Study of the genus Torreya (Taxaceae) based on chloroplast genomes.
Species of the genus Torreya are similar in morphology, and their morphological taxonomic characteristics are not stable because of environmentally induced changes. Therefore, morphology is insufficient for understanding their relationships. Chloroplast genome sequencing technology provides a powerful tool for molecular analysis to get more infomation for classification and identification of Torreya genus. A total of 4 chloroplast genome of Torreya, including T. Parvifolia, T. nucifera, T. fargesii var. Yunnanensis and T. grandis var. jiulongshanensis, were sequenced and annotated. Campartive genome and phylogenetic tree were provided for variation analysis. The chloroplast genome size of the four samples is about 137 kb, the inverted repeat (IR) regions are identified in the genus Torreya. Genome comparison using mVISTA showed high sequence similarity among different species. Regions with divergence in exon regions include accD, ndhB, ndhF, psbA, psbJ, rpl2, rps3, rps16, rps18, ycf1, and ycf2. The phylogenetic tree based on 73 single-copy genes showed a clearer relationships among different species of Torreya. All genomes of the four Torreya species consist of two short IR regions, and results of the phylogenetic analysis concluded that T. parvifolia should be considered as T. fargesii var. yunnanensis or treated as a sister species. T. grandis var. jiulongshanensis should be treated as a variety of T. grandis according to molecular evidence, supporting the originally published proposal.


Decreased expression and altered methylation of syncytin-1 gene in human placentas associated with preeclampsia.
Syncytin-1 is a protein coded by a human endogenous retrovirus (HERV) gene of the HERV-W family (HERVWE1). Syncytin- 1 mediates formation of syncytiotrophoblasts through fusion of cytotrophoblasts, a hallmark of terminal differentiation of placental trophoblast linage. Syncytin-1 also possesses nonfusogenic functions and regulates cell cycle progression. While decreased syncytin-1 expression and syncytium deficiency are considered important pathological changes in preeclampsia, the molecular mechanism(s) underlying syncytin-1 downregulation remains unclear. In this study, we confirmed that expression levels of syncytin-1 mRNA and protein were significantly lower in preeclamptic placentas compared to normal controls. Human chorionic somatomammotropin expression, a marker for syncytium function, was also decreased in preeclamptic placentas. The mRNA levels of ASCT2, the syncytin-1 receptor involved in cell fusion process, and GCMa, a transcriptional factor known to regulate syncytin-1 expression, were not significantly altered. Methylation in the 5'LTR of syncytin-1 promoter was quantified by COBRA, methylation-specific PCR, and DNA sequencing. Results from all three assays indicated significantly hypermethylated syncytin-1 promoter in preeclamptic placentas compared to normal controls. Methylation levels were inversely correlated with syncytin-1 mRNA levels, suggesting that hypermethylation may lead to syncytin-1 downregulation. Further experiments indicated that DNMT1 and DNMT3B3 mRNA and protein levels were increased in preeclamptic placentas, suggesting that higher DNA methyltransferase activity may contribute to the hypermethylation of syncytin-1 in preeclamptic placentas. These results indicated that aberrant hypermethylation is involved in downregulation of syncytin-1, and epigenetic alterations may play a significant role in the development of preeclampsia.


Differential interaction of normal and preneoplastic hamster bronchi with adriamycin.
Advanced bronchogenic carcinoma in humans is notoriously resistant to the cytocidal actions of cancer chemotherapy. The experiments reported here were undertaken as a first step in examining the mechanisms of resistance of carcinogen-altered bronchus to the actions of the commonly used cancerocidal agent Adriamycin. Syrian Golden hamsters were treated with an endobronchial carcinogen in order to produce bronchial neoplasms or with no carcinogen as controls. Hamsters were then given i.v. Adriamycin, and the amounts and metabolism of bronchial Adriamycin were determined. Peak uptake values were found 5 min after Adriamycin administration, and the amounts of Adriamycin in normal and carcinogen-altered bronchi were found to be similar. Whereas no metabolism of Adriamycin was observed in normal bronchi, 40-60% of total Adriamycin fluorescence was found to be due to Adriamycinol and Adriamycin aglycones in bronchi with premalignant changes. In separate experiments, the susceptibility of normal and carcinogen-altered bronchial extracts to drug-induced lipid peroxidation was measured in vitro. A 50% decrease was found in the ability of carcinogen-altered bronchi to act as a substrate for lipid peroxidation mediated by Adriamycin and an approximately 30% decrease for lipid peroxidation induced by t-butyl-hydroperoxide. These results demonstrate two different mechanisms by which bronchogenic carcinomas might become resistant to the chemotherapeutic actions of Adriamycin. These are by the carcinogen induction of metabolism of Adriamycin to less toxic products and by resistance of the bronchi to free radical damage.


A national survey of practice nurse involvement in mental health interventions.
The move in the United Kingdom (UK) from institutional to community care has led to an inevitable increase in the involvement of practice nurses (PNs) in mental health care. Around 20 000 PNs are currently working in the United Kingdom (UK). However, the extent and nature of PN involvement in delivering mental health interventions has not been adequately explored. This study aimed to quantify practice nurses' involvement in delivering mental health interventions in primary care settings. A questionnaire was sent to a random sample of 1500 practice nurses registered with the Practice Nurse Forum at the Royal College of Nursing. Sixty per cent of questionnaires were returned; however, once non-eligible respondents were removed an adjusted response rate of 54% was achieved. Practice nurses play a significant role in the assessment and treatment of mental health problems, most frequently via the administration of depot antipsychotics and the screening for depression. However, antipsychotic side-effects were infrequently monitored and PNs' understanding of treatment issues in depression is poor. These findings may be associated with the reported lack of mental health training that PNs have received. The findings of this study have important implications for the training of practice nurses in mental health, specifically in the areas of medication management and the detection of mental disorders.


Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection.
There is an increasingly severe trend of antibiotic-resistant Neisseria gonorrhoeae strains worldwide and new therapeutic strategies are needed against this sexually-transmitted pathogen. Despite the urgency, progress towards a gonococcal vaccine has been slowed by a scarcity of suitable antigens, lack of correlates of protection in humans and limited animal models of infection. N. gonorrhoeae gene expression levels in the natural human host does not reflect expression in vitro, further complicating in vitro-basedvaccine analysis platforms. We designed a novel candidate antigen selection strategy (CASS), based on a reverse vaccinology-like approach coupled with bioinformatics. We utilized the CASS to mine gonococcal proteins expressed during human mucosal infection, reported in our previous studies, and focused on a large pool of hypothetical proteins as an untapped source of potential new antigens. Via two discovery and analysis phases (DAP), we identified 36 targets predicted to be immunogenic, membrane-associated proteins conserved in N. gonorrhoeae and suitable for recombinant expression. Six initial candidates were produced and used to immunize mice. Characterization of the immune responses indicated cross-reactive antibodies and serum bactericidal activity against different N. gonorrhoeae strains. These results support the CASS as a tool for the discovery of new vaccine candidates.


Does footwear affect articular cartilage volume change after a prolonged run?
The aim of this study was to investigate knee intra-articular cartilage volume changes after a prolonged running bout in three footwear conditions. Twelve participants performed 75-minute running bouts in the three footwear conditions. Before and after each running bout, magnetic resonance imaging (MRI) scans were obtained using a high-resolution 3.0 Tesla MRI. Three-dimensional reconstruction of the cartilage plates of the patella, the femur, and the tibia was created to quantify cartilage volume change due to the 75-minute running bout. Three-dimensional biomechanical data were also collected using an integrated motion capture and force treadmill system. There were no statistically significant differences among shoe conditions for all anatomical regions. However, significant cartilage volume reductions at all anatomical sites were observed after the 75-minute running bout in each footwear condition. These data suggest that the intra-articular knee cartilage undergoes a significant reduction in cartilage volume during a prolonged run that may indicate an increase in joint loading. There was a considerable variation in cartilage volume between participants across footwear conditions indicating an individual cartilage volume response to footwear. An individualistic approach to footwear recommendations may help in minimizing this change in cartilage.


Contractures. A historical perspective.
Orthopedic history vividly documents the continuing battle between restoring tissue stability and preserving functional mobility. Prolonged and uninterrupted rest, popularized by Hilton and Thomas, but promoted by many before them and subsequently continued by Jones, Orr, and others, assures healing. Contractures that permanently limit function are not an uncommon consequence. Hippocrates, Hunter, Lucas-Championniere, and David advocated judicious motion. Timing and the interpretation of the patient's pathologic state have proved to be the critical criteria. Modern antibiotics, antiinflammatory medications, acute surgical repair, and techniques that combine stability and early motion provide today's orthopedic surgeons' great versatility and capability. Despite these advantages the threat of contractures remains. The dictum "rest until healed" persists. Physiologic posturing of inflamed or swollen joints to minimize tissue strain introduces resting positions of 15 degrees plantar flexion at the ankle, and 30 degrees flexion at the knee and hip. These will be perpetuated by contractures if not actively counteracted by timely mobilizing procedures. Each of these joint positions is a serious deterrent to walking without stressful substitutive posturing, and the patient's ability to function is impaired.


Efficiency of multiple imputation to test for association in the presence of missing data.
The presence of missing data in association studies is an important problem, particularly with high-density single-nucleotide polymorphism (SNP) maps, because the probability that at least one genotype is missing dramatically increases with the number of markers. A possible strategy is to simply ignore the missing data and only use the complete observations, and, consequently, to accept a significant decrease of the sample size. Using Genetic Analysis Workshop 15 simulated data on which we removed some genotypes to generate different levels of missing data, we show that this strategy might lead to an important loss in power to detect association, but may also result in false conclusions regarding the most likely susceptibility site if another marker is in linkage disequilibrium with the disease susceptibility site. We propose a multiple imputation approach to deal with missing data on case-parent trios and evaluated the performance of this approach on the same simulated data. We found that our multiple imputation approach has high power to detect association with the susceptibility site even with a large amount of missing data, and can identify the susceptibility sites among a set of sites in linkage disequilibrium.


