Optimization of a dual-energy contrast-enhanced technique for a photon-counting digital breast tomosynthesis system: I. A theoretical model.
Dual-energy (DE) iodine contrast-enhanced x-ray imaging of the breast has been shown to identify cancers that would otherwise be mammographically occult. In this article, theoretical modeling was performed to obtain optimally enhanced iodine images for a photon-counting digital breast tomosynthesis (DBT) system using a DE acquisition technique. In the system examined, the breast is scanned with a multislit prepatient collimator aligned with a multidetector camera. Each detector collects a projection image at a unique angle during the scan. Low-energy (LE) and high-energy (HE) projection images are acquired simultaneously in a single scan by covering alternate collimator slits with Sn and Cu filters, respectively. Sn filters ranging from 0.08 to 0.22 mm thickness and Cu filters from 0.11 to 0.27 mm thickness were investigated. A tube voltage of 49 kV was selected. Tomographic images, hereafter referred to as DBT images, were reconstructed using a shift-and-add algorithm. Iodine-enhanced DBT images were acquired by performing a weighted logarithmic subtraction of the HE and LE DBT images, The DE technique was evaluated for 20-80 mm thick breasts. Weighting factors, w(t) that optimally cancel breast tissue were computed. Signal-difference-to-noise ratios (SDNRs) between iodine-enhanced and nonenhanced breast tissue normalized to the square root of the mean glandular dose (MGD) were computed as a function of the fraction of the MGD allocated to the HE images. Peak SDNR/ mean square root of MGD and optimal dose allocations were identified. SDNR/ mean square root of MGD and dose allocations were computed for several practical feasible system configurations (i.e., determined by the number of collimator slits covered by Sn and Cu). A practicalsystem configuration an d Sn-Cu filterpair that accounts for the trade-off between SDNR, tube-output, and MGD were selected. w(t) depends on the Sn-Cu filter combination used, as well as on the breast thickness; to optimally cancel 0% with 50% glandular breast tissue, w(t) values were found to range from 0.46 to 0.72 for all breast thicknesses and Sn-Cu filter pairs studied. The optimal w(t) values needed to cancel all possible breast tissue glandularites vary by less than 1% for 20 mm thick breasts and 18% for 80 mm breasts. The system configuration where one collimator slit covered by Sn is alternated with two collimator slits covered by Cu delivers SDNR/ mean square root of MGD nearest to the peak value. A reasonable compromise is a 0.16 mm Sn-0.23 mm Cu filter pair, resulting in SDNR values between 1.64 and 0.61 and MGD between 0.70 and 0.53 mGy for 20-80 mm thick breasts at the maximum tube current. A DE acquisition technique for a photon-counting DBT imaging system has been developed and optimized.


[Pelvic congestion syndrome : from diagnosis to treatment].
Pelvic congestion syndrome is a debilitating condition that is often under-diagnosed and under-treated, defined by chronic pelvic pain in the presence of pelvic varicose veins in women or, more rarely, in men. The differential diagnosis of chronic abdominal pain is vast and often leads to lengthy and costly diagnostic procedures. Conservative treatment is often insufficient, and embolization of pelvic varices is the treatment of choice to improve symptoms. A multidisciplinary management algorithm is proposed to facilitate the clinical path for these patients.


Prehospital ultrasound by paramedics: results of field trial.
The objective was to determine if 9-1-1 paramedics trained in ultrasound (US) could adequately perform and interpret the Focused Assessment Sonography in Trauma (FAST) and the abdominal aortic (AA) exams in the prehospital care environment. Paramedics at two emergency medical services (EMS) agencies received a 6-hour training program in US with ongoing refresher education. Paramedics collected US in the field using a prospective convenience methodology. All US were performed in the ambulance without scene delay. US exams were reviewed in a blinded fashion by an emergency sonographer physician overreader (PO). A total of 104 patients had an US performed between January 1, 2008, and January 1, 2009. Twenty AA exams were performed and all were interpreted as negative by the paramedics and the PO. Paramedics were unable to obtain adequate images in 7.7% (8/104) of the patients. Eighty-four patients had the FAST exam performed. Six exams (6/84, 7.1%) were read as positive for free intraperitoneal/pericardial fluid by both the paramedics and the PO. FAST and AA US exam interpretation by the paramedics had a 100% proportion of agreement with the PO. This pilot study shows that with close supervision, paramedics can adequately obtain and interpret prehospital FAST and AA US images under protocol. These results support a growing body of literature that indicates US may be feasible and useful in the prehospital setting.


Structure of an experimentally evolved gene duplication encoding ribitol dehydrogenase in a mutant of Klebsiella aerogenes.
We have previously described a system of experimental evolution in which many of the mutants of Klebsiella aerogenes selected for faster growth on xylitol ('evolvants') synthesized elevated levels of ribitol dehydrogenase and have presented genetic evidence implicating gene duplication in the enzyme superproduction in some of the evolvants. Here we describe a physical approach to the screening for gene duplications and subsequent structure determination. Nick-translated, cloned ribitol operon (rbt) DNA was used as a hybridization probe to identify fragments containing rbt operon sequences in restriction digests of total bacterial DNA. Whilst several of the evolvants probably harbour duplications spanning the entire rbt operon, one of the spontaneously arising evolvants (strain A3) was shown to harbour a small (5.8 kilobase pairs) direct DNA repeat which encodes the dehydrogenase (but not the kinase) of the closely linked D-arabitol operon as well as the dehydrogenase (but not the kinase) of the rbt operon. The hybridization data suggest that there are 4 to 5 copies of the repeat arranged contiguously on the chromosome. The genetic instability of strain A3, the rbt fragment hybridization pattern of an A3 segregant and the activities of the pentitol catabolic enzymes in A3 are all consistent with the proposed gene duplication structure.


Intra-HLA recombinations localizing the 21-hydroxylase deficiency gene within the HLA complex.
Close linkage between HLA and the gene for 21-OH deficiency causing congenital virilizing adrenal hyperplasia (CVAH) has been well documented. HLA-A/B and HLA/GLO recombination data placed the CVAH gene within the HLA-A to GLO interval, with CVAH invariably segregating with HLA. HLA-A,B,C,DR and GLO typing and ACTH stimulation to determine carrier status was done on seven families. Carrier status correlated with the appropriate HLA haplotypes in all offspring, with two exceptions. Two intra-HLA recombinants were detected in one three-generation family. The father of the proband is homozygous for HLA-A2,Cw2,B27 but is a DR2/DR4 heterozygote. The CVAH gene segregated with DR2 in all but one of his offspring who is a carrier and is DR4. This finding is consistent with recombination between the CVAH gene and DR. Study of the father's family confirmed synteny of the CVAH gene and DR2. Three of four sibs of the father inherited this haplotype and were CVAH carrier, as was the paternal grandmother, whose other haplotype was A1, Bw44,DR1. One of the father's sibs was shown serologically to be a HLA-B/D maternal recombinant and a noncarrier. she inherited the A1,Bw44 of one maternal haplotype, but the DR2 of the other. In both recombinants in this family the CVAH gene segregated with the A to B interval, separate from D. While we cannot determine whether the CVAH gene is in the HLA-A to B or B to D interval, this is the first report of two intra-HLA recombinations in one family that unequivocally map the CVAH gene inside HLA-D.


MicroRNA-mediated gene regulation plays a minor role in the transcriptomic plasticity of cold-acclimated zebrafish brain tissue.
MicroRNAs (miRNAs) play important roles in regulating the expression of protein-coding genes by directing the degradation and/or repression of the translation of gene transcripts. Growing evidence shows that miRNAs are indispensable player in organismal development with its regulatory role in the growth and differentiation of cell lineages. However, the roles of miRNA-mediated regulation in environmental adaptation of organisms are largely unknown. To examine this potential regulatory capability, we characterized microRNAomes from the brain of zebrafish raised under normal (28 °C) and cold-acclimated (10 °C, 10 days) conditions using Solexa sequencing. We then examined the expression pattern of the protein-coding genes under these two conditions with Affymetrix Zebrafish Genome Array profiling. The potential roles of the microRNAome in the transcriptomic cold regulation in the zebrafish brain were investigated by various statistical analyses. Among the total 214 unique, mature zebrafish miRNAs deposited on the miRBase website (release 16), 175 were recovered in this study. In addition, we identified 399 novel, mature miRNAs using multiple miRNA prediction methods. We defined a set of 25 miRNAs differentially expressed under the cold and normal conditions and predicted the molecular functions and biological processes that they involve through Gene Ontology (GO) annotation of their target genes. On the other hand, microarray analysis showed that genes related to mRNA processing and response to stress were overrepresented among the up-regulated genes in cold-stress, but are not directly corresponding to any of the GO molecular functions and biological processes predicted from the differential miRNAs. Using several statistical models including a novel, network-based approach, we found that miRNAs identified in this study, either individually or together, and either directly or indirectly (i.e., mediated by transcription factors), only make minor contribution to the change in gene expression patterns under the low-temperature condition. Our results suggest that the cold-stress response of mRNA expression may be governed mainly through regulatory modes other than miRNA-mediated regulation. MiRNAs in animal brains might act more as developmental regulators than thermal adaptability regulators.


Temperature-related mortality impacts under and beyond Paris Agreement climate change scenarios.
The Paris Agreement binds all nations to undertake ambitious efforts to combat climate change, with the commitment to Bhold warming well below 2 °C in global mean temperature (GMT), relative to pre-industrial levels, and to pursue efforts to limit warming to 1.5 °C". The 1.5 °C limit constitutes an ambitious goal for which greater evidence on its benefits for health would help guide policy and potentially increase the motivation for action. Here we contribute to this gap with an assessment on the potential health benefits, in terms of reductions in temperature-related mortality, derived from the compliance to the agreed temperature targets, compared to more extreme warming scenarios. We performed a multi-region analysis in 451 locations in 23 countries with different climate zones, and evaluated changes in heat and cold-related mortality under scenarios consistent with the Paris Agreement targets (1.5 and 2 °C) and more extreme GMT increases (3 and 4 °C), and under the assumption of no changes in demographic distribution and vulnerability. Our results suggest that limiting warming below 2 °C could prevent large increases in temperature-related mortality in most regions worldwide. The comparison between 1.5 and 2 °C is more complex and characterized by higher uncertainty, with geographical differences that indicate potential benefits limited to areas located in warmer climates, where direct climate change impacts will be more discernible.


