Future directions in intraoperative radiation therapy.
It is difficult to establish the degree of effectiveness of IORT as a component of treatment in some of the malignancies currently being treated by IORT. Locally advanced pancreatic cancer is a typical example of a neoplasm for which it has been challenging to find effective advances in treatment. The survival time of patients who have this disease is limited to 9 to 12 months (median), with a 2-year survival rate of 10% to 20% following even the most effective chemoradiation. It is perhaps overly optimistic to expect that IORT will significantly enhance survival, because currently available systemic treatment options have not meaningfully affected either overall patient survival times or the rate of distant metastasis in either the adjuvant setting or for metastatic disease. It is encouraging, however, that Willett has reported five patients with 5-year survival times in the Massachusetts General Hospital IOERT series for unresectable pancreatic cancer (C.G. Willett, personal communication, 2002). Also encouraging is the report from the Medical College of Ohio of a 5-year rate of 33% in a small group of patients with resectable pancreatic cancers treated with single IORT doses (without EBRT or chemotherapy) as the sole adjuvant to surgical resection. At the same institution, during the same time period, the same group of surgeons observed that no patient with resectable pancreatic cancer survived longer than 13 months following surgical resection alone [7]. Exciting possibilities involve the use of IORT when treating early-stage malignant disease, as is detailed in the chapter on breast cancer. The use of [table: see text] IORT as adjuvant therapy seems to be associated with an extremely low incidence of in-breast local recurrence. Whether this is because of early stage of the disease or the adjuvant EBRT is not entirely clear at the time of this writing. (The results of ongoing randomized studies may not be powered sufficiently to resolve the question.) Because the local recurrence rate currently is extremely low (only one reported recurrence), however, this finding is promising. Also exciting is the use of IORT as the sole radiation [table: see text] treatment following limited excision of breast cancer. The results of the Lanciano and Milano trials (see chapter 12) are awaited with great interest. Equally exciting is the finding of meaningful survival of 20% to 40% of patients who have local or regionally recurrent cancers when IORT is used as a component of treatment together with EBRT, maximal resection, and chemotherapy, as indicated. Many of these patients still have excessive rates of both local and distant relapse, however, necessitating the rationale for well-controlled multi-institutional studies that involve alternate systemic therapies, radiation sensitizers, among other criteria.


Autophagy, programmed cell death and reactive oxygen species in sexual reproduction in plants.
Autophagy is one of the major cellular processes of recycling of proteins, metabolites and intracellular organelles, and plays crucial roles in the regulation of innate immunity, stress responses and programmed cell death (PCD) in many eukaryotes. It is also essential in development and sexual reproduction in many animals. In plants, although autophagy-deficient mutants of Arabidopsis thaliana show phenotypes in abiotic and biotic stress responses, their life cycle seems normal and thus little had been known until recently about the roles of autophagy in development and reproduction. Rice mutants defective in autophagy show sporophytic male sterility and immature pollens, indicating crucial roles of autophagy during pollen maturation. Enzymatic production of reactive oxygen species (ROS) by respiratory burst oxidase homologues (Rbohs) play multiple roles in regulating anther development, pollen tube elongation and fertilization. Significance of autophagy and ROS in the regulation of PCD of transient cells during plant sexual reproduction is discussed in comparison with animals.


Segmentation of vessels from mammograms using a deformable model.
Vessel extraction is a fundamental step in certain medical imaging applications such as angiograms. Different methods are available to segment vessels in medical images, but they are not fully automated (initial vessel points are required) or they are very sensitive to noise in the image. Unfortunately, the presence of noise, the variability of the background, and the low and varying contrast of vessels in many imaging modalities such as mammograms, makes it quite difficult to obtain reliable fully automatic or even semi-automatic vessel detection procedures. In this paper a fully automatic algorithm for the extraction of vessels in noisy medical images is presented and validated for mammograms. The main issue in this research is the negative influence of noise on segmentation algorithms. A two-stage procedure was designed for noise reduction. First, a global approach phase including edge detection and thresholding is applied. Then, the local approach phase performs vessel segmentation using a deformable model with a new energy term that reduces the noise still remaining in the image from the first stage. Experimental results on mammograms show that this method has an excellent performance level in terms of accuracy, sensitivity, and specificity. The computation time also makes it suitable for real-time applications within a clinical environment.


