The role of antibiotic prophylaxis in preterm premature rupture of membranes.
Preterm premature rupture of membranes (PPROM) occurs in 3 percent of all pregnancies and is responsible for, or associated with, approximately one-third of preterm births causing significant perinatal morbidity and fetal death. Preterm infants are very vulnerable to respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), periventricular leucomalacia (PVL), other neurological sequelae, infection and necrotizing enterocolitis (NEC). Chorioamnionitis based on clinical criteria occurs in approximately 3-30% of all PPROM pregnancies. The aim of this study was to analyze the role of antibiotic prophylaxis in delivery delay on neonatal outcome (body weight, Apgar scores, pulmonary complications, neurological complications--abnormal cerebral ultrasound scan prior to hospital discharge, perinatal infections) and to determine the possibility of an optimal antibiotic regimen. Therefore we retrospectively analyzed last 5 years of data from patients treated in our center and provided a coherent overview of the clinical course and outcome of patients with PPROM treated with prophylactic antibiotics and antenatal corticosteroids. There were 324 preterm newborns which fulfilled the inclusion criteria for our study; 190 in Study group (received empiric i.v. antibiotics) and 134 in Control group (without antibiotic). We found significant difference in gestational age (p < 0.0001), birth weight (p < 0.0001), Apgar scores (p < 0.0001) maternal C-reactive protein level (p < 0.0001) and latency period (5.54 days vs. 11.33 days, p = 0.001) between the groups. Histologic chorioamnionitis was significantly more frequent in s Study group (14.2% vs. 36.3%, p < 0.0001). We found significant difference in neonatal outcome according the different antibiotic treatment. Antenatal antibiotics and corticosteroid therapies have clear benefits and should be offered to all women without contraindications.


A Survey of Ticks Infesting Dogs and Cats in Ireland.
Ticks are important ectoparasites of dogs and cats. Infestations can result in itching and localised dermatitis. In addition, ticks can act as vector of a range of viral, bacterial and protozoal pathogens. This paper reports the results of a nationwide survey of ticks infesting dogs and cats in Ireland. Seventy veterinary practices submitted a total of 120 ticks collected from 56 dogs and 16 cats. Ixodes ricinus was the most abundant species on dogs while Ixodes hexagonus was the most abundant species on cats. The remainder were identified as Ixodes canisuga and a single Rhipicephalus sanguineus specimen. The garden was most frequently associated with tick exposure in both dogs and cats. Sporting dog breeds (n = 17; 31%) were more likely to be infested with ticks than any other breed. Nearly all (n = 56; 95%) veterinarians indicated that ticks are a concern to their clients when they are found on their pets. Pet owners used a variety of products to control ectoparasites on their animals but a significant number (n = 18, 31%) indicated that they felt that the products are less effective highlighting the need for further investigations. Field sampling indicated that ticks are present at a low level in much of the greater Dublin area.


Carnosol inhibits cell adhesion molecules and chemokine expression by tumor necrosis factor-α in human umbilical vein endothelial cells through the nuclear factor-κB and mitogen-activated protein kinase pathways.
Inflammatory bowel diseases (IBD) are gastrointestinal disorders associated with chronic inflammatory processes. Carnosol has been demonstrated to possess anti-inflammatory properties. This study examined the suppressive effect of carnosol on the expression of cell adhesion molecules (CAMs) and chemokines in human umbilical vein endothelial cells (HUVECs) and the possible underlying mechanism. The effect of carnosol on CAM and chemokine expression in HUVECs was identified by western blotting and ELISA, respectively. nuclear factor (NF)-κB activation of HUVECs was analyzed using the TransAM NF-κB Family kit. The effect of carnosol on the tumor necrosis factor (TNF)-α-induced activation of the NF-κB and mitogen-activated protein kinase (MAPK) pathways, and was subsequently analyzed using western blotting. Carnosol not only inhibited TNF-α-induced protein expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and E-selectin in HUVECs, but also suppressed interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 expression. In addition, carnosol inhibited the TNF-α-induced phosphorylation of p-65 and IκB-α, as well as the activation of NF-κB. The same result was observed in TNF-α-stimulated phosphorylation of ERK1/2 and p-38. It was demonstrated that carnosol inhibited TNF-α-induced CAM and chemokine expression in HUVECs. The underlying mechanism may be associated with the blocking of the NF-κB and MAPK pathways. These results indicate that carnosol may be a novel therapeutic agent for targeting endothelial cells in IBDs.


Design and implementation of a web-based patient portal linked to an electronic health record designed to improve medication safety: the Patient Gateway medications module.
In this article we describe the background, design, and preliminary results of a medications module within Patient Gateway (PG), a patient portal linked to an electronic health record (EHR). The medications module is designed to improve the accuracy of medication lists within the EHR, reduce adverse drug events and improve patient-provider communication regarding medications and allergies in several primary care practices within a large integrated healthcare delivery network. This module allows patients to view and modify the list of medications and allergies from the EHR, report non-adherence, side effects and other medication-related problems and easily communicate this information to providers, who can verify the information and update the EHR as needed. Usage and satisfaction data indicate that patients found the module easy to use, felt that it led to their providers having more accurate information about them and enabled them to feel more prepared for their forthcoming visits. Further analyses will determine the effects of this module on important medication-related outcomes and identify further enhancements needed to improve on this approach.


Daily collection of self-reporting sleep disturbance data via a smartphone app in breast cancer patients receiving chemotherapy: a feasibility study.
Improvements in mobile telecommunication technologies have enabled clinicians to collect patient-reported outcome (PRO) data more frequently, but there is as yet limited evidence regarding the frequency with which PRO data can be collected via smartphone applications (apps) in breast cancer patients receiving chemotherapy. The primary objective of this study was to determine the feasibility of an app for sleep disturbance-related data collection from breast cancer patients receiving chemotherapy. A secondary objective was to identify the variables associated with better compliance in order to identify the optimal subgroups to include in future studies of smartphone-based interventions. Between March 2013 and July 2013, patients who planned to receive neoadjuvant chemotherapy for breast cancer at Asan Medical Center who had access to a smartphone app were enrolled just before the start of their chemotherapy and asked to self-report their sleep patterns, anxiety severity, and mood status via a smartphone app on a daily basis during the 90-day study period. Push notifications were sent to participants daily at 9 am and 7 pm. Data regarding the patients' demographics, interval from enrollment to first self-report, baseline Beck's Depression Inventory (BDI) score, and health-related quality of life score (as assessed using the EuroQol Five Dimensional [EQ5D-3L] questionnaire) were collected to ascertain the factors associated with compliance with the self-reporting process. A total of 30 participants (mean age 45 years, SD 6; range 35-65 years) were analyzed in this study. In total, 2700 daily push notifications were sent to these 30 participants over the 90-day study period via their smartphones, resulting in the collection of 1215 self-reporting sleep-disturbance data items (overall compliance rate=45.0%, 1215/2700). The median value of individual patient-level reporting rates was 41.1% (range 6.7-95.6%). The longitudinal day-level compliance curve fell to 50.0% at day 34 and reached a nadir of 13.3% at day 90. The cumulative longitudinal compliance curve exhibited a steady decrease by about 50% at day 70 and continued to fall to 45% on day 90. Women without any form of employment exhibited the higher compliance rate. There was no association between any of the other patient characteristics (ie, demographics, and BDI and EQ5D-3L scores) and compliance. The mean individual patient-level reporting rate was higher for the subgroup with a 1-day lag time, defined as starting to self-report on the day immediately after enrollment, than for those with a lag of 2 or more days (51.6%, SD 24.0 and 29.6%, SD 25.3, respectively; P=.03). The 90-day longitudinal collection of daily self-reporting sleep-disturbance data via a smartphone app was found to be feasible. Further research should focus on how to sustain compliance with this self-reporting for a longer time and select subpopulations with higher rates of compliance for mobile health care.


Retinal vaso-occlusion in sickling hemoglobinopathies.
Sickle cell retinopathy, in all of its manifestations, represents the effects of arteriolar and capillary occlusions. Increased viscosity of circulating whole blood plus the microembolic action of individual sickled erythrocytes contribute to vasoocclusion. Decreased oxygenation and increased acidosis develop and lead to further sickling -- and further vaso-occlusion. The cycle of erythrostasis that characterizes sickling throughout the body is also applicable to the retina. The transparent media of the eye permit direct visualization of vaso-occlusions which occur preferentially in and about the macula and in the far periphery of the retina. Many of the occlusive episodes are transient. There dynamic events are simultaneously occurring elsewhere in the body but can only be visualized in the eye. The net effect in the retina is a remodeling of its vasculature, as some vessels close and others reopen. After the onset of arteriolar closure in the retina, affected blood vessels embark on a spontaneous, naturally evolving course of events leading to arteriolarvenular anastomoses, neovascular proliferations, vitreous hemorrhages, and retinal detachment. The advanced stages of proliferative sickle retinopathy are most commonly observed in SC disease and in Sthal, possibly because these two forms of sickling have significantly higher than normal whole blood viscosity. Retinal vaso-occlusions can also lead to blow-out hemorrhages which may evolve into salmon patches, iridescent spots, schisis cavities, and black sunbursts. In some respects sickle retinopathy is unique, but many of its manifestations are similar to those of retinopathies found in diabetes mellitus, AC hemoglobinopathy, Takayasu pulseless disease, sarcoidosis, chronic myelogenous leukemia, branch retinal vein occlusion, retrolental fibroplasia, and Eales disease.


Dimensionality and confinement effects in δ-doped Pd(Fe) layers.
We address the dimensionality aspects of the magnetic ordering in δ-doped Pd(Fe) structures. The key property we investigate, via magneto-optic Kerr measurements, is the magnetization induced by iron in palladium, over a wide temperature range 5 K < T < 300 K. The dimensional crossover we observe cannot be rationalized on the basis of structural considerations alone, since we find the dimensionality of the low temperature and of the critical region can differ. We discuss the crossover in terms of the temperature dependence of the magnon modes, giving rise to lower dimensionality at low temperatures.