Nursing and Focal Dyscognitive Seizures: A Clinical Update When Managing Risk Using Advanced Nursing Skills.
Focal seizures are divided into simple and dyscognitive, with the latter resulting in the alteration of consciousness. In the ictal and postictal stages, patients may present with confusion, delirium, and psychosis, presenting a risk of safety to themselves and others. This article presents 3 case studies where patients have been admitted for visual and electroencephalographic monitoring. Seizure activity is provoked for the diagnosis and development of a management plan. These cases illustrate the unique nursing implications when caring for patients experiencing focal dyscognitive seizures, highlighting the unique circumstances for the neuroscience nurse regarding risk management, safe administration of radioactive isotopes, detection of subtle seizure manifestation, and use of family as experts in patient-centered care. Through a deliberate onset of seizures, neuroscience nurses are placed in nontypical nursing situations, thus managing risk in unpredictable conditions and displaying advanced and distinctive nursing skills.


Recurrence Patterns and Outcomes of Salvage Surgery in Cases of Non-Curative Endoscopic Submucosal Dissection without Additional Radical Surgery for Early Gastric Cancer.
The outcomes of salvage surgery for recurrence after non-curative endoscopic submucosal dissection (ESD) without additional radical surgery for early gastric cancer (EGC) remain unclear. We determined the recurrence patterns and outcomes of salvage surgery in such cases using data from a multicenter, retrospective study. Of 15,785 patients who underwent ESD for EGC at 19 participating institutions between January 2000 and August 2011, 1,969 failed to meet the current curative criteria after ESD. Of these, 905 patients received no additional treatment. We evaluated the pattern of recurrence, clinical course after salvage surgery, and long-term survival rate for these patients. Over a median 64-month follow-up period, recurrence was detected in 27 patients. Two patients with missing data were excluded. Three, seven, and 15 (60%) patients showed intragastric relapse, regional lymph node metastasis, and distant metastasis, respectively. The first line of treatment for recurrence in 1, 7, 6, and 11 patients was endoscopic treatment, salvage surgery, chemotherapy, and best supportive care, respectively. One patient survived without recurrence for 31 months after salvage surgery, one died of acute myocardial infarction 1 month after salvage surgery, and 5 showed recurrence at 0, 2, 3, 5, and 30 months after salvage surgery and eventually succumbed to the disease. The median survival times for all patients with recurrence and the 7 patients who underwent salvage surgery were 5 months after recurrence and 7 months after salvage surgery, respectively. The survival rate after salvage surgery for recurrence after non-curative ESD without additional radical surgery for EGC is quite low, with distant metastasis being the most common recurrence pattern in these cases.


Empagliflozin in Heart Failure with a Preserved Ejection Fraction.
Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin. Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).


[Diagnosis of coccidia and microspores in specimens of diarrheal feces from Cuban HIV seropositive patients: first report of microspores in Cuba].
The numerous specimens of liquid diarrheas received at the clinical parasitology laboratory of "Pedro Kouri" Institute of Tropical Medicine were studied searching for the presence of pathogenic agents of Coccidium subclass and of the microspore family. The conditions to diagnose microsporidia were created on July 13, 2000, and the method was incorporated to the battery of diagnostic techniques used in the laboratory. A cut-off was made after 4 months to analyze the positivity found. A frequency distribution study was conducted and it was observed that of the 170 studied samples, 51 proved to be positive for some protozoon, which represents 30% of positivity. The most frequently found species were Cryptosporidium parvum and microsporidium. Association of various species in a same sample was found in 13.1% of the positive samples. The most frequent associations were: Cryptosporidium parvum and Cyclospora cayetanensis, Cryptosporidium parvum and microsporidium, and Cyclospora cayetanensis and microsporidium, each with 2 patients. Association of 3 different species in a same sample was also found. All the individuals in the series were HIV seropositive and the most affected had less than 200 TCD4+ lymphocytes/mL. This was the first report of microsporidia in feces in Cuba. It was possible after applying and interpreting the technique previously described to identify this phylum. As there is a trend towards the increase of cases with HIV/AIDS infection, it is necessary that the laboratories have the indispendable reagents to perform the modified Didier's trichromic staining and that the professionals and technicians of the parasitology laboratories of the country be trained in the procedures for identifying and recognizing these opportunistic protozoa.


Rural Latino immigrant caregivers' conceptions of their children's oral disease.
The aim of this study was to examine Latino immigrant caregivers' explanatory models of the causes of early childhood caries (ECC). In a rural area, we conducted 71 open-ended qualitative interviews with 26 Mexican immigrant and 12 Salvadoran immigrant caregivers of children under 6 about the causes of ECC. Two researchers independently read each interview and classified each interviewee's response. Caregivers mentioned three biomedical causes of oral disease (sweets, poor oral hygiene, and bottle-feeding) and two lay or popular causes (lack of milk consumption and "bad" genes). Although caregivers were aware that the consumption of sweet foods causes decay they expressed particular confusion about how bottle-feeding causes decay. Nineteen caregivers attributed decay specifically to bottle-feeding, yet 14 believed the cause of decay was the bottle's nipple. Seven Mexican immigrant caregivers attributed their children's decay specifically to a lack of calcium, and six immigrant caregivers to "bad teeth genes." Conceptions of oral disease derived from the caregivers' own dental experiences, their conceptions of the body, and interactions with dental professionals. The fact that biomedical explanations dominate the list of causes of caries for both groups indicates that the caregivers' explanatory models of oral disease are powerfully shaped by interactions with health professionals. Immigrant caregivers' mistaking of the baby bottle's nipple as the source of decay indicates the need for more effective oral health promotion. Yet the Mexican immigrants' conceptions of a lack of calcium as a major factor in their children's decay may illustrate a strong cultural link between teeth and milk.


Foot and ankle strength assessment using hand-held dynamometry: reliability and age-related differences.
Age-related reduction in lower limb muscle strength has been shown to be related to disability, falls and loss of independence. While there have been a number of studies on age-related changes in muscle strength, they have concentrated on more proximal muscle groups with little research into how ageing affects the muscles of the foot and ankle. To evaluate the intra- and interrater reliability of hand-held dynamometry for the assessment of foot and ankle strength, and to compare the values obtained between young and older people. The muscle groups which perform ankle dorsiflexion, plantar flexion, inversion, eversion and plantar flexion of the hallux and lesser digits were recorded for 36 young participants (17 males, 19 females, mean age 23.2 ± 4.3 years) and 36 older people (17 males, 19 females, mean age 77.1 ± 5.7 years) using a Citec hand-held dynamometer. Differences in muscle strength between the groups as well as intrarater and interrater reliability of two assessors were determined. The reliability of the hand-held dynamometry procedure was excellent for both intrarater (ICC(3,1) = 0.78-0.94) and interrater (ICC(3,1) = 0.77-0.88) comparisons. There were significant differences between the muscle strength of the young and older participants for all muscle groups tested (p < 0.001) with older participants being weaker than the young participants by a magnitude of between 24 and 37%. Hand-held dynamometry is a reliable instrument to measure the foot and ankle strength of young and older adults. Ageing is associated with a reduction in strength of between 24 and 37% for the muscles responsible for movement of the foot and ankle.


The end of the BSE saga: do we still need surveillance for human prion diseases?
The epidemics of classical bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) related to BSE-infected food are coming to an end. The decline in concern about these diseases may invite complacency and questions whether surveillance for human prion diseases is still necessary. This article reviews the main points of surveillance and why it is still needed: animal sources for human prion infection other than BSE cannot be excluded; the potentially increasing circulation of prions between humans by blood, blood products and medical procedures; the prevalence of vCJD prion carriers in the UK; and the scientific study of prion diseases as paradigm for other neurodegenerative diseases with "prion-like" spread of pathological proteins. We conclude that continuation of detailed surveillance of human prion disorders would be prudent in view of all these points that deserve clarification.


Geospatial analysis of condom availability and accessibility in urban Malawi.
Prevalence of HIV in sub-Saharan African countries persists at alarming rates. There are currently four promoted methods to prevent HIV infection: adherence to antiretroviral therapy, male circumcision, pre-exposure prophylaxis and use of condoms. This study aimed to assess the availability and accessibility of one of the prevention efforts, condoms, in Kawale, Lilongwe, Malawi. A total of 220 potential condom-selling establishments were surveyed in 2012. Data were collected with store owners or staff and locations were geocoded to assess store density. Descriptive analyses were conducted. Of those audited, 96 stores sold condoms, 13 of which distributed free condoms. The stores were most often small shops and located in markets or trading centres. Condoms were most often found at the back of the store in an open space. There were approximately 1.2 stores per ¼ mile; 44% of the businesses in the study region carried condoms. This one method of prevention exhibited multiple barriers in this region: few stores sold condoms, high costs, condom locations within stores and limited availability. The limited accessibility is likely to influence social norms surrounding condom use. Future research should incorporate assessing norms and addressing barriers to uptake of HIV prevention efforts.


Racial disparities in knowledge of stroke and heart attack risk factors and warning signs among Michigan adults.
To describe the level of knowledge regarding risk factors and warning signs for stroke and heart attack among White and African American adults in Michigan and to quantify racial disparities. Knowledge of stroke and heart attack risk factors and warning signs was assessed by using data from the 2004 Michigan Behavioral Risk Factor Survey. Prevalence estimates of knowledge were generated, and statistical differences in knowledge between Whites and African Americans were assessed. Adequate knowledge was defined as knowing 3 correct warning signs or risk factors. Logistic regression models were used to quantify the racial disparity in knowledge while controlling for potential confounding. Whites had substantially higher levels of adequate knowledge of risk factors (stroke: 31.6% vs 13.8%; heart attack: 52.6% vs 24.3%) and warning signs (stroke: 30.0% vs 17.2%; heart attack: 29.3% vs 13.8%) compared with African Americans (all observed differences were significant at P < .05). The odds of adequate knowledge of risk factors (stroke: adjusted odds ratio [AOR] 2.9; heart attack: AOR 3.4) and warning signs (stroke: AOR 2.0; heart attack: AOR 2.4) were significantly higher for Whites than for African Americans. A strong racial disparity in the knowledge of stroke and heart attack risk factors and warning signs exists among Michigan adults. Communitywide public education programs in conjunction with targeted interventions for at-risk populations are necessary to produce meaningful improvements in the awareness of stroke and heart attack risk factors and warning signs among Michigan adults.


