Alterations of the iNKT cell compartment in brain-injured patients.
Brain injury (BI) induces a state of immunodepression leading to pneumonia. We investigated the invariant natural killer T (iNKT) cell compartment. This is an observational study in two surgical intensive care units (ICUs) of a single institution and a research laboratory. Clinical data and samples from a prospective cohort were extracted. Severe brain-injured patients (n = 33) and sex- and age-matched healthy donors (n = 40) were studied. We observed the presence of IL-10 in serum, a loss of IFN-γ and IL-13 production by peripheral blood mononuclear cells (PBMCs) following IL-2 stimulation, and downregulation of HLA-DR expression on both monocytes and B cells early after BI. Inversely, CD1d, the HLA class I-like molecule involved in antigen presentation to iNKT cells, was over-expressed on patients' monocytes and B cells. The antigen-presenting activity to iNKT cells of PBMCs was increased in the patients who developed pneumonia, but not in those who remained free of infection. Frequencies of iNKT cells among PBMCs were dramatically decreased in patients regardless of their infection status. Following amplification, an increased frequency of CD4+ iNKT cells producing IL-4 was noticed in the group of patients free of infection compared with those who became infected and with healthy donors. Finally, serum from BI patients inhibited the iNKT cells' specific response as well as the non-specific IL-2 stimulation of PBMCs, and the expression of the beta-2 adrenergic receptor was elevated at the surface of patients T lymphocytes. We observed severe alterations of the iNKT cell compartment, including the presence of inhibitory serum factors. We demonstrate for the first time that the decreased capacity to present antigens is not a generalized phenomenon because whereas the expression of HLA-DR molecules is decreased, the capacity for presenting glycolipids through CD1d expression is higher in patients.


Quad bike injuries in Waikato, New Zealand: an institutional review from 2007-2011.
The aim of this study was to assess the burden of all-terrain vehicle (ATV) injuries within the Waikato region of New Zealand. From the local database of 13 400 trauma patients, 101 patients with ATV-related injury or death were identified. We analysed data on demographics, location and mechanism of accident, helmet use, length of hospital stay, injury severity score and type of injury. Only admissions to Waikato Hospital trauma centre between February 2007 and March 2011 were included. A total of 84% of patients were male, 16% were female. The mean age was 38.8 years (range 4-82). Twelve per cent of patients were within the paediatric age range (<16 years). No age group was at particular risk for an ATV injury. An increase in ATV injuries year-on-year within the Waikato area was found. A large number of head injuries were found. Helmet compliance was low. Injury severity score was significantly higher in Maori than in NZ Europeans (mean 16.8 versus 10.0 (P = 0.04)) and was comparable between children and adults as well as men and women. Our results display a 42% rise in admission incidence from 2009 to 2010, resulting in increased hospital bed occupancy. If the current trend of a growing number of quad bike accidents was to continue, this could amount to a cost of NZ$1 467 344 in 2012 from ATV injuries in Waikato hospital alone. Quad bike injuries are an increasing burden on Waikato health care. The best strategy to tackle this epidemic needs to be further debated.


Perioperative Precision Medicine: Where Are We in 2020?
The present review examines how targeted approaches to care, based on individual variability in patient characteristics, could be applied in the perioperative setting. Such an approach would enhance individualized risk assessment and allow for targeted preventive and therapeutic decision-making in patients at increased risk for adverse perioperative events. Prior and current studies highlight valuable lessons on how future investigations attempting to link specific patient-related characteristics or treatment modalities with outcomes and adverse drug responses might be designed in the perioperative setting. Our review highlights the past, present, and future directions of perioperative precision medicine. Current evidence provides important lessons on how a specific patient and disease tailored approach can help perioperative physicians in delivering the most appropriate and safest perioperative care.


A Review on the Usage of Bone Single-Photon Emission Computed Tomography/Computed Tomography in Detecting Skeletal Metastases in the Post-COVID-19 Era: Is it Time to Ditch Planar and Single-Photon Emission Computed Tomography only Gamma Camera Systems?
Planar whole-body bone scanning (WBS) is widely used to evaluate skeletal lesions seen in cancer and noncancer cases. Frequently, degenerative, or other benign bony changes may give rise to indeterminate lesions that mimic bone metastases. In the post-COVID-19 era, there is an evolutionary phase that puts importance on global development and adaptability, which encompasses to include nuclear medicine practices worldwide. Single-photon emission computed tomography/computed tomography (SPECT/CT) can be used to improve the characterization of these lesions and help to resolve the diagnostic conundrum while reducing the need for patients to undergo multiple different examinations at various imaging departments. The fusion of SPECT and CT allows morphological characterization of functional abnormality detected by focal tracer uptake on planar scintigraphy, which provides a one-stop center imaging in nuclear medicine departments. The objective of this study was to review the diagnostic accuracy of SPECT/CT in diagnosing bone metastases in a variety of oncology and nononcology cases and to determine the feasibility of performing bone SPECT/CT in all suspected cancer cases, including cases of bone infection instead of planar imaging alone. The utilization of hybrid SPECT/CT in indeterminate bone lesions detected on planar WBS can significantly increase the diagnostic confidence and accuracy of image interpretation. Recognition of patterns of disease identified using hybrid imaging can improve the management of patients with potentially lower costs in the long term. Currently, hybrid SPECT/CT machines are becoming a norm in nuclear medicine departments, thus potentially making single planar application machines obsolete in the near future. We hypothesize that in the interest of providing a meaningful interpretation of isotope bone scans, the default protocol should involve the option of acquiring SPECT/CT images rather than relying on whole-body scans only. Departments choosing to upgrade existing equipment or those choosing to invest in only one gamma camera should proactively opt for hybrid SPECT/CT systems.


Comparing the impact of oral disease in two populations of older adults: application of the geriatric oral health assessment index.
This study compares the distributional and psychometric properties of the Geriatric Oral Health Assessment Index (GOHAI) in two samples of older adults, and examines how the self-perceived impact of oral disease, as measured by the GOHAI, varies in accordance with sample sociodemographic and health characteristics. Results are based on survey data from two samples of older men: a Medicare sample of patients using community physicians (n = 799; mean age = 74) and users of VA ambulatory health care (n = 542; mean age = 72). The findings indicate significant differences between samples in mean GOHAI scores, with the VA sample exhibiting worse scores. A number of similarities in psychometric properties of the instrument across the two samples were found: high internal consistency reliability and similar inter-item and item-scale correlations. Factors analyses revealed somewhat different structures between the two samples, but explained similar amounts of variance; regression analyses indicated that income and self-rated oral health were significant predictors of GOHAI scores in both samples. The GOHAI exhibits satisfactory psychometric properties in both samples of older men. Results suggest continued use of the GOHAI as an indicator of the impact of oral conditions on functioning and well-being in a variety of samples.


Development and bottlenecks of renewable electricity generation in China: a critical review.
This review provides an overview on the development and status of electricity generation from renewable energy sources, namely hydropower, wind power, solar power, biomass energy, and geothermal energy, and discusses the technology, policy, and finance bottlenecks limiting growth of the renewable energy industry in China. Renewable energy, dominated by hydropower, currently accounts for more than 25% of the total electricity generation capacity. China is the world's largest generator of both hydropower and wind power, and also the largest manufacturer and exporter of photovoltaic cells. Electricity production from solar and biomass energy is at the early stages of development in China, while geothermal power generation has received little attention recently. The spatial mismatch in renewable energy supply and electricity demand requires construction of long-distance transmission networks, while the intermittence of renewable energy poses significant technical problems for feeding the generated electricity into the power grid. Besides greater investment in research and technology development, effective policies and financial measures should also be developed and improved to better support the healthy and sustained growth of renewable electricity generation. Meanwhile, attention should be paid to the potential impacts on the local environment from renewable energy development, despite the wider benefits for climate change.


The ab initio crystal structure solution of proteins by direct methods. II. The procedure and its first applications.
A direct phasing method is described that is potentially able to solve ab initio protein structures. The method uses the information contained in diffraction data of the native structure and of one isomorphous derivative. The various steps of the procedure are analysed in order to estimate their robustness against experimental errors in measurements and lack of isomorphism. Experimental tests involve four typical protein structures and show that crystal structure solution is attained in a rather straightforward way.


Bone and Mineral Disorder in Renal Transplant Patients: Overview of Pathology, Clinical, and Therapeutic Aspects.
Renal transplantation (RTx) allows us to obtain the resolution of the uremic status but is not frequently able to solve all the metabolic complications present during end-stage renal disease. Mineral and bone disorders (MBDs) are frequent since the early stages of chronic kidney disease (CKD) and strongly influence the morbidity and mortality of patients with CKD. Some mineral metabolism (MM) alterations can persist in patients with RTx (RTx-p), as well as in the presence of complete renal function recovery. In those patients, anomalies of calcium, phosphorus, parathormone, fibroblast growth factor 23, and vitamin D such as bone and vessels are frequent and related to both pre-RTx and post-RTx specific factors. Many treatments are present for the management of post-RTx MBD. Despite that, the guidelines that can give clear directives in MBD treatment of RTx-p are still missed. For the future, to obtain an ever-greater individualisation of therapy, an increase of the evidence, the specificity of international guidelines, and more uniform management of these anomalies worldwide should be expected. In this review, the major factors related to post-renal transplant MBD (post-RTx-MBD), the main mineral metabolism biochemical anomalies, and the principal treatment for post-RTx MBD will be reported.


Falcarindiol inhibits nitric oxide-mediated neuronal death in lipopolysaccharide-treated organotypic hippocampal cultures.
Excessive nitric oxide (NO) release from activated microglia has a predominant role in neuronal death. This study investigated the effect of falcarindiol, which was isolated from Cnidium officinale Makino, on the NO-mediated neuronal death in lipopolysaccharide (LPS)-treated organotypic hippocampal cultures. Falcarindiol dose-dependently reduced inducible NO synthase (iNOS)-mediated NO production without cytotoxic effects on LPS-activated BV-2 and microglia. Predictably, falcarindiol inhibited neuronal death by reducing NO production in the LPS-treated organotypic hippocampal cultures. N-monomethyl-L-arginine (NMMA), an iNOS inhibitor, also inhibited neuronal death at 500 microM. In contrast, massive neuronal death was induced by excessive NO production in the LPS-treated alone cultures. These results suggest that excessive NO production plays an important role in the neurotoxic effect, and falcarindiol is a potential inhibitor in NO-mediated neuronal death.


