Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Protective effects of ascorbic acid.
Cigarette smoke (CS) is known to contain a large number of oxidants. In order to assess the oxidative effects of CS on biological fluids, we exposed human blood plasma to filtered (gas phase) and unfiltered (whole) CS, and determined the rate of utilization of endogenous antioxidants in relation to the appearance of lipid hydroperoxides. Lipid peroxidation was measured with a specific and sensitive assay that can detect lipid hydroperoxides at plasma levels as low as 10 nM. We found that exposure of plasma to the gas phase of CS, but not to whole CS, induces lipid peroxidation once endogenous ascorbic acid has been oxidized completely. In addition, CS exposure caused oxidation of plasma protein thiols and albumin-bound bilirubin, whereas uric acid and alpha-tocopherol were not consumed at significant rates. In plasma exposed to the gas phase of CS, low-density lipoprotein exhibited slightly increased electrophoretic mobility, but there was no apparent degradation of apolipoprotein B. Our results support the concept of an increased vitamin C utilization in smokers, and suggest that lipid peroxidation induced by oxidants present in the gas phase of CS leads to potentially atherogenic changes in lipoproteins.


Manual or electroacupuncture as an add-on therapy to SSRIs for depression: A randomized controlled trial.
Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants, however, only around 60% of patients could benefit from them. Acupuncture is supported by insufficient evidence to help with symptom relieving and SSRIs tolerance. This pragmatic randomized controlled trial compared SSRIs alone versus SSRIs together with manual acupuncture (MA) or electroacupuncture (EA) in moderate to severe depressed patients. Patients were randomly allocated to receive MA + SSRIs (161), EA + SSRIs (160), or SSRIs alone (156) for six weeks, and then followed up for another four weeks. The primary outcome was response rate of the 17-item Hamilton Depression Scale (HAMD-17) at 6th week. The secondary outcomes were HAMD-17 (remission rate, early onset rate, total score), Self-Rating Depression Scale (SDS: total score), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS: total and domain scores), number of patients with adjusted dosage of SSRIs and adverse events (AEs). Both MA + SSRIs and EA + SSRIs were significantly better than SSRIs at 6th week on HAMD-17 response rate (RR = 1.21, 95% CI 1.04, 1.42, P = 0.013; RR = 1.27, 95% CI 1.09, 1.48, P = 0.0014), HAMD-17 early onset rate (P < 0.0001), HAMD-17 and SDS total scores (P < 0.05), CGI (P < 0.01), SERS total score (P < 0.01), number of patients with increased dosage of SSRIs (P < 0.01). For HAMD-17 remission rate, EA + SSRIs was significantly higher than SSRIs (P = 0.0083), while MA + SSRIs showed no significant difference at 6th week (P = 0.092). No unintended acupuncture-related severe AE was observed. This study identified that both MA and EA showed beneficial effects in addition to SSRIs alone in patients with moderate to severe depression, and were well tolerated. Clinical trials registration: ChiCTR-TRC-08000297.


Listeriolysin O activates mitogen-activated protein kinase in eucaryotic cells.
Infection with Listeria monocytogenes induces the activation of mitogen-activated protein (MAP) kinase in several tissue culture cell lines (P.Tang, I. Rosenshine, and B. B. Finlay, Mol. Biol. Cell 5:455-464, 1994). After various mutants were examined, the bacterial factor responsible for MAP kinase activation was identified as listeriolysin O (LLO). Growth supernatant containing LLO or purified LLO alone can induce MAP kinase tyrosine phosphorylation in HeLa cells. Single-amino-acid mutations in LLO that do not affect its membrane binding capacity but reduce its cytolytic activity also reduced its ability to induce MAP kinase activity in HeLa cells. Streptolysin O, another sulfhydryl-activated hemolysin, and the detergent saponin are also able to activate MAP kinase in target cells. Thus, the increased MAP kinase activity observed in L. monocytogenes-infected cells is most likely a result of the permeabilization of the host cell membrane by LLO and may not be linked with invasion.


Effect of thrombolytic therapy on platelet expression and plasma concentration of PECAM-1 (CD31) in patients with acute myocardial infarction.
Animal studies have shown that the administration of antibodies against platelet/endothelial cell adhesion molecule-1 (PECAM-1) before reperfusion can reduce infarct size. The purpose of the present study was to define the effects of thrombolytic therapy in acute myocardial infarction (AMI) patients on the platelet expression and plasma concentrations of PECAM-1 at prespecified time points after attempted reperfusion. The plasma concentration and platelet expression of PECAM-1 were determined in 23 AMI patients enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III) trial before thrombolysis and at 3, 6, 12, and 24 hours thereafter and compared with 22 healthy controls. At baseline, PECAM-1 was expressed significantly more on the platelet surface in the AMI patients than in controls (P=0.027) while soluble PECAM-1 plasma levels were almost identical between groups. There were no significant diurnal variations in both plasma and platelet PECAM-1 levels in controls. A significant decrease in platelet PECAM-1 expression was observed 3 hours after thrombolysis (P=0.03) compared with baseline, followed by a significant increase (P=0.004) in fluorescence intensity later at 24 hours after thrombolysis. Conversely, a significant increase in soluble PECAM-1 was observed 3 hours after thrombolysis (P=0.02), followed by a significant decrease later at 24 hours after attempted reperfusion (P=0.03). The expression of platelet-bound PECAM-1 is increased in AMI patients. Discordantly directed changes in soluble and platelet PECAM-1 after the first 24 hours after thrombolytic therapy may represent redistribution of the whole PECAM-1 pool. Further investigation of the possible role of PECAM-1 and the relationship between its soluble and platelet fractions in AMI are warranted.


Characterization of the bovine salivary gland transcriptome associated with Mycobacterium avium subsp. paratuberculosis experimental challenge.
Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of Johne's disease is spread between cattle via the fecal-oral route, yet the functional changes in the salivary gland associated with infection remain uncharacterized. In this study, we hypothesized that experimental challenge with MAP would induce stable changes in gene expression patterns in the salivary gland that may shed light on the mucosal immune response as well as the regional variation in immune capacity of this extensive gland. Holstein-Friesian cattle were euthanized 33 months' post oral challenge with MAP strain CIT003 and both the parotid and mandibular salivary glands were collected from healthy control (n = 5) and MAP exposed cattle (n = 5) for histopathological and transcriptomic analysis. A total of 205, 21, 61, and 135 genes were significantly differentially expressed between control and MAP exposed cattle in dorsal mandibular (M1), ventral mandibular (M2), dorsal parotid (P1) and ventral parotid salivary glands (P2), respectively. Expression profiles varied between the structurally divergent parotid and mandibular gland sections which was also reflected in the enriched biological pathways identified. Changes in gene expression associated with MAP exposure were detected with significantly elevated expression of BoLA DR-ALPHA, BOLA-DRB3 and complement factors in MAP exposed cattle. In contrast, reduced expression of genes such as polymeric immunoglobin receptor (PIGR), TNFSF13, and the antimicrobial genes lactoferrin (LF) and lactoperoxidase (LPO) was detected in MAP exposed animals. This first analysis of the transcriptomic profile of salivary glands in cattle adds an important layer to our understanding of salivary gland immune function. Transcriptomic changes associated with MAP exposure have been identified including reduced LF and LPO. These critical antimicrobial and immunoregulatory proteins are known to be secreted into saliva and their downregulation may contribute to disease susceptibility. Future work will focus on the validation of their expression levels in saliva from additional cattle of known infection status as a potential strategy to augment disease diagnosis.


Comparison of semi-quantitative endotracheal aspirates to quantitative non-bronchoscopic bronchoalveolar lavage in diagnosing ventilator-associated pneumonia.
Current strategies for diagnosing ventilator-associated pneumonia (VAP) favor the use of quantitative methods; however, semi-quantitative cultures of endotracheal aspirates are still commonly used. The microbiological results of patients with suspected VAP who had both quantitative cultures with non-bronchoscopic bronchoalveolar lavage (BAL) and semi-quantitative cultures of endotracheal aspirate obtained within 24 hours of each other were retrospectively reviewed and compared, using a quantitative threshold of >or=10(4) colony-forming units/mL as a reference standard. 256 patients with paired cultures were identified. Concordance between endotracheal aspirate (any growth of pathogens) and non-bronchoscopic BAL was complete in 58.2% and completely discordant in 23.8%. The sensitivity and specificity of endotracheal aspirate were 65.4% and 56.1%, which improved to 81.2% and 61.9% when antibiotic management decisions were considered in the analysis. Twenty-six patients had endotracheal aspirate cultures that were falsely negative for pathogens, with 61.5% of these patients demonstrating growth of non-fermenting Gram-negative rods or methicillin-resistant Staphylococcus aureus (MRSA) on non-bronchoscopic BAL. Overall, 45 patients (17.5%) among the entire cohort had false positive endotracheal aspirate cultures, with 19 of these patients (42.2%) demonstrating growth of non-fermenting Gram-negative rods or MRSA. Semi-quantitative cultures of endotracheal aspirate are poorly concordant with quantitative cultures obtained via non-bronchoscopic BAL. Although the performance of endotracheal aspirate improves when antibiotic treatment is considered, guiding therapy on the basis of semi-quantitative cultures may still result in failure to identify potentially multiple-drug-resistant pathogens, and would also tend to promote excessive antibiotic usage. Our data support the use of quantitative cultures in diagnosing VAP.


The regulation of human globin gene expression.
The haemopoietic system provides a well-characterized and accessible system for studying the mechanisms of developmental regulation and differentiation in higher eukaryotes. Our current understanding of the steps involved in the early stages of differentiation are poorly understood but a great deal is now known about the mechanisms by which globin expression is regulated in cells committed to the erythroid lineage. Many of the critical cis-acting sequences and some of the important trans-acting factors involved have been identified and current work is focusing on how these interact to produce high levels of tissue-specific and developmentally regulated expression of the human globin genes.


