Comparison of the polyoma virus early and late promoters by transcription in vitro.
Polyoma virus DNA was transcribed in the HeLa whole cell extract in vitro system (1). Early region transcripts with the same 5'-ends as in vivo mRNAs, located 31 +/- 2bp from 'TATA'-boxes, were synthesized by RNA polymerase II. Sequences sufficient for efficient expression of the early promoter were present in a substitution mutant lacking viral DNA from a position 55bp before the principal cap sites. Late region transcripts were synthesised inefficiently. Only one (at nt5129 +/- 2) of the many late mRNA cap sites functioned as an in vitro initiation point. This was the one 5'-end located 31 +/- 2bp from a sequence resembling the 'TATA' consensus. The proportion of late to early region RNA polymerase II transcripts decreased dramatically at suboptimal template concentrations. An hypothesis to explain the regulation of late gene expression in vivo based on these results is proposed. A linear templates were transcribed only by RNA polymerase II, transcripts with the same sense as late mRNAs and 5'-ends at nt5076 +/- 2 were produced from superhelical template by an alpha amanitin resistant enzyme.


Epigenetic intervention with a BET inhibitor ameliorates acute retinal ganglion cell death in mice.
The bromo and extraterminal (BET) epigenetic "reader" family is becoming an appealing new therapeutic target for several common diseases, yet little is known of its role in retinal neurodegeneration. We explored the potential of BET inhibition in the protection of retinal ganglion cells (RGCs). To test the therapeutic effect of JQ1, an inhibitor highly selective for the BET family of proteins, we used an acute RGC damage model induced by N-methyl-D-aspartic acid (NMDA) excitotoxicity. Adult C57BL/6 mice received an intravitreal injection of NMDA with (or without) JQ1 in one eye and vehicle control in the contralateral eye; RGC loss was assessed on retinal sections and whole mounts. Gene expression and apoptosis were analyzed by quantitative real time (RT)-PCR and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), respectively. For counting RGCs, immunostaining of the marker protein BRN3A was performed on whole mounts. NMDA treatment eliminated RGCs (day 7 and day 14 post injection) and diminished the expression (mRNAs) of RGC-selective genes, including Thy1, Nrn1, Sncg, and Nfl (day 3 and day 7). In contrast, co-injection with JQ1 maintained the number and gene expression of RGCs at ~2 fold of the control (NMDA only, no JQ1), and it decreased NMDA-induced TUNEL-positive cells in the RGC layer by 35%. While NMDA treatment dramatically upregulated mRNAs of inflammatory cytokines (TNFα, IL-1β, MCP-1, RANTES) in retinal homogenates, co-injection with JQ1 suppressed their upregulation by ~50%. Intravitreal injection of a BET inhibitor (JQ1) ameliorates NMDA-induced RGC death, revealing the RGC-protective potential of pharmacological blockage of the BET family. This new strategy of epigenetic intervention may be extended to other retinal degenerative conditions.


Group membership: Who gets to decide?
In this commentary, I focus on several problems that the authors' understanding of group identity raises: the legality of avoiding background diversity, the problem of effectively unshareable knowledge, the practical quality of some outcomes arrived at by groups with homogeneous backgrounds, and moral issues about fairness. I note also that much recent research challenges the view that background diversity is more likely to be a detriment than a benefit.


Intermittent hypoxia augments carotid body and ventilatory response to hypoxia in neonatal rat pups.
Carotid bodies are functionally immature at birth and exhibit poor sensitivity to hypoxia. Previous studies have shown that continuous hypoxia at birth impairs hypoxic sensing at the carotid body. Intermittent hypoxia (IH) is more frequently experienced in neonatal life. Previous studies on adult animals have shown that IH facilitates hypoxic sensing at the carotid bodies. On the basis of these studies, in the present study we tested the hypothesis that neonatal IH facilitates hypoxic sensing of the carotid body and augments ventilatory response to hypoxia. Experiments were performed on 2-day-old rat pups that were exposed to 16 h of IH soon after the birth. The IH paradigm consisted of 15 s of 5% O2 (nadir) followed by 5 min of 21% O2 (9 episodes/h). In one group of experiments (IH and control, n = 6 pups each), sensory activity was recorded from ex vivo carotid bodies, and in the other (IH and control, n = 7 pups each) ventilation was monitored in unanesthetized pups by plethysmography. In control pups, sensory response of the carotid body was weak and was slow in onset (approximately 100 s). In contrast, carotid body sensory response to hypoxia was greater and the time course of the response was faster (approximately 30 s) in IH compared with control pups. The magnitude of the hypoxic ventilatory response was greater in IH compared with control pups, whereas changes in O2 consumption and CO2 production during hypoxia were comparable between both groups. The magnitude of ventilatory stimulation by hyperoxic hypercapnia (7% CO2-balance O2), however, was the same between both groups of pups. These results demonstrate that neonatal IH facilitates carotid body sensory response to hypoxia and augments hypoxic ventilatory chemoreflex.


Reimplantation of the upper lobe bronchus after lower sleeve lobectomy or bilobectomy: long-term results.
The advantages of a bronchial sleeve resection are well established. A clear majority of reported cases are of upper lobe sleeve resection. Reimplantation of the upper lobe bronchus after a lower sleeve lobectomy or bilobectomy (the so-called Y-sleeve resection) is infrequent. Related technical peculiarities are the main issues. We present our experience and results in this setting. Between 1989 and 2015, we performed 28 Y-sleeve resections of the left lower lobe (n = 18) or right middle and lower lobes (n = 10). The lung-sparing reconstructive operation was performed for non-small-cell lung cancer in 23 cases, for bronchial carcinoid tumour in 4 cases and for a cystic adenoid carcinoma in 1 case. Anastomotic reconstruction was performed by interrupted 4-0 absorbable sutures (monofilament material). All the resections were complete (R0). Postoperative mortality was 3.6%. The rate of major complications was 10.7% (1 myocardial infarction, 1 anastomotic stenosis requiring dilatation and 1 anastomotic fistula). Among the 23 patients with non-small-cell lung cancer (18 men and 5 women; mean age 58 ± 12 years), 8 were Stage I, 9 were Stage II and 6 were Stage IIIa. At a mean follow-up of 46 months, the recurrence rate was 32%. There were 2 loco-regional recurrences. No endobronchial or perianastomotic recurrence occurred. The 3- and 5-year overall and disease-free survival rates of patients with non-small-cell lung cancer were 76.3% and 55.1% and 68.7% and 62.9%, respectively. A Y-sleeve resection with reimplantation of the upper load bronchus is a technically feasible and oncologically adequate operation.


Lack of appropriate investigations in making a diagnosis of syndrome of inappropriate antidiuretic hormone.
The syndrome of inappropriate antidiuretic hormone (SIADH) is reported as the most common cause of hyponatraemia. This retrospective cross-sectional study evaluated the diagnosis of SIADH in 110 hospitalised patients in an Australian tertiary hospital with reference to recently published clinical guidelines. Investigation of SIADH was incomplete in all but 20% of cases. Adrenal insufficiency and hypothyroidism were not excluded in a significant number of cases.


Skin biopsy and quantitative sensory testing do not predict response to lidocaine patch in painful neuropathies.
Predictors of response to neuropathic pain treatment in patients with painful distal sensory neuropathies are lacking. The 5% lidocaine patch is believed to exert its effects on neuropathic pain via a local stabilizing effect on cutaneous sensory afferents. As such, it provides a model to assess whether the status of epidermal innervation as determined by skin biopsy or quantitative sensory testing (QST) of small- and large-diameter sensory afferents might serve as predictors of response to topical, locally active treatment. In this study we assessed associations between epidermal nerve fiber (ENF) densities, sensory nerve conduction studies (NCS), QST, and response to a 5% lidocaine patch in patients with painful distal sensory neuropathies. We observed no association between distal leg epidermal and subepidermal innervation and response to the lidocaine patch. Several patients with complete loss of distal leg ENF showed a response to the lidocaine patch. Similarly we observed no consistent association between treatment response and QST for vibration, cooling, warm, heat-pain, and cold-pain thresholds, or distal sensory NCS. Thus, distal-leg skin biopsy, QST, and sensory NCS cannot be used to identify patients with painful polyneuropathy likely to respond to a lidocaine patch in clinical practice. Further studies are required to clarify precisely the mechanism and site of action of the lidocaine patch in patients with peripheral neuropathic pain.


Pathophysiological Mechanisms in Cardiorenal Syndrome.
Cardiorenal syndrome represents the confluence of intricate hemodynamic, neurohormonal, and inflammatory pathways that initiate and propagate the maladaptive cross talk between the heart and kidneys. Several of these pathophysiological principles were described in older historical experiments. The last decade has witnessed major efforts in streamlining its definition, clinical phenotypes, and classification to improve diagnostic accuracy and deliver optimal goal-directed medical therapies. The ability to characterize the various facets of cardiorenal syndrome based on its pathophysiology is poised in an exciting vantage point, in the backdrop of several advanced diagnostic strategies, notably cardiorenal biomarkers that may help with accurate delineation of clinical phenotype, prognosis, and delivery of optimal medical therapies in future studies. This promises to help integrate precision medicine into the clinical diagnosis and treatment strategies for cardiorenal syndrome and, through a heightened understanding of its pathophysiology, to deliver appropriate therapies that will reduce its associated morbidity and mortality.


Parental involvement and bullying among middle-school students in North Africa.
Bullying, especially in developing countries, has not been much examined, especially the influence of parents on the risk of being bullied. The aim of this study was to determine whether active parenting is associated with reduced peer victimization among middle-school students in North Africa. A secondary analysis of data from more than 13,000 middle-school students who participated in the Global School-based Student Health Survey (GSHS) in Egypt, Libya, Morocco and Tunisia between 2006 and 2008, was conducted using multiple logistic regression models. About 60% of students in Egypt and one-third of students in Libya, Morocco and Tunisia reported having been bullied in the past month. In all 4 countries, boys reported more peer victimization than girls. In Egypt, Morocco and Tunisia, students who reported that their parents checked their homework, were understanding, and knew how the student spent free time had a reduced likelihood of peer victimization but this association was not significant in Libya. Interventions for reducing bullying should consider the positive impact of involved parents.


[Thoraco-abdominal angiotomography. 280 explorations].
Angiotomography invariably imrpves the quality of the images obtained in vascular radiology, with respect to both vascular anatomy and pathology. Its contribution is obviously essential when, for technical reasons, arterial opacification is only mediocre (extended angiocardiopneumography). In the arteriolar study of deep seated or voluminous organs, its eliminates superimpositions, makes tri-dimensional study possible and provides a means of studying fine arterioles, useful in diagnosis and difficult to demonstrate using conventional techniques. Its principle limitations are technological in character. Accepting precise and clearly defined rules in its indications and realisation, appropriate equipment, and a constant effort in the analysis and reading of its results, it is reasonable to hope that angiotomography will quickly add a new dimension to vascular studies.