Imported Crimean-Congo hemorrhagic Fever.
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease that may also be transmitted through person-to-person transmission by exposure to infected body fluids. Despite its wide geographic distribution in animals, CCHF virus is rarely associated with recognized human diseases. We report the first case of imported CCHF in France.


[The value of computerized and magnetic resonance tomography for staging esophageal and cardiac cancer in comparison with conventional diagnosis].
The results of computed tomography and magnetic resonance imaging in patients with histologically proved carcinoma of the esophagus or of the cardia were correlated with previously administered barium swallow X-ray studies and postoperative pathologic-anatomic findings. A good estimation of resectability is achieved combining barium swallow and CT studies, but an accurate determination of the stage of involvement of the surrounding tissue and of the nodes does not appear possible at present. In the routine staging of upper digestive tract malignancy MRI was found less accurate and cannot be recommended.


Biodegradation of phenolic environmental pollutants by a surfactant-laccase complex in organic media.
Oxidative degradation of phenolic environmental pollutants in organic media was investigated using a laccase complexed with surfactants. The catalytic activity of the surfactant-laccase complex in isooctane was markedly enhanced by appropriately adjusting the water content of the reaction medium using reverse micelles. The surfactant-laccase complex showed little activity towards the oxidative reaction of bisphenol A in water-saturated isooctane (i.e., 0.0055% [v/v] water) while effectively catalyzed the same reaction in isooctane containing 4% (v/v) water, which is over the maximum water solubility. The latter system was homogeneous and was only achieved by the aid of reverse micelles. With respect to the oxidation of bisphenol A, two products, 4-isopropylphenol and 4-isopropenylphenol, were identified by gas chromatography-mass spectrometry (GC-MS) analyses, indicating the oxidative degradation of the bis-phenolic structure of bisphenol A. We also found that the surfactant-laccase complex turned out to handle other environmental pollutants, chlorophenols, by the simultaneous addition of water and a redox mediator into the reaction medium using reverse micelles.


Sensitivity of group C arboviruses (bunyaviridae) to human amnion interferon.
The sensitivity of several group C arboviruses (Bunyaviridae) to human amnion interferon was compared to that of vesicular stomatitis virus (VSV) and Sindbis virus. In CPE inhibition assays. Apeu virus was the most sensitive of the group C arboviruses tested; it was significantly more inhibited than VSV, but was in the same range as Sindbis virus. In plaque reduction assays, the increasing order of sensitivity was Apeu, Marituba, VSV and Sindbis viruses. Single-cycle yields of VSV and Apeu virus were reduced to the same extent with 1-10 interferon units; with 230 units, VSV growth was inhibited to a much greater extent (100-fold) than Apeu virus.


Chromosomal polymorphism in the yeast species Debaryomyces hansenii.
Pulse field gel electrophoresis karyotypes of 41 strains of the genus Debaryomyces, including 35 strains confirmed as D. hansenii species by D1/D2 ribosomal DNA sequence analysis, were performed. Electrophoretic karyotypes of the 41 strains exhibited 4 to 10 chromosomal bands ranging between 0.7 Mb and 4.2 Mb. Among D. hansenii species, the patterns of strains obtained from the CBS collection and cheese isolates differed strongly from D. hansenii var. hansenii CBS767T. Both D. hansenii var. hansenii and D. hansenii var. fabryii showed chromosome length polymorphism. Electrophoretic karyotypes of the D. hansenii strains were analyzed by Southern hybridization with various species-specific probes isolated from D. hansenii var. hansenii CBS767T. Repeated sequences including the F01pro, M18pro, the Ty1-copia retrotransposon Tdh5 and hypothetical telomeric sequence hybridized to several chromosomal bands, while a D1/D2 probe derived from the large ribosomal sub-unit hybridized only to the largest chromosome. Unique probes such as those hybridizing to actin ACT1, glycerol-3-phosphate dehydrogenase GPD1 and beta-glucosidase LAC4 encoding genes were assigned to specific chromosomal bands of D. hansenii var. hansenii CBS767T. These probes failed to hybridize to D. hansenii var. fabryii strongly suggesting that strains of this variety actually represent a different taxon.


Combined deletion of SCD1 from adipose tissue and liver does not protect mice from obesity.
Stearoyl-CoA desaturase 1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids (MUFA) from saturated FA. Mice with whole-body or skin-specific deletion of SCD1 are resistant to obesity. Here, we show that mice lacking SCD1 in adipose and/or liver are not protected from either genetic- (agouti; A(y)/a) or diet-induced obesity (DIO) despite a robust reduction in SCD1 MUFA products in both subcutaneous and epididymal white adipose tissue. Adipose SCD1 deletion had no effect on glucose or insulin tolerance or on hepatic triglyceride (TG) accumulation. Interestingly, lack of SCD1 from liver lowered the MUFA levels of adipose tissue and vice versa, as reflected by the changes in FA composition. Simultaneous deletion of SCD1 from liver and adipose resulted in a synergistic lowering of tissue MUFA levels, especially in the A(y)/a model in which glucose tolerance was also improved. Lastly, we found that liver and plasma TG show nearly identical genotype-dependent differences in FA composition, indicating that FA composition of plasma TG is predictive for hepatic SCD1 activity and TG FA composition. The current study suggests that SCD1 deletion from adipose and/or liver is insufficient to elicit protection from obesity, but it supports the existence of extensive lipid cross-talk between liver and adipose tissue.


Adamts1 responds to systemic cues and gates adipogenesis.
Intuitively, excess caloric intake causes adipose tissue expansion. However, the signals and mechanisms by which this systemic trigger directs a local response in the adipose tissue are incompletely understood. Both hypertrophy of existing adipocytes and the generation of new adipocytes through differentiation of adipocyte precursor cells (APCs), contribute to adipose tissue expansion in response to changes in the diet. Ex vivo studies of this process elucidated an elegant network of mostly transcription factors that drive APCs through the differentiation (adipogenesis) process. Here we discuss our study that identified an Adamts1 signal as a glucocorticoid and diet responsive regulator of an extracellular relay system that modulates the initiation of this intracellular adipogenesis program in APCs. Furthermore, we describe how we applied sensitive tools that enable monitoring of endogenous APC activity to study the early response to high-fat diet in vivo.


Seeing is believing: Larger Colavita effect in school-aged children with attention-deficit/hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that leads to visually relevant compensatory activities and cognitive strategies in children. Previous studies have identified difficulties with audiovisual integration in children with ADHD, but the characteristics of the visual dominance effect when processing multisensory stimuli are not clear in children with ADHD. The current study used the Colavita paradigm to explore the visual dominance effect in school-aged children with ADHD. The results found that, compared with typically developing children, children with ADHD had a higher proportion of "visual-auditory" trials and a lower proportion of "simultaneous" trials. The study also found that the proportion of visual-auditory trials in children with ADHD decreased as their Swanson, Nolan, and Pelham-IV rating scale (SNAP-IV) inattention scores increased. The results showed that school-aged children with ADHD had a larger Colavita effect, which decreased with the severity of inattentive symptoms. This may be due to an overreliance on visual information and an abnormal integration time window. The connection between multisensory cognitive processing performance and clinical symptoms found in the current study provides empirical and theoretical support for the knowledge base of multisensory and cognitive abilities in disorders.


Biological Characterization and Evolution of Bacteriophage T7-△holin During the Serial Passage Process.
Bacteriophage T7 gene 17.5 coding for the only known holin is one of the components of its lysis system, but the holin activity in T7 is more complex than a single gene, and evidence points to the existence of additional T7 genes with holin activity. In this study, a T7 phage with a gene 17.5 deletion (T7-△holin) was rescued and its biological characteristics and effect on cell lysis were determined. Furthermore, the genomic evolution of mutant phage T7-△holin during serial passage was assessed by whole-genome sequencing analysis. It was observed that deletion of gene 17.5 from phage T7 delays lysis time and enlarges the phage burst size; however, this biological characteristic recovered to normal lysis levels during serial passage. Scanning electron microscopy showed that the two opposite ends of E. coli BL21 cells swell post-T7-△holin infection rather than drilling holes on cell membrane when compared with T7 wild-type infection. No visible progeny phage particle accumulation was observed inside the E. coli BL21 cells by transmission electron microscopy. Following serial passage of T7-△holin from the 1st to 20th generations, the mRNA levels of gene 3.5 and gene 19.5 were upregulated and several mutation sites were discovered, especially two missense mutations in gene 19.5, which indicate a potential contribution to the evolution of the T7-△holin. Although the burst size of T7-△holin increased, high titer cultivation of T7-△holin was not achieved by optimizing the culture process. Accordingly, these results suggest that gene 19.5 is a potential lysis-related component that needs to be studied further and that the T7-△holin strain with its gene 17.5 deletion is not adequate to establish the high-titer phage cultivation process.


Who should receive subsidized psychotherapy?: Analysis of decision makers' think-aloud protocols.
Three groups of judges representing clinical, political, and laypersons' perspectives were given the task of prioritizing patients for subsidized psychotherapy within the Swedish health care system. The authors documented the judges' decision-making processes in think-aloud protocols and analyzed them qualitatively, focusing on the conflict between the urgency of a case and its suitability for treatment. In an earlier statistical analysis of the same material, clinicians had seemed to pay more attention to suitability criteria, whereas health care officials and laypersons prioritized based on urgency. The qualitative findings confirmed the centrality of this conflict and contributed to a deeper understanding of decision makers' ways of coping with it. Their conceptions of suitability and urgency were also elucidated by analysis of the think-aloud protocols.


