Educating healthcare workers to optimal hand hygiene practices: addressing the need.
The education of healthcare workers is essential to improve practices and is an integral part of hand hygiene promotional strategies. According to the evidence reviewed here, healthcare worker education has a positive impact on improving hand hygiene and reducing healthcare-associated infection. Detailed practical guidance on steps for the organization of education programmes in healthcare facilities and teaching-learning strategies are provided using the World Health Organization (WHO) Guidelines for Hand Hygiene in Health Care as the basis for recommendations. Several key elements for a successful educational programme are also identified. A particular emphasis is placed on concepts included in the tools developed by WHO for education, monitoring and performance feedback.


Influence of dissolved humic substances on the leaching of MCPA in a soil column experiment.
The influence of dissolved humic substances on the transport of (4-chloro-2-methylphenoxy) acetic acid (MCPA) in a sandy soil with a low organic carbon content was studied in a column experiment. Soil columns were eluted with aqueous solutions containing different fractions of humic substances. More than 70% of the applied compound was found in the leachate in all sandy soil experiments, but distinct differences were obtained depending on the composition of the eluent. The addition of both humic and fulvic acids to the eluent affected the leaching behaviour of MCPA. While the presence of humic acids increased and accelerated the movement of MCPA in the investigated sandy soil, fulvic acids caused the opposite effect: increased retention was observed relative to the control. We concluded that a possible carrier transport or retention strongly depends on the composition of the dissolved organic matter. Thus, changes in the composition of dissolved organic matter may affect MCPA movement into deeper soil layers.


Analysis of the correlation of CATSPER single nucleotide polymorphisms (SNPs) with idiopathic asthenospermia.
Idiopathic asthenospermia is the most common type of male infertility. Although the mechanisms causing asthenospermia are complex, recent studies have indicated an important role of cation channel of sperm (CATSPER) gene downregulation or abnormality in the etiology of idiopathic asthenospermia. In the present study, 192 patients with idiopathic asthenospermia and 288 healthy controls were enrolled, and a flight mass spectrometry using Sequenom's MassArray biochip system was applied for genotyping 16 CATSPER gene SNPs reported in the human single nucleotide polymorphism (SNP) database. Our results indicated a correlation between CATSPER1 SNPs and idiopathic asthenospermia. In particular, the exonal SNP rs1893316 in CATSPER1 significantly correlated with idiopathic asthenospermia risk and is a potential important factor in determining an individual's genetic susceptibility to idiopathic asthenospermia. These finding will help to further elucidate the role of CATSPER1 in idiopathic asthenospermia pathogenesis.


[Lambert-Eaton Myasthenic Syndrome associated with vocal cord carcinoma].
Lambert-Eaton Myasthenic Syndrome (LEMS) is an autoimmune channelopathy in which patients produce autoantibodies directed against voltage-gated calcium channels. LEMS is paraneoplastic in 50% of patients, most frequently associated with small cell lung carcinoma. We describe a case of paraneoplastic LEMS associated with a vocal cord carcinoma. A 64-year-old man developed in five months muscle weakness affecting gait. Clinical examination showed proximal muscular deficiency, areflexia and dysphonia. Electrophysiologic study showed potentiation greater than 500% after post exercise facilitation and 76 percent increment response at high-rate repetitive nerve stimulation (20Hz). Diagnosis of LEMS was confirmed by electrophysiologic study and anti-voltage gated calcium channel antibodies (90pM, positive value greater or equal to 70pM). Left vocal cord lesion histology showed epidermoid carcinoma. A combination of vocal cord tumor removal by endoscopy and treatment by pyridostigmine, 3-4 diaminopyridine and intravenous human immunoglobulin improved neurological symptoms. Paraneoplastic syndromes in association with cancers of the larynx and hypopharynx are unusual. Only two cases are reported with LEMS associated with larynx carcinoma. We describe an unusual case of LEMS associated with a left vocal cord carcinoma.


Copper and the estradiol receptor.
Copper is an essential element in living organisms and it appears to be involved in estrogen action. This study bears on the manner in which the metal may be linked to the mechanism of this action. Divalent copper was found to induce at 37 degrees C a several fold increase in estradiol binding to the receptors in rat uterine cytosols. An endogenous substance present in the uterine cytosol and separated from it by fractionation on a hydroxylapatite column was found to function as a potent inhibitor of the copper effect. This substance has been found so far also in human breast tissue and in some human breast tumors.


Anatomical study for SLAP lesion repair.
The purpose of this study was to meticulously observe the structures around the origin of the long head of the biceps tendon (LHB) in order to propose a method of anatomical superior labrum anterior and posterior repair. Twenty-eight shoulders of 16 cadavers with intact LHB origin were macroscopically investigated. Among them, 20 shoulders with an intact superior labrum were additionally observed, to determine whether the anterior edge of LHB on the labrum (point 'A') was anterior to the supraglenoid tubercle. Serial sections vertical to LHB were observed using ordinary light and polarized microscopy in three glenoids and scanning acoustic microscopy in one. The labrum had a meniscal appearance, and no LHB fibre was sent anterior to the anterior edge of the supraglenoid tubercle. 'A' was not located more posterior than the supraglenoid tubercle. All specimens had the so-called 'the sheet-like structure', in which the portion closer to the LHB origin tends to be stiffer. Fibres of the sheet-like structure ran vertically to LHB. Fibre orientation and the stiffness of the sheet-like structure suggest its support of LHB. As LHB fibres do not anteriorly cross over 'A', 'A' could be a landmark for the anterior border of LHB, independent from the sheet-like structure. Considering a previous report mentioning that the horizontal mattress suture maintains the meniscus-like structure which might be sufficient for proper motion of the normal superior labrum, the horizontal mattress suture not crossing over 'A' should be recommended from the viewpoint of functional anatomy.


The novel HLA-B*44:369 allele characterised by two different sequencing-based typing techniques.
The novel allele HLA-B*44:369 differs from HLA-B*44:02:01:01 by one non-synonymous nucleotide substitution in exon 3.


Aberrant Active cis-Regulatory Elements Associated with Downregulation of RET Finger Protein Overcome Chemoresistance in Glioblastoma.
RET finger protein (RFP) forms a complex with histone deacetylase 1, resulting in aberrant deacetylation of H3K27ac and dysregulation of cis-regulatory elements. We evaluated the modulatory effects of RFP knockdown on cis-regulatory elements, gene expression, and chemosensitivity to temozolomide both in glioblastoma cells and in an intracranial glioblastoma model. The combination of RFP knockdown and temozolomide treatment markedly suppressed the glioblastoma cell growth due to oxidative stress and aberrant cell cycle and increased survival time in mice with glioblastoma. ChIP-seq and RNA-seq revealed that RFP knockdown increased or decreased activity of numerous cis-regulatory elements that lie adjacent to genes that control functions such as apoptosis, mitosis, DNA replication, and cell cycle: FOXO1, TBP2, and PARPBP. This study suggests that RFP contributes to chemoresistance via aberrant deacetylation of histone H3 at K27, whereas dysregulation of RFP-associated cis-regulatory elements in glioma and RFP knockdown combined with temozolomide is an effective treatment strategy for lethal glioma.


A nested high-resolution unstructured grid 3-D ocean-sea ice-ice shelf setup for numerical investigations of the Petermann ice shelf and fjord.
Three-dimensional numerical simulation of circulation in fjords hosting marine-terminating ice shelves is challenging because of the complexity of processes involved in such environments. This often requires a comprehensive model setup. The following elements are needed: bathymetry (usually unknown beneath the glacier tongue), ice shelf draft (impacting water column thickness), oceanographic state (including tidal elevation, salinity, temperature and velocity of the water masses), sea ice and atmospheric forcing. Moreover, a high spatial resolution is needed, at least locally, which may be augmented with a coarser and computationally cheaper (nested) model that provides sufficiently realistic conditions at the boundaries. Here, we describe procedures to systematically create such a setup that uses the Finite Volume Community Ocean Model (FVCOM) for the Petermann Fjord, Northwest Greenland. The first simulations are validated against temperature and salinity observations from the Petermann Fjord in September 2019. We provide•Complete bathymetry, ice-draft and water column thickness datasets of the Petermann Fjord, with an improved representation of the topography underneath the glacier tongue.•Boundary conditions for ocean, atmosphere and sea ice derived from a suite of high-resolution regional models that can be used to initialize and run the regional ocean model with realistic geophysical settings.


ICU Management of Trauma Patients.
To describe the current state of the art regarding management of the critically ill trauma patient with an emphasis on initial management in the ICU. A PubMed literature review was performed for relevant articles in English related to the management of adult humans with severe trauma. Specific topics included airway management, hemorrhagic shock, resuscitation, and specific injuries to the chest, abdomen, brain, and spinal cord. The basic principles of initial management of the critically ill trauma patients include rapid identification and management of life-threatening injuries with the goal of restoring tissue oxygenation and controlling hemorrhage as rapidly as possible. The initial assessment of the patient is often truncated for procedures to manage life-threatening injuries. Major, open surgical procedures have often been replaced by nonoperative or less-invasive approaches, even for critically ill patients. Consequently, much of the early management has been shifted to the ICU, where the goal is to continue resuscitation to restore homeostasis while completing the initial assessment of the patient and watching closely for failure of nonoperative management, complications of procedures, and missed injuries. The initial management of critically ill trauma patients is complex. Multiple, sometimes competing, priorities need to be considered. Close collaboration between the intensivist and the surgical teams is critical for optimizing patient outcomes.


Succinate-dependent energy generation in Ascaris suum mitochondria.
Phosphorylation in isolated Ascaris suum mitochondria was much greater in the presence of malate than succinate, but, in the absence of added adenine nucleotides, incubations in succinate resulted in substantial elevations in intramitochondrial ATP levels. Succinate-dependent phosphorylation was stimulated aerobically and this stimulation was due almost entirely to a site I, rotenone-sensitive, phosphorylation. Increased substrate level phosphorylation, coupled to propionate formation, or additional sites of electron-transport associated ATP synthesis were not significant. Under aerobic conditions, 14CO2 evolution from 1,4-[14C]succinate was stimulated and NADH/NAD+ ratios were elevated, but the formation of [14C]propionate was unchanged. It appears that succinate was metabolized to pyruvate and acetate, and NADH, generated from the decarboxylations of malate and pyruvate, was the primary source of reducing power fueling electron-transport. The terminal oxidase and final electron-acceptor are still not clearly defined. However, ferricyanide, H2O2, and 100% oxygen all stimulated succinate-dependent phosphorylation. A possible role for cytochrome c peroxidase in A. suum mitochondrial metabolism is discussed.