Benign childhood focal epilepsies: assessment of established and newly recognized syndromes.
A big advance in epileptology has been the recognition of syndromes with distinct aetiology, clinical and EEG features, treatment and prognosis. A prime and common example of this is rolandic epilepsy that is well known by the general paediatricians for over 50 years, thus allowing a precise diagnosis that predicts an excellent prognosis. However, rolandic is not the only benign childhood epileptic syndrome. Converging evidence from multiple and independent clinical, EEG and magnetoencephalographic studies has documented Panayiotopoulos syndrome (PS) as a model of childhood autonomic epilepsy, which is also common and benign. Despite high prevalence, lengthy and dramatic features, PS as well as autonomic status epilepticus had eluded recognition because emetic and other ictal autonomic manifestations were dismissed as non-epileptic events of other diseases. Furthermore, PS because of frequent EEG occipital spikes has been erroneously considered as occipital epilepsy and thus confused with the idiopathic childhood occipital epilepsy of Gastaut (ICOE-G), which is another age-related but rarer and of unpredictable prognosis syndrome. Encephalitis is a common misdiagnosis for PS and migraine with visual aura for ICOE-G. Pathophysiologically, the symptomatogenic zone appears to correspond to the epileptogenic zone in rolandic epilepsy (sensory-motor symptomatology of the rolandic cortex) and the ICOE-G (occipital lobe symptomatology), while the autonomic clinical manifestations of PS are likely to be generated by variable and widely spread epileptogenic foci acting upon a temporarily hyperexcitable central autonomic network. Rolandic epilepsy, PS, ICOE-G and other possible clinical phenotypes of benign childhood focal seizures are likely to be linked together by a genetically determined, functional derangement of the systemic brain maturation that is age related (benign childhood seizure susceptibility syndrome). This is usually mild but exceptionally it may diverge to serious epileptic disorders such as epileptic encephalopathy with continuous spike and wave during sleep. Links with other benign and age-related seizures in early life such as febrile seizures, benign focal neonatal and infantile seizures is possible. Overlap with idiopathic generalized epilepsies is limited and of uncertain genetic significance. Taking all these into account, benign childhood focal seizures and related epileptic syndromes would need proper multi-disciplinary re-assessment in an evidence-based manner.


The impact of HLA-E polymorphisms in graft-versus-host disease following HLA-E matched allogeneic hematopoietic stem cell transplantation.
The non-classical MHC class-I mainly involves in the regulation of innate immune responses where HLA-E plays a significant role in the cell identification by natural killer cells. HLA-E is a main regulatory ligand for natural killer cells and given the importance of these effector cells in hematopoietic stem cell transplantation, we investigated the effect of HLA-E polymorphisms on post-hematopoietic stem cell transplantation outcomes. The study group included 56 donor-patient pairs with underlying malignant hematological disorders undergoing HLA-E matched allogeneic hematopoietic stem cell transplantation. They were genotyped for HLA-E locus using a sequence specific primer-polymerase chain reaction. The median follow-up was 20.6 months (range 0.2-114.8) and the parameters assessed were acute and chronic graft-versus-host disease and overall survival. We showed a lower frequency of acute graft-versus-host disease (grade II or more; p=0.02) and chronic graft-versus-host disease (extensive; p=0.04) in the patients with HLA-E*0103/0103 genotype compared to other genotypes of HLA-E. There was also an association between HLA-E*0103/0103 and improved overall survival (p=0.001). Conclusively, our results suggest a protective role for HLA-E*0103/0103 genotype against acute graft-versus-host disease (grade II or more) and chronic graft-versus-host disease (extensive) as well as an association between this genotype and a better overall survival after HLA-E matched allogeneic hematopoietic stem cell transplantation.


[Mycoplasma pneumoniae encephalitis in immunocompetent child].
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia, but this organism can also affect almost every organ system besides the lung. Neurological manifestations (meningitis, encephalitis, transverse myelitis, Guillain-Barrè syndrome) are the most frequent extrapulmonary complications of Mycoplasma pneumoniae. We report a case of a immunocompetent child affected by encephalitis caused by Mycoplasma pneumoniae.


Short-term continuous intraparenchymal intracranial pressure monitoring in presumed idiopathic intracranial hypertension.
The management of idiopathic intracranial hypertension (IIH) depends on a reliable assessment of intracranial pressure (ICP), particularly when visual function measures or ophthalmoscopic indicators are confusing and when invasive surgical procedures are being considered. Although ICP monitoring has been widely applied in many neurologic conditions as a more reliable measure of ongoing ICP than lumbar puncture (LP), it has not often been widely used in the management of IIH. We searched the records of the University of Michigan between 2001 and 2008 for patients with IIH who had undergone LP and continuous ICP monitoring with an intraparenchymal Codman ICP Monitoring System and in whom at least 1 year of follow-up information was available. Ten patients met entry criteria. There were no complications from the ICP monitoring. ICP monitoring influenced management in all 10 patients. In 8 patients, LP had shown elevated opening pressures; in 7 of them, ICP monitoring failed to confirm a consistently high ICP. In these patients, the decision to withdraw ICP-lowering agents or shunts, or not to revise indwelling shunts, produced no change in visual function or optic disc appearance over a follow-up period of at least 1 year. In 1 patient, ICP monitoring confirmed the high ICP suggested by LP, justifying placement of a ventriculoperitoneal shunt. In 1 patient, ICP monitoring was performed instead of LP because a petroclival mass posed a danger to the performance of LP; a shunt was subsequently placed due to elevated ICP. In providing more accurate information about ICP than about LP, short-term continuous ICP intraparenchymal monitoring may be a useful adjunct in the management of IIH when clinical data are confusing and invasive interventions are under consideration.


The Risk of Seizure Following Surgery for Brain Arteriovenous Malformation: A Prospective Cohort Study.
The evidence for the risk of seizures following surgery for brain arteriovenous malformations (bAVM) is limited. To determine the risk of seizures after discharge from surgery for supratentorial bAVM. A prospectively collected cohort database of 559 supratentorial bAVM patients (excluding patients where surgery was not performed with the primary intention of treating the bAVM) was analyzed. Cox proportional hazards regression models (Cox regression) were generated assessing risk factors, a Receiver Operator Characteristic curve was generated to identify a cut-point for size and Kaplan-Meier life table curves created to identify the cumulative freedom from postoperative seizure. Preoperative histories of more than 2 seizures and increasing maximum diameter (size, cm) of bAVM were found to be significantly (P < .01) associated with the development of postoperative seizures and remained significant in the Cox regression (size as continuous variable: P = .01; hazard ratio: 1.2; 95% confidence interval: 1.0-1.3; more than 2 seizures: P = .02; hazard ratio: 2.1; 95% confidence interval: 1.1-3.8). The cumulative risk of first seizure after discharge from hospital following resection surgery for all patients with bAVM was 5.8% and 18% at 12 mo and 7 yr, respectively. The 7-yr risk of developing postoperative seizures ranged from 11% for patients with bAVM ≤4 cm and with 0 to 2 preoperative seizures, to 59% for patients with bAVM >4 cm and with >2 preoperative. The risk of seizures after discharge from hospital following surgery for bAVM increases with the maximum diameter of the bAVM and a patient history of more than 2 preoperative seizures.


Preliminary phytochemical and biological study of Cirsium ehrenbergii.
Cirsium ehrenbergii ("red thistle") is a folk medicinal plant of the state of Hidalgo, Mexico. Its flowers and roots are used to prepare an infusion for drinking or applying vaginal douches; nevertheless, neither its secondary metabolites nor therapeutic properties have been described or confirmed. Flowers of C. ehrenbergii, were collected, dried and milled. Aqueous, methanol and hexane extracts were carried out by maceration to obtain polar and non-polar secondary metabolites. The presence of alkaloids was determined by Wagner, Mayer and Dragendorff techniques; both polar and non-polar extracts yielded positive results. Toxicity was quantified by the Artemia salina mortality method, the aqueous extract showed moderate toxicity, while methanol and hexane extracts yielded a very similar and high concentration-dependent mortality. Antibacterial activity was evidenced by cellular growth inhibition of six bacterial strains, wherein the aqueous extract was inactive; the methanol extract was almost ineffective, while the hexane extract showed a high concentration-dependent antibacterial activity on all strains. An isolated organ study was performed with rings of uterus from estrogen-treated female Wistar rats to evaluate relaxing effects on uterine smooth muscle. Rings were pre-contracted with KCl (60 mM). The methanol extract inhibited contraction modestly at the highest concentration (300 pg/mL). The hexane extract markedly inhibited contraction in a concentration-dependent manner. The hexane extract was biologically more effective than the methanol extract. The traditional use of C. ehrenbergii as a medicinal plant may be supported by pharmacological actions.