Concentrated albumin infusion as an aid to postoperative recovery after pelvic exenteration.
Twenty-eight patients underwent pelvic exenterations for gynecologic malignancies between June 1986 and June 1989. The postoperative fluid and electrolytes were managed by one of two regimens. One group of 10 patients was given concentrated 25% albumin infusion for the first 16 hr after surgery in addition to maintenance intravenous crystalloid solution according to ideal body weight. The second group of 18 patients received only a standard crystalloid solution. The albumin infusion group was found to have a more stable postoperative course as evidenced by less fluid boluses (P less than 0.01), fewer electrolyte bolus requirements (P less than 0.01), and easier management of blood pressure and urine output. There was a 50% decrease in total fluid requirement, a higher mean right atrial pressure (P less than 0.05), and a lower maintenance intravenous fluid rate (P less than 0.01). As a consequence, central hyperalimentation was started earlier (P less than 0.01) and the albumin infusion group left the Intensive Care Unit sooner than the non-albumin infusion group. There was not a single instance of clinical fluid overload with this slow infusion technique. Thus, concentrated albumin infusion was beneficial in the acute fluid management of these difficult patients.


Genome organization and transcription strategy in the complex GNS-L intergenic region of bovine ephemeral fever rhabdovirus.
A 1622 nucleotide region of the bovine ephemeral fever virus (BEFV) genome, located between the second glycoprotein (GNS) gene and the polymerase (L) gene, has been cloned and sequenced in Australian (BB7721) and Chinese (Beijing-1) isolates of the virus. In the Australian isolate, the region contains five long open reading frames (ORFs) organized into three coding regions (alpha, beta and gamma), each of which are bound by a consensus transcription initiation and transcription termination-polyadenylation-like sequences. The alpha coding region contains three long ORFs (alpha 1, alpha 2 and alpha 3). The alpha 1 ORF encodes a 10.6 kDa polypeptide which contains hydrophobic and highly basic regions characteristic of a viroporin. The alpha 2 ORF encodes a 13.7 kDa polypeptide and overlaps the alpha 3 ORF which encodes a 5.7 kDa polypeptide. The beta coding region contains a single long ORF encoding a polypeptide of 12.2 kDa. The gamma coding region, which does not occur in Adelaide River virus (ARV), contains a single long ORF encoding a polypeptide of 13.4 kDa. The Chinese isolate shares 91% nucleotide sequence identity with the Australian isolate. The organization of the alpha, beta and gamma coding regions is preserved and the sequences of the encoded polypeptides are similar to those of BB7721. The major transcription products of the region were identified in BB7721 as polycistronic alpha (alpha 1-alpha 2-alpha 3) and beta-gamma mRNAs. Sequence similarities in the BEFV alpha-beta and beta-gamma gene junctions, and the gamma-L and beta-L gene junctions of BEFV and ARV, suggest that the gamma gene may have evolved from the beta-gene by sequence duplication.


Evaluation of Prospectively Followed Adult Patients with Erythema Migrans Using the Beck Depression Inventory Second Edition.
The Beck Depression Inventory (BDI-II) may be used to evaluate individuals for symptoms of depression. In a 1-year prospective study, 52 adult Lyme disease patients with erythema migrans and 104 matched control subjects were clinically assessed and completed the BDI-II at study entry and approximately 6 and 12 months later following antibiotic treatment. The mean BDI-II score was significantly higher at the baseline visit among Lyme disease patients compared with controls (P = .002), but no significant differences between the groups were observed at either the 6- or 12-month study visits. Over the course of the study, the mean BDI-II scores decreased an average of approximately 0.22 points per month (P < .0005) for Lyme disease patients, whereas the mean scores changed very little for controls (mean change = -0.02 per month, P = .50). The total number of somatic symptoms, of the 12 symptoms evaluated, strongly and directly correlated with the BDI-II scores at the baseline visit for the Lyme disease patients. The mean BDI-II scores of patients with early Lyme disease significantly exceeded that of matched controls at study entry, but by 6 months the values did not differ significantly. There was a good-to-excellent direct correlation between the BDI-II score and the total number of symptoms, suggesting that the BDI-II scores were reflecting somatic rather than affective depressive symptoms. When using the BDI-II as an assessment tool of patients with Lyme disease, infection-related somatic symptoms per se need to be considered in the interpretation of the results.


Salient Band Selection for Hyperspectral Image Classification via Manifold Ranking.
Saliency detection has been a hot topic in recent years, and many efforts have been devoted in this area. Unfortunately, the results of saliency detection can hardly be utilized in general applications. The primary reason, we think, is unspecific definition of salient objects, which makes that the previously published methods cannot extend to practical applications. To solve this problem, we claim that saliency should be defined in a context and the salient band selection in hyperspectral image (HSI) is introduced as an example. Unfortunately, the traditional salient band selection methods suffer from the problem of inappropriate measurement of band difference. To tackle this problem, we propose to eliminate the drawbacks of traditional salient band selection methods by manifold ranking. It puts the band vectors in the more accurate manifold space and treats the saliency problem from a novel ranking perspective, which is considered to be the main contributions of this paper. To justify the effectiveness of the proposed method, experiments are conducted on three HSIs, and our method is compared with the six existing competitors. Results show that the proposed method is very effective and can achieve the best performance among the competitors.


Economic Insecurity and Deaths of Despair in US Counties.
Recent research has implicated economic insecurity in increasing midlife death rates and "deaths of despair," including suicide, chronic liver disease, and drug and alcohol poisoning. In this ecological longitudinal study, we evaluated the association between changes in economic insecurity and increases in deaths of despair and midlife all-cause mortality in US counties during 2000-2015. We extended a previously developed measure of economic insecurity using indicators from the Census and Federal Reserve Bank in US counties for the years 2000 and 2010. Linear regression models were used to estimate the association of change in economic insecurity with change in death rates through 2015. Counties experiencing elevated economic insecurity in either 2000 or 2010 had higher rates of deaths of despair and all-cause midlife mortality at baseline but similar rates of increase in deaths of despair from 2001 to 2015 compared with counties with stable low economic insecurity. Counties in the highest tertile of economic insecurity in 2000 and 2010 had 41% (95% confidence interval: 1.36, 1.47) higher midlife mortality rates at baseline and a rate of increase of 2% more per 5-year period (95% confidence interval: 1.00, 1.03) than counties with stable low economic insecurity. Economic insecurity may represent a population-level driver of US death trends.


The effect of hypertension on adult hippocampal neurogenesis in young adult spontaneously hypertensive rats and Dahl rats.
The dentate gyrus of the hippocampus is one of the few places in the brain where neurogenesis occurs in adulthood. Nowadays, an increasing number of children and young adults are affected by hypertension, one of the factors in the development of cerebrovascular diseases and age-related cognitive deficits. Since these cognitive deficits are often hippocampus-dependent, it is possible that hypertension exerts this effect via decreasing adult neurogenesis which has been shown to be essential for a range of cognitive tasks. We used spontaneously hypertensive rats, which develop hypertension in the first weeks of life. Half of them were treated with the antihypertensive drug captopril. We found that the drug-induced lowering of blood pressure in this period did not affect the rate of adult neurogenesis. In a second experiment, we used another animal model of hypertension - salt-sensitive and salt-resistant strains of Dahl rats. A high-salt diet induces hypertension in the salt-sensitive strain, but not in the salt-resistant strain. The high-salt diet led to salt-induced hypertension, but did not affect the level of adult neurogenesis in the dentate gyrus of the hippocampus. We conclude that hypertension does not significantly affect the rate of hippocampal neurogenesis in young adult rats.


Association Between a First-Degree Family History and Self-Reported Personal History of Obesity, Diabetes, and Heart and Blood Conditions: Results From the All of Us Research Program.
Background Family history reflects the complex interplay of genetic susceptibility and shared environmental exposures and is an important risk factor for obesity, diabetes, and heart and blood conditions (ODHB). However, the overlap in family history associations between various ODHBs has not been quantified. Methods and Results We assessed the association between a self-reported family history of ODHBs and their risk in the adult population (age ≥20 years) of the AoU (All of Us) Research Program, a longitudinal cohort study of diverse participants across the United States. We conducted a family history-wide association study to systematically assess the association of a first-degree family history of 15 ODHBs in AoU. We performed stratified analyses based on racial and ethnic categories, education, household income and gender minority status, and quantified associations by type of affected relatives. Of 125 430 participants, 76.8% reported a first-degree family history of any ODHB, most commonly hypertension (n=64 982, 51.8%), high cholesterol (49 753, 39.7%), and heart attack (29 618, 23.6%). We use the FamWAS method to estimate 225 familial associations among 15 ODHBs. The results include overlapping associations between family history of different types of cardiometabolic conditions (such as type 2 diabetes and coronary artery disease), and their risk factors (obesity, hypertension), where adults with a family history of 1 ODHB exhibited 1.1 to 5.6 times (1.5, on average) the odds of having a different ODHB. Conclusions Our findings inform the utility of family history data as a risk assessment and screening tool for the prevention of ODHBs and to provide additional insights into shared risk factors and pathogenic mechanisms.


Preoperative Evaluation, Anesthetic Considerations, and Perioperative Oral and Parenteral Medications in Total Knee Arthroplasty.
Effective pain management protocol is critical to early mobilization, early discharge, and increasing patient satisfaction for hip and knee arthroplasty. Surgeons have tried to minimize dependence on opioids and opioid-related adverse events through multimodal protocols that use periarticular injections as well as oral and parenteral medications. The efficacy, cost, and adverse effects of each of these components need to be considered when formulating an evidence-based multimodal pain protocol. Recent advancements have changed understanding of the variability in metabolism of commonly given agents around the time of surgery. It is important to provide a systematic approach to the preoperative evaluation, anesthetic considerations, and the administration of oral and parenteral medications routinely used in total knee arthroplasty.


