but a peptidoglycan layer has not been observed by conventional electron microscopy to date. Recently, a new metabolic labeling technique using a fluorescent probe was applied to visualize putative peptidoglycan surrounding the chloroplasts. The exact localization of the peptidoglycan, however, has not been clearly identified. Here we examined conventional electron micrographs of two types of moss materials (mutants or ampicillin-treated plants), one presumably having peptidoglycan and the other presumably lacking peptidoglycan, and analyzed in detail, by single-pixel densitometry, the electron density of the chloroplast envelope membranes and the intermembrane space. Statistical analysis showed that the relative electron density within the intermembrane space with respect to that of the envelope membranes was significantly higher in the materials presumably having peptidoglycan than in the materials presumably devoid of peptidoglycan. We consider this difference as bona fide evidence for the presence of peptidoglycan between the outer and the inner envelope membranes in the wild-type chloroplasts of the moss, although its density is lower than that in bacteria and cyanelles. We will also discuss this low-density peptidoglycan in the light of the phylogenetic origin of peptidoglycan biosynthesis enzymes.


Acalculous cholecystitis in a patient with hepatocellular carcinoma on sorafenib.
A 67-year-old woman with compensated cirrhosis type B associated with hepatocellular carcinoma was started on sorafenib for multiple pulmonary metastases. The patient developed right upper quadrant pain and high fever 4 weeks later. Imaging revealed marked enlargement of the gallbladder without calculi. Following percutaneous transhepatic gallbladder aspiration, her symptoms resolved, but the gallbladder remained enlarged. Laparoscopic cholecystectomy was performed. Arteriolar occlusion with intimal thickening in the muscular layer of the gallbladder was seen sporadically. The fact that this patient had no risk factors for acalculous cholecystitis suggested that the cholecystitis resulted from ischemia, implying a strong causal relationship with sorafenib.


Utilisation of acute care hospital beds by levels of care.
An exploratory analysis of utilisation patterns of acute care hospitals in the Province of Alberta, Canada was carried out to develop a methodology for assessing bed utilisation profiles of acute care hospitals by levels of care. The utilisation of Alberta acute care hospital beds was measured in terms of primary, secondary and tertiary levels of hospital services. Patient origin-destination methodology was applied and a regionalisation perspective employed. The data used for this study were hospital separation abstracts compiled by all Alberta acute care hospitals during year 1986, this coincided with the most recent available Canadian census data. It was estimated that approximately 10-11% of Alberta beds were used for tertiary care as derived from population based utilisation rates and patient flow patterns. With respect to per capita measurement, the number of beds used per 1,000 residents was: 3.5 to 3.9 for primary, 1.2 to 1.6 for secondary, and about 0.6 for tertiary levels of care. Regression analysis revealed that the marginal cost per bed at each level was approximately 75-79, 87-88, and 201-209 thousand Canadian dollars per year in 1986 for primary, secondary and tertiary care respectively. The profiles thus estimated explained about 65% of per bed hospital cost variation.


Central effects of endothelin-1 on vasopressin and atrial natriuretic peptide release and cardiovascular and renal function in conscious rats.
In order to investigate the central effect of endothelin-1 (ET-1) on arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) release and cardiovascular and renal function, either a high dose of ET-1 (3.5 ng/kg/min, HET-1) or a low dose (0.35 ng/kg/min, LET-1) was administered into the cerebral third ventricle in conscious rats. ET-1 increased the mean arterial blood pressure, but not heart rate, in a dose-related manner. LET-1 slightly stimulated AVP release, but not ANP release. HET-1 increased plasma AVP and ANP. Pretreatment with a V1-antagonist (TMeAVP) attenuated the blood pressure response to ET-1 and completely abolished increases in plasma ANP. Moreover, prazosin given i.v. completely prevented the residual pressure response. ET-1 did not significantly affect renal electrolytes and water handling. These results suggest that centrally administered ET-1 may increase the activity of the sympathetic nervous system and vasopressinergic neurons, resulting in an increase in blood pressure.


Biomedical Enhancement of Warfighters and the Legal Protection of Military Medical Personnel in Armed Conflict.
Under international law, military medical personnel and facilities must be respected and protected in the event of an armed conflict. This special status only applies to personnel and facilities exclusively engaged in certain enumerated medical duties, especially the treatment of the wounded and sick, and the prevention of disease. Military medical personnel have, however, been called upon to engage in the biomedical enhancement of warfighters, as exemplified by the supply of central nervous system stimulants as a fatigue countermeasure. This article argues that international law of armed conflict does not recognise human enhancement as a medical duty, and that engaging in enhancement that is harmful to the enemy results in the loss of special protection normally enjoyed by military medical personnel and units.


[Hallux valgus--several ways to treat].
Hallux valgus is a progressive exertional metatarsal disturbance altering the kinematics of walking. It may be accompanied by other problems of the foot, such as hammer toe or flatfoot syndrome, symptoms of metatarsalgia or arthrosis of the small joints of the foot. Conservative treatment aims to reactivate the muscles of the foot. Operatively, placement of the 1st metatarsal to its anatomical position over the sesamoid bones is attempted to support the action of the foot muscles. When choosing the operative technique the extent and severity of the disorder as well as the objectives and risk factors of the treatment should be considered.


A Review on Xerostomia and Its Various Management Strategies: The Role of Advanced Polymeric Materials in the Treatment Approaches.
The medical term xerostomia refers to the subjective sensation of oral dryness. The etiology seems to be multifactorial with the most frequently reported causes being the use of xerostomic medications, neck and head radiation, and systematic diseases (such as Sjögren's syndrome). Xerostomia is associated with an increased incidence of dental caries, oral fungal infections, and difficulties in speaking and chewing/swallowing, which ultimately affect the oral health-related quality of life. The development of successful management schemes is regarded as a highly challenging project due to the complexity of saliva. This is why, in spite of the fact that there are therapeutic options aiming to improve salivary function, most management approaches are alleviation-oriented. In any case, polymers are an integral part of the various formulations used in every current treatment approach, especially in the saliva substitutes, due to their function as thickening and lubricating agents or, in the case of mucoadhesive polymers, their ability to prolong the treatment effect. In this context, the present review aims to scrutinize the literature and presents an overview of the role of various polymers (or copolymers) on either already commercially available formulations or novel drug delivery systems currently under research and development.


Impairment of synaptic vesicle exocytosis and recycling during neuromuscular weakness produced in mice by 2,4-dithiobiuret.
Chronic treatment of rodents with 2,4-dithiobiuret (DTB) induces a neuromuscular syndrome of flaccid muscle weakness that mimics signs seen in several human neuromuscular disorders such as congenital myasthenic syndromes, botulism, and neuroaxonal dystrophy. DTB-induced muscle weakness results from a reduction of acetylcholine (ACh) release by mechanisms that are not yet clear. The objective of this study was to determine if altered release of ACh during DTB-induced muscle weakness was due to impairments of synaptic vesicle exocytosis, endocytosis, or internal vesicular processing. We examined motor nerve terminals in the triangularis sterni muscles of DTB-treated mice at the onset of muscle weakness. Uptake of FM1-43, a fluorescent marker for endocytosis, was reduced to approximately 60% of normal after either high-frequency nerve stimulation or K(+) depolarization. Terminals ranged from those with nearly normal fluorescence ("bright terminals") to terminals that were poorly labeled ("dim terminals"). Ultrastructurally, the number of synaptic vesicles that were labeled with horseradish peroxidase (HRP) was also reduced by DTB to approximately 60%; labeling among terminals was similarly variable. A subset of DTB-treated terminals having abnormal tubulovesicular profiles in their centers did not respond to stimulation with increased uptake of HRP and may correspond to dim terminals. Two findings suggest that posttetanic "slow endocytosis" remained qualitatively normal: the rate of this type of endocytosis as measured with FM1-43 did not differ from normal, and HRP was observed in organelles associated with this pathway- coated vesicles, cisternae, as well as synaptic vesicles but not in the tubulovesicular profiles. In DTB-treated bright terminals, end-plate potential (EPP) amplitudes were decreased, and synaptic depression in response to 15-Hz stimulation was increased compared with those of untreated mice; in dim terminals, EPPs were not observed during block with D-tubocurarine. Nerve-stimulation-induced unloading of FM1-43 was slower and less complete than normal in bright terminals, did not occur in dim terminals, and was not enhanced by alpha-latrotoxin. Collectively, these results indicate that the size of the recycling vesicle pool is reduced in nerve terminals during DTB-induced muscle weakness. The mechanisms by which this reduction occurs are not certain, but accumulated evidence suggests that they may include defects in either or both exocytosis and internal vesicular processing.