Low genetic diversity in Melanaphis sacchari aphid populations at the worldwide scale.
Numerous studies have examined the genetic diversity and genetic structure of invading species, with contrasting results concerning the relative roles of genetic diversity and phenotypic plasticity in the success of introduced populations. Increasing evidence shows that asexual lineages of aphids are able to occupy a wide geographical and ecological range of habitats despite low genetic diversity. The anholocyclic aphid Melanaphis sacchari is a pest of sugarcane and sorghum which originated in the old world, was introduced into the Americas, and is now distributed worldwide. Our purpose was to assess the genetic diversity and structuring of populations of this species according to host and locality. We used 10 microsatellite markers to genotype 1333 individuals (57 samples, 42 localities, 15 countries) collected mainly on sugarcane or sorghum. Five multilocus lineages (MLL) were defined, grouping multilocus genotypes (MLG) differing by only a few mutations or scoring errors. Analysis of a 658 bp sequence of mitochondrial COI gene on 96 individuals revealed five haplotypes, with a mean divergence of only 0.19 %. The distribution of MLL appeared to be strongly influenced by geography but not by host plant. Each of the five MLL grouped individuals from (A) Africa, (B) Australia, (C) South America, the Caribbean and the Indian Ocean including East Africa, (D) USA, and (E) China. The MLL A and C, with a wide geographic distribution, matched the definition of superclone. Among aphids, M. sacchari has one of the lowest known rates of genetic diversity for such a wide geographical distribution.


Effects of double-dose statin therapy for the prevention of post-stroke epilepsy: A prospective clinical study.
To determine treatment effects on the incidence of post-stroke epilepsy (PSE) using different doses of statin, a prospective hospital-based cohort study was designed to explore whether a double-dose statin treatment can better prevent the occurrence of PSE. A total of 1152 patients with newly diagnosed ischemic stroke admitted to our hospital from March to August 2017 were selected, 1033 of whom were followed-up. Patients were divided into two treatment groups:(1) standard-dose (20 mg atorvastatin or 10 mg rosuvastatin,daily oral; 788 patients); and (2) double-dose (40 mg atorvastatin or 20 mg rosuvastatin, daily oral; 245 patients).At 18 months follow-up was conducted to compare the incidence of PSE between groups. In general, in the standard-dose group we observed two cases of early seizure (ES) (0.25%), 22 cases oflate seizure (LS) (2.79%) and 20 cases of PSE (2.54%). In the double-dose group, onepatient had ES (0.41%), two patients had LS (0.82%), and onepatient had PSE (0.41%). The incidence of PSE was significantly lower in the double-dose group as compared to the standard-dose group. There was a higher proportion of PSE in patients younger than 65 years and in males. Three patients had ES; one presented with focal aware seizure (FAS), and two had focal to bilateral tonic-clonic seizure (FBTCS). Among the 21 patients with PSE, there were two cases of FAS, five cases of focal impaired awareness seizure (FIAS), five cases of FBTCS, and nine cases of GTCS, suggesting that partial seizure is the most common type of PSE. Cerebral cortex was involved in 85.75% of cases with PSE, and multiple lobes were involved in 61.9% of cases with PSE. Increasing the dose of statin treatment during the acute phase of ischemic stroke reduces the incidence of PSE. Further research is needed to understand the mechanisms underlying the potential preventative effects of statins against PSE.


Swiss Canine Cancer Registry 1955-2008: Occurrence of the Most Common Tumour Diagnoses and Influence of Age, Breed, Body Size, Sex and Neutering Status on Tumour Development.
This study is based on the Swiss Canine Cancer Registry, comprising 121,963 diagnostic records of dogs compiled between 1955 and 2008, in which 63,214 (51.83%) animals were diagnosed with tumour lesions through microscopical investigation. Adenoma/adenocarcinoma (n = 12,293, 18.09%) was the most frequent tumour diagnosis. Other common tumour diagnoses were: mast cell tumour (n = 4,415, 6.50%), lymphoma (n = 2,955, 4.35%), melanocytic tumours (n = 2,466, 3.63%), fibroma/fibrosarcoma (n = 2,309, 3.40%), haemangioma/haemangiosarcoma (n = 1,904, 2.80%), squamous cell carcinoma (n = 1,324, 1.95%) and osteoma/osteosarcoma (n = 842, 1.24%). The relative occurrence over time and the most common body locations of those tumour diagnoses are presented. Analyses of the influence of age, breed, body size, sex and neutering status on tumour development were carried out using multiple logistic regression. In certain breeds/breed categories the odds ratios (ORs) for particular tumours were outstandingly high: the boxer had higher ORs for mast cell tumour and haemangioma/haemangiosarcoma, as did the shepherd group for haemangioma/haemangiosarcoma, the schnauzer for squamous cell carcinoma and the rottweiler for osteoma/osteosarcoma. In small dogs, the risk of developing mammary tumours was three times higher than in large dogs. However, small dogs were less likely to be affected by many other tumour types (e.g. tumours of the skeletal system). Examination of the influence of sex and neutering status on tumour prevalence showed that the results depend on the examination method. In all sampling groups the risk for female dogs of developing adenoma/adenocarcinoma was higher than for male dogs. Females had a lower risk of developing haemangioma/haemangiosarcoma and squamous cell carcinoma than males. Neutered animals were at higher risk of developing specific tumours outside the genital organs than intact animals. The sample size allows detailed insight into the influences of age, breed, body size, sex and neutering status on canine tumour development. In many cases, the analysis confirms the findings of other authors. In some cases, the results are unique or contradict other studies, implying that further investigations are necessary.


Toward understanding evidence uptake: semirecumbency for pneumonia prevention.
Randomized trials show that the semirecumbent position compared with the supine position is associated with less gastroesophageal aspiration and pneumonia in patients receiving mechanical ventilation. However, semirecumbency is inconsistently used in practice. The objective of this study was to understand the perspectives of intensive care unit clinicians regarding the determinants and consequences of semirecumbency. Qualitative study using semistructured interviews and focus groups. Three university-affiliated intensive care units. A total of 93 intensive care unit clinicians, including bedside nurses, respiratory therapists, physiotherapists, nutritionists, residents, fellows, and intensivists. We elicited perceptions about benefits and harms of semirecumbency, factors promoting and deterring use, and health systems changes to encourage semirecumbency. Interview and focus group notes were analyzed inductively to identify emerging themes. Validation methods involved triangulation by multidisciplinary analysis of several data sources collected through multiple methods and member checking. Intensivists and nutritionists were familiar with semirecumbency as a potential pneumonia prevention strategy, whereas other clinicians were not. When made aware of the evidence, all participants endorsed semirecumbency. Nurses perceived that the main determinant of semirecumbency was physicians' orders, whereas intensivists perceived that the main determinant was nursing preference. Participants identified barriers to semirecumbency related to useful alternative positions (e.g., lateral position), contraindications (e.g., hemodynamic instability), risk of harm (e.g., decubitus ulcers), safety (e.g., sliding out of the bed), and resources (e.g., insufficient beds facilitating semirecumbency). Education, guidelines, reminders, audit and feedback, charting, and quality improvement initiatives were advocated to promote semirecumbency. Under-utilization of semirecumbency for pneumonia prevention is influenced by insufficient awareness of its benefit, real and perceived deterrents, poor agreement about implementation responsibility, and lack of enabling and reinforcing strategies. Cognitive, behavioral, and administrative approaches to enhancing evidence uptake may be needed in the complex, dynamic intensive care unit setting.


Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis.
Although several genes involved in mitochondrial function are direct Myc targets, the role of Myc in mitochondrial biogenesis has not been directly established. We determined the effects of ectopic Myc expression or the loss of Myc on mitochondrial biogenesis. Induction of Myc in P493-6 cells resulted in increased oxygen consumption and mitochondrial mass and function. Conversely, compared to wild-type Myc fibroblasts, Myc null rat fibroblasts have diminished mitochondrial mass and decreased number of normal mitochondria. Reconstitution of Myc expression in Myc null fibroblasts partially restored mitochondrial mass and function and normal-appearing mitochondria. Concordantly, we also observed in primary hepatocytes that acute deletion of floxed murine Myc by Cre recombinase resulted in diminished mitochondrial mass in primary hepatocytes. Our microarray analysis of genes responsive to Myc in human P493-6 B lymphocytes supports a role for Myc in mitochondrial biogenesis, since genes involved in mitochondrial structure and function are overrepresented among the Myc-induced genes. In addition to the known direct binding of Myc to many genes involved in mitochondrial structure and function, we found that Myc binds the TFAM gene, which encodes a key transcriptional regulator and mitochondrial DNA replication factor, both in P493-6 lymphocytes with high ectopic MYC expression and in serum-stimulated primary human 2091 fibroblasts with induced endogenous MYC. These observations support a pivotal role for Myc in regulating mitochondrial biogenesis.


Detection of human glioma-associated antigen by rat monoclonal antibody raised against syngeneic rat glioma cells.
A monoclonal antibody termed "FR77" was obtained from a hybridoma clone established by fusion between P3x63Ag8.653 mouse myeloma cells and spleen cells of a Fischer F344 rat hyperimmune to syngeneic 9L/R3 glioma cells. Immunoperoxidase staining of various cultured cells showed that FR77 was reactive to both rat and human glioma cells, but was not reactive with other nonglioma cells. Immunohistochemical examination of paraffin-embedded or cryostat-frozen sections of various human tissues revealed that FR77 was strongly reactive with glioblastoma, grade III astrocytoma, and craniopharyngioma; partially reactive with intracerebral primitive neuroectodermal tumor, pineoblastoma, and desmoplastic medulloblastoma; and weakly reactive with low-grade astrocytoma. It was not reactive with other types of brain tumors and normal human tissues tested. The FR77-defined antigen was observed to be predominantly localized in the cytoplasm of antigen-bearing cells as suggested by the immunostaining pattern, but part of it was also expressed on the cell surface of glioma cells as demonstrated by a complement-mediated cytotoxic test. Fractionation of the antigenic component and periodic acid treatment of tumor tissue bearing the FR77-defined antigen indicated that the antigen is of a neutral glycolipid nature and that the antigenic determinant to FR77 is present on its sugar portion.