Accelerating Discovery and Functional Analysis of Small RNAs with New Technologies.
Over the past decade, bacterial small RNAs (sRNAs) have gone from a biological curiosity to being recognized as a major class of regulatory molecules. High-throughput methods for sampling the transcriptional output of bacterial cells demonstrate that sRNAs are universal features of bacterial transcriptomes, are plentiful, and appear to vary extensively over evolutionary time. With ever more bacteria coming under study, the question becomes how can we accelerate the discovery and functional characterization of sRNAs in diverse organisms. New technologies built on high-throughput sequencing are emerging that can rapidly provide global insight into the numbers and functions of sRNAs in bacteria of interest, providing information that can shape hypotheses and guide research. In this review, we describe recent developments in transcriptomics (RNA-seq) and functional genomics that we expect to help us develop an integrated, systems-level view of sRNA biology in bacteria.


Effect of selenium on preservation quality of green tea during autumn tea-processing season.
Selenium-enriched green tea leaves were prepared by foliar applications of selenium-amended fertilizer during autumn season. The influence of selenium (Se) on preservation quality of tea during 4-month storage was determined. The results showed that the Se and vitamin C contents of green tea were significantly increased by selenium spraying during the autumn tea-producing season. The vitamin C content of Se-enriched green tea was higher and its decline was significantly slower during storage compared to normal green tea. However, there was no significant difference between the contents of chlorophyll and polyphenol of Se-enriched and regular tea. During the first 60 days, the color of green tea extract in Se-enriched green tea and normal tea showed no significant difference. However, the color of green tea extract in Se-enriched green tea was more stable compared with normal tea during the storage period. The sweetness and aroma of extracts of Se-enriched green tea were also significantly higher than that of normal tea and the bitterness of extracts of Se-enriched green tea was significantly lower compared with normal tea. These results showed that selenium application can slow the reduction of tea's major component and thus improve preservation qualities of green tea.


Update on treatment strategies for obesity.
Obesity is a disease that is defined as the accumulation of excessive amounts of body fat and is associated with increased risk of serious illness, disability, and death. In clinical practice, obesity is best assessed by calculating body mass index and measuring waist circumference. Treatment options are determined based on the body mass index, waist circumference, and adverse health consequences the patient is experiencing or is at an increased risk for facing in the future. Today, overweight and obesity impacts the majority of patients we treat in our clinical practices. Although endocrinologists are uniquely positioned to treat one of the major consequences of our current obesity epidemic, type 2 diabetes, we also need to be positioned and prepared to effectively treat one of its major causes-obesity. Type 2 diabetes and obesity are very much intertwined. Treatment of each disease affects the other. For these reasons, endocrinologists need to be experts in the treatment of obesity as well as diabetes. They should keep up with advances in obesity treatment including lifestyle, pharmaceutical, and surgical strategies. These strategies offer opportunities for improving the overall treatment for our obese patients today and will continue to improve and expand over the next decade.


Mode of action of cystathionine beta-lyase.
Cystathionine beta-lyase (CBL) is a member of the gamma-family of pyridoxal-5'-phosphate (PLP)-dependent enzymes (Alexander et al., 1994) that cleave C(beta,gamma)-S bonds of a broad variety of substrates. Recently, we reported the X-ray crystal structures of CBL and the CBL-trifluoroalanine inactivation complex at 1.83 A and 2.3 A resolution, respectively. The structures explicitly reveal the cofactor and substrate binding pockets. Spectral analysis of substrate turnover indicates a change of hydrophobicity in the microenvironment of the aldimine bond. In combination with further spectroscopic data, crystallographic evidence permits the formulation of a likely reaction mechanism.


[Magnetic resonance imaging as a prenatal diagnostic tool supplementary to ultrasound in diagnosing fetal and gestational abnormalities].
The use of Magnetic Resonance Imaging (MRI) as a prenatal and gestational imaging modality supplementary to ultrasound has become widespread with the advent of rapid MR sequences in the last few years. These sequences allow acquisition of high-resolution images of the fetus in a single breath-holding period of the mother, with minimal fetal motion artifacts. We describe our experience with this modality in the diagnosis of prenatal and gestational abnormalities. The study population consisted of 39 pregnant women who had a total of 40 MRI examinations from 7/1998 to 7/2000. The indication for all examinations was a suspected fetal or gestational abnormality as suggested by ultrasound scan, laboratory tests or by family history. In 31 cases (77.5%) a correlation was found between the ultrasound findings and the MR imaging, of which in 6 cases (15%) the MRI added new valuable information. In 9 cases (22.5%) the MRI ruled out findings suspected by ultrasound. The prenatal findings were compared with postnatal clinical follow-up, imaging or pathology report in 26 cases (66.6%). In two cases the clinical outcome and postnatal imaging were discordant with the prenatal imaging findings in ultrasound and MRI. Although not proven, MRI is considered safe during pregnancy because it does not use ionizing radiation. It depicts fetal anatomy and pathology well. Also uterine, placental and other maternal structures are well demonstrated. This tool is useful in cases in which there is a suspicion of a malformed fetus or abnormal placenta by an ultrasound examination or in cases in which an ultrasound examination is limited by technical factors. MRI was found to help parents and doctors decide about the fate of a suspected abnormal pregnancy by adding valuable information supplemental to ultrasound examination.


Mechanisms of progesterone action in inhibiting prematurity.
Progesterone is a steroid hormone that plays an integral role in each step of human pregnancy. In early pregnancy, progesterone produced by the corpus luteum is critical to the maintenance of early pregnancy until the placenta takes over this function at 7 to 9 weeks of gestation, hence its name (pro-gestational steroid hormone). The role of progesterone in later pregnancy, however, is less clear. It has been proposed that progesterone may be important in maintaining uterine quiescence in the latter half of pregnancy by limiting the production of stimulatory prostaglandins and inhabiting the expression of contraction-associated protein genes within the myometrium. Although systemic progesterone withdrawl may not correlate directly with the onset of labour in humans, there is increasing evidence to suggest that progesterone exerts its influence indirectly via a 'functional' withdrawl at the level of the uterus. The molecular mechanisms by which progesterone is able to maintain uterine quiescence and prevent preterm birth in some high-risk women are not clear. Six putative mechanisms have been proposed in the literature by both US and other investigators and are explored in this review.


Measles--United States, 2005.
Measles is a highly infectious, acute viral illness that can be complicated by severe pneumonia, diarrhea, and encephalitis and can result in death. In the prevaccine era, approximately 500,000 cases of measles occurred annually in the United States. During 2005, local and state health departments reported to CDC 66 confirmed cases of measles (incidence rate: less than one case per 1 million population), 34 of which were from a single outbreak in Indiana associated with infection in a traveler returning to the United States. This report describes the epidemiology of U.S. measles cases in 2005 and documents the absence of endemic measles and the continued risk for imported measles infections that can result in transmission within the United States. The findings underscore the need to maintain the highest possible measles vaccination coverage in the United States and to adhere to recommendations regarding measles vaccination.


Meta-analysis: High-dose vs. low-dose metronidazole-containing therapies for Helicobacter pylori eradication treatment.
The purpose of this study was to evaluate the efficacy of high dose of metronidazole in the treatment of Helicobacter pylori (H. pylori) infection. Studies were identified from databases (Pubmed, Embase, Cochrane Library, ClinicalTrials.gov) searched from January 1990 to September 2017 using a battery of keywords. We included randomized controlled trials (RCTs) of H. pylori treatment comparing the high-dose and low-dose metronidazole-containing therapies (high-dose and low-dose therapies). Two reviewers independently selected studies, extracted relevant data and assessed study quality. A meta-analysis was performed by using Review Manager 5.3. Dichotomous data were pooled to obtain the relative risk (RR) of the eradication rate, with 95% confidence intervals (CIs). Four randomized controlled trials, a total of 612 patients with a diagnosis of H. pylori infection were included. Overall the meta-analysis showed that both high-dose and low-dose therapies achieved similar efficacy of intention-to-treat (ITT) eradication rate 82% vs. 76%, RR 1.12 (95%CI: 0.96 to 1.30), P = 0.15, and adherence 94% vs. 94%, RR 1.00 (95%CI: 0.97 to 1.04), P = 0.81, but side effects were more likely in high-dose therapies [32% vs. 17%, RR 1.84 (95%CI: 1.17 to 2.88), P = 0.008]. In subgroup analysis, increasing the dose of metronidazole enhanced eradication rates in areas with high metronidazole resistance [74% vs 52%, RR 1.40 (95%CI: 1.08 to 1.82), P = 0.01] and in individuals with metronidazole-resistant strains [71% vs. 46%, RR 1.50 (95%CI: 1.02 to 2.19), P = 0.04]. Both high-dose and low-dose therapies can achieve similar eradication rates and adherence and generally low-dose therapies cause fewer side effects. In populations with high metronidazole resistance, high dose of metronidazole can increase the eradication rates of H. pylori infection.


The shape of the trochlea.
Dissections and serial sections of human orbits showed the shape of the trochlea to be more complex than has been previously described. A grooved cartilaginous flange extends posterolaterally from the front of the trochlea, guiding the reflected portion of the superior oblique tendon.


[Modulation of nuclear receptors on drug-metabolizing enzymes and transporters].
PXR, CAR and PPAR, widely distributed in the body, are important members of the nuclear receptors (NRs) family. The activities and gene expressions of drug-metabolizing enzymes (DMEs) and transporters can be regulated by the activation of NRs, which effect the drug disposition. Multidrug resistance (MDR) is the leading cause of failure in cancer therapy. NRs, including PXR, CAR and PPAR, were shown to regulate the expressions of DMEs and transporters involved in the drug metabolism and clearance, suggesting that the modulation of NRs can be considered as a new target to overcome MDR. This review described the research progress of NR family members PXR, CAR, PPAR and their transcriptional activation mechanism, the regulation of DMEs and transporters by NRs, which may provide a valuable reference for clinical medication and overcome of MDR.


