Electrophilic Fluorination-Nucleophilic Addition Reaction Mediated by Selectfluor: Mechanistic Studies and New Applications.
The electrophilic fluorination-nucleophilic addition reaction with Selectfluor-type reagents upon glycals has been studied and optimized. This reaction leads to selective fluorination at the 2-position with concomitant nucleophilic addition to the anomeric center. To understand the stereochemical outcome of this process, a mechanistic study has led to the discovery that, in the fucose series, Selectfluor adds specifically in a syn manner, yielding a 1-[TEDA-CH2Cl]-2-fluoro saccharide that anomerizes slowly to a more stable intermediate. The anomeric α/β distribution was studied as a function of reactants and conditions, and it was found that a judicious choice of protective group strategy can improve the stereoselectivity of both fluorination and nucleophilic addition. Furthermore, a hypersensitive radical probe was used to probe the reaction, and no product characteristic of a radical process was isolated, suggesting that no single electron transfer occurs during the attack of the glycal on Selectfluor. The importance of solvent effect, Selectfluor counterion, and stepwise procedure has also been discussed. This study has brought an important improvement of yields and a broader range of allowed nucleophiles such as secondary alcohols of carbohydrates, amino acids, phosphates, or phosphonates. This optimized process was further applied to the modification of important bioactive molecules, including the synthesis of fluorinated daunomycin and oleandrin analogues and the oxidation of thioglycosides to the corresponding sulfoxides.


Differences in cerebral extracellular response of interleukin-1β, interleukin-6, and interleukin-10 after subarachnoid hemorrhage or severe head trauma in humans.
Microdialysis has become a routine method for biochemical surveillance of patients in neurosurgical intensive care units. To analyze the intracerebral extracellular levels of 3 interleukins (ILs) during the 7 days after major subarachnoid hemorrhage or traumatic brain injury). Microdialysate from 145 severely injured neurosurgical intensive care unit patients (88 with subarachnoid hemorrhage, 57 with traumatic brain injury) was collected every 6 hours for 7 days. The concentrations of IL-1β and IL-6 were determined by fluorescence multiplex bead technology, and IL-10 was determined by enzyme-linked immunosorbent assay. Presented are the response patterns of 3 ILs during the first week after 2 different types of major brain injury. These patterns are different for each IL and also differ with respect to the kind of pathological impact. For both IL-1β and IL-6, the initial peaks (mean values for all patients at day 2 being 26.9 ± 4.5 and 4399 ± 848 pg/mL, respectively) were followed by a gradual decline, with IL-6 values remaining 100-fold higher compared with IL-1β. Female patients showed a stronger and more sustained response. The response of IL-10 was different, with mean values less than 23 pg/mL and with no significant variation between any of the postimpact days. For all 3 ILs, the responses were stronger in subarachnoid hemorrhage patients. The study also indicates that under normal conditions, IL-1β, IL-6, and IL-10 are present only at very low concentrations or not at all in the extracellular space of the human brain. This is the first report presenting in some detail the human cerebral response of IL-1β, IL-6, and IL-10 after subarachnoid hemorrhage and traumatic brain injury. The 3 ILs have different reaction patterns, with the response of IL-1β and IL-6 being related to the type of cerebral damage sustained, whereas the IL-10 response was less varied.


Congenital cardiac disease in dogs.
Pulmonic stenosis is caused by a malformed pulmonic valve, stricture of the right ventricular outflow tract or stricture of the pulmonary artery. English Bulldogs, Beagles, Samoyeds, Fox Terriers and Chihuahuas are predisposed. Clinical signs in severely affected dogs include exercise intolerance, stunting, dyspnea, syncope and ascites. Auscultation reveals a high-frequency, crescendo-decrescendo murmur during systole, loudest over the left side of the thorax, near the sternal cardiac border. An ECG may reveal a right-axis deviation of greater than 120 degrees, S waves in leads I, II and III, deep S waves in CV6LL, CV6LU and V10, Q waves deeper than 0.5 mv in leads II, III and AVF, and positive T waves in lead V10. Plain film LAT thoracic radiographs reveal an elevated carina, increased sternal contact of the heart, loss of the cranial cardiac waist and a widened cardiac silhouette, with normal pulmonary vasculature. A DV projection reveals an inverted "D" shape of the right ventricle and a pulmonary artery bulge. A nonselective angiocardiogram reveals poststenotic dilation of the main pulmonary artery. Treatment involves surgical correction of the stenosis.


Distribution of lengths of the normal femur and tibia in Korean children from three to sixteen years of age.
To develop a standard growth curve of the lower extremity in Korean children from 3 to 16 yr of age, the lengths from a total of 2087 normal long bone segments (582 femurs and 645 tibias in boys, and 417 femurs and 443 tibias in girls) were measured. Children were grouped by years of bone age, which was determined by using the Korean specific bone age standard; TW2-20 method. The growth spurt occurred in girls from eight to eleven years by bone age, and in boys from eleven to thirteen years. The mean tibial length relative to the mean femoral length was 0.78 in boys and 0.79 in girls. The overall growth pattern was similar to that observed in American children in the 1960s. Korean children and adolescents appear to have a different tempo of skeletal maturation during pubertal growth from that of English and American children and adolescents. The Korean standard growth curve and the Korean bone age chart allow determination of the presence of any existent growth abnormalities and prediction of future remaining growth in lower extremities. These normative growth standards can be used for leg-length equalization purposes in children with anisomelia.


Unilateral nevoid acanthosis nigricans: Uncommon variant of a common disease.
Acanthosis nigricans (AN) is a fairly common dermatosis characterized by hyperpigmented velvety plaques, having a predilection for the intertriginous areas. We herein present a case of unilateral nevoid acanthosis nigricans over the left lateral chest, in an adult male. The rarity of documentation of this entity in the world literature prompted us to report the case.


Passive Monitoring of Crowd-Level Cough Counts in Waiting Areas produces Reliable Syndromic Indicator for Total COVID-19 Burden in a Hospital Emergency Clinic.
Syndromic surveillance is an effective tool for enabling the timely detection of infectious disease outbreaks and facilitating the implementation of effective mitigation strategies by public health authorities. While various information sources are currently utilized to collect syndromic signal data for analysis, the aggregated measurement of cough, an important symptom for many illnesses, is not widely employed as a syndromic signal. With recent advancements in ubiquitous sensing technologies, it becomes feasible to continuously measure population-level cough incidence in a contactless, unobtrusive, and automated manner. In this work, we demonstrate the utility of monitoring aggregated cough count as a syndromic indicator to estimate COVID-19 cases. In our study, we deployed a sensor-based platform (Syndromic Logger) in the emergency room of a large hospital. The platform captured syndromic signals from audio, thermal imaging, and radar, while the ground truth data were collected from the hospital's electronic health record. Our analysis revealed a significant correlation between the aggregated cough count and positive COVID-19 cases in the hospital (Pearson correlation of 0.40, p-value < 0.001). Notably, this correlation was higher than that observed with the number of individuals presenting with fever (ρ = 0.22, p = 0.04), a widely used syndromic signal and screening tool for such diseases. Furthermore, we demonstrate how the data obtained from our Syndromic Logger platform could be leveraged to estimate various COVID-19-related statistics using multiple modeling approaches. Our findings highlight the efficacy of aggregated cough count as a valuable syndromic indicator associated with the occurrence of COVID-19 cases. Incorporating this signal into syndromic surveillance systems for such diseases can significantly enhance overall resilience against future public health challenges, such as emerging disease outbreaks or pandemics.


Warfarin-Related Nephropathy Manifested as Diffuse Mesangial Proliferative Glomerulonephritis.
Warfarin is associated with anticoagulant-related nephropathy (ARN), one of the potential side effects. This is evidenced by a progressively increasing number of detected cases of deterioration in the kidney function even in patients with normal baseline function (GFR {glomerular filtration rate}) in addition to the chronic kidney disease (CKD) patients who are already vulnerable to ARN. There has been a clinical correlation in a rapid decline of kidney function and international normalized ratio (INR) levels of greater than three. ARN is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. We want to emphasize the importance of monitoring kidney function regularly and adjusting the appropriate doses of warfarin. We present a case of a 57-year-old female who was on warfarin for the mechanical aortic valve, presented with acute kidney injury and supratherapeutic INR. Her renal biopsy showed diffuse mesangial proliferative glomerulonephritis.


Single strand DNA breaks in mitogen stimulated T lymphocytes are religated by a mechanism independent of accessory cells.
The phenomenon of religation of single-strand DNA breaks (nicks) in mitogenically stimulated human T lymphocytes is an event occurring within 8 h of mitogen stimulation. Many later events in lymphocyte activation are known to be dependent on accessory cells, whereas earlier events are often accessory-cell independent. To establish whether nick religation is dependent or independent of accessory-cell function, lymphocytes were stimulated with PHA in the presence of inhibitors thought to act, in part at least, on accessory cells (methylprednisolone and cyclosporine A), or under conditions in which accessory-cell function is limited (low-density culture, adherent-cell depleted populations). In each case DNA synthesis was inhibited but the religation process was retained, indicating that it is independent of accessory-cell function. Inhibition of DNA synthesis in these cells was shown to be readily reversible on addition of conditioned medium containing accessory-cell products, but there was no further change in ligation.


Effect of serum, cholesterol and low density lipoprotein on the functionality and structure of lung surfactant films.
Lung surfactant is a complex mixture of lipid and protein, responsible for alveolar stability, becomes dysfunctional due to alteration of its structure and function by leaked serum materials in disease. Serum proteins, cholesterol and low density lipoprotein (LDL) were studied with bovine lipid extract surfactant (BLES) using Langmuir films, and bilayer dispersions using Raman spectroscopy. While small amount of cholesterol (10 wt%) and LDL did not significantly affect the adsorption and surface tension lowering properties of BLES. However serum lipids, whole serum as well as higher amounts of cholesterol, and LDL dramatically altered the surface properties of BLES films, as well as gel-fluid structures formed in such films observed using atomic force microscopy (AFM). Raman-spectroscopic studies revealed that serum proteins, LDL and excess cholesterol had fluidizing effects on BLES bilayers dispersion, monitored from the changes in hydrocarbon vibrational modes during gel-fluid thermal phase transitions. This study clearly suggests that patho-physiological amounts of serum lipids (and not proteins) significantly alter the molecular arrangement of surfactant in films and bilayers, and can be used to model lung disease.