Evaluation of enhanced glucagon sensitivity as the cause of glucose intolerance in acutely uremic rats.
These studies were undertaken to evaluate the possibility that increased hepatic glucose output, secondary to enhanced glucagon sensitivity, contributes to the glucose intolerance of acute uremia. In order to accomplish this, we determined the effect of an infusion of glucagon (6 ng/kg per min) on hepatic glucose output from isolated perfused livers of acutely uremic and sham-operated rats. Hepatic glucose output by livers from sham-operated rats more than doubled during glucagon infusion. In contrast, hepatic glucose output did not increase when livers of acutely uremic rats were perfused with glucagon. Furthermore, glycogen content did not fall nor did urea formation increas when livers from acutely uremic rats perfused with glucagon. On the other hand, dibutyryl cAMP infusion led to a similar increase in hepatic glucose output by livers from sham-operated and acutely uremic rats. Furthermore, urea formation increased and glycogen content decreased when livers from acutely uremic rats were perfused with dibutyryl cAMP. These results indicate that livers from acutely uremic rats exhibit a diminished responsiveness to glucagon-induced glycogenolysis and gluconeogenesis, but respond normally to dibutyryl cAMP. Thus, an increase in hepatic glucose output, secondary to enhanced glucagon sensitivity, does not appears to contribute to glucose intolerance in acutely uremic rats.


High nationwide incidence of multiple sclerosis in Sweden.
Over recent years increased MS incidence, primarily in women, has been reported. We recently reported an unexpectedly high MS prevalence of 189/100,000 in Sweden. In the present study we estimated the nationwide age- and gender-specific MS incidence and the sex ratio in Sweden between 2001 and 2008. MS patients were identified by linking two nationwide health data registers, and the Swedish population register. The earliest registered date of MS diagnosis was determined. By logistic regression, the probability of the date of MS diagnosis being within the incidence period, depending on age and time was estimated for a subset of patients and applied to other patients. By Poisson regression, the hazard functions for the incidence of MS diagnosis were estimated. The expected number of MS patients was 7,361.4. The incidence in the average population of 9,054,658 was 10.2 per 100,000 person-years, and 6.2 and 14.0 per 100,000 person-years for men and women, respectively. The crude female to male ratio was 2.26. No increase of incidence or change of sex ratio was observed from 2001 to 2008. In conclusion, the average MS incidence in Sweden from 2001 to 2008 was 10.2 per 100.000, which was considerably higher than previous regional Swedish estimates of 4.3-6.4. No increase of female to male ratio of MS during the study period was observed. We provide supplementary data that can be used as tools for examining excess MS risk in different study materials.


Preservation of resting potential by magnesium in hypoxic canine cardiac cells.
This study was designed to test the hypothesis that Mg++ prevents the electrophysiologic changes caused by hypoxia in cardiac cells. Canine right ventricular false tendons (32 hearts) were pinned to the floor of a tissue bath and suffused with physiologic solution. Microelectrodes recorded the spontaneous action potentials. The isolated tissue was exposed to a hypoxic solution (PO2 less than 50 mm Hg) containing either normal [Mg++] (0.85 mmol/l) or high [Mg++] (3.4 mmol/l). Hypoxia with normal [Mg++] caused increased firing rate (+40%), depolarization of the resting (maximum diastolic) potential (from-72 to -55 mV), and reduction in amplitude (from 88 to 76 mV). The depolarization, reduction in amplitude, and most of the increased firing rate were completely blocked when [Mg++] was elevated to 3.4 mmol/l; propranolol (10 mg/l) blocked the residual increase in firing rate.


AI-Generated Images for Speech Pathology-An Exploratory Application to Aphasia Assessment and Intervention Materials.
Images are a core component of aphasia assessment and intervention that require significant resources to produce or source. Text-to-image generation is an Artificial Intelligence (AI) technology that has recently made significant advances and could be a source of low-cost, highly customizable images. The aim of this study was to explore the potential of AI image generation for use in aphasia by examining its efficiency and cost during generation of typical images. Two hundred targets (80 nouns, 80 verbs, and 40 sentences) were selected at random from existing aphasia assessments and treatment software. A widely known image generator, DALL-E 2, was given text prompts for each target. The success rate, number of prompts required, and costs were summarized across target categories (noun/verb/sentence) and compared to frequency and imageability. Of 200 targets, 189 (94.5%) successfully conveyed the key concept. The process took a mean of 2.3 min per target at a cost of $0.31 in U.S. dollars each. However, there were aesthetic flaws in many successful images that could impact their utility. Noun images were generated with the highest efficiency and accuracy, followed by verbs, while sentences were more challenging, particularly those with unusual scenes. Patterns of flaws and errors in image generation are discussed. The ability to rapidly generate low-cost, high-quality images using AI is likely to be a major contribution to aphasia assessment and treatment going forward, particularly as advances in this technology continue.


Assessment of the investigation of deaths from ill-defined causes in the state of Bahia in 2010.
The investigation of deaths from ill-defined causes (DIDC) has been a strategy of health services to reduce the proportion of these events. This study aimed to estimate the adherence of municipalities to the use of recommended forms in the investigation of DIDC and the impact of these investigations on the reduction of these deaths in the Mortality Information System. The use of the Investigation of Death from Ill-defined Cause (IOCMD) and Verbal Autopsy (VA)forms and the proportion of reclassified underlying cause of death following investigations were analyzed in a probabilistic sample of 27 municipalities of Bahia state, and its capital Salvador, in 2010. Of the 27 municipalities, approximately 50% used the recommended forms to investigate DIDCs. Of the 1,092DIDCs in the sample, 53.1% were investigated: in 40.5% of the cases, only the IOCMD form was used; in 15.3%, only the VA form was used; and both forms were used in 14.3% of the cases. The investigation of DIDCs reduced the percentages of these deaths from 16.5% to 9.9% and proved to be more effective when performed using the recommended forms.


Sex-Based Differences in Heart Failure: JACC Focus Seminar 7/7.
Sex-based differences exist in risk, symptoms, and management of heart failure (HF). Women have a higher incidence of HF with preserved ejection fraction compared with men. This may be partially caused by the cardiovascular effects of estrogen and sex-specific risk factors (eg, adverse pregnancy outcomes, premature menopause). Key gaps exist in understanding of gender-based differences in HF, which is a distinctly different concept than sex-based differences. Although evidence-based therapies for HF are available, only limited data address sex-specific efficacy, and no data address gender-based efficacy. Persistent shortcomings in representation of women and gender minority participants in clinical trials limit an actionable database. A comprehensive roadmap to close the sex/gender-based gap in HF includes the following: 1) sex/gender-specific personalized prevention; 2) sex/gender-neutral implementation of evidence-based therapies; and 3) sex/gender-appropriate policy-level initiatives to spur research assessing sex/gender-specific causes of HF; enhance sex/gender-specific subgroup reporting; and promote community engagement of these important patient cohorts.


The role of N6-methyladenosine RNA modification in platinum resistance.
N6-methyladenosine (m6A) RNA methylation, a dynamic regulator of transcript expression, plays a pivotal role in cancer by influencing diverse mRNA processes, including nuclear export, splicing, translation and decay. It intersects with cancer biology, impacting progression, treatment sensitivity and prognosis. Platinum-based compounds are essential in cancer treatment, while intrinsic or acquired resistance poses a formidable challenge, limiting therapeutic efficacy. Recent breakthroughs have established a direct association between m6A RNA methylation and platinum resistance in various cancer types. This review summarized related studies, aiming to provide profound insights into the interplay between m6A-associated regulation and platinum-resistance mechanisms in cancer. It explores therapeutic approaches, including personalized treatments based on m6A profiles, guiding future research to enhance clinical strategies for oncological prognostic outcomes.


How do clients in Australia experience Consumer Directed Care?
Our study explored client experience of Australian Consumer Directed Care. This evolving funding model enables consumer autonomy and choice, allowing older people to remain in their community as they age and need support through the creation of a personalised support service. Consumer Directed Care focuses on providing services that the consumer self-determines to meeting their needs including identifying their types of services, from whom, when and how these services are delivered. Semi-structured in-depth interviews were conducted in two Australian states between August 2015 and April 2016 with 14 participants, preferably in receipt of CDC services for at least the previous 12 months. Questions explored how the participant first learned about this service; the types of services they received; whether services met their needs; and any additional support services they personally purchased. Interviews were transcribed, coded and thematically analysed. Four main themes related to consumer experience emerged. Knowledge: Unsure what Consumer Directed Care Means. Acceptance: Happily taking any prescriptive service that is offered. Compliance: Unhappily acceding to the prescriptive service that is offered. External Influences: Previous aged care service experience, financial position, and cultural differences. Our results suggest that the anticipated outcomes of Consumer Directed Care providing a better service experience were limited by existing client knowledge of these services, how best to utilise their funding allocation, and their acceptance or compliance with what was offered, even if this was not personalised or sufficient. External influences, such as service experience, finances, cultural difference, impacted the way clients managed their allocation. Our study identified that ongoing engagement and discussion with the client is required to ensure that services are specific, directly relevant and effective to achieving a consumer directed care service.


Selecting Collective Variables and Free-Energy Methods for Peptide Translocation across Membranes.
The selective permeability of cellular membranes is a crucial property for controlled transport into and out of cells. Molecules that can bypass the cellular machinery and spontaneously translocate across membranes could be used as therapeutics or drug carriers. Peptides are a prominent class of such molecules, which include natural and man-developed antimicrobial and cell-penetrating peptides. However, the necessary peptide properties for translocation remain elusive. Computer simulations could uncover these properties once we have a good collective variable (CV) that accurately describes the translocation process. Here, we developed a new CV, which includes a description of peptide insertion, local membrane deformation, and peptide internal degrees of freedom related to its charged groups. By comparison of CVs, we demonstrated that all these components are necessary for an accurate description of peptide translocation. Moreover, the advantages and disadvantages of three common methods for free-energy calculations with our CV were evaluated using the MARTINI coarse-grained model: umbrella sampling, umbrella sampling with replica exchange, and metadynamics. The developed CV leads to the reliable and effective calculation of the free energy of peptide translocation, and thus, it could be useful in the design of spontaneously translocating peptides.