Mixing State and Fractal Dimension of Soot Particles at a Remote Site in the Southeastern Tibetan Plateau.
The mixing state and fractal dimension (Df) of soot particles are two major factors affecting their absorption capacity and their climate effects. Here we investigated these factors of soot particles found in a typical valley of the southeastern Tibetan Plateau where wood burning in local villages was one major source of soot particles. Our motivation revealed Df and the aging property of soot particles in remote air and discussed their regional climatic implications. We found that 64% of total analyzed particles by number were soot-bearing particles and most of them aged with sulfate or organic coating. The Df sequence is bare-like soot (1.75 ± 0.08) < partly coated soot (1.82 ± 0.05) < embedded soot (1.88 ± 0.05). The aging process enlarged the overall size of the soot-bearing particles and increased the compactness of soot. Soot aging critically depended on high relative humidity (RH) during nighttime. Besides emission sources and coating processes, the coating aerosol phase under different RHs is another important factor affecting the soot Df.


Production and characterization of a novel monoclonal antibody against phosphorylated T cell receptor zeta chain.
One of the earliest events following T cell receptor (TCR) triggering is the activation of the protein kinase Lck and induction of tyrosine phosphorylation of zeta, the major signal transduction subunit of the T cell receptor complex. Here we report the generation and characterization of a monoclonal antibody specific for human phosphozeta. The antibody was produced by immunizing mice with a truncated recombinant form of human zeta together with the Lck enzyme. The C415.9A antibody recognizes recombinant as well as cellular phosphozeta but is unreactive with unphosphorylated zeta or other tyrosine phosphorylated proteins. Using this antibody, we have demonstrated aberrant TCR-zeta tyrosine phosphorylation in Jurkat T cell transduction mutants. Therefore, this antibody can be used to elucidate T cell signal transduction mechanisms by analyzing and monitoring tyrosine phosphorylation of zeta in vitro and in vivo directly. Furthermore, this antibody could find application in the analysis of abnormal T cell signaling in autoimmune disease, cancer, and immunodeficiency disorders.


Progressively volumetrized deep generative models for data-efficient contextual learning of MR image recovery.
Magnetic resonance imaging (MRI) offers the flexibility to image a given anatomic volume under a multitude of tissue contrasts. Yet, scan time considerations put stringent limits on the quality and diversity of MRI data. The gold-standard approach to alleviate this limitation is to recover high-quality images from data undersampled across various dimensions, most commonly the Fourier domain or contrast sets. A primary distinction among recovery methods is whether the anatomy is processed per volume or per cross-section. Volumetric models offer enhanced capture of global contextual information, but they can suffer from suboptimal learning due to elevated model complexity. Cross-sectional models with lower complexity offer improved learning behavior, yet they ignore contextual information across the longitudinal dimension of the volume. Here, we introduce a novel progressive volumetrization strategy for generative models (ProvoGAN) that serially decomposes complex volumetric image recovery tasks into successive cross-sectional mappings task-optimally ordered across individual rectilinear dimensions. ProvoGAN effectively captures global context and recovers fine-structural details across all dimensions, while maintaining low model complexity and improved learning behavior. Comprehensive demonstrations on mainstream MRI reconstruction and synthesis tasks show that ProvoGAN yields superior performance to state-of-the-art volumetric and cross-sectional models.


Coverage-dependent quantum versus classical scattering of thermal neon atoms from Li/Cu(100).
We show that subtle variations in surface structure can enhance quantum scattering and quench atom-surface energy transfer. The scattering of thermal energy neon atoms from a lithium overlayer on a copper substrate switches between a classical regime, dominated by multiphonon interactions, and a quantum regime, dominated by elastic diffraction. The transition is achieved by simple tailoring of the lithium coverage and quantum scattering dominates only in the narrow coverage range of theta=0.3-0.6 ML. The results are described qualitatively using a modified Debye-Waller model that incorporates an approximate quantum treatment of the adsorbate-substrate vibration.


Successful Cost-Effective Prevention of Cytomegalovirus Disease in Kidney Transplant Recipients Using Low-Dose Valganciclovir.
Low-dose valganciclovir prophylaxis is still under investigation in renal transplant procedures. Our aim was to assess the cost effectiveness of 450 mg versus 900 mg valganciclovir prophylaxis in kidney transplant recipients. In this prospective trial, 201 kidney transplant patients were randomized (1:1) to receive 450 mg/d (group 1, n = 100) or 900 mg/d (group 2, n = 101) valganciclovir prophylaxis for the first 6 months after transplant. Patients were studied for incidence of cytomegalovirus disease, leucopenia episodes, rejection episodes, and graft outcomes along with associated costs over 1 year. Costs (in US dollars) of treatment of rejection were also analyzed. Demographic features of the studied groups were comparable. We found that the cost of cytomegalovirus care in group 1 patients was significantly lower (by 50% at 6 months; P < .001), with less leukopenia episodes (P = .04), lower doses of granulocyte colony-stimulating factor (by 30% at 6 months; P = .03), higher doses of mycophenolate mofetil (P = .04), and less rejection episodes (P = .01) compared with group 2. In group 2, there were more episodes of cytomegalovirus infection (P = .052) and BK virus nephropathy (P = .04). Graft and patient outcomes were satisfactory in both groups. Low-dose valganciclovir for cytomegalovirus prophylaxis after renal transplant is safer, effective and without breakthrough infection, and less costly than using the usual dose.


Effect of the lower third molars on the lower dental arch crowding.
Increasing lower dental arch crowding with the age is a recognized clinical problem, and one that has become more apparent in recent years as more adults retain their teeth longer. One of the theories is that the erupting third molars push anterior teeth forward and cause their crowding. On the other hand, a number of studies found no correlation between lower third molars and lower incisor crowding. Because of all these contrasting findings this study was started to re-evaluate correlation between third molars presence and lower dental arch crowding. The study group consisted of 91 subjects with an average age 21.01+/-4.13 years. The individual, quantitative and cast-based analytical registration of crowding was based on the measurements of mesiodistal width of teeth and related to the length of the appropriate segment of the lower dental arch. No statistically significant third molar presence-specific differences were recorded in the lower dental arch crowding between the groups with erupted, unerupted and agenesis of third molars. Although differences between the groups were not statistically significant, some tendency for crowding in the anterior part of lower dental arch was more expressed in the groups with the presence (erupted 0.57 mm and unerupted 0.74 mm) of third molars, than with agenesis (surplus space 0.03 mm). Nevertheless, the present study do not provide enough evidence to incriminate third molars as being the only or even major etiologic factor in the late lower dental arch crowding.


Methods of characterizing the distribution of exhaust emissions from light-duty, gasoline-powered motor vehicles in the U.S. fleet.
Mobile sources significantly contribute to ambient concentrations of airborne particulate matter (PM). Source apportionment studies for PM10 (PM < or = 10 microm in aerodynamic diameter) and PM2.5 (PM < or = 2.5 microm in aerodynamic diameter) indicate that mobile sources can be responsible for over half of the ambient PM measured in an urban area. Recent source apportionment studies attempted to differentiate between contributions from gasoline and diesel motor vehicle combustion. Several source apportionment studies conducted in the United States suggested that gasoline combustion from mobile sources contributed more to ambient PM than diesel combustion. However, existing emission inventories for the United States indicated that diesels contribute more than gasoline vehicles to ambient PM concentrations. A comprehensive testing program was initiated in the Kansas City metropolitan area to measure PM emissions in the light-duty, gasoline-powered, on-road mobile source fleet to provide data for PM inventory and emissions modeling. The vehicle recruitment design produced a sample that could represent the regional fleet, and by extension, the national fleet. All vehicles were recruited from a stratified sample on the basis of vehicle class (car, truck) and model-year group. The pool of available vehicles was drawn primarily from a sample of vehicle owners designed to represent the selected demographic and geographic characteristics of the Kansas City population. Emissions testing utilized a portable, light-duty chassis dynamometer with vehicles tested using the LA-92 driving cycle, on-board emissions measurement systems, and remote sensing devices. Particulate mass emissions were the focus of the study, with continuous and integrated samples collected. In addition, sample analyses included criteria gases (carbon monoxide, carbon dioxide, nitric oxide/nitrogen dioxide, hydrocarbons), air toxics (speciated volatile organic compounds), and PM constituents (elemental/organic carbon, metals, semi-volatile organic compounds). Results indicated that PM emissions from the in-use fleet varied by up to 3 orders of magnitude, with emissions generally increasing for older model-year vehicles. The study also identified a strong influence of ambient temperature on vehicle PM mass emissions, with rates increasing with decreasing temperatures.


Art Image Processing and Color Objective Evaluation Based on Multicolor Space Convolutional Neural Network.
A convolutional neural network's weight sharing feature can significantly reduce the cumbersome degree of the network structure and reduce the number of weights that need to be trained. The model can directly input the original image, without the process of feature extraction and data reconstruction in common classification algorithms. This kind of network structure has got a good performance in image processing and recognition. Based on the color objective evaluation method of the convolutional neural network, this paper proposes a convolutional neural network model based on multicolor space and builds a convolutional neural network based on VGGNet (Visual Geometry Group Net) in three different color spaces, namely, RGB (Red Green Blue), LAB (Luminosity a b), and HSV (Hue Saturation Value) color spaces. We carry out research on data input processing and model output selection and perform feature extraction and prediction of color images. After a model output selection judger, the prediction results of different color spaces are merged and the final prediction category is output. This article starts with the multidimensional correlation for visual art image processing and color objective evaluation. Considering the relationship between the evolution of artistic painting style and the color of artistic images, this article explores the characteristics of artistic image dimensions. In view of different factors, corresponding knowledge extraction strategies are designed to generate color label distribution, provide supplementary information of art history for input images, and train the model on a multitask learning framework. In this paper, experiments on multiple art painting data sets prove that this method is superior to single-color label classification methods.


A coincidental variation of the axillary artery: the brachioradial artery and the aberrant posterior humeral circumflex artery passing under the tendon of the latissimus dorsi muscle.
A case of anomalous terminal branching of the axillary artery was encountered and described in a left upper limb of a male cadaver. A series of 214 upper limbs of Caucasian race was dissected. A variant artery, stemming from the very end of the axillary artery followed a superficial course distally. It passed the cubital fossa, ran on the lateral side of the forearm as usual radial artery, crossed ventrally to the palm and terminated in the deep palmar arch. This vessel is a case of the brachioradial artery (incorrectly termed as the "radial artery with high origin"). Moreover, it was associated with another variation, concerning the aberrant posterior humeral circumflex artery passing under the tendon of the latissimus dorsi muscle. The anatomical knowledge of the axillary region is essential for radiodiagnostic, surgical and traumatologic procedures. The superficially located artery brings an elevated danger of heavy bleeding in all unexpected situations, its variant branching can cause problems in radial catheterization procedures and the anomalously coursing other arterial variant poses an elevated danger in surgical procedures concerning the surgical neck of humerus.