Synthesis and biological evaluation of 2-aryliminopyrrolidines as selective ligands for I1 imidazoline receptors: discovery of new sympatho-inhibitory hypotensive agents with potential beneficial effects in metabolic syndrome.
New 2-aryliminopyrrolidines (1-18) were synthesized and tested for their binding properties on I1 imidazoline receptors vs α2-adrenergic receptors and their blood pressure effects after both systemic and intracerebral administrations. The purposes of this study were: (i) to analyze structure-activity and affinity relationships on I1 imdazoline receptors and (ii) to propose some leader compounds for the development of new sympatho-inhibitory drugs with potential applications in hypertension and/or metabolic syndrome, i.e., a cluster of cardiovascular (hypertension) and metabolic disorders. Our study highlights decisive arguments of SAR concerning both the affinity for I1Rs and the hypotensive activity of 2-aryliminopyrrolidines. Binding assays showed high affinity and selectivity of some compounds for I1 imidazoline receptors over α2-adreergic receptors. Compound 13 (laboratory reference LNP599; Ki = 3.2 nM on I1imidazoline receptors) is the prototype for the development of new centrally acting agents targeting specifically I1imidazoline receptors to be used in the management of hypertension and/or metabolic syndrome.


Systematics of the Ceracis furcifer Species-Group (Coleoptera: Ciidae): The Specialized Consumers of the Blood-Red Bracket Fungus Pycnoporus sanguineus.
The Ceracis furcifer species-group (Coleoptera: Ciidae) originally comprised nine species names: Ceracis cornifer (Mellié, 1849); C. cylindricus (Brèthes, 1922); C. furcifer Mellié, 1849; C. hastifer (Mellié, 1849); C. monocerus Lawrence, 1967; C. ruficornis Pic, 1916; C. simplicicornis (Pic, 1916); C. semipallidus Pic, 1922 and C. unicornis Gorham, 1898. Ceracis semipallidus was synonymised with C. furcifer and then no further changes were made to the composition of the group. Here, we provide a taxonomic revision of the Ceracis furcifer species-group and new data on the geographic distribution and host fungi of the included species. Lectotypes are designated for C. cornifer, C. furcifer, C. hastifer, C. ruficornis, C. semipallidus and C. unicornis. As results we: (i) synonymise C. cylindricus, C. monocerus, C. simplicicornis, C. unicornis with C. cornifer; (ii) confirm the synonymy of C. semipallidus with C. furcifer; (iii) redescribe C. cornifer, C. hastifer, C. furcifer and C. ruficornis; and (iv) provide an identification key for species in the furcifer group. The frontoclypeal horn and body coloration showed great intraspecific variation. We show that species in the furcifer group have distributions wider than previously known and use mainly Pycnoporus sanguineus as host fungus. Species of the furcifer group are the only animals specialized in feeding on basidiomes of P. sanguineus.


A Context-Aware Method for Authentically Simulating Outdoors Shadows for Mobile Augmented Reality.
Visual coherence between virtual and real objects is a major issue in creating convincing augmented reality (AR) applications. To achieve this seamless integration, actual light conditions must be determined in real time to ensure that virtual objects are correctly illuminated and cast consistent shadows. In this paper, we propose a novel method to estimate daylight illumination and use this information in outdoor AR applications to render virtual objects with coherent shadows. The illumination parameters are acquired in real time from context-aware live sensor data. The method works under unprepared natural conditions. We also present a novel and rapid implementation of a state-of-the-art skylight model, from which the illumination parameters are derived. The Sun's position is calculated based on the user location and time of day, with the relative rotational differences estimated from a gyroscope, compass and accelerometer. The results illustrated that our method can generate visually credible AR scenes with consistent shadows rendered from recovered illumination.


Transcriptome Screening of Long Noncoding RNAs and Their Target Protein-Coding Genes Unmasks a Dynamic Portrait of Seed Coat Coloration Associated with Anthocyanins in Tibetan Hulless Barley.
Many plants have the capability to accumulate anthocyanins for coloration, and anthocyanins are advantageous to human health. In the case of hulless barley (Hordeum vulgare L. var. nudum), investigation into the mechanism of anthocyanin formation is limited to the level of protein-coding genes (PCGs). Here, we conducted a comprehensive bioinformatics analysis to identify a total of 9414 long noncoding RNAs (lncRNAs) in the seed coats of purple and white hulless barley along a developmental gradient. Transcriptome-wide profiles of lncRNAs documented several properties, including GC content fluctuation, uneven length, a diverse range of exon numbers, and a wide variety of transcript classifications. We found that certain lncRNAs in hulless barley possess detectable sequence conservation with Hordeum vulgare and other monocots. Furthermore, both differentially expressed lncRNAs (DElncRNAs) and PCGs (DEPCGs) were concentrated in the later seed development stages. On the one hand, DElncRNAs could potentially cis-regulate DEPCGs associated with multiple metabolic pathways, including flavonoid and anthocyanin biosynthesis in the late milk and soft dough stages. On the other hand, there was an opportunity for trans-regulated lncRNAs in the color-forming module to affect seed coat color by upregulating PCGs in the anthocyanin pathway. In addition, the interweaving of hulless barley lncRNAs and diverse TFs may function in seed coat coloration. Notably, we depicted a dynamic portrait of the anthocyanin synthesis pathway containing hulless barley lncRNAs. Therefore, this work provides valuable gene resources and more insights into the molecular mechanisms underlying anthocyanin accumulation in hulless barley from the perspective of lncRNAs, which facilitate the development of molecular design breeding in crops.


Viscosity at the dynamic crossover in o-terphenyl and salol under high pressure.
The viscosities of two prototypical glass formers, o-terphenyl and phenyl salicylate (salol), are shown to exhibit a change in their temperature and pressure dependences at a constant value of the viscosity. This is the first evidence of a dynamic crossover in the viscosity induced by pressure. The characteristic value associated with the change in dynamics is material dependent, but independent of temperature and pressure. These results are in accord with the previous finding, for other glass formers, that the dielectric relaxation time assumes a density-independent value at the dynamic crossover.


Oral cutaneous sinus tract, vertical root fracture, and bisphosphonate-related osteonecrosis: a case report.
Oral cutaneous sinus tracts (OCSTs) of dental origin are often initially misdiagnosed and inappropriately treated. Accurate diagnosis is especially important in cases of bisphosphonate (BP) therapy because extraction may lead to a risk of osteonecrosis. A case report of misdiagnosis related to a tooth with a vertical root fracture in an oncologic patient treated with BPs is reported here. In 2011, a 75-year-old woman was examined at the oral medicine clinic because of pain and swelling of the left submandibular area. The patient's medical history included oral and intravenous BP therapy because she was diagnosed with metastatic breast cancer and left maxillary stage 1 antiresorptive agent-induced osteonecrosis of the jaw. The lower left odontogenic region showed no signs or symptoms, and no apical pathosis was observed on imaging. Although antibiotics were applied, clinical symptoms worsened and an OCST appeared. Intravenous antibiotic treatment was pursued. Biopsy and direct smear from fistula were not conclusive. A diagnosis of a nonexposed variant of stage 3 antiresorptive agent-induced osteonecrosis of the jaw was established. Symptoms resolved after 2 weeks of antibiotic treatment and reappeared a month later. Endodontic examination revealed that the origin of the OCST was tooth no. 18 caused by a vertical root fracture, and the tooth was extracted. The patient was scheduled for routine checkups because of the fact that osteonecrosis may occur in intravenous BP-treated patients. Early correct diagnosis can prevent unnecessary and ineffective antibiotic therapy and surgical intervention, which is not recommended in intravenous BP cases.


Proximate determinants of bite force in Anolis lizards.
Performance measures associated with the vertebrate jaw system may provide important insights into vertebrate ecology and evolution because of their importance in many ecologically relevant tasks. Previous studies have shown that in many taxa, evolution toward higher bite force has gone hand in hand with the evolution of larger body size. However, independent of differences in overall body size, bite force may vary depending on head size and shape as well. Moreover, the underlying musculature may also drive variation in bite force. Here, we investigate the proximate determinants of bite force in lizards of the genus Anolis. We dissected the jaw muscles and quantified muscle mass, fibre length, and cross-sectional area. Data were analysed for both sexes independently given the sexual dimorphism detected in the dataset. Our results show that the traits that explain bite force are similar in both males and females with overall body size and muscle mass being the principal determinants. Among the different muscles examined, the adductor externus and the pseudotemporalis groups were the best determinants of bite force. However, models run for males predicted the variation in bite force better than models for females, suggesting that selection on morphology improving bite force may be stronger in males.


The Reelin Receptors Apolipoprotein E receptor 2 (ApoER2) and VLDL Receptor.
Apolipoprotein E receptor 2 (ApoER2) and VLDL receptor belong to the low density lipoprotein receptor family and bind apolipoprotein E. These receptors interact with the clathrin machinery to mediate endocytosis of macromolecules but also interact with other adapter proteins to perform as signal transduction receptors. The best characterized signaling pathway in which ApoER2 and VLDL receptor (VLDLR) are involved is the Reelin pathway. This pathway plays a pivotal role in the development of laminated structures of the brain and in synaptic plasticity of the adult brain. Since Reelin and apolipoprotein E, are ligands of ApoER2 and VLDLR, these receptors are of interest with respect to Alzheimer's disease. We will focus this review on the complex structure of ApoER2 and VLDLR and a recently characterized ligand, namely clusterin.


Usefulness of Total PSA Value in Prostate Diseases Diagnosis.
Analysis of total value of prostate specific antigen (PSAT), with the unavoidable digital rectal examination (DRE) is the basis of prostate cancer detection. The aim of this study was to determine the specificity and sensitivity of the total value of PSAT in the diagnosis of prostate cancer. The aim was also to determine the significance of PSAT in diagnosis of benign prostate hyperplasia, precancerous conditions and inflammatory and atrophic changes of the prostate. Data were collected from the "Register of PH biopsy" of Clinic of Urology, CCU Sarajevo. Analysis of correlation between the diagnosis and the PSAT value shows statistically significant negative correlation (r =-0,186; p = 0.006) in the sense that the value of the PSAT is highest in cancer patients, and the lowest in patients with benign prostatic hyperplasia. PSAT increases with age (r = 0.152; p = 0.025). For prostate cancer optimal sensitivity and specificity for PSAT value occurs at cut off value of> 8.6 ng /mL. Values lower than 2 ng/mL and higher than 10 ng/mL are most specific, and PPV increases with increasing value of PSAT. PSAT at values of <2 ng/mL and > 10 ng/mL are at high levels of specificity, and value > 10 ng / mL is also of high sensitivity in the detection of prostate cancer, and in this moment these values represent the optimal mode for the subsequent treatment. PSAT has a relative significance in the detection of prostate cancer, and should not be used as a guideline without DRE.