Neurocutaneous melanosis in association with Dandy-Walker malformation: case report and literature review.
Neurocutaneous melanosis (NCM) is a rare congenital noninheritable phacomatosis characterized by large and/or numerous cutaneous congenital melanocytic naevi (CMN) in combination with melanocytic leptomeningeal tumours. Dandy-Walker malformation (DWM) consists of a cystic dilatation of the fourth ventricle communicating with the posterior fossa, and a high insertion of the tentorium and hypoplasia/aplasia of the cerebellar vermis (partially caused by Zic1(+/-)Zic 4(+/-) on 3q2). An association of NCM and DWM is very rare, with only 15 previously reported cases to our knowledge. We present an 8-year-old girl with multiple CMN and DWM. A ventriculoperitoneal shunt operation was performed when she was 1 day old. Her neurological symptoms to date comprise headaches, nausea and vomiting as a result of ventriculoperitoneal shunt dislocation at the age of 4 years. The diagnosis is provisional asymptomatic multiple CMN-type NCM in association with DWM.


Perspective on a chemistry classification system for AI-assisted formulation development.
This perspective article draws a distinction between some of the well-known drug classification systems and a "Chemistry Classification System" (CCS). Rather than have drug classification based on some simple properties like solubility and permeability or route of systemic elimination, a CCS results in more than four or five classes and each class has distinct properties that impact formulation development. This perspective provides and outline of 13 classes, but a CCS is a flexible system that introduces a thought process for classification. The number of classes is not rigid, and chemists are encouraged to adapt these methods to their own situations. A CCS utilizes machine-learning models and artificial intelligence (AI) to estimate physicochemical properties that result in unique, frequently observed dissolution, Absorption, Distribution, Metabolism, and Excretion (ADME) properties to guide formulation development.


Phosphoinositide 3-Kinase γ Restrains Neurotoxic Effects of Microglia After Focal Brain Ischemia.
Phosphoinositide 3-kinase γ (PI3Kγ) is linked to neuroinflammation and phagocytosis. This study was conducted to elucidate conjectural differences of lipid kinase-dependent and kinase-independent functions of PI3Kγ in the evolvement of brain damage induced by focal cerebral ischemia/reperfusion. Therefore, PI3Kγ wild-type, knockout, and kinase-dead mice were subjected to middle cerebral artery occlusion followed by reperfusion. Tissue damage and cellular composition were assessed by immunohistochemical stainings. In addition, microglial cells derived from respective mouse genotypes were used for analysis of PI3Kγ effects on phagocytic activity, matrix metalloproteinase-9 release, and cAMP content under conditions of oxygen/glucose deprivation and recovery. Brain infarction was more pronounced in PI3Kγ-knockout mice compared to wild-type and kinase-dead mice 48 h after reperfusion. Immunohistochemical analyses revealed a reduced amount of galectin-3/MAC-2-positive microglial cells indicating that activated phagocytosis was reduced in ischemic brains of knockout mice. Cell culture studies disclosed enhanced metalloproteinase-9 secretion in supernatants derived from microglia of PI3Kγ-deficient mice after 2-h oxygen/glucose deprivation and 48-h recovery. Furthermore, PI3Kγ-deficient microglial cells showed a failed phagocytic activation throughout the observed recovery period. Lastly, PI3Kγ-deficient microglia exhibited strongly increased cAMP levels in comparison with wild-type microglia or cells expressing kinase-dead PI3Kγ after oxygen/glucose deprivation and recovery. Our data suggest PI3Kγ kinase activity-independent control of cAMP phosphodiesterase as a crucial mediator of microglial cAMP regulation, MMP-9 expression, and phagocytic activity following focal brain ischemia/recirculation. The suppressive effect of PI3Kγ on cAMP levels appears critical for the restriction of ischemia-induced immune cell functions and in turn tissue damage.


Is there sufficient evidence for the association between executive dysfunction and academic performance in adolescents with major depressive disorder?: a systematic review.
Adult depression, undoubtedly associated with executive dysfunction, leads to poor work performance. As depression in adolescents may have a negative impact on school performance, we aimed to analyse the possible relationship between selected executive deficits and academic performance. Executive dysfunctions may have more severe consequences on school performance at high school, as this stage of education requires engagement in long-term goals, whether writing an essay or preparing for an exam. Whilst inhibitory control is necessary at all educational stages, it seems that planning and decision-making play a greater role in high school than in primary school. We reviewed studies on executive functions conducted in adolescents diagnosed with major depressive disorder (MDD) to establish the possible relationship between executive processes and school performance in depressed adolescents. The search identified 5 studies addressing planning and decision-making in adolescents with MDD, but none of those studies reported educational achievement. We identified a considerable gap in the research on the functional impact of depression in adolescents. Identifying the link between specific executive deficits and school performance could guide tailored therapeutic interventions.


Transgender and Gender Diverse Fertility Choices: Supporting the Decision-Making Process for Adolescents and Young Adults.
To qualitatively examine the fertility-related decision making process of transgender and gender diverse (TGD) adolescents and young adults (AYAs) and their parents, in the setting of pursing gender affirming treatments. Twenty-five TGD AYAs and 6 parents of TGD AYAs participated in a focus group or individual semistructured interviews focused on participants' experience learning about the effects of gender affirming treatments on fertility as well as the process of making a fertility preservation decision. Using open coding, data were analyzed in an iterative process identifying emerging themes and relationships. A decisional satisfaction score was collected and/or coded for each participant. Four broad themes related to the decision-making process were identified: (1) Critical steps include awareness, gathering information, and conversations; (2) External constraints limit choices; (3) Expanding the conversation beyond preservation; and (4) Emotional distress, conflict, and decisional satisfaction. Despite reporting emotional distress or conflict during the decision, TGD AYAs and parents of TGD AYAs generally reported a high level of satisfaction with their fertility preservation decision. There are specific ways health care professionals and family members can support TGD AYAs in their fertility-related decision making process. Decisional satisfaction was common, regardless of whether TGD AYAs chose to pursue fertility preservation or not.


Characterization of calcium channel binding.
Voltage-dependent calcium channels are expressed in a variety of tissues including heart, muscles and brain. Saturation binding of a radioligand to the calcium channel is commonly used to characterize the expression level of the channel protein. Compound competition binding assay is a conventional screening method to determine the affinity of unlabeled compounds for the channel protein. This unit provides detailed experimental methods for two types of radioligand binding assays using [³H]PN200-100 and [¹²⁵I](conotoxin MVIIA. Voltage-dependent calcium channels are expressed in a variety of tissues including heart, muscles and brain.


Optical coherence tomography-signal strength index following trifocal and monofocal intraocular lens implantation.
To evaluate the influence of trifocal and monofocal intraocular lens implantation on the optical coherence tomography-signal strength index values obtained during macular and peripapillary scanning. Study group included 60 eyes of 60 patients with intraocular lens (Acriva BB UD 613 monofocal in 30 eyes and Acriva Trinova UD trifocal in 30 eyes) implantation after uneventful phacoemulsification. Thirty eyes of 30 healthy subjects without any intraocular surgery were selected as the control group. Eyes with best corrected visual acuity less than 20/20 due to any media opacity, high refractive errors excluded. Macular and retinal nerve fiber layer scans were generated by optical coherence tomography after pupillary dilation. Intergroup comparisons of signal strength index values of the macular and peripapillary scans were performed between eyes implanted with two different intraocular lenses and control group. The mean signal strength index of the peripapillary and macular scans obtained in the eyes implanted with both monofocal and trifocal intraocular lenses were statistically less than the control group (p < 0.05, for all). SSI's of macular and peripapillary scans recorded from the eyes implanted with either monofocal or trifocal intraocular lenses were not statistically different from each other (p = 0.957 and p = 0.877, respectively). In the present study despite different intraocular lenses properties, the image quality values were not found to be lower in eyes with trifocal sinusoidal intraocular lenses implantation compared to monofocal intraocular lenses during macular and peripapillary optical coherence tomography scans.


Ultra-extensible ribbon-like magnetic microswarm.
Various types of structures self-organised by animals exist in nature, such as bird flocks and insect swarms, which stem from the local communications of vast numbers of limited individuals. Through the designing of algorithms and wireless communication, robotic systems can emulate some complex swarm structures in nature. However, creating a swarming robotic system at the microscale that embodies functional collective behaviours remains a challenge. Herein, we report a strategy to reconfigure paramagnetic nanoparticles into ribbon-like swarms using oscillating magnetic fields, and the mechanisms are analysed. By tuning the input fields, the microswarm can perform a reversible elongation with an extremely high aspect ratio, as well as splitting and merging. Moreover, we investigate the behaviours of the microswarm when it encounters solid boundaries, and demonstrate that under navigation, the colloidal microswarm passes through confined channel networks towards multiple targets with high access rates and high swarming pattern stability.


Determination of trimethoprim-sulfamethoxazole resistance in Streptococcus pneumoniae by using the E test with Mueller-Hinton agar supplemented with sheep or horse blood may be unreliable. The Pneumococcal Study Group.
An international, multicenter study compared trimethoprim-sulfamethoxazole MICs for 743 Streptococcus pneumoniae isolates (107 to 244 isolates per country) by E test, using Mueller-Hinton agar supplemented with 5% defibrinated horse blood or 5% defibrinated sheep blood, with MICs determined by the National Committee for Clinical Laboratory Standards broth microdilution reference method. Agreement within 1 log2 dilution and minor error rates were 69.3 and 15.5%, respectively, on sheep blood-supplemented agar and 76.9 and 13.6%, respectively, with horse blood as the supplement. Significant interlaboratory variability was observed. E test may not be a reliable method for determining the resistance of pneumococci to trimethoprim-sulfamethoxazole.


Selective superoxide generation within mitochondria by the targeted redox cycler MitoParaquat.
Superoxide is the proximal reactive oxygen species (ROS) produced by the mitochondrial respiratory chain and plays a major role in pathological oxidative stress and redox signaling. While there are tools to detect or decrease mitochondrial superoxide, none can rapidly and specifically increase superoxide production within the mitochondrial matrix. This lack impedes progress, making it challenging to assess accurately the roles of mitochondrial superoxide in cells and in vivo. To address this unmet need, we synthesized and characterized a mitochondria-targeted redox cycler, MitoParaquat (MitoPQ) that comprises a triphenylphosphonium lipophilic cation conjugated to the redox cycler paraquat. MitoPQ accumulates selectively in the mitochondrial matrix driven by the membrane potential. Within the matrix, MitoPQ produces superoxide by redox cycling at the flavin site of complex I, selectively increasing superoxide production within mitochondria. MitoPQ increased mitochondrial superoxide in isolated mitochondria and cells in culture ~a thousand-fold more effectively than untargeted paraquat. MitoPQ was also more toxic than paraquat in the isolated perfused heart and in Drosophila in vivo. MitoPQ enables the selective generation of superoxide within mitochondria and is a useful tool to investigate the many roles of mitochondrial superoxide in pathology and redox signaling in cells and in vivo.