Clinical Implications of ESR1 Mutations in Hormone Receptor-Positive Advanced Breast Cancer.
Hormone receptor-positive breast cancer is the most frequent breast cancer subtype. Endocrine therapy (ET) targeting the estrogen receptor (ER) pathway represents the main initial therapeutic approach. The major strategies include estrogen deprivation and the use of selective estrogen modulators or degraders, which show efficacy in the management of metastatic and early-stage disease. However, clinical resistance associated with progression of disease remains a significant therapeutic challenge. Mutations of the ESR1 gene, which encodes the ER, have been increasingly recognized as an important mechanism of ET resistance, with a prevalence that ranges from 11 to 39%. The majority of these mutations are located within the ligand-binding domain and result in an estrogen-independent constitutive activation of the ER and, therefore, resistance to estrogen deprivation therapy such as aromatase inhibition. ESR1 mutations, most often detected from liquid biopsies, have been consistently associated with a worse outcome and are being currently evaluated as a potential biomarker to guide therapeutic decisions. At the same time, targeted therapy directed to ESR1-mutated clones is an appealing concept with preclinical and clinical work in progress.


Susceptibility-Weighted Imaging Identifies Iron-Oxide-Labeled Human Neural Stem Cells: Automated Computational Detection.
Neonatal hypoxic-ischemic brain injury (HII) can lead to devastating neurological outcomes such as cerebral palsy, epilepsy, and mental retardation. Human neural stem cell (hNSC) therapy provides new hope for the treatment of neonatal HII. These multipotent cells can aid in HII recovery by activating multiple reparative mechanisms including secretion of neurotrophic factors that enhance brain repair and plasticity. For clinical use of implanted hNSCs, methods are required to identify, quantify, track, and visualize migration and replication in an automated and reproducible fashion. In the current study, we used a model of unilateral HII in 10-day-old rat pups that were implanted with 250,000 Feridex-labeled hNSCs into the contralateral ventricle 3 days after HII. In addition to standard noninvasively acquired serial magnetic resonance imaging (MRI) sequences (11.7 and 4.7 T) that included diffusion-weighted imaging and T2-weighted imaging, we also acquired susceptibility-weighted imaging (SWI) 1-90 days after hNSC implantation. SWI is an advanced MRI method that enhances the visualization of iron-oxide-labeled hNSCs within affected regions of the injured neonatal brain. hNSC contrast was further enhanced by creating minimal intensity projections from the raw SWI magnitude images combined with phase information. Automated computational analysis using hierarchical region splitting (HRS) was applied for semiautomatic detection of hNSCs from SWI images. We found hNSCs in the ipsilateral HII lesion within the striatum and cortex adjacent to the lesion that corresponded to histological staining for iron. Quantitative phase values (radians) obtained from SWI revealed temporally evolving increased phase which reflects a decreased iron oxide content that is possibly related to cell division and the replicative capacity of the implanted hNSCs. SWI images also revealed hNSC migration from the contralateral injection site towards the ipsilateral HII lesion. Our results demonstrate that MRI-based SWI can monitor iron-labeled hNSCs in a clinically relevant manner and that automated computational methods such as HRS can rapidly identify iron-oxide-labeled hNSCs.


Force-velocity relationship on a cycle ergometer and knee-extensor strength indices.
Maximal anaerobic power (Pmax) is often measured on a friction loaded cycle ergometer by means of an all-out exercise against a single braking force or from the force-velocity relationship. The relationship between braking force (F) and peak velocity (V) in cycling is linear: V = V0(1-F/F0) where V0 and F0 correspond to the intercepts with the velocity axis and force axis, respectively. The aim of the present paper was to test the hypothesis that parameter F0 expresses strength ability. The first study (12 male volleyball players) showed significant correlations between F0 and maximal isometric voluntary force (MVF) or maximal isometric rate of force development (MRFD) during isometric knee extension with data expressed either in absolute units (0.66 < r < 0.81, P < 0.01) or related to quadriceps muscle mass kgQ or kgQ2/3 (0.58 < r < 0.82, 0.05 < P < 0.001). In the second study (24 male athletes), F0 was significantly correlated with the peak torques in isokinetic Biodex knee extension at four angular velocities (0, 1.57, 3.14 and 4.19 rad.s-1) with the values expressed in absolute units (0.49 < r < 0.83, 0.05 < P < 0.001). When the results were related to kgQ or kgQ2/3 the correlation coefficients increased with velocity (0.22 < r < 0.69) and were significant (0.05 < P < 0.001) except at 0 rad.s-1. Nevertheless, the interest of the determination of F0 in addition to Pmax is questionable because similar coefficients of correlation were obtained between Pmax and strength performances.


Concerns and hopes about outsourcing decisions regarding health information management services at two teaching hospitals in Semnan, Iran.
Changes in health programs in Iran have led to an increase in administrative costs. One cost-saving option available to hospital administrators is to outsource administrative services. This study aimed to explore the attitudes of hospital staff towards outsourcing health information management services in advance of a decision being taken, to assist healthcare organisations to assess the potential benefits and challenges of outsourcing such services. Six hundred and four clinical and allied health employees in two hospitals in Iran, who had had prior experience with outsourcing hospital services, responded to a survey designed to measure staff attitudes towards outsourcing health information management services, based on their perceptions of potential costs and benefits for the organisation and their own employment prospects. A 16-item attitude scale, developed by the researchers, was used in the study and demographic data were also collected. Summary statistics showed that approximately one third of the sample (34.53%) had a negative view of outsourcing, one third (35.16%) had a positive view, and 30.31% were neutral. An exploratory factor analysis of items on the attitude scale identified three underlying constructs, labelled: data security and management; workplace environment; and staff and customer satisfaction. One item (concern about the impact of outsourcing on staffing levels) did not load on any of the factors. A separate analysis of this single item showed a significant relationship between the sex of participants and their views on the impact of outsourcing on the number of hospital staff employed (p<0.05). While results of this study indicated that staff in hospitals surveyed held both positive and negative views of outsourcing, a large number of staff in these hospitals (a third of the total sample) had reservations about the skills of outside providers to securely manage hospital data, and did not consider that outsourcing health information management services would be positive for the organisation, their working environment or for staff and patient satisfaction. These findings have important implications for healthcare organisations planning to outsource health information services. Further research that focuses on communication skills of senior managers and their ability to provide team leadership is needed, as is research into the impact of geographical location and current market forces that impact on outsourcing tasks.


Estimating acoustic cue rates in bowhead whales, Balaena mysticetus, during their fall migration through the Alaskan Beaufort Sea.
Eight years of passive acoustic data (2007-2014) from the Beaufort Sea were used to estimate the mean cue rate (calling rate) of individual bowhead whales (Balaena mysticetus) during their fall migration along the North Slope of Alaska. Calls detected on directional acoustic recorders (DASARs) were triangulated to provide estimates of locations at times of call production, which were then translated into call densities (calls/h/km2). Various assumptions were used to convert call density into animal cue rates, including the time for whales to cross the arrays of acoustic recorders, the population size, the fraction of the migration corridor missed by the localizing array system, and the fraction of the seasonal migration missed because recorders were retrieved before the end of the migration. Taking these uncertainties into account in various combinations yielded up to 351 cue rate estimates, which summarize to a median of 1.3 calls/whale/h and an interquartile range of 0.5-5.4 calls/whale/h.


Acetabular reaming and sartorius muscle pedicle iliac bone grafting in the treatment of developmental dysplasia of the hip in older children: a retrospective study of 15 patients with more than two years follow-up.
Despite the early diagnosis and treatment of developmental dysplasia of the hip (DDH), some older children still need open reduction. It is usually difficult to get a satisfactory reduction particularly in patients with acetabular defect. The purpose of this study was to evaluate the short-term outcomes of acetabulum reaming and sartorius muscle pedicle iliac bone grafting in the treatment of older children with DDH and acetabular defect. The records of 15 patients with DDH (mean age 113.9 months (sd 29); 17 hips) who were treated with the reported technique between February 2015 and January 2017 were retrospectively reviewed. All patients acquired regular clinical and radiographic follow-ups, and alterations in the acetabular index, centre-edge angle and acetabular head index were measured. Joint function and radiographic results were evaluated with McKay and Severin modified criteria, respectively. A total of 15 patients were followed up for mean 32.4 months (sd 6.9). The percentages of excellent and good conditions were 94.1% (16/17) according to the Severin modified criteria and 88.2% (15/17) according to the McKay modified criteria. Avascular necrosis of the femoral head and redislocation only occurred in one hip. No cases of ankylosis or bone graft absorption occurred during the follow-up. Reaming the acetabulum and sartorius muscle pedicle iliac bone grafting for repairing the acetabular defect can recover the arcuate structure by increasing the volume of the acetabulum, which is beneficial for achieving a concentric reduction. The short-term outcome was satisfactory, while the long-term results need to be further observed. IV - retrospective study.


Determination of conversion factors from air kerma to operational dose equivalent quantities for low-energy X-ray spectra.
The conversion coefficients from air kerma to ICRU operational dose equivalent quantities for STUK's realisation of the X-radiation qualities N-15 to N-60 of the ISO narrow (N) spectrum series were determined by utilising X-ray spectrum measurements. The pulse-height spectra were measured using a planar high-purity germanium spectrometer and unfolded to fluence spectra using Monte Carlo generated data of the spectrometer response. To verify the measuring and unfolding method, the first and second half-value layers and the air kerma rate were calculated from the fluence spectra and compared with the values measured using an ionisation chamber. For each radiation quality, the spectrum was characterised by the parameters given in ISO 4037-1. The conversion coefficients from the air kerma to the ICRU operational quantities Hp(10), Hp(0.07), H'(0.07) and H*(10) were calculated using monoenergetic conversion coefficients at zero angle of incidence. The results are discussed with respect to ISO 4037-4, and compared with published results for low-energy X-ray spectra.


Oxidation of thiol drugs and biochemicals by the lactoperoxidase/hydrogen peroxide system.
The thiol moiety is prone to oxidative free radical formation, which may be important in mediating the toxicity of some thiol-containing compounds. The oxidation of the compounds cysteine, cysteamine, N-acetylcysteine, glutathione, penicillamine, and captopril were studied using ESR and oxygen uptake techniques. Lactoperoxidase, with hydrogen peroxide to provide oxidizing equivalents, was used to initiate the oxidation. The reaction appears to be strongly peroxide dependent, with either exogenous H2O2 or thiol-derived peroxide driving the reaction.