Projecting the incidence and costs of major cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: a cost-effectiveness analysis.
Whether sodium-glucose co-transporter 2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cost-effective based solely on their cardiovascular and kidney benefits is unknown. We projected the health and economic outcomes due to myocardial infarction (MI), stroke, heart failure (HF) and end-stage kidney disease (ESKD) among people with type 2 diabetes, with and without CVD, under scenarios of widespread use of these drugs. We designed a microsimulation model using real-world data that captured CVD and ESKD morbidity and mortality from 2020 to 2040. The populations and transition probabilities were derived by linking the Australian Diabetes Registry (1.1 million people with type 2 diabetes) to hospital admissions databases, the National Death Index and the ESKD Registry using data from 2010 to 2019. We modelled four interventions: increase in use of SGLT2is or GLP-1 RAs to 75% of the total population with type 2 diabetes, and increase in use of SGLT2is or GLP-1 RAs to 75% of the secondary prevention population (i.e. people with type 2 diabetes and prior CVD). All interventions were compared with current use of SGLT2is (20% of the total population) and GLP-1 RAs (5% of the total population). Outcomes of interest included quality-adjusted life years (QALYs), total costs (from the Australian public healthcare perspective) and the incremental cost-effectiveness ratio (ICER). We applied 5% annual discounting for health economic outcomes. The willingness-to-pay threshold was set at AU$28,000 per QALY gained. The numbers of QALYs gained from 2020 to 2040 with increased SGLT2i and GLP-1 RA use in the total population (n=1.1 million in 2020; n=1.5 million in 2040) were 176,446 and 200,932, respectively, compared with current use. Net cost differences were AU$4.2 billion for SGLT2is and AU$20.2 billion for GLP-1 RAs, and the ICERs were AU$23,717 and AU$100,705 per QALY gained, respectively. In the secondary prevention population, the ICERs were AU$8878 for SGLT2is and AU$79,742 for GLP-1 RAs. At current prices, use of SGLT2is, but not GLP-1 RAs, would be cost-effective when considering only their cardiovascular and kidney disease benefits for people with type 2 diabetes.


5-hydroxytryptamine 3-receptor antagonist modulates gallbladder emptying and motilin release induced by erythromycin.
In the present study we evaluated the effect of ondansetron (formerly indicated as GR38032F), a potent and selective type-3 5-hydroxytryptamine receptor antagonist, on erythromycin-induced gallbladder emptying and motilin release, as well as gallbladder emptying induced by a regular meal in healthy volunteers. Gallbladder emptying was evaluated by sonography. Ondansetron, at the dose of 0.05 mg/kg, significantly reduced (P < 0.001 by ANOVA) the gallbladder emptying induced by 2 mg/kg/hr erythromycin, but did not increase basal gallbladder volume or inhibit gallbladder emptying induced by a regular meal. Ondansetron also inhibited the motilin release induced by erythromycin (P < 0.001, by ANOVA). These results suggest that serotoninergic mechanisms modulate the effects of erythromycin on the gastrointestinal tract. The exact site of action of ondansetron remains to be identified.