Stereoselective effect of tranylcypromine enantiomers on brain serotonin.
Brain levels of 5-HT, 5-HIAA and L-tryptophan were measured in reserpinized rats given the enantiomers of tranylcypromine (TCP). (+)-TCP (1.5-30 mg/kg) increased levels of 5-HT, whereas (-)-TCP failed to affect 5-HT levels. (+)-TCP at high dosage (30 mg/kg) decreased brain levels of 5-HIAA, whereas (-)-TCP failed to affect 5-HIAA levels. Neither (+)-TCP nor (-)-TCP influenced brain levels of L-tryptophan. The effects of (+)-TCP on behavior resembled those of drugs which influence 5-HT processes, whereas (-)-TCP failed to produce 5-HT-dependent behaviors. The findings support the notion that TCP enantiomers have stereoselective effects on serotonergic mechanisms.


Molecular dissection of CHARGE syndrome highlights the vulnerability of neural crest cells to problems with alternative splicing and other transcription-related processes.
CHARGE syndrome is characterized by co-occurrence of multiple malformations due to abnormal development of neural crest cells. Here, we review the phenotypic and molecular overlap between CHARGE syndrome and similar pathologies, and further discuss the observation that neural crest cells appear especially sensitive to malfunction of the chromatin-transcription-splicing molecular hub.


Association between serum vitamin A levels and premature ovarian insufficiency: a case-control, cross-sectional survey study.
Although vitamin A is known to play an important role in ovarian function, its association with ovarian insufficiency has not been reported yet. Therefore, the aim of the study was to explore the association between serum vitamin A levels and premature ovarian insufficiency (POI). This cross-sectional survey included women with POI (n = 47) and normo-ovulatory controls (n = 67) who were enrolled between December 2016 and May 2018 in Zhejiang, China. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), vitamin A, and total cholesterol (TC) were measured for each participant. The association of TC-adjusted vitamin A levels with the risk of POI was assessed using binary logistic regression analysis. Serum vitamin A levels appeared to be slightly higher in the POI group than in the control group, but there was no evidence of a statistically significant difference (728.00 ± 176.00 µg/L vs. 503.93 ± 145.64 µg/L, p = 0.13). After adjustment for serum lipid levels, the serum vitamin A/TC ratio was significantly lower in the POI group than in the control group (143.14 ± 35.86 vs. 157.56 ± 35.21 µg/mmol, p = 0.04). Further, the serum vitamin A/TC ratio was significantly and inversely associated with POI risk (unadjusted odds ratio [OR] = 0.988, 95% confidence interval [CI]: 0.977-0.999, p = 0.04). The association remained after adjusting for confounding factors (age, BMI, annual household income, and education) (OR = 0.986, 95% CI: 0.972-0.999, p = 0.04). Serum vitamin A/TC ratio was inversely associated with POI risk. Therefore, the serum vitamin A/TC ratio may serve as a predictive factor for POI, and vitamin A supplementation may play help prevent or treat POI.


Collision of millimetre droplets induces DNA and protein transfection into cells.
Nonperturbing and simple transfection methods are important for modern techniques used in biotechnology. Recently, we reported that electrospraying can be applied to DNA transfection in cell lines, bacteria, and chicken embryos. However, the transfection efficiency was only about 2%. To improve the transfection rate, physical properties of the sprayed droplets were studied in different variations of the method. We describe a highly efficient technique (30-93%) for introduction of materials such as DNA and protein into living cells by electrospraying droplets of a high conductivity liquid onto cells incubated with the material for transfection. Electric conductivity has a sizable influence on the success of transfection. In contrast, molecular weight of the transfected material, types of ions in the electrospray solution, and the osmotic pressure do not influence transfection efficiency. The physical analysis revealed that collision of cells with millimetre-sized droplets activates intracellular uptake.


Does higher education promote sustainable development? Role of green technology and financial performance.
How do digitalizing businesses help them achieve sustainable growth? This research examines the mediating function of green technology innovation in answering this question by defining sustainable development performance in terms of corporations' financial and environmental success. The educational system in China is examined to see how much of an impact it has on eco-innovation, as well as the relationship between green technology and innovation. The IFE test was utilized to determine whether or not the associations between variables such as GDP per capita, urbanization, green technology, higher education, and carbon dioxide emissions will continue to exist between 2004 and 2020 in China. The data for this analysis came from 30 of China's provinces. The findings of both the short-term and long-term CS-ARDL estimations demonstrated a positive link between eco-innovation and GDP per capita, green technology, higher education, and CO2 emissions. On the other hand, a negative correlation was found between urbanization and eco-innovation. The next topic covered in the research was how the effects of green technology might be seen in areas such as GDP per capita, higher education, and carbon dioxide emissions. The findings might provide valuable knowledge that developing economies can use to construct a feasible, sustainable path.


Detection of Epigenetic Modifications During Microspore Embryogenesis: Analysis of DNA Methylation Patterns Dynamics.
Methylation of 5-deoxy-cytidines of DNA constitutes a prominent epigenetic modification of the chromatin fiber which is locked in a transcriptionally inactive conformation. Changes in global DNA methylation are involved in many plant developmental processes during proliferation and differentiation events. The analysis of the changes of global DNA methylation distribution patterns during microspore embryogenesis induction and progression will inform on the regulatory mechanisms of the process, helping in the design of protocols to improve its efficiency in different species. To investigate the DNA methylation dynamics during microspore embryogenesis in the different cell types present in the cultures, the analysis of spatial and temporal pattern of nuclear distribution of 5-methyl-deoxy-cytidine (5mdC) constitutes a potent approach. The immunolocalization of 5mdC on sections and subsequent confocal laser microscopy analysis have been developed for in situ cellular analysis of a variety of plant samples, including embryogenic microspore and anther cultures. Quantification of 5mdC immunofluorescence intensity by image analysis software also permits to estimate differences in global DNA methylation levels among different cell types during development.


HMGB3 promotes the malignant phenotypes and stemness of epithelial ovarian cancer through the MAPK/ERK signaling pathway.
Ovarian cancer, particularly epithelial ovarian cancer (EOC), is the leading cause of cancer-related mortality among women. Our previous study revealed that high HMGB3 levels are associated with poor prognosis and lymph node metastasis in patients with high-grade serous ovarian carcinoma; however, the role of HMGB3 in EOC proliferation and metastasis remains unknown. MTT, clonogenic, and EdU assays were used to assess cell proliferation. Transwell assays were performed to detect cell migration and invasion. Signaling pathways involved in HMGB3 function were identified by RNA sequencing (RNA-seq). MAPK/ERK signaling pathway protein levels were evaluated by western blot. HMGB3 knockdown inhibited ovarian cancer cell proliferation and metastasis, whereas HMGB3 overexpression facilitated these processes. RNA-seq showed that HMGB3 participates in regulating stem cell pluripotency and the MAPK signaling pathway. We further proved that HMGB3 promotes ovarian cancer stemness, proliferation, and metastasis through activating the MAPK/ERK signaling pathway. In addition, we demonstrated that HMGB3 promotes tumor growth in a xenograft model via MAPK/ERK signaling. HMGB3 promotes ovarian cancer malignant phenotypes and stemness through the MAPK/ERK signaling pathway. Targeting HMGB3 is a promising strategy for ovarian cancer treatment that may improve the prognosis of women with this disease. Video Abstract.


Radiotherapy for endometrial cancer.
The first intent upfront treatment of endometrial cancer is surgery. External radiotherapy and brachytherapy; however, are important tools in adjuvant setting, according to histopathological risk factors for locoregional recurrence or in the event of an inoperable tumor. We present the update of the recommendations of the French society of oncological radiotherapy on the indications and technical methods of performing radiotherapy and brachytherapy for endometrial cancer.


Development of hybrid scaffolds with biodegradable polymer composites and bioactive hydrogels for bone tissue engineering.
The development of treatments for critical-sized bone defects has been considered an important topic in the biomedical field because of the high demand for transplantable bone grafts. Following the concept of tissue engineering, implantation of biocompatible porous scaffolds carrying cells and regulating factors is the most efficient strategy to stimulate clinical bone regeneration. With the advancement in the development of 3D-printing techniques, scaffolds with highly controllable architectures can be fabricated to further improve healing efficacies. However, challenges such as the limited biocompatibility of resin materials and poor cell-carrying capacities still exist in the application of current scaffolds. In this study, a novel biodegradable polymer, poly (ethylene glycol)-co-poly (glycerol sebacate) acrylate (PEGSA), was synthesized and blended with hydroxyapatite (HAP) nanoparticles to produce osteoinductive and photocurable resins for 3D printing. The composites were optimized and applied in the fabrication of gyroid scaffolds with biomimetic characteristics and high permeability, followed by the combination of bioactive hydrogels containing Wharton's jelly-derived mesenchymal stem cells (WJMSC) to increase the efficiency of cell delivery. The promotion of osteogenesis from 3D-printed scaffolds was confirmed in-vivo while the hybrid scaffolds were proven to be great platforms for WJMSC culture and differentiation in-vitro. These results indicate that the proposed hybrid systems, combining osteoinductive 3D-printed scaffolds and cell-laden hydrogels, have great potential for bone tissue engineering and are expected to be applied in the treatment of bone defects based on active tissue regeneration.


Insufficient voluntary intake of nutrients and energy in hospitalized patients.
The aim of our study was to evaluate the inadequacy of voluntary energy and nutrient intake on the first day of hospital admission. A cross-sectional study was carried out in two terciary care hospitals, with a probabilistic sample of 50% of in-patients. Dietary intake was evaluated by a 24-hour dietary recall, and undernutrition was screened through the Nutritional Risk Screening 2002 tool. The overall frequency of inadequate energy and nutrient intake was estimated using Dietary Reference Intakes. Energy and nutrient intakes from 258 patients showed very low values for both men and women. No significant differences were found for energy and nutrient intakes across age groups (< 65 years and > or = 65 years). When the proportion of study subjects with inadequate nutrient intakes was analysed, a high degree of inadequacy was found. The degree of inadequacy was higher for fibre, niacin, folate, vitamin B12, magnesium and zinc. No significant differences were found for energy and nutrients studied and for intakes below 1/3 of dietary recommendations from nutritionally-at-risk (n = 89) and well nourished (n = 169) patients. Voluntary nutrient and energy intakes in the first 24 hour of hospital admission are highly inadequate. No differences were found between undernourished and well-nourished patients or patients < 65 years and > or = 65 years.