Faecal bulking index: A physiological basis for dietary management of bulk in the distal colon.
Bulk in the distal colon provides protection against a range of large bowel disorders, but a simple standardized measure of the relative bulking efficacy of foods, for use in dietary management of distal colonic bulk, has not been available. This paper describes a faecal bulking index (FBI) for standardized measurement of the relative colonic bulking efficacy of foods relative to a reference material. Faecal bulking index is defined as the mass of fully rehydrated faecal matter accumulated by the distal colon per gram of a food consumed, as a percentage of the matter accumulated from the same weight of a reference food. The FBI of foods was measured after feeding adult rats at moderate levels by partially or completely replacing sucrose in a baseline diet already containing mixed dietary fiber. Faeces were collected, dried, weighed, allowed to imbibe water until fully rehydrated, reweighed and their mass and water holding capacity measured. The FBI was calculated as the increase over baseline in rehydrated faecal mass induced by a test food as a percentage of the increase due to wheat bran (reference). The FBI values were measured for 69 diets including breakfast cereals, breads and other bakery products, fruits, vegetables, food ingredients and polysaccharides. Values for most foods ranged between almost zero for some starch-based foods to about 50 for wheat bran-enriched breakfast cereals, but laxatives based on fermentation-resistant hydrated polysaccharide had FBI values well in excess of 100 (FBI for psyllium = 500). The FBI values allow foods to be ranked according to their faecal bulking efficacy on an equal edible weight basis. They can also be used to calculate the bulking action of any amount of food in terms of equivalents to a reference material such as wheat bran. Wheat bran equivalents allow the cumulative intake of potential distal colonic bulk to be monitored for single foods or mixed meals, and shortfalls to be quantified for dietary modification or supplementation. Measures such as FBI or wheat bran equivalents would prove more useful than dietary fiber in controlling 'functional foods' promoted as effective bulking agents.


Ultrasonographic findings of small bowel intussusception, focusing on differentiation from ileocolic intussusception.
The purpose of this study was to evaluate the typical ultrasonographic findings of transient small bowel intussusception (SBI) and to differentiate it from ileocolic intussusception (ICI) in paediatrics. 22 transient SBI (male:female = 13:9, age: 7-132 months (mean 38 months)) and 27 ICI (male:female = 19:8, age: 1-60 months (mean 13 months)) patients diagnosed on ultrasonography were retrospectively evaluated. The findings of location, diameter, thickness of outer rim, and inclusion of mesenteric lymph nodes within intussuscipiens were compared. In the transient SBI, the head of intussusception was located in the right lower quadrant (RLQ) in 11 (50%), the right upper quadrant (RUQ) in 2 (9.1%) and the periumbilical area in 9 (40.9%) cases. The anteroposterior (AP) diameter ranged from 0.84-2.4 cm (mean 1.38 cm), and thickness of outer rim ranged from 0.10-0.34 cm (mean 0.26 cm). No mesenteric lymph nodes were contained within the intussuscipiens. In the ICI, the head was located in the RUQ in 17 (63%), the epigastrium in 7 (25.9%) and the left upper quadrant in 3 (11.1%) cases. The AP diameter ranged from 1.89-3.32 cm (mean 2.53 cm), and the thickness of the outer rim ranged from 0.30-0.86 cm (mean 0.53 cm). Mesenteric lymph nodes were contained within the intussuscipiens in 26 (96.3%) cases. In conclusion, when compared with ICI, the transient SBI occurs predominantly in the RLQ or periumbilical region, has a smaller AP diameter, a thinner outer rim, and dose not contain mesenteric lymph nodes.


Neurosurgical suite of the future. II.
The role of imaging in diagnosis and therapy has been accepted by physicians. This favorable reception of minimally invasive procedures resulted in the recognition of the feasibility of image-guided approaches. Although radiology has combined imaging with various novel therapeutic methods, the full use of advanced imaging technology has not yet been accomplished. The current trend is the evolution of integrated therapy delivery systems in which advanced imaging modalities are closely linked with high performance computing. Obviously, the operating room of the future will accommodate various instruments, tools and devices, which are attached to the imaging systems and controlled by image-based feedback.


Plant programmed cell death and the point of no return.
The point of no return during programmed cell death (PCD) is defined as the step beyond which the cell is irreversibly committed to die. Some plant cells can be saved before this point by inducing the formation of functional chloroplasts. A visibly senescent tissue will then become green again and live for months or years. The mechanism of this reversal is only partially known. The point of no return in fungi and animals is often associated with lack of mitochondrial function. In plant cells that do not regreen, there is no evidence for PCD reversal that results in a long life. It is unclear why chloroplast-containing cells, in contrast to those with only mitochondria, have long lives after PCD reversal.


Famous people recognition through personal name: a normative study.
In this normative study, we investigated famous people recognition through personal name, using as stimuli the names of the same 40 Italian famous persons whose faces and voices had been utilized for the normative study of the Famous People Recognition Battery. For each famous people, we assessed name familiarity, person identification (when the name had been considered as familiar), and false alarms. The investigation was carried out on 143 normal subjects who varied in age and education. Name familiarity and semantic scores were affected by educational level, whereas age influenced false alarms. A comparison between results obtained with names in this research and with faces and voices of the same famous people in our previous study showed that familiarity scores were higher for personal names than those for faces and voices, which obtained the worst scores. Person identification scores were not significantly different from names and from faces, but both these scores were significantly higher than the semantic scores obtained by voices. Taken together, these results are inconsistent with the influential interactive activation and competition model of person recognition.


[The efficacy of early intervention for infants and toddlers with hearing loss].
To investigate the efficacy of early intervention on language, pronunciation and cognitive developments of infants and toddlers with hearing loss and to build up an early intervention model. Fifty-six children with moderate to profound sensorineural hearing loss aged 10 months to 2 years were divided into two groups. 20 children, aged 10 months to 2 years, received early intervention services after wearing hearing aids for 6 - 18 months, and 36 children, aged 11 months to 2 years, didn't receive any intervention. The type and degree of hearing loss were measured by a series of auditory tests. Language and cognitive developments of the children with hearing loss and 28 age, and sex-matched children with normal hearing, aged 10 to 23 months, were evaluated by the Gesell developmental schedules. The results were expressed as developmental quotient (DQ). Pronunciation test in mandarin Chinese was adopted to evaluate the speech development of the 56 children with hearing loss. (1) The language DQ according the Gesell developmental schedules of the children with hearing loss who received early intervention was (92.25 +/- 17.32), significantly higher than those children with hearing loss who didn't receive intervention (70.44 +/- 29.99, P = 0.00), whish was significantly lower than that of the normal hearing children (P = 0.00). However, there was no significant difference in language DQ between the children who received early intervention and the normal hearing children. There was no significant correlation between the degree of hearing loss and language DQ in the children who received early intervention (P = 0.27). (2) The personal-social developmental quotient (DQ) of the children who received intervention was (101.40 +/- 7.66), significantly higher than that of the children who didn't receive intervention (83.94 +/- 22.09, P = 0.00), that were significantly lower than that of the children with normal hearing (P = 0.00). However, there were no significant difference in the personal-social DQ between the children who received early intervention and the children with normal hearing. No significant differences in the gross motor ability, fine motor ability and adaptive ability were observed between the two groups of children with hearing loss and normal hearing children. (3) The consonant pronunciation of the children with moderate to severe hearing loss who received early intervention was normal. Among those children only one case with profound hearing loss had/d/error. The consonant pronunciation of the children with moderate hearing loss who didn't receive early intervention of those was normal. One case with moderate-severe hearing loss and one case with severe hearing loss had/d/errors. Six cases with profound hearing loss had/d, m/errors. The tone of the children with moderate to severe hearing loss who received early intervention was normal. Three cases with profound hearing loss exhibited tone errors. Among the children who didn't receive early intervention, tone errors were found in two cases with moderate hearing loss, one case with moderate-severe hearing loss, one case with severe hearing loss, and twelve cases with profound hearing loss showed. The language, pronunciation and cognitive developments of the children who don't receive early intervention are significantly lower than those of the children with normal hearing. Early intervention can significantly improve the language, speech and cognitive abilities of children with hearing loss.


Production of a halotolerant biofilm from green coffee beans immobilized on loofah fiber (Luffa cylindrica) and its effect on phenanthrene degradation in seawater.
A biofilm developed from low quality green coffee beans was tested for its capacity to degrade the polynuclear aromatic hydrocarbon (PAH), phenanthrene (Phe), in seawater. Microorganisms were immobilized on two types of Luffa cylindrica (with three and four placental cavities), and the effects of moisture content (20, 30 and 40% of water holding capacity) and particle size (<0.42 mm, 0.42-0.86 mm and 0.86-2.0 mm) of green coffee beans on microbial activity were considered. Biofilm growth determined by respirometry showed a highest microbial activity at a moisture content of 40% and particle size of 0.42-0.86 mm. The loofah fiber with three placental cavities showed the highest adherence of microorganisms. The kinetics of microbial growth in both seawater and distilled water and the scanning electron microscopies indicated that the microorganisms associated with green coffee beans are halotolerant. In fact, I-GCB-SW-G biofilm degraded 67.56% of Phe (50 mg L-1) in seawater, at a significantly higher rate than in distilled water (I-GCB-DW-W).


Impact of Chemical Analogs of 4-Hydroxybenzoic Acid on Coenzyme Q Biosynthesis: From Inhibition to Bypass of Coenzyme Q Deficiency.
Coenzyme Q is a lipid that participates to important physiological functions. Coenzyme Q is synthesized in multiple steps from the precursor 4-hydroxybenzoic acid. Mutations in enzymes that participate to coenzyme Q biosynthesis result in primary coenzyme Q deficiency, a type of mitochondrial disease. Coenzyme Q10 supplementation of patients is the classical treatment but it shows limited efficacy in some cases. The molecular understanding of the coenzyme Q biosynthetic pathway allowed the design of experiments to bypass deficient biosynthetic steps with analogs of 4-hydroxybenzoic acid. These molecules provide the defective chemical group and can reactivate endogenous coenzyme Q biosynthesis as demonstrated recently in yeast, mammalian cell cultures, and mouse models of primary coenzyme Q deficiency. This mini review presents how the chemical properties of various analogs of 4-hydroxybenzoic acid dictate the effect of the molecules on CoQ biosynthesis and how the reactivation of endogenous coenzyme Q biosynthesis may achieve better results than exogenous CoQ10 supplementation.