T-helper 17 cells mediate the osteo/odontoclastogenesis induced by excessive orthodontic forces.
The aim of this study was to investigate how T-helper 17 cells (Th17 cells), interleukin (IL)-17, and interleukin-6 contribute to root resorption during orthodontic tooth movement. Fifteen male 6-week-old Wistar rats were subjected to orthodontic force of 10 or 50 g to induce a mesially tipping movement of the upper first molars for 7 days. The expression levels of TRAP, IL-17, the IL-17 receptor (IL-17R), and IL-6 proteins were determined in periodontal ligament (PDL) by immunohistochemical analysis. Moreover, the fluorescent localization immunoassay was performed to detect Th17 cells. Furthermore, the effects of IL-17 on IL-6 release were investigated using human PDL cells in vitro. The effect of IL-17 on osteoclastogenesis was evaluated by TRAP staining, actin ring staining, and the pit formation assay. The immunoreactivity for Th17, IL-17, IL-17R, and IL-6 was detected in PDL tissue subjected to the orthodontic force on day 7. IL-17 increased the release of IL-6 from human periodontal ligament cells in a time-dependent manner. Moreover, IL-17 stimulated osteoclastogenesis from human osteoclast precursor cells, and these effects were partially suppressed by an anti-IL-6 antibody. These results suggest that Th17 cells may aggravate the process of orthodontically induced inflammatory root resorption.


Factors Associated with Conjunctival Erosions after Ahmed Glaucoma Valve Implantation.
To investigate the frequency of conjunctival erosions in a series of patients who underwent Ahmed valve implantation in a tertiary referral center and to study risk factors associated with the conjunctival erosions. This is a single-center, retrospective case-control study of all patients who underwent Ahmed valve implantation between October 2006 and July 2016 at the Kresge Eye Institute in Detroit, Michigan. The series consisted of 306 eyes (277 patients) that underwent Ahmed valve implantation. The rate of conjunctival erosions was determined. Univariate, bivariate, and Cox-proportional hazard analyses were performed to identify factors associated with conjunctival erosions. During the study period, 23 erosions occurred in 306 eyes (7.52%). Aphakia was significantly more common in eyes with erosions (P < 0.05). Aphakia (P = 0.02), uveitic glaucoma (P = 0.03), and longer post-operative use of topical steroids (P < 0.04) significantly increased the risk of erosions based on the Cox model. There were similar rates of erosions with each type of patch graft. No conjunctival erosion was observed after using the modified scleral tunnel method (n = 10). The overall erosion rate was 7.52% in our series. Uveitic glaucoma, aphakia, and longer post-operative use of topical steroids were significantly associated with conjunctival erosions.


Neuropsychological impairment in Parkinson's disease with and without depression.
To compare quantitative and qualitative aspects of neuropsychological test performance in patients with Parkinson's disease who currently had depression (PDD) and those without depression (PDN) so as to evaluate the influence of depression on cognition in Parkinson's disease. Cross-sectional comparisons among PDN, PDD, and normal control (NC) groups. The setting was a neurodegenerative disease research center in a teaching hospital. Groups consisted of 44 patients with PDN and 44 patients with PDD matched for age, education, gender, age at onset of disease, disease duration, and disease severity; a group of 44 NC subjects matched for age, education, and gender; and a second set of comparisons between 15 patients with PDN and 15 patients with PDD also matched for overall severity of cognitive impairment. The neuropsychological measures used were the Mattis Dementia Rating Scale, Beck Depression Inventory, Wisconsin Card Sorting Test, Controlled Oral Word Association Test, Logical Memory subtest of the Wechsler Memory Scale-Revised, Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised, and the Boston Diagnostic Aphasia Examination's Animal Naming test and Boston Naming Test. Relative to the NC group, both PDN and PDD groups demonstrated impairments in immediate and delayed verbal recall, semantic fluency, and problem solving. When PDN and PDD groups were matched for demographic and disease variables, only the PDD group evidenced impairment relative to NC in visual confrontation naming, and in lexical and semantic fluency. In addition, impairments on immediate recall and semantic fluency in the PDD group were more pronounced than those in the PDN group. However, when PDN and PDD groups were also matched for overall severity of cognitive impairment, no significant differences emerged among the two groups' neuropsychological test performances. Depression exacerbates some memory and language impairments associated with PD, even when the PDN and PDD groups are matched for demographic and disease variables. However, the extent and pattern of cognitive impairment is similar in PDN and PDD when the groups are also matched also for overall severity of cognitive impairment. Depression influences the quantity rather than the quality of cognitive impairment associated with Parkinson's disease.


Isolation of transcription factor complexes by in vivo biotinylation tagging and direct binding to streptavidin beads.
Efficient tagging methodologies are an integral aspect of protein complex characterization by proteomic approaches. Owing to the very high affinity of biotin for avidin and streptavidin, biotinylation tagging offers an attractive approach for the efficient purification of protein complexes. The very high affinity of the biotin/(strept)avidin system also offers the potential for the single-step capture of lower abundance protein complexes, such as transcription factor complexes. The identification of short peptide tags that are efficiently biotinylated by the bacterial BirA biotin ligase led to an approach for the single-step purification of transcription factor complexes by specific in vivo biotinylation tagging. A short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1. The direct binding to streptavidin of biotinylated GATA-1 in nuclear extracts resulted in the single-step capture of the tagged factor and associated proteins, which were eluted and identified by mass spectrometry. This led to the characterization of several distinct GATA-1 complexes with other transcription factors and chromatin remodeling cofactors, which are involved in activation and repression of gene targets. Thus, BirA-mediated tagging is an efficient approach for the direct capture and characterization of transcription factor complexes.


Cloning, Prokaryotic Expression, and Purification of Acetyl-CoA C-Acetyltransferase from Atractylodes lancea.
Cangzhu (Atractylodes lancea), a valuable and common traditional Chinese medicinal herb, is primarily used as an effective medicine with various health-promoting effects. The main pharmacological bioactive ingredients in the rhizome of A. lancea are terpenoids. Acetyl-CoA C-acetyltransferase (AACT) is the first enzyme in the terpenoid synthesis pathway and catalyzes two units of acetyl-CoA into acetoacetyl-CoA. The objective of the present work was to clone and identify function of AlAACT from Atractylodes lancea. A full-length cDNA clone of AlAACT was isolated using PCR and expressed in Escherichia coli. The expressed protein was purified using Ni-NTA agarose column using standard protocols. AlAACT was transiently expressed in N. benthamiana leaves to determine their subcellular location. The difference in growth between recombinant bacteria and control bacteria under different stresses was observed using the droplet plate experiment. In this study, a full-length cDNA of AACT (AlAACT) was cloned from A. lancea, which contains a 1,227 bp open reading frame and encodes a protein with 409 amino acids. Bioinformatic and phylogenetic analysis clearly suggested that AlAACT shared high similarity with AACTs from other plants. The recombinant protein pET32a(+)/AlAACT was successfully expressed in Escherichia coli BL21 (DE3) cells induced with 0.4 mM IPTG at 30°C as the optimized condition. The recombinant enzyme pET-32a-AlAACT was purified using the Ni-NTA column based on the His-tag, and the molecular weight was determined to be 62 kDa through SDS-PAGE and Western Blot analysis. The recombinant protein was eluted with 100, 300, and 500 mM imidazole; most of the protein was eluted with 300 mM imidazole. Under mannitol stress, the recombinant pET-32a- AlAACT protein showed a substantial advantage in terms of growth rates compared to the control. However, this phenomenon was directly opposite under NaCl abiotic stress. Subcellular localization showed that AlAACT localizes to the nucleus and cytoplasm. The expression and purification of recombinant enzyme pET-32a-AlAACT were successful, and the recombinant strain pET-32a-AlAACT in showed better growth in a drought stress. The expression of AlAACT-EGFP fusion protein revealed its localization in both nuclear and cytoplasm compartments. This study provides an important foundation for further research into the effects of terpenoid biosynthesis in A. lancea.


[Cardioprotection of adenosine treatment in cadaver donor rats with warm ischemia].
To determine the cardioprotection of adenosine treatment in cadaver donor rats with warm ischemia. Rats were randomly divided into 7 groups. Group C was a control group. Group I(5), I(15), and I(30): The donor hearts from the cadaver rats that died of acute hemorrhagic shock and within warm ischemic durations of 5, 15, and 30 min, respectively, and the donor hearts were perfused with STH-1 for 30 min before cervical heterotopic heart transplantation. Group A(5), A(15), and A(30) were adenosine treatment groups and the donor hearts were obtained as mentioned above and perfused with STH-1 plus adenosine (adenosine concentration 1.2 mmol/L) before cervical heterotopic heart transplantation. We detected the change of the grafts including ultrastructure, the level of ATP, SOD, and MDA, NF-kappaB mRNA, TNF-alpha, and IL-6 24 h after the transplantation. At the same time point, compared with Group I(5), I(15), and I(30), Group A(5), A(15), and A(30) showed increased ATP and SOD in the myocardial tissues, and decreased MDA, NF-kappaB mRNA, TNF-alpha, and IL-6 (P<0.05). Adenosine treatment can protect the graft in cadaver donor rats with warm ischemia. The mechanism may improve the myocardial energy metabolism, attenuate lipid peroxidation injury, suppress the expression of NF-kappaB mRNA, and decrease the inflammatory damage of TNF-alpha and IL-6.