Population structure and adaptation of a bacterial pathogen in California grapevines.
Xylella fastidiosa subsp. fastidiosa causes Pierce's disease of grapevine (PD) and has been present in California for over a century. A singly introduced genotype spread across the state causing large outbreaks and damaging the grapevine industry. This study presents 122 X. fastidiosa subsp. fastidiosa genomes from symptomatic grapevines, and explores pathogen genetic diversity associated with PD in California. A total of 5218 single-nucleotide polymorphisms (SNPs) were found in the dataset. Strong population genetic structure was found; isolates split into five genetic clusters divided into two lineages. The core/soft-core genome constituted 41.2% of the total genome, emphasizing the high genetic variability of X. fastidiosa genomes. An ecological niche model was performed to estimate the environmental niche of the pathogen within California and to identify key climatic factors involved in dispersal. A landscape genomic approach was undertaken aiming to link local adaptation to climatic factors. A total of 18 non-synonymous polymorphisms found to be under selective pressures were correlated with at least one environmental variable highlighting the role of temperature, precipitation and elevation on X. fastidiosa adaptation to grapevines in California. Finally, the contribution to virulence of three of the genes under positive selective pressure and of one recombinant gene was studied by reverse genetics.


Transrectal ultrasound of the prostate bed after collagen injection.
Transurethral injection of collagen (TCI) may be used to treat urinary incontinence following radical prostatectomy for prostate cancer. The transrectal ultrasound (TRUS) findings after TCI are described in this report. TRUS exams of four postprostatectomy patients who had undergone TCI were reviewed. Findings were correlated with pathologic specimens obtained at TRUS-guided core biopsy. These histologic specimens were compared with others from postprostatectomy patients who had not undergone TCI. Well defined bladder apex masses of uniform echogenicity, hypoechoic to adjacent fat and muscle, were identified sonographically in all TCI patients. Masses from which positive biopsies were obtained were similar in appearance to those with no malignancy. Hypocellular fibrous tissue and foci of acellular loose connective tissue were identified in the biopsies of those patients who had undergone TCI. No acellular areas were identified in specimens from patients who had not had TCI. Sequelae of TCI should be included in the differential diagnosis of perianastomotic masses in postprostatectomy patients. However, the need for biopsy is not obviated as residual or recurrent prostate carcinoma may coexist.


Cholecystokinin receptors: biochemical demonstration and autoradiographical localization in rat brain and pancreas using [3H] cholecystokinin8 as radioligand.
Since cholecystokinin8 (CCK8) seems to be the physiological ligand of CCK receptors in the brain, it would be the most suitable probe for the characterization of CCK receptors in radioligand binding studies. [3H]CCK8 was synthetized with a specific radioactivity sufficient for the detection of high affinity binding sites. [3H]CCK8 binds saturably and reversibly to distinct sites in rat brain and pancreas with nanomolar affinity. While the C-terminal tetrapeptide of CCK is the minimal structure required for nanomolar affinity in the brain, the entire octapeptide sequence is required for binding affinity in pancreas. Desulfated CCK8 and several gastrin-I peptides, which are likewise unsulfated, show virtually no affinity to the binding sites in pancreas but high affinity in cerebral cortex. The ligand specificity of the CCK peptides corresponds to their electrophysiological potency in the brain and their stimulation of secretion in pancreas, respectively. Autoradiographically, high densities of [3H]CCK8 binding sites were found in cerebral cortex and olfactory bulb, medium levels in nucleus accumbens, hippocampus, dentate gyrus, and striatum with virtually no labeling in cerebellum. This pattern is similar to the distribution of CCK-like immunoreactivity in the brain. In pancreas, equally high levels of [3H]CCK8 labeling were found in the exocrine and endocrine region. [3H]CCK8 binding sites differ from those identified previously with [125I]Bolton-Hunter-CCK33 by their sensitivity to guanyl nucleotides in the brain, their ion dependency in the brain, and pancreas, and their different autoradiographical localization in some parts of the brain. The distribution of CCK binding sites labeled with [3H]CCK8 appears to correlate better with the CCK immunoreactivity than those labeled with [125I]Bolton-Hunter-CCK33. Thus, [3H]CCK8 appears to be the radioligand of choice for the investigation of CCK receptors.


Conjugated linoleic acids alter the fatty acid composition and physical properties of egg yolk and albumen.
Effects of dietary conjugated linoleic acids (CLAs) and docosahexaenoic acid (DHA) on the fatty acid composition of different egg compartments after storage were studied. Four dietary treatments [supplemented with safflower oil (SAFF, control group), DHA, CLAs plus DHA (CAD), and CLAs alone] were administered to Single Comb White Leghorn (SCWL) laying hens. Eggs from the different treatment groups were collected and stored for 10 weeks at 4 degrees C before analysis. Fatty acids from the yolk (yolk granules and plasma), egg albumen, and vitelline membrane were analyzed by gas chromatography. The yolk of eggs from hens given CLAs had significantly higher amounts of saturated fatty acids, typically 16:0 and 18:0, but lower amounts of polyunsaturated fatty acids (PUFAs) compared to eggs from the control group (SAFF). CLA content was highest in the yolk and present in both neutral and polar lipids, with the greatest concentrations in neutral lipids. DHA was incorporated mainly into yolk polar lipids. Lipids in yolk plasma and granules contained similar amounts of CLAs. The fatty acid compositions of vitelline membrane and egg albumen mirrored that of the egg yolk. CLA supplementation resulted in hard and rubbery yolks when compared to hard-cooked eggs from the control group. This study showed that feeding CLAs to hens led to accumulation of the isomers in polar and neutral lipids of the egg yolk and that these isomers migrated into egg albumen. Because the sensory properties of hard-cooked eggs were negatively affected by the enrichment of a mixture of CLA isomers in this study, further research should be conducted to evaluate how the different isomers alter the properties of egg yolk and albumen so that the quality of designed eggs containing CLAs and DHA can be improved.


Binding Mechanisms of Amyloid-like Peptides to Lipid Bilayers and Effects of Divalent Cations.
In several neurodegenerative diseases, cell toxicity can emerge from damage produced by amyloid aggregates to lipid membranes. The details accounting for this damage are poorly understood including how individual amyloid peptides interact with phospholipid membranes before aggregation. Here, we use all-atom molecular dynamics simulations to investigate the molecular mechanisms accounting for amyloid-membrane interactions and the role played by calcium ions in this interaction. Model peptides known to self-assemble into amyloid fibrils and bilayer made from zwitterionic and anionic lipids are used in this study. We find that both electrostatic and hydrophobic interactions contribute to peptide-bilayer binding. In particular, the attraction of peptides to lipid bilayers is dominated by electrostatic interactions between positive residues and negative phosphate moieties of lipid head groups. This attraction is stronger for anionic bilayers than for zwitterionic ones. Hydrophobicity drives the burial of nonpolar residues into the interior of the bilayer producing strong binding in our simulations. Moreover, we observe that the attraction of peptides to the bilayer is significantly reduced in the presence of calcium ions. This is due to the binding of calcium ions to negative phosphate moieties of lipid head groups, which leaves phospholipid bilayers with a net positive charge. Strong binding of the peptide to the membrane occurs less frequently in the presence of calcium ions and involves the formation of a "Ca2+ bridge".


Clinical Use of a Home Sleep Apnea Test: An American Academy of Sleep Medicine Position Statement.
The diagnosis and effective treatment of obstructive sleep apnea (OSA) in adults is an urgent health priority. It is the position of the American Academy of Sleep Medicine (AASM) that only a physician can diagnose medical conditions such as OSA and primary snoring. Throughout this statement, the term "physician" refers to a medical provider who is licensed to practice medicine. A home sleep apnea test (HSAT) is an alternative to polysomnography for the diagnosis of OSA in uncomplicated adults presenting with signs and symptoms that indicate an increased risk of moderate to severe OSA. It is also the position of the AASM that: the need for, and appropriateness of, an HSAT must be based on the patient's medical history and a face-to-face examination by a physician, either in person or via telemedicine; an HSAT is a medical assessment that must be ordered by a physician to diagnose OSA or evaluate treatment efficacy; an HSAT should not be used for general screening of asymptomatic populations; diagnosis, assessment of treatment efficacy, and treatment decisions must not be based solely on automatically scored HSAT data, which could lead to sub-optimal care that jeopardizes patient health and safety; and the raw data from the HSAT device must be reviewed and interpreted by a physician who is either board-certified in sleep medicine or overseen by a board-certified sleep medicine physician.


Allelic combinations of soybean maturity Loci E1, E2, E3 and E4 result in diversity of maturity and adaptation to different latitudes.
Soybean cultivars are extremely diverse in time to flowering and maturation as a result of various photoperiod sensitivities. The underlying molecular genetic mechanism is not fully clear, however, four maturity loci E1, E2, E3 and E4 have been molecularly identified. In this report, cultivars were selected with various photoperiod sensitivities from different ecological zones, which covered almost all maturity groups (MG) from MG 000 to MG VIII and MG X adapted from latitude N 18° to N 53°. They were planted in the field under natural daylength condition (ND) in Beijing, China or in pots under different photoperiod treatments. Maturity-related traits were then investigated. The four E maturity loci were genotyped at the molecular level. Our results suggested that these four E genes have different impacts on maturity and their allelic variations and combinations determine the diversification of soybean maturity and adaptation to different latitudes. The genetic mechanisms underlying photoperiod sensitivity and adaptation in wild soybean seemed unique from those in cultivated soybean. The allelic combinations and functional molecular markers for the four E loci will significantly assist molecular breeding towards high productivity.


[Anorexia nervosa and music therapy].
Advanced practice nurses (APNs) are finding it difficult to establish themselves once they have completed their training. Nearly half (49%) of graduates interviewed in a survey said they were not working as APNs, which raises real questions about the future of new graduates and their establishment in local areas. Under such conditions, the future of IPAs sometimes seems compromised, especially those in private practice.