Transgene-free disease-specific induced pluripotent stem cells from patients with type 1 and type 2 diabetes.
The induced pluripotent stem cell (iPSC) technology enables derivation of patient-specific pluripotent stem cells from adult somatic cells without using an embryonic cell source. Redifferentiation of iPSCs from diabetic patients into pancreatic islets will allow patient-specific disease modeling and autologous cell replacement therapy for failing islets. To date, diabetes-specific iPSCs have been generated from patients with type 1 diabetes using integrating retroviral vectors. However, vector integration into the host genome could compromise the biosafety and differentiation propensities of derived iPSCs. Although various integration-free reprogramming systems have been described, their utility to reprogram somatic cells from patients remains largely undetermined. Here, we used nonintegrating Sendai viral vectors to reprogram cells from patients with type 1 and type 2 diabetes (T2D). Sendai vector infection led to reproducible generation of genomic modification-free iPSCs (SV-iPSCs) from patients with diabetes, including an 85-year-old individual with T2D. SV-iPSCs lost the Sendai viral genome and antigens within 8-12 passages while maintaining pluripotency. Genome-wide transcriptome analysis of SV-iPSCs revealed induction of endogenous pluripotency genes and downregulation of genes involved in the oxidative stress response and the INK4/ARF pathways, including p16(INK4a), p15(INK4b), and p21(CIP1). SV-iPSCs and iPSCs made with integrating lentiviral vectors demonstrated remarkable similarities in global gene expression profiles. Thus, the Sendai vector system facilitates reliable reprogramming of patient cells into transgene-free iPSCs, providing a pluripotent platform for personalized diagnostic and therapeutic approaches for diabetes and diabetes-associated complications.


Tempol suppresses micronuclei formation in astrocytes of newborn rats exposed to 50-Hz, 10-mT electromagnetic fields under bleomycin administration.
A number of epidemiological studies have suggested that exposure to environmental and occupational electromagnetic fields (EMFs) contribute to the induction of brain tumors. The aim of this study was to investigate the mutagenetic effects of co-exposure to 50-Hz, 10-mT EMFs and bleomycin (BLM) using an ex vivo newborn rat astrocyte micronucleus assay. We also investigated whether the mutagenetic effects of EMFs were related to active oxygen species by using 4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl (tempol), a superoxide radical scavenger. Three-day-old male Sprague-Dawley rats were co-exposed to 50-Hz EMFs and BLM (5 or 10mg/kg body weight (BW)) in each group (n=6; total 6 group), and were co-exposed to 50-Hz EMFs and 10mg/kg BW BLM with administration of 200μmol/kg BW tempol in each group (total 4 group). Brain cells were dissociated into single cells, cultured for 96h, incubated with an antibody against glial fibrillary acidic protein, and stained with acridine orange. The frequency of micronucleated astrocytes was determined using a fluorescence microscope. The frequency of micronucleated astrocytes in the 10mg/kg BW bleomycin plus EMF exposure group (Mean±SD: 19.8±5.2‰) was 1.6 times higher than that in the 10mg/kg BW bleomycin plus sham-exposure group (Mean±SD: 12.7±3.3‰) (p<0.05). Analysis of the frequency of micronuclei in astrocytes after co-exposure to EMF and bleomycin for 72h and administration of tempol revealed that, in the EMF exposure group, the frequency of micronuclei in rats administered with 10mg/kg BW bleomycin and treated with tempol (Mean±SD: 11.2±1.9‰) was 40% of that in rats administered with the same dose of bleomycin and physiological saline (Mean±SD: 28.0±15.0‰) (p<0.01). Results of the current study suggested that the mechanism responsible for the elevated frequency of micronuclei in astrocytes of rats co-exposed to BLM and EMFs is related to active oxygen species.


The Forgotten Responders: The Ongoing Impact of 9/11 on the Ground Zero Recovery Workers.
In the years following the September 11, 2001 terrorist attacks (9/11; New York USA), emergency first responders began experiencing a range of physical health and psychosocial impacts. Publications documenting these tended to focus on firefighters, while emerging reports are starting to focus on other first responders, including paramedics, emergency medical technicians (EMTs), and police. The objective of this research was to explore the long-term impact on another important group of 9/11 responders, the non-emergency recovery workers who responded to the World Trade Center (WTC) site of the 9/11 terrorist attacks. In the 16 years following 9/11, Ground Zero recovery workers have been plagued by a range of long-term physical impacts, including musculoskeletal injuries, repetitive motion injuries, gait deterioration, and respiratory disorders. Psychosocial issues include posttraumatic stress disorder, anxiety, depression, insomnia, support system fatigue, and addictive and risk-taking behaviors. These findings go some way to filling the current gap in the understanding on the long-term impact of 9/11 and to provide an important testimony of the "forgotten responders" - the Ground Zero recovery workers. SmithEC BurkleFMJr. The forgotten responders: the ongoing impact of 9/11 on the Ground Zero recovery workers. Prehosp Disaster Med. 2018;33(4):436-440.


Evaluation of radioprotective effects of propolis and its flavonoid constituents: in vitro study on human white blood cells.
This in vitro study aimed to evaluate the possible radioprotective effects of the natural substances WSDP, caffeic acid, chrysin and naringin on gamma-irradiated human white blood cells. The effectiveness of tested compounds was evaluated using the alkaline comet assay, the analysis of structural chromosome aberration and the cytokinesis-block micronucleus assay. The results obtained by the alkaline comet study indicate favourable toxicity profiles of propolis and its polyphenolic components, and confirmed the radioprotective abilities comparable to the chemical radioprotector AET. WSDP and its polyphenolic components were able to reduce the number of necrotic cells. None of tested compounds induced significant genotoxicity, but all of them offered a quite measurable protection against DNA damage. WSDP was found to be the most effective in diminishing the levels of primary and more complex cytogenetic DNA damage in white blood cells. Considering its complex composition, to undoubtedly explain the underlying mechanisms of cyto/radioprotective effects, further studies are needed.


Dietary supplementation of krill oil attenuates inflammation and oxidative stress in experimental ulcerative colitis in rats.
To evaluate the effects of krill oil (KO) on inflammation and redox status in dextran sulfate sodium (DSS)-induced colitis in rats. Thirty male Wistar rats were divided into three groups: Control, DSS, and DSS + KO 5% in a 4-week diet study. Colitis was induced by 5% DSS in the drinking water the last week of the experiment. Weight and disease activity index (DAI), colon length, histological combined score (HCS), colon levels of selected cytokines and prostaglandins, markers of protein oxidative damage, fatty acid profile, and expression of selected genes were measured. Rats in the DSS group increased their DAI and HCS compared with healthy controls. The colon length was significantly preserved after KO diet. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β were elevated in the DSS group compared with controls. Cytokines and HCS were nonsignificantly lower in the KO versus the DSS group. Prostaglandin (PG)E(3) increased significantly in the KO versus the other groups. Peroxisome proliferator-activated receptor (PPAR)-γ expression was nonsignificantly increased while PPAR-γ coactivator 1α (Pparg1α) expression increased significantly after KO. The levels of protein oxidation markers decreased significantly. KO showed protective potential against DSS colitis based on the preservation of colon length, reduction of oxidative markers and the consistent beneficial changes of HCS, cytokine, and (PG)E(3) levels, as well as PPAR-γ and Pparg1α expression compared with DSS alone. These findings indicate an anti-inflammatory and a protein antioxidant effect of KO.


Unspecific abdominal symptoms and pneumobilia: a rare case of gastrointestinal obstruction.
The case of a 77-year-old woman with symptoms of gastric outlet obstruction is presented. Transabdominal ultrasonography findings were suspicious of Bouveret's syndrome. Upper endoscopy confirmed this diagnosis. Bouveret's syndrome is a rare complication of gallstone disease caused by a bilioenteric fistula leading to gastric outlet obstruction by a gallstone and should be suspected in any patient who presents with pneumobilia without recent endoscopic retrograde cholangiopancreatography or biliary surgery.


A Framework for Integrating Oncology Palliative Care in Doctor of Nursing Practice (DNP) Education.
Doctor of Nursing Practice (DNP) faculty play a critical role in preparing students to meet the complex needs of the nation as the number of cancer rates and survivors rise (National Cancer Institute, 2018) and as an unprecedented number of older Americans enter into the healthcare system with complicated comorbidities (Whitehead, 2016). Palliative care has dramatically expanded over the past decade and has been increasingly accepted as a standard of care for people with cancer and other serious, chronic, or life-limiting illnesses. Advanced practice registered nurses (APRNs) are recognized as important providers of palliative care (Walling et al., 2017). A 2-day course was held with support from the National Cancer Institute to enhance integration of palliative oncology care into DNP curriculum. The course participants (N = 183), consisting of DNP faculty or deans, practicing DNP clinicians, and students, received detailed annotated slides, case studies, and suggested activities to increase student engagement with the learning process. Course content was developed and delivered by palliative care experts and DNP faculty skilled in curriculum design. Participants were required to develop goals on how to enhance their school's DNP curriculum with the course content. They provided updates regarding their progress at integrating the content into their school's curriculum at 6, 12, and 18 months post course. Results demonstrated an increase in incorporating oncology palliative care in DNP scholarly projects and clinical opportunities. Challenges to inclusion of this content in DNP curricula included lack of: perceived time in curriculum; faculty educated in palliative care; and available clinical sites.


Multi-Omic Analysis of the Microbiome and Metabolome in Healthy Subjects Reveals Microbiome-Dependent Relationships Between Diet and Metabolites.
The human microbiome has been associated with health status, and risk of disease development. While the etiology of microbiome-mediated disease remains to be fully elucidated, one mechanism may be through microbial metabolism. Metabolites produced by commensal organisms, including in response to host diet, may affect host metabolic processes, with potentially protective or pathogenic consequences. We conducted multi-omic phenotyping of healthy subjects (N = 136), in order to investigate the interaction between diet, the microbiome, and the metabolome in a cross-sectional sample. We analyzed the nutrient composition of self-reported diet (3-day food records and food frequency questionnaires). We profiled the gut and oral microbiome (16S rRNA) from stool and saliva, and applied metabolomic profiling to plasma and stool samples in a subset of individuals (N = 75). We analyzed these multi-omic data to investigate the relationship between diet, the microbiome, and the gut and circulating metabolome. On a global level, we observed significant relationships, particularly between long-term diet, the gut microbiome and the metabolome. Intake of plant-derived nutrients as well as consumption of artificial sweeteners were associated with significant differences in circulating metabolites, particularly bile acids, which were dependent on gut enterotype, indicating that microbiome composition mediates the effect of diet on host physiology. Our analysis identifies dietary compounds and phytochemicals that may modulate bacterial abundance within the gut and interact with microbiome composition to alter host metabolism.