Chromoplast differentiation: current status and perspectives.
Chromoplasts are carotenoid-accumulating plastids conferring color to many flowers and fruits as well as to some tubers and roots. Chromoplast differentiation proceeds from preexisting plastids, most often chloroplasts. One of the most prominent changes is remodeling of the internal membrane system associated with the formation of carotenoid-accumulating structures. During the differentiation process the plastid genome is essentially stable and transcriptional activity is restricted. The buildup of the chromoplast for specific metabolic characteristics is essentially dependent upon the transcriptional activity of the nucleus. Important progress has been made in terms of mediation of the chloroplast-to-chromoplast transition with the discovery of the crucial role of the Or gene. In this article we review recent developments in the structural, biochemical and molecular aspects of chromoplast differentiation and also consider the reverse differentiation of chromoplasts into chloroplast-like structures during the regreening process occurring in some fruit. Future perspectives toward a full understanding of chromoplast differentiation include in-depth knowledge of the changes occurring in the plastidial proteome during chromoplastogenesis, elucidation of the role of hormones and the search for signals that govern the dialog between the nuclear and the chromoplastic genome.


Molecular responses of human dermal fibroblasts to dual cues: contact guidance and mechanical load.
Fibroblast contraction in wound healing involves the interaction of several cell types, cytokines, and extracellular matrix molecules. We have previously developed fibroblast alignment models using precise uniaxial mechanical loads in 3D culture and using contact guidance on fibronectin strands. Our aim here was to use contact guidance to place fibroblasts in their potentially most sensitive configuration, i.e., perpendicular to the axis of loading, to present cells with conflicting guidance cues. Gene expression at the mRNA level of cells recovered from different zones of the 3D collagen gel (with distinct orientation) was determined by quantitative RT-PCR for the matrix proteases MMP1, 2, and 3, and inhibitors TIMP1 and 2. Our results show a 2-, 4-, and 3-fold increase in MMP1, 2, and 3, respectively, in the non-aligned strain zone, relative to the aligned strain zone. These results suggest that cells unable to align to applied loads remodel their matrix far more rapidly than orientated cells. Where fibroblasts were held in an alignment perpendicular to the applied load by contact guidance, the fall in MMP mRNA expression was largely abolished, indicating that these cells remained in a mechano-activated state. The protease inhibitors TIMP1 and 2 were poorly mechano-responsive, further suggesting that changes in MMP expression result in functional matrix remodelling. These results indicate how mechanical loading in tissues may influence matrix remodelling, particularly under conflicting guidance cues.


Insulin-like growth factor binding protein-1 and ovarian stimulation.
Serum concentrations of insulin-like growth factor binding protein-1 (IGFBP-1) were measured in 42 patients with tubal infertility undergoing two different regimens of ovarian stimulation for in-vitro fertilization. The first group comprised 24 women given a luteinizing hormone-releasing hormone agonist analogue (buserelin, LHRHa) on cycle days 1-4 followed by follicle-stimulating hormone and human menopausal gonadotrophin (LHRHa group). The second group of 18 women received clomiphene citrate and gonadotrophins (CC group). On the day of human chorionic gonadotrophin administration, the sum of follicular diameters (P less than 0.05) and the number of follicles punctured in the LHRHa group (P less than 0.01) were significantly higher than in the CC group. In spite of the greater number of follicles, the oestrogen levels were similar in both groups, but women in the LHRHa group had significantly higher serum IGFBP-1 concentrations during the last 5 days of stimulation. These results suggest that the stimulated preovulatory follicles may contribute to the elevation of serum IGFBP-1.


Factors affecting estimates of the prevalence of asthma and wheezing in childhood.
Nine recent studies of the prevalence of asthma and wheezing in childhood are reviewed. Sample prevalences are found to range from 5 to 31% and possible reasons for this are considered; it is shown that the prevalence of asthma found is highly dependent on the criteria used for diagnosis. Some clinical and research implications are discussed.


Cross-Sectional Area of the Median Nerve as a Prognostic Indicator in Carpal Tunnel Syndrome Treated With Local Steroid Injection.
Local steroid injection is an effective treatment modality for carpal tunnel syndrome. This study aimed to investigate the success rate of ultrasonography-guided local steroid injection and determine the prognostic value of the cross-sectional area (CSA) of the median nerve for steroid injection. We retrospectively evaluated 40 patients with carpal tunnel syndrome whose median nerve CSA was >15 mm2 (large-CSA group; n = 16) or ≤15 mm2 (small-CSA group; n = 24). The CSA was measured using ultrasonography, and all the patients were treated with ultrasonography-guided corticosteroid injection. Demographic characteristics, symptoms, initial QuickDASH score, Boston Carpal Tunnel Questionnaires, and results of the nerve conduction study were assessed at baseline. Treatment success was defined in this study as the absence of symptom recurrence within the entire follow-up period. The treatment success rate was 45% (n = 18) after an average follow-up of 16 months. Overall, 11 patients (28%) underwent carpal tunnel release on an average of 11 months after steroid injection. The large-CSA group showed a significantly worse grade of electrodiagnostic testing at baseline than did the small-CSA group; however, there was no significant difference in final Boston Carpal Tunnel Questionnaires symptom score (1.7 vs 1.8, respectively) and the rate of continued treatment success at the last follow-up (42% vs 50%, respectively). The proportions of patients who required carpal tunnel decompression were 29% and 25% in the small-CSA and large-CSA groups, respectively. Local steroid injection for carpal tunnel syndrome has an overall success rate of 45% after a mean follow-up of 16 months. Preinjection CSA was not associated with whether the steroid injection was considered successful. This indicates that increased median nerve CSA does not preclude the possibility of symptomatic relief after a local steroid injection. Therapeutic IV.


Peptides that regulate food intake: separable mechanisms for dorsal hindbrain CART peptide to inhibit gastric emptying and food intake.
We investigated whether dorsal hindbrain and/or peripheral cocaine- and amphetamine-regulated transcript peptide (CARTp) acts to suppress gastric emptying of a caloric stimulus. Furthermore, effects of dorsal hindbrain CARTp on sucrose consumption and licking microstructure was studied, as well as the possible contribution of corticotropin-releasing factor (CRF) receptors to mediate effects of CARTp downstream on emptying and sucrose intake. Rats bearing gastric fistulas received intragastric infusions (1.0 ml/min) of 12 ml 12.5% glucose. Gastric samples were withdrawn immediately after the intragastric infusion to reflect emptying during gastric fill. CARTp injected in the fourth ventricle intracerebroventricularly (0.5 and 1.0 microg) suppressed gastric emptying. CARTp reduced sucrose intake at similar doses and altered a variety of lick microstructure variables (no. of licks, bursts, clusters, licks/burst, licks/clusters, interlick interval, first meal size, and first meal duration). Pretreatment with the CRF antagonist alpha-helical CRF-(9-41) blocked the effect of 1.0 microg CARTp on gastric emptying but not on sucrose consumed or on any of the licking microstructure parameters. These data demonstrate differential mediation of the feeding and gastric inhibitory effects of CARTp and suggest that CARTp-induced inhibition of gastric emptying does not contribute to this peptide's ability to inhibit food intake.


Clinical value of left atrial appendage flow velocity for predicting of cardioversion success in patients with non-valvular atrial fibrillation.
Echocardiographic parameters for predicting cardioversion outcome in patients with non-valvular atrial fibrillation are not accurately defined. To evaluate the role of left atrial appendage flow velocity detected by transoesophageal echocardiography for prediction of cardioversion outcome in patients with non-valvular atrial fibrillation enrolled in a prospective. multicentre, international study. Four hundred and eight patients (257 males, mean age: 66 +/- 10 years) with non-valvular atrial fibrillation lasting more than 48 h but less than 1 year underwent transthoracic echocardiography and transoesophageal echocardiography before either electrical (n=324) or pharmacological (n=84) cardioversion. Cardioversion was successful in restoring sinus rhythm in 328 (80%) and unsuccessful in 80 patients (20%). Mean left atrial appendage peak emptying flow velocity was significantly higher in patients with successful than in those with unsuccessful cardioversion (32.4 +/- 17.7 vs 23.5 +/- 13.6 cm x s(-1); P<0.0001). At multivariate logistic regression analysis, three parameters proved to be independent predictors of cardioversion success: the atrial fibrillation duration <2 weeks (P=0.011, OR=4.9, CI 95%=1.9-12.7), the mean left atrial appendage flow velocity >31 cm x s(-1) (P=0.0013, OR=2.8, CI 95%=1.5-5.4) and the left atrial diameter <47 mm (P=0.093, OR=2.0, CI 95%=1.2-3.4). These independent predictors of cardioversion success outperformed other univariate predictors such as left ventricular end-diastolic diameter <58 mm, ejection fraction >56% and the absence of left atrial spontaneous echo contrast. In patients with non-valvular atrial fibrillation, measurement of the left atrial appendage flow velocity profile by transoesophageal echocardiography before cardioversion provides valuable information for prediction of cardioversion outcome.


A Curriculum for Perioperative Nurse Deployment During a Pandemic.
As the coronavirus disease 2019 (COVID-19) pandemic spread around the world, the US Surgeon General called for the cancellation of elective surgeries. At a large academic medical center in the Northeast, there was a resulting surplus of perioperative nurses who were deployed to inpatient units in need of skilled nursing care for a surge of COVID-19 patients. To prepare them for deployment to inpatient units, perioperative leaders developed a core curriculum to ensure that the OR nurses possessed the skills and knowledge required to successfully care for patients outside the OR with the same level of care and compassion that they provided to perioperative patients. The leaders employed available resources at the hospital to design and implement the course in a short amount of time. This article describes the development of a curriculum for OR nurses to manage a surging patient volume on inpatient units because of the COVID-19 pandemic.