Strategies to reduce external ventricular drain-related infections: a multicenter retrospective study.
OBJECTIVEVarious strategies have been proposed to reduce the incidence of external ventricular drain (EVD)-related infections. The authors retrospectively studied the impact of EVD care management on EVD-related infections at 3 French university hospital intensive care units.METHODSBetween 2010 and 2014, 462 consecutive adult patients with no evidence of a preexisting CSF infection received EVDs as part of their care at one of the following sites: Grenoble (221 patients), Saint-Etienne (130 patients), and Marseille (111 patients). Written protocols describing the EVD placement procedure, management, and removal were implemented at the 3 sites. Daily CSF sampling and intraventricular administration of antibiotics prior to EVD removal were performed at the Grenoble site only. EVD-related infection was considered for any confirmed ventriculostomy-related infection (VRI) and ventriculitis. VRI was defined as one or more positive CSF cultures or Gram stain with CSF pleocytosis and biochemical abnormalities. Ventriculitis was defined as CSF pleocytosis and biochemical abnormalities with degradation of neurological status and fever.RESULTSA total of 6945 EVD days were observed in the entire population. In the Grenoble cohort, the mean cumulative incidence of EVD-related infections was significantly lower than that in the 2 other cohorts: 1.4% (95% CI 0.0%-2.9%) versus 9.2% (95% CI 4.2%-14.2%) and 7.2% (95% CI 2.4%-12.0%) at Saint-Etienne and Marseille, respectively (p < 0.01). Accounting for the duration of external ventricular drainage at each site, the risk for EVD-related CSF infections was significantly higher at Saint-Etienne and Marseille than at Grenoble, with ORs of 15.9 (95% CI 3.6-71.4, p < 0.001) and 10.0 (95% CI 2.2-45.5, p = 0.003), respectively.CONCLUSIONSThese findings indicate that it is possible to attain a low incidence of EVD-related infections, provided that an EVD care bundle, which can include routine daily CSF sampling, is implemented and strongly adhered to.


Nanoparticles adsorbed at the water/oil interface: coverage and composition effects on structure and diffusion.
Dissipative particle dynamics simulations are performed to study the structural and dynamical properties of various systems of nanoparticles accumulated at the water/oil interface. Homogeneous and Janus nanoparticles with different surface compositions are studied. For all nanoparticles, as the surface density increases, a transition from a liquidlike to a solidlike state is observed, as expected. At a high density of nanoparticles, hexagonal structures emerge and the nanoparticles' self-diffusion coefficient decreases because of caging effects. Similar results are observed for nanoparticles with different surface chemistry. Because different nanoparticles have different contact angles at the water/oil interface, the results obtained for systems containing mixed nanoparticles are more interesting. For example, our results show that the self-diffusion coefficient is not a monotonic function of the system composition, caused by the complex relation between hydrodynamic interactions and effective nanoparticle-nanoparticle interactions.


Why are Hanoi students giving up on bus ridership?
University students are regarded as a readily available market segment for public transport. In Hanoi, as elsewhere, they constitute a large portion of bus passengers. However, one portion has been quitting buses, and the reasons were so far unknown. Nor was it clear whether they planned on retuning. Through a survey of more than 800 students in seven higher education institutions, this study aimed to find the answers to these questions. The study revealed that bus ridership was determined by socio-demographic variables (year of studies, household income, employment status, motorcycle ownership), environmental variables (home-university distance), and psychological variables (convenience, bus staff behaviour, risk of sexual harassment, reliability and health, image and status). A negative disruptor such as the fear of Covid-19 infection had little effect on the decision to continue riding buses. Meanwhile, the prospect of riding 'clean and green' electric buses, which were introduced in a pilot program, was a positive disruptor that may lead a portion of students to return to public transport.


Mutational analysis of the MPZ, PMP22 and Cx32 genes in patients of Spanish ancestry with Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies.
Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (HNPP) are two inherited peripheral neuropathies. The most prevalent mutations are a reciprocal 1.5-Mb duplication and 1.5-Mb deletion, respectively, at the CMT1A/HNPP locus on chromosome 17p11.2. Point mutations in the coding region of the myelin genes, peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) or connexin 32 (Cx32) have been reported in CMT patients, including CMT type 1 (CMT1), CMT type 2 (CMT2) and Déjérine-Sottas neuropathy (DS) patients, and only in the coding region of PMP22 in HNPP families lacking a deletion. We have investigated point and small mutations in the MPZ, PMP22 and Cx32 genes in a series of patients of Spanish ancestry: 47 CMT patients without duplications, and 5 HNPP patients without deletions. We found 15 different mutations in 16 CMT patients (34%). Nine different mutations in ten patients were detected in the Cx32 gene, this being the most frequently involved gene in this series, whereas five mutations involved the MPZ gene and only one the PMP22 gene. Six out of nine nucleotide substitutions in the Cx32 gene involved two codons encoding arginine at positions 164 and 183, suggesting that these two codons may constitute two Cx32 regions prone to mutate in the Spanish population. Analysis of HNPP patients revealed a 5' splicing mutation in intron 1 of the PMP22 gene in a family with autosomal dominance, which confirms allelic heterogeneity in HNPP. Ectopic mRNA analysis on leukocytes suggests that this mutation might behave as a null allele.


[Retroperitoneoscopic renal pedicle lymphatic disconnection for chyluria via extra-adipose capsule].
To evaluate the clinical effect of retroperitoneoscopic renal pedicle lymphatic disconnection via extra-adipose capsule in the management of chyluria and to discuss the management of its complications. From August 2013 to June 2008, five patients with chyluria were admitted. All the patients were female, aged from 26 to 73 years, and disease course from 1 to 10 years. All the five patients had complained of intermittently voiding milky urine with varying degrees of weight loss, and fatigue, of whom two presented with flank pain and one with anemia. Their urine chyle tests were confirmed to be positive. Preoperative cystoscopy found that chyluria was from the left side in 3 cases,and from the right side in 2 cases. Their proteinuria ranged from + to ++++. All the cases had been treated with the modified procedure by which lymphatic ligation was performed to hilar vessels and proximalureter via extra-adipose capsule without disconnection of perirenal fat tissues. The operation time, intraoperative blood loss, postoperative intestinal function recovery, catheter time, drainage tube removal time and complications during operation were collected. All the five cases were performed successfully. The operation time ranged from 75 to 170 minutes, mean (126.0±39.6) minutes, with the intraoperative blood loss 20 to 60 mL, mean (38.0±16.4) mL, and the postoperative intestinal function recovery time 1 to 3 days, mean (1.9±0.4) days. The catheter time was 1 to 4 days, mean (2.1±0.3) days and the drainage tube removal time ranged from 3 to 15 days, mean (9.3±1.8) days. Postoperatively lymphorrhagia was found in two cases. No renal vessels injury occurred during operation. Chyluria of all the patients disappeared on the operation day with negative chyluria test after surgery. Furthermore, urine test revealed that proteinuria was totally negative. No recurrence was detected in our patients in the 9 to 31 months' follow-up. This modified procedure does not have to disconnect perirenal fat tissues and nephropexy during operation. It was characterized with shorter operation time, definitive effect and fewer complications.


Increased carboxyhemoglobin in a patient with a large retroperitoneal hematoma.
In humans, the sole endogenous source of carbon monoxide is heme degradation. We report the development of prolonged carboxyhemoglobinemia in a critically ill mechanically ventilated patient who required massive transfusion because of retroperitoneal hemorrhage secondary to pheochromocytoma. After the transfusion of 27 U of packed red blood cells, the maximum carboxyhemoglobin level was 6.4%. Although ventilation was controlled with a fraction of inspired oxygen of 0.35-0.5 and external drainage of blood occurred, the concentration of carboxyhemoglobin remained at 1.7%-5.6% for days. Red blood cells for transfusion may be contaminated with carbon monoxide and may have carboxyhemoglobin levels of up to 12%; this may also have contributed to carboxyhemoglobinemia in our patient. If significantly increased concentrations of carboxyhemoglobin develop, therapy to decrease the concentration of carboxyhemoglobin (such as fraction of inspired oxygen of 1.0 and/or minute ventilation or hyperbaric oxygen) or removal of the source should be considered.


Increased susceptibility of aging gastric mucosa to injury: the mechanisms and clinical implications.
This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-"aging gastropathy"-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older patients have much greater risk of gastroduodenal ulcers and gastrointestinal complications (e.g., NSAIDs-induced gastric injury) than younger patients; and (3) increased susceptibility of aging gastric mucosa to injury can be potentially reduced or reversed pharmacologically.


Nonplanar porphyrins: synthesis, properties, and unique functionalities.
Porphyrins are variously substituted tetrapyrrolic macrocycles, with wide-ranging biological and chemical applications derived from metal chelation in the core and the 18π aromatic surface. Under suitable conditions, the porphyrin framework can deform significantly from regular planar shape, owing to steric overload on the porphyrin periphery or steric repulsion in the core, among other structure modulation strategies. Adopting this nonplanar porphyrin architecture allows guest molecules to interact directly with an exposed core, with guest-responsive and photoactive electronic states of the porphyrin allowing energy, information, atom and electron transfer within and between these species. This functionality can be incorporated and tuned by decoration of functional groups and electronic modifications, with individual deformation profiles adapted to specific key sensing and catalysis applications. Nonplanar porphyrins are assisting breakthroughs in molecular recognition, organo- and photoredox catalysis; simultaneously bio-inspired and distinctly synthetic, these molecules offer a new dimension in shape-responsive host-guest chemistry. In this review, we have summarized the synthetic methods and design aspects of nonplanar porphyrin formation, key properties, structure and functionality of the nonplanar aromatic framework, and the scope and utility of this emerging class towards outstanding scientific, industrial and environmental issues.