Efficacy, dose-response, and aerosol delivery of dry powder synthetic lung surfactant treatment in surfactant-deficient rabbits and premature lambs.
Dry powder (DP) synthetic lung surfactant may be an effective means of noninvasive delivery of surfactant therapy to premature infants supported with nasal continuous positive airway pressure (nCPAP) in low-resource settings. Four experimental DP surfactant formulations consisting of 70% of phospholipids (DPPC:POPG 7:3), 3% Super Mini-B (SMB) or its sulfur-free derivate B-YL as SP-B peptide mimic, 25% of lactose or trehalose as excipient, and 2% of NaCl were formulated using spray drying. In vitro surface activity was confirmed with captive bubble surfactometry. Surfactant particle size was determined with a cascade impactor and inhaled dose was quantified using a spontaneously breathing premature lamb lung model supported with CPAP. In vivo surfactant efficacy was demonstrated in three studies. First, oxygenation and lung compliance were monitored after intratracheal instillation of resuspended DP surfactant in intubated, ventilated, lavaged, surfactant-deficient juvenile rabbits. In dose-response studies, ventilated, lavaged, surfactant-deficient rabbits received 30, 60, 120 or 240 mg/kg of DP B-YL:Lactose or B-YL:Trehalose surfactant by aerosol delivery with a low flow aerosol chamber via their endotracheal tube. Noninvasive aerosolization of DP B-YL:Trehalose surfactant via nasal prongs was tested in spontaneous breathing premature lambs supported with nCPAP. Intratracheal administration of 200 mg/kg of Curosurf®, a liquid porcine surfactant, was used as a positive control. Mass median aerosol diameter was 3.6 μm with a geometric standard deviation of 1.8. All four experimental surfactants demonstrated high surface efficacy of intratracheal instillation of a bolus of ~ 100 mg/kg of surfactant with improvement of oxygenation and lung compliance. In the dose-response studies, rabbits received incremental doses of DP B-YL:Lactose or B-YL:Trehalose surfactant intratracheally and showed an optimal response in oxygenation and lung function at a dose of 120-240 mg/kg. Aerosol delivery via nasal prongs of 1 or 2 doses of ~ 100 mg/kg of B-YL:Trehalose surfactant to premature lambs supported with nCPAP resulted in stabilization of spontaneous breathing and oxygenation and lung volumes comparable to the positive control. These studies confirm the clinical potential of DP synthetic lung surfactant with B-YL peptide as a SP-B mimic to alleviate surfactant deficiency when delivered as a liquid bolus or as an aerosol.


Cochlear implantation in children with auditory neuropathy spectrum disorder: an updated systematic review.
The goal of managing auditory neuropathy spectrum disorder (ANSD) is to restore the children's ability to discriminate auditory information. Children who are not making sufficient progress in speech comprehension, and speech and language development after receiving adequate auditory re/habilitation and/or acoustic amplification may be candidates for cochlear implantation (CI). Despite the growing number of published literature on CI outcomes in children with ANSD, the current evidence is primarily based on case reports or retrospective chart reviews some of which had a limited number of children. In addition, the outcomes of CI seem to vary between children with ANSD. Thus, compelling evidence is lacking. This updated systematic review evaluated the speech perception, language, and speech intelligibility outcomes of children with ANSD post-CI. An online bibliographic search was conducted in PubMed, Scopus, Web of Science, and CENTRAL databases. We included both interventional and observational studies that assessed the outcomes of the CI in children with ANSD. Thirty-three studies were included in this systematic review. Several tests were used to assess speech perception following CI in children with ANSD. The findings of this study revealed that children with ANSD had mean Categories of Auditory Performance scores ranging from 4.3 to 7 post-operatively, this result was better than the pre-operative scores which ranged between 0.4 to 2.5. Likewise, the Infant-Toddler Meaningful Auditory Integration Scale, Phonetically Balanced Kindergarten, and multisyllabic lexical neighborhood test showed clinically relevant improvement after CI. The same findings were reported for language and speech intelligibility scores. One study investigated the quality of life/children satisfaction after CI and showed overall good satisfaction with the outcomes. The present systematic review suggests that CI is a feasible and effective hearing rehabilitation modality for children with ANSD. PROSPERO ID: CRD42021279140.