The definition and epidemiology of clusters of suicidal behavior: a systematic review.
Suicide clusters are a rare and underresearched phenomenon which attract wide media attention and result in heightened concern in the communities where they occur. We conducted a systematic literature review covering the definition and epidemiology of the time-space clustering of suicidal behavior. Of the 890 articles identified by electronic searching, 82 were selected for inclusion and the extracted data were analyzed by narrative synthesis. Less than a third of studies included a definition of a suicide cluster, and definitions varied considerably. Clusters occurred in various settings, including psychiatric hospitals, schools, prisons, indigenous communities, and among the general population. Most clusters involved young people. The proportion of all episodes that occurred in clusters varied considerably between studies and partly depended on study methodology (e.g., a larger proportion was found in studies of specific clusters compared with general population studies). Future studies should aim to combine the statistical analysis of time-space clustering with a case study of events, which examines potential links between individuals and the wider environmental context.


Vertebra and femur neck bone mineral density values in healthy Turkish children.
The bone mineral density (BMD) of the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry (DEXA) in 102 healthy Turkish children, aged 3-15, and values were correlated with age, height, weight and pubertal status. BMD increased with age in children of both sexes. The increase was steeper at the time of puberty. There were no significant differences between boys and girls until the age of 10. After the age of 10, lumbar BMD was higher in girls than in boys, probably because of the earlier onset of puberty in females. BMD was also highly correlated with height and weight. Because of low irradiation exposure, rapid scanning and high precision, DEXA is a non-invasive method, which is well adapted to children with diseases impairing bone metabolism.


Differential expression of ezrin and CLP36 in the two layers of syncytiotrophoblast in rats.
The syncytiotrophoblast, which regulates maternal-fetal transfer of drugs, consists of a single layer in humans, but two layers, i.e., SynI and SynII, in rodents. Polar distribution of transporters in the apical and basal plasma membranes of syncytiotrophoblast is important for placental function in terms of vectorial transport of substrates, but the mechanisms that control protein distribution in the syncytiotrophoblast remain unclear. We have previously established rat syncytiotrophoblast cell lines, TR-TBT 18d-1 and TR-TBT 18d-2, which retain characteristics of SynI and SynII, respectively. In this study, we aimed to characterize the gene expression profiles in the two layers by using these cell lines. DNA microarray analysis indicated that more than 25 mRNAs, including cytoskeleton binding proteins, ezrin and CLP36, are differentially expressed between TR-TBT 18d-1 and TR-TBT 18d-2. Quantitative real time-polymerase chain reaction (PCR) analysis indicated that mRNA expression of ezrin, CLP36, CCN1, and CCN2 is higher in TR-TBT 18d-1 and mRNA expression of elf-1a, hsc70 and flot2 is higher in TR-TBT 18d-2, compared with their counterparts. Immunohistochemical analysis indicated that ezrin is expressed in rat placental villi in vivo, and is located on the apical membranes of TR-TBT 18d-1, while CLP36 is located in the apical and basal sides of TR-TBT 18d-1. The expression of ezrin was highest at gestational days 14 and 18 and was highest among the ezrin/radixin/moesin (ERM) family members. These results may help to clarify the mechanisms controlling polarization of the syncytiotrophoblast and the significance of the double epithelial layers in rat and mouse.


Discordance between Serum Neutralizing Antibody Titers and the Recovery from COVID-19.
The recent pandemic of COVID-19 has caused a tremendous alarm around the world. Details of the infection process in the host have significant bearings on both recovery from the disease and on the correlates of the protection from the future exposures. One of these factors is the presence and titers of neutralizing Abs (NAbs) in infected people. In the current study, we set out to investigate NAbs in the recovered subjects discharged from the hospital in full health. Serum samples from a total of 49 documented consecutive COVID-19 subjects were included in the study. All the subjects were adults, and serum samples collected during the discharge were tested in viral neutralization, enzyme immunoassay (EIA), and Western immunoblot tests against viral Ags. Even though a majority of the recovered subjects had raised significant NAb titers, there is a substantial number of recovered patients (10 out of 49) with no or low titers of NAbs against the virus. In these cohorts as well as in patients with high NAb titers, viral Ag binding Abs were detectable in EIA tests. Both NAb titers and EIA detectable Abs are increased in patients experiencing a severe form of the disease, and in older patients the Ab titers were heightened. The main conclusion is that the recovery from SARS-CoV-2 infection is not solely dependent on high NAb titers in affected subjects, and this recovery process is probably produced by a complex interplay between many factors, including immune response, age of the subjects, and viral pathology.


Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial.
Recent efforts in malaria control have resulted in great gains in reducing the burden of Plasmodium falciparum, but P. vivax has been more refractory. Its ability to form dormant liver stages confounds control and elimination efforts. To compare the efficacy and safety of primaquine regimens for radical cure, we undertook a randomized controlled trial in Ethiopia. Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P. vivax mono-infection were enrolled and randomly assigned to receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent episodes were treated with the same treatment allocated at enrolment. The primary endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%-10.4%) after CQ treatment and 0% (95% CI 0%-4.0%) after CQ+PQ. The corresponding risks were 12.0% (95% CI 6.8%-20.6%) following AL alone and 2.3% (95% CI 0.6%-9.0%) following AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%-28.0%) after CQ, 1.2% (95% CI 0.2%-8.0%) after CQ+PQ, 29.9% (95% CI 21.6%-40.5%) after AL, and 5.9% (95% CI 2.4%-13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk of recurrence by day 42 appeared greater following AL treatment than CQ treatment (HR = 1.8 [95% CI 1.0-3.2]; p = 0.059). At the end of follow-up, the incidence rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9-9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ (rate ratio: 6.4 [95% CI 3.6-11.3]; p < 0.001). There was no difference in the occurrence of adverse events between treatment arms. The main limitations of the study were the early termination of the trial and the omission of haemoglobin measurement after day 42, resulting in an inability to estimate the cumulative risk of anaemia. Despite evidence of CQ-resistant P. vivax, the risk of recurrence in this study was greater following treatment with AL unless it was combined with a supervised course of PQ. PQ combined with either CQ or AL was well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y. ClinicalTrials.gov NCT01680406.


Blended Learning: The Student Viewpoint.
Blended learning (BL) is defined as "a way of meeting the challenges of tailoring learning and development to the needs of individuals by integrating the innovative and technological advances offered by online learning with the interaction and participation offered in the best of traditional learning." The Gulf Medical University (GMU), Ajman, UAE, offers a number of courses which incorporate BL with contact classes and online component on an E-learning platform. Insufficient learning satisfaction has been stated as an obstacle to its implementation and efficacy. To determine the students' perceptions toward BL which in turn will determine their satisfaction and the efficacy of the courses offered. This was a cross-sectional study conducted at the GMU, Ajman between January and December 2013. Perceptions of BL process, content, and ease of use were collected from 75 students enrolled in the certificate courses offered by the university using a questionnaire. Student perceptions were assessed using Mann-Whitney U-test and Kruskal-Wallis test on the basis of gender, age, and course enrollment. The median scores of all the questions in the three domains were above three suggesting positive perceptions on BL. The distribution of perceptions was similar between gender and age. However, significant differences were observed in the course enrollment (P = 0.02). Students hold a positive perception of the BL courses being offered in this university. The difference in perceptions among students of different courses suggest that the BL format offered needs modification according to course content to improve its perception.


A Targeted Approach for Congenital Cytomegalovirus Screening Within Newborn Hearing Screening.
Congenital cytomegalovirus (cCMV) infection remains a leading cause of childhood hearing loss. Currently universal CMV screening at birth does not exist in the United States. An alternative approach could be testing infants who do not pass their newborn hearing screening (NHS) for cCMV. This study was undertaken to evaluate whether a targeted approach will identify infants with CMV-related sensorineural hearing loss (SNHL). Infants born at 7 US medical centers received NHS and were also screened for cCMV while in the newborn nursery. Infants who tested positive for CMV received further diagnostic audiologic evaluations to identify or confirm hearing loss. Between 2007 and 2012, 99 945 newborns were screened for both hearing impairment and cCMV. Overall, 7.0% of CMV-positive infants did not pass NHS compared with 0.9% of CMV-negative infants (P < .0001). Among the cCMV infants who failed NHS, diagnostic testing confirmed that 65% had SNHL. In addition, 3.6% of CMV-infected infants who passed their NHS had SNHL confirmed by further evaluation during early infancy. NHS in this cohort identified 57% of all CMV-related SNHL that occurred in the neonatal period. A targeted CMV approach that tests newborns who fail their NHS identified the majority of infants with CMV-related SNHL at birth. However, 43% of the infants with CMV-related SNHL in the neonatal period and cCMV infants who are at risk for late onset SNHL were not identified by NHS.


Characterization of an alpine tree line using airborne LiDAR data and physiological modeling.
Understanding what environmental drivers control the position of the alpine tree line is important for refining our understanding of plant stress and tree development, as well as for climate change studies. However, monitoring the location of the tree line position and potential movement is difficult due to cost and technical challenges, as well as a lack of a clear boundary. Advanced remote sensing technologies such as Light Detection and Ranging (LiDAR) offer significant potential to map short individual tree crowns within the transition zone despite the lack of predictive capacity. Process-based forest growth models offer a complementary approach by quantifying the environmental stresses trees experience at the tree line, allowing transition zones to be defined and ultimately mapped. In this study, we investigate the role remote sensing and physiological, ecosystem-based modeling can play in the delineation of the alpine tree line. To do so, we utilize airborne LiDAR data to map tree height and stand density across a series of altitudinal gradients from below to above the tree line within the Swiss National Park (SNP), Switzerland. We then utilize a simple process-based model to assess the importance of seasonal variations on four climatically related variables that impose non-linear constraints on photosynthesis. Our results indicate that all methods predict the tree line to within a 50 m altitudinal zone and indicate that aspect is not a driver of significant variations in tree line position in the region. Tree cover, rather than tree height is the main discriminator of the tree line at higher elevations. Temperatures in fall and spring are responsible for the major differences along altitudinal zones, however, changes in evaporative demand also control plant growth at lower altitudes. Our results indicate that the two methods provide complementary information on tree line location and, when combined, provide additional insights into potentially endangered forest/grassland transition zones.