Autoimmune Regulator Deficiency Results in a Decrease in STAT1 Levels in Human Monocytes.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by biallelic autoimmune regulator (AIRE) mutations that manifests with chronic mucocutaneous candidiasis (CMC) and autoimmunity. Patients with STAT1 gain-of-function (GOF) mutations also develop CMC and autoimmunity; they exhibit increased STAT1 protein levels at baseline and STAT1 phosphorylation (pSTAT1) upon interferon (IFN)-γ stimulation relative to healthy controls. AIRE interacts functionally with a protein that directly regulates STAT1, namely protein inhibitor of activated STAT1, which inhibits STAT1 activation. Given the common clinical features between patients with AIRE and STAT1 GOF mutations, we sought to determine whether APECED patients also exhibit increased levels of STAT1 protein and phosphorylation in CD14+ monocytes. We obtained peripheral blood mononuclear cells from 8 APECED patients and 13 healthy controls and assessed the levels of STAT1 protein and STAT1 tyrosine phosphorylation at rest and following IFN-γ stimulation, as well as the levels of STAT1 mRNA. The mean STAT1 protein levels in CD14+ monocytes exhibited a ~20% significant decrease in APECED patients both at rest and after IFN-γ stimulation relative to that of healthy donors. Similarly, the mean peak value of IFN-γ-induced pSTAT1 level was ~20% significantly lower in APECED patients compared to that in healthy controls. The decrease in STAT1 and peak pSTAT1 in APECED patients was not accompanied by decreased STAT1 mRNA or anti-IFN-γ autoantibodies; instead, it correlated with the presence of autoantibodies to type I IFN and decreased AIRE-/- monocyte surface expression of IFN-γ receptor 2. Our data show that, in contrast to patients with STAT1 GOF mutations, APECED patients show a moderate but consistent and significant decrease in total STAT1 protein levels, associated with lower peak levels of pSTAT1 molecules after IFN-γ stimulation.


Autologous embryo-cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study.
In repeated implantation failure, the co-culture of human embryos with somatic cells has been reported to promote the improvement of embryos quality, implantation and pregnancy rate. It was reported that feeder cells can be more beneficial to the oocyte and embryo by detoxifying the culture medium and supporting embryo development via different pathways. In this study, 432 patients, each with a minimum of three repeated implantation failures, were accepted for a prospective randomized study with or without autologous cumulus cell embryo co-culture and transfer at day 3 or day 5-6. We also investigated the expression of leukaemia inhibitor factor (LIF) and platelet activating factor receptor (PAF-R) on day 3 confluent cumulus cells. The statistic analysis of the data showed significant difference of implantation and clinical pregnancy rates between classical culture and day 3 compared with co-culture and day 5-6 transfer. The molecular analysis showed that cumulus cells express the LIF and the PAF-R genes and confirmed the possible positive role of growth factors and cytokines in early embryo development. Embryo co-culture systems with autologous cells can be beneficial in routine in vitro fertilization for embryo selection and implantation improvement. More molecular investigations need to be done to improve elucidation of the complex dialogue between the embryo and feeder cells prior to implantation and to understand the involved biological function and molecular process during embryo development.


[Fatal hepatic necrosis due to a treatment course of rheumatoid arthritis with gold salts].
Gold salts are still a first choice for treatment of rheumatoid arthritis. Although adverse reactions are relatively frequent, hepatic abnormalities are rare. They consist largely of reversible cholestasis, and, exceptionally, the evolution can prove rapidly fatal due to extensive hepatic necrosis. We present an additional case of this kind which occurred after a total dose of 450 mg intramuscular Aurothiopropanol over 6 weeks. The pathogenetic mechanism is complex, toxic and/or immuno-allergic. Nevertheless, regular hepatic enzyme testing is not recommended.


Water-leaving contribution to polarized radiation field over ocean.
The top-of-atmosphere (TOA) radiation field from a coupled atmosphere-ocean system (CAOS) includes contributions from the atmosphere, surface, and water body. Atmospheric correction of ocean color imagery is to retrieve water-leaving radiance from the TOA measurement, from which ocean bio-optical properties can be obtained. Knowledge of the absolute and relative magnitudes of water-leaving signal in the TOA radiation field is important for designing new atmospheric correction algorithms and developing retrieval algorithms for new ocean biogeochemical parameters. In this paper we present a systematic sensitivity study of water-leaving contribution to the TOA radiation field, from 340 nm to 865 nm, with polarization included. Ocean water inherent optical properties are derived from bio-optical models for two kinds of waters, one dominated by phytoplankton (PDW) and the other by non-algae particles (NDW). In addition to elastic scattering, Raman scattering and fluorescence from dissolved organic matter in ocean waters are included. Our sensitivity study shows that the polarized reflectance is minimized for both CAOS and ocean signals in the backscattering half plane, which leads to numerical instability when calculating water leaving relative contribution, the ratio between polarized water leaving and CAOS signals. If the backscattering plane is excluded, the water-leaving polarized signal contributes less than 9% to the TOA polarized reflectance for PDW in the whole spectra. For NDW, the polarized water leaving contribution can be as much as 20% in the wavelength range from 470 to 670 nm. For wavelengths shorter than 452 nm or longer than 865 nm, the water leaving contribution to the TOA polarized reflectance is in general smaller than 5% for NDW. For the TOA total reflectance, the water-leaving contribution has maximum values ranging from 7% to 16% at variable wavelengths from 400 nm to 550 nm from PDW. The water leaving contribution to the TOA total reflectance can be as large as 35% for NDW, which is in general peaked at 550 nm. Both the total and polarized reflectances from water-leaving contributions approach zero in the ultraviolet and near infrared bands. These facts can be used as constraints or guidelines when estimating the water leaving contribution to the TOA reflectance for new atmospheric correction algorithms for ocean color imagery.


Eco-Friendly and Facile Synthesis of Antioxidant, Antibacterial and Anticancer Dihydromyricetin-Mediated Silver Nanoparticles.
Dihydromyricetin (DMY), a natural flavonoid, has reportedly antibacterial, antioxidant, anticancer and other properties. In the present study, DMY was used as a reducing agent and stabilizer to synthesize silver nanoparticles (AgNPs), and the optimal conditions for its synthesis were studied. The DMY-AgNPs were investigated for their DPPH scavenging properties and their potential against human pathogenic and food-borne bacteria viz. Escherichia coli (E. coli), and Salmonella. In addition, DMY-AgNPs also showed excellent inhibitory effects on cancer Hela, HepG2 and MDA-MB-231 cell lines. The dihydromyricetin-mediated AgNPs (DMY-AgNPs) were characterized by ultraviolet-visible spectrophotometer (UV-Vis spectra), scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray powder diffraction (XRD). Antioxidant activity of DMY-AgNPs was determined by 1.1-diphenyl-2-picrylhydrazyl (DPPH) scavenging. The antibacterial activity was determined by 96-well plate (AGAR) gradient dilution, while anticancer potential was determined by MTT assay. The results showed that the dispersion of AgNPs had the maximum UV-visible absorption at about 410 nm. The synthesized nanoparticles were almost spherical. FTIR was used to identify functional groups that may lead to the transformation of metal ions into nanoparticles. The results showed that the prepared AgNPs were coated with biological molecules in the extraction solution. The biosynthesized DMY-AgNPs exhibited good antioxidant properties, at various concentrations (0.01-0.1mg/mL), the free radical scavenging rate was about 56-92%. Furthermore, DMY-AgNPs possessed good antibacterial properties against Escherichia coli (E. coli), and Salmonella at room temperature. The minimum inhibitory concentrations (MIC) were 10-6 g/L, and 10-4 g/L, respectively. The bioactivity of DMY-mediated AgNPs was studied using MTT assay against Hela, HepG2 and MDA-MB-231 cancer cell lines, and all showed good inhibitory effects. The present study provides a green approach for the synthesis of DMY-AgNPs which exhibited stronger antioxidant, antibacterial and anticancer properties compared to the dihydromyricetin. DMY-AgNPs can serve as an economical, efficient, and effective antimicrobial material for its applications in food and pharmaceutical fields.


Functional MRI study of semantic and phonological language processing in bilingual subjects: preliminary findings.
The objective of the study was to explore differences in regional fMRI activation topography and lateralization between semantic and phonological tasks performed in English and Spanish in bilingual individuals. Eight bilingual (primary Spanish and secondary English-speaking) individuals performed fMRI noun-verb association and rhyming tasks in both Spanish and English. Functional dataset analysis within Statistical Parametric Mapping (SPM99) with overlay on T1-weighted anatomic images was performed. Significantly higher laterality indices were noted in the semantic tasks as compared with the phonological tasks in the anterior regions of interest comprising the frontal and superior temporal lobes. A task subtraction analysis demonstrated right hemispheric (inferior frontal gyrus and supramarginal gyrus) foci of significantly increased activation in the combined language phonological tasks compared to the combined language semantic tasks; similarly prominent right hemispheric activation was seen in the English phonological-English semantic subtraction, but the analogous Spanish task subtraction revealed no task-related differences. This divergence in activation topography between semantic and phonological tasks performed in the nonnative language, but not in the primary language, suggests that neural networks utilized for phonological and semantic language processing in the nonnative language may not be as similar as those in the primary language.