CD36-mediated activation of endothelial cell apoptosis by an N-terminal recombinant fragment of thrombospondin-2 inhibits breast cancer growth and metastasis in vivo.
Thus far the clinical benefits seen in breast cancer patients treated with drugs targeting the vascular endothelial growth factor (VEGF) pathway are only modest. Consequently, additional antiangiogenic approaches for treatment of breast cancer need to be investigated. Thrombospondin-2 (TSP-2) has been shown to inhibit tumor growth and angiogenesis with a greater potency than the related molecule TSP-1. The systemic effects of TSP-2 on tumor metastasis and the underlying molecular mechanisms of the antiangiogenic activity of TSP-2 have remained poorly understood. We generated a recombinant fusion protein consisting of the N-terminal region of TSP-2 and the IgG-Fc1 fragment (N-TSP2-Fc) and could demonstrate that the antiangiogenic activity of N-TSP2-Fc is dependent on the CD36 receptor. We found that N-TSP2-Fc inhibited VEGF-induced tube formation of human dermal microvascular endothelial cells (HDMEC) on matrigel in vitro and that concurrent incubation of anti-CD36 antibody with N-TSP2-Fc resulted in tube formation that was comparable to untreated control. N-TSP2-Fc potently induced apoptosis of HDMEC in vitro in a CD36-dependent manner. Moreover, we could demonstrate a CD36 receptor-mediated loss of mitochondrial membrane potential and activation of caspase-3 in HDMEC in vitro. Daily intraperitoneal injections of N-TSP2-Fc resulted in a significant inhibition of the growth of human MDA-MB-435 and MDA-MB-231 tumor cells grown in the mammary gland of immunodeficient nude mice and in reduced tumor vascularization. Finally, increased serum concentrations of N-TSP2-Fc significantly inhibited regional metastasis to lymph nodes and distant metastasis to lung as shown by quantitative real-time alu PCR. These results identify N-TSP2-Fc as a potent systemic inhibitor of tumor metastasis and provide strong evidence for an important role of the CD36 receptor in mediating the antiangiogenic activity of TSP-2.


Pitfalls in the categorization of behaviour: a comparison of dolphin whistle classification methods.
The categorization of behaviour patterns into separate classes is crucial to the study of animal behaviour. Traditionally researchers have classified behaviour patterns through careful observation by eye. Recently this method has been increasingly replaced by computer methods. While the definition and fine scale analysis that can be achieved with computers is desirable, only a few studies have actually looked at how these methods perform in comparison with human observation. I compared the classification of bottlenose dolphin, Tursiops truncatus, whistles by human observers with the performance of three computer methods: (1) a method developed by McCowan (1995, Ethology, 100, 177-193); (2) a comparison of cross-correlation coefficients using hierarchical cluster analysis; and (3) a comparison of average difference in frequency along two whistle contours also using hierarchical cluster analysis. The whistle sample consisted of 104 randomly chosen whistles from a group of four captive bottlenose dolphins recorded both during periods when one was separate from the rest of the group and while they all swam in the same pool. The sample contained five individual-specific signature whistles and several nonsignature whistles. Five human observers, without knowledge of the recording context, were more likely than the computer methods to identify signature whistles that were used only while an animal was isolated from the rest of the group. I discuss the limitations of methods commonly used for pattern recognition in communication studies. The discrepancies between methods show how crucial it is to obtain an external validation of the behaviour classes used in studies of animal behaviour. Copyright 1999 The Association for the Study of Animal Behaviour.


[Plasticity of tissue stem cells].
In the early stages of embryonic development, cells have the capability of dividing indefinitely and then differentiating into any type of cell in the body. Recent studies have revealed that much of this remarkable developmental potential of stem cells is retained by small populations of cells within most tissues in the adult. Intercellular signals that control the proliferation, differentiation and survival of tissue stem cells in their niches are being identified and include a diverse array of morphogens, cytokines, chemokines and cell adhesion molecules. Adult tissue stem cells, moreover, can also differentiate into developmentally unrelated cell types, such as nerve stem cells into blood cells. Currently, we can only speculate about the mechanisms involved in such dramatic changes in cell fate. For example, the emergence of, say, hematopoietic stem cells from brain neurospheres could involve either transdifferentiation (brain-->blood) or dedifferentiation (brain-->pluripotent cells), or by the actions of rare, but residual pluripotent stem cells. This issue is central to understanding the molecular basis of commitment and lies at the heart of debates about plasticity and the reversibility of developmental restriction.


An Explorative Study of Common Themes of Patient Experiences With Migraine.
Objective: To explore important themes in patient experiences with migraine and to understand the relationship of these themes with external factors such as the health care system and societal influences. Methods: This qualitative study was part of a larger online survey (conducted for a period of 2 months from March 1, 2013, to April 30, 2013) that recruited participants with migraine through nonprobability-based sampling techniques. Respondents were asked an open-ended question to describe their experience with migraine. A codebook was developed based on existing literature and new categories that emerged from the responses. Deductive and inductive content analysis was conducted followed by axial coding of the themes based on the codebook. Results: The open-ended question resulted in 154 eligible responses. The final codebook contained 28 categories. The categories were combined into 6 distinct themes. The 6 themes included quality of life and health status, disease condition, societal response to disease, health care and medications, support, and patient response to disease. The most frequently occurring categories were pain and quality of life (QoL) (work functioning). The least frequent themes were cognitive symptoms, QoL economic functioning, and caregiver burden. Axial coding of the themes showed that QoL was the central theme. Aspects of the disease condition and negative societal responses were found to substantially affect QoL, leading to caregiver burden and absence/presence of social support. Conclusions: The findings demonstrate that pain and QoL are central to patient experience with migraine. Attention should be paid to improve the treatment and social support provided to patients and reduce stigma and invalidation.


Deep Learning on Oral Squamous Cell Carcinoma Ex Vivo Fluorescent Confocal Microscopy Data: A Feasibility Study.
Ex vivo fluorescent confocal microscopy (FCM) is a novel and effective method for a fast-automatized histological tissue examination. In contrast, conventional diagnostic methods are primarily based on the skills of the histopathologist. In this study, we investigated the potential of convolutional neural networks (CNNs) for automatized classification of oral squamous cell carcinoma via ex vivo FCM imaging for the first time. Tissue samples from 20 patients were collected, scanned with an ex vivo confocal microscope immediately after resection, and investigated histopathologically. A CNN architecture (MobileNet) was trained and tested for accuracy. The model achieved a sensitivity of 0.47 and specificity of 0.96 in the automated classification of cancerous tissue in our study. In this preliminary work, we trained a CNN model on a limited number of ex vivo FCM images and obtained promising results in the automated classification of cancerous tissue. Further studies using large sample sizes are warranted to introduce this technology into clinics.


From a Single Cell to a Whole Human Liver: Disease Modeling and Transplantation.
Although the underlying cause may vary across countries and demographic groups, liver disease is a major cause of morbidity and mortality globally. Orthotopic liver transplantation is the only definitive treatment for liver failure but is limited by the lack of donor livers. The development of drugs that prevent the progression of liver disease and the generation of alternative liver constructs for transplantation could help alleviate the burden of liver disease. Bioengineered livers containing human induced pluripotent stem cell (iPSC)-derived liver cells are being utilized to study liver disease and to identify and test potential therapeutics. Moreover, bioengineered livers containing pig hepatocytes and endothelial cells have been shown to function and survive after transplantation into pig models of liver failure, providing preclinical evidence toward future clinical applications. Finally, bioengineered livers containing human iPSC-derived liver cells have been shown to function and survive after transplantation in rodents but require considerable optimization and testing prior to clinical use. In conclusion, bioengineered livers have emerged as a suitable tool for modeling liver diseases and as a promising alternative graft for clinical transplantation. The integration of novel technologies and techniques for the assembly and analysis of bioengineered livers will undoubtedly expand future applications in basic research and clinical transplantation.


Effects of 2-(4-phenylpiperidino)cyclohexanol (AH5183) and barium ions on frog neuromuscular transmission.
1. By applying electrophysiological techniques such as frequency facilitation, tetanic run-down and depression, recovery from depression and post-tetanic potentiation (PTP) of the end-plate potential (EPP), the effects on frog neuromuscular transmission of 2-(4-phenylpiperidino)cyclohexanol (AH5183), a compound known to inhibit specifically the loading of newly synthesized acetylcholine (ACh) molecules into synaptic vesicles, and Ba2+, a selective activator of the augmentation phase of PTP, were investigated to elucidate whether these were related to ACh turnover. 2. Effects of AH5183 and Ba2+ ions were frequency dependent. At low frequency of stimulation, both agents showed essentially no effects on the EPPs recorded from Mg2+-blocked preparations. 3. AH5183 pivoted the log-linear frequency facilitation relation clockwise without altering the intercept on the ordinate, whereas Ba2+ ions did so counter-clockwise. As is the case with Ca2+ ions, Sr2+ ions shifted the relation upwards leaving its slope unaffected. 4. AH5183 selectively depressed the component of potentiation in PTP while the effect of Ba2+ ions was a specific increase in the augmentation phase of PTP. 5. Ba2+ ions increased the amplitude of EPPs in the late depressed phase during the tetanic run-down and depression experiment, but 4-aminopyridine and Ca2+ ions failed to do so. 6. AH5183 increased, Ba2+ ions reduced but Ca2+ ions did not change the constant of recovery from depression of the EPP measured on curarized preparations. 7. The present results suggested that mobilization of the ACh quanta readily available for release might be a common mechanism underlying both frequency facilitation and two components of PTP (augmentation and potentiation). The term 'frequency facilitation' would be more comprehensive if it were re-termed 'frequency augmentation' or 'frequency potentiation'.