The virtues (and vices) of the four principles.
Despite tendencies to compete for a prime place in moral theory, neither virtue ethics nor the four principles approach should claim to be superior to, or logically prior to, the other. Together they provide a more adequate account of the moral life than either can offer on its own. The virtues of principlism are clarity, simplicity and (to some extent) universality. These are well illustrated by Ranaan Gillon's masterly analysis of the cases he has provided. But the vices of this approach are the converse of its virtues: neglect of emotional and personal factors, oversimplification of the issues, and excessive claims to universality. Virtue ethics offers a complementary approach, providing insights into moral character, offering a blend of reason and emotion, and paying attention to the context of decisions. The cases provided can be more adequately understood if we combine the approaches. Both should foster the virtues of humility and magnanimity.


Lymphomatoid papulosis type D: a newly described variant easily confused with cutaneous aggressive CD8-positive cytotoxic T-cell lymphoma.
Lymphomatoid papulosis (LyP) is defined as a chronic recurrent skin disease characterized by waxing and waning papules and nodules with histologic features of a CD30-positive T-cell lymphoma. Three histological subtypes (A, B, and C) were already recognized, and only more recently, a further variant simulating histologically an aggressive epidermotropic CD8-positive T-cell lymphoma was described, which was named LyP type D by the authors. We report the case of a 38-year-old woman presenting with a 1-year history of recurrent self-healing papules and nodules, predominantly affecting her upper and lower limbs but also the face, including the lower lip, with no associated systemic symptoms. A biopsy from 1 lesion revealed an infiltrate of atypical lymphoid cells extending throughout the dermis with massive epidermotropism displaying a pagetoid reticulosis-like pattern and a CD8(+)CD30(+) cytotoxic T-cell phenotype. The clinicopathologic features conformed to the newly described type D variant of LyP. Diagnostic studies did not reveal any systemic involvement, and the patient remains otherwise well with no active treatment. In the present report, we discuss the need for clinicopathologic correlation to establish an accurate diagnosis and its importance for an adequate management of these patients.


Efficacy of the lateral decubitus position in preventing pneumothorax after needle biopsy of the lung.
We evaluated the efficacy of the lateral decubitus position in preventing the development of pneumothorax after percutaneous needle biopsy of a well defined lung lesion. Fifty patients had such a procedure and were immediately placed in the lateral decubitus position for ten minutes, with the biopsied lung below. A chest x-ray film was obtained after the ten minute period, four to six hours later, and on the following morning. The number of pneumothoraces and the type of treatment needed in each case were recorded. Results in these 50 patients were compared to those previously obtained in 132 patients who had had an identical procedure and follow-up during the preceding four years. In all patients included as controls, we did the biopsy using an identical technique and in accordance with a specific written protocol. Both groups of patients were closely comparable in age and sex distribution, baseline values for arterial blood gases, results of prebiopsy tests of pulmonary function, and type, size, location, and distance from the pleural surface of the pulmonary lesions. A postbiopsy pneumothorax developed in 21 of 50 (42%) study patients, and in 46 of 132 (35%) controls (P not significant). Specific therapy was needed in ten (48%) and 26 (56%) of these cases, respectively (P = NS). We conclude that placing patients in the lateral decubitus position is not effective in significantly reducing the incidence of postbiopsy pneumothorax or the proportion of patients who will require specific therapy for this complication.


Measurement of offline exhaled nitric oxide in a study of community exposure to air pollution.
As part of a large panel study in Seattle, Washington, we measured levels of exhaled nitric oxide (eNO) in children's homes and fixed-site particulate matter with aerodynamic diameters of 2.5 micro m or less (PM(2.5)) outside and inside the homes as well as personal PM(2.5) during winter and spring sessions of 2000-2001. Nineteen subjects 6-13 years of age participated; 9 of the 19 were on inhaled corticosteroid (ICS) therapy. Exhaled breath measurements were collected offline into a Mylar balloon for up to 10 consecutive days. Mean eNO values were 19.1 (SD +/- 11.4) ppb in winter sessions and 12.5 +/- 6.6 ppb in spring sessions. Fixed-site PM(2.5) mean concentrations were 10.1 +/- 5.7 microg/m(3) outside homes and 13.3 +/- 1.4 inside homes; the personal PM(2.5) mean was 13.4 +/- 3.2 microg/m(3). We used a linear mixed-effects model with random intercept and an interaction term for medications to test for within-subject-within-session associations between eNO and various PM(2.5) values. We found a 10 microg/m(3) increase in PM(2.5) from the outdoor, indoor, personal, and central-site measurements that was associated with increases in eNO in all subjects at lag day zero. The effect was 4.3 ppb [95% confidence interval (CI), 1.4-7.29] with the outdoor monitor, 4.2 ppb (95% CI, 1.02-7.4) for the indoor monitor, 4.5 ppb (95% CI, 1.02-7.9) with the personal monitor, and 3.8 ppb (95% CI, 1.2-6.4) for the central monitors. The interaction term for medication category (ICS users vs. nonusers) was significant in all analyses. These findings suggest that eNO can be used as an assessment tool in epidemiologic studies of health effects of air pollution.


Oral health care--a low priority in nursing. In-depth interviews with nursing staff.
In this study we examined how nursing home staff experienced assisting patients with oral health care. The results of a previous questionnaire indicated that oral health care is a low priority in nursing. The 22 in-depth interviews administered in this study showed that the quality of the oral health care received by the patients depended on several factors. It was found that often there were no specific routines for assisting oral health care in the nursing homes and that other activities were given higher priority. Assisting oral health care was described as passing a barrier, where the main problem was to gain access to the oral cavity. It was concluded that nursing staff working with geriatric patients need to be better educated in oral health care and should be seen by themselves and others as part of a team, where oral health care is clearly defined and included among other daily nursing activities.


An Update on Drug-eluting Technology in Peripheral Arteries to Treat Peripheral Arterial Disease.
For the treatment of peripheral arterial disease, drug-eluting technology is a widely accepted therapeutic option, with significant reduction in intimal hyperplasia and, consequently, use of target lesion revascularization. Nevertheless, the reputation of such devices was damaged after a meta-analysis, published in December 2018, showed increased mortality in patients receiving paclitaxel-eluting devices. Although subsequent studies have failed to establish such correlation, the use of paclitaxel-eluting devices remains heavily restricted. As such, other options and drugs have been developed, for instance sirolimus. In this article we present the available data on drug-eluting technology.


Early diagnosis by genetic analysis of differentiated thyroid cancer metastases in small lymph nodes.
We report a PCR-based technique for detecting thyroid cancer metastases in small nodes <1.5 cm diameter by the amplification of thyroid specific transcripts TSH-receptor and thyroglobulin. A 100% correspondence with the histopathological diagnosis was observed in the 41/46 nodes (89%) in which an adequate sample was obtained at fine needle aspiration. The genetic analysis resulted more sensitive and accurate than both the cytological analysis (28% inadequate samples, 17% false negative diagnoses) and the thyroglobulin measurement in the aspirates (39% false negatives). The PCR-based genetic analysis may provide a useful tool for diagnosis and follow-up of thyroid cancer.


A-kinase-anchoring protein 95 functions as a potential carrier for the nuclear translocation of active caspase 3 through an enzyme-substrate-like association.
Caspase-mediated proteolysis is a critical and central element of the apoptotic process, and caspase 3, one of the effector caspases, is proposed to play essential roles in the nuclear morphological changes of apoptotic cells. Although many substrates for caspase 3 localize in the nucleus and caspase 3 translocates from the cytoplasm to the nuclei after activation in apoptotic cells, the molecular mechanisms of nuclear translocation of active caspase 3 have been unclear. Recently, we suggested that a substrate-like protein(s) served as a carrier to transport caspase 3 from the cytoplasm into the nucleus. In the present study, we identified A-kinase-anchoring protein 95 (AKAP95) as a caspase 3-binding protein. Small interfering RNA-mediated depletion of AKAP95 reduced apoptotic nuclear morphological changes, suggesting that AKAP95 is involved in the process of apoptotic nuclear morphological changes. The association of AKAP95 with active caspase 3 was analogous to an enzyme-substrate interaction. Furthermore, overexpression of AKAP95 with nuclear localization sequence mutations inhibited nuclear morphological changes in apoptotic cells. These results indicate that AKAP95 is a potential carrier protein for active caspase 3 from the cytoplasm into the nuclei in apoptotic cells.


Computational analysis of the effects of interprosthetic distance on normal and reduced cortical thickness femur models.
Distal femoral fractures associated with the femoral stem in a well-fixed hip arthroplasty pose a risk of an interprosthetic fracture, the treatment of which is known as difficult. To effectively prevent and treat IP fractures, biomechanical effects must be demonstrated. We defined eight variations of the interprosthetic distance ranging from 48 mm overlap to 128 mm gap. Femoral geometries with normal and reduced cortical thickness were modeled to evaluate the effects of cortical thickness. In addition to the intact model, a total of 16 finite element models were analyzed under physiological boundary conditions. Maximum and minimum principal strains on the lateral and medial cortex surfaces were always found to be greater in models with reduced cortical thickness than in normal femurs. The model with 48 mm overlapping interprosthetic distance produced the least peak strain and the model with 16 mm interprosthetic gap produced the greatest strain with both normal and reduced cortical thickness. The screw holes produced local strain concentrations and increased the peak strains on the cortex surfaces, especially close to the stem tip. Statistically, a significant correlation (R2 = 0.9483) was found between strain shielding and interprosthetic distance. Axial stiffness, interfragmentary shear motion, and maximum von-Mises stress on the distal plate showed a high correlation with the interprosthetic distance. It was concluded that the overlapping structures are superior to other fixations we analyzed in that they offer better mechanical stability and eliminates the local strain concentrations.