Color Coded Perfusion Imaging with Contrast Enhanced Ultrasound (CEUS) for Post-Interventional Success Control Following Irreversible Electroporation (IRE) of Primary and Secondary Malignant Liver Lesions.
Evaluation of the post-interventional success following irreversible electroporation (IRE) using a new color coded perfusion quantification software with contrast-enhanced ultrasound (CEUS) in patients with malignant lesions of the liver. Thirty-eight patients with 68 malignant liver lesions underwent IRE. All malignant lesions were investigated with CEUS before and within 24 hours following IRE to detect residual tumor tissue. The parameters analyzed by color coded perfusion quantification software were: the peak enhancement (pE), time to peak (TTP), mean transit time (mTT), rise (Ri) and wash-in area under the curve (WiAUC). Perfusion in the center, the margins of the lesions and in the surrounding liver were evaluated using these parameters. Hepatocellular carcinoma (HCC) with complete ablation showed significantly different changes between the center and the margin of the lesions for WiAUC (p<0.05) and pE (p<0.01). Also significant differences were noted between the center of the lesions and the surrounded tissue for the same parameters (p<0.01). In the completely ablated metastatic lesions, significant differences were found between the center of the lesion and the margins (p < 0.01) and between the center of the lesion and the surrounding liver (p < 0.05) for WiAUC. mTT, TTP and Ri showed no significant changes between the center of the lesions, margin of the lesions or surrounding tissue. Also, no significant differences were found for these parameters in the different regions of interest for HCC or the metastatic lesions with partial ablation success. CEUS with perfusion imaging is a valuable supporting tool for the post-interventional evaluation of liver lesions following IRE. Focus should be placed on the peak enhancement (pE) and the wash-in area under the curve (WiAUC).


Cone selective adaptation influences L- and M-cone driven signals in electroretinography and psychophysics.
To assess the influence of selective adaptation of long (L) and middle (M) wavelength sensitive cones with electroretinography (ERG) and psychophysics, a novel adaptation procedure was developed, which comprises a selective and quantifiable change in the state of adaptation in the different cone types. One adaptation condition was used as a reference. In four additional conditions, the M-cones or the L-cones were selectively adapted, so that they absorbed either more or less photons. At each of these five states of adaptation, the ERG response amplitudes to 30Hz L- and to M-cone selective stimuli were measured. Furthermore, the psychophysical sensitivities to L- and M-cone selective stimuli were measured at different temporal frequencies. In subjects with normal color vision, adaptation can have a strong influence on the L- and M-cone driven response amplitudes in the ERG and on both the L- and the M-cone sensitivities in the psychophysical luminance channel. As a result, the L- to M-cone ERG and psychophysical ratios can change dramatically at the different states of adaptation. The cone sensitivity thresholds and the L- to M-cone sensitivity ratio in the psychophysical chromatic channel are about unity at all states of adaptation, suggesting the presence of a compensatory mechanism. In dichromats, the responses and sensitivities to stimulation of the absent cone type were generally small at all states of adaptation. But, with reddish backgrounds residual ERG responses and residual psychophysical sensitivities were observed, indicating the presence of either a robust rod driven signal or an additional adaptation mechanisms that are not cone driven and that have not been described before.


Histopathologic specificity of systemic vasculitis.
A definitive diagnosis of vasculitis almost always requires histologic documentation of a true inflammatory disease of the blood vessels. Although each major type of systemic vasculitis may have its own characteristic and unique features, variability and overlaps still exist, and histopathologic specificity is rarely an absolute discriminator. The correct interpretation of biopsy specimens for the diagnosis of vasculitis remains more an art than a science; it is subject to such variables as the examining pathologist's interest and expertise, tissue selection and sample size, the age of the disease from onset to the time of biopsy, and whether there was drug treatment prior to the biopsy.


Drosophila males transfer antibacterial proteins from their accessory gland and ejaculatory duct to their mates.
The male fruitfly, Drosophila melanogaster, transfers to his mate proteins that increase his reproductive success by causing changes in her behavior and physiology. Here we show that among the transferred proteins are ones with antibacterial activity. We performed Escherichia coli overlay assays of native PAGE or renatured SDS-PAGE of reproductive tissue extracts of wild-type or transgenic males deficient in accessory gland function. We detected a 28 kDa male accessory gland-derived protein and two ejaculatory duct-derived proteins all with antibacterial activity. Based on its gel mobility and tissue of synthesis, one of the ejaculatory duct proteins is likely to be andropin, a previously-reported 6 kDa antibacterial peptide. All three proteins are transferred to females during mating. Therefore, they could assist in protecting the male's reproductive tract and, after transfer to the female, the female's reproductive tract or eggs against bacterial infection. Since seminal fluid proteins are transferred before the sperm, these antibacterial proteins may also protect sperm from bacterial infection.


Synthesis and hyperpolarisation of eNOS substrates for quantification of NO production by 1H NMR spectroscopy.
Hyperpolarization enhances the intensity of the NMR signals of a molecule, whose in vivo metabolic fate can be monitored by MRI with higher sensitivity. SABRE is a hyperpolarization technique that could potentially be used to image nitric oxide (NO) production in vivo. This would be very important, because NO dysregulation is involved in several pathologies, including cardiovascular ones. The nitric oxide synthase (NOS) pathway leads to NO production via conversion of l-arginine into l-citrulline. NO is a free radical gas with a short half-life in vivo (≈5s), therefore direct NO quantification is challenging. An indirect method - based on quantifying conversion of an l-Arg- to l-Cit-derivative by 1H NMR spectroscopy - is herein proposed. A small library of pyridyl containing l-Arg derivatives was designed and synthesised. In vitro tests showed that compounds 4a-j and 11a-c were better or equivalent substrates for the eNOS enzyme (NO2- production=19-46μM) than native l-Arg (NO2- production=25μM). Enzymatic conversion of l-Arg to l-Cit derivatives could be monitored by 1H NMR. The maximum hyperpolarization achieved by SABRE reached 870-fold NMR signal enhancement, which opens up exciting future perspectives of using these molecules as hyperpolarized MRI tracers in vivo.


Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats.
Metallothioneins (MTs) perform important regulatory and cytoprotective functions in tissues including the brain. While it is known that energy restriction (ER) and dietary n-3 polyunsaturated fatty acid (PUFA) deficiency impact postnatal brain growth and development, little data exist regarding the impact of undernutrition upon MT expression in growing animals. We tested the hypothesis that ER with and without dietary n-3 PUFA deficiency reduces MT expression in juvenile rats. ER rats were individually pair-fed at 75% of the ad libitum (AL) intake of control rats provided diets consisting of either soybean oil (SO) that is α-linolenic acid (ALA; 18:3n-3) sufficient or corn oil (CO; ALA-deficient). Fatty acids (FA) and metal concentrations of liver and brain regions were analyzed. Tissue expression of MTs (Mt1-3) and modulators of MT expression including glucocorticoid receptors (Nr3c1 and Nr3c2) and several mediators of thyroid hormone regulation (Dio1-3, Mct8, Oatp1c1, Thra, and Thrb) were measured. Plasma corticosterone and triiodothyronine levels were also evaluated. ER, but not metal deficiency, reduced Mt2 expression in the cerebellum (50%) and cerebral cortex (23%). In liver, a reduction in dietary n-3 PUFA reduced Mt1, Mt2, Nr3c1, Mct8, and Thrb. ER elevated Nr3c1, Dio1, and Thrb and reduced Thra in the liver. Given MT's role in cellular protection, further studies are needed to evaluate whether ER or n-3 PUFA deficiency may leave the juvenile brain and/or liver more susceptible to endogenous or environmental stressors.


Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation.
Chronic high-glucose exposure results in the production of advanced glycation end-products (AGEs) leading to reactive oxygen species (ROS) generation, which contributes to the development of diabetic cardiomyopathy. PKCδ activation leading to ROS production and mitochondrial dysfunction involved in AGE-induced cardiomyocyte apoptosis was reported in our previous study. Diallyl trisulfide (DATS) is a natural cytoprotective compound under various stress conditions. In this study, the cardioprotective effect of DATS against rat streptozotocin (STZ)-induced diabetic mellitus (DM) and AGE-induced H9c2 cardiomyoblast cell/neonatal rat ventricular myocyte (NRVM) damage was assessed. We observed that DATS treatment led to a dose-dependent increase in cell viability and decreased levels of ROS, inhibition of PKCδ activation, and recuded apoptosis-related proteins. Most importantly, DATS reduced PKCδ mitochondrial translocation induced by AGE. However, apoptosis was not inhibited by DATS in cells transfected with PKCδ-wild type (WT). Inhibition of PKCδ by PKCδ-kinase-deficient (KD) or rottlerin not only inhibited cardiac PKCδ activation but also attenuated cardiac cell apoptosis. Interestingly, overexpression of PKCδ-WT plasmids reversed the inhibitory effects of DATS on PKCδ activation and apoptosis in cardiac cells exposed to AGE, indicating that DATS may inhibit AGE-induced apoptosis by downregulating PKCδ activation. Similar results were observed in AGE-induced NRVM cells and STZ-treated DM rats following DATS administration. Taken together, our results suggested that DATS reduced AGE-induced cardiomyocyte apoptosis by eliminating ROS and downstream PKCδ signaling, suggesting that DATS has potential in diabetic cardiomyopathy (DCM) treatment.


Comparison of measured total suspended particulate matter concentrations using tapered element oscillating microbalance and a total suspended particulate sampler.
A comparison of the concentration of the total suspended particulate (TSP) matter measured by the tapered element oscillating microbalance (TEOM) monitor and the isokinetic TSP samplers developed at the University of Illinois was carried out in several types of confinement livestock buildings. In a majority of the measurements done, the dust concentration measured by the TEOM monitor was lower than the University of Illinois at Urbana-Champaign (UIUC) isokinetic TSP sampler; the TEOM monitor tended to underestimate the total dust concentration by as much as 54%. The difference in measurements can be attributed to the sampling efficiency of the TEOM monitor sampling head and the loss of some semivolatile compounds and particle-bound water because of heating of the TEOM monitor sampling stream to 50 degrees C. Although several articles in the literature supported the latter argument, this study did not investigate the effect of heating the sampling stream or the effect of moisture on the relative difference in dust concentration measurements. The model that best describes the relationship between the two methods was site specific, that is, the linear regression model was applicable only to four of the sites monitored. The measured total dust concentration in livestock buildings range from approximately 300 to 4000 microg/m3; a higher correlation coefficient between TEOM-TSP and UIUC-TSP monitors was obtained in swine facilities than those obtained in a laying facility.