Expression and purification of aspartate beta-semialdehyde dehydrogenase from infectious microorganisms.
l-Aspartate-beta-semialdehyde dehydrogenase (ASA DH) lies at the first branch point in the aspartate metabolic pathway that leads to the formation of the amino acids lysine, isoleucine, methionine, and threonine in most plants, bacteria, and fungi. Since the aspartate pathway is not found in humans, but is necessary for bacterial cell wall biosynthesis, the enzymes in this pathway are potential targets for the development of new antibiotics. The asd gene that encodes for ASA DH has been obtained from several infectious organisms and ligated into a pET expression vector. ASA DHs from Haemophilus influenza, Pseudomonas aeruginosa, and Vibrio cholerae were expressed as soluble proteins in Escherichia coli, while ASA DH from Helicobacter pylori was obtained primarily as inclusion bodies. The V. cholerae genome contains two asd genes. Both enzymes have been expressed and purified, and each displays significant ASA DH activity. The purification of highly active ASA DH from each of these organisms has been achieved for the first time, in greater than 95% purity and high overall yield. Kinetic parameters have been determined for each purified enzyme, and the values have been compared to those of E. coli ASA DH.


Recovery and brain reorganization after stroke in adult and aged rats.
Stroke is a prevalent and devastating disorder, and no treatment is currently available to restore lost neuronal function after stroke. One unique therapy that improves recovery after stroke is neutralization of the neurite inhibitory protein Nogo-A. Here, we show, in a clinically relevant model, improved functional recovery and brain reorganization in the aged and adult rat when delayed anti-Nogo-A therapy is given after ischemic injury. These results support the efficacy of Nogo-A neutralization as treatment for ischemic stroke, even in the aged animal and after a 1-week delay, and implicate neuronal plasticity from unlesioned areas of the central nervous system as a mechanism for recovery.


Development of specific radiopharmaceuticals for infection imaging by targeting infectious micro-organisms.
Infectious diseases remain a major health problem and cause of death worldwide. A variety of radiopharmaceuticals are used for the imaging of infections and inflammation in the practice of nuclear medicine. Long-term clinical use has shown that the majority of radiolabeled probes cannot distinguish between inflammation and infection. Gallium-67-citrate binds to bacteria, but also to proteins accumulating at both sterile inflammation and bacterial infection sites. Other agents are used to interact with receptors or domains on circulating and infiltrating leukocytes or to label them directly. However, these probes cannot distinguish between infection and inflammation because they are not specific to infectious micro-organisms. This review examines the recent developments and applications of radiolabeled specific agents, such as antiviral drugs, antifungal, antibiotics and antimicrobial peptides, to visualize infectious foci by targeting viruses, fungi or bacteria.


Growth hormone treatment for burned children.
Several growth hormones show promise in the treatment of burn injuries, particularly for paediatric patients. Animal studies and clinical trials indicate that growth hormones help modulate the devastating effects of the hypermetabolic response to burn injury and improve wound healing. Recombinant human growth hormone (rhGH) has been shown to reduce loss of body weight, stimulate protein synthesis, increase epithelial cell proliferation, and accelerate wound healing. Accelerated wound closure reduces the risk of infection, shortens hospital stay, and lowers overall medical costs. Current investigations are in progress to determine the effects of rhGH on anabolic growth arrests experienced by paediatric burn survivors.


Demonstration of ligand decoration, and ligand-induced perturbation, of G-quadruplexes in a plasmid using atomic force microscopy.
G-Quadruplexes are nucleic acid secondary structures consisting of a planar arrangement of four guanine residues. Potential G-quadruplex-forming sequences are widely distributed throughout the genome. Significantly, they are present in telomeres and are enriched in gene promoters and first introns, raising the possibility that perturbation of G-quadruplex stability might have therapeutic potential, for example in the treatment of cancer. Ligands that interact selectively with G-quadruplexes include both proteins and small molecules, although the interactions between ligands and their G-quadruplex targets have been monitored using indirect methods. In addition, the G-quadruplex targets have often been short DNA fragments. Here, we have used atomic force microscopy imaging to examine directly at the single-molecule level the interaction of ligands with G-quadruplexes generated during transcription of a plasmid containing a G-rich insert. We show that the structures produced during transcription are decorated specifically by the single-chain antibody HF1 and by the nuclear protein PARP-1, both of which are known to recognize G-quadruplexes. Our results provide clear structural evidence of G-quadruplex formation in a transcription-dependent case and demonstrate directly how small-molecule stabilizers and destabilizers can manipulate these structures in a biochemically functional system.


Temporal stability of receptiveness to clinical research on Alzheimer disease.
Research advance directives are a proposed mechanism for ensuring that decisions with regard to research participation adhere to preferences voiced by persons with Alzheimer disease (AD) before losing decisional capacity. Although this approach rests on the assumption that preferences with regard to research participation are consistent over time, little is known about the stability of such preferences. The purpose of this study was to evaluate the temporal stability of older adults' receptiveness to participation in clinical trials, neuroimaging studies, and psychosocial investigations on AD. One hundred and four participants in the University of Pittsburgh Alzheimer Disease Research Center were annually surveyed with regard to their willingness to be contacted with regard to clinical drug trials, neuroimaging studies, and psychosocial research for which they might be eligible. Receptiveness to contact with regard to AD research was compared at 2 time points, 1 year apart. At baseline, most respondents were willing to be contacted with regard to their eligibility for drug trials, imaging studies, and psychosocial research. Thirty-seven percent of respondents voiced a different set of preferences at year 2 as compared with year 1. Differences included both increased and decreased willingness to be contacted. Neither stability of preferences nor direction of change (more vs. less willing) varied by diagnostic group. Bivariate analyses revealed that participation in at least 1 ancillary research study was associated with an overall increase in willingness to be contacted. We conclude that a significant proportion of research-friendly individuals voice different sets of preferences with regard to the possibility of research participation when queried at different points in time. Amenability to participating in clinical research on AD is a relatively dynamic personal attribute that may be influenced by personal experience with research participation. This finding has relevance for the policy debate around research advance directives, an approach which assumes that preferences with regard to research participation are consistent over time.


Inclusion of phone use while driving data in predicting distraction-affected crashes.
Given the tremendous number of lives lost or injured, distracted driving is an important safety area to study. With the widespread use of cellphones, phone use while driving has become the most common distracted driving behavior. Although researchers have developed safety performance functions (SPFs) for various crash types, SPFs for distraction-affected crashes are rarely studied in the literature. One possible reason is the lack of critical distracted behavior information in the commonly used safety data (i.e., roadway inventory, traffic, and crash counts). Recently, the frequency of phone use while driving (referred to as phone use data) is recorded by mobile application companies and has become available to safety researchers. The primary objective of this study is to examine if phone use data can potentially predict distracted-affected crashes. The authors first integrated phone use data with roadway inventory, traffic, and crash data in Texas. Then, the Random Forest (RF) algorithm was applied to assess the significance of the feature - phone use while driving - for predicting the number of distraction-affected crashes on a road segment. Further, this study developed two SPFs for distraction-affected crashes with and without the phone use data, separately. Both SPFs were assessed in terms of model fitting and prediction performances. RF results rank the frequency of phone use as an important factor contributing to the number of distraction-affected crashes. Performance evaluations indicated that the inclusion of phone use data in the SPFs consistently improved both fitting and prediction abilities to predict distracted-affected crashes. Practical Applications: The phone use data provide new insights into the safety analyses of distraction-affected crashes, which cannot be achieved by only using the conventional roadway inventory and crash data. Therefore, safety researchers and practitioners are encouraged to incorporate the emerging data sources in reducing distraction-affected crashes.


Mechanism of dexamethasone 21-mesylate antiglucocorticoid action: II. Receptor-antiglucocorticoid complexes do not interact productively with mouse mammary tumor virus long terminal repeat chromatin.
We have studied the interaction of covalent dexamethasone 21-mesylate (DM) labeled, activated glucocorticoid receptor with mouse mammary tumor virus (MMTV) chromatin. Studies were performed on a murine cell line (904.13) which contains 200 copies per cell of a MMTV long terminal repeat (LTR) v-rasH casette mobilized on bovine papilloma virus based episomes. DM binds covalently to glucocorticoid receptors and displays almost full antagonist activity in this cell line. In situ transcription extension assays indicate that activated receptor-DM complex cannot stimulate LTR-initiated transcription. The receptor-DM complex also fails to induce DNase I hypersensitivity (HSR) and transcription factor loading at the MMTV promoter. Transcription activation, HSR formation, and factor binding induced with the agonist dexamethasone are blocked by covalent occupation of the receptor by DM. Although DM-activated receptor binds specifically to receptor sites on purified LTR DNA, the antagonist receptor complex does not interact productively with MMTV LTR chromatin in vivo.