Temporary Inferior Vena Cava Filters: How Do We Move Forward?
Despite their widespread use, the indications for the selective use of temporary inferior vena cava (IVC) filters remains uncertain with few trials supporting their use. Additionally, the risks of long-term temporary IVC filter insertion are being increasingly discussed amongst the mainstream media and through multiple class action lawsuits. Retrievable IVC filters were specifically designed to have a less secure implantation in order to facilitate retrieval. However, multiple reports have demonstrated significant filter-related complications, most commonly related to duration of implantation. Furthermore, the risk is not isolated to one manufacturer alone. The incidence of filter-related complications is linearly related to its duration of time on the market. Currently, the FDA recommends that IVC filters be removed within 25-54 days of their implantation. Unfortunately, little evidence exists to show that this recommendation is followed routinely. Recently, the PRESERVE Trial (NCT02381509) was initiated as a multicenter non-randomized open label study to determine the safety and effectiveness of commercially available IVC filters (both temporary and permanent) in individuals who require mechanical prophylaxis against pulmonary embolism. Until such evidence is developed, temporary IVC filters should be implanted based on best available evidence and routinely removed within the guidelines of the FDA of 25-54 days. A fair question at this point is whether the design features themselves that are required to manufacture a low profile removable IVC filter can achieve effective prophylaxis against pulmonary embolism at a low rate of short and long-term complications.


Adiposity is associated with structural properties of the adolescent brain.
Obesity, a major risk factor for cardiometabolic disease, is associated with variations in a number of structural properties in the adult brain, as assessed with magnetic resonance imaging (MRI). In this study, we investigated the cross-sectional relationship between visceral fat (VF), total body fat (TBF) and three MRI parameters in the brains of typically developing adolescents: (i) T1-weighted (T1W) signal intensity; (ii) T1W signal contrast between white matter (WM) and gray matter (GM); and (iii) magnetization transfer ratio (MTR). In a community-based sample of 970 adolescents (12-18 years old, 466 males), VF was quantified using MRI, and total body fat was measured using a multifrequency bioimpedance. T1W images of the brain were used to determine signal intensity in lobar GM and WM, as well as WM:GM signal contrast. A magnetization transfer (MT) sequence of MT(ON) and MT(OFF) was used to obtain MTR in GM and WM. We found that both larger volumes of VF and more TBF were independently associated with higher signal intensity in WM and higher WM:GM signal contrast, as well as higher MTR in both GM and WM. These relationships were independent of a number of potential confounders, including age, sex, puberty stage, household income and height. Our results suggest that both visceral fat and fat deposited elsewhere in the body are associated independently with structural properties of the adolescent brain. We speculate that these relationships suggest the presence of adiposity-related variations in phospholipid composition of brain lipids.


Methylenedioxymethamphetamine suppresses production of the proinflammatory cytokine tumor necrosis factor-alpha independent of a beta-adrenoceptor-mediated increase in interleukin-10.
Recent data suggest that 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") has marked immunosuppressive properties. In this study, we investigate the effect of MDMA on production of the anti-inflammatory cytokine interleukin (IL)-10 in response to an in vivo challenge with bacterial lipopolysaccharide (LPS). Our data demonstrate that both acute and repeated administration of MDMA increases production of LPS-induced IL-10 in vivo, and this increase correlates inversely with the ability of MDMA to suppress the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. Despite this correlation, immunoneutralization of IL-10 does not reverse the suppressive effect of MDMA on LPS-induced TNF-alpha production, indicating that suppression of this proinflammatory cytokine is not mediated by IL-10. In vitro exposure to MDMA does not mimic the immunosuppressive cytokine phenotype induced in vivo, suggesting that these immunosuppressive effects are not mediated by a direct action on monocytes per se. As MDMA activates that hypothalamic pituitary adrenal axis and sympathetic nervous system, we examined the role of glucocorticoids and catecholamines in its immunosuppressive actions. However, the immunosuppressive cytokine phenotype induced by MDMA was not altered by adrenalectomy, sympathetic denervation, or ganglionic blockade, indicating that neither glucocorticoids nor adrenal/sympathetic-derived catecholamines mediate these immunosuppressive effects of MDMA. Interestingly, beta-adrenoceptor blockade completely inhibited the increase in IL-10 induced by MDMA without altering the suppression of TNF-alpha. Taken together, these data demonstrate a role for beta-adrenoceptor activation in the ability of MDMA to increase LPS-induced IL-10 and highlight a mechanistic dissociation between the ability of MDMA to increase IL-10 and suppress production of the proinflammatory cytokine TNF-alpha.


Critical role for bone marrow stromal antigen 2 in acute Chikungunya virus infection.
Bone marrow stromal antigen 2 (BST-2; also known as tetherin or CD317) is an IFN-inducible gene that functions to block the release of a range of nascent enveloped virions from infected host cells. However, the role of BST-2 in viral pathogenesis remains poorly understood. BST-2 plays a multifaceted role in innate immunity, as it hinders retroviral infection and possibly promotes infection with some rhabdo- and orthomyxoviruses. This paradoxical role has probably hindered exploration of BST-2 antiviral function in vivo. We reported previously that BST-2 tethers Chikungunya virus (CHIKV)-like particles on the cell plasma membrane. To explore the role of BST-2 in CHIKV replication and host protection, we utilized CHIKV strain 181/25 to examine early events during CHIKV infection in a BST-2(-/-) mouse model. We observed an interesting dichotomy between WT and BST-2(-/-) mice. BST-2 deficiency increased inoculation site viral load, culminating in higher systemic viraemia and increased lymphoid tissues tropism. A suppressed inflammatory innate response demonstrated by impaired expression of IFN-α, IFN-γ and CD40 ligand was observed in BST-2(-/-) mice compared with the WT controls. These findings suggested that, in part, BST-2 protects lymphoid tissues from CHIKV infection and regulates CHIKV-induced inflammatory response by the host.


Effect of storage time, thermocycling and resin coating on durability of dentin bonding systems.
Along with development of different dental adhesives, concerns about hydrolytic deg-radation of the adhesive components have arisen. The purpose of this study was to evaluate the in vitro influence of thermocycling, water storage and resin coating on the microshear bond strength of total etch and self etch adhesive systems to dentin. The superficial coronal dentin of eighty intact third molars were exposed and divided into 5 equal groups. Dental adhesives including Scotch Bond Multi Purpose (SBMP), Single Bond (SB), Clearfil SE Bond (CSE), Prompt L-Pop (PLP), and Prompt L-Pop plus Margin bond (PLPM) were applied according to the manufacturers' instructions on prepared surfaces in the study groups, respectively. Then composite cylinders were bonded and specimens were divided into two subgroups. One subgroup was stored in water for 24 hours. The second subgroup was subjected to 3000 thermocycle shocks and then was stored in 37°C water for 3 months. Finally, all teeth were subjected to the microshear bond strength test. Data were analyzed using two-way ANOVA and Tukey HSD tests. One specimen similar to each subgroup was also prepared for SEM evaluation. After one-day storage, the SBMP showed the highest bond strength followed by CSE, PLPM, SB and PLP. After three months storage, the highest bond strength was observed in SBMP followed by PLPM, CSE, SB, and PLP. SBMP showed the best bond strength while CSE represented acceptable bond durability. Resin coating on PLP improved bond strength and durability.


Population-based epidemiology: The Glostrup Population Studies 1964-2021.
The Glostrup Population Studies are population-based cohorts undertaken in the south-western part of Greater Copenhagen since 1964. The participants were randomly selected from the adult general population. The first cohort was established to assess cardiovascular risk factors and, since, the objectives have been broadened to describe and analyse the health of the general population. The studies are health-examination studies with clinical and biochemical data in addition to data from self-administered questionnaires and, in some studies, interviews. Fasting blood and urine samples were collected and stored in our biobank for further studies. Several of the cohorts were performed according to standardized methods in international consortia, hence data have been pooled with other, both Danish and international, cohorts. To date more than 30,000 individuals, both men and women, aged 15-85 years, have participated in The Glostrup Population Studies and participants have been re-examined up to eight times. The data can be used for disease-specific epidemiology, social epidemiology, genetic epidemiology, ageing, lifestyle and health interventions nested within the cohorts. The Glostrup Population Studies represent a great resource; the possibility of merging the different cohorts enables large datasets, as well as trends over time. Furthermore, the long follow-up in both the national registers and with follow-up examinations is unique. The purpose of this commentary is to inform about The Glostrup Population Studies and to invite collaborations to continue utilizing this great resource to combat current and future challenges within health promotion and disease prevention.


[The seroprevalence of HCV in patients submitted to hemodialysis and health professionals in the State of Minas Gerais, southwest of Brazil].
Patients with chronic renal failure(CRF) in hemodialysis(HD) programs comprise a risk group for acquisition of hepatitis C virus(HCV) infection. The objectives were to evaluate the seroprevalence of HCV in patients submitted to HD in State of Minas Gerais(MG), southwest of Brazil; to correlate this seroprevalence with the time of treatment on HD; to investigate the anti-HCV seropositivity in health professionals, to investigate the existence of a correlation between mean HCV seroprevalence and the human development index (HDI). Patients from 66 healthcare units(HU) were studied using a validated questionnaire and considering the positive values of anti-HCV(Elisa III) tests performed in these units between january and december 2003. the majority of patients were male (56.2%), between 41 and 60 years old. The mean seroprevalence of HCV in the 66 healthcare units was 13+/-9.5%; the three-monthly seroprevalence was below 20%, 15% and 10% in 75%, 50% and 40% of healthcare units, respectively. When the HU were grouped according to HCV seroprevalence into low(<5%), medium(5-15%) and high seroprevalence(>15%), 20% of the units have low, 42% medium and 37.5% were found to have high seroprevalence. No correlation was found between HDI and HCV seroprevalence (r=0.42; p=0.174) but in the regions in which the HDI was higher, HCV seroprevalence was also higher. There was a positive correlation between HCV seroprevalence and time on HD in 884 patients in the 4 HU (p<0.001). The seroprevalence of HCV was investigated in 387 healthcare professionals(29%) working in 14 HU. They were divided into two groups according to their time of professional activity: <10 y (G1) and >10 y (G2). In G1, there were no cases of anti-HCV seropositivity. In G2, 3 members of the staff were anti-HCV seropositive. The mean time of work of the seropositive staff in the HU was 15.6 years. The seroprevalence of HCV was 0.8% when all the healthcare professionals were taken into consideration. There was no statistically significant difference with respect to HCV seroprevalence between G1 and G2 with respect to the time of occupational exposure (p=0.27). the seroprevalence of HCV in patients on HD in MG is 13+/-9.5% and was <10% in 40% of the HU; there was no statistically significant correlation between HDI and seroprevalence of HCV in the healthcare units evaluated; there was a statistically significant correlation between HCV seroprevalence and time of treatment on HD; HCV seroprevalence in the health professionals studied was 0.8% and similar to the literature.