Molecular cloning and characterization of novel cystatin gene in leaves Cakile maritima halophyte.
Cakile maritima (Brassicaceae) is a halophyte that thrives on dunes along Mediterranean seashores, with high tolerance to salty and dry environments. We have previously shown that there is great morphological and physiological diversity between ecotypes. We investigated the expression of cysteine protease inhibitor (cystatin) genes in the response to hydric and saline constraints, as cystatins are known to participate in the response to environmental constraints in plants. We isolated, from C. maritime, a new cystatin cDNA (CmC) that encodes a 221 amino acid protein with a calculated molecular mass of 25 kDa. It displays a moderate-to-high amino acid sequence similarity with previously reported phytocystatin genes. The predicted protein is hydrophilic, with only one hydrophobic region, just at its N-terminus, and a calculated isoelectric point of 6.7. Sequence analysis revealed a monocystatin structure with one cystatin-like domain. The predicted protein CmC contains the main conserved motifs characteristic of the plant cystatins, and a putative site of phosphorylation by casein kinase II (TPSD). As some cystatins, it contains a C-terminal extension of 106 amino acid residues, with several conserved cystatin motifs. The expression was constitutive in non-stressed plants, with different levels between the ecotypes, and without apparent relation to the climatic area of origin. Augmented expression was observed under severe salinity except in the ecotype from the arid region. Water deficit also increased CmC expression in two ecotypes, with the highest value observed in the ecotype from the humid region. These results indicate that C. maritima responds to high salinity and water deficit by expressing a cystatin gene that is a known component of defense against abiotic constraints or biotic aggression and survival machinery.


Novel chromium(VI) catalyzed oxidation of N-alkylamides to imides with periodic acid.
A novel and practical procedure for preparation of imides is described using chromium(VI) oxide to catalyze the oxidation of N-alkylamides with periodic acid in the presence of acetic anhydride in acetonitrile.


moody encodes two GPCRs that regulate cocaine behaviors and blood-brain barrier permeability in Drosophila.
We identified moody in a genetic screen for Drosophila mutants with altered cocaine sensitivity. Hypomorphic mutations in moody cause an increased sensitivity to cocaine and nicotine exposure. In contrast, sensitivity to the acute intoxicating effects of ethanol is reduced. The moody locus encodes two novel GPCRs, Moody-alpha and Moody-beta. While identical in their membrane-spanning domains, the two Moody proteins differ in their long carboxy-terminal domains, which are generated by use of alternative reading frames. Both Moody forms are required for normal cocaine sensitivity, suggesting that they carry out distinct but complementary functions. Moody-alpha and Moody-beta are coexpressed in surface glia that surround the nervous system, where they are actively required to maintain the integrity of the blood-brain barrier in the adult fly. We propose that a Moody-mediated signaling pathway functions in glia to regulate nervous system insulation and drug-related behaviors.


Single-cell RNA sequencing reveals an altered gene expression pattern as a result of CRISPR/cas9-mediated deletion of Gene 33/Mig6 and chronic exposure to hexavalent chromium in human lung epithelial cells.
Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We recently reported that depletion of this protein promotes lung epithelial cell transformation induced by hexavalent chromium [Cr(VI)]. However, the early molecular events that mediate this process are not clear. In the present study, we used single-cell RNA sequencing to compare gene expression profiles between BEAS-2B lung epithelial cells chronically exposed to a sublethal dose of Cr(VI) with or without CRISPR/cas9-mediated deletion of Gene 33. Our data reveal 83 differentially expressed genes. The most notable changes are genes associated with cell adhesion, oxidative stresses, protein ubiquitination, epithelial-mesenchymal transition/metastasis, and WNT signaling. Up-regulation of some neuro-specific genes is also evident, particularly ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a deubiquitinase and potential biomarker for lung cancer. Gene 33 deletion and/or Cr(VI) exposure did not cause discernable changes in cell morphology. However, Gene 33 deletion led to a modest but significant reduction of cells in the G2/M phase of the cell cycle regardless of Cr(VI) exposure. Gene 33 deletion also significantly reduced cell proliferation. Interestingly, Cr(VI) exposure eliminated the difference in cell proliferation between the two genotypes. Gene 33 deletion also significantly elevated cell migration. Our data indicate that combined Gene 33 deletion and chronic Cr(VI) exposure produces a gene expression pattern and a phenotype resemble those of the transformed lung epithelial cells. Given the known association of UCHL1 with lung cancer, we propose that UCHL1 is an important player in the early stage of lung epithelial cell transformation and tumorigenesis.


Rearranged clerodane diterpenoid from Tinospora crispa.
A new rearranged clerodane diterpenoid, tinocrispide was isolated from the stems of Tinospora crispa along with thirteen known compounds including eight clerodane diterpenoids. Among the known compounds baenzigeride A, (6S, 9 R)-vomifoliol and steponine are being reported for the first time from T. crispa. Their structures were elucidated by 1 D and 2 D NMR and confirmed by HRESIMS. The 13C NMR data of borapetol A has been revised.


Serotonin and its role in colonic function and in gastrointestinal disorders.
Serotonin (5-HT) is most commonly thought of as a neurotransmitter in the central nervous system. However, the predominant site of serotonin synthesis, storage, and release is the enterochromaffin cells of the intestinal mucosa. Within the intestinal mucosa, serotonin released from EC cells activates neural reflexes associated with intestinal secretion, motility, and sensation. Two important receptors for serotonin that are located in the neural circuitry of the intestines are the 5-HT(3) and 5-HT(4) receptors; these are the targets of drugs designed to treat gastrointestinal disorders. 5-HT(3) receptor antagonists are used to treat nausea and emesis associated with chemotherapy and for functional disorders associated with diarrhea. 5-HT(4) receptor agonists are used as promotility agents to promote gastric emptying and to alleviate constipation. Because of the importance of serotonin in normal gut function and sensation, a number of studies have investigated potential changes in mucosal serotonin signaling in pathologic conditions. Despite the inconsistencies in the current literature, changes in serotonin signaling have now been demonstrated in inflammatory bowel disease, irritable bowel syndrome, postinfectious irritable bowel syndrome, and idiopathic constipation. Emerging evidence has led to many contradictory theories regarding serotonin signaling and its roles in the pathology of gut disorders. This review summarizes the current medications affecting serotonin signaling and provides an overview of our current knowledge of the changes in serotonin that occur in pathologic conditions.


Evolving a legacy system: restructuring the Mendelian Inheritance in Man database.
Mendelian Inheritance in Man (MIM) is an encyclopedia of medical genetics that has been in electronic form for over 30 years. In its lifetime, MIM has undergone many organizational and software changes. In 1994, a major transition was made based on three basic principles: industry standards, open systems architecture, and extensibility. The resulting MIM database allows users to navigate to other genomic databases, permits the delivery of multimedia information, and improves the quality of data. The new MIM database also improved its administration because of 1) an internal format that enforces consistency; 2) a lower maintenance cost of software; and 3) a better ability to migrate MIM content. In addition, the new architecture will allow MIM easily to adopt emergent technologies as they mature.


Surgical castration in hormone-refractory metastatic prostate cancer patients can be an alternative for medical castration.
Background. Most patients with metastatic prostate cancer are endocrinologically treated with LHRH agonist, but finally castration-refractory and hormone-refractory cancers occur. Serum testosterone levels get low to "the castration level" by LHRH agonists but may not get low enough against castration-refractory prostate cancer. Methods. As case series, twelve patients suffering from hormone-refractory prostate cancer continuously on LHRH agonist underwent surgical castration. Additionally, one hundred and thirty-nine prostate cancer patients on LHRH agonist or surgical castration were tested for serum total testosterone levels. Results. Surgical castration caused decrease in serum PSA in one out of 12 hormone-refractory prostate cancer patients with PSA reduction rate 74%. Serum total testosterone levels were below the sensitivity threshold (0.05 ng/mL) in 40 of 89 (44.9%) medically castrated patients and 33 of 50 (66.0%) surgically castrated patients (P = .20). Conclusion. Even hormone-refractory prostate cancer patients are candidates for surgical castration because of endocrinological, oncological, and economical reasons.


Dynamic scaling study of vapor deposition polymerization: a Monte Carlo approach.
The morphological scaling properties of linear polymer films grown by vapor deposition polymerization are studied by 1+1D Monte Carlo simulations. The model implements the basic processes of random angle ballistic deposition (F) , free-monomer diffusion (D) and monomer adsorption along with the dynamical processes of polymer chain initiation, extension, and merger. The ratio G=D/F is found to have a strong influence on the polymer film morphology. Spatial and temporal behavior of kinetic roughening has been extensively studied using finite-length scaling and height-height correlations H(r,t). The scaling analysis has been performed within the no-overhang approximation and the scaling behaviors at local and global length scales were found to be very different. The global and local scaling exponents for morphological evolution have been evaluated for varying free-monomer diffusion by growing the films at G=10 , 10(2), 10(3), and 10(4) and fixing the deposition flux F. With an increase in G from 10 to 10(4), the average growth exponent beta approximately 0.50 was found to be invariant, whereas the global roughness exponent alpha(g) decreased from 0.87 (1) to 0.73 (1) along with a corresponding decrease in the global dynamic exponent z(g) from 1.71(1) to 1.38(2). The global scaling exponents were observed to follow the dynamic scaling hypothesis, z(g)=alpha(g)/beta. With a similar increase in G however, the average local roughness exponent alpha(l) remained close to 0.46 and the anomalous growth exponent beta(*) decreased from 0.23(4) to 0.18(8). The interfaces display anomalous scaling and multiscaling in the relevant height-height correlations. The variation in H(r,t) with deposition time t indicates nonstationary growth. A comparison has been made between the simulational findings and the experiments wherever applicable.


Vitamins B6 and C and mitomycin C-efficiency under irradiation.
The radiation-induced effect of Vitamin B6 (Vit. B6) on mitomycin C (MMC) was investigated by using Escherichia coli bacteria AB 1157 as a model in air-free media as well as in media saturated with nitrous oxide (N20) or air, respectively. In all three types of media Vit.B6 showed cytostatic abilities. The highest synergistic effect of Vit.B6 on MMC was observed in an air-free environment. It decreased 2.8-fold in aerated solution and showed the opposite effect in solutions saturated with N20. The addition of Vitamin C (Vit.C) to the Vit.B6/MMC-mixture in air-free media reduced the MMC-efficiency by a factor of 3.6, whereas the presence of air led to a MMC enhancement of 1.6-fold. Considerations based on the involvement of the primary transients of water radiolysis were made in order to explain the observed effects.