Efflux and uptake transporters involved in the disposition of bazedoxifene.
Bazedoxifene, a novel selective estrogen receptor modulator, has complex pharmacokinetics with rapid absorption, high metabolic clearance, low oral bioavailability (6.25 %) and a slow elimination phase. Our hypothesis is that drug uptake and efflux transporters may play an important role in its disposition. To adequately cover all aspects of bazedoxifene transport, several approaches were undertaken: PAMPA assay, ATPase assay, membrane inside-out vesicles and Caco-2 and CHO cell lines. The results obtained from PAMPA experiments showed moderate passive permeability of bazedoxifene (P app ≈ 2 × 10(-6)cm/s), suggesting the existence of an active transport during the rapid absorption phase. The Caco-2 transport assay showed large and significant changes in the measured efflux ratios of bazedoxifene when selective transporter inhibitors were applied: verapamil (a Pgp inhibitor), MK571 (an MRP inhibitor), Ko143 (a BCRP inhibitor) and DIDS (an OATP inhibitor). Additionally, membrane preparation experiments demonstrated the interaction of bazedoxifene with P-gp, MRP2 and BCRP. CHO experiments did not show any interactions of bazedoxifene with OATP1B1 or OATP1B3; therefore, bazedoxifene may be a substrate of other OATP isoform(s). The comprehensive in vitro study indicates a strong involvement of Pgp, MRP, BCRP and OATP in bazedoxifene disposition.


Clinicopathological Features and Therapeutic Responses of Chinese Patients with Advanced Lung Adenocarcinoma Harboring an Anaplastic Lymphoma Kinase Rearrangement.
Presence of anaplastic lymphoma kinase (ALK) rearrangement is an indication for crizotinib in the treatment of patients with advanced or metastatic lung adenocarcinoma. Here, we sought to elucidate the association between clinicopathological features and ALK rearrangement status in Chinese patients with advanced lung adenocarcinoma harboring an ALK rearrangement. ALK rearrangement status was determined using immunohistochemistry (IHC) in tumor tissues from 120 patients with advanced lung adenocarcinoma, and further assessed by fluorescence in situ hybridization (FISH) assay. The associations between ALK rearrangement status and clinicopathological features were analyzed. According to IHC testing, the ALK-positive rate among the advanced lung adenocarcinoma patients was 6.67% (8/120). FISH validation found 5 patients with ALK rearrangement among the 8 IHC-positive cases. No significant difference was observed regarding age, sex, or smoking status between FISH-positive and -negative patients (p > 0.05). None of the 5 FISH-positive patients benefited from first-line chemotherapy. IHC can be used as a reliable method for ALK rearrangement screening in patients with lung adenocarcinoma, but further FISH validation is imperative. Presence of ALK rearrangement predicts a more aggressive biological behavior of the tumor and might be indicative of poor response to chemotherapy.


Different metrics (number, surface area, and volume concentration) of urban particles with varying sizes in relation to fractional exhaled nitric oxide (FeNO).
There have been increasing concerns on potential health effects of ultrafine particles (UFP); but little is known as to what are the most biologically relevant metrics for these particles that make up very little mass concentration. We examined a range of particle metrics (number, surface area, active surface area, and volume concentration) in relation to fractional exhaled nitric oxide (FeNO), a well-established biomarker of pulmonary inflammation. We conducted a panel study in 17 non-asthmatic children who attended schools and resided near a monitoring site at which particles in the size range of 3-800 nm were measured using a TDMPS and particles in the size range of 0.5 to 10 µm were measured using an APS. Particles were classified by size into the nucleation, Aitken, accumulation, or coarse mode, respectively, for calculating mode-specific number, surface area, active surface area, and volume concentrations. Each participating child was measured for FeNO daily for 30 days. We used linear mixed-effects models to assess the associations between various particle metrics and FeNO. In terms of number concentration, ambient particles in the Aitken mode and in the accumulation mode were significantly and positively associated with FeNO; but particles in the nucleation mode were significantly and negatively associated with FeNO. Moreover, UFP as a lump sum of both nucleation-mode and Aikten-mode particles did not show a significant association with FeNO. In terms of surface area concentration, ambient particles only in the accumulation mode were significantly and positively associated with FeNO. In terms of volume concentration, ambient particles in both the accumulation mode and the coarse mode were significantly and positively associated with FeNO. Analyses of the relationships between FeNO and metrics for particles deposited in the respiratory tract generated consistent findings, showing a negative association for the number concentration of deposited particles (driven by nucleation-mode particles), a positive association for the surface area concentration of deposited particles (driven by accumulation-mode particles), and a positive association for the volume concentration of deposited particles (driven by accumulation-mode and coarse-mode particles). Particles contributing largely to the surface area concentration and/or the volume concentration of ambient particles or particles deposited in the respiratory tract had a significant positive association with pulmonary inflammation. Nucleation-mode particles, that have large number concentrations but contribute little to the surface area or volume concentration of ambient or deposited particles, had a significant negative association with FeNO. This may indicate a different biological process or may simply be due to the negative and strong correlation between nucleation-mode and accumulation-mode particles. Given that particles in different modes may have different biological actions, measuring UFP as a whole may not necessarily be useful from a biological effect standpoint.


Video teleconsultation service: who is needed to do what, to get it implemented in daily care?
In telemedicine, technology is used to deliver services. Because of this, it is expected that various actors other than those involved in traditional care are involved in and need to cooperate, to deliver these services. The aim of this study was to establish a clear understanding of these actors and their roles and interrelationships in the delivery of telemedicine. A video teleconsultation service is used as a study case. A business modeling approach as described in the Freeband Business Blueprint Method was used. The method brings together the four domains that make up a business model, that is, service, technology, organization, and finance, and covers the integration of these domains. The method uses several multidisciplinary workshops, addressing each of the four domains. Results of the four domains addressed showed that (1) the video teleconsultation service is a store and put-forward video teleconsult for healthcare providers. The service is accepted and has added value for the quality of care. However, the market is small; (2) the technology consists of a secured Internet Web-based application, standard personal computer, broadband Internet connection, and a digital camera; (3) a new role and probably entity, responsible for delivering the integrated service to the healthcare professionals, was identified; and finally (4) financial reimbursement for the service delivery is expected to be most successful when set up through healthcare insurance companies. Pricing needs to account for the fee of healthcare professionals as well as for technical aspects, education, and future innovation. Implementation of the video teleconsult service requires multidisciplinary cooperation and integration. Challenging aspects are the small market size and the slow implementation speed, among others. This supports the argument that accumulation of several telemedicine applications is necessary to make it financially feasible for at least some of the actors.


A 4-Week Pecan-Enriched Diet Improves Postprandial Lipid Peroxidation in Aging Adults.
Pecans are rich in bioactive compounds known to reduce oxidative stress and provide glucoregulatory benefits. Few studies assessing the effect of a pecan-enriched diet on such health outcomes suggest potential improvements to cardiometabolic health; however, this has not been studied in an older adult population. Thus, we aimed to examine the effect of daily pecan consumption for 4-weeks on fasting and postmeal antioxidant status, oxidative stress, and markers of glycemia in healthy aging adults. In this randomized, parallel, controlled trial, 41 healthy adults (50-75 years) either consumed 68 g of pecans/day (pecan; n = 21) or avoided all nuts (control; n = 20). At pre- (V1) and postintervention visits (V2), blood samples were obtained at fasting, and 30, 60, and 120 min following a high saturated fat meal to assess changes in malondialdehyde, which is a measure of lipid peroxidation, total antioxidant capacity (TAC), glucose, and insulin. Across the intervention, there were no differences in fasting or postprandial TAC, glucose, or insulin for pecan versus control. There was a trend for a difference in fasting lipid peroxidation from V1 to V2 by treatment (P = .06) driven by a slight reduction for pecan versus control (Δpecan: -2.0 ± 1.1 vs. Δcontrol: +0.6 ± 0.8 μM). In addition, postprandial lipid peroxidation was suppressed at V2 for pecan, and this was different from control (pecan areas under the curve (AUC): 10.6 ± 1.3 μM/h to 9.1 ± 1.2 μM/h vs. control AUC: 8.9 ± 1.3 μM/h to 9.2 ± 1.1 μM/h; P = .03). These findings suggest that a 1 month, pecan-enriched diet is protective against postmeal oxidative stress. Longer interventions or a diabetic population may be needed to observe glucoregulatory benefits. Clinical Trial Registration: NCT04385537.


High folate and low vitamin B-12 intakes during pregnancy are associated with small-for-gestational age infants in South Indian women: a prospective observational cohort study.
Folic acid supplementation in those with a low vitamin B-12 intake or status may have adverse effects. These effects are unknown with regard to birth outcome in pregnant Indian women who are routinely supplemented with high doses of folic acid. The objective was to examine the association of unbalanced vitamin B-12 and total folate (folic acid supplement + dietary folate) intakes during pregnancy with outcomes in small-for-gestational-age (SGA) infants. This was a prospective observational cohort study of 1838 pregnant women in South India. Low intake of dietary vitamin B-12 in the presence of high total folate intake was examined as the ratio of vitamin B-12 intake to total folate intake. The inadequacy of vitamin B-12 intake (<1.2 μg/d) assessed by a food-frequency questionnaire in the first, second, and third trimesters of pregnancy was 25%, 11%, and 10%, respectively. Multivariate log binomial regression showed that low vitamin B-12 and folate intakes in the first trimester were independently associated with a higher risk of SGA. In a subgroup of women with high supplemental folic acid intakes in the second trimester, those with the lowest tertile of vitamin B-12:folate ratio had a higher risk of SGA outcome than did those in the highest tertile (adjusted RR: 2.73; 95% CI: 1.17, 6.37). A similar trend was observed in the analysis of blood micronutrient status in a random subset (n = 316) of the sample. These findings suggest that, in addition to vitamin B-12 and folate deficiencies alone, there may be adverse birth outcomes associated with unbalanced vitamin B-12 and folate intakes or status during pregnancy. These findings have important implications for the antenatal B vitamin supplementation policy in India. This trial was registered at the Clinical Trial Registry of India as 2013/07/005342.