Life-threatening retro-pharyngeal bleed in a case of systemic lupus erythematosus--an uncommon but important evil of a common disease.
Acquired inhibitors of coagulation are antibodies that interfere with the coagulation system either by functional inhibition of the activity of clotting factors or by their increased clearance from the plasma. They can be idiopathic or seen in various physiologic (pregnancy and postpartum) or pathologic states (systemic lupus erythematosus (SLE), malignancies, rheumatoid arthritis) and can result in a variety of haemorrhagic sequelae. SLE can be associated with antibodies to multiple clotting factors and bleeding though rare can be an important haematologic manifestation with life-threatening consequences in these patients.


Spanish normative studies (NEURONORMA-Plus project): norms for the Delis Kaplan-Design Fluency Test, Color Trails Test, and Dual Task.
Complex attention and non-verbal fluency tasks are used in neuropsychological assessments with the aim of exploring subdomains of executive function. The purpose of this study is to provide norms and age-, education-, and sex-adjusted data for the Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Test (CTT), and Dual Task (DT) as part of the NEURONORMA-Plus project. The sample included 308 cognitively unimpaired individuals aged between 18 and 92 years. Raw scores were converted to age-adjusted scaled scores. These were further converted into education- and sex-adjusted scaled scores by applying linear regression, with 2 age groups (< 50 and ≥ 50 years). Overall, age had a negative impact on DK-DFT and CTT performance. We observed a positive effect of education on DK-DFT scores only in the older group (≥ 50 years). Moreover, younger men performed slightly better in the basic condition of this test. Education was positively associated with all CTT scores in both age groups, with the exception of the CTT-1 subtest in the younger group. Age and education did not influence DT performance, whereas sex did, with young women performing slightly better. These normative data may be useful in the interpretation of neuropsychological assessments in the Spanish population.


[Preparation and characterization of the monoclonal antibody against HIV-1 p24 antigen].
To establish hybridoma cells secreting monoclonal antibodies (mAbs) against HIV-1 p24 antigen and characterize their properties. BALB/c mice were immunized with purified p24 protein and then the from splenocytes immunized mice were fused with Sp2/0 cells. Monoclonal hybridoma cell lines were obtained by limiting dilution, HAT and HT-selective culture. The specificity of mAbs was identified by Dot blot and indirect ELISA. We had established two hybridoma cell lines secreting mAbs against HIV-1 p24 antigen. The titers of two mAbs in ascitic fluid were 1 x 10(-5) and 1.7 x 10(4)-1.8 x 10(4) mol/L, respectively. Both mAbs belonged to IgG1. Indirect ELISA detection demonstrated that both mAbs had no cross-reactivities with other viral antigens, such as HBcAg, HCV RNA positive sera and HIVgp41. Two hybridoma cell lines secreting mAbs against HIV-1 p24 antigen have been established successfully, which lays the foundation for detecting HIV-1 p24 antigen.


[Functional morphology of the outer hair cells of the human: new aspects].
Serial sections through the outer hair cells of the human organ of Corti were investigated using high-resolution electron microscopy. Delicate monostratified tubular structures of differing lengths are located on the cytoplasmic side of the hair-cell membrane. They are connected to the cell membrane via short fibers (pillars) arranged in pairs. The tubular structures, which are also termed subsurface cisterns (SSC), constitute an extensive network. This network lines the entire inner surface of the outer hair-cell membrane, and in contrast to the mammals investigated so far, also lines the base of the cell. The postsynaptic cisterns of the efferent synapses are integrated into this system. At the surface of the inner lamina of the cisterns, pores 8.5 nm in diameter are to be found. These are surrounded by protein complexes with a stellate arrangement. Similar protein complexes are located on the inner lamina of the postsynaptic cisterns. Pores 8.5 nm in diameter are also present in the outer lamina of the SSC. These constitute the base for the pillar filaments. At high magnification, the pillars are seen to have a lumen about 6 nm in diameter. Pores about 8 nm in diameter are again to be found where the pillars are anchored in the outer cell membrane. The pillars, consisting of actin, are probably ionic channels, and the pores of the inner lamina of the SSC surrounded by protein complexes are thought to be acetylcholine receptors. Since the postsynaptic cisterns of the efferent innervation of the outer hair cells are part of the overall system of the SSC, and acetylcholine is regarded as the neurotransmitter of efferent innervation, it would seem possible to regulate the subsurface cisterns, as a wall-stabilizing, contractile system, via the efferent innervation. On the basis of serial sections, a three-dimensional, true-to-scale model of the contractile wall system of the human outer hair cell was reconstructed.


o-Benzyne fragmentation and isomerization pathways: a CASPT2 study.
The mechanisms of the fragmentation and isomerization pathways of o-benzyne were studied at the multi-configurational second-order perturbative level [CAS(12,12)-PT2]. The direct fragmentation of o-benzyne to C2H2 + C4H2 follows two mechanisms: a concerted mechanism and a stepwise mechanism. Although the concerted mechanism is characterized by a single closed-shell transition structure, the stepwise pathway is more complex and structures with a strong diradical character are seen. A third diradicaloid fragmentation pathway of o-benzyne yields C6H2 as the final product. As an alternative to fragmentation, o-benzyne can also undergo rearrangement to its meta and para isomers and to the open chain cis and trans isomers of hexa-3-en-1,6-diyne (HED). These easily fragment to C2H2 + C4H2 or C6H2. Kinetic modelling at several different temperatures between 800 and 3000 K predicted that the thermal decomposition of o-benzyne should yield C2H2, C4H2 and C6H2 as the main products. Small amounts of the HED isomers accumulated at temperatures <1200 K, but they rapidly decompose at higher temperatures. Between 1000 and 1400 K, C2H2 + C4H2 are formed exclusively from the decomposition of trans-HED. At temperatures >1400 K, C2H2 + C4H2 also form from the direct fragmentation of o-benzyne. The formation of C2H2 + C4H2 prevails up to 1600 K but above this temperature the formation of C6H2 prevails. At temperatures >2400 K, the direct fragmentation of o-benzyne again leads to the formation of C2H2 + C4H2. The formation of hydrogen atoms is also explained by our proposed mechanisms.


Are Total and Domain-Specific Sedentary Time Associated with Overweight in Older Taiwanese Adults?
This study investigated the associations between total and domain-specific sedentary time with the risk of overweight in older adults. A cross-sectional study was conducted by administering computer-assisted telephone interviews to 1046 Taiwanese older adults (aged ≥65 years) residing in two regions in Taiwan in 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to examine the associations between self-reported total and six domain-specific sedentary times and body mass index status (calculating by self-reported height and weight) by using logistic regression analyses. The results showed that compared with older women in the lowest quartile of the total sedentary time, those in the highest quartile were 1.87 (95% CI: 1.10-3.21) times more likely to be overweight, after adjustment for potential confounders. The total sedentary time was stratified into six specific domains, and only watching television more than 2 h per day was positively associated with overweight (OR, 1.55; 95% CI: 1.08-2.25) in older women, whereas no other sedentary time domains were associated with the risk of overweight. No significant associations were observed in older men. Further studies using prospective designs are required to confirm the presently observed effects of total and domain-specific sedentary behavior on the health of older adults.


Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study.
The epidemiologic correlation between the poor prognosis of SARS-CoV-2 infection and vitamin D deficiency has been observed worldwide, however, their molecular mechanisms are not fully understood. In this study, we used combined molecular docking, molecular dynamics simulations and binding free energy analyses to investigate the potentials of vitamin D3 and its hydroxyderivatives as TMPRSS2 inhibitor and to inhibit the SARS-CoV-2 receptor binding domain (RBD) binding to angiotensin-converting enzyme 2 (ACE2), as well as to unveil molecular and structural basis of 1,25(OH)2D3 capability to inhibit ACE2 and SARS-CoV-2 RBD interactions. The results show that vitamin D3 and its hydroxyderivatives are favorable to bind active site of TMPRSS2 and the binding site(s) between ACE2 and SARS-CoV2-RBD, which indicate that vitamin D3 and its biologically active hydroxyderivatives can serve as TMPRSS2 inhibitor and can inhibit ACE2 binding of SARS-CoV-2 RBD to prevent SARS-CoV-2 entry. Interaction of 1,25(OH)2D3 with SARS-CoV-2 RBD and ACE2 resulted in the conformation and dynamical motion changes of the binding surfaces between SARS-CoV-2 RBD and ACE2 to interrupt the binding of SARS-CoV-2 RBD with ACE2. The interaction of 1,25(OH)2D3 with TMPRSS2 also caused the conformational and dynamical motion changes of TMPRSS2, which could affect TMPRSS2 to prime SARS-CoV-2 spike proteins. Our results propose that vitamin D3 and its biologically active hydroxyderivatives are promising drugs or adjuvants in the treatment of COVID-19. Communicated by Ramaswamy H. Sarma.


Implementing shared decision making for early-stage breast cancer treatment using a coproduction learning collaborative: the SHAIR Collaborative protocol.
Shared decision making (SDM) in breast cancer care improves outcomes, but it is not routinely implemented. Results from the What Matters Most trial demonstrated that early-stage breast cancer surgery conversation aids, when used by surgeons after brief training, improved SDM and patient-reported outcomes. Trial surgeons and patients both encouraged using the conversation aids in routine care. We will develop and evaluate an online learning collaborative, called the SHared decision making Adoption Implementation Resource (SHAIR) Collaborative, to promote early-stage breast cancer surgery SDM by implementing the conversation aids into routine preoperative care. Learning collaboratives are known to be effective for quality improvement in clinical care, but no breast cancer learning collaborative currently exists. Our specific aims are to (1) provide the SHAIR Collaborative resources to clinical sites to use with eligible patients, (2) examine the relationship between the use of the SHAIR Collaborative resources and patient reach, and (3) promote the emergence of a sustained learning collaborative in this clinical field, building on a partnership with the American Society of Breast Surgeons (ASBrS). We will conduct a two-phased implementation project: phase 1 pilot at five sites and phase 2 scale up at up to an additional 32 clinical sites across North America. The SHAIR Collaborative online platform will offer free access to conversation aids, training videos, electronic health record and patient portal integration guidance, a feedback dashboard, webinars, support center, and forum. We will use RE-AIM for data collection and evaluation. Our primary outcome is patient reach. Secondary data will include (1) patient-reported data from an optional, anonymous online survey, (2) number of active sites and interviews with site champions, (3) Normalization MeAsure Development questionnaire data from phase 1 sites, adaptations data utilizing the Framework for Reporting Adaptations and Modifications-Extended/-Implementation Strategies, and tracking implementation facilitating factors, and (4) progress on sustainability strategy and plans with ASBrS. The SHAIR Collaborative will reach early-stage breast cancer patients across North America, evaluate patient-reported outcomes, engage up to 37 active sites, and potentially inform engagement factors affecting implementation success and may be sustained by ASBrS.