Ag+ insertion into 3D hierarchical rose-like Cu(1.8)Se nanocrystals with tunable band gap and morphology genetic.
In this study, novel hierarchical rose-like Cu1.8Se microspheres with a porous three-dimensional (3D) framework were successfully synthesized by using a one-pot in situ growth method at low temperature (60 °C). The Cu1.8Se microspheres covered the surface of the 3D porous framework. The formation mechanism was investigated in detail by adjusting the volume ratio of DMF and EDA, as the blend solvents, and the reaction time. Then, the chemical composition of the Cu1.8Se microspheres was altered by Ag(+) exchange without changing their morphology and structure. In this way, the binary Cu1.8Se was efficiently converted into the ternary CuAgSe. Notably, the band gap of materials was tuned continuously from 3.83 eV to 3.03 eV, and CuAgSe was produced continuously by adjusting the replacement time. This work provides a novel concept and a simple method that can serve as a good reference for improving the performance of tunable materials and the preparation of multielement alloy materials.


A population-based study comparing patterns of care delivery on the quality of care for persons living with HIV in Ontario.
Physician specialty is often positively associated with disease-specific outcomes and negatively associated with primary care outcomes for people with chronic conditions. People with HIV have increasing comorbidity arising from antiretroviral therapy (ART) related longevity, making HIV a useful condition to examine shared care models. We used a previously described, theoretically developed shared care framework to assess the impact of care delivery on the quality of care provided. Retrospective population-based observational study from 1 April 2009 to 31 March 2012. 13 480 patients with HIV and receiving publicly funded healthcare in Ontario were assigned to one of five patterns of care. Cancer screening, ART prescribing and healthcare utilisation across models using adjusted multivariable hierarchical logistic regression analyses. Models in which patients had an assigned family physician had higher odds of cancer screening than those in exclusively specialist care (colorectal cancer screening, exclusively primary care adjusted OR (AOR)=3.12, 95% CI (1.90 to 5.13), family physician-dominant co-management AOR=3.39, 95% CI (1.94 to 5.93), specialist-dominant co-management AOR=2.01, 95% CI (1.23 to 3.26)). The odds of having one emergency department visit did not differ among models, although the odds of hospitalisation and HIV-specific hospitalisation were lower among patients who saw exclusively family physicians (AOR=0.23, 95% CI (0.14 to 0.35) and AOR=0.15, 95% CI (0.12 to 0.21)). The odds of antiretroviral prescriptions were lower among models in which patients' HIV care was provided predominantly by family physicians (exclusively primary care AOR=0.15, 95% CI (0.12 to 0.21), family physician-dominant co-management AOR=0.45, 95% CI (0.32 to 0.64)). How care is provided had a potentially important influence on the quality of care delivered. Our key limitation is potential confounding due to the absence of HIV stage measures.


Exome sequencing of a multigenerational human pedigree.
Over the next few years, the efficient use of next-generation sequencing (NGS) in human genetics research will depend heavily upon the effective mechanisms for the selective enrichment of genomic regions of interest. Recently, comprehensive exome capture arrays have become available for targeting approximately 33 Mb or approximately 180,000 coding exons across the human genome. Selective genomic enrichment of the human exome offers an attractive option for new experimental designs aiming to quickly identify potential disease-associated genetic variants, especially in family-based studies. We have evaluated a 2.1 M feature human exome capture array on eight individuals from a three-generation family pedigree. We were able to cover up to 98% of the targeted bases at a long-read sequence read depth of > or = 3, 86% at a read depth of > or = 10, and over 50% of all targets were covered with > or = 20 reads. We identified up to 14,284 SNPs and small indels per individual exome, with up to 1,679 of these representing putative novel polymorphisms. Applying the conservative genotype calling approach HCDiff, the average rate of detection of a variant allele based on Illumina 1 M BeadChips genotypes was 95.2% at > or = 10x sequence. Further, we propose an advantageous genotype calling strategy for low covered targets that empirically determines cut-off thresholds at a given coverage depth based on existing genotype data. Application of this method was able to detect >99% of SNPs covered > or = 8x. Our results offer guidance for "real-world" applications in human genetics and provide further evidence that microarray-based exome capture is an efficient and reliable method to enrich for chromosomal regions of interest in next-generation sequencing experiments.


Pedigree and herd characterization of a donkey breed vulnerable to extinction.
Most donkey and local horse breeds are vulnerable to extinction as mechanization of agriculture progress throughout the world. The present study analyzed the pedigree and herd records of the donkey Asinina de Miranda breed (RAM), identifying genealogical and human factors that may affect the breed genetic diversity in the future and suggesting suitable strategies to breed preservation, early on the conservation program. The breeding rate was very low, with a ratio of foaling/live animals of 0.23 (178/760). The estimated number of founders and ancestors contributing to the reference population was 128 and 121. The number of founder herds in the reference population was 64, with an effective number of founder herds for the reference population of 7.6. The mean age of herd owners was 65.50 ± 0.884 years, with a negative association among the herd size and owner's age (P<0.001). In contrast, the size of the herd and the ownership of a male were both positively associated (P<0.001) with the herd number of in-born foals. Both the owners' age and the herd location (RAM home region v. dispersal region) were negatively associated with the foaling number (P<0.001). The main identified risk factors were: low breeding rates; low number of males and their unequal contribution to the genetic pool; unequal contribution of the herds to genetic pool; and advanced age of herd owners.


Flexible Bionanocomposites from Epoxidized Hemp Seed Oil Thermosetting Resin Reinforced with Halloysite Nanotubes.
Hemp seed (Cannabis sativa L.) oil comprises a variety of beneficial unsaturated triglycerides with well-documented nutritional and health benefits. However, it can become rancid over a relatively short time period, leading to increased industrial costs and waste of a valuable product. The development of sustainable polymers is presented as a strategy, where both the presence of unsaturation and peroxide content could be effectively used to alleviate both the waste and financial burden. After the reaction with peroxyacetic acid, the incorporation of halloysite nanotubes (HNTs), and the subsequent thermal curing, without the need for organic solvents or interfacial modifiers, flexible transparent materials with a low glass-transition temperature were developed. The improvement in the thermal stability and both the static and dynamic mechanical properties of the bionanocomposites were significantly enhanced with the well-dispersed HNT filler. At an optimum concentration of 0.5 wt % HNTs, a simultaneous increase in stiffness, strength, ductility, and toughness was observed in comparison to the unfilled cured resin. These sustainable food-waste-derived bionanocomposites may provide an interesting alternative to petroleum-based materials, particularly for low-load-bearing applications, such as packaging.


Linkage analysis of a large pedigree with hereditary sideroblastic anaemia.
A large pedigree showing a history of pyridoxine responsive X linked sideroblastic anaemia was screened with several polymorphic DNA markers from the X chromosome. Linkage analysis between each marker and disease status was performed, giving a maximum two point lod score of 3.64 at zero recombination with the microsatellite marker PGK1P1 at Xq11.2-12. Close linkage to PGK at Xq13.3, one of the candidate regions for X linked sideroblastic anaemia, was excluded. Linkage to DNA markers distal to PGK and at Xp21 was also excluded. Multipoint linkage analysis was performed with markers located between Xq11.2-21. The maximum map specific lod score obtained was 3.56 at PGK1P1 (Xq11.2-12). Linkage remained significant over the interval 20 cM proximal to PGK1P1 and 5 cM distal to PGK1P1, with definite exclusion around the PGK locus. The most likely location of the gene involved in sideroblastic anaemia in this pedigree is therefore within the pericentromeric region of the X chromosome. This region includes the erythroid 5-aminolaevulinate synthetase gene of the haem synthesis pathway, which is a candidate gene for X linked sideroblastic anaemia located at Xp11.21.


The influence of antigenic variation on cytotoxic T lymphocyte responses in HIV-1 infection.
The propensity of HIV-1 for genetic variation, a consequence of error-prone reverse transcription combined with high rates of replication, is thought to contribute to the establishment of persistent infection in the host despite the presence of a vigorous antiviral immune response. Protective immunity to viruses is mediated primarily by cytotoxic T lymphocytes, which recognize viral peptides of 8-11 amino acids bound to major histocompatibility complex class I molecules on the surface of infected cells. In this review we examine the mechanisms by which mutation within peptide antigen-encoding regions of the viral genome enables HIV-1 to evade recognition by virus-specific cytotoxic T lymphocytes. The discussion is relevant to other genetically unstable viruses and more generally to intracellular pathogens of variable antigenicity.


Trehalose metabolism by Bacillus popilliae.
Trehalose was found to be utilized more readily than glucose for the growth of Bacillus popilliae NRRL B-2309MC. The pathway of degradation of trehalose was elucidated and found to differ from that reported for other organisms. Trehalase and trehalose phosphorylase activities could not be detected. Rather, trehalose was found to undergo phosphoenolpyruvate (PEP)-dependent phosphorylation, and the resulting trehalose 6-phosphate was cleaved by a phosphotrehalase to equimolar amounts of glucose and glucose 6-phosphate. The phosphotrehalase was purified 34-fold and shown to have a pH optimum of 6.5 to 7.0 and a K(m) for trehalose 6-phosphate of 1.8 mM. A mutant missing the phosphotrehalase failed to grow on trehalose but grew normally on other sugars. The mutant accumulated [(14)C]trehalose as [(14)C]trehalose 6-phosphate. Phosphorylation of trehalose by dialyzed extracts was at least 25 times faster with PEP than with adenosine 5'-triphosphate, and the phosphorylation activity was associated primarily with the particulate fraction. These data and the results of studies of [(14)C]trehalose uptake suggest that trehalose is transported into the cell as trehalose 6-phosphate by a PEP:sugar phosphotransferase system. Cell extracts of other strains of B. popilliae were also found to produce [(14)C]sugar phosphate from [(14)C]trehalose and to have phosphotrehalase activity.


Passive combination of multiple beams in an optical fiber via stimulated Brillouin scattering.
We demonstrate passive combination of multiple beams in an optical fiber via stimulated Brillouin scattering (SBS). Four off-axis beams are combined in a long multimode optical fiber using a novel all-optical mount. The combined beam has the high spatial coherence properties of the LP(01) mode owing to the beam cleanup properties of SBS. The threshold for SBS when off-axis pumps are used is shown to be a factor of 13 times higher than for on-axis pump beams. We propose this method would improve the brightness of an array of fiber amplifiers.