Laparoscopic repair of ventral incisional hernia.
Laparoscopic repair of ventral incisional hernias was first reported in 1993. Since then, there have been sporadic case reports and small series published about this procedure, but it has not been widely adopted. Newer types of composite prosthetic mesh may reduce the potential problem of bowel adhesion. Thirty cases of laparoscopic ventral incisional hernia repairs (carried out by two surgeons or their senior registrars) have been retrospectively reviewed and reported in this article. The data were obtained from patient records and subsequent phone surveys. Thirty patients between 29 and 82 years (mean: 58 years) underwent this procedure. There were 14 men and 16 women. The average weight of the patients was 81 kg. The hernias were up to 6 or 7 cm in diameter. Mesh was used in 28 cases (polypropylene in 25 cases, expanded polytetrafluoroethylene in two cases and composite mesh in one case). Most meshes were laid intraperitoneally and fixed into position with laparoscopic spiral tacks. Twenty-nine cases were completed laparoscopically. One operation (3.3%) was converted to an open procedure because of severe bowel adherence to the hernia sac. The mean operating time was 52 min for laparoscopic ventral incisional hernia repairs only. All but two patients tolerated an oral diet within 24 h. The postoperative hospital stay ranged from 0 to 11 days, with 17 patients (57%) staying overnight and eight patients (27%) staying another day. Over 80% of the patients returned to house duties within a week. There was no mortality, and minor complications occurred in four patients (14%). One patient had a small bowel obstruction treated successfully by repeat laparoscopy with division of fibrinous adhesions to polypropylene mesh on day four. Follow up ranged from 1 to 69 months (mean: 12 months). One patient did not attend follow-up appointments. There were three cases of hernia recurrence (10%). The results suggest that laparoscopic repair of ventral incisional hernias is a safe, effective and technically feasible operation for small- to medium-sized hernias allowing shorter hospital stay, early recovery and resumption of normal activities. However, recurrence rates are comparable to open mesh hernioplasty especially for larger hernias.


Branched aliphatic alkanes with quaternary substituted carbon atoms in modern and ancient geologic samples.
A pseudohomologous series of branched aliphatic alkanes with a quaternary substituted carbon atom (BAQCs, specifically 2,2-dimethylalkanes and 3,3- and 5,5-diethylalkanes) were identified in warm (65 degrees C) deep-sea hydrothermal waters and Late Cretaceous black shales. 5,5-Diethylalkanes were also observed in modern and Holocene marine shelf sediments and in shales spanning the last 800 million years of the geological record. The carbon number distribution of BAQCs indicates a biological origin. These compounds were observed but not identified in previous studies of 2.0 billion- to 2.2 billion-year-old metasediments and were commonly misidentified in other sediment samples, indicating that BAQCs are widespread in the geological record. The source organisms of BAQCs are unknown, but their paleobiogeographic distribution suggests that they have an affinity for sulfides and might be nonphotosynthetic sulfide oxidizers.


The quality control in pancreatic surgery.
Over the past decade, several centralization programs for major pancreatic surgery have been implemented in hospitals with high procedural volumes. Although the impact of this process was altogether positive, also possible negative effects have been evidenced, above all the lack of comprehensive coverage and access to specialized centers. In order to solve these problems, it was proposed the utilization of an outcome-based and not volume-based center selection. For this purpose the choice of an appropriate outcome assessment system is crucial. We retrospectively reviewed 74 patients undergoing pancreatoduodenectomy. The outcomes were evaluated utilizing the Accordion Severity Classification of Postoperative Complications. The morbidity of 58 % and the mortality of 4 % were comparable with the ones reported in large series utilizing the same classification system. The Accordion system is an effective method of quality control for pancreatic surgery both in high- and low-volume hospitals.


[Painful thoracic neuropathy disclosing Sjögren's syndrome: first report].
Thoracic neuropathy is rare, and is usually associated with diabetes mellitus. We report a first case of isolated multi-metameric thoracic neuropathy revealing Sjögren's disease. A 64-year old man consulted for symptoms suggesting a progressive and extensive (from T7 to T10) bilateral thoracic neuropathy. Diabetes mellitus and other causes of neuropathy were excluded. Spinal MRI, electromyography and CSF analysis were normal. Though the patient had no sicca syndrome symptoms, the diagnosis of Sjögren's syndrome was made on hypergammaglobulinemia, elevated ACAN (1/5000) with anti-SSA specificity and a grade III minor salivary gland biopsy. He improved spectacularly on corticosteroids (prednisone, 1 mg/kg/d). Sicca syndrome became clinically evident in April 2006. Pure sensitive thoracic neuropathy can reveal Sjögren's syndrome.


Topical tretinoin in the treatment of aging skin.
We review the use of topical tretinoin (all-trans-retinoic acid) in the treatment of aging skin. We have found topical tretinoin capable of improving aged-appearing skin in both a double-blind, vehicle-controlled trial and our clinic patients. The most impressive improvement occurs after application of tretinoin 0.1% cream for 8 to 12 months. Side effects have been limited to a mild, transient, and clinically insignificant burning sensation in the eyes and mild irritation of tretinoin-exposed skin.


Synthesis of new photosensitive H2BBQ2+[ZnCl4]2-/[(ZnCl)2(μ-BBH)] complexes, through selective oxidation of H2O to H2O2.
A new two-electron photosensitizer, H2BBQ2+[ZnCl4]2-/[(ZnCl)2(μ-BBH)] (BBQ stands for 2,5-bis[bis(pyridin-2-ylmethyl)amino]-1,4-quinone and BBH stands for 2,5-bis[bis(pyridin-2-ylmethyl)amino]-1,4-hydroquinone), has been synthesized and the oxidation state of the ligand was determined by X-ray crystallography and NMR spectroscopy. Under light illumination the H2BBQ2+[ZnCl4]2- + ZnCl2 is reduced quantitatively to [(ZnCl)2(μ-BBH)] (pH ∼ 5) oxidizing H2O to H2O2 as is evident by trap experiments. Electrochemistry gave a reversible two-electron ligand-centered redox wave for [(ZnCl)2(μ-BBH)]. UV-Vis, luminescence and EPR spectroscopies reveal the slow formation of a stable quinone diradical, intermediate of the reaction. DFT calculations are in agreement with the proposed mechanism. Based on this property an aqueous {[(ZnCl)2(μ-BBH)]||H2O2} solar rechargeable galvanic cell has been constructed.


Complex karyotypes in flow cytometrically DNA-diploid squamous cell carcinomas of the head and neck.
In squamous cell carcinoma of the head and neck (SCCHN), DNA ploidy as determined by flow cytometry (FCM) has been found to yield prognostic information but only for tumours at oral sites. Cytogenetic findings have indicated complex karyotype to be a correlate of poor clinical outcome. In the present study, 73 SCCHN were investigated with the two techniques. Aneuploid cell populations were identified in 49 (67%) cases by FCM but in only 21 (29%) cases by cytogenetic analysis. The chromosome index (CI), calculated as the mean chromosome number divided by 46, was compared with the respective DNA index (DI) obtained by FCM in 15 tumours, non-diploid according to both techniques, DI being systematically 12% higher than CI in this subgroup. Eight (33%) of the 24 tumours diploid according to FCM had complex karyotypes, three of the tumours being cytogenetically hypodiploid, three diploid and two non-diploid. The findings in the present study may partly explain the low prognostic value of ploidy status as assessed by FCM that has been observed in SCCHN. In addition, we conclude that FCM yields information of the genetic changes that is too unspecific, and that cytogenetic analysis shows a high rate of unsuccessful investigations, thus diminishing the value of the two methods as prognostic factors in SCCHN.


Goblet cell carcinoid of the appendix. An ultrastructural and histochemical study.
In a patient with a goblet cell carcinoid tumor of the appendix, light and electron microscopical studies demonstrated mucinous material and enterochromaffin granules within the same cell. Transitions between cells containing primarily mucin and cells containing numerous argentaffin granules were observed. Fluorescence studies demonstrated that the tumor cells contain biogenic amines.


Use of ranitidine is associated with infections in newborns hospitalized in a neonatal intensive care unit: a cohort study.
The inhibition of gastric acid secretion with ranitidine is frequently prescribed off-label to newborns admitted to neonatal intensive care units (NICU). Some studies show that the use of inhibitors of gastric acid secretion (IGAS) may predispose to infections and necrotising enterocolitis (NEC), but there are few data to confirm this association. This study aimed to compare the rates of neonatal infections and NEC among preterm infants (<37 weeks gestation) hospitalised in a NICU exposed or not to treatment with ranitidine. A retrospective cohort study was conducted with all consecutive preterm newborns admitted to a NICU between August-2014 and October-2015. The rates of infection, NEC, and death of newborns exposed or not to ranitidine were recorded. A total of 300 newborns were enrolled, of which 115 had received ranitidine and 185 had not. The two groups were similar with regard to the main demographic and clinical characteristics. Forty-eight (41.7%) of the 115 infants exposed to ranitidine and 49 (26.5%) of the 185 infants not exposed were infected (RR = 1.6, 95%CI 1.1-2.2, p = 0.006). The late onset (>48 h) blood culture positive infection rate was higher in the group exposed to ranitidine than in the untreated group (13.0% vs. 3.8%, p = 0.001). There was no significant association between the use of ranitidine and NEC (Bell stage >II) (p = 0.36). The mortality rate risk was 4-fold higher in infants receiving ranitidine (16.5% vs. 8.6%, p < 0.001). Ranitidine use in neonates was associated with an increased risk of infections and mortality, but not with NEC.


Periconceptional undernutrition in normal and overweight ewes leads to increased adrenal growth and epigenetic changes in adrenal IGF2/H19 gene in offspring.
Adverse conditions in early life result in increased activation of the hypothalamo-pituitary-adrenal axis and in stress responsiveness in offspring. We have developed a model in which "donor" ewes are either normally nourished or overnourished prior to a period of dietary restriction, before transfer of the embryo at 6-7 d after conception to a ewe of normal weight and nutritional history. A moderate restriction of energy intake during the periconceptional period in both normal weight and overweight ewes resulted in increased adrenal mass in male and female lambs and an increased cortisol response to stress in female lambs. The increase in adrenal weight in lambs exposed to periconceptional undernutrition was associated with a decrease in the adrenal mRNA expression of IGF2 and decreased methylation in the proximal CTCF-binding site in the differentially methylated region of the IGF2/H19 gene. Thus, weight loss in both normal and overweight mothers during the periconceptional period results in epigenetic modification of IGF2 in the adrenal gland, adrenal overgrowth, and increased vulnerability to stress in offspring. Determining the appropriate approach to weight loss in the periconceptional period may therefore be important in overweight or obese women seeking to become pregnant.