Recurrent headache in chinese children: any agreement between clinician diagnosis and symptom-based diagnoses using the International Classification of Headache Disorders (Second Edition)?
There has been a lack of published data on the pattern of recurrent headache in Chinese children. The validity of the International Classification of Headache Disorders criteria has not been evaluated in Chinese children. We performed a retrospective medical record review of 124 children aged <18 years with an International Classification of Diseases coding of headache followed up in a general outpatient clinic in a university-based hospital over a 3-year period (2000-2002). The aims of our study were to (1) study the pattern of recurrent headache in Chinese children and (2) study any agreement between clinical diagnoses made by our board-certified pediatricians and symptom-based diagnoses using the second edition of the International Classification of Headache Disorders (International Classification of Headache Disorders-II). The most common type was unclassified headache (70.2%), followed by infrequent episodic tension-type headache (24.2%) and migraine without aura (5.6%). A family history of headache or migraine was more commonly found in children with infrequent episodic tension-type headache or migraine without aura (P = .0109). The co-occurrence of abdominal pain with infrequent episodic tension-type headache was 30%; for unclassified headache, it was 19.5%. Dysmenorrhea occurred in 7.1% of girls with infrequent episodic tension-type headache and 8.6% of girls with unclassified headache. However, migraine without aura was not associated with abdominal pain or dysmenorrhea. Children with migraine without aura were more frequently referred to child neurologists (P = .0207) and admitted (P = .0000). Neurologic investigations, including electroencephalography, computed tomography, or magnetic resonance imaging of the brain, were performed in less than 30% of cases. Abnormal results were found in only seven cases; with two referred to a neurosurgeon and none requiring surgical intervention. Thus, by using the clinical diagnosis of our board-certified pediatricians as the standard, the sensitivity and specificity of International Classification of Headache Disorders-II-based definition of migraine without aura was 23.1% and 93.4%, respectively, and for infrequent episodic tension-type headache, it was 37.5% and 76%, respectively. The typical characteristics of migraine tend to emerge later and might have led to underdiagnosis of the younger age group, with a higher rate of referral and inpatient management. The new edition of the International Classification of Headache Disorders criteria is still restrictive in clinical practice and might not be able to reflect current pediatric practice. Further studies with a defined study period or recurrent headache might be more useful in analyzing the use of these new International Classification of Headache Disorders criteria in the diagnosis of recurrent headache in children.


Field studies on health effects from the application of two organophosphorus insecticide formulations by hand-held ULV to cotton.
Two field studies to assess the health implications for farmers applying two different formulations containing organophosphorus (OP) pesticides to cotton by hand-held ULV are described. The first study, carried out in the Ivory Coast, involved the application of an endrin/DDT/methylparathion (MEP) formulation in an aromatic hydrocarbon solvent. The second study took place in Indonesia with a 20% monocrotophos formulation in a mixture of a glycol and a glycol ether. Both studies were carried out under actual field conditions. The purpose of the studies was to get a good assessment of the health hazards of the particular formulation, used under the specific circumstances and agronomic requirements of the area of application and taking into account all local, climatic and cultural conditions that could be of possible influence. The results showed that in both studies skin exposures took place during application and especially during handling, filling and cleaning, and that inhalation of spray mist was negligible. Absorption was confirmed by the presence in urine of metabolites of endrin and methylparathion in the Ivory Coast study, and of dimethyl phosphate in the Indonesia study. No clinical signs or symptoms of intoxication were discovered in either study, nor were inhibitions of cholinesterase (ChE) activity of health significance established under the conditions of the studies. In addition, various practical aspects such as choice of apparatus, of formulation, the application procedures etc. are discussed.


HUA ENHANCER1 is involved in posttranscriptional regulation of positive and negative regulators in Arabidopsis photomorphogenesis.
Light regulates growth and developmental processes in plants via global transcriptome adjustment, translational control, and multilayered posttranslational modification of proteins. The transcriptional activation and repression of light-responsive genes has been well documented; however, the impact of posttranscriptional regulation on conveying light signals has been less addressed. Here, we examined whether optimal photomorphogenesis in Arabidopsis thaliana requires the proper biogenesis of small regulatory RNAs that play pivotal roles in the posttranscriptional regulation of gene expression. Arabidopsis carrying a mutation in HUA ENHANCER1 (HEN1), required for stabilization of small regulatory RNAs, showed defects in multiple aspects of photomorphogenic and skotomorphogenic development. HEN1 negatively regulated Arabidopsis photomorphogenesis. Light-activated HEN1 expression depended on the photoreceptors phytochrome A (phyA), phyB, cryptochrome 1 (cry1), and cry2 and key transcriptional regulators ELONGATED HYPOCOTYL5 (HY5) and HY5-HOMOLOG. We also demonstrate the involvement of the small regulatory RNAs miR157d and miR319 in modulating the expression of a positive regulator, HY5, and negative regulators TEOSINTE BRANCHED1, CYCLOIDEA AND PCF family proteins, respectively, for optimal photomorphogenic development in Arabidopsis.


Molecular preservation.
The differing patterns of molecular abundances in organisms are fundamental to the understanding of the biomolecular palaeontological record. All organisms contain DNA, RNA, protein, polysaccharides and lipid components, together with glycolipids, lipopolysaccharides and other complex molecules. Certain biopolymers, however, are restricted in their distributions; for example, lignin, cutin and sporopollenin are found only in terrestrial plants. The detailed chemical structures, namely the bond types present and their precise intramolecular environments, determine resistance to degradation. Observations of biomolecular preservation are compared with predictions based on chemical structure and on conditions encountered during decay.


Scanning electron microscopy of intracardiac myxoma.
Scanning electron microscopy was utilized to study the surface morphology of intracardiac myxomas and to compare it with that of an atrial thrombus. The thrombus was only partially endothelialized, whereas myxomas were almost always completely covered by endothelial cells. Endothelium-lined crevices and clefts were a striking feature of the myxoma, and they were not seen in the atrial thrombus. In areas where the surface endothelium was denuded, fibrin and platelet aggregates were noted in both the myxoma and the thrombus.


Hemorrhagic erosive gastritis. A clinical study.
Four hundred consecutive patients, in a representative Southern California population, hospitalized for upper gastrointestinal hemorrhage, had endoscopic examinations performed within 24 hours of arrival in the emergency room. Seventy-four (18.5 percent) of these were found to have the typical lesions of acute hemorrhagic erosive gastritis. The clinical spectrum of this group is examined and a comparison made with a Veterans Hospital population reported previously.


Lumbo-sacral fusion with spring fixation.
A method of posterior lumbo-sacral fusion is described in which springs are used to fix the grafts and to maintain immobilisation. Fifty patients with lumbar disc degeneration or spondylolisthesis have been reviewed. The results have been assessed clinically by grading the symptoms before and after operation. Stay in hospital has been short and return to work rapid. There has been a high proportion of good results.


Ultrafast structural pathway of charge transfer in n,n,n',n'-tetramethylethylenediamine.
We have explored the ultrafast molecular structural dynamics associated with charge transfer in N,N,N',N'-tetramethylethylenediamine using Rydberg fingerprint spectroscopy in conjunction with self-interaction corrected density functional theory. Excitation at 239 nm prepares the molecule in the Franck-Condon region of the 3s state with the charge localized on one of the two amine groups. As seen from the time-dependent Rydberg electron binding energies, the pathway of the rapidly ensuing dynamics leads through several structurally distinct conformers with various degrees of charge localization before reaching the fully charge-delocalized structure on a picosecond time scale. At several steps along the reaction path, the transient structures are identified through a comparison of the spectroscopically observed binding energies with computed values. The molecular structure is seen to evolve dynamically from an initially folded conformer to the stretched form that supports charge delocalization before an equilibrium sets in with forward and backward time constants of 1.19 (0.14) and 2.61 (0.31) ps, respectively. A coherent wavepacket motion in the charge-localized state with a period of 270 (17) fs and damping of 430 (260) fs is observed and tentatively assigned to the nitrogen umbrella motion. The damping time constant indicates the rate of the energy flow into other vibrations that are not activated by the optical excitation.


Molecular morphology and function of bull spermatozoa linked to histones and associated with fertility.
Sub-par fertility in bulls is influenced by alterations in sperm chromatin, and it might not be solved with increased sperm concentration in artificial insemination. Appropriate histone retention during sperm chromatin condensation plays critical roles in male fertility. The objective of this study was to determine failures of sperm chromatin condensation associated with abnormal persistence or accessibility of histones by aniline blue (ANBL) test, expression levels, and cellular localizations of one variant and two core histones (H3.3, H2B, and H4 respectively) in the spermatozoa of low-fertility (LF) vs high-fertility (HF) bulls. The expression levels and cellular localizations of histones in spermatozoa were studied using immunoblotting, immunocytochemistry, and staining methods. The bioinformatics focused on the sequence identity and evolutionary distance of these proteins among three mammalian species: bovine, mouse, and human. We demonstrated that ANBL staining was different within the LF (1.73 (0.55, 0.19)) and HF (0.67 (0.17, 0.06)) groups (P<0.0001), which was also negatively correlated with in vivo bull fertility (r=-0.90, P<0.0001). Although these histones were consistently detectable and specifically localized in bull sperm cells, they were not different between the two groups. Except H2B variants, H3.3 and H4 showed 100% identity and were evolutionarily conserved in bulls, mice and humans. The H2B variants were more conserved between bulls and humans, than in mice. In conclusion, we showed that H2B, H3.3, and H4 were detectable in bull spermatozoa and that sperm chromatin condensation status, changed by histone retention, is related to bull fertility.