Interest in fertility status assessment among young adult survivors of childhood cancer.
Cancer survivors who received gonadotoxic treatment are at-risk for future infertility and may desire a fertility status assessment (FSA), defined as semen analysis for males and consultation with a reproductive specialist for females. The purpose of this study was to describe the proportion of, and factors associated with, interest in FSA among young adult survivors of childhood cancer. This retrospective single-institution review included patients with prior gonadotoxic treatment, aged 18-25 years and >1 year from cancer treatment completion, who received a fertility-focused discussion during survivorship. Documentation of interest in and completion of FSA, worry about infertility, sociodemographic, and clinical characteristics were abstracted from medical records. Multivariable logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with interest in FSA. Survivors (N = 259) were on average 19.2 ± 1.2 years at their fertility discussion; 55.6% were male and 57.9% non-Hispanic white. Interest in FSA was reported by 50.7% of males and 46.1% of females. Factors related to interest in FSA for males and females respectively, included worry about infertility (OR 2.40, 95%CI 1.11-5.27, p = 0.026 and OR 4.37, 95%CI 1.71-12.43, p = 0.003) and ≥2 fertility discussions (OR 3.78, 95%CI 1.70-8.75, p = 0.001 and 2.45, 95%CI 1.08-5.67, p = 0.033). Among males, fertility preservation consult/procedure at diagnosis (OR 3.02, 95%CI 1.09-9.04, p = 0.039) and high-risk for infertility (OR 2.47, 95%CI 1.07-5.87, p = 0.036) were also associated with interest in FSA. Cancer survivors are interested in FSA, particularly those who have had repeated fertility-focused discussions during survivorship care and who report worry about infertility.


Metabolomics coupled with pattern recognition and pathway analysis on potential biomarkers in liver injury and hepatoprotective effects of yinchenhao.
Metabolomics can provide an opportunity to develop the systematic analysis of the metabolites in biological samples and has been increasingly applied to discovering and identifying biomarkers and perturbed pathways. It enables us to better understand the metabolic pathways which can clarify the mechanism of traditional Chinese medicines (TCM). Yinchenhao (YCH, Artemisia annua L), a famous TCM plant, has been used clinically for more than a thousand years to relieve liver diseases in Asia, and its mechanisms are not still completely clear. Here, metabolomic techniques may provide additional insight, and our investigation was designed to assess the effects and possible mechanisms of YCH on α-naphthylisothiocyanate (ANIT)-induced liver injury. Metabolite profiling was performed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) combined with pathway analysis and pattern recognition approaches including independent component analysis (ICA) and partial least squares-discriminant analysis (PLS-DA). Biochemistry test was also performed for the liver tissue and plasma samples. The changes in metabolic profiling were restored to their baseline values after YCH treatment according to the ICA score plots. Of note, YCH has a potential pharmacological effect through regulating multiple perturbed pathways to normal state, correlating well to the assessment of biochemistry test. Five different potential biomarkers in the positive mode contributing to the treatment of YCH were discovered. Pathway analysis showed that these metabolites were associated with perturbations in pyrimidine metabolism, primary bile acid biosynthesis, and propanoate metabolism, which may be helpful to further understand the action mechanisms of YCH. It showed that changed biomarkers and pathways may provide evidence to insight into drug action mechanisms and drug discovery.


Antiviral action of interferon-alpha against porcine transmissible gastroenteritis virus.
Swine testis (ST) cell cultures were treated with various doses of recombinant human interferon-alpha 2a (IFN), and assayed for 2',5' oligoadenylate synthetase (2-5 A synthetase) activity. Treatment with 100 or 1000 units/ml of IFN resulted in increased 2-5 A synthetase activity, but there was no significant response to 1 unit/ml of IFN. Titres of porcine transmissible gastroenteritis virus (TGEV) were reduced between 6 and 15 hours post-infection in ST cells treated with 1000 or 2500 units/ml of IFN. Polyacrylamide gel electrophoresis of lysates of TGEV-infected ST cells, and of lysates immunoprecipitated with anti-TGEV antibodies, revealed that the synthesis of the N and S proteins of TGEV was reduced in cells treated with 100 or 1000 units/ml of IFN. Viral RNA production, as determined with a probe which hybridized to the S gene of TGEV, was found to be reduced in ST cells treated with 1000 units/ml of IFN, but not in cells treated with 100 units/ml. It was concluded that, in IFN-treated ST cells, TGEV protein production may be decreased in the absence of reduced viral RNA production, and that 2-5 A synthetase may not be a significant factor in the antiviral activity of IFN against TGEV.


Macrolide biosynthesis: stereochemistry of the hydroxylation of brefeldin C.
Brefeldin C (2) is the penultimate intermediate in the biosynthetic pathway to brefeldin A (1). Using stereospecifically 2H-labeled forms of 2, the hydroxylation of 2 to 1 is shown to involve stereospecific removal of the 7 pro-S hydrogen from 2.


Effects of co-digestion of food waste, corn straw and chicken manure in two-stage anaerobic digestion on trace element bioavailability and microbial community composition.
Co-digestion is known to effectively alleviate trace elements (TEs) deficiency in mono-substrates; however, the bioavailability of TEs is crucial for the stability of anaerobic digestion. Therefore, this study investigated the effects of co-digestion of food waste (FW), corn straw (CS) and chicken manure (CM) in two-stage anaerobic digestion on TEs bioavailability and microbial community composition. Various VSFW:(VSCS:VSCM) ratios of 8:2, 7:3, 4:6, and 2:8 were evaluated in two-stage (group A, B, C, D) anaerobic digestion in which the VSCS:VSCM ratio was fixed at 3:1. Results showed that the highest hydrogen production of 106 mL/g VS and methane production co-efficiency of 125.3% was obtained in group A. Group A has a high close range of easily bioavailable TEs (32-64%) compared to other groups, especially the mono-substrate, where almost all TEs ranged between 10 and 36%. The increased relative abundance of the obligate hydrogenotrophic methanogens reflected a positive two-stage methane co-digestion efficiency.


Construction of chub mackerel (Scomber japonicus) fishing ground prediction model in the northwestern Pacific Ocean based on deep learning and marine environmental variables.
Accurate prediction of the central fishing grounds of chub mackerel is substantial for assessing and managing marine fishery resources. Based on the high-seas chub mackerel fishery statistics and multi-factor ocean remote-sensing environmental data in the Northwest Pacific Ocean from 2014 to 2021, this article applied the gravity center of the fishing grounds, 2DCNN, and 3DCNN models to analyze the spatial and temporal variability of the chub mackerel catches and fishing grounds. Results:1) the primary fishing season of chub mackerel fishery was April-November which catches were mainly concentrated in 39°∼43°N, 149°∼154°E. 2) Since 2019, the annual gravity center of the fishing grounds has continued to move northeastward; the monthly gravity center has prominent seasonal migratory characteristics. 3) 3DCNN model was better than the 2DCNN model. 4) For 3DCNN, the model prioritized learning information on the most easily distinguishable ocean remote-sensing environmental variables in different classifications.


Providing staff feedback to nurse managers using internal resources.
In many regions of the country, hospitals are faced with increasingly serious nursing shortages. Many hospitals have developed incentive packages to recruit nurses. However, the literature clearly demonstrates that the nurses' work environments must be addressed if nurses are to be retained. The authors created a questionnaire to measure registered nurses' attitudes toward their work environments. Information from this questionnaire can provide timely feedback and enable nurse managers to identify and correct organizational factors that could lead to turnover. The questionnaire takes fewer than 10 minutes for each nurse to complete, and nurse managers can easily calculate the results. The questionnaire can be modified for use in other healthcare facilities.


Preparation, 252Cf-plasma-desorption mass spectrometry and radiometal exchange of the Pb2+ and Bi3+ complexes of a hexalactam macrocycle.
A macrocyclic tricatechol hexalactam ligand readily forms complexes with Pb2+ and Bi3+ ions. Solid samples were isolated and characterized by 252Cf-plasma-desorption mass spectroscopy (252Cf-PDMS). Radioactive metal exchange studies employing 210Pb and 210Bi showed the compounds to be kinetically inert to exchange. The feasibility of using an available source of 203Pb, a potential imaging agent, with this class of compound was shown by synthesis of the labelled hexalactam complex.


In vivo coefficient of kinetic friction: study of urinary catheter biocompatibility.
An animal model was developed to measure objectively the in vivo intrinsic coefficient of kinetic friction (COFk) of various catheter materials. Uncoated red rubber catheters had the highest COFk of the three materials tested. The Biocath catheter exhibited less COFk when compared with the standard silicone catheter. Although the etiology of urethral strictures is multifactorial, better biocompatibility as measured by in vivo COFk may be an important factor in the inevitable urethral trauma and irritation associated with indwelling catheterization and possibly with postcatheterization urethral stricture formation.


Raising the Index of Suspicion: Red Flags That Represent Credible Threats to Patient Safety.
The index of suspicion: red flags warn of safety threats.


Surface-enhanced Raman spectroscopy of polymerase chain reaction (PCR) products of Rifampin resistant and susceptible tuberculosis patients.
Raman spectroscopy is an effective tool for detecting and discriminating microorganisms that is robust, reliable, and rapid. To develop a polymerase chain reaction technique (PCR) based on Surface Enhanced Raman Spectroscopy (SERS) technique with principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to assess diagnostic capability of SERS for distinguishing between tuberculosis (TB) positive rifampin resistant and tuberculosis (TB) positive rifampin susceptible samples. Silver nanoparticles (Ag NPs) were used as SERS substrates and technique was used to distinguish TB positive rifampin (RIF) resistant and TB positive rifampin (RIF) susceptible patients on the basis of characteristic SERS spectral features of their respective PCR products. SERS spectra were acquired from 52 samples of PCR products including 22 samples of TB positive rifampin susceptible, 30 samples of TB positive rifampin resistant and negative control samples. All these samples were collected from individuals of same age. Furthermore, multivariate data analyses techniques such as PCA and PLS-DA were used to assess diagnostic capability of SERS for distinguishing between TB positive rifampin resistant and TB positive rifampin susceptible samples. PCA is found helpful for successful differentiation among these two groups of spectral data sets. Moreover, PLS-DA provides this classification quantitatively by predicting the class of SERS spectral data set with 73% area under curve, 96% sensitivity, 95.6% specificity and 95% accuracy. SERS can be employed for the rapid distinguishing between TB positive rifampin resistant and TB positive rifampin susceptible samples.