Transition-metal single atoms in nitrogen-doped graphenes as efficient active centers for water splitting: a theoretical study.
Highly active single-atom catalysts (SACs) have recently been intensively studied for their potential in the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). Due to the existence of many such SAC systems, a general understanding of the trend and designing principle is necessary to discover an optimal SAC system. In this work, by using density functional theory (DFT), we investigated a series of late single transition metals (TM = Fe, Co, Ni, Cu, and Pd) anchored on various N doped graphenes (xN-TM, x = 1-4) as electrocatalysts for both the HER and OER. Solvent effects were taken into account using an implicit continuum model. Our results reveal that the catalytic activity of SACs is determined by the local coordination number of N and TM in the catalysts. Among the considered catalysts, a low-coordinated Co site, i.e. a triple-coordinated Co, exhibits a high catalytic activity toward the HER with a calculated hydrogen adsorption free energy of -0.01 eV, whereas a high-coordinated Co center, i.e. a quadruple-coordinated Co is a promising candidate for the OER with a low computed overpotential of -0.39 V, which are comparable to those of noble metal catalysts, indicating superior HER and OER performance of N-Co co-doped graphenes. The results shed light on the potential applications of TM and N co-doped graphenes as efficient single-atom bifunctional catalysts for water splitting, thereby functioning as promising candidates for hydrogen/oxygen production.


Isolation, Behavioral Identification, and Pathogenicity Assessment of Entomopathogenic Fungi from a Forest Wood Borer.
Forest wood borers (FWB) cause severe tree damage and economic losses worldwide. The release of entomopathogenic fungi (EPF) during the FWB emergence period is considered an acceptable alternative to chemical control. However, EPF resources have been significantly less explored for FWBs, in contrast to agricultural insect pests. This paper presents a protocol for exploring EPF resources from FWBs using wild Monochamus alternatus populations as an example. In this protocol, the assignment of traps baited with M. alternatus attractants to different populations guaranteed the collection of adequate samples with natural infection symptoms, during the emergence periods of the beetle. Following finely dissecting integuments and placing them onto a selective medium, fungal species were isolated from each part of beetle bodies and identified based on both molecular and morphological traits. Several fungal species were certified as parasitic EPFs via re-infection of healthy M. alternatus with spore suspensions. Their behavioral phenotypes on M. alternatus were observed using scanning electron microscopy and further compared with those on the Coleopteran model insect Tribolium castaneum. For EPFs that present consistent parasitism phenotypes on both beetle species, evaluation of their activities on T. castaneum provided valuable information on lethality for future study on M. alternatus. This protocol helped the discovery of EPF newly reported on M. alternatus populations in China, which could be applied as an efficient approach to explore more EPF resources from other FWBs.


Effect of Gibberellin on the biosynthesis of tocopherols in Oilseed rape (Brassica napus L.) and arabidopsis.
Elevating the yield and altering the composition of seed tocopherols (Toc's) are important to rapeseed breeding and production. However, little is known about the biosynthesis of Toc's in response to environmental signals. In this study, we investigated the effects of exogenous gibberellin (GA3) and paclobutrazol (PAC) on Toc biosynthesis. We also explored the interactive effects between the two plant growth regulators (PGRs) and other factors, such as PGR treatment duration, genotype, and growing location on the total Toc yield and composition in oilseed rape seed. GA3 significantly enhanced the production of Toc's and elevated the α-/γ-Toc ratio in a time- and genotype-dependent manner. By contrast, PAC significantly reduced Toc yield. Genotypic differences were observed in the effects of GA3 on Toc yield and composition in the seeds. GA3 significantly increased the Toc yield and α-/γ-Toc ratio in Zheyou-50, a genotype with a low proportion of very long chain fatty acids (VLCFAs). However, GA3 did not significantly influence these parameters in Jiu-Er-13Xi, a genotype with a high VLCFA proportion. The increased Toc yield induced by GA3 was mediated by the upregulation of genes (BnPDS1 and BnVTE1) that catalyze the production of Toc precursors. Therefore, applying GA3 can improve rapeseed quality by increasing Toc yield and improving Toc composition.


Capturing children's response to parental conflict and making use of it.
To read this article's abstract in both Spanish and Mandarin Chinese, please visit the article's full-text page on Wiley InterScience (http://interscience.wiley.com/journal/famp). The aim of our study is to examine the interface between children's physiological changes and the specificities of parental conflict, and to develop a procedure in which such information can be shared with the family for therapeutic change. Children from 20 families were exposed to parental conflict discussion (CD) while their arousals were measured through skin conductance and heart rate sensors. It was found that regardless of the subject of the argument, 80% of the time they were complaining about each other. Likewise, 80% of the time the children were responding to the parents' own interpersonal tension, including moments of silence. The protocol established for the study, consisting of CD and debriefing, was found to be a powerful tool in moving parents toward conflict resolution.


Development of a binary classifier model from extended facial codes toward video-based pain recognition in cancer patients.
The Automatic Pain Assessment (APA) relies on the exploitation of objective methods to evaluate the severity of pain and other pain-related characteristics. Facial expressions are the most investigated pain behavior features for APA. We constructed a binary classifier model for discriminating between the absence and presence of pain through video analysis. A brief interview lasting approximately two-minute was conducted with cancer patients, and video recordings were taken during the session. The Delaware Pain Database and UNBC-McMaster Shoulder Pain dataset were used for training. A set of 17 Action Units (AUs) was adopted. For each image, the OpenFace toolkit was used to extract the considered AUs. The collected data were grouped and split into train and test sets: 80 % of the data was used as a training set and the remaining 20 % as the validation set. For continuous estimation, the entire patient video with frame prediction values of 0 (no pain) or 1 (pain), was imported into an annotator (ELAN 6.4). The developed Neural Network classifier consists of two dense layers. The first layer contains 17 nodes associated with the facial AUs extracted by OpenFace for each image. The output layer is a classification label of "pain" (1) or "no pain" (0). The classifier obtained an accuracy of ∼94 % after about 400 training epochs. The Area Under the ROC curve (AUROC) value was approximately 0.98. This study demonstrated that the use of a binary classifier model developed from selected AUs can be an effective tool for evaluating cancer pain. The implementation of an APA classifier can be useful for detecting potential pain fluctuations. In the context of APA research, further investigations are necessary to refine the process and particularly to combine this data with multi-parameter analyses such as speech analysis, text analysis, and data obtained from physiological parameters.


Childhood alcohol use may predict adolescent binge drinking: a multivariate analysis among adolescents in Brazil.
To test the hypothesis that first alcohol use during childhood is associated with heavy drinking patterns during adolescence and with parental drinking patterns and parental rules about alcohol consumption. A national cross-sectional survey of 17,371 high-school students. Students were drawn from 789 public and private schools in all the Brazilian state capitals using a multistage probabilistic sampling method and a self-report questionnaire. Weighted data were analyzed through logistic regression testing for differences on the associated factors for first use of alcohol during childhood. Survival analysis and Cox proportional hazard models were used to confirm results. Among the 82% alcohol lifetime users, 11% had first used alcohol before age 12 years. The lack of perception of possible punishment by parents is associated with childhood alcohol use (OR 2.22, 95% CI 1.67-2.95). Adolescents who first used alcohol during childhood compared with those who only used alcohol at later ages are more likely to engage in binge drinking behaviors (OR 1.57, 95% CI 1.17-2.10), to have a pattern of heavy alcohol use (OR 1.98, 95% CI 1.26-3.09), and to have recently used illegal drugs (OR 1.74, 95% CI 1.39-2.16). According to hazard ratios, students with an earlier age of onset were more likely to have used tobacco and any illegal drug in the past year. Childhood alcohol may be a risk factor for the most dangerous patterns of alcohol use in adolescence and is associated with parental alcohol use. Parental rules about child alcohol use must be clear because perception of punishment might delay the age of first alcohol use.


Potential antioxidant activity of celecoxib and amtolmetin guacyl: in vitro studies.
1. In vitro studies of the potential antioxidant activity of the selective cyclo-oxygenase-2 inhibitor celecoxib and the non-steroid anti-inflammatory drug amtolmetin guacyl (AMG) were carried out. The study included experiments on the ability of these drugs to affect some indices of the oxidative stress [lipid peroxidation (LP), activity of antioxidant enzymes, glutathione (GSH) level] in rat stomach and colon mucosa and in liver. 2. Celecoxib and AMG did not change the activity of the enzymes GSH-peroxidase, oxidased glutathione (GSSG)-reductase and glucose-6-phosphate-dehydrogenase, as well as the GSH level in all tissue preparations. An increased superoxide dismutase (SOD) activity and a tendency to a decreased Fe/ascorbic acid-induced LP in stomach and colon mucosa were found, but only in the presence of AMG. 3. In the liver, both celecoxib and AMG decreased spontaneous and Fe/ascorbic acid-induced LP. SOD activity was enhanced only in the presence of AMG. 4. Experiments aimed at studying celecoxib and AMG in free oxygen radical-generating systems were also carried out. AMG and tolmetin (the main metabolite of AMG) inhibited OH*-provoked deoxyribose degradation in a Fenton system. Celecoxib had no effect on free radicals when tested in the same system. 5. In conclusion, the results of the present in vitro studies suggest that AMG and celecoxib possess antioxidant and metal-chelating abilities, which might contribute to their beneficial effects.