Roseovarius crassostreae sp. nov., a member of the Roseobacter clade and the apparent cause of juvenile oyster disease (JOD) in cultured Eastern oysters.
An alpha-proteobacterium has been identified which is believed to be the causative agent of juvenile oyster disease (JOD). Since its first isolation in 1997, the bacterium has been recovered as the numerically dominant species from JOD-affected animals throughout the north-eastern United States (Maine, New York and Massachusetts). Colonies are usually beige to pinkish-beige, although the majority of isolates recovered in 2003 from an epizootic in Martha's Vineyard, Massachusetts, produce colonies with a greenish-yellow appearance. The cells are Gram-negative, aerobic, strictly marine and rod or ovoid in appearance. They are actively motile by one or two flagella, but cells are also observed to produce tufts of polar fimbriae. The principal fatty acid in whole cells is C(18:1)omega7c and other characteristic fatty acids are C(16:0), C(10:0) 3-OH, 11-methyl C(18:1)omega7c and C(18:0). Almost without exception, isolates have 16S rRNA gene sequences that are 100% identical to each other. Phylogenetic analyses place the organism within the Roseobacter clade of the alpha-Proteobacteria, with moderate bootstrap support for inclusion in the genus Roseovarius. DNA-DNA relatedness values from pairwise comparisons of this organism with the type species of the genus (Roseovarius tolerans) and the only other described species in this genus, Roseovarius nubinhibens, were 11 and 47%, respectively. Phenotypic and biochemical dissimilarities also support the assignment of this bacterium to a novel species. The name Roseovarius crassostreae sp. nov. is proposed, with the type strain CV919-312(T) (=ATCC BAA-1102(T)=DSM 16950(T)).


Vive la résistance: genome-wide selection against introduced alleles in invasive hybrid zones.
Evolutionary and ecological consequences of hybridization between native and invasive species are notoriously complicated because patterns of selection acting on non-native alleles can vary throughout the genome and across environments. Rapid advances in genomics now make it feasible to assess locus-specific and genome-wide patterns of natural selection acting on invasive introgression within and among natural populations occupying diverse environments. We quantified genome-wide patterns of admixture across multiple independent hybrid zones of native westslope cutthroat trout and invasive rainbow trout, the world's most widely introduced fish, by genotyping 339 individuals from 21 populations using 9380 species-diagnostic loci. A significantly greater proportion of the genome appeared to be under selection favouring native cutthroat trout (rather than rainbow trout), and this pattern was pervasive across the genome (detected on most chromosomes). Furthermore, selection against invasive alleles was consistent across populations and environments, even in those where rainbow trout were predicted to have a selective advantage (warm environments). These data corroborate field studies showing that hybrids between these species have lower fitness than the native taxa, and show that these fitness differences are due to selection favouring many native genes distributed widely throughout the genome.


In Vitro Evaluation of Betafoam, a New Polyurethane Foam Dressing.
A new polyurethane foam dressing impregnated with 3% povidone-iodine (Betafoam; Genewell, Seoul, Korea) was recently developed based on the hypothesis that its physical properties, including improved moisture-retention capacity and antimicrobial activity, are at least as good as those achieved with the current foam dressings that contain silver, but also associated with reduced cost and cytotoxicity to host cells. The purpose of this in vitro study was to evaluate the efficacy of Betafoam by comparing its physical properties, antimicrobial activity, and cytotoxicity with those of 3 silver foam dressings (Allevyn-Ag [Smith & Nephew, Hull, United Kingdom]; Mepilex-Ag [Mölnlycke Health Care, Gothenburg, Sweden]; and PolyMem-Ag [Ferris MFG Corp, Burr Ridge, Illinois]) used worldwide. This study measured each dressing's pore size, fluid absorption time, fluid absorption capacity, fluid retention capacity, antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa, and cytotoxicity to mouse fibroblasts. Betafoam had the smallest pore size, the fastest fluid absorption time, greatest fluid absorption, and best retention capacities among the tested foam dressings. Antimicrobial activity was not significantly different among the dressings. However, Betafoam also demonstrated the lowest cytotoxicity to the fibroblasts. Betafoam may result not only in desirable rapid regulation of exudation but also antimicrobial activity with minimal cytotoxicity to host cells that are key requirements for wound healing.


Early post-operative results after repair of traumatic brachial plexus palsy.
Treatment options for traumatic brachial plexus injuries include nerve grafting, or neurotization. The type of lesion and the reconstructive procedures affect functional results and postoperative pain relief. A total number of twenty five patients suffering from post-traumatic brachial plexus injury were included in the study. The patients underwent exploration and primary repair of the affected plexus, based on case by case policy. Spinal accessory nerve transfer to suprascapular nerve procedure regained 78.95% of functional muscle power, 10.50% of non functional muscle power and only 10.5 % of non innervated muscle. The Oberlin procedure regained 83.33% with elbow flexion muscle power, 16.67% with non functional muscle power. Intercostal nerve transfer to musculocutaneous nerve regained 62.5% with functional muscle power, 25% with non functional muscle power and only 12.5 % with non innervated muscle. The shoulder, elbow and wrist extension functions were significantly improved early post-operatively. In addition, the post-operative improvement of shoulder, elbow and wrist extension functions had significant negative correlations with the pre-operative elapsed time, and accompanied by a significant positive correlation with post-operative follow up period. Early intervention for traumatic brachial plexus palsy is recommended to get good results with pain relief.


An electronic medical record-linked biorepository to identify novel biomarkers for atherosclerotic cardiovascular disease.
Atherosclerotic vascular disease (AVD), a leading cause of morbidity and mortality, is increasing in prevalence in the developing world. We describe an approach to establish a biorepository linked to medical records with the eventual goal of facilitating discovery of biomarkers for AVD. The Vascular Disease Biorepository at Mayo Clinic was established to archive DNA, plasma, and serum from patients with suspected AVD. AVD phenotypes, relevant risk factors and comorbid conditions were ascertained by electronic medical record (EMR)-based electronic algorithms that included diagnosis and procedure codes, laboratory data and text searches to ascertain medication use. Up to December 2012, 8800 patients referred for vascular ultrasound examination and non-invasive lower extremity arterial evaluation were approached, of whom 5268 consented. The mean age of the initial 2182 patients recruited was 70.4 ± 11.2 years, 62.6% were men and 97.6% were whites. The prevalences of AVD phenotypes were: carotid artery stenosis 48%, abdominal aortic aneurysm 21% and peripheral arterial disease 38%. Positive predictive values for electronic phenotyping algorithms were>0.90 for cases (and>0.95 for controls) for each AVD phenotype, using manual review of the EMR as the gold standard. The prevalences of risk factors and comorbidities were as follows: hypertension 78%, diabetes 29%, dyslipidemia 73%, smoking 70%, coronary heart disease 37%, heart failure 12%, cerebrovascular disease 20% and chronic kidney disease 19%. Our study demonstrates the feasibility of establishing a biorepository of plasma, serum and DNA, with relatively rapid annotation of clinical variables using EMR-based algorithms.


Ovum aging and pH imbalance as a cause of chromosomal anomalies in the hamster.
Using female hamsters mated in estrus, we have produced triploid embryos as manifestations of pregnancy wastage by combining delays of 3 to 4 hours in ferilization with exposure of the animals to hypoxia. Among the triploid embryos only XXX and XXY karotypes occurred, indicating derivation from XX-containing ova. These findings have relevance to human reproduction.


Host-specific toxins: effectors of necrotrophic pathogenicity.
Host-specific toxins (HSTs) are defined as pathogen effectors that induce toxicity and promote disease only in the host species and only in genotypes of that host expressing a specific and often dominant susceptibility gene. They are a feature of a small but well-studied group of fungal plant pathogens. Classical HST pathogens include species of Cochliobolus, Alternaria and Pyrenophora. Recent studies have shown that Stagonospora nodorum produces at least four separate HSTs that interact with four of the many quantitative resistance loci found in the host, wheat. Rationalization of fungal phylogenetics has placed these pathogens in the Pleosporales order of the class Dothideomycetes. It is possible that all HST pathogens lie in this order. Strong evidence of the recent lateral gene transfer of the ToxA gene from S. nodorum to Pyrenophora tritici-repentis has been obtained. Hallmarks of lateral gene transfer are present for all the studied HST genes although definitive proof is lacking. We therefore suggest that the Pleosporales pathogens may have a conserved propensity to acquire HST genes by lateral transfer.


Shortening the questionnaire for identifying children with chronic conditions: what is the consequence?
To determine whether a reduced item set can identify children who have chronic conditions with a level of at least 90% accuracy compared with the complete Questionnaire for Identifying Children With Chronic Conditions (QuICCC). The QuICCC was developed to operationalize a conceptually based, noncategorical definition of chronic conditions developed by Stein et al. It contains 39 item sequences administered to a parent that assess 3 types of consequences: functional limitations; reliance on compensatory mechanisms or assistance; and service use or need above usual for age. The QuICCC has been validated and widely adopted as a means of identifying children without using a diagnosis checklist, but there is considerable interest in shortening it. Through secondary analyses of 3 data sets (Ns = 1265, 1388, and 4831), we identified a short list of items that identified >90% of children who were identified by the 39-item QuICCC. We administered these 16 items to 2 new samples of parents. In Study 1 we administered the 16 items in the shortened version first, followed by the other 23 items, and compared the results on the short and reordered long versions. In Study 2, the 39- and 16-item versions were each administered, one in person and the other by phone, in random order to the same respondent within a 2-week period. These data were analyzed to compare the short and longer versions at the 2 time points and within the single, longer 39-item format (simultaneous data). In Study 1 (N = 630) only 4 children were missed by the 16-item version who were identified by the longer version (sensitivity 98.6%; specificity 100%; positive predictive value 100%; negative predictive value 98.8% kappa 0.987). In Study 2 (N = 552), no children were missed by the 16-item subset of the 39 items when looking at the simultaneous data. When the two forms were administered 2 weeks apart, the 16-item version had a sensitivity of 87%, specificity of 90%, positive predictive value of 93%, negative predictive value of 82%, and kappa of 0.78 compared with the longer QuICCC. These results correspond exactly to the data obtained in a 2-week test-retest study for the QuICCC itself. The new form (the QuICCC-R) takes <2 minutes to administer on average (range 1-4 minutes) compared with 7 to 8 minutes for the full QuICCC. The results met our criteria for agreement, and we conclude that the QuICCC-R is a satisfactory alternative for screening populations. However, the full QuICCC has other applications beyond screening that may not apply to the QuICCC-R, the shorter version.