Local dexamethasone improves periodontal healing of replanted dogs' teeth.
The purpose of the present investigation was to evaluate histologically the effect of dexamethasone on root resorption in stored and replanted dogs' teeth. Twenty-nine roots from three beagle dogs were endodontically treated to prevent subsequent inflammatory root resorption of pulpal origin. The teeth were extracted and randomly assigned to three groups for 48-h storage. Group 1: control group teeth (n = 13) were stored in vials containing ViaSpan only; Group 2: topical treatment teeth (n = 10) were stored in vials containing ViaSpan and dexamethasone (16 micrograms/ml); and Group 3: systemic treatment teeth (n = 6) were stored in vials containing ViaSpan without any additives. Dexamethasone was administered intramuscularly (0.5 mg/kg body weight) 2 days prior to, on the day of, and every other day after extraction and replantation for two administrations. After 12 weeks, the dogs were sacrificed, and the teeth histologically prepared and evaluated according to the analysis of Andreasen. Significant differences were found for complete healing (P = 0.0583) and inflammatory root resorption (P = 0.0568) but not for replacement resorption (P = 0.1952). In addition, comparing local to systemic administration of dexamethasone (Group 2 vs. Group 3), statistically significant differences were found for healing, 85% (Group 2) vs. 67% (Group 3) (P = 0.0125) and inflammatory root resorption, 13% (Group 2) vs. 28% (Group 3) (P = 0.0126). This study indicated that topical use of dexamethasone enhances healing and results in fewer resorption complications.


Empathy and social perspective taking in children with Attention-Deficit/Hyperactivity Disorder.
This study explored empathy and social perspective taking in 8 to 12 year old children with and without Attention-Deficit/Hyperactivity Disorder (ADHD). The sample comprised 92 children, 50 with a diagnosis of ADHD and 42 typically developing comparison children. Although children with ADHD were rated by their parents as less empathic than children without ADHD, this difference was accounted for by co-occurring oppositional and conduct problems among children in the ADHD sample. Children with ADHD used lower levels of social perspective taking coordination in their definition of problems, identification of feelings, and evaluation of outcomes than children without ADHD, and these differences persisted after the role of language abilities, intelligence and oppositional and conduct problems were taken into account. Girls were more empathic and had higher overall social perspective taking scores than boys. Implications for research and practice are discussed.


Compositional analysis of Helicobacter pylori rough-form lipopolysaccharides.
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to analyze the macromolecular heterogeneity of lipopolysaccharides (LPS) from seven fresh clinical isolates and three culture collection strains of the human pathogen Helicobacter pylori. All the clinical isolates produced smooth-form LPS with O side chains of relatively homogeneous chain length, whereas the culture collection strains yielded rough-form LPS. A better yield of the latter LPS was obtained when combined protease pretreatment and hot phenol-water extraction were used than when the conventional phenol-water technique alone was used for extraction. The LPS of the three culture collection strains (S-24, C-5437, and NCTC 11637) were chemically characterized. Constituents common to all the LPS were fucose, D-mannose, D-glucose, D-galactose, D-glycero-D-manno-heptose, L-glycero-D-manno-heptose, and 3-deoxy-D-manno-2-octulosonic acid. The molar ratios of the hexoses differed between different strains, thereby reflecting structural differences. Phosphate, phosphorylethanolamine, and pyrophosphorylethanolamine were present also. Free lipid A contained D-glucosamine and fatty acids, with phosphate and a minor amount of ethanolamine. The major fatty acids were ester- and amide-bound 3-hydroxyoctadecanoic acid and ester-bound octadecanioc and 3-hydroxyhexadecanoic acids, with minor amounts of ester-bound tetradecanoic and hexadecanoic acids. In addition to the uncommonly long 3-hydroxy fatty acids, an unusual phosphorylation pattern was deduced to be present in the lipid A.


Feasibility of disinfection kinetics and minimum inhibitory concentration determination on bacterial cultures using flow cytometry.
Disinfection kinetics has been well established for selected antimicrobial agents on isolated bacterial strains. Due to the difficulties of culturing most bacteria, the majority of these studies have been limited to readily cultivable microorganisms of a single type or family. This study explores the feasibility of using flow cytometry for characterising the disinfection kinetics and minimum inhibitory concentration (MIC) of an Escherichia coli culture and a microbial consortium. The proposed method relies on fluorescent dye molecules to indicate the morphological and physiological status of numerous individual cells. Biocides of varying effectiveness and inactivation mechanisms (chlorine, iodine, and silver) were used to evaluate this novel application. Using pseudo-first-order kinetics, the coefficients of specific lethality of chlorine and iodine on Escherichia coli were 4.71 and 3.78 x 10(-3) L mg(-1) min(-1) and MIC of silver ion was between 60 and 80 microg L(-1). The coefficients of specific lethality of chlorine and iodine on the microbial consortium were 4.96 and 8.89 x 10(-3) L mg(-1) min(-1) and MIC of silver ion was between 40 and 60 microg L(-1). This method can be used to provide a rapid and consistent way of determining disinfection kinetics and MICs for pure and mixed bacterial cultures and can potentially be used to examine water and wastewater disinfection efficiency. However, caution should be used to ensure that the physiological and morphological status characterised by cytodyes is a result of the inactivation mechanisms of the disinfectants evaluated.


Prehospital COVID-19 patients discharged at the scene - an observational study.
Emergency medical services (EMS) were the first point of contact for many COVID-19 patients during the pandemic. The aim of this study was to investigate whether the non-conveyance decision of a COVID-19 patient was more frequently associated with a new EMS call than direct ambulance transport to the hospital. All confirmed COVID-19 patients with an EMS call within 14 days of symptom onset were included in the study. Patients were compared based on their prehospital transport decision (transport vs. non-conveyance). The primary endpoint was a new EMS call within 10 days leading to ambulance transport. A total of 1 286 patients met the study criteria; of these, 605 (47.0%) were male with a mean (standard deviation [SD]) age of 50.5 (SD 19.3) years. The most common dispatch codes were dyspnea in 656 (51.0%) and malaise in 364 (28.3%) calls. High-priority dispatch was used in 220 (17.1%) cases. After prehospital evaluation, 586 (45.6%) patients were discharged at the scene. Oxygen was given to 159 (12.4%) patients, of whom all but one were transported. A new EMS call leading to ambulance transport was observed in 133 (10.3%) cases; of these, 40 (30.1%) were in the group primarily transported and 93 (69.9%) were among the patients who were primarily discharged at the scene (p<.001). There were no significant differences in past medical history, presence of abnormal vital signs, or total NEWS score. Supplemental oxygen was given to 33 (24.8%) patients; 3 (2.3%) patients received other medications. Nearly half of all prehospital COVID-19 patients could be discharged at the scene. Approximately every sixth of these had a new EMS call and ambulance transport within the following 10 days. No significant deterioration was seen among patients primarily discharged at the scene. EMS was able to safely adjust its performance during the first pandemic wave to avoid ED overcrowding.


Adherence to safety practices and risks associated with health care waste management at an academic hospital, Pretoria, South Africa.
Adequate knowledge on hazards of healthcare waste and proper handling methods can result in its safe disposal and protection of workers and communities. The study assessed perceptions of healthcare workers on the adherence and risks associated with the practices of healthcare waste management. A total of 126 questionnaires were administered in selected wards at an academic hospital to establish training and knowledge on legislations regarding healthcare waste and health hazards associated with such waste. Sixty nine percent (69.0%) of participants had received training on healthcare waste handling. The highest number of cleaning staff (85.7%) received training from work while 34.8% of the doctors also received training from work. Only 44.1% of the nurses had knowledge about policies on healthcare waste. The majority of the participants (82.0%) had knowledge on the risks associated with handling of healthcare waste. However, only 20.0% of the participants re-capped needles after use and of these 43.5% were doctors. Most of the nurses (64.0%) had been exposed to needle pricks. Even though 82.0% of the participants believed there were enough management practices enforced with regards to the healthcare waste, it was recommended that there should be more education on the handling of healthcare waste.


Impaired osteoclast formation in bone marrow cultures of Fgf2 null mice in response to parathyroid hormone.
Fibroblast growth factor (FGF)-2 and parathyroid hormone (PTH) are potent inducers of osteoclast (OCL) formation, and PTH increases FGF-2 mRNA and protein expression in osteoblasts. To elucidate the role of endogenous FGF-2 in PTH responses, we examined PTH-induced OCL formation in bone marrow cultures from wild type and mice with a disruption of the Fgf2 gene. FGF-2-induced OCL formation was similar in marrow culture from both genotypes. In contrast, PTH-stimulated OCL formation in bone marrow cultures or co-cultures of osteoblast-spleen cells from Fgf2-/mice was significantly impaired. PTH increased RANKL mRNA expression in osteoblasts cultures from both genotypes. After 6 days of treatment, osteoprotegerin protein in cell supernatants was 40-fold higher in vehicle-treated and 30-fold higher in PTH-treated co-cultures of osteoblast and spleen cells from Fgf2-/mice compared with Fgf2+/+ mice. However, a neutralizing antibody to osteoprotegerin did not rescue reduced OCL formation in response to PTH. Injection of PTH caused hypercalcemia in Fgf2+/+ but not Fgf2-/mice. We conclude that PTH stimulates OCL formation and bone resorption in mice in part by endogenous FGF-2 synthesis by osteoblasts. Because RANKL- and interleukin-11-induced OCL formation was also reduced in bone marrow cultures from Fgf2-/mice, we further conclude that endogenous FGF-2 is necessary for maximal OCL formation by multiple bone resorbing factors.


Perceptions of healthcare providers on benefits, risks and barriers regarding intradialytic exercise among haemodialysis patients.
Clinical guidelines call for the inclusion of exercise interventions in every patient's dialysis session, but these recommendations are rarely adopted. Healthcare providers play a key role in this. Therefore, the aim of this study was to explore how healthcare providers perceive the benefits, risks and barriers of intradialytic exercise (IDE). We conducted 21 individual, semi-structured interviews with 11 nurses, 5 nephrologists, 3 training assistants and 2 managers from two dialysis centres in Slovakia. Verbatim transcripts of digitally recorded interviews were thematically analysed using MAXQDA®. Participants reported the benefits of IDE as improvements in patients' physical and psychosocial functioning, independence and self-efficacy, clinical profile and quality of therapy. As risks of IDE, they most frequently reported exercise-related damage to vascular access, insufficient individualization of training and musculoskeletal injuries. The presence of psychological problems among patients was reported as a major barrier for initiating and maintaining patients' exercise. Other reported barriers included limitations in financial and personnel resources of haemodialysis care. Safe and sustainable implementation of IDE, which might improve a patient's well-being, need to be prescribed in alignment with the patient's clinical profile, be delivered individually according to the patient's characteristics and requires adjustments in the available resources.