Ozonation enhancement of low cost double-stranded DNA binding dye based fluorescence measurement of total bacterial load in water.
We demonstrated the feasibility of using ozonation to enhance the performance of dsDNA binding dye SYBR Green I in the fluorescence measurement of total bacterial load in water. Unlike its membrane permeable but expensive equivalent such as SYTO82 dye, SYBR Green I is many times cheaper but membrane impermeable. Ozonation allowed SYBR Green I dye to permeate the membrane and bind with the dsDNA within by first breaching it. Using E. coli K12 bacteria at serial dilution ratios from 1/1 (980 CFU mL-1) to 1/200, we achieved corresponding quantification from 618.7 ± 9.4 to 68.0 ± 1.9 RFU (100 to 11.00% normalized RFU). In comparison, plate counting and optical density measurement were only able to quantify up till a serial dilution ratio of 1/50 (40 CFU mL-1 and 0.0421, respectively). Most importantly with ozonation, the sensitivity of SYBR Green I dye based fluorescence measurement was improved by ∼140 to 210% as compared to that without ozonation. Given its low electrical power consumption, lab-on-chip compatibility and reagent-less nature, ozonation is highly compatible with portable fluorimeters to realize low-cost monitoring of total bacterial load in water.


Interspecies interactions result in enhanced biofilm formation by co-cultures of bacteria isolated from a food processing environment.
Bacterial attachment and biofilm formation can lead to poor hygienic conditions in food processing environments. Furthermore, interactions between different bacteria may induce or promote biofilm formation. In this study, we isolated and identified a total of 687 bacterial strains from seven different locations in a meat processing environment and evaluated their biofilm formation capability. A diverse group of bacteria was isolated and most were classified as poor biofilm producers in a Calgary biofilm device assay. Isolates from two sampling sites, the wall and the meat chopper, were further examined for multispecies biofilm formation. Eight strains from each sampling site were chosen and all possible combinations of four member co-cultures were tested for enhanced biofilm formation at 15 °C and 24 °C. In approximately 20% of the multispecies consortia grown at 15 °C, the biofilm formation was enhanced when comparing to monospecies biofilms. Two specific isolates (one from each location) were found to be present in synergistic combinations with higher frequencies than the remaining isolates tested. This data provides insights into the ability of co-localized isolates to influence co-culture biofilm production with high relevance for food safety and food production facilities.


LadRa-Net: Locally Aware Dynamic Reread Attention Net for Sentence Semantic Matching.
Sentence semantic matching requires an agent to determine the semantic relation between two sentences, which is widely used in various natural language tasks, such as natural language inference (NLI) and paraphrase identification (PI). Much recent progress has been made in this area, especially attention-based methods and pretrained language model-based methods. However, most of these methods focus on all the important parts in sentences in a static way and only emphasize how important the words are to the query, inhibiting the ability of the attention mechanism. In order to overcome this problem and boost the performance of the attention mechanism, we propose a novel dynamic reread (DRr) attention, which can pay close attention to one small region of sentences at each step and reread the important parts for better sentence representations. Based on this attention variation, we develop a novel DRr network (DRr-Net) for sentence semantic matching. Moreover, selecting one small region in DRr attention seems insufficient for sentence semantics, and employing pretrained language models as input encoders will introduce incomplete and fragile representation problems. To this end, we extend DRr-Net to locally aware dynamic reread attention net (LadRa-Net), in which local structure of sentences is employed to alleviate the shortcoming of byte-pair encoding (BPE) in pretrained language models and boost the performance of DRr attention. Extensive experiments on two popular sentence semantic matching tasks demonstrate that DRr-Net can significantly improve the performance of sentence semantic matching. Meanwhile, LadRa-Net is able to achieve better performance by considering the local structures of sentences. In addition, it is exceedingly interesting that some discoveries in our experiments are consistent with some findings of psychological research.


Proteomic characterization of the colorectal cancer response to chemoradiation and targeted therapies reveals potential therapeutic strategies.
Chemoradiation and targeted therapies are the major treatments for colorectal cancer (CRC); however, molecular properties associated with therapy resistance are incompletely characterized. Here, we profile the proteome of 254 tumor tissues from patients with CRC undergoing chemotherapy, chemoradiation, or chemotherapy combined with targeted therapy. Proteome-based classification reveals four subtypes featured with distinct biological and therapeutic characteristics. The integrative analysis of CRC cell lines and clinical samples indicates that immune regulation is significantly associated with drug sensitivity. HSF1 can increase DNA damage repair and cell cycle, thus inducing resistance to radiation, while high expression of HDAC6 is negatively associated with response of cetuximab. Furthermore, we develop prognostic models with high accuracy to predict the therapeutic response, further validated by parallel reaction monitoring (PRM) assay in an independent validation cohort. This study provides a rich resource for investigating the mechanisms and indicators of chemoradiation and targeted therapy in CRC.


The epidemiology of schistosomiasis in Egypt: patterns of Schistosoma mansoni infection and morbidity in Kafer El-Sheikh.
This is a descriptive report of the Epidemiology 1, 2, 3 project in Egypt that made use of large probability sampling methods. These results focus on Schistosoma mansoni infection in the northern Nile Delta governorate of Kafr El Sheikh. A probability sample of 18,777 persons, representing the rural population of the entire governorate, was drawn. The sample was designed not to exclude villages based on location or presence of health care facilities and to include representation of the smaller ezbas or hamlets. The objective was to obtain detailed estimates on age- and sex-specific patterns of S. mansoni infection, and to provide a baseline for prospective studies. Stool specimens were examined by the Kato method. The estimated mean +/- SE prevalence of S. mansoni infection in the rural population was 39.3 +/- 3.3% in 44 villages and ezbas after weighing for the effects of the sample design. The estimated mean +/- SE geometric mean egg count per gram of stool (GMEC) was 72.9 +/- 7.3. Prevalence and GMEC varied considerably by village and ezba, with ezbas having a significantly higher prevalence. Villages and ezba-specific prevalence was strongly associated with GMEC (r2 = 0.61, P < 0.001). The prevalence of S. mansoni infection increased by age to 55.4 +/- 3.2% at age 16 without a significant change in the adult ages. There were no gender differences until age 6, after which males were consistently higher until middle age, when the differences converged. The age- and sex-specific pattern of GMEC varied widely; however, when the GMEC data were collapsed into 5-year age groups, the GMEC peaked at 81.5 +/- 12.1 eggs/g in the 10-14-year-old age group. These estimates provide the basis for evaluating control measures for reducing prevalence, intensity of infection, and transmission.


Essential roles of Windei and nuclear monoubiquitination of Eggless/SETDB1 in transposon silencing.
Eggless/SETDB1 (Egg), the only essential histone methyltransferase (HMT) in Drosophila, plays a role in gene repression, including piRNA-mediated transposon silencing in the ovaries. Previous studies suggested that Egg is post-translationally modified and showed that Windei (Wde) regulates Egg nuclear localization through protein-protein interaction. Monoubiquitination of mammalian SETDB1 is necessary for the HMT activity. Here, using cultured ovarian somatic cells, we show that Egg is monoubiquitinated and phosphorylated but that only monoubiquitination is required for piRNA-mediated transposon repression. Egg monoubiquitination occurs in the nucleus. Egg has its own nuclear localization signal, and the nuclear import of Egg is Wde-independent. Wde recruits Egg to the chromatin at target gene silencing loci, but their interaction is monoubiquitin-independent. The abundance of nuclear Egg is governed by that of nuclear Wde. These results illuminate essential roles of nuclear monoubiquitination of Egg and the role of Wde in piRNA-mediated transposon repression.


A Study of Effects of MultiCollinearity in the Multivariable Analysis.
A multivariable analysis is the most popular approach when investigating associations between risk factors and disease. However, efficiency of multivariable analysis highly depends on correlation structure among predictive variables. When the covariates in the model are not independent one another, collinearity/multicollinearity problems arise in the analysis, which leads to biased estimation. This work aims to perform a simulation study with various scenarios of different collinearity structures to investigate the effects of collinearity under various correlation structures amongst predictive and explanatory variables and to compare these results with existing guidelines to decide harmful collinearity. Three correlation scenarios among predictor variables are considered: (1) bivariate collinear structure as the most simple collinearity case, (2) multivariate collinear structure where an explanatory variable is correlated with two other covariates, (3) a more realistic scenario when an independent variable can be expressed by various functions including the other variables.


The effects of cholera toxin on cellular energy metabolism.
Multianalyte microphysiometry, a real-time instrument for simultaneous measurement of metabolic analytes in a microfluidic environment, was used to explore the effects of cholera toxin (CTx). Upon exposure of CTx to PC-12 cells, anaerobic respiration was triggered, measured as increases in acid and lactate production and a decrease in the oxygen uptake. We believe the responses observed are due to a CTx-induced activation of adenylate cyclase, increasing cAMP production and resulting in a switch to anaerobic respiration. Inhibitors (H-89, brefeldin A) and stimulators (forskolin) of cAMP were employed to modulate the CTx-induced cAMP responses. The results of this study show the utility of multianalyte microphysiometry to quantitatively determine the dynamic metabolic effects of toxins and affected pathways.


Vitamin E therapy beyond cancer: Tocopherol versus tocotrienol.
The discovery of vitamin E (α-tocopherol) began in 1922 as a vital component required in reproduction. Today, there are eight naturally occurring vitamin E isoforms, namely α-, β-, γ- and δ-tocopherol and α-, β-, γ- and δ-tocotrienol. Vitamin E is potent antioxidants, capable of neutralizing free radicals directly by donating hydrogen from its chromanol ring. α-Tocopherol is regarded the dominant form in vitamin E as the α-tocopherol transfer protein in the liver binds mainly α-tocopherol, thus preventing its degradation. That contributed to the oversight of tocotrienols and resulted in less than 3% of all vitamin E publications studying tocotrienols. Nevertheless, tocotrienols have been shown to possess superior antioxidant and anti-inflammatory properties over α-tocopherol. In particular, inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase to lower cholesterol, attenuating inflammation via downregulation of transcription factor NF-κB activation, and potent radioprotectant against radiation damage are some properties unique to tocotrienols, not tocopherols. Aside from cancer, vitamin E has also been shown protective in bone, cardiovascular, eye, nephrological and neurological diseases. In light of the different pharmacological properties of tocopherols and tocotrienols, it becomes critical to specify which vitamin E isoform(s) are being studied in any future vitamin E publications. This review provides an update on vitamin E therapeutic potentials, protective effects and modes of action beyond cancer, with comparison of tocopherols against tocotrienols. With the concerted efforts in synthesizing novel vitamin E analogs and clinical pharmacology of vitamin E, it is likely that certain vitamin E isoform(s) will be therapeutic agents against human diseases besides cancer.