Trisomy 11 in chronic myelomonocytic leukemia: report of two cases and review of the literature.
Two cases of chronic myelomonocytic leukemia (CMMoL) with trisomy 11 as the sole chromosome abnormality are reported. A simple trisomy 11 also has been reported in 11 patients with myeloproliferative disorders, including CMMoL and acute nonlymphocytic leukemia (ANLL) in the literature. From data on these 13 patients, leukemia with trisomy 11 may be characterized by a nonlymphoid origin and myelomonocytic features. Patients with this abnormality were mostly elderly, and often had a preleukemic phase and a short survival. We propose that trisomy 11 and nonlymphocytic leukemia with myelomonocytic features may be a new association in human neoplasia.


Iso- and cross-oriented columns in cat striate cortex: a study with simultaneous single- and multi-unit recordings.
The constancy of orientation tuning in vertical columns of the visual cortex of the cat was examined with conventional and newly developed multi-electrode methods. Preferred orientation was measured with single- and multi-unit recordings in 68 penetrations approximately perpendicular to the cortical layers and with inter-recording steps of only 40-70 microns. The tuning curves obtained revealed three types of penetration sequences: no-shift penetrations (37%), one-shift penetrations (41%) and double-shift penetrations (22%). Particular attention was paid to the orientation tuning at the transition zones below layer IV. The use of the multi-unit recording technique enabled the measurement of cross-oriented activity within a single electrode position mostly around the border between layers IV and V. Altering the type of anaesthesia (ventilation with room air or nitrous oxide-oxygen) produced only a quantitative change in the percentage of the encountered penetration types. The results suggest that upper and lower layers follow different principles of functional organization. As a consequence different types of columns, especially iso- and cross-oriented ones, are produced in a systematic way.


Effects of dopamine receptor agonists and antagonists at peripheral neuronal and vascular dopamine receptors in the anaesthetised dog.
The interactions between several putative dopamine receptor agonists and antagonists have been examined at neuronal and vascular dopamine receptors in the femoral and mesenteric vascular beds, respectively, of anaesthetised dogs. N,N-di-n- propyldopamine (DPDA) and apomorphine caused vasodilatation in both vascular beds. Cis alpha-flupenthixol, fluphenazine, and sulpiride were much more potent at antagonising DPDA at neuronal than at vascular dopamine receptors. Fluphenazine and sulpiride were as potent against apomorphine as against DPDA at neuronal receptors, but cis alpha-flupenthixol was much less effective. Fluphenazine antagonised the vasodilator effect of apomorphine in the mesenteric vascular bed, but cis alpha-flupenthixol and sulpiride did not, even when used in doses much larger than were effective against DPDA. Further experiments, in dogs pretreated with phenoxybenzamine and propranolol, revealed that cis alpha-flupenthixol, fluphenazine, and sulpiride also antagonised the mesenteric vasodilator effects of dopamine, 2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene, and 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, suggesting a common site of action of these drugs and DPDA. Only fluphenazine antagonised responses to apomorphine. The results support the view that neuronal and vascular dopamine receptors in the dog are different. They also show that apomorphine stimulates different receptors from DPDA in the mesenteric vascular bed and, perhaps, in the femoral vascular bed as well.


Hypothermia for spinal cord injury.
Interest in systemic and local hypothermia extends back over many decades, and both have been investigated as potential neuroprotective interventions in a number of clinical settings, including traumatic brain injury, stroke, cardiac arrest, and both intracranial and thoracoabdominal aortic aneurysm surgery. The recent use of systemic hypothermia in an injured National Football League football player has focused a great deal of attention on the potential use of hypothermia in acute spinal cord injury. To provide spinal clinicians with an overview of the biological rationale for using hypothermia, the past studies and current clinical applications of hypothermia, and the basic science studies and clinical reports of the use of hypothermia in acute traumatic spinal cord injury. A review of the English literature on hypothermia was performed, starting with the original clinical description of the use of systemic hypothermia in 1940. Pertinent basic science and clinical articles were identified using PubMed and the bibliographies of the articles. Each article was reviewed to provide a concise description of hypothermia's biological rationale, current clinical applications, complications, and experience as a neuroprotective intervention in spinal cord injury. Hypothermia has a multitude of physiologic effects. From a neuroprotective standpoint, hypothermia slows basic enzymatic activity, reduces the cell's energy requirements, and thus maintains Adenosine Triphosphate (ATP) concentrations. As such, systemic hypothermia has been shown to be neuroprotective in patients after cardiac arrest, although its benefit in other clinical settings such as traumatic brain injury, stroke, and intracranial aneurysm surgery has not been demonstrated. Animal studies of local and systemic hypothermia in traumatic spinal cord injury models have produced mixed results. Local hypothermia was actively studied in the 1970s in human acute traumatic spinal cord injury, but no case series of this intervention has been published since 1984. No peer-reviewed clinical literature could be found, which describes the application of systemic hypothermia in acute traumatic spinal cord injury. Animal studies of acute traumatic spinal cord injury have not revealed a consistent neuroprotective benefit to either systemic or local hypothermia. Human studies of local hypothermia after acute traumatic spinal cord injury have not been published for over two decades. No peer-reviewed studies describing the use of systemic hypothermia in this setting could be found. Although a cogent biological rationale may exist for the use of local or systemic hypothermia in acute traumatic spinal cord injury, there is little scientific literature currently available to substantiate the clinical use of either in human patients.