Exploring the potential mechanism of Heng-Gu-Gu-Shang-Yu-He-Ji therapy for osteoporosis based on network pharmacology and transcriptomics.
Heng-Gu-Gu-Shang-Yu-He-Ji (Osteoking, OK) is a well-known formula for fracture therapy. In clinic, OK is effective in treating fractures while alleviating osteoporosis (OP) symptoms. However, active components of OK and the associated molecular mechanisms remain not fully elucidated. This study aims to systematically evaluate the anti-osteoporosis efficacy of OK and for the first time combine network pharmacology with high-throughput whole gene transcriptome sequencing to study its underlying mechanism. In this study, the osteoporosis model was established by the castration of both ovaries. The level of serum bone turnover factor was detected by enzyme-linked immunosorbent assay. Micro-CT and HE staining were used to observe the changes of bone histopathology, and nano-indentation technique was used to detect the biomechanical properties of rat bone. The main active Chemical components of OK were identified using UPLC-DAD. Efficacy verification and mechanism exploration were conducted by network pharmacology, molecular docking, whole gene transcriptomics and in vivo experiments. In our study, OK significantly improved bone microarchitecture and bone biomechanical parameters in OVX rats, reduced osteoclast indexes such as C-telopeptide of type I collage (CTX-I) and increased Osteoprotegerin (OPG)/Receptor activator of NF-κB ligand (RANKL) levels. Mechanistically, PI3K/AKT pathway was a common pathway for genome enrichment analysis (KEGG) of both network pharmacology and RNA-seq studies. G protein-β-like protein (GβL), Ribosomal-protein S6 kinase homolog 2 (S6K2), and Phosphoinositide 3-kinase (PI3K) appeared differentially expression in the PI3K-AKT signaling pathway. These results were also confirmed by qRT-PCR and immunohistochemistry. OK may be used to treat osteoporosis, at least partly by activating PI3K/AKT/mTORC1 signaling pathway.


In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.
The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV.


Violence: a glossary.
Violence has been explicitly identified as a significant public health problem. This glossary clarifies widely used definitions and concepts of violence within the public health field, building on those promoted through the 2002 World Report on Violence and Health. We provide definitions and concepts that can be usefully applied to identify points for public health intervention to prevent the social and health impacts of violence.


Central venous catheter use in severe malaria: time to reconsider the World Health Organization guidelines?
To optimize the fluid status of adult patients with severe malaria, World Health Organization (WHO) guidelines recommend the insertion of a central venous catheter (CVC) and a target central venous pressure (CVP) of 0-5 cmH2O. However there are few data from clinical trials to support this recommendation. Twenty-eight adult Indian and Bangladeshi patients admitted to the intensive care unit with severe falciparum malaria were enrolled in the study. All patients had a CVC inserted and had regular CVP measurements recorded. The CVP measurements were compared with markers of disease severity, clinical endpoints and volumetric measures derived from transpulmonary thermodilution. There was no correlation between the admission CVP and patient outcome (p = 0.67) or disease severity (p = 0.33). There was no correlation between the baseline CVP and the concomitant extravascular lung water (p = 0.62), global end diastolic volume (p = 0.88) or cardiac index (p = 0.44). There was no correlation between the baseline CVP and the likelihood of a patient being fluid responsive (p = 0.37). On the occasions when the CVP was in the WHO target range patients were usually hypovolaemic and often had pulmonary oedema by volumetric measures. Seven of 28 patients suffered a complication of the CVC insertion, although none were fatal. The WHO recommendation for the routine insertion of a CVC, and the maintenance of a CVP of 0-5 cmH2O in adults with severe malaria, should be reconsidered.


Reproductive flexibility: genetic variation, genetic costs and long-term evolution in a collembola.
In a variable yet predictable world, organisms may use environmental cues to make adaptive adjustments to their phenotype. Such phenotypic flexibility is expected commonly to evolve in life history traits, which are closely tied to Darwinian fitness. Yet adaptive life history flexibility remains poorly documented. Here we introduce the collembolan Folsomia candida, a soil-dweller, parthenogenetic (all-female) microarthropod, as a model organism to study the phenotypic expression, genetic variation, fitness consequences and long-term evolution of life history flexibility. We demonstrate that collembola have a remarkable adaptive ability for adjusting their reproductive phenotype: when transferred from harsh to good conditions (in terms of food ration and crowding), a mother can fine-tune the number and the size of her eggs from one clutch to the next. The comparative analysis of eleven clonal populations of worldwide origins reveals (i) genetic variation in mean egg size under both good and bad conditions; (ii) no genetic variation in egg size flexibility, consistent with convergent evolution to a common physiological limit; (iii) genetic variation of both mean reproductive investment and reproductive investment flexibility, associated with a reversal of the genetic correlation between egg size and clutch size between environmental conditions ; (iv) a negative genetic correlation between reproductive investment flexibility and adult lifespan. Phylogenetic reconstruction shows that two life history strategies, called HIFLEX and LOFLEX, evolved early in evolutionary history. HIFLEX includes six of our 11 clones, and is characterized by large mean egg size and reproductive investment, high reproductive investment flexibility, and low adult survival. LOFLEX (the other five clones) has small mean egg size and low reproductive investment, low reproductive investment flexibility, and high adult survival. The divergence of HIFLEX and LOFLEX could represent different adaptations to environments differing in mean quality and variability, or indicate that a genetic polymorphism of reproductive investment reaction norms has evolved under a physiological tradeoff between reproductive investment flexibility and adult lifespan.


The first step in vision: femtosecond isomerization of rhodopsin.
The kinetics of the primary event in vision have been resolved with the use of femtosecond optical measurement techniques. The 11-cis retinal prosthetic group of rhodopsin is excited with a 35-femtosecond pump pulse at 500 nanometers, and the transient changes in absorption are measured between 450 and 580 nanometers with a 10-femtosecond probe pulse. Within 200 femtoseconds, an increased absorption is observed between 540 and 580 nanometers, indicating the formation of photoproduct on this time scale. These measurements demonstrate that the first step in vision, the 11-cis----11-trans torsional isomerization of the rhodopsin chromophore, is essentially complete in only 200 femtoseconds.


An automated method to quantify and visualize colocalized fluorescent signals.
The most commonly used method to analyze colocalization of fluorescent signal in paired images is based on superimposition of images ("merging") and visual inspection. A method based on the comparison of the mean deviation of fluorescent signal intensity has recently been proposed to quantify colocalization within a user-defined area [Li Q, Lau A, Morris TJ, Guo L, Fordyce CB, Stanley EF. A syntaxin 1, Galpha(o), and N-type calcium channel complex at a presynaptic nerve terminal: analysis by quantitative immunocolocalization. J Neurosci 2004;24:4070-81]. Unfortunately, the latter quantification method does not provide a spatial representation of the correlation between the two fluorescent signals. Here we propose a new method that combines quantification and imaging of colocalization. We describe an algorithm based on edge detection and calculation of signal intensity deviation. The method is illustrated and validated on both simulated images and experimental data. This new and automated method calculates a correlation index (I(corr)) and generates an image of the correlated signals from the two original images. In addition to help in comparing and quantifying colocalization between two fluorescent stainings, this method can be adapted to measure the distribution of ions, proteins, organelles and cells in a large array of techniques.


The Outcome of Complex Pelvic Fracture after Internal Fixation Surgery.
Introduction: Complex pelvic fracture, which has a very high mortality and even higher morbidity, needs internal fixation surgery as an integral part for its management. It was necessary to conduct a study regarding outcome of complex pelvic fractures after internal fixation surgery. Material & Method: Twenty-six patients with complex pelvic fractures that had been treated with internal fixation surgery during 2011-2014 were enrolled. These patients had an open pelvic fractures or Tile type B or C pelvic fracture who had undergone internal fixation surgery with at least 6 months follow-up. Evaluation of the morbidity and functional scoring was performed using Majeed and Hannover Score. Results and Discussions: Average of age was 31 years old and follow up time was 25 months. There were 7 patients with open pelvic fracture and 19 with closed fracture. Excellent Majeed Score were found on 78.6% cases in Tile B fractures and 50% in Tile C. Good Hannover Score was found in 64.3% Tile B cases and 80% Tile C cases. Fracture type was statistically insignificant with acquired sexual dysfunction (p>0.05), but significant with the chronic pain (p=0,.017). We also found that urogenital injury is associated with sexual dysfunction (p=0.005). Conclusions: The outcome of complex pelvic fracture after internal fixation surgery was excellent. More than 90% patients got an excellent and good result on Majeed Score, and also very good and good result on Hannover Score.


Genetic polymorphisms in sigma-1 receptor and apolipoprotein E interact to influence the severity of Alzheimer's disease.
Apolipoprotein E (APOE) ε4 allele and sigma-1 receptor (SIGMAR1) c.5C (Q2P) polymorphisms have been acknowledged as risk factors for developing Alzheimer's disease (AD). However, whether these polymorphisms influence the disease process is unclear. Therefore, two cohorts with a clinical diagnosis of AD were recruited, a postmortem confirmed Australian cohort (82 cases) from the Australian Brain Bank Network, and a Chinese cohort with detailed clinical assessments recruited through an epidemiology study in Shanghai and through the neurology department outpatients clinic of Shanghai Ruijin Hospital (330 cases). SIGMAR1 Q2P and APOE genotyping was performed on all cases. Dementia severity in the Chinese cohort was assessed using MMSE scores, and the stages of senile plaques and neurofibrillary tangles (NFT) assessed in the Australian cohort. Associations between SIGMAR1 Q2P and APOE genotypes and disease severity were assessed using SPSS. Results confirmed that APOE 4 allele associated with increased NFT stages and cognitive decline, with carriers with one APOE ε2 or ε3 allele often having better clinical outcomes compared to carriers with none or two ε2 or ε3 alleles respectively. SIGMAR1 c.5C polymorphism alone did not associate with MMSE score variability in Chinese or with pathological stages in Caucasians. However, the association studies revealed a significant genetic interaction between the APOE ε4 allele and SIGMAR1 2P carriers in both populations, i.e., in APOE non ε4 allele carriers, SIGMAR1 2P variant had increased cognitive dysfunction and more advanced stages of NFT. Our data demonstrate that SIGMAR1 and APOE interact to influence AD severity across ethnic populations.