Improvement of hepatocyte engraftment by co-transplantation with pancreatic islets in hepatocyte transplantation.
Because of the fragility of isolated hepatocytes, extremely poor engraftment of transplanted hepatocytes remains a severe issue in hepatocyte transplantation. Therefore, improving hepatocyte engraftment is necessary to establish hepatocyte transplantation as a standard therapy. Since the pancreatic islets are known to have favorable autocrine effects, we hypothesized that the transplanted islets might influence not only the islets but also the nearby hepatocytes, subsequently promoting engraftment. We evaluated the effects of islet co-transplantation using an analbuminemic rat model (in vivo model). Furthermore, we established a mimicking in vitro model to investigate the underlying mechanisms. In an in vivo model, the hepatocyte engraftment was significantly improved only when the islets were co-transplanted to the nearby hepatocytes (p < 0.001). Moreover, the transplanted hepatocytes appeared to penetrate the renal parenchyma together with the co-transplanted islets. In an in vitro model, the viability of cultured hepatocytes was also improved by coculture with pancreatic islets. Of particular interest, the coculture supernatant alone could also exert beneficial effects comparable to islet coculture. Although insulin, VEGF, and GLP-1 were selected as candidate crucial factors using the Bio-Plex system, beneficial effects were partially counteracted by anti-insulin receptor antibodies. In conclusion, this study demonstrated that islet co-transplantation improves hepatocyte engraftment, most likely due to continuously secreted crucial factors, such as insulin, in combination with providing favorable circumstances for hepatocyte engraftment. Further refinements of this approach, especially regarding substitutes for islets, could be a promising strategy for improving the outcomes of hepatocyte transplantation.


[Post-meningitis Dumping Syndrome: A Case Report and Literature Review].
Dumping syndrome has long been associated with gastric surgery. The authors experienced an adult patient presenting with dumping syndrome after meningitis without any previous surgical procedures on the stomach and small bowel. Dysfunction of the autonomic nervous system after infective meningitis may originate from postinfectious sequelae or an immunologic mechanism. A comprehensive study and proper management of autonomic symptoms of patients with a central nervous system infection are needed.


Heterogeneity of Campylobacter species isolated from serial stool specimens of Egyptian children using pulsed field gel electrophoresis.
The genus Campylobacter spp. is a common cause of human acute bacterial enteritis and travellers' diarrhoea worldwide. To determine whether multiple serial isolations of Campylobacter spp., when obtained from a single child, represented the same or a different organism. In a birth cohort study conducted in Egypt, numerous children showed serial isolations of Campylobacter spp. Of these, 13 children were selected from different households based on the successive isolation of six or more Campylobacter isolates from stool samples. Eighty isolates were recovered and identified as either Campylobacter coli (n = 25) or Campylobacter jejuni (n = 55). Pulsed-field gel electrophoresis (PFGE) revealed the presence of 38 unique C. jejuni and 24 C. coli profiles at a similarity level of ≥ 90%. Although no serially-identical isolates were detected in six children, others demonstrated at least one identical couple of isolates; all identified serially between one to six weeks. Two children demonstrated > 80% similar couples of isolates that appeared seven months apart. PFGE could be a useful tool for differentiating reinfection, relapse and convalescent excretion phases. Our data suggest that Campylobacter infection in children is a complex process; children are exposed to multiple species in endemic environments and strains of the same bacterium appear to be shed serially between one to six weeks after the first exposure. Isolates that persisted for longer periods were relatively less similar, as shown from the results of this study.


Pharmacokinetics of Temozolomide in a Patient With Glioblastoma Undergoing Hemodialysis: A Short Communication.
Temozolomide (TMZ) is an alkylating agent used to treat glioblastoma. However, the pharmacokinetics of TMZ to establish a treatment strategy for patients undergoing hemodialysis (HD) remain unclear. In this case report, we evaluated the pharmacokinetics and HD removal rate of TMZ in a patient with glioblastoma undergoing HD to determine optimal dosing of TMZ. A 78-year-old man with glioblastoma who underwent HD 3 times a week was treated with TMZ concomitant with radiotherapy. One dose of TMZ was prescribed at 75 mg/m2 on the day before HD and another dose of 37.5 mg/m2 on the day before non-HD. Peak and trough concentrations (1 hour and 12 hours after dosing, respectively) were evaluated before HD and on non-HD days. HD removal rate of TMZ was calculated based on the predialyzer and postdialyzer plasma concentrations. Furthermore, the TMZ plasma concentrations were measured using liquid chromatography-tandem mass spectrometry. The mean plasma peak and trough concentrations ± SD after 75 mg/m2 TMZ were 2917 ± 914 and 108 ± 17.6 ng/mL, respectively. Those after 37.5 mg/m2 TMZ dosage were 1305 ± 650 and 53.8 ± 11.8 ng/mL, respectively. The mean HD TMZ removal rate was 84.9 ± 1.9%. TMZ was tolerable in patients undergoing HD. Based on the data from a single individual pharmacokinetic perspective, the pharmacokinetics of TMZ in this patient undergoing HD were comparable with those observed in patients with normal renal function. In addition, it may be reasonable to administer TMZ after HD because of the high HD removal rate.


Distal Radial Access in Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the PROGRESS-CTO Registry.
The outcomes of distal radial access (dRA) in chronic total occlusion percutaneous coronary intervention (CTO-PCI) have received limited study. We compared the clinical, angiographic, and procedural characteristics of 120 CTO-PCIs performed via dRA access with 2625 CTO-PCIs performed via proximal radial access (pRA) in a large, multicenter registry. The dRA group had lower mean PROGRESS-CTO score than the pRA group (1.0 ± 1 vs 1.2 ± 1, respectively; P=.05), while J-CTO score (2.4 ± 1.2 vs 2.3 ± 1.3; P=.43) and PROGRESS-CTO Complications score (2.8 ± 1.8 vs 2.6 ± 1.9; P=.16) were similar in the dRA vs pRA groups, respectively. Technical success was similar in the 2 groups (90% dRA vs 86% pRA; P=.14). Concomitant use of femoral access did not alter procedural success. The incidence of major periprocedural adverse cardiac events was similar in the 2 groups (0.8% dRA vs 2.4% pRA; P=.26), whereas the incidence of tamponade requiring pericardiocentesis was lower with dRA (0% dRA vs 4.69% pRA; P<.001), as was air kerma radiation dose (median, 1.7 Gy; interquartile range [IQR], 0.97-2.63 Gy in the dRA group vs median, 2.27 Gy; IQR, 1.2-3.9 Gy in the pRA group; P<.001). Use of dRA in CTO-PCI is associated with similar procedural success and risk of complications as compared with pRA.


Association between baseline vitamin D metabolite levels and long-term cardiovascular events in patients with rheumatoid arthritis from the CIMESTRA trial: protocol for a cohort study with patient-record evaluated outcomes.
Cardiovascular morbidity and mortality is increased in patients with rheumatoid arthritis (RA), and among these patients, the prevalence of hypovitaminosis D is high. Moreover, low vitamin D levels have been associated with increased cardiovascular risk in healthy subjects. To evaluate the long-term risk of cardiovascular events in patients having low total 25-hydroxyvitamin D levels at baseline compared with patients with normal levels, in an efficiently treated, closed cohort of patients with an early diagnosis of RA. This study is a prospective, closed, blinded endpoint cohort study, based on secondary analyses from a previous randomised trial (CIMESTRA study; NCT00209859, approved September 1999) including 160 patients with an early diagnosis of RA from Danish University clinics. Primary outcome will be the proportion of patients with any cardiovascular event in the follow-up period, evaluated using systematic journal audits. Logistic regression models will test the hypothesis that there are more cardiovascular events in enrolled patients with a low level of vitamin D (< 50 nmol/L). Secondarily, Cox regression models, based on survival analysis, will determine the extent to which independent variables (including different levels of vitamin D at baseline) predict whether a cardiovascular event will occur, and also when this will be. All patients have received verbal and written information before enrolment, and have given written consent at baseline. To disseminate comprehension of factors of prognostic importance to cardiovascular outcome in RA, we will attempt to have a first draft ready no later than 1 year after the adjudication process has finished. If low vitamin D levels can predict cardiovascular events in RA, it is relevant to take into account in a prediction model, to be considered by patients, physicians and other decision-makers. The parental controlled trial is registered as NCT00209859.


How green is green chemistry? Chlorophylls as a bioresource from biorefineries and their commercial potential in medicine and photovoltaics.
As the world strives to create a more sustainable environment, green chemistry has come to the fore in attempts to minimize the use of hazardous materials and shift the focus towards renewable sources. Chlorophylls, being the definitive "green" chemical are rarely used for such purposes and this article focuses on the exploitation of this natural resource, the current applications of chlorophylls and their derivatives whilst also providing a perspective on the commercial potential of large-scale isolation of these pigments from biomass for energy and medicinal applications.


Anti-aquaporin-4 antibody-positive optic neuritis treated with double-filtration plasmapheresis.
The anti-aquaporin-4 (AQP4) antibody was recently reported to be associated with neuromyelitis optica (NMO). Optic nerve involvements in many NMO cases are bilateral and the prognosis is poor. However, it has been suggested that plasma exchange is effective for those patients when steroid pulse therapy is ineffective. Herein, we report successful treatment of a patient with NMO using double-filtration plasmapheresis (DFPP). A 22-year-old woman consulted a neurologist for neck pain in March 2008. High-intensity lesions were shown in the cervical spinal cord by T2-weighted magnetic resonance imaging. On July 15, the patient was referred to our department for a headache and pain and blurred vision in the left eye. The best-corrected visual acuity was 20/50 and 20/500 in the right and left eyes, respectively, with visual field defects observed in both. After 3 courses of steroid pulse therapy, anti-AQP4 antibodies were positive. In November, the patient again noticed visual acuity loss in the left eye and was treated by additional steroid pulse therapy, which was not effective. Next, she underwent plasma exchange therapy, though it was stopped due to hypotension and dyspnea. The next day, the patient underwent DFPP treatment and visual function gradually recovered. It is important to consider NMO when steroid pulse therapy is not effective. We successfully and safely treated NMO in a young adult patient using DFPP.