Adaptable neighbours: movement patterns of GPS-collared leopards in human dominated landscapes in India.
Understanding the nature of the interactions between humans and wildlife is of vital importance for conflict mitigation. We equipped five leopards with GPS-collars in Maharashtra (4) and Himachal Pradesh (1), India, to study movement patterns in human-dominated landscapes outside protected areas. An adult male and an adult female were both translocated 52 km, and exhibited extensive, and directional, post release movements (straight line movements: male = 89 km in 37 days, female = 45 km in 5 months), until they settled in home ranges of 42 km2 (male) and 65 km2 (female). The three other leopards, two adult females and a young male were released close to their capture sites and used small home ranges of 8 km2 (male), 11 km2 and 15 km2 (females). Movement patterns were markedly nocturnal, with hourly step lengths averaging 339±9.5 m (SE) during night and 60±4.1 m during day, and night locations were significantly closer to human settlements than day locations. However, more nocturnal movements were observed among those three living in the areas with high human population densities. These visited houses regularly at nighttime (20% of locations <25 m from houses), but rarely during day (<1%). One leopard living in a sparsely populated area avoided human settlements both day and night. The small home ranges of the leopards indicate that anthropogenic food resources may be plentiful although wild prey is absent. The study provides clear insights into the ability of leopards to live and move in landscapes that are extremely modified by human activity.


Site-selected introduction of modified purine and pyrimidine ribonucleosides into RNA by automated phosphoramidite chemistry.
The study of modified nucleoside contributions to RNA chemistry, structure and function has been thwarted by the lack of a site-selected method of incorporation which is both versatile and adaptable to present synthetic technologies. A reproducible and versatile site-selected incorporation of nine differently modified nucleosides into hepta- and octadecamer RNAs has been achieved with automated phosphoramidite chemistry. The 5'-O-(4,4'-dimethoxytrityl-2'-O-tert-butyldimethylsilyl-ribonucleoside- 3'-O-(2-cyanoethyl-N,N-diisopropyl)phosphoramidite syntheses of m5C, D, psi, riboT, s2U, mnm5U, m1G and m2A were designed for compatibility with the commercially available major and 2'OH methylated ribonucleoside phosphoramidites. The synthesis of the m5C phosphoramidite was uniquely designed, and the first syntheses and incorporation of the two modified purine ribonucleosides are reported in detail along with that of psi, s2U, and mnm5U. Cleavage of RNA product from the synthesis support column, deprotection of the RNA, its purification by HPLC and nucleoside composition analysis are described. Modified nucleoside-containing tRNA domains were synthesized and purified in mumol quantities required for biophysical, as well as biochemical, studies. The anticodon domain of yeast tRNA(Phe) was synthesized with modified nucleosides introduced at the native positions: Cm32, Gm34, m1G37 (precursor to Y), psi 39 and m5C40. The T loop and stem was synthesized with riboT54 and the D loop and stem with D16 and D17. The E coli tRNA(Glu2) anti-codon codon domain was synthesized with mnm5U at wobble position 34, but an attempt at incorporating s2U at the same position failed. The unprotected thio group was labile to the oxidation step of the cyclical process. Chemically synthesized anticodon and T domains have been used in assays of tRNA structure and function (Guenther et al (1994) Biochimie 76, 1143-1151).


Platinum (IV)-fatty acid conjugates overcome inherently and acquired Cisplatin resistant cancer cell lines: an in-vitro study.
Platinum-based drugs are used as cancer chemotherapeutics for the last 40 years. However, drug resistance and nephrotoxicity are the major limitations of the use of platinum-based compounds in cancer therapy. Platinum (IV) complexes are believed to act as platinum prodrugs and are able to overcome some of platinum (II) limitations. A number of previously sensitized platinum (IV) complexes were evaluated for their anti-cancer activity by monitoring ability to affect proliferation, clonigenicity and apoptosis induction of Cisplatin sensitive and resistant cancer cells. In addition, the uptake of Cisplatin and the platinum (IV) derivatives to Cisplatin sensitive and resistant cancer cells was monitored. The bis-octanoatoplatinum (IV) complex (RJY13), a Cisplatin derivative with octanoate as axial ligand, exhibited strong anti-proliferative effect on the Cisplatin resistant and sensitive ovarian cells, A2780cisR and A2780, respectively. Moreover, RJY13 exhibited good activity in inhibiting clonigenicity of both cells. Anti-proliferative activity of RJY13 was mediated by induction of apoptosis. Interestingly, a bis-lauratopaltinum (IV) complex (RJY6) was highly potent in inhibiting clonigenicity of both Cisplatin sensitive and Cisplatin resistant cells, however, exhibited reduced activity in assays that utilize cells growing in two dimensional (2D) conditions. The uptake of Cisplatin was reduced by 30% in A2780 in which the copper transporter-1 (Ctr1) was silenced. Moreover, uptake of RJY6 was marginally dependent on Ctr1, while uptake of RJY13 was Ctr1-independent. Our data demonstrated the potential of platinum (IV) prodrugs in overcoming acquired and inherited drug resistance in cancer cell lines. Moreover, our data demonstrated that the uptake of Cisplatin is partially dependent on Ctr1 transporter, while uptake of RJY6 is marginally dependent on Ctr1 and RJY13 is Ctr1-independent. In addition, our data illustrated the therapeutic potential of platinum (IV) prodrugs in cancer therapy.


miR-200c Targets CDK2 and Suppresses Tumorigenesis in Renal Cell Carcinoma.
miRNA expression profiles are widely investigated in the major cancers, but their specific roles and functions in cancers have not yet to be fully elucidated. In this study, miRNA expression profiles were determined in clear cell renal cell carcinomas (ccRCC) and in matched normal kidney tissues by using a miRNA microarray platform which covers a total of 851 human miRNAs. Differential expression of 74 miRNAs were identified between ccRCC specimens and their matched adjacent noncancerous tissues, of which 30 were significantly upregulated in ccRCCs, and the other 44 were downregulated (fold change ≥ 2, P < 0.05). Interestingly, miR-200c was commonly downregulated in ccRCC specimens and ccRCC cell lines with significant functional consequences. Growth curve and FACS assay indicated that overexpression of miR-200c suppressed cell growth and induced cell-cycle arrest at G0-G1 phases in SN12-PM6 and 786-O cells. Furthermore, miR-200c could suppress in vivo tumor growth of SN12-PM6 cells in mice. Bioinformatics exposed cyclin-dependent kinase 2 (CDK2) as a potential target of miR-200c, which was validated using a luciferase reporter assay. Mechanistic investigations revealed that miR-200c was directly responsible for suppressing the expression of CDK2 in ccRCC cell lines and xenografts. Taken together, miR-200c plays an antioncogenic role in ccRCC, through controlling cell growth and cell-cycle progression by downregulating the G1-S regulator CDK2. miR-200c exerts its novel antioncogenic function in renal cell carcinoma by controlling CDK2-dependent cell growth and cell-cycle progression.


Abdominal seat belt marks in the era of focused abdominal sonography for trauma.
Focused abdominal sonography for trauma (FAST) is an unreliable method for assessing intra-abdominal injury in patients with seat belt marks. Retrospective review of trauma patients with intestinal injury and seat belt marks during a 3-year period. Records were reviewed for patient demographics, FAST results, computed tomographic (CT) scan results, and operative findings. The CT scan results were considered positive if bowel wall thickening, extraluminal air, or free fluid without solid organ injury were present. University hospital designated as a level I trauma center. Twenty-three patients who required operation for intestinal or mesenteric injury and who had an abdominal seat belt mark. Sensitivity of FAST in these patients. All patients were evaluated using both FAST and CT scan of the abdomen and pelvis. Eighteen patients (78%) had either negative or equivocal FAST results when significant intestinal injury was present. All 23 patients had CT scan findings suggestive of bowel or mesenteric injury. Moderate-to-large free intraperitoneal fluid without solid organ injury was the most common finding (n = 21, 91%). Operative findings included small-bowel perforation (n = 18, 78%), colonic perforation (n = 7, 30%), bowel deserosalization (n = 8, 35%), and isolated mesenteric injury (n = 5, 22%). Sixteen patients (70%) had multiple intra-abdominal injuries. All patients were taken directly from the emergency department to the operating room. Seventeen percent of operative explorations (4/23) were nontherapeutic (no repairs required). This study confirms that FAST cannot reliably exclude intestinal injury in patients with seat belt marks.


Clustering of malaria in households in the Greater Mekong Subregion: operational implications for reactive case detection.
Malaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases. It is included in national malaria control programmes of countries in the Greater Mekong Subregion to accelerate malaria elimination. Yet the value of reactive case detection in the control and elimination of malaria remains controversial because of the low yield, limited evidence for impact, and high demands on resources. Data from the epidemiological assessments of large mass drug administration (MDA) studies in Myanmar, Vietnam, Cambodia and Laos were analysed to explore malaria infection clustering in households. The proportion of malaria positive cases among contacts screened in a hypothetical reactive case detection programme was then determined. The parasite density thresholds for rapid diagnostic test (RDT) detection was assumed to be > 50/µL (50,000/mL), for dried-blood-spot (DBS) based PCR > 5/µL (5000/mL), and for ultrasensitive PCR (uPCR) with a validated limit of detection at 0.0022/µL (22/mL). At baseline, before MDA, 1223 Plasmodium infections were detected by uPCR in 693 households. There was clustering of Plasmodium infections. In 637 households with asymptomatic infections 44% (278/637) had more than one member with Plasmodium infections. In the 132 households with symptomatic infections, 65% (86/132) had more than one member with Plasmodium infections. At baseline 4% of households had more than one Plasmodium falciparum infection, but three months after MDA no household had more than one P. falciparum infected member. Reactive case detection using DBS PCR would have detected ten additional cases in six households, and an RDT screen would have detected five additional cases in three households among the 169 households with at least one RDT positive case. This translates to 19 and 9 additional cases identified per 1000 people screened, respectively. Overall, assuming all febrile RDT positive patients would seek treatment and provoke reactive case detection using RDTs, then 1047 of 1052 (99.5%) Plasmodium infections in these communities would have remained undetected. Reactive case detection in the Greater Mekong subregion is predicted to have a negligible impact on the malaria burden, but it has substantial costs in terms of human and financial resources.