Topical antimicrobial testing of burn wound microorganisms: evaluation of a new technique.
A new system of determining susceptibility of burn wound microorganisms to topical antimicrobial therapy was studied. The new method, TOPITEST, employs a methacrylate vehicle impregnated with various antimicrobial agents and an agar overlay. Test plates can be inoculated by a direct swab culture of the wound or with micro-organisms isolated by other methods. This new technique was compared to an agar well diffusion (AWD) method using commercially compounded antimicrobials and biopsy-recovered organisms. The new test method provided comparable results to the more established AWD test when using biopsy-recovered organisms. Using the swab culture technique, however, TOPITEST had a high rate of failure to recover sufficient organisms from the burn wound for testing. The new, more standardized test provided results earlier than the AWD test, but may prove to be less cost effective.


Antipsychotic and benzodiazepine use and brain morphology in schizophrenia and affective psychoses - Systematic reviews and birth cohort study.
The aim of this paper was to investigate differences in brain structure volumes between schizophrenia and affective psychoses, and whether cumulative lifetime antipsychotic or benzodiazepine doses relate to brain morphology in these groups. We conducted two systematic reviews on the topic and investigated 44 schizophrenia cases and 19 with affective psychoses from the Northern Finland Birth Cohort 1966. The association between lifetime antipsychotic and benzodiazepine dose and brain MRI scans at the age of 43 was investigated using linear regression. Intracranial volume, sex, illness severity, and antipsychotic/benzodiazepine doses were used as covariates. There were no differences between the groups in brain structure volumes. In schizophrenia, after adjusting for benzodiazepine dose and symptoms, a negative association between lifetime antipsychotic dose and the nucleus accumbens volume remained. In affective psychoses, higher lifetime benzodiazepine dose associated with larger volumes of total gray matter and hippocampal volume after controlling for antipsychotic use and symptoms. It seems that in addition to antipsychotics, the severity of symptoms and benzodiazepine dose are also associated with brain structure volumes. These results suggest, that benzodiazepine effects should also be investigated also independently and not only as a confounder.


HPV and Covid-19 Era: effects of nonpharmaceutical interventions on HPV transmission.
Human papillomavirus (HPV) is considered the commonest viral cause of sexually transmitted infections. The impact of social distance measures due to Covid-19 pandemic on HPV spread is unknown. Therefore, this study has analyzed the seven-year trend of HPV prevalence in all patients tested for HPV DNA at the Microbiology and Virology Unit at Bari Policlinico. Moreover, the HPV prevalence in 2020 has been compared with the previous year ones in order to evaluate the consequences of lockdown and social distancing measures on transmission risks. From 2013 to 2020, we retrospectively analyzed 64 anal swabs, 418 biopsies, 5925 cervical-vaginal swabs, 512 cervical swabs, 104 gland swabs, 154 oral swabs, 21 seminal fluids and 503 urethral swabs. HPV DNA detection was initially performed using nested-polymerase chain reaction (PCR) and subsequently multiplex real-time PCR assay. All statistical tests were carried out by the open-source environment R 4.0.3 (R Core Team). The data were analyzed according to yearly positivity rates, temporal trend and prevalence of HPV genotypes (HPV-6, HPV-11, HPV-16, HPV-18, high risk and low risk) by age category and sex. The number of patients increased steadily from 2016 to 2019 and then decreased in 2020. There were significant differences in prevalence between females and males for HPV-6 (6.16% in females Vs 30.80% in males), HPV-11 (0.82% Vs 7.16%) and HPV-16 (7.77% Vs 5.01%). The prevalence of HPV-6 and HPV-11 significantly increased in 2020 compared to 2013-2019 (15.72% Vs 8.52 and 3.18% Vs 1.44%). On the contrary, the overall prevalence of HPV DNA remained constant in 2020 (52.84% Vs 48.44%). Over time, the prevalence of HPV DNA (Coefficient=-0.020, p-value = 0.036) and particularly high-risk genotypes (Coefficient=-0.030, p-value = 0.005) decreased in females, while low-risk genotypes (Coefficient = 0.141, p-value= < 0.001) and the prevalence of HPV DNA increased in males (Coefficient = 0.068, p-value = 0.008). During the pandemic, the number of screened patients declined, although HPV prevalence compared to 2013-2019 remained constant or increased as in the case of low-risk genotypes. It can be assumed that the reduction of the screening coverage favored the emerging of the more symptomatic low-risk infections. In conclusion, nonpharmaceutical interventions due to Covid-19 pandemic did not reduce the risk of HPV infection but it likely caused a decrease in access to health services resulting in an increased risk of undiagnosed HPV.


Characterization, scaling, and partial representation of diffuse and discrete input junctions to CA3 hippocampus.
This paper applies a general mathematical system for characterizing and scaling functional connectivity and information flow across the diffuse (EC) and discrete (DG) input junctions to the CA3 hippocampus. Both gross connectivity and coordinated multiunit informational firing patterns are quantitatively characterized in terms of 32 defining parameters interrelated by 17 equations, and then scaled down according to rules for uniformly proportional scaling and for partial representation. The diffuse EC-CA3 junction is shown to be uniformly scalable with realistic representation of both essential spatiotemporal cooperativity and coordinated firing patterns down to populations of a few hundred neurons. Scaling of the discrete DG-CA3 junction can be effected with a two-step process, which necessarily deviates from uniform proportionality but nonetheless produces a valuable and readily interpretable reduced model, also utilizing a few hundred neurons in the receiving population. Partial representation produces a reduced model of only a portion of the full network where each model neuron corresponds directly to a biological neuron. The mathematical analysis illustrated here shows that although omissions and distortions are inescapable in such an application, satisfactorily complete and accurate models the size of pattern modules are possible. Finally, the mathematical characterization of these junctions generates a theory which sees the DG as a definer of the fine structure of embedded traces in the hippocampus and entire coordinated patterns of sequences of 14-cell links in CA3 as triggered by the firing of sequences of individual neurons in DG.


Failure of chronic physostigmine to ameliorate working memory deficits after medial septal lesions.
To assess the potential usefulness of chronic acetylcholinesterase inhibition in the treatment of learning/memory disorders arising from central cholinergic deficient states, physostigmine was administered chronically to rats with medial septal lesions and the retention of a spatial/working memory task investigated. Three dose levels of physostigmine (0.025, 0.05, 0.075 mg/kg) were administered three times per day following medial septal lesions. Retention of a standard radial 8-arm maze task was assessed. Although the lesions transiently disrupted task performance, physostigmine therapy did not improve either daily performance or total recovery time. Our results suggest that chronic acetylcholinesterase inhibition is not effective in ameliorating the working memory deficits that occur after medial septal lesions.


Metabolism as a central regulator of β-cell chromatin state.
Pancreatic β-cells are critical mediators of glucose homeostasis in the body, and proper cellular nutrient metabolism is critical to β-cell function. Several interacting signaling networks that uniquely control β-cell metabolism produce essential substrates and co-factors for catalytic reactions, including reactions that modify chromatin. Chromatin modifications, in turn, regulate gene expression. The reactions that modify chromatin are therefore well-positioned to adjust gene expression programs according to nutrient availability. It follows that dysregulation of nutrient metabolism in β-cells may impact chromatin state and gene expression through altering the availability of these substrates and co-factors. Metabolic disorders such as type 2 diabetes (T2D) can significantly alter metabolite levels in cells. This suggests that a driver of β-cell dysfunction during T2D may be the altered availability of substrates or co-factors necessary to maintain β-cell chromatin state. Induced changes in the β-cell chromatin modifications may then lead to dysregulation of gene expression, in turn contributing to the downward cascade of events that leads to the loss of functional β-cell mass, and loss of glucose homeostasis, that occurs in T2D.


Chinese patients with p.Arg756 mutations of ATP1A3: Clinical manifestations, treatment, and follow-up.
The phenotypes of ATP1A3 gene mutations are diverse. Relapsing encephalopathy with cerebellar ataxia and fever-induced paroxysmal weakness and encephalopathy (FIPWE) are considered non-classical phenotypes caused by p.Arg756 mutations of ATP1A3. To summarize the clinical manifestations, treatment, and follow-up of Chinese patients with p.Arg756 mutations of ATP1A3. We analyzed the clinical features, treatment, and genotypes of eight children with p.Arg756 mutations of ATP1A3 who were treated in Beijing Children's Hospital from January 2014 to December 2019. Eight patients (six boys and two girls) were included; seven had been misdiagnosed with encephalitis. The age of onset ranged from 0.8 to 4.5 years. All patients had encephalopathy and had at least one episode of FIPWE. Cerebellar ataxia was present in nine episodes. Reversible splenial lesions of the corpus callosum were found in two patients in the acute phase. Three types of heterozygous ATP1A3 mutations were found: c.2267G > T (p.R756L) (patient 3 [P3]), c.2266C > T (p.R756C) (P2 and P4), and c.2267G > A (p.R756H) (P1, P5, P6, P7, and P8). Six mutations were de novo; two mutations were inherited. Both patients with p.R756C and one patient (P7) with p.R756H had four episodes of severe ataxia as the main manifestations. However, in the other three episodes, limb weakness was more prominent than ataxia. P5 with p.R756H exhibited overlap with FIPWE and rapid-onset dystonia-parkinsonism. Acute encephalopathy followed by febrile disease was characteristic of the disease in patients with p.Arg756 mutations of ATP1A3. However, the weakness and ataxia were variable. Phenotypic crossover and overlap were observed among these patients.


Slowing life history (K) can account for increasing micro-innovation rates and GDP growth, but not macro-innovation rates, which declined following the end of the Industrial Revolution.
Baumard proposes that life history slowing in populations over time is the principal driver of innovation rates. We show that this is only true of micro-innovation rates, which reflect cognitive and economic specialization as an adaptation to high population density, and not macro-innovation rates, which relate more to a population's level of general intelligence.