Gold nanoparticles: a revival in precious metal administration to patients.
Gold has been used as a therapeutic agent to treat a wide variety of rheumatic diseases including psoriatic arthritis, juvenile arthritis, and discoid lupus erythematosus. Although the use of gold has been largely superseded by newer drugs, gold nanoparticles are being used effectively in laboratory based clinical diagnostic methods while concurrently showing great promise in vivo either as a diagnostic imaging agent or a therapeutic agent. For these reasons, gold nanoparticles are therefore well placed to enter mainstream clinical practice in the near future. Hence, the present review summarizes the chemistry, pharmacokinetics, biodistribution, metabolism, and toxicity of bulk gold in humans based on decades of clinical observation and experiments in which gold was used to treat patients with rheumatoid arthritis. The beneficial attributes of gold nanoparticles, such as their ease of synthesis, functionalization, and shape control are also highlighted demonstrating why gold nanoparticles are an attractive target for further development and optimization. The importance of controlling the size and shape of gold nanoparticles to minimize any potential toxic side effects is also discussed.


Copper physiology in ruminants: trafficking of systemic copper, adaptations to variation in nutritional supply and thiomolybdate challenge.
Ruminants are recognised to suffer from Cu-responsive disorders. Present understanding of Cu transport and metabolism is limited and inconsistent across vets and veterinary professionals. There has been much progress from the studies of the 1980s and early 1990s in cellular Cu transport and liver metabolism which has not been translated into agricultural practice. Cu metabolism operates in regulated pathways of Cu trafficking rather than in pools of Cu lability. Cu in the cell is chaperoned to enzyme production, retention within metallothionein or excretion via the Golgi into the blood. The hepatocyte differs in that Cu-containing caeruloplasmin can be synthesised to provide systemic Cu supply and excess Cu is excreted via bile. The aim of the present review is to improve understanding and highlight the relevant progress in relation to ruminants through the translation of newer findings from medicine and non-ruminant animal models into ruminants.


Smoking status identification: two managed care organizations' experiences with a pilot project to implement identification systems in independent practice associations.
To determine whether managed care organizations (MCOs) can effectively promote the sustained use of smoking status identification systems among independent practice associations. Quasi-experimental design measuring smoking status documentation before and after an intervention. A chart review of the MCOs' patients at 4 participating primary care clinics determined the baseline for smoking status documentation before intervention. Baseline data were unavailable from a fifth participating clinic. Two quality improvement personnel were sent by the MCOs to help the clinics chose and implement a system for identifying smoking status. All of the clinics chose a sticker system. The change in smoking status documentation was assessed by chart reviews of patients enrolled in the MCOs who were seen during the period between 3 and 16 months after implementation of the system. Following the intervention, a significant increase in smoking status documentation was noted among participating clinics. The proportion of patients whose smoking status was identified and documented by any method increased from 50% to 87% (P < .01) at the 4 clinics with baseline data. By clinic, the increase varied from 6% to 60%. The sticker system was the method by which most patients' smoking status was documented (77%). There were no controls, so the influence of outside factors, including a regional smoking cessation campaign that coincided with this study, cannot be quantified. Managed care organizations may be an effective change agent for implementing the guidelines for tobacco use and dependence treatment.


Mono-ovulatory cycles: a key goal in profertility programmes.
Mono-ovulatory cycles for women are optimal because singleton pregnancies have a better outcome than multiples. Multiple births began to increase in the 1950s after the first appearance of effective ovulation induction for the treatment of anovulation. Since the 1980s when ovulation induction and IVF were more broadly applied to the treatment of unexplained and persistent infertility, there has been an unprecedented rise in multiple births. Strategies to achieve mono-ovulation during treatment of anovulatory patients are distinct from those for the treatment of ovulating patients who have unexplained and persistent infertility. Anovulatory patients with hypogonadotrophic hypogonadism can be treated with exogenous pulsatile GnRH, which restores normal gonadotrophin secretion, ovulation rates and conception rates. The multiple pregnancy rate is not increased with GnRH treatment. In patients with normogonadotrophic anovulation, attention should be given to diet and exercise before any other interventions are considered. Pharmacological induction of ovulation can be achieved with antiestrogen, gonadotrophin or pulsatile GnRH treatment; antiestrogen is the first choice with gonadotrophin more widely used for clomiphene citrate (CC)-resistant patients. Obesity and polycystic ovaries are common in this group, so that gonadotrophin and GnRH treatment are associated with lower responses compared with hypogonadotrophic hypogonadism, and higher multiple pregnancy rates. Low dosage protocols are being tested that may lower the multiple birth rates. The role of drugs enhancing sensitivity to insulin, e.g. metformin, remains undetermined. Laparoscopic ovarian diathermy achieves conception rates that are equivalent to gonadotrophin treatment, with fewer multiple births. Augmenting normal ovulation processes for couples with unexplained and persistent infertility is less effective. Pregnancy rates are statistically significantly higher with CC but the size of the increase is not clinically important. CC with intrauterine insemination is associated with a clinically important effect on conception. Achieving mono-ovulation is more difficult in assisted reproductive technology cycles because success depends on maintaining the level of FSH above the threshold level longer than normal in order to increase the number of mature follicles. Milder stimulation for IVF and IVF in the untreated cycle show great potential, however, especially in view of the trend toward transfer of a single embryo in assisted reproductive treatment cycles.


Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects.
Non-syndromic arthrogryposis multiplex congenita (AMC) is characterized by multiple congenital contractures resulting from reduced fetal mobility. Genetic mapping and whole exome sequencing (WES) were performed in 31 multiplex and/or consanguineous undiagnosed AMC families. Although this approach identified known AMC genes, we here report pathogenic mutations in two new genes. Homozygous frameshift mutations in CNTNAP1 were found in four unrelated families. Patients showed a marked reduction in motor nerve conduction velocity (<10 m/s) and transmission electron microscopy (TEM) of sciatic nerve in the index cases revealed severe abnormalities of both nodes of Ranvier width and myelinated axons. CNTNAP1 encodes CASPR, an essential component of node of Ranvier domains which underlies saltatory conduction of action potentials along the myelinated axons, an important process for neuronal function. A homozygous missense mutation in adenylate cyclase 6 gene (ADCY6) was found in another family characterized by a lack of myelin in the peripheral nervous system (PNS) as determined by TEM. Morpholino knockdown of the zebrafish orthologs led to severe and specific defects in peripheral myelin in spite of the presence of Schwann cells. ADCY6 encodes a protein that belongs to the adenylate cyclase family responsible for the synthesis of cAMP. Elevation of cAMP can mimic axonal contact in vitro and upregulates myelinating signals. Our data indicate an essential and so far unknown role of ADCY6 in PNS myelination likely through the cAMP pathway. Mutations of genes encoding proteins of Ranvier domains or involved in myelination of Schwann cells are responsible for novel and severe human axoglial diseases.


The role of Urtica dioica and Nigella sativa in the prevention of carbon tetrachloride-induced hepatotoxicity in rats.
The role of Nigella sativa L. (Ranunculaceae) (NS) and Urtica dioica L. was investigated (UD) in the prevention of carbon tetrachloride (CCl4) induced liver fibrosis and cirrhosis. Fifty Sprague-Dawley rats were allocated into fi ve groups (I, IIA and B, IIIA and B) and CCl4 was injected biweekly to all groups. Group I (control, CCl4 only), group IIA and B (NS fixed oil and volatile oil), group IIIA and B (UD fixed oil and UD decoction extract) rats were killed at the end of week 12 and histopathological and immunohistochemical examinations of liver tissues were performed. In the control group, coagulation necrosis and hydropic degeneration were marked in the periacinar regions (zone 3) associated with fibrosis in the periacinar regions and in the portal tracts. In groups IIA-B and IIIA-B (NS and UD), none of the serious histopathological findings were detected except for sparse coagulation necrosis in the periacinar regions. ASMA-positive perisinusoidal cells with myo fibroblastic transformation and lysosomal enzyme activity suggesting fibrogenesis were also significantly more common in the control group than in the NS and UD groups. UD and NS seem to be significantly effective in the prevention of carbon tetrachloride induced hepatotoxicity in rats.


The Fragility of Statistically Significant Findings From Randomized Controlled Trials in Hip and Knee Arthroplasty.
The Fragility Index (FI) is a method for evaluating the robustness of statistically significant findings from randomized controlled trials (RCTs) beyond the P value in trials with dichotomous outcomes. The FI is defined as the number of patients in one arm of a trial that would have to have a different outcome to change the results of the trial from statistically significant to nonsignificant. This review assessed the FI in arthroplasty RCTs. A systematic search was conducted in MEDLINE, Embase, and Web of Science for RCTs related to primary total joint arthroplasty (TJA) from 2010 to 2020. Trials with a statistically significant dichotomous primary outcome were included. The FI was calculated using Fisher's exact test to determine how many events would need to be reversed to change a study from statistically significant to nonsignificant. A total of 34 RCTs were included. The median sample size was 103 patients (range 24-791). The median FI was 1 (range 0-45), meaning that reversing the outcome of just one patient in either treatment group of each trial would change it from a significant to a nonsignificant result. Hip and knee arthroplasty RCTs with statistically significant dichotomous outcomes in TJA are fragile. The median FI in TJA is lower than the FI in any of the other previously reported orthopedic subspecialties. Fragility is another reason to be cautious when conducting or interpreting small trials, and to continue to strive toward large trials to answer important questions in TJA. Level I.


Ambulatory surgery center ownership models.
Outpatient spine surgery performed in ambulatory surgery centers (ASCs) has grown dramatically over the last decade because of significant clinical and economic advantages to patients, physicians and the health care industry. Physicians benefit from the efficiencies of the outpatient setting and potential profit from ownership. There are various ownership models which differ primarily on the amount of ownership attributed to physicians, management companies and hospital systems, the key players in the space. The majority of ASCs are still solely owned by physicians, which gives physicians the benefit of maximum control but brings the challenges of management and contracting as well. Joint ventures involving various combinations of physicians, ASC management companies and hospital systems strive to find a balance between physician influence and management expertise from their partners. ASCs owned solely by hospital systems are on the rise and seek to involve physicians in a co-management role. Overall, the ASC market will continue to grow and alternative business models will arise as the key players look for the right combination to maximize efficiency and clinical success.