[Composition, abundance and distribution of populations of commercially important gastropods in La Guajira, Colombian Caribbean].
In the continental Colombian Caribbean the conch resource exploitation and the status of snails populations has been poorly studied, which are reflected in the lack of fisheries management. This study assesses composition, population density and distribution of the gastropods species that make conch resource in La Guajira region. Underwater visual censuses for snails were performed between September-November 2009 in 145100x4m (400m2) transects, spanning a total area of 56920m2 between Riohacha and Cabo de la Vela. The study was complemented with the evaluation of composition, abundance and size of gastropods conch found in the discarded-by-fishermen shell mounds in 13 beaches. In October 2010 another 40 transects were evaluated (16 000 m2) from the Southern of Riohacha to the Camarones village (La Guajira). We found a total of 9911 snails belonging to 12 species, the most abundant being Strombus pugilis with 8 912 individuals and an average density of 1 538.4 +/- 3 662.6 ind./ha, followed by Vasum muricatum with 374 individuals and an average density of 51.8 +/- 91.2 ind./ha. Calculating the importance value index (IVI) for both living organisms as the empty shells on beaches, shows that Turbinella angulata is the most used species by artisanal fishermen in the region. Cassis madagascariensis and Cassis tuberosa are also important snail resources in the region (as suggested by the number of empty shells found in beaches), but its densities were low. Strombus gigas, with only three living organisms found in the area, presented the lowest abundance ever found in the Colombian Caribbean (0.52 +/- 3.6 ind./ha), showing that queen conch population in La Guajira cannot support commercial exploitation. The abundance of discarded S. gigas shells on beaches suggests resource exploitation in the recent past. Results remarks the urgency of implementing management plans for snail fisheries in the region.


Timing Matters: HIV Testing Rates in the Emergency Department.
Study Objectives. In response to the 2010 New York State HIV testing law, we sought to understand the contextual factors that influence HIV testing rates in the emergency department (ED). Methods. We analyzed electronic health record logs from 97,655 patients seen in three EDs in New York City. We used logistic regression to assess whether time of day, day of the week, and season significantly affected HIV testing rates. Results. During our study period, 97,655 patients were evaluated and offered an HIV test. Of these, 7,763 (7.9%) agreed to be tested. Patients arriving between 6 a.m. and 7:59 p.m. were significantly (P < 0.001) more likely to be tested for HIV, followed by patients arriving between 8:00 p.m. and 9:59 p.m. (P < 0.01) and followed by patients arriving between 5-5:59 a.m. and 10-10:59 p.m. (P < 0.05) compared to patients arriving at midnight. Seasonal variation was also observed, where patients seen in July, August, and September (P < 0.001) were more likely to agree to be tested for HIV compared to patients seen in January, while patients seen in April and May (P < 0.001) were less likely to agree to be tested for HIV. Conclusion. Time of day and season affect HIV testing rates in the ED, along with other factors such as patient acuity and completion of other blood work during the ED visit. These findings provide useful information for improving the implementation of an HIV testing program in the ED.


The L-tartrate/succinate antiporter TtdT (YgjE) of L-tartrate fermentation in Escherichia coli.
Escherichia coli ferments L-tartrate under anaerobic conditions in the presence of an additional electron donor to succinate. The carrier for L-tartrate uptake and succinate export and its relation to the general C(4)-dicarboxylate carriers DcuA, DcuB, and DcuC were studied. The secondary carrier TtdT, encoded by the ttdT (previously called ygjE) gene, is required for the uptake of L-tartrate. The ttdT gene is located downstream of the ttdA and ttdB genes, encoding the L-tartrate dehydratase TtdAB. Analysis of mRNA by reverse transcription-PCR showed that ttdA, ttdB, and ttdT are cotranscribed. Deletion of ttdT abolished growth by L-tartrate and degradation of L-tartrate completely. Bacteria containing TtdT catalyze L-tartrate or succinate uptake and specific heterologous L-tartrate/succinate antiporting. D-Tartrate is not a substrate for TtdT. TtdT operates preferentially in the direction of tartrate uptake and succinate excretion. The Dcu carriers do not support anaerobic growth on L-tartrate or L-tartrate transport. TtdT is related in sequence and function to CitT, which catalyzes heterologous citrate/succinate antiporting in citrate fermentation.


Erlotinib for Patients with EGFR Wild-Type Metastatic NSCLC: a Retrospective Biomarkers Analysis.
Erlotinib is approved for the treatment of patients with EGFR mutation positive, metastatic NSCLC. It is also approved as second/third line therapy for EGFR mutation negative patients, but in this setting the benefit of erlotinib is modest and there is no validated biomarker for selecting EGFR wild-type patients who may benefit the most from the treatment. We retrospectively assessed EGFR and K-RAS mutational status, and EGFR, c-MET and IGF1-R expression in tumor samples of 72 patients with metastatic NSCLC treated with erlotinib after at least one prior line of chemotherapy, from 2008 to 2012. We analyzed the association between biomarkers and outcome (RR, PFS, and OS). EGFR mutated patients achieved a better RR (56% vs 8%, p = .002), PFS (10 vs 3 months, HR 0.53, p = 0.48) and OS (20 vs 6 months, HR 0.55, p = .07), compared to EGFR wild-type patients. Among 63 EGFR wild-type patients, those with EGFR high-expression had a better outcome in terms of RR (40% vs 2%, p = .002), PFS (7.5 vs 2 months, HR 0.45, p = .007) and OS (30 vs 5 months, HR 0.34, p < .001) compared to patients with EGFR intermediate or low/negative-expression. IGF1-R expression, c-MET expression and K-RAS mutational status did not significantly affect the outcome; however, no patients with K-RAS mutation or c-MET high-expression achieved an objective response. In patients with metastatic, chemo-refractory EGFR wild-type NSCLC, EGFR high-expression may represent a positive predictor of activity for erlotinib, whereas K-RAS mutation and c-MET high-expression may predict lack of activity. These findings deserve further prospective evaluation.


pH-Controlled molecular switches and the substrate-directed self-assembly of molecular capsules with a calix[4]pyrrole derivative.
10alpha,20alpha-Bis(4-nitrophenyl)calix[4]pyrrole (1) forms 1:1 complexes with anions of selected aromatic hydroxy acids in which the host orientation within the guest is controlled by a change in the pH value. Some bis-anionic guests, including those obtained from 4-hydroxybenzoic acid, 1,4- and 1,3-benzenedicarboxylic acids, induce the self-assembly of molecular capsules involving two molecules of the receptor. (1)H NMR data and solid-state structures of the 1:1 complex of 1 with p-C(6)H(4)(COOH)(COO(-))(+)NMe(4) and the 2:1 capsule [(1)(2)m-C(6)H(4)(COO(-))(2)((+)NMe(4))(2)] provide structural details in solution and in the solid state.


Helminth control used by trainers of thoroughbreds in England.
A telephone survey was conducted of the methods used to control parasitic worms at 106 thoroughbred training yards. Most of the horses were allowed access to grass and were therefore at risk of infection. The control methods relied primarily on the use of anthelmintics and appeared reasonably successful because only 44 per cent of trainers reported observing clinical signs of nematode infections. They dosed their horses frequently, 40 per cent treating every four to six weeks and 25 per cent treating every seven to eight weeks. New arrivals on yards were usually treated with anthelmintic but the strategies used would be unlikely to prevent the introduction of anthelmintic-resistant nematodes on most yards or to deal with encysted cyathostomes. Trainers were responsible for the design of most control schemes, and only 42 per cent of them based their choice of anthelmintic on veterinary advice.


Femur fractures in chest-injured patients: is reaming contraindicated?
To determine if reamed femoral intramedullary nailing increases the pulmonary complications seen in chest-injured patients. Retrospective review of prospectively collected trauma database data from January 1991 to October 1994. Methodist Hospital, Indianapolis, Indiana, Level I Trauma Center. Group I: Chest-injured patients [chest Abbreviated Injury Score (AIS) > or = 2] without femur or tibia fractures. Group II: Chest-injured patients (chest AIS > or = 2) with femoral reamed intramedullary fixation. Group III: Chest-injured patients (chest AIS > or = 2) with femoral shaft fixation using nonreamed fixation (rush rods, plating, or external fixation). Group IV: Non-chest-injured patients (chest AIS < 2) with femoral reamed intramedullary fixation. MAIN OUTCOME MEASUREMENT/HYPOTHESIS: Reamed femoral intramedullary nailing does not alter pulmonary outcomes, even in chest-injured patients. Groups I and II had a very similar incidence of adult respiratory distress syndrome (ARDS), pneumonia, and number of ventilator days. Group III had a significantly higher incidence of ARDS and number of ventilator days than did Group I or II. Group III did not have a chest AIS score significantly different than Groups I and II. Group II had significantly higher ARDS and more ventilator days than did Group IV when only analyzing raw data. When injury severity was adjusted, there were no significant differences in pulmonary outcomes. Reamed intramedullary femoral fixation did not increase pulmonary morbidity in chest-injured patients.


Genome-Wide Identification of Loci Associated With Phenology-Related Traits and Their Adaptive Variations in a Highbush Blueberry Collection.
Genetic variation in phenological traits is the key in expanding production areas of crops. Southern highbush blueberry (SHB) is a blueberry cultivar group adapted to warmer climates and has been developed by multiple interspecific hybridizations between elite northern highbush blueberry (NHB) (Vaccinium corymbosum L.) and low-chill Vaccinium species native to the southern United States. In this study, we employed a collection of diverse SHB accessions and performed a genome-wide association study (GWAS) for five phenology-related traits [chilling requirement (CR), flowering date, ripening date, fruit development period, and continuous flowering] using polyploid GWAS models. Phenology-related traits showed higher heritability and larger correlation coefficients between year replications, which resulted in the detection of robust phenotype-genotype association peaks. Notably, a single association peak for the CR was detected on Chromosome 4. Comparison of genotypes at the GWAS peaks between NHB and SHB revealed the putative introgression of low-chill and late-flowering alleles into the highbush genetic pool. Our results provide basic insights into the diversity of phenological traits in blueberry and the genetic establishment of current highbush cultivar groups.