Prophages and plasmids can display opposite trends in the types of accessory genes they carry.
Mobile genetic elements (MGEs), such as phages and plasmids, often possess accessory genes encoding bacterial functions, facilitating bacterial evolution. Are there rules governing the arsenal of accessory genes MGEs carry? If such rules exist, they might be reflected in the types of accessory genes different MGEs carry. To test this hypothesis, we compare prophages and plasmids with respect to the frequencies at which they carry antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) in the genomes of 21 pathogenic bacterial species using public databases. Our results indicate that prophages tend to carry VFGs more frequently than ARGs in three species, whereas plasmids tend to carry ARGs more frequently than VFGs in nine species, relative to genomic backgrounds. In Escherichia coli, where this prophage-plasmid disparity is detected, prophage-borne VFGs encode a much narrower range of functions than do plasmid-borne VFGs, typically involved in damaging host cells or modulating host immunity. In the species where the above disparity is not detected, ARGs and VFGs are barely found in prophages and plasmids. These results indicate that MGEs can differentiate in the types of accessory genes they carry depending on their infection strategies, suggesting a rule governing horizontal gene transfer mediated by MGEs.


[[The apothecaries of the district of Les Halles in Paris in the 17th century. Molière's ancestors in Les Halles].
Les Halles were created by King Louis VI at the begining of the 12th century as a central market for food and trade. Apothecaries conducted their trade there from that time. In the 17th century, eleven apothecaries were established in this district, bordered on the south by the rue Saint-Honoré, on the east by the rue Saint-Denis, on the west by the rue de la Tonnellerie, and the north by the rue Montmartre. Their biographies have been analysed, and the data that has been collected has enabled their précise location to be fixed on a map of 1700. Molière's ancestors, both maternal (the Cressé family) and paternal (the Pocquelin's), lived in this district. Details of their relationships with their apothecary neighbours have been revealed.


HIV epidemic among young Thai Men, 1991-2000.
Characterization of the HIV epidemic in Thailand has benefited from the systematic testing of young men upon entry into the military. These data, which have shown that public health measures can reverse an HIV epidemic, have been reanalyzed with current geographic information systems methods. The resulting maps are, thus far, the best means of visualizing the geography of the dynamic HIV epidemic in Thailand.


Quadrupole relaxation enhancement--application to molecular crystals.
A general theory of field dependent spin-lattice relaxation for nuclei of the spin quantum number 1/2 (1H, 19F, 13C) caused by dipole-dipole interactions with neighboring quadrupolar nuclei (nuclei possessing a quadrupolar moment) is presented. The theory is valid for arbitrary motional conditions and should be treated as a quadrupolar counterpart of the paramagnetic relaxation enhancement theory. When the energy level splitting of the dipolar spin (I=1/2) matches one of the transition frequencies of the quadrupolar nuclei one can observe a local enhancement of the dipolar spin relaxation (referred to as "quadrupolar peaks"). To see such effects the dynamics modulating the spin interactions has to be relatively slow. This brings the system beyond the validity range of perturbation approaches and requires the stochastic Liouville equation to be applied. The presented theory describes the quadrupolar relaxation enhancement (QRE) for an arbitrary spin quantum number of the quadrupolar nuclei and includes the asymmetry of the quadrupolar coupling. It has been applied to interpret the shape of magnetization curves (amplitude of 1H magnetization versus magnetic field) for the molecular crystal [C3N2H5]6[Bi4Br18] ([C3N2H5]-imidazolium). The magnetization curves show several dips (local minima) attributed to 1H-14N quadrupolar relaxation enhancement effects. In addition, as a limiting case a perturbation approach to QRE has been presented and its validity conditions have been discussed.


A role for the Tec family kinase ITK in regulating SEB-induced interleukin-2 production in vivo via c-jun phosphorylation.
Exposure to Staphylococcal Enterotoxin B (SEB), a bacterial superantigen secreted by the Gram-positive bacteria Staphyloccocus aureus, results in the expansion and eventual clonal deletion and anergy of Vbeta8+ T cells, as well as massive cytokine release, including Interleukin-2 (IL-2). This IL-2 is rapidly secreted following exposure to SEB and may contribute to the symptoms seen following exposure to this bacterial toxin. The Tec family kinase ITK has been shown to be important for the production of IL-2 by T cells stimulated in vitro and may represent a good target for blocking the production of this cytokine in vivo. In order to determine if ITK represents such a target, mice lacking ITK were analyzed for their response to SEB exposure. It was found that T cells from mice lacking ITK exhibited significantly reduced proliferative responses to SEB exposure in vitro, as well as in vivo. Examination of IL-2 production revealed that ITK null mice produced reduced levels of this cytokine in vitro, and more dramatically, in vivo. In vivo analysis of c-jun phosphorylation, previously shown to be critical for regulating IL-2 production, revealed that this pathway was specifically activated in SEB reactive Vbeta8+ (but not non-reactive Vbeta6+) T cells from WT mice, but not in Vbeta8+ T cells from ITK null mice. However, toxicity analysis indicated that both WT and ITK null animals were similarly affected by SEB exposure. These data show that ITK is required for IL-2 production induced by SEB in vivo, and may regulate signals leading IL-2 production, in part by regulating phosphorylation of c-jun. The data also suggest that perturbing T cell activation pathways leading to IL-2 does not necessarily lead to improved responses to SEB toxicity.


Anesthetic considerations in the patient with acute spinal cord injury.
The extent and level of the spinal cord injury as well as the presence of associated injuries affects the choice of anesthetic agents, techniques, and monitoring modalities. The role of the anesthesiologist is not limited only to the administration of anesthesia, but frequently his active participation in the team approach care of the spinal cord injury patient is needed during preoperative treatment and postoperatively in the ICU setting. Understanding of the pathophysiologic changes related to the spinal cord injury helps in the delivery of better anesthetic care for severely handicapped patients.


Autofluorescence imaging as a noninvasive tool of risk stratification for malignant transformation of oral leukoplakia: A follow-up cohort study.
There is few longitudinal study on oral potentially malignant disorder (OPMDs) focusing on oral leukoplakia (OLK) with clinical endpoints to investigate the role of autofluorescence imaging (AFI) for surveilling the malignant transformation. Based on our previous prospective diagnostic study enrolled 517 OPMD patients, 184 OLK patients were retrieved to further investigate the role of AFI using VELscope in predicting malignant transformation. During a median follow-up period of 44 months, 19 (10.33%) developed into oral cancer. OLK patients were divided into loss of autofluorescence (LAF, n = 124) and retention of autofluorescence (RAF, n = 60) groups according to the results of AFI. Interestingly, difference between malignant transformation rate (MTR, 14.52%) of group LAF and overall MTR (10.33%) was not significant, but MTR (1.67%) of group RAF was significantly lower than overall MTR. Kaplan-Meier and Cox-regression analyses revealed that LAF could not directly distinguish the high-risk lesions, but RAF significantly discriminate the low-risk lesions. Importantly, time-dependent ROC curve analysis found that the sensitivity and negative predictive value (NPV) of AFI for the prediction of malignant transformation was 100% and 100% (2-year follow-up), 94.7% and 98.3% (5-year follow-up), respectively. Also, calibration curve and decision curve analyses showed high levels of predictive value and clinical relevance. This follow-up cohort study firstly evaluated AFI using VELscope for risk stratification of OLK malignant transformation. Whether conservative management is appropriate for OLK patients with RAF imaging due to minimal rate and risk of malignant transformation and great specificity and NPV is required to be further investigated.


The administration of Alda-1, an activator of ALDH2, inhibits relapse-like ethanol intake in female alcohol-preferring UChB rats.
Alcohol relapse is a main limitation for the treatment of alcohol use disorders. Previous studies have shown that Alda-1, a pharmacological activator of ALDH2, inhibits both acquisition and chronic ethanol intake in rats; however, its effects on relapse-like ethanol intake are unknown. The aim of this study was to assess the effect of Alda-1 on post-deprivation and reaccess relapse-like ethanol intake in alcohol-preferring UChB rats. We also aimed to assess the possible mechanisms associated with the effects of Alda-1 by measuring the levels of glutamate transporter (GLT-1), oxidative stress and neuroinflammation markers in different regions of the mesocorticolimbic system. In Experiment I, UChB female rats were exposed for 100 days to voluntary ethanol intake followed by 2-weeks of ethanol withdrawal and 1 week of ethanol reaccess. Alda-1 (25 mg/kg, intragastric, i.g) or vehicle was administered daily for 14 days during the withdrawal/re-access period. Experiment II was similar to Experiment I, but after the withdrawal period, ethanol re-access was not allowed, and Alda-1 was administered during the last week of withdrawal. At the end of both experiments, the levels of GLT-1, oxidative stress (GSH, MDA), and neuroinflammation markers (GFAP, Iba-1) were assessed in nucleus accumbens and/or hippocampus. The results showed that Alda-1 administration markedly blocked (90 %, p < 0.001) relapse-like ethanol intake in UChB rats. Alda-1 increased Iba-1 reactivity (microglial marker) in the NAc of ethanol-deprived rats. Alda-1 administration did not influence the levels of GLT-1, oxidative stress markers (MDA, GSH) or GFAP reactivity in the mesocorticolimbic system. These preclinical findings support the use of activators of ALDH2, such as Alda-1, as a potential pharmacological strategy in the treatment of alcohol relapse.


Baseline exploratory activity predicts anxiolytic responsiveness to diazepam in five mouse strains.
Inbred mouse strains showing variability in spontaneous exploratory behaviors displayed differential responsiveness to diazepam in an anxiety-related exploration model. C57B1/6J, BALB/cJ, Swiss Webster/NIH, Swiss Webster/Harlan Sprague-Dawley, and CF-1 mice demonstrated a significant correlation between baseline exploratory activity and maximal percentage increase in exploratory behavior induced by diazepam. No correlation was seen between those behavioral responses and the characteristics of brain benzodiazepine binding sites in the different strains. Anti-anxiety responsiveness appears to be a function of some genetically-determined substrate for spontaneous exploratory behaviors which may have multiple neurochemical substrates.