Origin of enhanced water oxidation activity in an iridium single atom anchored on NiFe oxyhydroxide catalyst.
The efficiency of the synthesis of renewable fuels and feedstocks from electrical sources is limited, at present, by the sluggish water oxidation reaction. Single-atom catalysts (SACs) with a controllable coordination environment and exceptional atom utilization efficiency open new paradigms toward designing high-performance water oxidation catalysts. Here, using operando X-ray absorption spectroscopy measurements with calculations of spectra and electrochemical activity, we demonstrate that the origin of water oxidation activity of IrNiFe SACs is the presence of highly oxidized Ir single atom (Ir5.3+) in the NiFe oxyhydroxide under operating conditions. We show that the optimal water oxidation catalyst could be achieved by systematically increasing the oxidation state and modulating the coordination environment of the Ir active sites anchored atop the NiFe oxyhydroxide layers. Based on the proposed mechanism, we have successfully anchored Ir single-atom sites on NiFe oxyhydroxides (Ir0.1/Ni9Fe SAC) via a unique in situ cryogenic-photochemical reduction method that delivers an overpotential of 183 mV at 10 mA ⋅ cm-2 and retains its performance following 100 h of operation in 1 M KOH electrolyte, outperforming the reported catalysts and the commercial IrO2 catalysts. These findings open the avenue toward an atomic-level understanding of the oxygen evolution of catalytic centers under in operando conditions.


A density functional theory study on the thermodynamic and dynamic properties of anthraquinone analogue cathode materials for rechargeable lithium ion batteries.
Organic redox compounds have become the emerging electrode materials for rechargeable lithium ion batteries. The high electrochemical performance provides organic electrode materials with great opportunities to be applied in electric energy storage devices. Among the different types of organic materials, conjugated carbonyl compounds are the most promising type at present, because only they can simultaneously achieve, high energy density, high cycling stability, and high power density. In this research, a series of heteroatom substituted anthraquinone (AQ) derivatives were designed theoretically so that the high theoretical capacity of AQ remained. The discharge and charge mechanism as well as the thermodynamic and dynamic properties of AQ and its derivatives were investigated using first-principles density functional theory. Using heteroatom substitution, both the thermodynamic and dynamic properties of AQ as cathode materials could be largely improved. Among these conjugated carboxyl compounds, BDOZD and BDIOZD with a simultaneously high theoretical capacity and high working potential exhibit the largest energy density of about 780 W h kg-1, which is 41% larger than that of AQ. The PQD with the smallest value of λ gives the largest charge transfer rate constant, which is about four times as large as the prototype molecule, AQ. The most interesting finding is that the lithium ion transfer plays a very important role in influencing both the discharge potential and electrochemical charge transfer rate. The present study illustrates that theoretical calculations provide a highly effective way to discover potential materials for use with rechargeable lithium ion batteries.


Digital Approaches for a Reliable Early Diagnosis of Psoriatic Arthritis.
Psoriatic arthritis (PsA) is a chronic inflammatory disease that develops in up to 30% of patients with psoriasis. In the vast majority of cases, cutaneous symptoms precede musculoskeletal complaints. Progression from psoriasis to PsA is characterized by subclinical synovio-entheseal inflammation and often non-specific musculoskeletal symptoms that are frequently unreported or overlooked. With the development of increasingly effective therapies and a broad drug armamentarium, prevention of arthritis development through careful clinical monitoring has become priority. Identifying high-risk psoriasis patients before PsA onset would ensure early diagnosis, increased treatment efficacy, and ultimately better outcomes; ideally, PsA development could even be averted. However, the current model of care for PsA offers only limited possibilities of early intervention. This is attributable to the large pool of patients to be monitored and the limited resources of the health care system in comparison. The use of digital technologies for health (eHealth) could help close this gap in care by enabling faster, more targeted and more streamlined access to rheumatological care for patients with psoriasis. eHealth solutions particularly include telemedicine, mobile technologies, and symptom checkers. Telemedicine enables rheumatological visits and consultations at a distance while mobile technologies can improve monitoring by allowing patients to self-report symptoms and disease-related parameters continuously. Symptom checkers have the potential to direct patients to medical attention at an earlier point of their disease and therefore minimizing diagnostic delay. Overall, these interventions could lead to earlier diagnoses of arthritis, improved monitoring, and better disease control while simultaneously increasing the capacity of referral centers.


Disrespect and abuse of women during childbirth in Nigeria: A systematic review.
Promoting respectful care at childbirth is important to improve quality of care and encourage women to utilize skilled delivery services. However, there has been a relative lack of public health research on this topic in Nigeria. A systematic review was conducted to synthesize current evidence on disrespect and abuse of women during childbirth in Nigeria in order to understand its nature and extent, contributing factors and consequences, and propose solutions. Five electronic databases were searched for relevant published studies, and five data sources for additional grey literature. A qualitative synthesis was conducted using the Bowser and Hill landscape analytical framework on disrespect and abuse of women during childbirth. Fourteen studies were included in this review. Of these studies, eleven were cross sectional studies, one was a qualitative study and two used a mixed method approach. The type of abuse most frequently reported was non-dignified care in form of negative, poor and unfriendly provider attitude and the least frequent were physical abuse and detention in facilities. These behaviors were influenced by low socioeconomic status, lack of education and empowerment of women, poor provider training and supervision, weak health systems, lack of accountability and legal redress mechanisms. Overall, disrespectful and abusive behavior undermined the utilization of health facilities for delivery and created psychological distance between women and health providers. This systematic review documented a broad range of disrespectful and abusive behavior experienced by women during childbirth in Nigeria, their contributing factors and consequences. The nature of the factors influencing disrespectful and abusive behavior suggests that educating women on their rights, strengthening health systems to respond to specific needs of women at childbirth, improving providers training to encompass interpersonal aspects of care, and implementing and enforcing policies on respectful maternity care are important. This review has also shown that more robust research is needed to explore disrespect and abuse of women during childbirth in Nigeria and propose compelling interventions.


Predictors of Response to Endobronchial Coil Therapy in Patients With Advanced Emphysema.
The Lung Volume Reduction Coil Treatment in Patients With Emphysema (RENEW) trial reported improvements in quality of life, pulmonary function, and exercise performance following endobronchial coil treatment. The purpose of this post hoc analysis was to identify baseline predictors, including quantitative CT measures, that identify patients most likely to significantly benefit from endobronchial coil therapy. Quantitative CT analysis by an independent radiology laboratory and a qualitative evaluation by five blinded experts of the baseline thoracic CT imaging were performed. Univariate and multivariate logistic regression analyses were performed to elucidate characteristics associated with clinical response. In total, 125 patients underwent coil treatment and had evaluable 12-month follow-up results. Of these, 78 patients received treatment of lobes with the highest emphysematous destruction determined by quantitative CT analysis (quantitative visual match [QVM]+), and 47 received treatment in at least one lobe that was not the most destroyed (QVM-). From the 78 patients with QVM+ treatment, a subgroup of 50 patients (64%) was identified with baseline residual volume > 200% predicted, emphysema score > 20% low attenuation area, and absence of airway disease. In this subgroup, greater lobar residual volume reduction in the treated lobes was achieved, which was associated with significant mean ± SE improvement in FEV1 (15.2 ± 3.1%), St. George's Respiratory Questionnaire (-12 ± 2 points), and residual volume (-0.57 ± 0.13 L). This post hoc analysis found that both significant hyperinflation (residual volume ≥ 200% predicted) and CT analysis are critical for patient selection and treatment planning for endobronchial coil therapy. Quantitative CT analysis is important to identify optimal lobar treatment and to exclude patients with insufficient emphysema (< 20% low attenuation area), whereas visual assessment identifies patients with signs of airway disease associated with worse outcomes. ClinicalTrials.gov; No.: NCT01608490; URL: www.clinicaltrials.gov.


A pilot study of donepezil for memory problems in epilepsy.
We performed a pilot 3-month, open-label study of 5-10 mg donepezil, an anticholinesterase inhibitor, as treatment for memory problems in people with epilepsy. The Buschke Selective Reminding Test was administered at baseline and after 3 months of donepezil. In 18 completing patients, the total number of words recalled across learning trials was greater on donepezil (P = 0.4). No change was noted in attention, visual sequencing, mental flexibility, psychomotor speed, or reported quality-of-life scores. Mean 3-month seizure frequency at baseline was 2.70 ± 4.60, and during treatment, 3.06 ± 4.52 (P = 0.19, not significant). Two patients experienced increased tonic-clonic seizures. Side effects included diarrhea, stomach cramps, insomnia, depression, and blurred vision. Cholinergic medication is worthy of investigation as treatment for memory problems in people with epilepsy, but attention must be paid to possible exacerbation of seizures.


Spontaneous Eye Blink Patterns in Dry Eye: Clinical Correlations.
To evaluate spontaneous eye blink patterns and their correlations with clinical tests in dry eye disease (DED). Twenty-five DED patients and 25 healthy subjects were included in this prospective case-controlled study. Clinical evaluations included the Ocular Surface Disease Index (OSDI), lipid layer thickness (LLT), spontaneous eye blink pattern analysis, fluorescein tear film break-up time (FBUT), and so on. Eye blinks were recorded for 20 seconds with a high-speed camera. Eye blink patterns were divided into the following five phases: the eyelid closing phase (ECP), eyelid closed phase (CDP), early opening phase (EOP), late opening phase (LOP), and interblink intervals (IBI). The correlations between blink parameters and clinical tests were analyzed. Compared with the control group, mean ECP, CDP, and EOP were significantly longer in DED patients (P < 0.001, P = 0.029, and P < 0.001, respectively). DED patients also had significantly shorter LOP and blink intervals (both P < 0.001) and more partial blinks as compared with control subjects (P = 0.001). FBUT was negatively correlated with ECP (r = -0.618, P=0.001) and the number of partial blinks (r = -0.413, P = 0.040). There was a positive correlation between OSDI and the number of partial blinks (r = 0.446, P = 0.026). The LLT coefficient of variation (LLT-CV) also showed a positive correlation with ECP, CDP, and LOP (P = 0.001, P = 0.050, P = 0.049, respectively). Corneal and conjunctival staining was positively correlated with ECP, CDP, and the number of blinks (r = 0.449, P = 0.024; r = 0.526, P = 0.007; r = 0.456, P = 0.022, respectively) and negatively correlated with IBI (r = -0.420, P = 0.037). Partial blinks, prolonged eyelid closed time and short blink intervals were the three main characteristics of DED patients' spontaneous blink patterns.