The embryonic mir-35 family of microRNAs promotes multiple aspects of fecundity in Caenorhabditis elegans.
MicroRNAs guide many aspects of development in all metazoan species. Frequently, microRNAs are expressed during a specific developmental stage to perform a temporally defined function. The C. elegans mir-35-42 microRNAs are expressed abundantly in oocytes and early embryos and are essential for embryonic development. Here, we show that these embryonic microRNAs surprisingly also function to control the number of progeny produced by adult hermaphrodites. Using a temperature-sensitive mir-35-42 family mutant (a deletion of the mir-35-41 cluster), we demonstrate three distinct defects in hermaphrodite fecundity. At permissive temperatures, a mild sperm defect partially reduces hermaphrodite fecundity. At restrictive temperatures, somatic gonad dysfunction combined with a severe sperm defect sharply reduces fecundity. Multiple lines of evidence, including a late embryonic temperature-sensitive period, support a role for mir-35-41 early during development to promote subsequent sperm production in later larval stages. We further show that the predicted mir-35 family target sup-26 (suppressor-26) acts downstream of mir-35-41 in this process, suggesting that sup-26 de-repression in mir-35-41 deletion mutants may contribute to temperature-sensitive loss of fecundity. In addition, these microRNAs play a role in male fertility, promoting proper morphogenesis of male-specific mating structures. Overall, our results demonstrate that robust activity of the mir-35-42 family microRNAs not only is essential for embryonic development across a range of temperatures but also enables the worm to subsequently develop full reproductive capacity.


Synthesis of salicylic acid from wintergreen oil by green chemistry overcomes its cytotoxicity in keratinocyte cells and teratogenicity in zebrafish embryos.
Salicylic acid topical is used to treat variety of skin conditions. However, salicylic acid in these products is generated through industrial synthesis and has been shown to negatively impact fetal development and cause congenital abnormalities. We hypothesized that teratogenic effects reported in salicylic acid can be prevented by naturally synthesizing salicylic acid from wintergreen oil using green chemistry method. For this purpose, we investigated the effects of natural salicylic acid (NSA) synthesized from wintergreen oil using green chemistry and synthetic salicylic acid (SSA) on keratinocyte cell (HaCaT) proliferation and zebrafish embryo development. NSA structures were analyzed by 1H NMR, 13C NMR, and GC/MS methods. Percentage inhibition against HaCaT cell was determined by MTS assay. xCelligence system was used for cellular activities. Zebrafish embryos were exposed to NSA and SSA for 72 h post-fertilization. Lipid peroxidation, nitric oxide, sialic acid, glutathione-S-transferase, catalase, and superoxide dismutase were evaluated using biochemical methods. Expressions of nqO1, gfap, bdnf, vtg, egr, cyp1a, and igf2 were determined by RT-PCR as developmental indicators. MTS and RT-cell analysis showed increased cell viability by NSA, whereas SSA decreased cell viability. NSA beneficially affected zebrafish embryo development while SSA exerted deleterious effects through oxidant-antioxidant status, inflammation, and development. Results of our study showed for the first time that synthesis of salicylic acid from wintergreen oil by green chemistry overcomes its cytotoxicity in keratinocyte cells and teratogenicity in zebrafish embryos. This finding is important for drug research on safe topical applications during pregnancy, when preventing exposure to drug and chemical-derived teratogens is vital.


Impaired endothelium-derived hyperpolarization-type relaxation in superior mesenteric arteries isolated from female Otsuka Long-Evans Tokushima Fatty rats.
Endothelium-derived hyperpolarization (EDH) is an important signaling mechanism of endothelium-dependent vasorelaxation, and little attention has been paid to the EDH-type responses in female metabolic syndrome such as that observed with type-2 diabetes. We previously reported that EDH-type relaxation was impaired in superior mesenteric arteries from male Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type-2 diabetes, however, the response was unclear in female OLETF rat. Thus, the aim of this study was to examine if EDH-type relaxation was altered in superior mesenteric arteries isolated from female OLETF rats compared to age-matched, control female Long-Evans Tokushima Otsuka (LETO) rats at age 50-59 weeks. We investigated concentration-relaxation curves for acetylcholine (at age 50-53 weeks), NS309 (an activator of small- and intermediate-conductance calcium-activated potassium channels) (at age 50-53 weeks), and GSK1016790A (an agonist of transient receptor potential vanilloid type 4, TRPV4) (at age 58 or 59 weeks) in the presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine and the cyclooxygenase inhibitor indomethacin to investigate EDH-type responses in the superior mesenteric artery. Obesity, mild hyperglycemia, hyperinsulinemia, and hyperlipidemia (i.e., increased total cholesterol, triglyceride, and non-esterified fatty acids) were more frequent in OLETF rats than in age-matched LETO rats at age 50-53 weeks. Acetylcholine-, NS309-, and GSK1016790A-induced relaxations in arteries from OLETF rats were all significantly reduced compared to those in LETO rats. These results indicated that EDH-type relaxations were impaired in female OLETF rats. This novel experimental model may provide new insights into vascular dysfunction in metabolic syndrome in females.


Which academic search systems are suitable for systematic reviews or meta-analyses? Evaluating retrieval qualities of Google Scholar, PubMed, and 26 other resources.
Rigorous evidence identification is essential for systematic reviews and meta-analyses (evidence syntheses) because the sample selection of relevant studies determines a review's outcome, validity, and explanatory power. Yet, the search systems allowing access to this evidence provide varying levels of precision, recall, and reproducibility and also demand different levels of effort. To date, it remains unclear which search systems are most appropriate for evidence synthesis and why. Advice on which search engines and bibliographic databases to choose for systematic searches is limited and lacking systematic, empirical performance assessments. This study investigates and compares the systematic search qualities of 28 widely used academic search systems, including Google Scholar, PubMed, and Web of Science. A novel, query-based method tests how well users are able to interact and retrieve records with each system. The study is the first to show the extent to which search systems can effectively and efficiently perform (Boolean) searches with regards to precision, recall, and reproducibility. We found substantial differences in the performance of search systems, meaning that their usability in systematic searches varies. Indeed, only half of the search systems analyzed and only a few Open Access databases can be recommended for evidence syntheses without adding substantial caveats. Particularly, our findings demonstrate why Google Scholar is inappropriate as principal search system. We call for database owners to recognize the requirements of evidence synthesis and for academic journals to reassess quality requirements for systematic reviews. Our findings aim to support researchers in conducting better searches for better evidence synthesis.


Estimation of the Composition of the Resting State fMRI Networks in Subjects with Mild Depression and Healthy Volunteers.
Depressive disorders can be associated with changes in not only interaction between neural networks, but also in their composition. Resting state fMRI scanning was performed for 4 min twice for each subject and the results of patients with mild depression (N=15) and healthy subjects (N=19) were analyzed. The fMRI signal was reduced into the independent components and the contrasts between the groups and between the first and second records were constructed for each component. During the first scanning, the auditory network of individuals with depression involved greater volume in the left insular region and lower volume in the right hemisphere. In record 2, depression patients were characterized by expansion of the executive network in the left hemisphere in the region of the middle and inferior frontal cortex. In healthy people, from record 1 to record 2, representation of the dorsal default mode network (DMN) increased in the left medial prefrontal area, the precuneus network expanded in the left hemisphere, and presentation of the ventral DMN in the right precuneus decreased. In the depression group, the auditory network lost some part of the left temporo-insular cortex; the sensorimotor network expanded in the left hemisphere to the cerebellum or to the central parietal region depending on the evaluation method, and the visuospatial network included or excluded a cluster in the left parietal lobe (in different points). Our findings indicate that connection of the auditory network with the left insular cortex could be a possible depression marker and also demonstrate a possibility of evaluating the composition of cerebral networks in intergroup comparisons and in dynamics without interventions.


Plasticity in the organization of adult cerebral cortical maps: a computer simulation based on neuronal group selection.
Recent experimental evidence from the somatosensory, auditory, and visual systems documents the existence of functional plasticity in topographic map organization in adult animals. This evidence suggests that an ongoing competitive organizing process controls the locations of map borders and the receptive field properties of neurons. A computer model based on the process of neuronal group selection has been constructed that accounts for reported results on map plasticity in somatosensory cortex. The simulations construct a network of locally connected excitatory and inhibitory cells that receives topographic projections from 2 receptor sheets corresponding to the glabrous and dorsal surfaces of the hand (a typical simulation involves approximately 1500 cells, 70,000 intrinsic and 100,000 extrinsic connections). Both intrinsic and extrinsic connections undergo activity-dependent modifications according to a synaptic rule based on heterosynaptic interactions. Repeated stimulation of the receptor sheet resulted in the formation of neuronal groups-local sets of strongly interconnected neurons in the network. Cells in most groups were found to have similar receptive fields: they were exclusively glabrous or dorsal despite equal numbers of anatomical connections from both surfaces. The sharpness of map borders was due to the sharpness of the underlying group structure; shifts in the locations of these borders resulted from competition between groups. Following perturbations of the input, the network underwent changes similar to those observed experimentally in monkey somatosensory cortex. Repeated local tapping on the receptor sheet resulted in a large increase in the magnification factor of the stimulated region. Transection of the connections from a glabrous region resulted in the organization of a new representation of corresponding dorsal region. The detailed simulations provide several insights into the mechanisms of such changes, as well as a series of predictions about cortical behavior for further experimental test.