Spatial distribution, source identification, and risk assessment of heavy metals in riparian soils of the Tibetan plateau.
Riparian soils in the lower sections of the Lhasa River were chosen as the research focus, to examine the characteristics and sources of heavy metals in riparian soils of high-cold regions. To investigate the influence of various factors on the geographical distribution of heavy metals, three horizontal and one vertical profiles were considered. The geoaccumulation index, prospective ecological risk index, and enrichment factor were used to evaluate the extent of soil contamination. Correlation analysis and the positive-matrix-analysis receptor model were used to quantitatively examine the sources of the elements. According to the soil-evaluation, the topsoil was more polluted than the deep soil. Overall, the soil was slightly degraded and posed minor ecological concern. Cd was the primary contributor to the overall contamination, with moderate and considerable risk levels at certain locations. Five sources were identified for the six heavy metals. Transportation and agricultural production were the principal sources of Cd. Ni and Cr were mostly connected to agricultural practices and weathering of parent-soil materials. Pb and Zn were mostly related to geological history, geothermal development, and traffic pollution. Mineral resource development has had a major impact on Cu. Non-carcinogenic risk index of each heavy metal and their total value were <1, indicating they are not harmful to human health. The riparian soil of the Lhasa River Basin contains heavy metals from various sources; therefore, it is important to monitor these heavy metals. This study provides a scientific foundation for the safe utilization and classification of soils in high cold regions.


Sharp-wave ripple doublets induce complex dendritic spikes in parvalbumin interneurons in vivo.
Neuronal plasticity has been shown to be causally linked to coincidence detection through dendritic spikes (dSpikes). We demonstrate the existence of SPW-R-associated, branch-specific, local dSpikes and their computational role in basal dendrites of hippocampal PV+ interneurons in awake animals. To measure the entire dendritic arbor of long thin dendrites during SPW-Rs, we used fast 3D acousto-optical imaging through an eccentric deep-brain adapter and ipsilateral local field potential recording. The regenerative calcium spike started at variable, NMDA-AMPA-dependent, hot spots and propagated in both direction with a high amplitude beyond a critical distance threshold (~150 µm) involving voltage-gated calcium channels. A supralinear dendritic summation emerged during SPW-R doublets when two successive SPW-R events coincide within a short temporal window (~150 ms), e.g., during more complex association tasks, and generated large dSpikes with an about 2.5-3-fold amplitude increase which propagated down to the soma. Our results suggest that these doublet-associated dSpikes can work as a dendritic-level temporal and spatial coincidence detector during SPW-R-related network computation in awake mice.


Correlation between refractive and measured corneal power changes after myopic excimer laser photorefractive surgery.
To determine the correlation between the refractive and measured corneal power changes after myopic photorefractive surgery. Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan. Eighty-six eyes that had myopic photorefractive surgery were analyzed. The data included preoperative and 1-year postoperative subjective refraction, standard automated keratometry, and computerized videokeratography. Statistical analysis was performed to determine the relationship between the changes in subjective refraction in the corneal plane (Delta SEQco) and in 4 corneal power measurements including the power measured by automated keratometry (Delta Auto K), topographic-simulated keratometric power (Delta Sim K), the power of the first photokeratoscopic ring on videokeratography (Delta Central K), and the average videokeratographic power on the pupil margin (Delta Pupil K). The measured corneal power always underestimated the Delta SEQco, with Delta SEQco > Delta Central K > Delta Sim K > Delta Pupil K > Delta Auto K. All the changes in measured corneal power could predict the Delta SEQco with more than 90.00% (90.19% to 92.31%) reliability at 1 year as calculated by the regression formulas (P <.001). The underestimation of measured corneal power changes was correlated with the amount of myopic correction, especially the Auto K (all P <.001). Direct corneal power measurements using automatic keratometry underestimated the actual corneal flattening after photorefractive surgery, which could be adjusted by a linear regression formula. Measuring the power of the first photokeratoscopic ring on videokeratography might provide a better estimation of actual corneal flattening after photorefractive surgery.


Risk Factors for the Development of Febrile Recurrences in Children with a History of Urinary Tract Infection.
To identify risk factors for febrile recurrence of urinary tract infections (UTIs) in children with a history of UTI. We included 500 children aged 2-72 months with a history of UTI who were followed prospectively for approximately 2 years in the context of 2 previously conducted studies (Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation). We identified significant risk factors for febrile recurrences among children not receiving antimicrobial prophylaxis using univariate and multivariate logistic regression. On univariate analysis, non-Black race, febrile index UTI, bowel-bladder dysfunction, grade IV vesicoureteral reflux, renal scarring at baseline, and renal-bladder ultrasound abnormalities were associated with febrile recurrence. On multivariate analysis, the following variables independently increased the odds of febrile recurrences (OR; 95% CI): non-Black race (7.1; 1.5-127.9), bowel-bladder dysfunction (2.6; 1.1-5.3), febrile index UTI (2.5; 1.1-6.9), abnormalities on renal-bladder ultrasound scan (2.6; 1.2-5.6), grade IV vesicoureteral reflux (3.9; 1.4-10.5), and renal scarring at baseline (4.7; 1.2-19.1). Non-Black race and grade IV vesicoureteral reflux increased the odds of febrile recurrence of UTI. Although our findings should stimulate other studies to further explore the relationship between race and UTIs, given that the link between race and UTI recurrence is unclear, race should not be used to make decisions regarding management of children with a UTI.


Comparison of [18F]FDOPA, [18F]FMT and [18F]FECNT for imaging dopaminergic neurotransmission in mice.
The clinically established positron emission tomography (PET) tracers 6-[(18)F]-fluoro-l-DOPA ([(18)F]FDOPA), 6-[(18)F]-fluoro-l-m-tyrosine ([(18)F]FMT) and 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-[(18)F]-fluoroethyl)-nortropane ([(18)F]FECNT) serve as markers of presynaptic integrity of dopaminergic nerve terminals in humans. This study describes our efforts to adopt the methodology of human Parkinson's disease (PD) PET studies to mice. The PET imaging characteristics of [(18)F]FDOPA, [(18)F]FMT and [(18)F]FECNT were analyzed in healthy C57BL/6 mice using the dedicated small-animal PET tomograph quad-HIDAC. Furthermore, [(18)F]FECNT was tested in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. [(18)F]FDOPA and [(18)F]FMT failed to clearly visualize the mouse striatum, whereas PET experiments using [(18)F]FECNT proved that the employed methodology is capable of delineating the striatum in mice with exquisite resolution. Moreover, [(18)F]FECNT PET imaging of healthy and MPTP-lesioned mice demonstrated that the detection and quantification of striatal degeneration in lesioned mice can be accomplished. This study shows the feasibility of using [(18)F]FECNT PET to analyze noninvasively the striatal degeneration in the MPTP mouse model of PD. This methodology can be therefore considered as a viable complement to established in vivo microdialysis and postmortem techniques.


Resting-state connectivity deficits associated with impaired inhibitory control in non-treatment-seeking adolescents with psychotic symptoms.
Psychotic symptoms are common in the population and index risk for a range of severe psychopathological outcomes. We wished to investigate functional connectivity in a community sample of adolescents who reported psychotic symptoms (the extended psychosis phenotype). This study investigated intrinsic functional connectivity (iFC) during resting-state functional magnetic resonance imaging (fMRI; rs-fMRI). Following screening in schools, 11 non-treatment seeking, youth with psychotic symptoms (aged 11-13) and 14 community controls participated in the study. Seed regions of interest comprised brain regions previously shown to exhibit aberrant activation during inhibitory control in adolescents with psychotic symptoms. Relative to controls, adolescents with psychotic symptoms exhibited reduced iFC between regions supporting inhibitory control. Specifically, they showed weaker iFC between the right inferior frontal gyrus (IFG) and the cingulate, IFG and the striatum, anterior cingulate and claustrum, and precuneus and supramarginal gyrus. Conversely, the psychotic symptoms group exhibited stronger iFC between the superior frontal gyrus and claustrum and IFG and lingual gyrus. The present findings are the first to reveal aberrant functional connectivity in resting-state networks in a community sample of adolescents with psychotic symptoms and suggest that disruption in integration between distributed neural networks (particularly between prefrontal, cingulate and striatal brain regions) may be a key neurobiological feature of the extended psychosis phenotype.


[Gastroduodenostomy and duodenogastric reflux (author's transl)].
In 36 pigs the intragastric C14 bile acid reflux and the concentration of lysolecithin is measured following different types of hemigastrectomy and gastroduodenostomy. Termino-terminal, termino-lateral and supraduodenal termino-lateral anastomosisses were as well studied as an isoperistaltic jejunal transposition of 15 cm resp. 25 cm length.-After all types of direct gastroduodenostomy the amounts of intragastral C14 bile acids and lysolecithin were significantly elevated. An additional jejunal transposition decrease the reflux in relation to the length of the transposed jejunal segment. The importance of the duodenogastric reflex of bile acids and lysolecithin for the development of alkaline reflux gastritis and carcinoma of the gastric stump is discussed. For clinical purpose a replacement of the pyloric reflux barrier by a primary jejunal transposition in case of pylorectomy has to be discussed.


Use of angiotensin II receptor blockers in animal models of atherosclerosis.
Long considered independent risk factors for end-stage vascular disease, hypertension and atherosclerosis may be intimately linked through their effects on vascular endothelial dysfunction, which are mediated by the renin-angiotensin system (RAS). Angiotensin II, a potent vasoconstrictor and the principal active peptide of the RAS, can also produce structural changes in the vessel wall associated with atherosclerosis. The role of RAS in the pathogenesis of atherosclerosis is supported by several lines of evidence, including the presence and upregulation of angiotensin-converting enzyme (ACE) and angiotensin II in the walls of atherosclerotic arteries. This article reviews recent research showing that administration of the angiotensin II type 1-receptor blocking agents (ARB) losartan and olmesartan medoxomil to cynomolgus monkeys with diet-induced hyperlipidemia prevents the progression of atherosclerosis. Since these effects have been achieved without altering blood pressure or plasma cholesterol levels significantly, it is suggested that these novel effects of angiotensin II receptor blocker treatment may extend the therapeutic profile of this class of agents in the prevention of human vascular disease.


Pharmacists subjected to disciplinary action: characteristics and risk factors.
OBJECTIVE To establish whether there are any characteristics of pharmacists that predict their likelihood of being subjected to disciplinary action. METHODS The setting was the Royal Pharmaceutical Society of Great Britain's Disciplinary Committee. One hundred and seventeen pharmacists, all of whom had been referred to the Disciplinary Committee, were matched with a quota sample of 580 pharmacists who had not been subjected to disciplinary action but that matched the disciplined pharmacists on a set of demographic factors (gender, country of residence, year of registration). Frequency analysis and regression analysis were used to compare the two groups of pharmacists in terms of sector of work, ethnicity, age and country of training. Descriptive statistics were also obtained from the disciplined pharmacists to further explore characteristics of disciplinary cases and those pharmacists who undergo them. KEY FINDINGS While a number of characteristics appeared to increase the likelihood of a pharmacist being referred to the disciplinary committee, only one of these - working in a community pharmacy - was statistically significant. Professional misconduct accounted for a greater proportion of referrals than did clinical malpractice, and approximately one-fifth of pharmacists who went before the Disciplinary Committee had previously been disciplined by the Society. CONCLUSIONS This study provides initial evidence of pharmacist characteristics that are associated with an increased risk of being disciplined, based upon the data currently available. It is recommended that follow-up work is carried out using a more extensive dataset in order to confirm the statistical trends identified here.