Almond Consumption during Energy Restriction Lowers Truncal Fat and Blood Pressure in Compliant Overweight or Obese Adults.
The inclusion of almonds in an energy-restricted diet has been reported both to enhance or to have no effect on weight loss. Their effects specifically on visceral body fat stores during energy restriction have not been widely examined. In addition, almond consumption has been associated with reduced blood pressure (BP), but whether this is linked to or independent of changes in body composition has to our knowledge not been examined. We evaluated the effects of consuming almonds as part of an energy-restricted diet on body composition, specifically visceral adipose tissue (VAT) and BP, compared to a nut-free energy-restricted diet. A randomized controlled 12-wk clinical trial of 86 healthy adults [body mass index (in kg/m2): 25-40] was conducted. Participants were randomly assigned to 1 of 2 energy-restricted (500-kcal deficit/d) diets: an almond-enriched diet (AED) (15% energy from almonds) or a nut-free diet (NFD). A linear mixed-model analysis on primary outcomes such as body weight, body fat, VAT, and BP was performed on all participants [intention-to-treat (ITT) analysis] and compliant participants (complier analysis). Body weight, truncal and total fat percentage, VAT, and systolic BP decreased after 12 wk of energy restriction in both the ITT and complier analyses (P < 0.05). The complier analysis (but not the ITT analysis) indicated a greater mean ± SEM reduction in truncal fat (AED: -1.21% ± 0.26%; NFD: -0.48% ± 0.24%; P = 0.025), total fat (AED: -1.79% ± 0.36%; NFD: -0.74% ± 0.33%; P = 0.035), and diastolic BP (AED: -2.71 ± 1.2 mm Hg; NFD: 0.815 ± 1.1 mm Hg; P = 0.029), and a greater tendency for VAT loss (AED: -8.19 ± 1.8 cm2; NFD: -3.99 ± 1.7 cm2; P = 0.09) over time in the AED group than the NFD group. Moderate almond consumption by compliant overweight and obese individuals during energy restriction results in greater proportional reductions of truncal and total body fat as well as diastolic BP and hence may help to reduce metabolic disease risk in obesity. This trial was registered at clinicaltrials.gov as NCT02360787.


Representations in learning new faces: evidence from prosopagnosia.
We report the performance of a prosopagnosic patient on face learning tasks under different encoding instructions (i.e., levels of processing manipulations). R.J. performs at chance when given no encoding instructions or when given "shallow" encoding instruction to focus on facial features. By contrast, he performs relatively well with "deep" encoding instructions to rate faces in terms of personality traits or when provided with semantic and name information during the study phase. We propose that the improvement associated with deep encoding instructions may be related to the establishment of distinct visually derived and identity-specific semantic codes. The benefit associated with deep encoding in R.J., however, was found to be restricted to the specific view of the face presented at study and did not generalize to other views of the same face. These observations suggest that deep encoding instructions may enhance memory for concrete or pictorial representations of faces in patients with prosopagnosia, but that these patients cannot compensate for the inability to construct abstract structural codes that normally allow faces to be recognized from different orientations. We postulate further that R.J.'s poor performance on face learning tasks may be attributable to excessive reliance on a feature-based left hemisphere face processing system that operates primarily on view-specific representations.


Bone sialoprotein and osteopontin distribution at the osteocartilaginous interface.
In situ hybridization and ultrastructural immunohistochemistry were used to study the synthesis and distribution of 2 bone matrix proteins, bone sialoprotein and osteopontin, in the proximal tibial epiphysis in 21-, 32-, and 84-day-old rats. Bone sialoprotein messenger ribonucleic acid expression was restricted to cells close to the osteocartilaginous interfaces, whereas osteopontin messenger ribonucleic acid was shown also in the central epiphysis. Moreover, bone sialoprotein synthesis decreased with age, while osteopontin synthesis remained unchanged. Bone sialoprotein and osteopontin immunolabeling were concentrated to a 1-micron thick zone at the border between mineralized articular cartilage and subchondral bone. Compared with the youngest animals, total bone sialoprotein immunolabeling increased in the 32-day-old group, but did not increase further in the oldest group. In contrast, osteopontin immunolabeling increased only in the oldest rats with a decelerating rate of growth. The accumulation and localization of osteopontin at osteocartilaginous interfaces differ from previous observations in metaphyseal bone where osteopontin has been found at the mineralization front of the osteoid, possibly reflecting different roles in the mineralization process in the 2 regions. The different pattern of synthesis of the 2 proteins in the epiphysis corroborates previous indications of different biological roles.


Tarsal navicular position after complete soft-tissue clubfoot release.
The navicular position was evaluated (according to Simons' criteria) on anteroposterior and lateral roentgenograms of 45 clubfeet that were treated with complete soft-tissue release without internal fixation. The evaluation was performed an average of 28 months after surgery. Position of the navicular correlates well with the functional rating score system. Navicular position can be viewed as an indicator for clubfoot correction. Internal fixation of the talonavicular joint was correlated with favorable correction of deformity.


PhenoDB: an integrated client/server database for linkage and population genetics.
In this paper we describe PhenoDB, an Internet-accessible client/server database application for population and linkage genetics. PhenoDB stores genetic marker data on pedigrees and populations. A database for population and linkage genetics requires two core functions: data management tasks, such as interactive validation during data entry and editing, and data analysis tasks, such as generating summary population statistics and performing linkage analyses. In PhenoDB we attempt to make these tasks as easy as possible. The client/server architecture allows efficient management and manipulation of large datasets via an easy-to-use graphical interface. PhenoDB data (73 populations, 34 pedigrees, approximately 4200 individuals, and close to 80,000 typings) are stored in a generic format that can be readily exported to (or imported from) the file formats required by various existing analysis programs such as LIPED and Lathrop and Lalouel's Multipoint Linkage. PhenoDB allows performance of complex ad-hoc queries and can generate reports for use in project management. Finally, PhenoDB can produce statistical summaries such as allele frequencies, phenotype frequencies, and Chi-square tests of Hardy-Weinberg ratios of population/pedigree data.


MR Enterography of Complicated Crohn Disease: Stricturing and Penetrating Disease.
Stricturing and penetrating disease are complications of Crohn disease (CD) that significantly affect patient outcomes. Careful evaluation for such complications is critical to the interpretation of magnetic resonance enterography. This manuscript outlines the key findings related to stricturing and penetrating CD and discusses current understanding of the pathophysiology and prognosis of complicated CD based on the literature.


EEG, quantitative EEG, BAEP and ERP in centenarians.
In 11 healthy centenarians, the principal EEG and qEEG abnormalities were background frequency slower and power lower than in younger adults. The frequency and amplitude of anterior and posterior head regions on the EEG showed no difference, but qEEG demonstrated that posterior was higher than anterior. In 5 of 11 persons the frequencies of the temporal lobe were asymmetric. BAEP and ERP were measured in 6 persons. The latencies of I, III waves of BAEP were prolonged in only 1 subject. The latencies of exogenous components (P80, N100) of ERP were in the normal range. The latencies of endogenous components (N200, P300) of these 6 persons were prolonged, but in 1 person the N200 was normal and in 2 the P300 was normal.


Complications of surgery for nasal polyposis and chronic rhinosinusitis: the results of a national audit in England and Wales.
The objective of this study was to determine the rate of complications of surgery for nasal polyposis and chronic rhinosinusitis as well as their risk factors. STUDY DESIGN, SETTING, PARTICIPANTS, AND OUTCOME MEASURES: The authors conducted a prospective study of 3,128 patients who underwent sinonasal surgery during 2000 and 2001 in 87 National Health Service hospitals in England and Wales. Patients completed a preoperative questionnaire that included the Sino-Nasal Outcome Test, a measure of sinonasal symptoms severity and health-related quality of life. Surgeons provided information about polyp extent, opacity of the sinuses on computed tomography (Lund-Mackay score), comorbidity (American Society of Anesthesiologists score), and the occurrence of perioperative complications. Major complications (orbital or intracranial complications, bleeding requiring ligation or orbital decompression, or return to the operating room) occurred in 11 patients (0.4%). Minor complications (all other untoward events) occurred in 207 patients (6.6%). Most frequently reported minor complications were excessive perioperative hemorrhage bleeding (5.0%) as well as postoperative hemorrhage requiring treatment (0.8%). Multivariate analysis indicated that the complication rate was linked to the extent of disease measured in terms of symptom severity and health-related quality of life, the extent of polyposis, level of opacity of the sinuses on computed tomography, and the presence of comorbidity, but not surgical characteristics (extent of surgery, use of endoscope or microdebrider, grade of surgeon, and adjunctive turbinate surgery). The risk of complications depended on patient characteristics rather than on the surgical technique used. Measures of the extent of disease and comorbidity may help in identifying patients at high risk of complications.