Comparison of dissection speed during colorectal ESD between the novel Multiloop (M-loop) traction method and ESD methods without traction.
Background and study aims We previously reported on a novel traction method called Multiloop (M-loop) for faster colorectal endoscopic submucosal dissection (ESD). In this study, we retrospectively compared the difference in submucosal dissection time (SDT), and submucosal dissection speed (SDS) between groups of patients who were treated using traction with the M-loop method, and with non-traction methods of colorectal ESD. Patients and methods We reviewed and timed duration of colorectal ESD by the non-traction method from videos recorded between June 2016 and December 2017. From January 2018 onward, we used the M-loop method during all colorectal ESDs and timed it until August 2018. Outcomes of colorectal ESD with the M-loop method and non-traction methods were compared. The study involved two experts and eight non-experts and was carried out at a tertiary endoscopic center in Japan. Results The study included 50 patients who treated with the M-loop method and 115 patients treated with the non-traction method. Submucosal dissection time (SDT) was not significantly different (M-loop group, 42.1 ± 4.2 min, non-traction ESD group, 51.9 ± 3.3 min) ( P = 0.098), but submucosal dissection speed (SDS) was significantly greater (M-loop group, 28.0 ± 2.9 mm 2 /min, non-traction ESD group, 19.9 ± 2.0 mm 2 /min) ( P = 0.0014) in the M-loop method group. Multivariate analysis showed that the M-loop method increased SDS by odds ratio of 1.46 ( P = 0.001) when compared to the non-traction ESD method. A significant difference was also observed for SDT and SDS when the two methods were compared after propensity score matching ( P = 0.001). No differences in unfavorable outcomes were observed. Conclusions The M-loop method improved SDS compared to non-traction methods of ESD. The method is an effective tool to assist colorectal ESD.


TiO2 nanoparticles induce DNA double strand breaks and cell cycle arrest in human alveolar cells.
TiO2 nanoparticles (NPs) have the second highest global annual production (∼3000 tons) among the metal-containing NPs. These NPs are used as photocatalysts for bacterial disinfection, and in various other consumer products including sunscreen, food packaging, therapeutics, biosensors, surface cleaning agents, and others. Humans are exposed to these NPs during synthesis (laboratory), manufacture (industry), and use (consumer products, devices, medicines, etc.), as well as through environmental exposures (disposal). Hence, there is great concern regarding the health effects caused by exposure to NPs and, in particular, to TiO2 NPs. In the present study, the genotoxic potential of TiO2 NPs in A549 cells was examined, focusing on their potential to induce ROS, different types of DNA damage, and cell cycle arrest. We show that TiO2 NPs can induce DNA damage and a corresponding increase in micronucleus frequency, as evident from the comet and cytokinesis-block micronucleus assays. We demonstrate that DNA damage may be attributed to increased oxidative stress and ROS generation. Furthermore, genomic and proteomic analyses showed increased expression of ATM, P53, and CdC-2 and decreased expression of ATR, H2AX, and Cyclin B1 in A549 cells, suggesting induction of DNA double strand breaks. The occurrence of double strand breaks was correlated with cell cycle arrest in G2/M phase. Overall, the results indicate the potential for genotoxicity following exposure to these TiO2 NPs, suggesting that use should be carefully monitored.


Sudden death and anomalous origin of the coronary arteries from the aorta. A case report and review.
Based on a case report of sudden death in a young boy, this paper reviews the available information concerning the various combinations of anomalous origins of coronary arteries and associated sudden death. Left coronary arteries arising from the right sinus of Valsalva and passing between the aorta and pulmonary arteries are often associated with sudden death and myocardial ischemia in young people. Although right coronary arteries originating from the left sinus of Valsalva and passing between the aorta and pulmonary artery are less frequently associated with symptoms, this condition may be associated with sudden death. The incidence of symptoms associated with other anomalous origins is also discussed.


Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.
Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p = 0.0001), and MMP-3 (p = 0.0005) and -9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p = 0.0408) and MMP-9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP-2 (p = 0.0023) and -9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion.


Extracellular Matrix Alterations and Deposit Formation in AMD.
Age related macular degeneration (AMD) is the primary cause of vision loss in the western world (Friedman et al., Arch Ophthalmol 122:564-572, 2004). The first clinical indication of AMD is the presence of drusen. However, with age and prior to the formation of drusen, extracellular basal deposits accumulate between the retinal pigment epithelium (RPE) and Bruch's membrane (BrM). Many studies on the molecular composition of the basal deposits and drusen have demonstrated the presence of extracellular matrix (ECM) proteins, complement components and cellular debris. The evidence reviewed here suggests that alteration in RPE cell function might be the primary cause for the accumulation of ECM and cellular debri found in basal deposits. Further studies are obviously needed in order to unravel the specific pathways that lead to abnormal formation of ECM and complement activation.


Mitochondrial DNA control region polymorphisms: genetic markers for ecological studies of marine turtles.
We describe a rapid and sensitive method for the detection of population-specific genetic markers in mitochondrial DNA (mtDNA) and the use of such markers to analyse population structure of marine turtles. A series of oligonucleotide primers specific for the amplification of the mtDNA control region in Cheloniid turtles were designed from preliminary sequence data. Using two of these primers, a 384-385-bp sequence was amplified from the 5' portion of the mtDNA control region of 15 green turtles Chelonia mydas from 12 different Indo-Pacific rookeries. Fourteen of the 15 individuals, including some with identical whole-genome restriction fragment patterns, had sequences that differed by one or more base substitutions. Analysis of sequence variation among individuals identified a total of 41 nucleotide substitutions and a 1-bp insertion/deletion. Comparison with evidence from whole-genome restriction enzyme analysis of the same individuals indicated that this portion of the control region is evolving approximately eight times faster than the average rate and that the sequence analysis detected approximately one fifth of the total variation present in the genome. Restriction enzyme analysis of amplified products from an additional 256 individuals revealed significant geographic structuring in the distribution of mtDNA genotypes among five of the 10 rookeries surveyed extensively. Additional geographic structuring of genotypes was identified through denaturing gradient gel electrophoresis (DGGE) of amplified products. Only two of the 10 rookeries surveyed could not be differentiated, indicating that the Indo-Pacific C. mydas include a number of genetically differentiated populations, with minimal female-mediated gene flow among them. Important applications for genetic markers in the conservation and management of marine turtles include the identification of appropriate demographic units for research and management (i.e. genetically discrete populations) and assessment of the composition of feeding and harvested populations.


Influence of arsenate imposition on modulation of antioxidative defense network and its implication on thiol metabolism in some contrasting rice (Oryza sativa L.) cultivars.
Globally, many people have been suffering from arsenic poisoning. Arsenate (AsV) exposure to twelve rice cultivars caused growth retardation, triggered production of As-chelatin biopeptides and altered activities of antioxidants along with increase in ascorbate (AsA)-glutathione (GSH) contents as a protective measure. The effects were more conspicuous in cvs. Swarnadhan, Tulaipanji, Pusa basmati, Badshabhog, Tulsibhog and IR-20 to attenuate oxidative-overload mediated adversities. Contrastingly, in cvs. Bhutmuri, Kumargore, Binni, Vijaya, TN-1 and IR-64, effects were less conspicuous in terms of alterations in the said variables due to reduced generation of oxidative stress. Under As(V) imposition, the protective role of phytochelatins (PCs) were recorded where peaks height and levels of PCs (PC2, PC3 and PC4) were elevated significantly in the test seedlings with an endeavour to detoxify cells by sequestering arsenic-phytochelatin (As-PC) complex into vacuole that resulted in reprogramming of antioxidants network. Additionally, scatter plot correlation matrices, color-coded heat map analysis and regression slopes demonstrated varied adaptive responses of test cultivars, where cvs. Bhutmuri, Kumargore, Binni, Vijaya, TN-1 and IR-64 found tolerant against As(V) toxicity. Results were further justified by hierarchical clustering. These findings could help to grow identified tolerant rice cultivars in As-prone soil with sustainable growth and productivity after proper agricultural execution.


Discontinuing cannabis improves depression in people with multiple sclerosis: A short report.
To assess whether symptoms of depression change when people with multiple sclerosis (pwMS) discontinue cannabis use, 40 cognitively impaired pwMS who smoked cannabis almost daily were randomly assigned to either a cannabis continuation (CC) or cannabis withdrawal (CW) group. Both groups were followed for 28 days. All participants completed the Hospital Anxiety and Depression Scale. At day 28 the 11-nor-9-carboxy-Δ9-tetrahydro-cannabinol (THCCOOH)/creatinine ratio in the CW group declined to zero (p = 0.0001), but remained unchanged in the CC group (p = 0.709). Depression scores in those pwMS who were using cannabis to manage their depression remained statistically unchanged in the CC group, but declined in the CW group (p = 0.006). Despite pwMS using cannabis to help their mood, depression improved significantly off the drug. Our finding provides a cautionary note in relation to cannabis use in pwMS, at least with respect to depression.


The Effect of Transitional Care on 30-Day Outcomes in Patients Hospitalised With Acute Heart Failure.
Patients admitted to hospital with acute heart failure (AHF) are at increased risk of readmission and mortality post-discharge. The aim of the study was to examine health service utilisation within 30 days post-discharge from an AHF hospitalisation. This was a prospective, observational, non-randomised study of consecutive patients hospitalised with acute HF to one of 16 Victorian hospitals over a 30-day period each year and followed up for 30 days post-discharge. The project was conducted annually over three consecutive years from 2015 to 2017. Of the 1,197 patients, 56.3% were male with an average age of 77±13.23 years. Over half of the patients (711, 62.5%) were referred to an outpatient clinic and a third (391, 34.4%) to a HF disease management program. In-hospital mortality was 5.1% with 30 day-mortality of 9% and readmission rate of 24.4%. Patients who experienced a subsequent readmission less than 10 days post-discharge and between 11 and 20 days post-discharge had a five- to six-fold increase in risk of mortality (adjusted OR 5.02, 95% CI 2.11-11.97; OR 6.45, 95% CI 2.69-15.42; respectively) compared to patients who were not readmitted to hospital. An outpatient appointment within 30 days post-discharge significantly reduced the risk of 30-day mortality by 81% (95% CI 0.09-0.43). Patients admitted to hospital with AHF who experience a subsequent readmission within 20 days post-discharge are at increased risk of dying. However, early follow-up post-discharge may reduce this risk. Early post-discharge follow-up is vital to address this vulnerable period after a HF admission.