Accelerated wound closure in mice deficient for interleukin-10.
The impact of the local inflammatory response on the process of wound healing has been debated for decades. In particular, the question whether infiltrating macrophages and granulocytes promote or impede tissue repair has received much attention. In the present study, we show that wound healing is accelerated in mice deficient for the anti-inflammatory cytokine interleukin (IL)-10. IL-10-/- mice closed excisional wounds significantly earlier compared with IL-10-competent control littermates. This effect was attributable to accelerated epithelialization as well as enhanced contraction of the wound tissue in the mutant animals. Increased alpha-smooth muscle actin expression in IL-10-deficient mice suggests that augmented myofibroblast differentiation is responsible for the enhanced contraction of wounds in mutant mice. The number of macrophages infiltrating the wound tissue was significantly increased in IL-10-/- mice compared with control littermates suggesting that this cell type mediates the accelerated tissue repair. These results show for the first time that IL-10 can impede wound repair.


[Endothelin receptor antagonist].
Pulmonary arterial hypertension(PAH) is an uncommon disease characterised by a progressive increase in pulmonary vascular resistance. An imbalance between vasoconstrictor/vasodilator activities could be responsible for altered pulmonary vascular tone and structure. In PAH patients, endothelin are increased. Restoration of this imbalance by targeted therapies such as endothelin receptor antagonists should further improve treatment options for the management of PAH. Current treatment algorithms for PAH recommend bosentan as first-line treatment for PAH in functional class III. Recent many trials suggested that endothelin receptor antagonist, bosentan, caused good results in idiopathic PAH and PAH associated with chronic thromboembolism, collagen diseases, and congenital heart diseases.


Plasma ionization source for atmospheric pressure mass spectrometry imaging using near-field optical laser ablation.
Mass spectrometry imaging (MSI) at ambient pressures with submicrometer resolution is challenging, due to the very low amount of material available for mass spectrometric analysis. In this work, we present the development and characterization of a method for MSI based on pulsed laser ablation via a scanning near-field optical microscopy (SNOM) aperture tip. SNOM allows laser ablation of material from surfaces with submicrometer spatial resolution, which can be ionized for further chemical analysis with MS. Efficient ionization is realized here with a custom-built capillary plasma ionization source. We show the applicability of this setup for mass spectrometric analysis of three common MALDI matrices, α-4-hydroxycyanocinnamic acid, 3-aminobenzoic acid, and 2,5-dihydroxybenzoic acid. Although the ultimate goal has been to optimize sensitivity for detecting material ablated from submicrometer diameter craters, the effective lateral resolution is currently limited by the sensitivity of the MS detection system. In our case, the sensitivity of the MS was about 1 fmol, which allowed us to achieve a spatial resolution of 2 μm. We also characterize the analytical figures of merit of our method. In particular, we demonstrate good reproducibility, a repetition rate in the range of only a few seconds, and we determined the amount of substance required to achieve optimal resolution and sensitivity. Moreover, the sample topography is available from SNOM scans, a parameter that is missing in common MSI methods.


Hepatic β-arrestins: potential roles in liver health and disease.
Β-arrestins are intracellular scaffolding proteins that have multifaceted roles in different types of disorders. In this review article, we gave a summary about the discovery, characterization and classification of these proteins and their intracellular functions. Moreover, this review article focused on the hepatic expression of β-arrestins and their hepatocellular distribution and function in each liver cell type. Also, we showed that β-arrestins are key regulators of distinct types of hepatic disorders. On the other hand, we addressed some important points that have never been studied before regarding the role of β-arrestins in certain types of hepatic disorders which needs more research efforts to cover.


Rare, common, alien and native species follow different rules in an understory plant community.
Biological invasions are a leading threat to biodiversity globally. Increasingly, ecosystems experience multiple introductions, which can have significant effects on patterns of diversity. The way these communities assemble will depend partly on whether rare and common alien species respond to environmental predictors in the same manner as rare and common native species, but this is not well understood. To examine this question across four national parks in south-eastern Australia, we sampled the understory plant community of eucalypt-dominated dry forest subject to multiple plant introductions. The drivers of diversity and turnover in alien and native species of contrasting frequency of occurrence (low, intermediate, and high) were each tested individually. We found alien species diversity and turnover were both strongly associated with abiotic conditions (e.g., soil pH), while distance had little influence because of the greater extent of occurrence and more homogeneous composition of common aliens. In contrast, native species diversity was not associated with abiotic conditions and their turnover was as strongly influenced by distance as by abiotic conditions. In both alien and native species, however, the most important predictors of turnover changed with frequency of occurrence. Although local coexistence appears to be facilitated by life history trade-offs, species richness of aliens and natives was negatively correlated and native species might face greater competition in areas with more neutral soils (e.g., pH > ~5.5) where alien richness and relative frequency were both highest. We conclude that diversity and turnover in the generally more widespread alien species are mainly driven by species sorting along an environmental gradient associated with pH and nutrient availability, whereas turnover of native species is driven by more neutral processes associated with dispersal limitation. We show alien and native plant species respond to different environmental factors, as do rare and common species within each component.


CCL2, CCL5, IL4 and IL15 Gene Polymorphisms in Women with Gestational Diabetes Mellitus.
Gestational diabetes mellitus (GDM) is a glucose intolerance that occurs during pregnancy. Several studies suggest that inflammation contributes to pregnancy-induced insulin resistance and the development of glucose intolerance. The aim of this study is to examine the association between the CCL2, CCL5, IL4 and IL15 gene polymorphisms and the development of GDM. This study included 411 pregnant women who underwent a 75 g oral glucose tolerance test at 24-28 weeks of gestation. Participants were categorised into 2 groups according to results of the oral glucose tolerance test (OGTT). The GDM group included 204 pregnant women who were diagnosed with GDM. The normal glucose tolerance group included 207 pregnant women with normal values in the OGTT. To discriminate the CCL2 rs1024611 and rs4586, CCL5 rs2107538, IL4 rs2243250, IL15 rs2857261 and rs2254514 alleles, TaqMan® Pre-Designed SNP Genotyping Assays were used. GDM was significantly associated with genotypes and alleles of the CCL2 rs1024611 and rs4586 polymorphisms, while there was no statistically significant association between the CCL5 rs2107538, IL4 rs2243250, IL15 rs2857261, and rs2254514 gene polymorphisms and GDM. In a multivariate regression analysis, age and BMI before pregnancy were independent significant predictors of a higher risk of GDM, while a lower number of G alleles CCL2 rs1024611 was protective against GDM. Moreover, women with the GG CCL2 rs1024611 and CC rs4586 genotype tended to have lower body mass and BMI increases during pregnancy, as well as lower newborn body mass. The results of our study suggest an association between CCL2 gene polymorphisms and GDM.


Peptidergic innervation of the vasoconstrictor muscle of the abdominal aorta in Aplysia kurodai.
The arterial system of the marine mollusc Aplysia consists of three major arteries. One of them, the abdominal aorta, has a sphincter (the vasoconstrictor muscle) at the base of the artery. Contraction of this muscle reduces the blood flow into the abdominal aorta, thereby, playing a role in the regulation of the blood distribution in Aplysia. Here, we show the contractility of the vasoconstrictor muscle is modulated by three types of endogenous peptides, Aplysia mytilus inhibitory peptide-related peptides (AMRP), enterin and NdWFamide. Immunohistochemistry showed that putative neuronal processes containing the three peptides exist in the vasoconstrictor muscle. Enterin inhibited the muscle contraction elicited by the nerve stimulation or the application of a putative excitatory transmitter, acetylcholine (ACh). Enterin hyperpolarized the resting potential of the muscle and decreased the amplitude of the excitatory junction potential (EJP). AMRP also inhibited the nerve-evoked contraction although its action on the ACh-induced contraction was variable. AMRP also reduced the size of EJP, but had no effect on the resting potential of the muscle. NdWFamide enhanced the nerve-evoked contraction but not the ACh-induced contraction. NdWFamide augmented EJP without affecting the resting potential of the muscle. These results suggest that AMRP, enterin and NdWFamide are endogenous modulators of the contractile activity of the vasoconstrictor muscle, and that the peptidergic innervations of this muscle contribute to fine tuning of the blood distribution in Aplysia.


Facial feminization surgery: current state of the art.
Facial feminization surgery (FFS) is a group of surgical procedures; the objectives of which are to change the features of a male face to that of a female face. This surgery does not aim to rejuvenate the face. FFS is carried out almost exclusively on transsexual women (males who are transitioning into females) and who have gender dysphoria. Some non-transsexual women may undergo some feminizing surgical procedures if they feel that they have male facial characteristics. Most transsexual women will have lived in role for sometime and they often undergo FFS before any other form of gender reassignment surgery as it assists them in passing as a female and integrating into everyday society. Various specific facial surgical procedures are utilized to feminize the face, often involving sculpture and contouring of the facial skeleton. These include correction of the hairline by scalp advance, contouring the forehead, brow lift, rhinoplasty, cheek implants, resection of the buccal fat pads of Bichat, lip lift and lip augmentation with dermis graft, mandible angle reduction and taper, genioplasty and thyroid shave. This article discusses the current state of the art in facial feminization surgery.


The diagnostic utility of dual phase Tc-99m sestamibi parathyroid imaging.
Primary hyperparathyroidism is a disease of uncertain etiology that results from hypersecretion of parathyroid hormone (PTH) by the parathyroid gland. In most institutions, the preferred imaging protocol utilizes a dual-phase technique with Tc-99m sestamibi which is reported to be more sensitive than earlier protocols involving TI-201 with Tc-99m pertechnetate subtraction. The purpose of this study is to evaluate the accuracy and clinical utility of Tc-99m sestamibi dual-phase scintigraphy for localizing hyperfunctioning parathyroid tissue. We retrospectively reviewed thirty-nine consecutive hyperparathyroid patients who received a dual-phase Tc-99m sestamibi parathyroid scan. Thirty-seven of the subjects subsequently underwent a bilateral neck exploration and parathyroidectomy. Each scan interpretation was then correlated with the histopathologic diagnosis and the patients' post-surgical clinical course. The sestamibi dual-phase imaging protocol correctly localized 21 of 25 parathyroid adenomas and identified 8 out of 10 cases of hyperplasia. Our overall sensitivity and specificity were 83% and 75%, respectively. In addition, four of the adenomas were successfully localized intraoperatively using a gamma probe. Parathyroid imaging with sestamibi appears to be superior to TI-201/Tc-99m pertechnetate subtraction based on the reported results of both techniques at various institutions. Dual-phase sestamibi imaging appears to be useful and cost-effective for presurgical localization of hyperfunctioning parathyroid tissue. In addition, sestamibi imaging in conjunction with an intraoperative probe is a very promising technique that has the potential to provide both localization information of a suspected parathyroid adenoma and to facilitate its surgical removal by reducing operation time.