Monoclonal antibodies to human urokinase identify the single-chain pro-urokinase precursor.
Monoclonal antibodies have been obtained that recognize either the A or B chain of human urinary urokinase. These antibodies identify human urokinase-producing cells and the product of urokinase mRNA. Anti-urokinase monoclonal antibodies precipitate an approximately equal to 54,000-dalton protein synthesized in vitro in a rabbit reticulocyte cell-free system. This pro-urokinase appears to be the precursor of both A and B chains of human urinary urokinase. Urokinase mRNA in human kidney constitutes only 0.1% or less of total poly(A)+ RNA.


Effect of glutathione on arecanut treated normal human buccal fibroblast culture.
Experimental studies have shown arecanut to be a cytotoxic substance with mutagenic and carcinogenic potential. The present study was undertaken to evaluate the effect of glutathione on arecanut treated human buccal fibroblast culture and its potential as a chemopreventive agent. Fibroblast culture was done in Dulbecco's Modified Eagle's Medium MEM) supplemented with 10% Fetal Calf Serum (FCS) and antibiotic at 370C degrees in an atmosphere of 5% carbon di-oxide and 95% air. The fibroblast cells were subjected to different concentrations of aqueous extracts of raw and boiled arecanut. Fibroblasts were plated in two 24-well culture plates and in each plate, cells were dividt,ednto 2 groups; 600gg microml of reduced glutathione was added to the first group of cells; subsequently, aqueous extracts of raw and boiled arecanut at least and highest concentrations i.e., 20j. microml and 100lg microml were added to the first group of cells in the respective plates whereas the second group served as a control. The morphological alterations and cell survival were assayed at 24, 48, 72, and 96 hours. Results Morphologically, the initial (10 hours) attached fibroblast cells were converted from spheroidal shape towards hexagonal and finally to a fully extended spindle shaped configuration. The three morphological types of fibroblasts at 48 hours were F-I, F-II and F-III. Aqueous extract of raw arecanut exhibited significant cytotoxicity (p < .0 001) at all time periods studied, when compared against the control values of untreated fibroblasts. Addition of reduced glutathione to cultures showed a significant (p < 0. 001) reduction in cytotoxicity, as indicated by higher optical density values and morphological reversion to the spindle-shaped configuration. Co Addition of glutathione reduced the cytotoxic and morphological alterations of the fibroblasts treated with aqueous extracts of both raw and boiled arecanut.


Metabolic Syndrome Predicts Uric Acid Stones in the Upper Urinary Tract: Development and Validation of a Nomogram Model.
Accurately identifying uric acid stones is pivotal in determining the appropriate treatment strategy for patients. This study aimed to design an innovative nomogram to predict the occurrence of uric acid stones in the upper urinary tract. This retrospective study examined 680 patients with urinary stones from October 2019 to September 2022. Risk factors were identified through univariate and multivariate logistic regression, leading to the development of a nomogram. This model's validity was then assessed internally using receiver operating characteristic (ROC) curves, the area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Our findings revealed that metabolic syndrome (odds ratio (OR) = 4.347, 95% confidence interval (CI) 1.306-14.466, p = 0.017), serum urea levels (OR = 1.004, 95% CI 1.143-2.002, p = 0.004), urinary pH (OR = 0.185, 95% CI 0.059-0.583, p = 0.004), urinary potassium (OR = 0.926, 95% CI 0.875-0.981, p = 0.009), and urinary calcium (OR = 0.693, 95% CI 0.492-0.977, p = 0.037) are independent factors for upper urinary tract uric acid stones. Utilizing the five variables, we developed a predictive nomogram. The AUC of the training cohort and the validation cohort were 0.917 (95% CI 0.871-0.963) and 0.914 (95% CI 0.850-0.978), respectively. Calibration curves indicated strong consistency in both cohorts, and the DCA revealed the model's clinical utility. We devised a reliable and user-friendly nomogram to predict uric acid stones in the upper urinary tract. It is based on metabolic syndrome, serum biochemical markers, and 24-hour urinary parameters. Key determinants include metabolic syndrome, serum urea, urinary pH, urinary potassium and urinary calcium.


Preparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(l-lysine) block copolymer: potential implications on diabetic nephropathy.
The poly(ethylene glycol)-b-brush poly(l-lysine) polymer (PEG-b-(PELG50-g-PLL3)) was synthesized and evaluated as a nanocarrier for prolonging delivery of exenatide through the abdominal subcutaneous injection route. The isoelectric point of exenatide was 4.86, and exenatide could combine with PEG-b-(PELG50-g-PLL3) polymers via electrostatic interactions at pH 7.4. This polymer was a good candidate for achieving prolonged drug delivery for exenatide, considering its high molecular weight. Besides the physicochemical characterization of the polymer, in vitro and in vivo applications were researched as a sustained exenatide delivery system. In the in vitro release research, 20.16%-76.88% of total exenatide was released from the PEG-b-(PELG50-g-PLL3) polymer within 7 days. The synthesized block-brush polymers and exenatide-block-brush polymers were analyzed by nuclear magnetic resonance spectroscopy, gel permeation chromatography, transmission electron microscopy, nanoparticle size instrument, and scanning electron microscopy. The best formulation was selected for in vivo experimentation to achieve blood glucose control in diabetic rat models using free exenatide as the control. The hypoglycemic action of the formulation following subcutaneous injection in diabetic rats lasted 7 days, and the results indicated that exenatide-block-brush polymers demonstrate enhanced long-acting hypoglycemic action. Besides the hypoglycemic action, exenatide-block-brush polymers significantly alleviated diabetic nephropathy via improving renal function, decreasing oxidative stress injury, decreasing urinary albumin excretion rate, mitigating albumin/creatinine ratio, reducing blood lipids, abating kidney index, weakening apoptosis, and downregulating expression of connective tissue growth factor. All of the results suggested that PEG-b-(PELG50-g-PLL3) polymers could be used as potential exenatide nanocarriers, with efficient encapsulation and sustained release.


Racial differences in tumor stage and survival for colorectal cancer in an insured population.
Despite declining death rates from colorectal cancer (CRC), racial disparities have continued to increase. In this study, the authors examined disparities in a racially diverse group of insured patients. This study was conducted among patients who were diagnosed with CRC from 1993 to 1998, when they were enrolled in integrated healthcare systems. Patients were identified from tumor registries and were linked to information in administrative databases. The sample was restricted to non-Hispanic whites (n = 10,585), non-Hispanic blacks (n = 1479), Hispanics (n = 985), and Asians/Pacific Islanders (n = 909). Differences in tumor stage and survival were analyzed by using polytomous and Cox regression models, respectively. In multivariable regression analyses, blacks were more likely than whites to have distant or unstaged tumors. In Cox models that were adjusted for nonmutable factors, blacks had a higher risk of death from CRC (hazard ratio [HR], 1.17; 95% confidence interval [95% CI], 1.06-1.30). Hispanics had a risk of death similar to whites (HR, 1.04; 95% CI, 0.92-1.18), whereas Asians/Pacific Islanders had a lower risk of death from CRC (HR, 0.89; 95% CI, 0.78-1.02). Adjustment for tumor stage decreased the HR to 1.11 for blacks, and the addition of receipt of surgical therapy to the model decreased the HR further to 1.06. The HR among Hispanics and Asians/Pacific Islanders was stable to adjustment for tumor stage and surgical therapy. The relation between race and survival from CRC was complex and appeared to be related to differences in tumor stage and therapy received, even in insured populations. Targeted interventions to improve the use of effective screening and treatment among vulnerable populations may be needed to eliminate disparities in CRC.


Pharmacokinetic study of Strongylocentrotus nudus egg polysaccharide in rats and beagles using a 3H-labeling method.
Strongylocentrotus nudus egg polysaccharide (SEP) extracted from sea urchins has potential anticancer activity. However, little is known about its pharmacokinetic properties. To investigate the pharmacokinetics of SEP, it was radiolabeled with tritium. Furthermore, a sensitive, selective, and rapid liquid scintillation counter (LSC) method for quantifying 3H-SEP in biological matrix was validated. The lower quantification limit of the method was 4 Bq. The relative standard deviations (RSDs) of the intra- and inter-day precision were <3.0% and <3.9%, respectively. 3H-SEP was successfully applied to investigate the pharmacokinetics of SEP after intravenous administration of 20, 40, and 80 mg/kg (40 μCi/kg) in rats and 5, 10, and 20 mg/kg (6 μCi/kg) in beagles. The AUC(0-t) of SEP at three different doses was 487.81 ± 39.99 mg/L*h, 1,003.10 ± 95.94 mg/L*h, and 2,188.84 ± 137.73 mg/L*h in rats and 144.12 ± 3.78 mg/L*h, 322.62 ± 28.03 mg/L*h, and 754.17 ± 37.79 mg/L*h in beagles. The terminal elimination half-life (t1/2) of SEP was longer in beagles (204.29 ± 139.34 h) than in rats (35.48 ± 6.04 h). The concentration of SEP in plasma declined rapidly in both rats and beagles. All the study results provide detailed pharmacokinetic profiles of SEP in two kinds of animals, which will be helpful for further development.


Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia.
The authors undertook a multiinstitutional Phase II cooperative group study to examine the potential of oral fish oil fatty acid supplements administered at high doses to slow weight loss and to improve quality of life in patients with malignancy-related cachexia. Patients with advanced malignancy and weight loss > or = 2% of body weight in the preceding month took concentrated, high-dose omega-3 fatty acid capsules (7.5 g eicosapentaenoic acid plus docosahexaenoic acid for a 70 kg individual) that were supplied by the National Institutes of Health. Forty-three patients with moderate or severe malnutrition were enrolled. The median time receiving treatment was 1.2 months. For the 36 patients who took at least 1 capsule and did not have edema, there was a weight change ranging from -6.2 kg to +3.5 kg and an overall median weight loss of 0.8 kg. Twenty-four patients had weight stabilization (a gain of < or = 5% or a loss of < 5%), 6 patients gained > 5% of their body weight, and 6 patients lost > or = 5% of their body weight. There was marked variability in the tolerability of the capsules, and many patients had gastrointestinal side effects. There was a correlation between time receiving treatment and weight gain for the 22 patients who were able to tolerate the capsules for at least 1 month. Quality-of-life scores were superior for patients who gained weight. A majority of patients did not gain weight, and in that sense, the results of the study were unfavorable. However, a small but definite subset of patients had weight stabilization or weight gain. This suggests that omega-3 fatty acids have potential utility at the study doses, which were more than twice the doses used in published Phase III studies.