Climate change and spring frost damages for sweet cherries in Germany.
Spring frost can be a limiting factor in sweet cherry (Prunus avium L.) production. Rising temperatures in spring force the development of buds, whereby their vulnerability to freezing temperatures continuously increases. With the beginning of blossom, flowers can resist only light frosts without any significant damage. In this study, we investigated the risk of spring frost damages during cherry blossom for historical and future climate conditions at two different sites in NE (Berlin) and SW Germany (Geisenheim). Two phenological models, developed on the basis of phenological observations at the experimental sweet cherry orchard in Berlin-Dahlem and validated for endodormancy release and for warmer climate conditions (already published), were used to calculate the beginning of cherry blossom in Geisenheim, 1951-2015 (external model validation). Afterwards, on the basis of a statistical regionalisation model WETTREG (RCP 8.5), the frequency of frost during cherry blossom was calculated at both sites for historical (1971-2000) and future climate conditions (2011-2100). From these data, we derived the final flower damage, defined as the percentage of frozen flowers due to single or multiple frost events during blossom. The results showed that rising temperatures in this century can premature the beginning of cherry blossom up to 17 days at both sites, independent of the used phenological model. The frequency and strength of frost was characterised by a high temporal and local variability. For both sites, no significant increase in frost frequency and frost damage during blossom was found. In Geisenheim, frost damages significantly decreased from the middle of the twenty-first century. This study additionally emphasises the importance of reliable phenological models which not only work for current but also for changed climate conditions and at different sites. The date of endodormancy release should always be a known parameter in chilling/forcing models.


Catalytic properties of RNA polymerases IV and V: accuracy, nucleotide incorporation and rNTP/dNTP discrimination.
All eukaryotes have three essential nuclear multisubunit RNA polymerases, abbreviated as Pol I, Pol II and Pol III. Plants are remarkable in having two additional multisubunit RNA polymerases, Pol IV and Pol V, which synthesize noncoding RNAs that coordinate RNA-directed DNA methylation for silencing of transposons and a subset of genes. Based on their subunit compositions, Pols IV and V clearly evolved as specialized forms of Pol II, but their catalytic properties remain undefined. Here, we show that Pols IV and V differ from one another, and Pol II, in nucleotide incorporation rate, transcriptional accuracy and the ability to discriminate between ribonucleotides and deoxyribonucleotides. Pol IV transcription is considerably more error-prone than Pols II or V, which may be tolerable in its synthesis of short RNAs that serve as precursors for siRNAs targeting non-identical members of transposon families. By contrast, Pol V exhibits high fidelity transcription, similar to Pol II, suggesting a need for Pol V transcripts to faithfully reflect the DNA sequence of target loci to which siRNA-Argonaute silencing complexes are recruited.


Utilizing dual energy CT to improve CT diagnosis of posterior fossa ischemia.
Evaluation of posterior fossa ischemia on conventional CT is limited. The goal of our study was to determine if virtual monochromatic CT increases the diagnostic accuracy for the detection of posterior infarcts relative to standard CT while using diffusion-weighted MRI as a reference standard. Thirty consecutive subjects who meet the following inclusion criteria were retrospectively enrolled: (1) symptoms of posterior fossa stroke (e.g. vertigo, fainting, and dizziness), (2) unenhanced dual-energy CT of the head performed upon admission to the emergency department, and (3) MRI of the brain within 7 days following the CT. Eight of the 30 subjects were determined to have MRI diffusion-weighted imaging findings consistent with acute posterior fossa ischemia. Monochromatic energy reconstructions at 60, 80, 100, 120keV and the clinical CT were interpreted independently by two fellowship-trained neuroradiologists, who assessed the images for posterior fossa infarcts and for imaging quality. Reconstructions obtained at 80keV provided the best artifact reduction and overall maximization of image quality and were statistically significantly better than standard head CT (P<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value were at least not less than standard CT, and there was a trend toward better values at 100keV (P=0.096). Monoenergetic 80 or 100keV reconstructions may improve the detection of posterior fossa ischemia compared to conventional CT. However, if clinical suspicion for posterior fossa ischemia warrants, a brain MRI with diffusion-weighted imaging should still be obtained, even in the presence of a negative dual energy CT of the brain.


Simultaneous mesenteric and renal bypass for visceral ischemia and renovascular hypertension.
Severe visceral ischemia and uncontrollable hypertension in a patient with previous aortofemoral and right aortorenal bypasses underwent surgical correction for stenosis of the celiac, superior mesenteric and left renal arteries. A Dacron jump graft from the junction of the aorto-celiac trunk to the superior mesenteric artery artery alleviated the mesenteric ischemia. A nonreversed vein graft connected the side of the Dacron prosthesis to the end of the left renal artery improved the renovascular hypertension. This modified, simple surgical approach, successfully corrected visceral ischemia and renovascular hypertension and avoided using the severely calcified aorta for celiac and mesenteric bypasses.


Vision in chameleons-A model for non-mammalian vertebrates.
Chameleons (Chamaeleonidae, Reptilia) are known for their extreme sensory and motor adaptations to arboreal life and insectivoury. They show most distinct sequences of visuo-motor patterns in threat avoidance and in predation with prey capture being performed by tongue strikes that are unparalleled in vertebrates. Optical adaptations result in retinal image enlargement and the unique capacity to determine target distance by accommodation cues. Ocular adaptations result in complex eye movements that are context dependent, not independent, as observed in threat avoidance and predation. In predation, evidence from the chameleons' capacity to track multiple targets support the view that their eyes are under individual controls. Eye movements and body movements are lateralised, with lateralisation being a function of many factors at the population, individual, and specific-situation levels. Chameleons are considered a potentially important model for vision in non-mammalian vertebrates. They provide exceptional behavioural tools for studying eye movements as well as information gathering and analysis. They open the field of lateralisation, decision making, and context dependence. Finally, chameleons allow a deeper examination of the relationships between their unique visuo-motor capacities and the central nervous system of reptiles and ectotherms, in general, as compared with mammals.


Lipokines and oxysterols: novel adipose-derived lipid hormones linking adipose dysfunction and insulin resistance.
The expansion of adipose tissue (AT) is, by definition, a hallmark of obesity. However, not all increases in fat mass are associated with pathophysiological cues. Indeed, whereas a "healthy" fat mass accrual, mainly in the subcutaneous depots, preserves metabolic homeostasis, explaining the occurrence of the metabolically healthy obese phenotype, "unhealthy" AT expansion is importantly associated with insulin resistance/type 2 diabetes and the metabolic syndrome. The development of a dysfunctional adipose organ may find mechanistic explanation in a reduced ability to recruit new and functional (pre)adipocytes from undifferentiated precursor cells. Such a failure of the adipogenic process underlies the "AT expandability" paradigm. The inability of AT to expand further to store excess nutrients, rather than obesity per se, induces a diabetogenic milieu by promoting the overflow and the ectopic deposition of fatty acids in insulin-dependent organs (i.e., lipotoxicity), the secretion of various metabolically detrimental adipose-derived hormones (i.e., adipokines and lipokines), and the occurrence of local and systemic inflammation and oxidative stress. Hitherto, fatty acids (i.e., lipokines) and the oxidation by-products of cholesterol and polyunsaturated fatty acids, such as nonenzymatic oxysterols and reactive aldehyde species, respectively, emerge as key modulators of (pre)adipocyte signaling through Wnt/β-catenin and MAPK pathways and potential regulators of glucose homeostasis. These and other mechanistic insights linking adipose dysfunction, oxidative stress, and impairment of glucose homeostasis are discussed in this review article, which focuses on adipose peroxidation as a potential instigator of, and a putative therapeutic target for, obesity-associated metabolic dysfunctions.


Mode of action of a novel anti-Listeria bacteriocin (CAMT2) produced by Bacillus amyloliquefaciens ZJHD3-06 from Epinephelus areolatus.
Bacteriocin CAMT2, produced by Bacillus amyloliquefaciens ZJHD3-06, has been shown to exhibit protective activity against important food spoilage and food-borne bacterial pathogens. This study was conducted to investigate the mode of action of bacteriocin CAMT2 against highly pathogenic Listeria monocytogenes ATCC 19111. The addition of bacteriocin CAMT2 at 64 AU/ml inhibited L. monocytogenes ATCC 19111. An efflux of K+ ions, lactic acid dehydrogenase and an increase in extracellular electrical conductivity was observed in CAMT2-treated L. monocytogenes. Electron microscopy showed morphological alterations such as uneven cell surface, accumulation of cell debris and bacterial lysis. These results show that bacteriocin CAMT2 inhibit L. monocytogenes by increasing cell permeability and inducing membrane damage, hence it has the great application potentials in ensuring food safety.


Increased incidence of urinary matrix metalloproteinases as predictors of disease in pediatric patients with inflammatory bowel disease.
Matrix metalloproteinases (MMPs) are a family of metal-dependent enzymes responsible for the degradation and remodeling of extracellular matrix and basement membrane proteins that occurs during both normal physiologic activity and disease. It has been suggested that MMPs may also play a role in the pathogenesis of inflammatory bowel disease (IBD) by mediating mucosal breakdown in response to an enhanced inflammatory cascade. We previously demonstrated that elevated urinary MMP levels are independent predictors of disease status in cancer patients. Here we demonstrate that elevated urinary MMP levels may be biomarkers of disease activity in patients with IBD. We analyzed 95 urine samples prospectively collected from 55 children and young adults with known or suspected IBD who presented for evaluation to the Gastrointestinal Procedure Unit at Children's Hospital Boston. Urinary MMPs were analyzed in patients by zymography and compared to 40 age- and sex-matched controls. Urinary MMP levels were significantly elevated (P < 0.0001) in patients with IBD, as well as in each subgroup (Crohn's disease or ulcerative colitis), relative to controls. Multiple logistic regression revealed that urinary MMP-2 and MMP-9 NGAL levels were independent predictors of Crohn's disease and ulcerative colitis (P < 0.0001). These data are the first to demonstrate that urinary MMPs may represent novel noninvasive biomarkers for use in the evaluation of patients with IBD.