Nonhomologous chromosomal integration of foreign DNA is completely dependent on MUS-53 (human Lig4 homolog) in Neurospora.
Homologous integration of a foreign DNA segment into a chromosomal target sequence enables precise disruption or replacement of genes of interest and provides an effective means to analyze gene function. However, integration after transformation is predominantly nonhomologous in most species other than yeast. Here, we show that homologous integration in the filamentous fungus Neurospora requires the homologous-recombination proteins MEI-3 (yeast Rad51 homolog) and MUS-25 (yeast Rad54 homolog), whereas nonhomologous integration requires nonhomologous end-joining protein MUS-52 (yeast Ku80 homolog). Two additional minor integration pathways are present, one MEI-3-independent and homologous, the other MUS-52-independent and nonhomologous. Homologous and nonhomologous mechanisms compete when external DNA is integrated. In Neurospora, both nonhomologous integration pathways, MUS-52-dependent and MUS-52-independent, require MUS-53 (a homolog of human Lig4), which functions in the final step of nonhomologous end-joining. Because nonhomologous integration is eliminated in a LIG4-disrupted strain, integration occurs only at the targeted site in mus-53 mutants, making them an extremely efficient and safe host for gene targeting.


Relationship between late potentials and myocardial viability assessed by dobutamine echocardiography in the early postinfarction period.
In the postmyocardial infarction period, late potentials (LPs) are a sensitive marker for the occurrence of sustained ventricular tachycardia and ventricular fibrillation. The relationship between positive signal-averaged electrocardiogram (SAECG) and myocardial viability remains controversial. The aim of the present study was to assess prospectively the possible relationship between LPs and myocardial viability detected by dobutamine stress echocardiography (DSE) in the early period after myocardial infarction (AMI), before hospital discharge. Ninety-nine patients with AMI were included prospectively in the study. The mean age was 58 +/- 11 years, 17 were women and 82 were men. All patients had SAEG and DSE, and 94 had coronary angiography before hospital discharge. In the overall population, presence of viability was demonstrated in fewer patients with LPs [37 of 70 (52%)] than absence of viability [18 of 29 (62%)] but the difference did not reach statistical significance. In the subgroup of patients with left ventricular ejection fraction (LVEF) lower than 40%, at higher risk of arrhythmias, the presence of viability was associated with the absence of LPs: 80% of the patients without LPs had viability by DSE (P < 0.01) and only 35% of patients with LPs had viability by DSE (not significant). In patients with an acute myocardial infarction and with low ejection fraction (<40%), the absence of LPs is related to the presence of viable myocardium as assessed by DSE early after the acute event. These data also suggest that myocardial viability is not the substrate for LPs in this population.


Patient acuity and nurse staffing challenges in Norwegian neonatal intensive care units.
To describe fluctuations in patient numbers, patient acuity and the need for nurses in neonatal intensive care units based on population data. Neonatal intensive care units are difficult to staff appropriately due to fluctuations in patient volume and acuity. Staffing guidelines have been developed and applied in some countries to offer the neonatal population safe patient care. National data were used to describe patient load and acuity for two consecutive years. The need for nurses was calculated by combining these data with guidelines for nurse staffing. A total of 11.3% of all neonatal patients in Norway were categorised as intensive care patients. There were no differences in the need for nurses in weekends vs. weekdays or during summer holidays vs. days in the rest of the year. Small units have increased variability in staffing needs, and sufficient staffing is more challenging compared to that of larger units. Planning for reduced staffing for weekends and summer seasons is ineffective. Staffing planned for most of the days in a year instead of the median need for nurses will result in a greater increase in the need for nurses in small units compared to larger units.


The uPA System Differentially Alters Fibroblast Fate and Profibrotic Ability in Skin Fibrosis.
Skin fibrosis is a common pathological feature of various diseases, and few treatment strategies are available because of the molecular pathogenesis is poorly understood. The urokinase-type plasminogen activator (uPA) system is the major serine protease system, and its components uPA, urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1(PAI-1) are widely upregulated in fibrotic diseases, including hypertrophic scars, keloids, and scleroderma. Here, we found that the successful binding of uPA and uPAR activates the downstream peroxisome proliferator-activated receptor (PPAR) signalling pathway to reduce the proliferation, migration, and contraction of disease-derived fibroblasts, contributing to the alleviation of skin fibrosis. However, increased or robust upregulation of the inhibitor PAI-1 inhibits these effects, suggesting of the involvement of PAI-1 in skin fibrosis. Subsequent in vivo studies showed that uPAR inhibitors increased skin fibrosis in mouse models, while uPA agonists and PAI-1 inhibitors reversed these effects. Our findings demonstrate a novel role for the uPA system and highlights its relationships with skin fibrosis, thereby suggesting new therapeutic approaches targeting the uPA system.


Distances walked in the six-minute walk test: suggestion of defining characteristic for the nursing diagnosis Ineffective Peripheral Tissue Perfusion.
Distances walked in walking tests are important functional markers, although they are not accepted as defining characteristics of Ineffective Peripheral Tissue Perfusion. The aims of this study were to verify the distances participants with and without this nursing diagnosis walked in the six-minute walk test and if these measures may be considered defining characteristics of this phenomenon. Participants with (group A; n=65) and without (group B; n=17) this nursing diagnosis were evaluated regarding physical examination, vascular function and functional capacity. Participants of group A seemed to have worse vascular function and functional capacity compared with those of group B. Pain-free travelled distance was predictive of the nursing diagnosis. These results are important for the refinement of this diagnosis. In conclusion, this study provides evidences that the distances walked in the six-minute walk test may be considered defining characteristics of Ineffective Peripheral Tissue Perfusion.


Analyses of Time Series InSAR Signatures for Land Cover Classification: Case Studies over Dense Forestry Areas with L-Band SAR Images.
As demonstrated in prior studies, InSAR holds great potential for land cover classification, especially considering its wide coverage and transparency to climatic conditions. In addition to features such as backscattering coefficient and phase coherence, the temporal migration in InSAR signatures provides information that is capable of discriminating types of land cover in target area. The exploitation of InSAR signatures was expected to provide merits to trace land cover change in extensive areas; however, the extraction of suitable features from InSAR signatures was a challenging task. Combining time series amplitudes and phase coherences through linear and nonlinear compressions, we showed that the InSAR signatures could be extracted and transformed into reliable classification features for interpreting land cover types. The prototype was tested in mountainous areas that were covered with a dense vegetation canopy. It was demonstrated that InSAR time series signature analyses reliably identified land cover types and also recognized tracing of temporal land cover change. Based on the robustness of the developed scheme against the temporal noise components and the availability of advanced spatial and temporal resolution SAR data, classification of finer land cover types and identification of stable scatterers for InSAR time series techniques can be expected. The advanced spatial and temporal resolution of future SAR assets combining the scheme in this study can be applicable for various important applications including global land cover changes monitoring.


The role of myeloid derived suppressor cells in musculoskeletal disorders.
The immune system is closely linked to bone homeostasis and plays a pivotal role in several pathological and inflammatory conditions. Through various pathways it modulates various bone cells and subsequently sustains the physiological bone metabolism. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous immature myeloid-derived cells that can exert an immunosuppressive function through a direct cell-to-cell contact, secretion of anti-inflammatory cytokines or specific exosomes. These cells mediate the innate immune response to chronic stress on the skeletal system. In chronic inflammation, MDSCs act as an inner offset to rebalance overactivation of the immune system. Moreover, they have been found to be involved in processes responsible for bone remodeling in different musculoskeletal disorders, autoimmune diseases, infection, and cancer. These cells can not only cause bone erosion by differentiating into osteoclasts, but also alleviate the immune reaction, subsequently leading to long-lastingly impacted bone remodeling. In this review, we discuss the impact of MDSCs on the bone metabolism under several pathological conditions, the involved modulatory pathways as well as potential therapeutic targets in MDSCs to improve bone health.


Phase II study of sequential high-dose methotrexate (MTX) and 5-fluorouracil (F) alternated with epirubicin (E) and cisplatin (P) [FEMTX-P] in advanced gastric cancer.
FAMTX (5-fluorouracil, adriamycin, methotrexate) is one of the most effective drug combinations in gastric cancer. Therefore, modifications of FAMTX appear of interest and the FEMTX-P regiment was conceived. Fifty patients with unresectable locally advanced and/or metastatic gastric carcinoma were treated with methotrexate 1500 mg/m2 i.v. and 5-fluorouracil 1500 mg/m2 i.v. on day 1; leucovorin rescue 15 mg/m2 orally every 6 hours for 8 doses on days 2 and 3; epirubicin 60 mg/m2 i.v. and cisplatin 50 mg/m2 i.v. on day 15, q 4 weeks. Of forty-seven patients evaluable for response, five (11%) achieved complete responses and seventeen (36%) partial responses (total response rate 47%). The median duration of response was 8+ months (range: 5-25+ months). Four of 14 patients with locally advanced disease were successfully downstaged and subsequently resected. The median duration of survival of all patients was 10 months (range: 1-25+ months). Leukopenia grade 4 occurred in 18% of patients and thrombocytopenia grade 4 and mucositis grade 4 in 4% and 2%, respectively. Treatment postponement for hematologic toxicity was necessary in 54% of patients. The FEMTX-P regimen is an active regimen in advanced gastric carcinoma, with acceptable toxicity.


Modeling the formation of N-nitrosodimethylamine (NDMA) from the reaction of natural organic matter (NOM) with monochloramine.
This paper presents mechanistic studies on the formation of NDMA, a newly identified chloramination disinfection byproduct, from reactions of monochloramine with natural organic matter. A kinetic model was developed to validate proposed reactions and to predict NDMA formation in chloraminated water during the time frame of 1-5 days. This involved incorporating NDMA formation reactions into an established comprehensive model describing the oxidation of humic-type natural organic matter by monochloramine. A rate-limiting step involving the oxidation of NOM is theorized to control the rate of NDMA formation which is assumed to be proportional to the rate of NOM oxidized by monochloramine. The applicability of the model to describe NDMA formation in the presence of three NOM sources over a wide range in water quality (i.e., pH, DOC, and ammonia concentrations) was evaluated. Results show that with accurate measurement of monochloramine demand for a specific supply, NDMA formation could be modeled over an extended range of experimental conditions by considering a single NOM source-specific value of thetaNDMA, a stoichiometric coefficient relating the amount of NDMA produced to the amount of NOM oxidized, and several kinetic parameters describing NOM oxidation. Furthermore, the oxidation of NOM is the rate-limiting step governing NDMA formation. This suggests that NDMA formation over a 1-5 day time frame may be estimated from information on the chloramine or free chlorine demand of the NOM and the source-specific linear relationship between this demand and NDMA formation. Although the proposed model has not yet been validated for shorter time periods that may better characterize the residence time in some distribution systems, the improved understanding of the important reactions governing NDMA formation and the resulting model should benefit the water treatment industry as a tool in developing strategies that minimize NDMA formation.