[Na+,K(+)-ATPase activity in polarized cells].
The novel views on fundamental role of Na+,K(+)-ATPase in regulation of the polarized morphology of the epithelial cells, enzyme involvement in signal transduction, assembly of intermolecular signaling complexes have been reviewed. The modern state of researches are considered in detail, including: sorting specificity in polarized cells, Na+,K(+)-ATPase involvement in epithelial cell interactions, enzyme arrangement in combined structural and functional ensemble with adhesion and cytoskeleton proteins, their coordinated exp ression. The mechanisms of the Na+,K(+)-ATPase association with its molecular partners and the role of specific domains, motives and binding sites are analysed. The available data, including own researches indicate the Na+,K(+)-ATPase involvement in certain pathologies that develop with aberration of polarized epithelial phenotype, malignant growth in particular.


Advanced glycation end products in age-related macular degeneration.
To investigate the localization of N epsilon-(carboxymethyl)lysine (CML), a component and major immunologic epitope of advanced glycation end products, in aged eyes and choroidal neovascular membranes (CNVMs) surgically excised from eyes with age-related macular degeneration. Immunohistochemistry for CML was performed using 8 snap-frozen, surgically excised CNVMs. Twelve eyes from patients aged 69 to 82 years and 2 donor eyes, 1 each from a 23-week-old fetus and 21-year-old patient, without age-related macular degeneration or diabetic retinopathy were also examined. To determine if retinal pigment epithelial cells in CNVMs accumulate advanced glycation end products, cytokeratin and CML were stained in paired serial sections. Soft, macular drusen and/or basal laminar and basal linear deposits were observed in 8 of 12 aged eyes. Each case showed CML accumulation, while overlying retinal pigment epithelial cells showed no accumulation in all 12 eyes. In CNVMs, however, retinal pigment epithelial cells showed CML accumulation in their cytoplasm. The additional accumulation of advanced glycation end products in soft, macular drusen and/or retinal pigment epithelial cells may play a role in the pathogenesis of CNVM formation in age-related macular degeneration. Recently, advanced glycation end products have been found to play a role both in aging changes and neovascularization. Localization of advanced glycation end products in the above-mentioned tissue may lead to a better understanding of the pathogenesis of age-related macular degeneration.


Clinical and cost outcomes of multifactorial, cardiovascular risk management interventions in worksites: a comprehensive review and analysis.
This paper is a critical review of the clinical and cost outcome evaluation studies of multifactorial, comprehensive, cardiovascular risk management programs in worksites. A comprehensive international literature search conducted under the auspices of the National Heart, Lung and Blood Institute identified 17 articles based on 12 studies that examined the clinical outcomes of multifactorial, comprehensive programs. These articles were identified through MEDLINE, manual searches of recent journals, and through direct inquiries to worksite health promotion researchers. All studies were conducted between 1978 and 1995, with 1978 being the date of the first citation of a methodologically rigorous evaluation. Of the 12 research studies, only 8 utilized the worksite as both the unit of assignment and as the unit of analysis. None of the studies analyzed adequately for cost effectiveness. Given this limitation, this review briefly considers the relevant worksite research that has demonstrated cost outcomes. Worksite-based, multifactorial cardiovascular intervention programs reviewed for this article varied widely in the comprehensiveness, intensity, and duration of both the interventions and evaluations. Results from randomized trials suggest that providing opportunities for individualized, cardiovascular risk reduction counseling for high-risk employees within the context of comprehensive programming may be the critical component of an effective worksite intervention. Despite the many limitations of the current methodologies of the 12 studies, the majority of the research to date indicates the following: (1) favorable clinical and cost outcomes; (2) that more recent and more rigorously designed research tends to support rather than refute earlier and less rigorously designed studies; and (3) that rather than interpreting the methodological flaws and diversity as inherently negative, one may consider it as indicative of a robust phenomena evident in many types of worksites, with diverse employees, differing interventions, and varying degrees of methodological sophistication. Results of these studies reviewed provide both cautious optimism about the effectiveness of these worksite programs and insights regarding the essential components and characteristics of successful programs.


The identification of Hoxc8 target genes.
Hox genes encode transcription factors that control spatial patterning during embryogenesis. To date, downstream targets of Hox genes have proven difficult to identify. Here, we describe studies designed to identify target genes under the control of the murine transcription factor Hoxc8. We used a mouse 16,463 gene oligonucleotide microarray to identify mRNAs whose expression was altered by the overexpression of Hoxc8 in C57BL/6J mouse embryo fibroblasts (MEF) in cell culture (in vitro). We identified a total of 34 genes whose expression was changed by 2-fold or greater: 16 genes were up-regulated, and 18 genes were down-regulated. The majority of genes encoded proteins involved in critical biological processes, such as cell adhesion, migration, metabolism, apoptosis, and tumorigenesis. Two genes showed high levels of regulation: (i) secreted phosphoprotein 1 (Spp1), also known as osteopontin (OPN), was down-regulated 4.8-fold, and (ii) frizzled homolog 2 (Drosophila) (Fzd2) was up-regulated 4.4-fold. Chromatin immunoprecipitation (ChIP) analysis confirmed the direct interaction between the OPN promoter and Hoxc8 protein in vivo, supporting the view that OPN is a direct transcriptional target of Hoxc8.


Acute progressive paravascular placoid neuroretinopathy with negative-type electroretinography in paraneoplastic retinopathy.
Paraneoplastic retinopathy can be the first manifestation of systemic malignancy. A subset of paraneoplastic retinopathy is characterized by negative-type electroretinography (ERG) without fundus abnormality. Here we describe the multimodal imaging and clinico-pathological correlation of a unique case of acute progressive paravascular placoid neuroretinopathy with suspected retinal depolarizing bipolar cell dysfunction preceding the diagnosis of metastatic small cell carcinoma of the prostate. ERG was performed according to the International Society for Clinical Electrophysiology of Vision standards. Imaging modalities included near-infrared reflectance, blue-light autofluorescence, fluorescein and indocyanine green angiographies, spectral domain optical coherence tomography, ultra-widefield colour and green-light autofluorescence imaging, microperimetry and adaptive optics imaging. Patient serum was screened for anti-retinal antibodies using western blotting. Immunostaining and histological analyses were performed on sections from human retinal tissues and a patient prostate biopsy. Serial multimodal retinal imaging, microperimetry and adaptive optics photography demonstrated a paravascular distribution of placoid lesions characterized by hyper-reflectivity within the outer nuclear layer resembling type 2 acute macular neuroretinopathy. There was no visible lesion within the inner nuclear layer despite electronegative-type ERG. Six months later, the patient presented with metastatic small cell carcinoma of the prostate. Tumour cells were immunopositive for glyceraldehyde-3-phosphate dehydrogenase, enolase and recoverin as well as neuroendocrine markers. The patient's serum reacted to cytoplasmic and nuclear antigens in the prostate biopsy and in human retina. Anti-retinal antibodies against several antigens were detected by both commercial and in-house western blots. A spectrum of autoreactive anti-retinal antibodies is associated with a unique phenotype of acute progressive paravascular placoid neuroretinopathy resulting in degeneration of photoreceptor cells, inner retinal dysfunction and classic electronegative ERG in paraneoplastic retinopathy. Detailed clinical, functional and immunological phenotyping of paraneoplastic retinopathy illustrated the complex mechanism of paraneoplastic syndrome.


Design of adaptive ensemble classifier for online sentiment analysis and opinion mining.
DataStream mining is a challenging task for researchers because of the change in data distribution during classification, known as concept drift. Drift detection algorithms emphasize detecting the drift. The drift detection algorithm needs to be very sensitive to change in data distribution for detecting the maximum number of drifts in the data stream. But highly sensitive drift detectors lead to higher false-positive drift detections. This paper proposed a Drift Detection-based Adaptive Ensemble classifier for sentiment analysis and opinion mining, which uses these false-positive drift detections to benefit and minimize the negative impact of false-positive drift detection signals. The proposed method creates and adds a new classifier to the ensemble whenever a drift happens. A weighting mechanism is implemented, which provides weights to each classifier in the ensemble. The weight of the classifier decides the contribution of each classifier in the final classification results. The experiments are performed using different classification algorithms, and results are evaluated on the accuracy, precision, recall, and F1-measures. The proposed method is also compared with these state-of-the-art methods, OzaBaggingADWINClassifier, Accuracy Weighted Ensemble, Additive Expert Ensemble, Streaming Random Patches, and Adaptive Random Forest Classifier. The results show that the proposed method handles both true positive and false positive drifts efficiently.


Substrata formed by combinations of extracellular matrix components alter neural crest cell motility in vitro.
Extracellular matrix components such as collagen, fibronectin and sulphated glycosaminoglycans can act as substrata that promote neural crest motility in vitro, in the absence of serum. The cells appear to be less adhesive and move more randomly on collagen or chondroitin sulphate substrata than on fibronectin substrata. Cells do not spread or become motile on plastic dishes to which hyaluronate has been bound, presumably owing to weak adhesion to this surface. Hyaluronate added to the medium alone has little effect on cell motility. When combinations of matrix molecules are used as substrata, however, the presence of fibronectin increases spreading, directional persistence of cell motility and speed of movement above that observed on collagen alone. When added to fibronectin, chondroitin sulphate appears to reduce adhesions slightly, since the cells are more rounded. Hyaluronate added in the medium significantly reduces the extent, speed and directionality of movement on fibronectin substrata. The presence of collagen in combination with fibronectin plus glycosaminoglycans does not have a noticeable effect on cell motile behaviour, beyond that observed with fibronectin alone. The effects of combinations of matrix compounds on neural crest cell motility are thus predictable, and can be explained in terms of the known adhesive properties and reported binding interactions of these molecules. These studies in vitro are compared with neural crest cell motility in vivo.


Colonization, diversity, and seasonality of fishes at pelagic fish aggregating devices.
The pelagic zone of the ocean can be a challenging environment in which to conduct research and as a result we lack the robust baseline abundance and diversity data, compared to what is available in more accessible coastal habitats, to be able to track changes or stressors to the biota in this environment. Many large-scale fisheries target pelagic fish, and much of the information available on these species is based on fisheries-dependent data that may be biased towards hotspots and commercially valuable fishes. Here, a long-term video and visual fish survey was conducted on two subsurface moored fish aggregating devices (FADs) in the pelagic waters of the central Bahamas to determine the feasibility of using moored pelagic FADs as tools for collecting fish abundance and diversity data. A wide range of species was documented, including large migratory fish that are the focus of commercial and recreational fisheries, and smaller often overlooked species on which little abundance or seasonality information exists. We found that FADs colonize quickly and reach a peak stable (albeit seasonally cyclical) abundance and diversity within the first several months after deployment. Species richness was higher in video surveys, but abundance was higher in visual surveys, except for sharks. Our results highlight the need to tailor survey methods to fit the context and study objective, and provide further evidence for the importance of fisheries-independent data in monitoring pelagic species.