[Rattlesnake bite poisoning, health damage and treatment in children].
In Mexico, we do not know the exact number of cases and the magnitude of health damage conditioned by poisonous rattlesnake bites, and little relative information exists in pediatric population. To inform on continued follow-up of 55 patients at a children's hospital, and to propose a therapeutic sequence adequate for children. We reviewed clinical records and variables were origin, age, sex, time of year, previous care measures, time passed, hospital treatment complications and care cost. Rattlesnake bite occurred around the home at times and at times inside the home in rural areas; we did not observe any noticeable difference in gender; snake variety most involved was Crotalus atrox, anatomic site most injured were the lower extremities in 78%. Prior to admission, 50% received insufficient antivenom serum doses; the most frequent complication was hematologic in 69%. One patient died with multiple organ failure and disseminated intravascular coagulation (DIC). The treatment protocol that we have recommended since 1986 at the Hospital Infantil del Estado de Sonora, revised and modified in 1996, reduced hospital stay from 15 to 5 days. The protocol used avoided further complications and had a favorable influence on cost reduction.


Superadditivity of two quantum information resources.
Entanglement is one of the most puzzling features of quantum theory and a principal resource for quantum information processing. It is well known that in classical information theory, the addition of two classical information resources will not lead to any extra advantages. On the contrary, in quantum information, a spectacular phenomenon of the superadditivity of two quantum information resources emerges. It shows that quantum entanglement, which was completely absent in any of the two resources separately, emerges as a result of combining them together. We present the first experimental demonstration of this quantum phenomenon with two photonic three-partite nondistillable entangled states shared between three parties Alice, Bob, and Charlie, where the entanglement was completely absent between Bob and Charlie.


Degenerative and regenerative responses of injured neurons in the central nervous system of adult mammals.
In adult mammals, the severing of the optic nerve near the eye is followed by a loss of retinal ganglion cells (RGCs) and a failure of axons to regrow into the brain. Experimental manipulations of the non-neuronal environment of injured RGCs enhance neuronal survival and make possible a lengthy axonal regeneration that restores functional connections with the superior colliculus. These effects suggest that injured nerve cells in the mature central nervous system (CNS) are strongly influenced by interactions with components of their immediate environment as well as their targets. Under these conditions, injured CNS neurons can express capacities for growth and differentiation that resemble those of normally developing neurons. An understanding of this regeneration in the context of the cellular and molecular events that influence the interactions of axonal growth cones with their non-neuronal substrates and neuronal targets should help in the further elucidation of the capacities of neuronal systems to recover from injury.


A DNAzyme Feedback Amplification Strategy for Biosensing.
We report a signal amplification strategy termed DNAzyme feedback amplification (DFA) that takes advantage of rolling-circle amplification (RCA) and an RNA-cleaving DNAzyme (RCD). DFA employs two specially programmed DNA complexes, one composed of a primer and a circular template containing the antisense sequence of an RCD, and the other composed of the same circular template and an RNA-containing substrate for the RCD. RCA is initiated at the first complex to produce RCD elements that go on to cleave the substrate in the second complex. This cleavage event triggers the production of more input complexes for RCA. This reaction circuit continues autonomously, resulting in exponential DNA amplification. We demonstrate the versatility of this approach for biosensing through the design of DFA systems capable of detecting a microRNA sequence and a bacterium, with sensitivity improvements of 3-6 orders of magnitude over conventional methods.


The Landscape of Rural and Remote Radiology in Canada: Opportunities and Challenges.
Diagnostic and interventional radiology play a crucial role in healthcare, facilitating diagnosis of disease, treatment planning, interventional therapies, and assessment for response to treatment. However, many rural and remote regions are disproportionately limited in accessing high-quality radiological services. Challenges include limited imaging infrastructure in these communities, geographic isolation, and workforce shortages impacting provision of interventional image-guided procedures and subspecialty imaging in particular. However, a career in rural or remote radiology also presents unique opportunities including a deep sense of community, broad scope of practice, and immense benefit to patient care. This review aims to explore the landscape of rural and remote radiology with a focus on Canada, including opportunities, challenges, and potential strategies. Some of the challenges are shared by both rural and remote communities while others are distinct. Factors that have contributed to challenges in recruitment and retention of rural and remote radiologists include workload burden, inadequate or suboptimal imaging and interventional equipment, and limited exposure during training. Additionally, strategies to improve the provision of radiology services in rural and remote communities are highlighted, addressing both the workforce shortage and the lack of essential equipment and other resources.


Fibromyalgia--new concepts of pathogenesis and treatment.
Fibromyalgia (FMS) is a debilitating disorder characterized by chronic diffuse muscle pain, fatigue, sleep disturbance, depression and skin sensitivity. There are no genetic or biochemical markers and patients often present with other comorbid diseases, such as migraines, interstitial cystitis and irritable bowel syndrome. Diagnosis includes the presence of 11/18 trigger points, but many patients with early symptoms might not fit this definition. Pathogenesis is still unknown, but there has been evidence of increased corticotropin-releasing hormone (CRH) and substance P (SP) in the CSF of FMS patients, as well as increased SP, IL-6 and IL-8 in their serum. Increased numbers of activated mast cells were also noted in skin biopsies. The hypothesis is put forward that FMS is a neuro-immunoendocrine disorder where increased release of CRH and SP from neurons in specific muscle sites triggers local mast cells to release proinflammatory and neurosensitizing molecules. There is no curative treatment although low doses of tricyclic antidepressants and the serotonin-3 receptor antagonist tropisetron, are helpful. Recent nutraceutical formulations containing the natural anti-inflammatory and mast cell inhibitory flavonoid quercetin hold promise since they can be used together with other treatment modalities.


What are the Most Widely used and Effective Attack Coverage Systems in Men's Volleyball?
In volleyball, attack coverage is one of the play actions most neglected in coaching and research. The purpose of this study was to find out which attack coverage systems are used by high-level men's teams in different game situations and the characteristics of the most effective systems. We analysed 15 matches from the 2010 Men's Pan-American Volleyball Cup, with a total of 1,415 coverage actions. Chi-square tests for independence, adjusted residuals analysis and calculations of standardised mean difference were performed. The results show that high-level men's volleyball uses many coverage systems other than the traditional 3-2-0 and 2-3-0. At this level of play, the most frequent systems were 1-3-1 and 1-2-2, which occurred significantly often at the culmination of a third-tempo attack at the wing. The most effective systems consisted of three coverage lines, with fewer than five players covering the spiker and at least one player in the first coverage line, in both the attack and counterattack phases. Given the large number of coverage systems identified in different game situations, we recommend flexible, loosely structured training in these systems, based on a set of guiding principles that all players on a team must internalise for the specific position they are playing. Regarding the systems' efficacy, the main watchword is that on each coverage line there should always be at least one player, but the first line should not be exposed.


Development of 3D architecture of uropathogenic Proteus mirabilis batch culture biofilms-A quantitative confocal microscopy approach.
This work studies the development of the 3D architecture of batch culture P. mirabilis biofilms on the basis of morpho-topological descriptors calculated from confocal laser scanning microscopy (CLSM) stacks with image processing routines. A precise architectonical understanding of biofilm organization on a morpho-topological level is necessary to understand emergent interactions with the environment and the appearance of functionally different progeny swarmer cells. P. mirabilis biofilms were grown on glass coverslips for seven days on LB broth and subjected to in situ immunofluorescence. Confocal image stacks were deconvolved prior to segmentation of regions of interest (ROI) that identify individual bacteria and extracellular material, followed by 3D reconstruction and calculation of different morpho-topological key descriptors. Results showed that P. mirabilis biofilm formation followed a five stage process: (i) reversible adhesion to the surface characterized by slow growth, presence of elongated bacteria, and absence of extracellular material, (ii) irreversible bacterial adhesion concomitant to decreasing elongation, and the beginning of extracellular polymer production, (iii) accelerated bacterial growth concomitant to continuously decreasing elongation and halting of extracellular polymer production, (iv) maturation of biofilm defined by maximum bacterial density, volume, minimum elongation, maximum extracellular material, and highest compaction, and (v) decreased bacterial density and extracellular material through detachment and dispersion. Swarmer cells do not play a role in P. mirabilis biofilm formation under the applied conditions. Our approach sets the basis for future studies of 3D biofilm architecture using dynamic in vivo models and different environmental conditions that assess clinical impacts of P. mirabilis biofilm.


Partnerships in nursing homes: How do family caregivers of residents with dementia perceive collaboration with staff?
Partnerships between family and nursing staff in nursing homes are essential to address residents' needs and wishes. Collaboration is needed to create partnerships; nonetheless, challenges exist. This study aimed to gain insights into the experiences of families collaborating with staff. Semi-structured interviews were held with 30 family caregivers of nursing home residents with dementia. Data reflected three themes, which shaped collaboration with staff from families' perspective, 'communication', 'trust and dependency' and 'involvement'. Good communication appeared to be a requisite condition for having trust in staff and quality of involvement in residents' life. Good communication was described as having informal contact with staff, which enabled family and staff to build a personal connection. Consequently, this seemed to increase trust and satisfaction regarding involvement. Findings suggest that increasing informal contact and building a personal connection should be a priority for staff in order to improve collaboration and to create partnerships with families.