On status epilepticus and pins: A systematic content analysis.
Status epilepticus (SE) can be defined as abnormally prolonged, persistent, or recurrent clinical and/or electrographic epileptic activity and, as such, is a challenging medical emergency requiring an aggressive treatment aimed at promptly terminating the seizures. It imposes a relevant clinical burden, both in terms of comorbidity and mortality. In the era of the Web 2.0, most people search the Web to obtain SE-related information. The current investigation aimed at qualitatively characterizing the pins related to SE: Pinterest, "the world's catalog of ideas", is a visual social networking site that enables users to freely upload visual material, to bookmark, and to share it (repin). Using SE as a keyword, 192 pins were extracted and analyzed on the basis of their content. Fifty-five were found to meet the inclusion criteria. Fifty-six point four percent of the pins reported at least one cause of SE, the most quoted of which being remote brain injuries (47.3% of the pins); 54.5% and 45.5% of the included pins reported SE symptoms and diagnosis, respectively; 72.7% and 40.0% of pins focused on SE treatment and on prognosis, respectively; and 50.9%, 30.9%, and 40.0% of the pins were intended for physicians, medical/nursing students, and lay people, respectively. Only 12.7% of pins were patient-centered and devoted to fund-raising and advocacy. In the field of neurological diseases, Pinterest, despite being a "pinstructive" tool, is too much overlooked and underused for advocacy purposes. Healthcare workers and stakeholders should be aware of the opportunities offered by Pinterest and exploit this visual social networking site for raising awareness of the life-threatening condition of SE, promoting fund-raising campaigns.


beta 2-Microglobulin: structure, function and significance.
beta 2-Microglobulin is a low molecular weight protein with sequence homology to immunoglobulins. As a portion of the HLA complex this protein is an important cell-surface structure. Under normal conditions beta 2-microglobulin is synthesized and shed by many cells, particularly lymphocytes, and is detectable in the circulation of normal individuals. Because of its small size it is normally filtered readily at the glomerulus and is catabolized by proximal tubular cells of the kidney. Impaired renal function and hyperproduction of beta 2-microglobulin are both associated with increased serum levels. A function for beta 2-microglobulin as a modulator of lymphocyte surface and as a potential regulator of the immune system is proposed.


The effect of graft-versus-host disease on T cell production and homeostasis.
The aim of this work was to decipher how graft-versus-host disease (GVHD) affects T cell production and homeostasis. In GVHD+ mice, thymic output was decreased fourfold relative to normal mice, but was sufficient to maintain a T cell repertoire with normal diversity in terms of Vbeta usage. Lymphoid hypoplasia in GVHD+ mice was caused mainly by a lessened expansion of the peripheral postthymic T cell compartment. In 5-bromo-2'-deoxyuridine pulse-chase experiments, resident T cells in the spleen of GVHD+ mice showed a normal turnover rate (proliferation and half-life). When transferred into thymectomized GVHD- secondary hosts, T cells from GVHD+ mice expanded normally. In contrast, normal T cells failed to expand when injected into GVHD+ mice. Thus, the reduced size of the postthymic compartment in GVHD+ mice was not due to an intrinsic lymphocyte defect, but to an extrinsic microenvironment abnormality. We suggest that this extrinsic anomaly is consistent with a reduced number of functional peripheral T cell niches. Therefore, our results show that GVHD-associated T cell hypoplasia is largely caused by a perturbed homeostasis of the peripheral compartment. Furthermore, they suggest that damage to the microenvironment of secondary lymphoid organs may represent an heretofore unrecognized cause of acquired T cell hypoplasia.


Artificial intelligence for detecting temporomandibular joint osteoarthritis using radiographic image data: A systematic review and meta-analysis of diagnostic test accuracy.
In this review, we assessed the diagnostic efficiency of artificial intelligence (AI) models in detecting temporomandibular joint osteoarthritis (TMJOA) using radiographic imaging data. Based upon the PRISMA guidelines, a systematic review of studies published between January 2010 and January 2023 was conducted using PubMed, Web of Science, Scopus, and Embase. Articles on the accuracy of AI to detect TMJOA or degenerative changes by radiographic imaging were selected. The characteristics and diagnostic information of each article were extracted. The quality of studies was assessed by the QUADAS-2 tool. Pooled data for sensitivity, specificity, and summary receiver operating characteristic curve (SROC) were calculated. Of 513 records identified through a database search, six met the inclusion criteria and were collected. The pooled sensitivity, specificity, and area under the curve (AUC) were 80%, 90%, and 92%, respectively. Substantial heterogeneity between AI models mainly arose from imaging modality, ethnicity, sex, techniques of AI, and sample size. This article confirmed AI models have enormous potential for diagnosing TMJOA automatically through radiographic imaging. Therefore, AI models appear to have enormous potential to diagnose TMJOA automatically using radiographic images. However, further studies are needed to evaluate AI more thoroughly.


Winners and losers of national and global efforts to reconcile agricultural intensification and biodiversity conservation.
Closing yield gaps within existing croplands, and thereby avoiding further habitat conversions, is a prominently and controversially discussed strategy to meet the rising demand for agricultural products, while minimizing biodiversity impacts. The agricultural intensification associated with such a strategy poses additional threats to biodiversity within agricultural landscapes. The uneven spatial distribution of both yield gaps and biodiversity provides opportunities for reconciling agricultural intensification and biodiversity conservation through spatially optimized intensification. Here, we integrate distribution and habitat information for almost 20,000 vertebrate species with land-cover and land-use datasets. We estimate that projected agricultural intensification between 2000 and 2040 would reduce the global biodiversity value of agricultural lands by 11%, relative to 2000. Contrasting these projections with spatial land-use optimization scenarios reveals that 88% of projected biodiversity loss could be avoided through globally coordinated land-use planning, implying huge efficiency gains through international cooperation. However, global-scale optimization also implies a highly uneven distribution of costs and benefits, resulting in distinct "winners and losers" in terms of national economic development, food security, food sovereignty or conservation. Given conflicting national interests and lacking effective governance mechanisms to guarantee equitable compensation of losers, multinational land-use optimization seems politically unlikely. In turn, 61% of projected biodiversity loss could be avoided through nationally focused optimization, and 33% through optimization within just 10 countries. Targeted efforts to improve the capacity for integrated land-use planning for sustainable intensification especially in these countries, including the strengthening of institutions that can arbitrate subnational land-use conflicts, may offer an effective, yet politically feasible, avenue to better reconcile future trade-offs between agriculture and conservation. The efficiency gains of optimization remained robust when assuming that yields could only be increased to 80% of their potential. Our results highlight the need to better integrate real-world governance, political and economic challenges into sustainable development and global change mitigation research.


Post-traumatic mitral regurgitation and ventricular septal defect in absence of left pericardium.
A six-year-old boy was hospitalized following a car accident. Cardiac catheterization demonstrated acute post-traumatic mitral regurgitation (MR) and ventricular septal defect (VSD). The patient was operated on for mitral valve replacement and closure of the VSD. On opening the chest absence of the left pericardium was noted. Cardiac catheterization performed in the postoperative period demonstrated a residual left-to-right shunt at ventricular level. The patient was reoperated on 10 months later for closure of the residual VSD. Six months after the last operation the patient is in good condition. The congenital absence of the pericardium is considered as favoring both the post-traumatic cardiac lesions and the postoperative pulmonary problems on the left side.


Hydroxylamine Promoted Goethite Surface Fenton Degradation of Organic Pollutants.
In this study, we construct a surface Fenton system with hydroxylamine (NH2OH), goethite (α-FeOOH), and H2O2 (α-FeOOH-HA/H2O2) to degrade various organic pollutants including dyes (methyl orange, methylene blue, and rhodamine B), pesticides (pentachlorophenol, alachlor, and atrazine), and antibiotics (tetracycline, chloramphenicol, and lincomycin) at pH 5.0. In this surface Fenton system, the presence of NH2OH could greatly promote the H2O2 decomposition on the α-FeOOH surface to produce ·OH without releasing any detectable iron ions during the alachlor degradation, which was different from some previously reported heterogeneous Fenton counterparts. Moreover, the ·OH generation rate constant of this surface Fenton system was 102-104 times those of previous heterogeneous Fenton processes. The interaction between α-FeOOH and NH2OH was investigated with using attenuated total reflectance Fourier transform infrared spectroscopy and density functional theory calculations. The effective degradation of organic pollutants in this surface Fenton system was ascribed to the efficient Fe(III)/Fe(II) cycle on the α-FeOOH surface promoted by NH2OH, which was confirmed by X-ray photoelectron spectroscopy analysis. The degradation intermediates and mineralization of alachlor in this surface Fenton system were then systematically investigated using total organic carbon and ion chromatography, liquid chromatography-mass spectrometry, and gas chromatography-mass spectrometry. This study offers a new strategy to degrade organic pollutants and also sheds light on the environmental effects of goethite.


The utility of the MMPI-3 in predicting substance use related problems in a clinical neuropsychology sample.
Assessing for problematic substance use in neuropsychological assessments is crucial for differential diagnosis and attribution of symptom causes. The current investigation examines the utility of the Minnesota Multiphasic Personality Inventory-3 (MMPI-3 in predicting such substance use in a clinical neuropsychology sample. Participants included 208 outpatient neuropsychological examinees. Correlations and risk ratios were calculated for externalizing-psychopathology-related scales and external substance use criteria. Hierarchical regressions examined the incremental prediction of criteria by MMPI-3 externalizing scales above the Substance Abuse (SUB) scale. Results indicate that MMPI-3 externalizing scales are associated with substance-use-related criteria as conceptually expected. Additionally, we report significantly increased risk of experiencing substance-use-related problems at various T score elevations on multiple externalizing scales. Finally, SUB served as the primary predictor of substance-use-related criteria. These findings support the ability of the MMPI-3 to assess for past or current substance use and negative consequences of substance use in a clinical neuropsychology setting.