Job strain among rubber-glove-factory workers in central Thailand.
Job strain has become a major concern because of its potential impacts on worker well-being and performance. This cross-sectional study aimed to assess the prevalence of, and examine factors associated with, job strain among workers in a rubber-glove factory, in a central province of Thailand. A total of 200 workers aged 18-55 yr, who had worked at the factory for at least 6 months, completed the Job Content Questionnaire (JCQ) (Thai Version). Two of 5 scales in the JCQ were used to measure job strain, i.e.; job control and psychological job demand. The prevalence of job strain was 27.5%. Multiple logistic regression analysis indicated two variables significantly associated with job strain: low supervisor social support (adjusted OR=3.08; 95%CI: 1.38-6.91) and high job insecurity (adjusted OR=2.25; 95%CI: 1.04-4.88). Effective training for supervisors, to create good relationships among workers and supervisors, and ensuring steady and secure jobs for good employees, are necessary.


Transport in rough self-affine fractures.
Transport properties of three-dimensional self-affine rough fractures are studied by means of an effective-medium analysis and numerical simulations using the Lattice-Boltzmann method. The numerical results show that the effective-medium approximation predicts the right scaling behavior of the permeability and of the velocity fluctuations, in terms of the aperture of the fracture, the roughness exponent, and the characteristic length of the fracture surfaces, in the limit of small separation between surfaces. The permeability of the fractures is also investigated as a function of the normal and lateral relative displacements between surfaces, and it is shown that it can be bounded by the permeability of two-dimensional fractures. The development of channel-like structures in the velocity field is also numerically investigated for different relative displacements between surfaces. Finally, the dispersion of tracer particles in the velocity field of the fractures is investigated by analytic and numerical methods. The asymptotic dominant role of the geometric dispersion, due to velocity fluctuations and their spatial correlations, is shown in the limit of very small separation between fracture surfaces.


Triple valve replacement in a patient with severe carcinoid heart disease.
We report on the case of a 34-year-old male patient suffering from end-stage carcinoid heart disease with severe tricuspid, pulmonary and mitral valve regurgitation. In addition, a persisting foramen ovale was present. The primary carcinoid tumor was never discovered. However, urine 5-hydroxy-indole-acetic-acid (5-HIAA) were consistently elevated after the first diagnosis of carcinoid disease and after eight years of medication with Octreotide and Interferon alpha-2b our patient developed significant cardiac insufficiency mainly due to severe valvular dysfunction. Ultimately, mechanical tricuspid, mitral and pulmonary valve replacement was performed. Twelve hours following the operation the patient had to be returned to the operating room for persisting intrathoracic hemorrhage. He recovered uneventfully and was discharged from hospital on day 37. Twelve months following triple valve replacement the cardiac status recovered from preoperative NYHA-IV to NYHA-I.


Treatment by long haemodialysis sessions with high cut-off filters in myeloma cast nephropathy: our experience.
Multiple myeloma (MM) is the uncontrolled proliferation of plasma cells with variable amounts of production of immunoglobulins or their chains. Acute renal failure can be a symptom of MM, and it is sometimes its form of presentation. Circulating free light chains (FLC) could lead to renal failure due to their intratubular precipitation, causing a cast nephropathy. The treatment of myeloma, adequate hydration and the removal of FLC by apheresis techniques are currently the treatments that are accepted for this disease. Several apheresis techniques have been attempted for the removal of FLC, with long haemodialysis sessions with filters for the removal of these light chains (high cut-off filters) being proposed as the most effective treatment for myeloma nephropathy. We report 5 cases of myeloma nephropathy: three had cast nephropathy (CN) diagnosed by renal biopsy and the other two had a high probability of CN (FLC levels >500 mg/l). They were treated with long haemodialysis sessions with a high cut-off membrane. All patients had suffered acute renal failure; four required renal replacement therapy and one patient had advanced renal failure. In all patients, FLC levels were very high. They received specific treatment for myeloma in addition to high cut-off haemodialysis until they achieved FLC levels of <500 mg/l. Four of the five patients recovered renal function, and became independent of dialysis. The progression time for myeloma from the time the first symptoms appeared varied (1-6 months). The number of treatment sessions ranged from 8-16. The patient with the longest progression time required more sessions and did not recover renal function. Long haemodialysis sessions with high cut-off filters in addition to specific myeloma chemotherapy seems to be an effective treatment for acute renal failure due to myeloma nephropathy. The early initiation of treatment could be a determining factor for the response.


Hospital response to a case-based payment scheme under regional global budget: The case of Guangzhou in China.
Both developed and developing countries have been searching for effective provider payment methods to control health expenditure inflation. In January 2018, Guangzhou city in Southern China initiated an innovative case-based payment method for inpatient care under the framework of the regional global budget, called the Diagnosis-Intervention Packet (DIP). Contrary to the usual practice of the case-based payment, the DIP payment scheme includes a price adjustment mechanism through which the actual reimbursement for each case is determined ex post. By employing the difference-in-difference method and data from Beijing and Guangzhou, we evaluate the effects of the DIP payment on medical expenditures and provider behaviors. We find that total health expenditures per case have decreased by 3.5%, which is mainly driven by a substantial decrease in drug expenditures. It suggests that the DIP payment reform achieved a short-term success in slowing down the growth of health expenditures. However, the average point volume per case for local inpatients with social health insurance coverage has increased by more than 3%, primarily due to an increasing likelihood of performing at least one procedure. We also find suggestive evidence of up-coding. All these results suggest that healthcare providers have taken strategic behaviors in response to the DIP payment. These findings hold lessons for the ongoing payment reforms in China and other countries.


Constitutive Model Parameter Identification Based on Optimization Method and Formability Analysis for Ti6Al4V Alloy.
Titanium alloy is widely applied in aerospace, medical, shipping and other fields due to its high specific strength and low density. The purpose of this study was to analyze the formability of Ti6Al4V alloys at elevated temperatures. An accurate constitutive model is the basic condition for accurately simulating the plastic forming of materials, and it is an important basis for optimizing the parameters of the hot forging forming process. In this study, the optimization algorithm was used to accurately identify the high-temperature constitutive model parameters of Ti6Al4V titanium alloy, and the hot working diagram was established to optimize the hot forming process parameters. The optimal forming conditions of Ti6Al4V titanium alloy are given. Ti6Al4V alloy was subjected to high-temperature compression tests at 800-1000 °C and at strain rates of 0.01-5 s-1 on a Gleeble-1500D thermal/mechanical simulation machine. Each parameter of the Hansel-Spittel constitutive model was taken as an independent variable, and the accumulated error between the stress calculated by the constitutive model and the stress obtained by experimentation was used as an objective function. Based on response surface methodology, an inverse optimization method for identifying the parameters of the high-temperature constitutive model of Ti6Al4V alloy is proposed in this paper. An orthogonal test design was adopted to obtain sample point data, and a third-order response surface approximate model was established. The genetic algorithm (GA) was applied to reversely optimize the parameters of the constitutive model. To verify the accuracy of the optimized constitutive model, the average absolute relative error (AARE) and correlation coefficient (R) were used to evaluate the reliability of optimized constitutive model. The R value of the model was 0.999, and the AARE value was 0.048, respectively, indicating that the established high-temperature constitutive model for Ti6Al4V alloy has good calculation accuracy. The flow stress behavior of the material could be accurately delineated. Meanwhile, in order to study the formability of Ti6Al4V alloy, the hot processing map of the alloy, based on a dynamic material model, was established in this paper. The optimum hot working domains of the Ti6Al4V alloy were determined within 840-920 °C/0.01-0.049 s-1 and 940-980 °C/0.11-1.65 s-1; the hot processing map was verified in combination with the microstructure, and the fine and equiaxed grains and a large amount of β phase could be found at 850 °C/0.01 s-1.


A Motion and Illumination Resistant Non-Contact Method Using Undercomplete Independent Component Analysis and Levenberg-Marquardt Algorithm.
Heart Rate (HR) estimation is of utmost importance due to its applicability in diverse fields. Conventional methods for HR estimation require skin contact and are not suitable in certain scenarios such as sensitive skin or prolonged unobtrusive HR monitoring. Therefore remote photoplethysmography (rPPG) methods have become an active area of research. These methods utilize the facial videos acquired using a camera followed by extracting the Blood Volume Pulse (BVP) signal for heart rate calculation. The existing rPPG methods either utilized a single color channel or weighted color differences, which has certain limitations dealing with motion and illumination artifacts. This study considered BVP extraction as an undercomplete problem and proposed a method resistant to motion and illumination variation artifacts. This method is based on an undercomplete independent component analysis, aiming to estimate the unmixing matrix using a non-linear Cumulative Density Function (CDF) that has been optimized using the customized Levenberg-Marquardt algorithm. Therefore, the method is named U-LMA. The proposed method was tested under three scenarios: constrained, motion, and illumination variations scenarios. High Pearson correlation coefficient values and smaller lower-upper statistical limits of Bland-Altman plots justified the outstanding performance of the proposed U-LMA. Furthermore, its comparative analysis with the state-of-the-art methods demonstrated its efficacy and reliability, which was proven by the lowest error and highest correlation values (0.01 significance level). Additionally, higher accuracy satisfying the clinically accepted error differences also justified its clinical relevance.