Trials with proxy-reported outcomes registered on the Australian New Zealand Clinical Trials Registry (ANZCTR).
A proxy is someone other than a patient who reports a patient's outcomes as if they are the patient. Due to known discordance with patient reports, proxies are often not recommended in clinical trials; however, proxies may be needed in certain research contexts. We aimed to identify and describe trials registered on the Australian New Zealand Clinical Trials Registry (ANZCTR) with proxy-reported endpoints. ANZCTR was systematically searched from inception (2005) to 31 March 2017 for trials with proxy-reported endpoints. Primary and secondary endpoints for each trial retrieved by the search were individually coded (proxy-reported: yes/no), and trials with confirmed proxy-reported endpoints were included in the analysis. Of 13,666 registered trials, 469 (3.4%) included a proxy-reported endpoint (867 individual proxy-reported endpoints in total: 62% family member proxy, 22% health professional). Proxy endpoint inclusion did not significantly increase over time (r = 0.18, p = 0.59). Mental health (11.5%), stroke (10.3%) and neurological (8.3%) trials had the highest proportion of trials using proxies. Of the 469 trials, 123 (26.2%) studies involved paediatric patients. Proxy-reported endpoints are included in a small but notable number of studies, which may indicate other types of outcomes are used for patients unable to self-report, or that these patients are under-researched.


[Mechanisms of resistance in Enterobacteriaceae towards beta-lactamase antibiotics].
Except for Salmonella spp., all Enterobacteriaceae produce intrinsic chromosomal encoded beta-lactamases which, beside their physiologic role in cell-wall synthesis and natural beta-lactam protection, are responsible for intrinsic resistance of individual species among Enterobacteriaceae. E. coli and Shigella spp. produce a small amount of AmpC beta-lactamases and are susceptible to ampicillin and other beta-lactam antibiotic agents. Enterobacter spp, C. freundii, Serratia spp., M. morganii, P. stuarti and P. rettgeri produce small amounts of inducible AmpC beta-lactamases which are not inhibited by beta-lactamases inhibitor, causing intrinsic resistance to ampicillin, co-amoxiclav and first-generation cephalosporins. K. pneumoniae produces small amounts of SHV-1 beta-lactamases, and K. oxytoca chromosomal K1 beta-lactamase, causing resistance to ampicillin, carbencillin, ticarcillin and attenuated zone of inhibition to piperacillin, compared to piperacillin with tazobactam. They are susceptible to beta-lactamase inhibitors. Whereas P. mirabilis shows a minor chromosomal expression of beta-lactamases, P. vulgaris produces chromosomal beta-lactamases of class A (cefuroximases), causing resistance to ampicillin, ticarcillin, and first- and second-generation cephalosporins. Antibiotics have caused the appearance of acquired or secondary beta-lactamases, with the sole function of protecting bacteria from antibiotics. The production of broad-spectrum beta-lactamases (TEM-1, TEM-2, SHV-1, OXA-1) results in resistance to ampicillin, ticarcillin, first-generation cephalosporins and piperacillin. A high level of beta-lactamases leads to resistance to their inhibitors. The plasmid-mediated extended-spectrum beta-lactamases (ESBLs) are of increasing concern. Most are mutants of classic TEM- and SHV-beta-lactamases types. Unlike these parent enzymes, ESBLs hydrolyze oxymino-cephalosporins such as cefuroxime, cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefpirome and cefepime, aztreonam, as well as penicillins and other cephalosporins, except for cephamycin (cefoxitin and cefotetan). They are inhibited by beta-lactamase inhibitors. AmpC beta-lactamases are chromosomal and inducible in most Enterobacter spp., C. freundii, Serratia spp., M. morganii and Providentia spp. They are resistant to almost all penicillins and cephalosporins, to beta-lactamase inhibitors and aztreonam, and are susceptible to cefepime and carbapenems as well. Plasmid-mediated AmpC beta-lactamases have arisen through the transfer of chromosomal genes for the inducible AmpC beta-lactamase onto plasmids. All plasmid-mediated AmpC beta-lactamases have similar substrate profiles to the parental enzymes from which they appear to be derived. With one exception, plasmid-mediated AmpCs differ from chromosomal AmpCs in being uninducible. The National Committee for Clinical Laboratory Standards (NCCLS) has issued recommendations for ESBL screening and confirmation for isolates of E. coli, K. pneumoniae and K. oxytoca. No NCCLS recommendations exist for ESBLs detection and reporting for other organisms or for detecting plasmid-mediated AmpC beta-lactamases. High-level expression of AmpC may prevent recognition of an ESBL in species that produce a chromosomally encoded inducible AmpC beta-lactamase. AmpC-inducible species (e. g. Enterobacter spp. and C. freundii) can be recognized by cefoxitin/cefotaxime disk antagonism tests. Since clinical laboratories are first to encounter bacteria with new forms of antibiotic resistance, they need appropriate tools to recognize these bacteria, including trained staff with sufficient time and equipment to follow up important observations. Because bacterial pathogenes are constantly changing, training must be an ongoing process.


Health-Related Quality of Life in Patients on Home Oxygen Therapy with Telemonitoring.
Home oxygen therapy (HOT) is an important treatment for patients with chronic respiratory diseases. Recently, telemonitoring of HOT has been become available. In the present study, we examined whether telemonitoring of HOT could improve health-related quality of life (HRQOL). Twelve patients receiving HOT participated in this study. The oxygen flow rates, use of the oxygen concentrator, and the values of percutaneous arterial oxygen saturation measured by each patient with a pulse oximeter were checked using a telemonitoring system for a period of one month. Interventions based on the results obtained were carried out in order to optimize oxygen use in this patient cohort. We evaluated the results of the SF-36 questionnaire before the initiation of telemonitoring and at 3 months after completion of the study. We identified significant improvements in SF-36 sub-scores after completion of this intervention. We conclude that telemonitoring may be a useful method to improve HRQOL.


Concerns about ceramics in THA.
Currently available ceramic materials are superior to those used originally in total hip arthroplasty, which should translate into a much lower complication rate than what has been reported previously. In spite of this, a number of concerns remain. The ceramic-on-ceramic articulation is not immune to wear and surface damage. Conditions associated with ceramic wear include vertical cup position, femoral neck impingement, and femoral head separation. A unique pattern of stripe wear has been described as something that results from microseparation during gait. Catastrophic failure, although rare, continues to be a concern, and not all fractures can be predicted by proof testing. Revisions needed because of ceramic fractures can be extensive, and the results of the revision procedures can be compromised by the presence of highly abrasive particulate debris that is retained. Other concerns include the generation of debris from modular interfaces, neck damage and debris generation from impingement of some designs, inability to use a ceramic head a second time on a metal trunnion, and the dramatic loss of head and liner options intraoperatively. Although ceramics show great promise as a lower wear articulation, manufacturing and design modifications and improvements will continue in an attempt to address the substantial concerns that persist.


Expression analysis of protein inhibitor of activated STAT (PIAS) genes in IFNβ-treated multiple sclerosis patients.
Protein inhibitors of activated STAT (PIAS) are transcription co-regulator of the Janus kinase/signal transducer and activator of transcription signaling pathway as well as nuclear factor-κB family of transcription factors. Both of them are involved in cytokine release during inflammatory response. Considering the role of cytokine imbalance in the pathogenesis of multiple sclerosis (MS), we compared blood expressions of PIAS1-4 genes in 48 interferon β (IFNβ)-treated MS patients with those of healthy subjects by means of real time PCR. Although the expression levels of these genes were not significantly different between MS patients and healthy subjects, significant inverse correlations have been found between PIAS1 expression and age at disease onset. PIAS2 and PIAS3 expressions were inversely correlated with Expanded Disability Status Scale (EDSS) in patients. Moreover, PIAS3 expression was correlated with disease duration in patients and with age in controls. In addition, PIAS4 expression was inversely correlated with EDSS and age at disease onset while it was positively correlated with disease duration. The present study provides evidences for altered expression of PIAS genes in IFNβ-treated MS patients compared with healthy subjects. However, future studies are needed for elaboration of their exact function in this disorder.


"Big" Food, Tobacco, and Alcohol: Reducing Industry Influence on Noncommunicable Disease Prevention Laws and Policies Comment on "Addressing NCDs: Challenges From Industry Market Promotion and Interferences".
The food, tobacco and alcohol industries have penetrated markets in low- and middle-income countries (LMICs), with a significant impact on these countries' burden of noncommunicable diseases (NCDs). Tangcharoensathien and colleagues describe the aggressive marketing of unhealthy food, alcohol and tobacco in LMICs, as well as key tactics used by these industries to resist laws and policies designed to reduce behavioural risk factors for NCDs. This commentary expands on the recommendations made by Tangcharoensathien and colleagues for preventing or managing conflicts of interest and reducing undue industry influence on NCD prevention policies and laws, focusing on the needs of LMICs. A growing body of research proposes ways to design voluntary industry initiatives to make them more effective, transparent and accountable, but governments should also consider whether collaboration with health-harming industries is ever appropriate. More fundamentally, mechanisms for identifying, managing and mitigating conflicts of interest and reducing industry influence must be woven into - and supported by - broader governance and regulatory structures at both national and international levels.


Regulation and function of histone acetyltransferase MOF.
The mammalian MOF (male absent on the first), a member of the MYST (MOZ, YBF2, SAS2, and Tip60) family of histone acetyltransferases (HATs), is the major enzyme that catalyzes the acetylation of histone H4 on lysine 16. Acetylation of K16 is a prevalent mark associated with chromatin decondensation. MOF has recently been shown to play an essential role in maintaining normal cell functions. In this study, we discuss the important roles of MOF in DNA damage repair, apoptosis, and tumorigenesis. We also analyze the role of MOF as a key regulator of the core transcriptional network of embryonic stem cells.