Computational and structure-guided design of phosphoinositide substrate specificity into the tyrosine specific LMW-PTP enzyme.
We have used a combination of computational and structure-based redesign of the low molecular weight protein tyrosine phosphatase, LMW-PTP, to create new activity towards phosphoinositide substrates for which the wild-type enzyme had little or no activity. The redesigned enzymes retain catalytic activity despite residue alterations in the active site, and kinetic experiments confirmed specificity for up to four phosphoinositide substrates. Changes in the shape and overall volume of the active site where critical to facilitate access of the new substrates for catalysis. The kinetics data suggest that both the position and the combination of amino acid mutations are important for specificity towards the phosphoinositide substrates. The introduction of basic residues proved essential to establish new interactions with the multiple phosphate groups in the inositol head, thus promoting catalytically productive complexes. The crystallographic structures of the top-ranking designs confirmed the computational predictions and showed that residue substitutions do not alter the overall folding of the phosphatase or the conformation of the active site P-loop. The engineered LMW-PTP mutants with new activities can be useful reagents in investigating cell signalling pathways and offer the potential for therapeutic applications.


CHRNA5 rs16969968 Polymorphism Association with Risk of Lung Cancer--Evidence from 17,962 Lung Cancer Cases and 77,216 Control Subjects.
Genetic studies have shown a possible relationship between the rs16969968 polymorphism in CHRNA5 and the risk of lung cancer. However, the results have been conflicting. Thus we rigorously conducted a meta-analysis to clarify any association. A total of 10 case-control studies involving 17,962 lung cancer cases and 77,216 control subjects were analysed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of the association. We found the CHRNA5 rs16969968 polymorphism to be associated with the risk of lung cancer (AA vs GG: OR=1.60, 95%CI=1.51-1.71). On stratified analysis by smoking status, a statistically significant increased risk was observed in the smoking group (AA vs GG: OR=1.80, 95%CI=1.61-2.01). However, this polymorphism was not associated with lung cancer risk in Asians (AA vs GG: OR=0.95, 95%CI=0.35-2.59), whereas it was linked to increased risk of lung cancer among Caucasians (AA vs GG: OR=1.65, 95%CI=1.55-1.76). Our meta-analysis provided statistical evidence for a strong association between rs16969968 polymorphism and the risk of lung cancer, especially in smokers and Caucasians. Application of this relationship may contribute to identification of individuals at high risk of lung cancer and indicate a chemoprevention target.


Perceptions of a dental career among successful applicants for dentistry compared with those of fifth-year dental students.
A focused and vocational university programme such as dentistry may limit the opportunities for graduates who find that clinical dentistry is not for them. It is important that those advising and recruiting people into the profession should ascertain whether applicants have a realistic idea of what lies ahead. On the presumption that final-year undergraduate students have acquired a more realistic impression of the profession that potential entrants, it was of interest to investigate possible differences in the perceptions of dentistry between the two groups. The perceptions of dentistry have been categorised and compared by anonymous questionnaire between final-year dental students (n = 79) and successful undergraduate applicants (n = 109) at the same institution in the United Kingdom. The overall response rate was 100% in both cases. It is clear that both groups are concerned with personal and professional matters followed by career opportunities and financial matters, respectively. Health matters pose the least concern. However a number of significant differences have emerged. Significantly fewer students (p = 0.001) considered the dental career as a positive contribution to society. A greater proportion of applicants considered the study of mathematics at school to be useful (p = 0.001). Significantly more applicants valued technical and manual skills as contributing to a 'good' dentist (p = 0.001). More students mentioned occupational flexibility, security and independence as a positive aspect of a career (p = 0.001); however students identified more job stresses in dentistry (p = 0.001). Applicants appeared to have a more 'idealistic' view of dentistry than the senior students, however similarities between the responses of students and applicants are encouraging for the future of the profession.


Goal-directed therapy in high-risk surgical patients: a 15-year follow-up study.
Goal-directed therapy in the perioperative setting has been shown to be associated with short-term improvements in outcome. This study assesses the longer-term survival of patients from a previous randomized controlled trial of goal-directed therapy in high-risk surgical patients. All patients from a previous randomized controlled study were followed up for 15 years following randomization to ascertain their length of survival following surgery. Factors that may be associated with increased survival were evaluated to determine what influenced long-term outcomes. Data from 106 of the original 107 patients (99%) were available for analysis. At 15 years, 11 (20.7%) of the goal-directed therapy patients versus 4 (7.5%) of the control group were alive (p = 0.09). Median survival for the goal-directed group was increased by 1,107 days (1,781 vs. 674 days, p = 0.005). Long-term survival was associated with three independent factors: age [hazard ratio (HR) 1.04 (1.02-1.07), p < 0.0001], randomization to the goal-directed group of the study [HR 0.61 (0.4-0.92), p = 0.02], and avoidance of a significant postoperative cardiac complication [HR 3.78 (2.16-6.6), p = 0.007]. Long-term survival after major surgery is related to a number of factors, including patient age and avoidance of perioperative complications. Short-term goal-directed therapy in the perioperative period may improve long-term outcomes, in part due to its ability to reduce the number of perioperative complications.


Helping the helpers: family support for social workers mobilized during Desert Storm/Shield.
This study identifies the types of social support available to the families of social work officers activated during Operation Desert Storm/Shield and determines which social supports were utilized by these families and the degree of perceived satisfaction with those social supports. This is a post-event assessment on a one-time basis. A Social Support Questionnaire was sent to the spouses of all activated Social Work Officers. Findings suggest no correlation between amount of social support and perceived effectiveness. Findings also suggest a need to assist families of military social work officers with informal and formal social support connections.


First artificial receptors and chemosensors toward phosphorylated peptide in aqueous solution.
The first fluorescent chemosensors toward a native phosphorylated peptide are successfully synthesized. Dinuclear zinc(II)-dipicolylamine-based anthracene (1, 2) can selectively recognize and sense phosphorylated species with an increase in the fluorescence intensity. We also demonstrated that these artificial receptors fluorometrically detect a phosphorylated peptide with high affinity (>107 M-1) in aqueous solution.


Thermal conductivity versus depth profiling of inhomogeneous materials using the hot disc technique.
Transient measurements of thermal conductivity are performed with hot disc sensors on samples having a thermal conductivity variation adjacent to the sample surface. A modified computational approach is introduced, which provides a method of connecting the time-variable to a corresponding depth-position. This allows highly approximate-yet reproducible-estimations of the thermal conductivity vs. depth. Tests are made on samples incorporating different degrees of sharp structural defects at a certain depth position inside a sample. The proposed methodology opens up new possibilities to perform non-destructive testing; for instance, verifying thermal conductivity homogeneity in a sample, or estimating the thickness of a deviating zone near the sample surface (such as a skin tumor), or testing for presence of other defects.


Smart Wireless Sensor Technology for Healthcare Monitoring System Using Cognitive Radio Networks.
Programmable Object Interfaces are increasingly intriguing researchers because of their broader applications, especially in the medical field. In a Wireless Body Area Network (WBAN), for example, patients' health can be monitored using clinical nano sensors. Exchanging such sensitive data requires a high level of security and protection against attacks. To that end, the literature is rich with security schemes that include the advanced encryption standard, secure hashing algorithm, and digital signatures that aim to secure the data exchange. However, such schemes elevate the time complexity, rendering the data transmission slower. Cognitive radio technology with a medical body area network system involves communication links between WBAN gateways, server and nano sensors, which renders the entire system vulnerable to security attacks. In this paper, a novel DNA-based encryption technique is proposed to secure medical data sharing between sensing devices and central repositories. It has less computational time throughout authentication, encryption, and decryption. Our analysis of experimental attack scenarios shows that our technique is better than its counterparts.


Comparative properties of feline coronaviruses in vitro.
Two feline coronaviruses were characterized to determine their biological properties in vitro and their antigenic relatedness to a previously recognized feline infectious peritonitis virus and canine coronavirus. The viruses, designated WSU 79-1146 and WSU 79-1683, were shown to have comparable growth curves with the prototype feline infectious peritonitis virus. Treatment of the feline infectious peritonitis virus strains with 0.25% trypsin indicated that they were relatively resistant to proteolytic inactivation when compared with the feline enteric coronavirus strain. This observation may serve as a useful in vitro marker to distinguish closely related members of the feline coronavirus group. Plaque assay results indicated that the feline infectious peritonitis virus strains produced large homogeneous plaques in comparison to the feline enteric coronavirus strain and canine coronavirus, which showed a heterogenous plaque size distribution. No naturally temperature sensitive mutants were detected in either of the feline coronavirus populations. Both of the viruses were antigenically related to feline infectious peritonitis virus and to a lesser extent to canine coronavirus by virus neutralization.


Development and Application of a Novel Pluri-Residue Method to Determine Polar Pesticides in Fruits and Vegetables through Liquid Chromatography High Resolution Mass Spectrometry.
Nowadays, highly polar pesticides are not included in multiresidue methods due to their physico-chemical characteristics and therefore, specific analytical methodologies are required for their analysis. Laboratories are still looking for a pluri-residue method that encompasses the largest number of polar pesticides. The aim of this work was the simultaneous determination of ethephon, 2-hydroxyethylphosphonic acid (HEPA), fosetyl aluminum, glyphosate, aminomethylphosphonic acid (AMPA), N-acetyl-glyphosate and N-acetyl-AMPA in tomatoes, oranges, aubergines and grapes. For that purpose, an ultra high performance liquid chromatography (UHPLC) coupled to a high resolution single mass spectrometer Orbitrap-MS were used. Different stationary phases were evaluated for chromatographic separation, and among them, the stationary phase Torus DEA provided the best separation of the selected compounds. The QuPPe method was used for the extraction of the analytes, but slight modifications were needed depending on the matrix. The developed method was validated, observing matrix effect in all matrices. Intra- and inter-day precision were estimated, and relative standard deviation were lower than 19%. Recoveries were satisfactory, and mean values ranged from 70% to 110%. Limits of quantification were between 25 and 100 µg kg-1. Finally, the analytical method was applied to different fruits and vegetables (oranges, tomatoes, aubergines and grapes).