Spinal Cord Stimulation for Gait Disorders in Parkinson's Disease and Atypical Parkinsonism: A Systematic Review of Preclinical and Clinical Data.
Falls in extrapyramidal disorders, particularly Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP), are key milestones affecting patients' quality of life, incurring increased morbidity/mortality and high healthcare costs. Unfortunately, gait and balance in parkinsonisms respond poorly to currently available treatments. A serendipitous observation of improved gait and balance in patients with PD receiving spinal cord stimulation (SCS) for back pain kindled an interest in using SCS to treat gait disorders in parkinsonisms. We reviewed preclinical and clinical studies of SCS to treat gait dysfunction in parkinsonisms, covering its putative mechanisms and efficacies. Preclinical studies in animal models of PD and clinical studies in patients with PD, PSP, and MSA who received SCS for gait disorders were included. The main outcome assessed was clinical improvement in gait, together with outcome measures used and possible mechanism of actions. We identified 500 references, and 45 met the selection criteria and have been included in this study for analysis. Despite positive results in animal models, the outcomes in human studies are inconsistent. The lack of blind and statistically powered studies, the heterogeneity in patient selection and study outcomes, and the poor understanding of the underlying mechanisms of action of SCS are some of the limiting factors in the field. Addressing these limitations will allow us to draw more reliable conclusions on the effects of SCS on gait and balance in extrapyramidal disorders.


Efficient CRISPR/Cas9-Mediated Mutagenesis in Primary Murine T Lymphocytes.
The ability to alter gene expression directly in T lymphocytes has provided a powerful tool for understanding T cell biology, signaling, and function. Manipulation of T cell clones and primary T cells has been accomplished primarily through overexpression or gene-silencing studies using cDNAs or shRNAs, respectively, which are often delivered by retroviral or lentiviral transduction or direct transfection methods. The recent development of CRISPR/Cas9-based mutagenesis has revolutionized genomic editing, allowing unprecedented genetic manipulation of many cell types with greater precision and ease. This article outlines a protocol for CRISPR/Cas9-mediated mutagenesis in primary T lymphocytes from Cas9 transgenic mice using retroviral delivery of guide RNAs. © 2018 by John Wiley & Sons, Inc.


Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: the ARIC (Atherosclerosis Risk In Communities) study.
We evaluated whether carotid intima-media thickness (CIMT) and the presence or absence of plaque improved coronary heart disease (CHD) risk prediction when added to traditional risk factors (TRF). Traditional CHD risk prediction schemes need further improvement as the majority of the CHD events occur in the "low" and "intermediate" risk groups. On an ultrasound scan, CIMT and presence of plaque are associated with CHD, and therefore could potentially help improve CHD risk prediction. Risk prediction models (overall, and in men and women) considered included TRF only, TRF plus CIMT, TRF plus plaque, and TRF plus CIMT plus plaque. Model predictivity was determined by calculating the area under the receiver-operating characteristic curve (AUC) adjusted for optimism. Cox proportional hazards models were used to estimate 10-year CHD risk for each model, and the number of subjects reclassified was determined. Observed events were compared with expected events, and the net reclassification index was calculated. Of 13,145 eligible subjects (5,682 men, 7,463 women), approximately 23% were reclassified by adding CIMT plus plaque information. Overall, the CIMT plus TRF plus plaque model provided the most improvement in AUC, which increased from 0.742 (TRF only) to 0.755 (95% confidence interval for the difference in adjusted AUC: 0.008 to 0.017) in the overall sample. Similarly, the CIMT plus TRF plus plaque model had the best net reclassification index of 9.9% in the overall population. Sex-specific analyses are presented in the manuscript. Adding plaque and CIMT to TRF improves CHD risk prediction in the ARIC (Atherosclerosis Risk In Communities) study.


The Common p.R114W HNF4A Mutation Causes a Distinct Clinical Subtype of Monogenic Diabetes.
HNF4A mutations cause increased birth weight, transient neonatal hypoglycemia, and maturity onset diabetes of the young (MODY). The most frequently reported HNF4A mutation is p.R114W (previously p.R127W), but functional studies have shown inconsistent results; there is a lack of cosegregation in some pedigrees and an unexpectedly high frequency in public variant databases. We confirm that p.R114W is a pathogenic mutation with an odds ratio of 30.4 (95% CI 9.79-125, P = 2 × 10(-21)) for diabetes in our MODY cohort compared with control subjects. p.R114W heterozygotes did not have the increased birth weight of patients with other HNF4A mutations (3,476 g vs. 4,147 g, P = 0.0004), and fewer patients responded to sulfonylurea treatment (48% vs. 73%, P = 0.038). p.R114W has reduced penetrance; only 54% of heterozygotes developed diabetes by age 30 years compared with 71% for other HNF4A mutations. We redefine p.R114W as a pathogenic mutation that causes a distinct clinical subtype of HNF4A MODY with reduced penetrance, reduced sensitivity to sulfonylurea treatment, and no effect on birth weight. This has implications for diabetes treatment, management of pregnancy, and predictive testing of at-risk relatives. The increasing availability of large-scale sequence data is likely to reveal similar examples of rare, low-penetrance MODY mutations.


A native antigen "reverse capture" microarray platform for autoantibody profiling of prostate cancer sera.
Cancer sera contain antibodies that react with autologous cellular antigens. Here, we report the use of a novel native antigen-based platform, the "reverse capture" autoantibody microarray, for identification of autoantigens against which autoantibody expression may be used to differentiate between patients with prostate cancer and benign prostate hyperplasia (BPH). Serum samples were collected at our institution from patients with BPH and patients with prostate carcinoma with similar blood prostate-specific antigen levels. IgG was purified from individual prostate cancer sera, differentially labeled with fluorescent dyes, and competitively hybridized against purified IgG from a group of well-characterized BPH control patients on our reverse capture microarray platform. For each experiment, we performed a two-slide dye-swap. Using this platform, we identified 28 unique antigen-autoantibody reactivities that have the potential to discriminate prostate cancer from BPH. These autoantigens, with p-values ≤0.01, can be placed into the following general categories: protein kinases, cell-cycle regulators, cancer-growth factors, apoptosis mediators, and transcription factors. In addition, only 1 of the 28 autoantigens remained differentially targeted by autoantibodies in post-surgical prostate cancer patients after a minimum 1-year follow-up. Autoantibody profiling using this platform may be a useful tool for differentiating between malignant and benign diseases of the prostate.


Impact on early outcomes and immune reconstitution of high-dose post-transplant cyclophosphamide vs anti-thymocyte globulin after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation.
We have compared prospectively the outcome and immune reconstitution of patients receiving either post-transplant cyclophosphamide (PTCY) (n = 30) or anti-thymocyte globulin ATG (n = 15) as Graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation (allo-SCT). The outcome and immune reconstitution of patients receiving either of these two regimens were compared prospectively. This study allowed also to investigate the impact of PTCY between haplo-identical vs matched donors and of clofarabine as part of the RIC regimen. The γ/δ T-cells, α/β T-cells (CD8+ and CD4+), NK T-cells, NK cells, B-cells, Tregs and monocytes were analyzed by flow cytometry from a total of 583 samples. In the PTCY group significant delayed platelets recovery, higher CD3+ donor chimerism, higher HHV-6 and lower EBV reactivations were observed. Early survival advantage for CD4+ T-cells, Tregs and α/β T-cells was documented in the PTCY group while it was the case for α/β T-cells, NK cells and monocytes in the ATG group. Higher counts of NK and monocytes were observed at days +30 and/or day+60 in the ATG group. Both results were retained even in the case of mismatched donors. However, higher percentages of CD4+ T-cells, α/β T-cells and Tregs were observed with haplo-identical donors in the PTCY group. Finally, clofarabine was responsible for early survival advantage of NK T-cells in the PTCY group while it abrogated the early survival advantage of γ/δ T-cells in the ATG group. In conclusion, there are marked differences in the immunological effects of ATG vs PTCY as GVHD prophylaxis for RIC PBSC allo-SCT.


Neural and Molecular Mechanisms of Biological Embedding of Social Interactions.
Animals operate in complex environments, and salient social information is encoded in the nervous system and then processed to initiate adaptive behavior. This encoding involves biological embedding, the process by which social experience affects the brain to influence future behavior. Biological embedding is an important conceptual framework for understanding social decision-making in the brain, as it encompasses multiple levels of organization that regulate how information is encoded and used to modify behavior. The framework we emphasize here is that social stimuli provoke short-term changes in neural activity that lead to changes in gene expression on longer timescales. This process, simplified-neurons are for today and genes are for tomorrow-enables the assessment of the valence of a social interaction, an appropriate and rapid response, and subsequent modification of neural circuitry to change future behavioral inclinations in anticipation of environmental changes. We review recent research on the neural and molecular basis of biological embedding in the context of social interactions, with a special focus on the honeybee.


Intimate Partner Maltreatment Recidivism in U.S. Air Force Families.
Research has demonstrated that perpetrator characteristics (gender, age, and military status) and incident characteristics (perpetrator substance use and initial incident severity) are associated with intimate partner maltreatment recidivism. This study assessed whether these variables were associated with intimate partner maltreatment recidivism in U.S. Air Force families during a 16-yr period (1997-2013). During the study period, 21% of the intimate partner maltreatment perpetrators in the U.S. Air Force committed more than one incident of maltreatment. In terms of perpetrator characteristics, male perpetrators reoffended more than female perpetrators, younger perpetrators reoffended more than older perpetrators, and active duty perpetrators reoffended more than civilians. Whether a perpetrator was enlisted or an officer was not associated with the likelihood of recidivism. In terms of incident characteristics, substance use (which was mainly alcohol use) during an initial maltreatment incident was associated with recidivism, but the severity of perpetrators' initial maltreatment incident was not. However, for perpetrators who reoffended, the severity of their initial incident was associated with the severity of subsequent incidents. On the basis of these findings, the need for targeted interventions to reduce intimate partner maltreatment recidivism is discussed.


A new species of the genus Ochthebius (Coleoptera, Hydraenidae) from the Ogasawara Islands, Japan, with a description of the larva.
A new species of the genus Ochthebius, O. (O.) sasakiisp. nov., is described from the Ogasawara Islands, Japan, with a description of the larva. This record is the first of the family Hydraenidae from the Ogasawara Islands. This species belongs to the punctatus species group and is similar to two Japanese species, O. (O.) inermis Sharp, 1884 and O. (O.) danjo Nakane, 1990, but it differs from them in both adult and larval characters. The larva of O. (O.) inermis is also described for comparison.