Corneal Biomechanics for Ocular Hypertension, Primary Open-Angle Glaucoma, and Amyloidotic Glaucoma: A Comparative Study by Corvis ST.
To evaluate biomechanical parameters of the cornea provided by Corvis ST in patients with ocular hypertension, primary open-angle glaucoma, and amyloidotic glaucoma and to compare with healthy controls. This was a cross-sectional study of patients with ocular hypertension, primary open-angle glaucoma, and amyloidotic glaucoma that underwent Corvis ST imaging. Primary outcome was the comparison of corneal biomechanical parameters between study groups after adjusting for age, gender, Goldmann intraocular pressure (GAT-IOP), and prostaglandin analogues medication. Secondary outcome was the comparison of different IOP measurements in each group. One hundred and eighty-three eyes from 115 patients were included: 61 with primary open-angle glaucoma, 32 with amyloidotic glaucoma, 37 with ocular hypertension and 53 were healthy controls. Amyloidotic glaucoma group had smaller radius (p=0.025), lower deflection amplitude at highest concavity (p=0.019), and higher integrated radius (p=0.014) than controls. Ocular hypertension group had higher stiffness parameter at first applanation (p=0.043) than those with primary open-angle glaucoma, and higher stress-strain index (p=0.049) than those with amyloidotic glaucoma. Biomechanically corrected intraocular pressure was significantly lower than Goldmann intraocular pressure in group with primary open-angle glaucoma (p=0.005) and control group (p=0.013), and Goldmann intraocular pressure adjusted for pachymetry in group with primary open-angle glaucoma (p=0.01). Eyes with amyloidotic glaucoma have more deformable corneas, while eyes with ocular hypertension have less deformable corneas. These findings may be linked to the susceptibility to glaucomatous damage and progression. There were significant differences between Goldmann applanation tonometry and biomechanically corrected intraocular ocular pressure provided by Corvis ST.


Cytomegalovirus infection in burns: a review.
Sepsis is responsible for significant morbidity and mortality in patients suffering from severe burn injuries. Burn patients are known to be immunocompromised, and it is generally accepted that the immunosuppressed patient may experience human cytomegalovirus (HCMV) infection and disease. Review of the very limited available literature identifies a seroconversion rate of between 18 and 22% for burn patients who were seronegative for HCMV prior to suffering their burn injury. Furthermore, approximately 50% of HCMV antibody-positive patients may reactivate. Blood products and allografted skin have clinically been identified as possible sources of HCMV transmission in burn patients. Experience in the treatment of infection or disease in burn patients is very scarce and limited to immunoglobulin therapy. Animal experiments have demonstrated that murine cytomegalovirus (MCMV)-seropositive skin grafts are able to infect immunodeficient mice as well as burned mice. Murine studies have also demonstrated that infection with MCMV enhances susceptibility to secondary bacterial infection and increases mortality in these animals. Burned mice challenged with MCMV have a significantly higher level of bacterial translocation to mesenteric lymph nodes than either control thermally injured mice without MCMV inoculation or non-burned mice injected with MCMV alone. In summary, it remains controversial whether HCMV infection per se alters outcome for the majority of burn patients. Subgroups of severely burned, seronegative patients may benefit from blood products and skin from seronegative donors. Antiviral strategies are not yet evaluated for the burn patient. Further investigations utilizing modern diagnostic techniques seem necessary.


Chemerin is a novel adipokine associated with obesity and metabolic syndrome.
Soluble protein hormones are key regulators of a number of metabolic processes, including food intake and insulin sensitivity. We have used a signal sequence trap to identify genes that encode secreted or membrane-bound proteins in Psammomys obesus, an animal model of obesity and type 2 diabetes (T2D). Using this signal sequence trap, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), was significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared with lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes, whereas CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation, whereas CMKLR1 was down-regulated during differentiation. Serum chemerin levels were measured by ELISA in human plasma samples from 114 subjects with T2D and 142 normal glucose tolerant controls. Plasma chemerin levels were not significantly different between subjects with T2D and normal controls. However, in normal glucose tolerant subjects, plasma chemerin levels were significantly associated with body mass index, circulating triglycerides, and blood pressure. Here we report, for the first time, that chemerin is an adipokine, and circulating levels of chemerin are associated with several key aspects of metabolic syndrome.


Spine update. The management of scoliosis in neurofibromatosis.
When evaluating patients with neurofibromatosis and scoliosis, a careful search for the evidence of dystrophic changes should done, because prognosis and management depend highly on the presence of these changes. Preoperative imaging studies including computed tomography or magnetic resonance imaging are recommended, especially in cases of dystrophic scoliosis, to detect unrecognized intraspinal lesions. The radiographic findings and the response to treatment in patients with nondystrophic scoliosis are similar to those in patients with idiopathic scoliosis, and the same decision-making process for idiopathic scoliosis is applicable. Careful follow-up evaluation is mandatory, however, because of the tendency for extraordinary progression to occur with growth. Brace treatment of the short, angulated, dystrophic curves is ineffective; early and aggressive surgical intervention is strongly recommended. In most cases, dystrophic curvatures are best treated with combined anterior and posterior spinal arthrodesis. The fusion area should be generous, and the entire structural area of the deformity both anteriorly and posteriorly should be fused.


Efficacy and safety of traction-assisted endoscopic submucosal dissection: a meta-regression of randomized clinical trials.
Endoscopic submucosal dissection (ESD) is widely used to treat gastrointestinal lesions. A traction-assisted (TA) strategy has been recently developed for ESD. In this study, we evaluated the safety and efficacy of TA-ESD compared with conventional ESD (C-ESD). We searched PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure to identify randomized clinical trials that compared TA-ESD and C-ESD. No filters for language or date of publication were used. Outcomes included complete resection rate, resected specimen size, procedure time, hemostasis usage (frequency), overall complication rate, perforation rate, and delayed bleeding rate. We used the mean difference (MD) for continuous outcomes in a random-effects model and Peto odds ratio (POR) for binary outcomes where any zero cell existed. Effect sizes and their 95 % confidence intervals (CIs) were determined. 12 out of 929 identified articles, including 1499 patients, were analyzed. According to pooled results, TA-ESD produced similar R0 resections to C-ESD, but its procedure time (minutes) was shorter than that of C-ESD (MD - 16.02, 95 %CI - 22.71 to - 9.33). Moreover, TA-ESD had a lower complication rate (POR 0.47, 95 %CI 0.29 to 0.76) and perforation rate (POR 0.24, 95 %CI 0.10 to 0.56) than C-ESD. A nonsignificant difference in delayed bleeding rate was observed, although there was a trend toward this being lower in TA-ESD than C-ESD (POR 0.90, 95 %CI 0.46 to 1.75, I 2 = 12 %). The traction-assisted strategy improves safety and efficacy in the treatment of patients with ESD. However, we observed different effect sizes in the esophagus, stomach, and colorectum.


Triplex addressability as a basis for functional DNA nanostructures.
Here, we present the formation of a fully addressable DNA nanostructure that shows the potential to be exploited as, for example, an information storage device based on pH-driven triplex strand formation or nanoscale circuits based on electron transfer. The nanostructure is composed of two adjacent hexagonal unit cells (analogous to naphthalene) in which each of the eleven edges has a unique double-stranded DNA sequence, constructed using novel three-way oligonucleotides. This allows each ten base-pair side, just 3.4 nm in length, to be assigned a specific address according to its sequence. Such constructs are therefore an ideal precursor to a nonrepetitive two-dimensional grid on which the "addresses" are located at a precise and known position. Triplex recognition of these addresses could function as a simple yet efficient means of information storage and retrieval. Future applications that may be envisaged include nanoscale circuits as well as subnanometer precision in nanoparticle templating. Characterization of these precursor nanostructures and their reversible targeting by triplex strand formation is shown here using gel electrophoresis, atomic force microscopy, and fluorescence resonance energy transfer (FRET) measurements. The durability of the system to repeated cycling of pH switching is also confirmed by the FRET studies.


Blood N-terminal proBNP as a potential indicator of cardiac preload in patients with high volume load.
Stroke volume is mainly determined by preload, afterload and contractility. Accordingly, measuring cardiac preload provides essential information for treatment of hemodynamically unstable patients. Hemodynamic monitoring is widely used to measure cardiac preload, but the monitoring method is time-consuming and invasive. It is therefore important to establish a simple and non-invasive test for monitoring cardiac preload. Brain natriuretic peptide (BNP), which lowers systemic vascular resistance, is synthesized as proBNP in response to myocardial wall stretch, and blood BNP has been used as an indicator of preload. Here, we measured blood level of N-terminal proBNP (NT-proBNP), which is generated during processing of proBNP, because NT-proBNP is stable and easily measured at the bedside. To assess the correlation between blood NT-proBNP and preload, we also measured the global end-diastolic volume index (GEDVI) that reflects the cardiac preload. GEDVI was calculated with the volumes in all chambers of the heart at the time of end-diastole. Eight male patients (57.6 +/- 25.3 years old) with high volume load (1,000 ml within 4 hours) were included in the present study: 3 subjects with burn, 3 subjects with sepsis, a patient with alcoholic ketoacidosis and a resuscitated patient. Blood levels of NT-proBNP were 1,316.3 +/- 1,154.5 pg/ml (47 blood samples from the eight patients; the normal range, < 125 pg/ml). Notably, the increase in the NT-proBNP levels was associated with the increased GEDVI (r = 0.61, p < 0.0001). Therefore, blood NT-proBNP may be a good indicator of cardiac preload in patients with high volume load.