The use of Doppler waveform analysis in the evaluation of the high-risk fetus.
The development of Doppler ultrasound evaluation of the uteroplacental and fetoplacental circulations is one of the most important achievements of modern obstetrics. For the first time, the obstetrician has the ability to evaluate, in a noninvasive way, circulatory systems critical to fetal development and the outcome of pregnancy and to obtain information of great value for the management of complicated pregnancies. At this time, Doppler examination of the umbilical artery has become a fundamental part of the evaluation of pregnancies complicated by retarded fetal growth. Doppler examination of the umbilical and uterine arteries has become the most accurate test to establish a fetal prognosis in patients with hypertension in pregnancy. Other indications for the use of this methodology (twins, diabetes, Rh isoimmunization, etc.) are being studied, and the role of Doppler ultrasound probably will extend significantly beyond the now well-established indications for its use.


Preparation of Poloxamer188-b-PCL and Study on in vitro Radioprotection Activity of Curcumin-Loaded Nanoparticles.
A novel polymer of poloxamer188-b-PCL was synthesized via a ring-opening polymerization. Fourier transform infrared spectroscopy (FTIR), Raman, and 1H nuclear magnetic resonance (1H NMR) spectra were used to study the structures of obtained poloxamer188-b-PCL. The thermo-stability of poloxamer188 -b-PCL was carried out with a thermal gravimetric analyzer (TGA), and cytotoxicity was obtained using the CCK8 method. Cargo-free and curcumin (CUR)-loaded poloxamer188-b-PCL NPs were fabricated via the solvent evaporation method. The morphology, particle size distribution, and stability of cargo-free NPs were studied with a scanning electron microscope (SEM) and laser particle analyzer. The in vitro radioprotection activity of CUR-loaded NPs was performed. FTIR, Raman, and 1H NMR spectra confirmed that poloxamer188-b-PCL was obtained. TGA curves suggested poloxamer188-b-PCL had better thermo-stability than original poloxamer188. Cell tests suggested that the cargo-free NPs had no cytotoxicity. SEM image showed that the cargo-free NPs were spherical with a diameter of 100 nm. Free radical scavenging experiments proved that CUR-loaded NPs had better antioxidant activity than CUR solutions. CUR-loaded NPs could be detected in all tissues, including liver, kidneys and lung. In summary, this work demonstrated a feasibility of developing an injective formulation of CUR and provided a protection agent in caner radiotherapy.


Distribution of receptors for acetylcholine and 5-hydroxytryptamine on identified leech neurones growing in culture.
The spatial distribution of receptors on identified leech neurones removed from the C.N.S. and grown in culture has been studied by applying acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) ionophoretically and by pressure. Two cells were selected: a neurone called anterior Pagoda (Ap), that shows responses to ACh, and the pressure sensory neurone (P cell), upon which 5-HT synapses form in culture. ACh receptors of Ap neurones in culture had properties similar to those of their counterparts in situ. Thus, ACh responses of Ap cells were mediated by Cl- and were blocked by curare and alpha-bungarotoxin. The cell bodies of these neurones in culture had low (10 mV/nC) and uniform sensitivity to ACh over the surface of the soma. When a sprout grew out from the Ap cell, a region of increased sensitivity appeared at its base, with a gradient of sensitivity decreasing toward the tip of the neurite. Characteristically, the base was 3-5 times more sensitive to ACh than the soma or the growth cone. Cells with multipolar processes developed a similar pattern of sensitivity for each sprout. P sensory neurones in culture showed similar distributions of sensitivity to 5-HT and ACh. Experiments made with voltage clamp suggested that the non-uniform responses to transmitter represent true differences in sensitivity. Together these findings suggest that the receptors for ACh and 5-HT have a greater density at the base of each neurite compared to that of the soma and the tip.


[C gene-targeting short hairpin RNA suppresses the replication and expression of hepatitis B virus in BHK-21 cells].
The vaccines currently developed against infectious diseases fail to induce effective antiviral immune responses to control an abrupt outbreak of viral diseases epidemic in a short space of time. Hence there is an urgent need to develop emergency vaccines capable of producing prophylactic effects against infectious diseases. RNA interference (RNAi) is a mechanism that inhibits gene expression by causing the degradation of specific RNA molecules or hindering the transcription of specific genes. The rapidity and uniqueness of RNAi responses can make up for the current inadequacy of antiviral preventive regimes. Here we evaluate the antiviral potential of short hairpin RNA (shRNA) targeting C (core) gene of hepatitis B virus (HBV). It plays essential roles in HBcAg encoding and viral attachment to susceptible cells during its life cycle. The present study was intended to investigate the inhibitory effect of C-specific shRNAs on HBV replication and expression in BHK-21 cells. The reporter gene expression vector of pC-EGFP-N1 was constructed by cloning the DNA (PCR product) of HBV C into the EcoRI-HindIII sites of pEGFP-N1 to fuse C to enhanced green fluorescent protein (EGFP) for providing a reporting system for monitoring siRNA function. Plasmid pC was constructed by cloning the DNA of HBV C into the EcoRI-HindIII sites of pCDNA3.1B(-) directly under the control of cytomegalovirus promoter. Two plasmids (S1 & S2) were constructed to express shRNAs targeting C of HBV with the length of 24 nucleotide (nt) homologous in sequence to the HBV C gene. Plasmids were designed and synthesized according to the HBV genome (HBV genotype B, ayw1 subtype) of chronic hepatic B patients from 56 ethnic minorities in China. After cloning and sequencing, the investigators registered them with the GenBank accession numbers of AY517488 (CYN/2002) and AY517489 (CYN/2000), etc. Simultaneously, one of nonspecific shRNA-S3 with a length of 24 nt was also designed randomly for negative control. After cloning into vector pU6 for constructing shRNA-expressing plasmids, they were then cotransfected into BHK-21 cells along with reporter gene expression vector of pC-EGFP-N1. First, upon a determination of the number of cells exhibiting EGFP expression in BHK-21 cells as detected by an Olympus BH-2 fluorescence microscope and FACS-440 flow cytometry (Becton-Dickinson, USA) at different times after cotransfection, the investigators evaluated the gene inhibitory efficiency of both plasmids by an EGFP reporter system in BHK-21 cells. Subsequently, the antiviral efficacy of both plasmids in BHK-21 cells was further investigated by real-time quantitative polymerase chain reaction. In comparison with single plasmid transfection pC-EGFP-N1 or pEGFP-N1, fluorescence microscope and flow cytometry detection at 24 h post-cotransfection revealed that the expression of reporter gene EGFP in cotransfection group involving S1 or S2 and S1 + S2 cotransfection group was reduced significantly by about 90% in EGFP signal versus the control. And the EGFP expression in control plasmid cotransfected S3 or pU6 was not significantly reduced in BHK-21 cells (P < 0.01). It was found that the expression of mRNAs of HBV C and EGFP gene as detected by real-time quantitative PCR was the same as that detected by fluorescence microscope and flow cytometry (P < 0.01), thereby further corroborating the antiviral efficacy of RNAi. The antiviral efficacy extended to almost 48 hours. The results indicted that a DNA vector-based RNAi technology could effectively and specifically inhibit the replication and expression of HBV in BHK-21 cells. For the first time it has been found that RNAi induced by shRNA targeting C gene exerts an effective and unique inhibition of HBV replication and expression in BHK-21 cells. Thus RNAi may provide an effective emergency vaccine against major infectious diseases such as HBV infection.


Anti-nuclear antibodies, anti-DNA and C4 complement evolution in rheumatoid arthritis and ankylosing spondylitis treated with TNF-alpha blockers.
To investigate autoantibody induction in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in a cohort of French patients treated with TNF-alpha blockers. We tested the serum of patients for antinuclear antibodies (ANA), anti-DNA antibodies and C4 complement at baseline, and for each infusion for infliximab, and at month 3, 6 and 12 for etanercept. We looked for all signs suggesting a drug-induced lupus. We tried to correlate ANA and anti-DNA development with various clinical data, especially the response to treatment. 229 patients were included in the study. 159 were treated with infliximab (98 RA and 61 AS) and 125 with etanercept (116 RA and 9 AS). In the infliximab group, 43.6% of RA patients and 27.1% of AS had significant levels of ANA at baseline. This proportion increased during the follow up to 73% in RA patients and 52% in AS patients. The proportion of patients positive for anti-DNA antibodies increased from 0% to 9.5% in RA group, and from 0% to 2% in AS group. In the etanercept group, 58.5% of these patients had significant levels of ANA at baseline; this proportion raised to 63.3% in patients previously treated with infliximab, and fell to 20.6% in the patients who never received TNF-alpha blockers. No significant variation of ANA, anti-DNA and C4 levels was observed in the etanercept group. Only three patients developed clinical manifestations (chilblain lupus) possibly related to these auto-antibodies, two with infliximab and one with etanercept. The ANA induction was only observed under infliximab therapy. Thus, ANA induction seems not to be a therapeutic class effect. This difference between infliximab and etanercept treatment may be the consequence of differential capacity of a monoclonal antibody and a soluble receptor in inducing apoptotic cell death of the cells expressing TNF on their membrane.


Nasal saline irrigation facilitates control of allergic rhinitis by topical steroid in children.
This study was designed to determine whether nasal saline irrigation improved the symptoms and signs of allergic rhinitis (AR) and whether nasal saline irrigation could be used as a complementary management of AR in children while less steroids were used. 26 children with AR were divided into three groups and were given nasal saline irrigation and/or topical steroid. Symptoms and signs of AR and mucociliary clearance (MCC) were evaluated, and concentration of soluble intercellular adhesion molecule (sICAM)-1 in nasal secretion was detected. In AR children treated with nasal irrigation and tapered topical steroid at week 8 and week 12, a significant improvement in symptoms and signs was observed, and a significant decrease in the mean values of MCC and the mean concentrations of sICAM-1 in nasal secretions was also detected. Nasal saline irrigation can be viewed as a good adjunctive treatment option for AR. It permitted the use of less topical steroids for controlling AR in children, which will contribute to fewer side effects and less economic burden.