[1-year follow-up of astigmatism after cataract operation. Wound closure with cross-stitch suture vs. no-stitch suture technique].
Like the type of wound opening, wound closure has an important influence on postoperative astigmatism. In a series of 300 patients, for 1 year we examined postoperative astigmatism after cataract surgery with sutured scleral wound closure and the no-stitch technique. In the early postoperative period, the no-stitch technique. (1.00 dpt +/- 0.83) had less induced astigmatism (vector analysis of Jaffé), compared with sutured scleral wound closure (1.77 dpt +/- 1.36), as well as a smaller standard deviation. Furthermore, with the no-stitch technique a nearly stable situation is reached within the first 4 weeks. In the late postoperative period, the astigmatism induced after sutured scleral wound closure (1.01 dpt +/- 0.57) is only a little greater than with the no-stitch technique (0.85 dpt +/- 0.65). On both techniques more than every second patient shows astigmatism (sutured scleral wound closure: 61%; no-stitch technique: 52%).


Machine Learning and Virtual Reality on Body Movements' Behaviors to Classify Children with Autism Spectrum Disorder.
Autism spectrum disorder (ASD) is mostly diagnosed according to behavioral symptoms in sensory, social, and motor domains. Improper motor functioning, during diagnosis, involves the qualitative evaluation of stereotyped and repetitive behaviors, while quantitative methods that classify body movements' frequencies of children with ASD are less addressed. Recent advances in neuroscience, technology, and data analysis techniques are improving the quantitative and ecological validity methods to measure specific functioning in ASD children. On one side, cutting-edge technologies, such as cameras, sensors, and virtual reality can accurately detect and classify behavioral biomarkers, as body movements in real-life simulations. On the other, machine-learning techniques are showing the potential for identifying and classifying patients' subgroups. Starting from these premises, three real-simulated imitation tasks have been implemented in a virtual reality system whose aim is to investigate if machine-learning methods on movement features and frequency could be useful in discriminating ASD children from children with typical neurodevelopment. In this experiment, 24 children with ASD and 25 children with typical neurodevelopment participated in a multimodal virtual reality experience, and changes in their body movements were tracked by a depth sensor camera during the presentation of visual, auditive, and olfactive stimuli. The main results showed that ASD children presented larger body movements than TD children, and that head, trunk, and feet represent the maximum classification with an accuracy of 82.98%. Regarding stimuli, visual condition showed the highest accuracy (89.36%), followed by the visual-auditive stimuli (74.47%), and visual-auditive-olfactory stimuli (70.21%). Finally, the head showed the most consistent performance along with the stimuli, from 80.85% in visual to 89.36% in visual-auditive-olfactory condition. The findings showed the feasibility of applying machine learning and virtual reality to identify body movements' biomarkers that could contribute to improving ASD diagnosis.


Determination of preference-equivalent levels for fan noise and their prediction by indices based on specific loudness patterns.
In a previous study by the authors, two indices were identified as appropriate descriptors for perceptual dimensions of fan noise. The index Nlow describes the amount of low-frequency loudness relative to the overall loudness. The index Nratio represents the ratio between the amount of loudness resulting from mid-frequency content and that from high frequencies. The aim of this study is to quantify how variations in these two indices affect subjects' preferences and loudness judgments. In listening experiments, fan noise signals were adjusted separately to equal loudness and equal preference compared to a common reference sound by varying their level in an adaptive procedure. The fan noises used in the listening tests consisted of 11 typical signals from three major groups of fan sounds from the earlier study and 18 signals that were parametrically varied in terms of the two indices. Reductions in A-weighted sound pressure level of up to 15 dB were necessary to make unpleasant fan sounds equally preferred as the fixed reference sound. A regression model based on the index Nratio explains 81% of the variation in the evaluation data with a root-mean-squared error of 2.53 dB.


Rifampicin reduces plasma concentrations of moxifloxacin in patients with tuberculosis.
The long duration of the current tuberculosis (TB) treatment is demanding and warrants the development of new drugs. Moxifloxacin shows promising results and may be combined with rifampicin to shorten the duration of TB treatment. Rifampicin induces the phase II metabolic enzymes that are involved in the biotransformation of moxifloxacin. Therefore, the interaction between rifampicin and moxifloxacin should be investigated. Nineteen Indonesian patients with pulmonary TB who were in the last month of their TB treatment completed a 1-arm, 2-period, fixed-order pharmacokinetic study. In phase 1 of the study, they received 400 mg of moxifloxacin every day for 5 days in addition to 450 mg of rifampicin and 600 mg of isoniazid 3 times per week. In phase 2 of the study, after a 1-month washout period, patients received moxifloxacin for another 5 days (without rifampicin and isoniazid). A 24-h pharmacokinetic curve for moxifloxacin was recorded on the last day of both study periods, and its pharmacokinetic parameters were evaluated for an interaction with rifampicin, using a bioequivalence approach. Coadministration of moxifloxacin with rifampicin and isoniazid resulted in an almost uniform decrease in moxifloxacin exposure (in 18 of 19 patients). The geometric means for the ratio of phase 1 area under the curve to phase 2 area under the curve and for the ratio of phase 1 peak plasma concentration to phase 2 peak plasma concentration were 0.69 (90% confidence interval, 0.65-0.74) and 0.68 (90% confidence interval, 0.64-0.73), respectively. The median time to reach peak plasma concentration for moxifloxacin was prolonged from 1 h to 2.5 h when combined with rifampicin and isoniazid (P=.003). Coadministration of moxifloxacin with intermittently administered rifampicin and isoniazid results in reduced moxifloxacin plasma concentrations, which is most likely the result of induced glucuronidation or sulphation by rifampicin. Further studies are warranted to evaluate the impact of the interaction on the outcome of TB treatment.


A spontaneous rupture of the external iliac vein revealed as a phlegmasia cerulea dolens with acute lower limb ischemia: Case report and review of the literature.
We reported a case in a previously healthy 45-year-old woman of spontaneous rupture of the left external iliac vein, which was revealed as a phlegmasia cerulea dolens with acute lower limb ischemia. A tear on the anterior surface of the vein was discovered during an emergency laparotomy, and the rent was repaired successfully. Twenty-four hours later, the leg swelling increased, and at the reexploration, the common iliac vein was found to be occluded by an organized thrombus as the result of a well-endothelialized membranous band (Cockett or May-Turner syndrome). A Palma-Dale operation (crossover saphenous bypass grafting) was performed secondarily. The swelling in the leg diminished slowly, and the patient was discharged 10 days later with an oral anticoagulant therapy and elastic stockings.


NGF acts via p75 low-affinity neurotrophin receptor and calpain inhibition to reduce UV neurotoxicity.
The relative roles of the high-affinity nerve growth factor (NGF) receptor, TrkA, and low-affinity p75 neurotrophin receptor (p75NTR) in neuronal survival are an active research area. We reported previously that UV treatment induces a calpain-dependent, delayed neuronal death. We show here that NGF inhibits this UV-induced cortical neuron death. Interestingly, NGF neuroprotection requires p75NTR. Because it has been reported that NGF binding to p75NTR leads to ceramide generation, we evaluated whether ceramide was also neuroprotective. We found that ceramide also inhibits UV toxicity, and that the actions of ceramide and NGF were not additive. Moreover, cycloheximide inhibited ceramide and NGF neuroprotection, suggesting that their actions require new protein synthesis. Consistent with this possibility, we found that NGF activates the expression of genes such as calbindin. Lastly, we explored the role of calpain in NGF actions. NGF and ceramide both reduced the level of calpain activation after UV treatment. This NGF effect was p75NTR dependent. Overall, we interpret these results as consistent with an NGF neuroprotective pathway wherein p75NTR activation leads sequentially to ceramide generation, new protein synthesis, and inhibition of calpain activation. Overall, these results provide insight into a p75NTR dependent pathway of NGF neuroprotection.


Comparison of truncal and caudal lesions in the vertebral column of the sand rat (Psammomys obesus).
Caudal vertebrae of sand rats (Psammomys obesus) of two age-groups were examined histologically, and the findings were compared with those obtained previously in the truncal spines of these animals. Degenerative processes were basically similar in both locations, although they were somewhat attenuated in the tail. By contrast, the incidences of disk herniation and of spondylosis were much more common in the trunk than in the tail. We concluded that in the sand rat there is a common, probably systemic, denominator for disk degeneration at all sites, and suggest that this factor is related to the peculiar water and/or electrolyte metabolism of these desert animals. Factors causing herniation of the degenerated disk and spondylosis seem to be related to local stresses which, in the presence of marked disk degeneration, may not exceed physiological limits.


[Missed diagnosis of Achilles tendon ruptures most common in elderly patients].
We audited forty-six patients with a rupture of the Achilles tendon notified to the Swedish regulatory authority (the Health and Social Care Inspectorate) due to suspicion of malpractice. The patients' history and clinical presentation differed from those with a more classical acute rupture. The diagnostic errors were often found in patients older than 60 years, they were just as common in women as in men and the symptoms often had a subacute start. In most patients, the diagnostic errors were due to an incomplete clinical examination. More than one fourth of the patients were on medication with statins or quinolones.


Pentoxifylline decreases the incidence of multiple organ failure in patients after major cardio-thoracic surgery.
We assessed the safety and efficacy of intravenous pentoxifylline [3,7-dimethyl-1-(5-oxohexyl)-xanthine] in patients at risk for developing multiple organ failure after major cardio-thoracic surgery in a single-center, randomized, placebo-controlled study. Of 816 consecutive patients who underwent major cardio-thoracic surgery, 40 who had Acute Physiology and Chronic Health Evaluation II score values > or = 19 at the first postoperative day after the surgery were included. Patients were randomized to receive either placebo (control; n = 25) or intravenous pentoxifylline treatment (pentoxifylline; n = 15) at a dosage of 1.5 mg/kg/h as an adjunct to standard supportive therapy. Main outcome measurements were duration of required ventilator support, intensive care unit stay, and incidence of renal failure. Thirty-seven patients were eligible for evaluation. No significant adverse events related to pentoxifylline treatment were observed. The duration of mechanical ventilation was significantly greater for control patients (8.3 +/- 3.1 days) compared with pentoxifylline-treated patients (3.1 +/- .9 days; p < .05). Patients treated with pentoxifylline experienced fewer days on hemofiltration (1.2 +/- .8 vs. 6.8 +/- 3.3; p < .05) and a shorter intensive care unit stay (5.2 +/- 1.1 vs. 11.4 +/- 3.1 days). There were no intergroup differences in mortality. Mortality was 33% in the pentoxifylline group and 36% among control group patients. In conclusion, supplemental pentoxifylline treatment may decrease the incidence of multiple organ failure in patients at risk of systemic inflammatory response syndrome after cardiac surgery. Additional studies are required to determine the validity of the observed effects.