Periodontal wound healing/regeneration of two-wall intrabony defects following reconstructive surgery with cross-linked hyaluronic acid-gel with or without a collagen matrix: a preclinical study in dogs.
In-vitro data have shown that cross-linked hyaluronic acid (HA) enhances the proliferative and migratory properties of cells involved in periodontal wound healing/regeneration, stabilizes the blood clot, reduces the inflammatory response, and facilitates angiogenesis. The aim of this study was to histologically evaluate the effects of cross-linked HA alone or combined with a collagen matrix (CM) on the periodontal wound healing/regeneration in intrabony defects. Two-wall intrabony defects (5 mm wide, 5 mm deep) were surgically created at the distal and mesial aspects of mandibular premolars in six beagle dogs. The 24 defects were randomly treated as follows: open flap debridement (OFD) + HA, OFD + CM, OFD + HA + CM (HA/CM), and OFD alone (control). At 2 months, the animals were euthanized for histologic evaluation. The HA (2.43 ± 1.25 mm) and HA/CM (2.60 ± 0.99 mm) groups yielded statistically significantly (P < .05) greater formation of new attachment (ie, linear length of new cementum adjacent to newly formed bone, with inserting collagen fibers) compared with the OFD (0.55 ± 0.99 mm) group. Among the four treatment groups, the HA/CM group demonstrated the highest amount of regenerated tissues, although no statistically significant differences in any of the histometric parameters were observed between the HA and HA/CM groups. Within their limits, it can be concluded that cross-linked HA alone or combined with CM promotes periodontal wound healing/regeneration in two-wall intrabony defects in dogs.


Novel antibiotic combinations against infections with almost completely resistant Pseudomonas aeruginosa and Acinetobacter species.
For infections with antibiotic-susceptible strains of Pseudomonas aeruginosa, most studies have suggested that combination therapy, usually with a beta -lactam antibiotic plus an aminoglycoside, is preferable for patients with bacteremia and neutropenia. Against infections with Pseudomonas aeruginosa or Acinetobacter baumannii isolates that are resistant to all antibiotics except the polymyxins, several novel antibiotic combinations demonstrate increased activity in vitro compared with that of any single agent. Whether these combinations yield outcomes that are improved over those seen with a polymyxin or other agent alone remains to be determined. However, against infections with species resistant to all antibiotics, including polymyxins, novel combinations are the only remaining therapeutic option.


Nd:YAG laser-assisted angioplasty in femoropopliteal artery occlusions: "hot" versus "cold" recanalization with transparent contact probe.
Percutaneous recanalization of femoropopliteal artery occlusions (1-21 cm; median, 8 cm) was attempted in 50 patients. A 2.2-mm-diameter contact probe catheter connected to a continuous-wave neodymium yttrium aluminum garnet (Nd:YAG) laser was used. The laser was activated (15 W, 1-second pulses) only if too much resistance was met. Balloon angioplasty was performed after successful traversal of the occlusion. Primary success was achieved in 40 of 50 patients (80%). In 20 cases, recanalization was achieved mechanically (cold group). In the other 20 cases, recanalization was achieved with the help of laser irradiation (hot group: 15-405 J; median, 90 J). Except for the length of the obstruction (longer in the cold group), the two groups did not differ in baseline characteristics. Neither the length of the occlusion nor the duration of symptoms correlated with failure or success or with the delivered laser energy. Cold and hot groups did not differ with regard to functional improvement and angiographic patency at 3 and 12 months (94% +/- 4). Thus, brief laser activation doubled the cold primary success rate, but the major action of the laser contact probe is mechanical remodeling of the obstruction.


Europe without internal frontiers and international migration.
"This paper documents the process by which the freedom of movement of workers has been established in the European Community and uses data on migrant flows and stocks to assess whether such freedom of movement has had a significant effect in increasing intra-Community migration. Although the evidence suggests that the presence of Community workers increased in newly admitted Community member States, such as the United Kingdom during the 1970s and, more recently, Greece, Portugal and Spain, the numbers involved are small in relative terms. In contrast, the enactment of freedom of movement provisions has not contributed to a noticeable increase in the outflow of workers from the poorer to the richer member States."


Phagocytosis of Staphylococcus aureus by macrophages exerts cytoprotective effects manifested by the upregulation of antiapoptotic factors.
It is becoming increasingly apparent that Staphylococcus aureus are able to survive engulfment by macrophages, and that the intracellular environment of these host cells, which is essential to innate host defenses against invading microorganisms, may in fact provide a refuge for staphylococcal survival and dissemination. Based on this, we postulated that S. aureus might induce cytoprotective mechanisms by changing gene expression profiles inside macrophages similar to obligate intracellular pathogens, such as Mycobacterium tuberculosis. To validate our hypothesis we first ascertained whether S. aureus infection could affect programmed cell death in human (hMDMs) and mouse (RAW 264.7) macrophages and, specifically, protect these cells against apoptosis. Our findings indicate that S. aureus-infected macrophages are more resistant to staurosporine-induced cell death than control cells, an effect partly mediated via the inhibition of cytochrome c release from mitochondria. Furthermore, transcriptome analysis of human monocyte-derived macrophages during S. aureus infection revealed a significant increase in the expression of antiapoptotic genes. This was confirmed by quantitative RT-PCR analysis of selected genes involved in mitochondria-dependent cell death, clearly showing overexpression of BCL2 and MCL1. Cumulatively, the results of our experiments argue that S. aureus is able to induce a cytoprotective effect in macrophages derived from different mammal species, which can prevent host cell elimination, and thus allow intracellular bacterial survival. Ultimately, it is our contention that this process may contribute to the systemic dissemination of S. aureus infection.


Viral Interference between Respiratory Viruses.
Multiple respiratory viruses can concurrently or sequentially infect the respiratory tract and lead to virus‒virus interactions. Infection by a first virus could enhance or reduce infection and replication of a second virus, resulting in positive (additive or synergistic) or negative (antagonistic) interaction. The concept of viral interference has been demonstrated at the cellular, host, and population levels. The mechanisms involved in viral interference have been evaluated in differentiated airway epithelial cells and in animal models susceptible to the respiratory viruses of interest. A likely mechanism is the interferon response that could confer a temporary nonspecific immunity to the host. During the coronavirus disease pandemic, nonpharmacologic interventions have prevented the circulation of most respiratory viruses. Once the sanitary restrictions are lifted, circulation of seasonal respiratory viruses is expected to resume and will offer the opportunity to study their interactions, notably with severe acute respiratory syndrome coronavirus 2.


Gait Improvements After Peroneal or Tibial Nerve Transfer in Patients with Foot Drop: A Retrospective Study.
Background: Injury to the common peroneal nerve disrupts the motor control pathway to ankle dorsiflexors and evertors, as well as toe extensors, resulting in pathological gait and foot drop. Direct external compression on the fibular head is the most frequent cause of peroneal nerve impairment and has poor prognosis. Methods and Patients: Here, we report the surgical outcome of 21 patients with foot drop (9 males and 12 females) who underwent nerve transfer procedure of either the superficial peroneal nerve or the tibial nerve fascicles to the motor branch of the tibialis anterior and to the deep peroneal nerve. They had at least 6 months postoperative follow-up (mean = 17; range, 6-32 months). Results: Among 21 patients who had no ankle dorsiflexion (BMRC 0/5) preoperatively, 9 patients had successful restoration of ankle dorsiflexion (BMRC 4 to 4+/5), 7 patients had BMRC 2 to 3+/5, and 4 patients had no or poor restoration of dorsiflexion (BMRC 0 to 1+/5) but achieved good ankle eversion (BMRC 3 to 4+/5). Overall statistically significant clinical improvement of ankle dorsiflexion and eversion from preoperative BMRC grade 2.6 ± 0.5 to postoperative BMRC grade 3.6 ± 0.7 (P = .0000004) was achieved. Conclusion: Overall statistically significant clinical improvement of ankle dorsiflexion and eversion was achieved in 80% of our study patients. Most of these patients gained antigravity and were able to walk with minimal steppage gait. In the other 4 patients (20%), there was good improvement in ankle eversion but poor or no ankle dorsiflexion.


Do hospitals have a higher mortality rate on weekend admissions? An observational study to analyse weekend effect on urgent admissions to hospitals in Catalonia.
'Weekend effect' is a term used to describe the increased mortality associated with weekend emergency admissions to hospital, in contrast with admission on weekdays. The objective of the present study is to determine whether the weekend effect is present in hospitals in Catalonia. We analysed all urgent admissions in Catalonia in 2018, for a group of pathologies. Two groups were defined (those admitted on a weekday and those admitted on a weekend). We obtained mortality at 3, 7, 15 and 30 days, and applied a proportions test to both groups. Additionally, we used Cox's regression for mortality at 30 days, using the admission on a weekend as the exposition, adjusting by socioeconomic and clinical variables. We used the hospital discharge database and the Central Registry of the Insured Population. 72 427 admissions for the selected pathologies during 2018 were found. No statistically significant differences in mortality at 30 days (p=0.524) or at 15 days (p=0.119) according to the day of admission were observed. However, significant differences were found in mortality at 7 days (p=0.025) and at 3 days (p=0.002). The hazard rate associated with the weekend was 1.13 (95% CI: 1.04 to 1.23). By contrast, the adjusted HR of the weekend interaction with time was 0.99 (95% CI: 0.99 to 1.00). There is a weekend effect, but it is not constant in time. This could suggest the existence of dysfunctions in the quality of care during the weekend.