Outcomes after acute ischemic stroke in patients with thrombocytopenia or thrombocytosis.
Thrombocytopenia may be associated with a greater risk of cerebral hemorrhage and thrombocytosis may be associated with a greater risk of cerebral thrombosis. There is a paucity of studies focused on the potential association between blood platelet count (BPC) and outcomes after acute ischemic stroke (AIS). We hypothesized that abnormal BPC is associated with poorer outcomes after AIS. This study included data from the Ontario Stroke Registry on consecutive patients with AIS admitted between July 2003 and March 2008. Patients were divided into groups as follows: low BPC (<150,000/mm(3)), normal BPC (150,000 to 450,000/mm(3)) and high BPC (>450,000/mm(3)). Primary outcome measures were the frequency of moderate/severe strokes on admission (Canadian Neurologic Scale: <8), greater degree of disability at discharge (modified Rankin score: 3-6), and 30-day and 90-day mortality. We included 9230 patients. Both low and high BPC were associated with higher 30-day mortality (p≤0.0335) and 90-day mortality (p≤0.048) following AIS. The Kaplan-Meier curves indicate that abnormal BPC is associated with greater mortality after AIS (p=0.0002). Nonetheless, abnormal BPC was not associated with initial stroke severity (p≥0.225), degree of disability (p≥0.3761), or length of stay in the acute stroke care center (p≥0.7818) after adjustment for major potential confounders. Thrombocytopenia and thrombocytosis on the initial admission are associated with higher mortality after AIS. Abnormal BPC does not adversely affect the degree of initial impairment, disability at discharge, or length of stay in the acute care hospital after AIS.


Towards the realization of label-free biosensors through impedance spectroscopy integrated with IDES technology.
Impedance spectroscopy (IS) is a powerful technique for analysis of the complex electrical impedance of a large variety of biological systems, because it is sensitive both to surface phenomena and to changes of bulk properties. A simple and convenient method of analysis of cell properties by IS is described. An interdigitated electrodes configuration was used for the measurements; human epithelial cells were grown on the device to investigate the complex dielectric response as a function of frequency, in order to test the suitability of the device for use as a label-free biosensor. To test the ability of the device to detect channels in the cell membrane, the effect of drugs known to affect membrane integrity was also investigated. The frequency response of the admittance (i.e. the reciprocal of the impedance) can be well fitted by a model based on very simple assumptions about the cells coating the device surface and the current flow; from the calculations, membrane-specific capacitance and information about cell adhesion can be inferred. These preliminary efforts have shown that our configuration could lead to a label-free non-invasive technique for biosensing and cellular behavior monitoring which might prove useful in investigation of the basic properties of cells and the effect of drugs by estimation of some fundamental properties and modification of the electrical characteristics of the device.


Pelvic ultrasound evaluation in patients with Turner syndrome during treatment with growth hormone.
Treatment with growth hormone (GH), alone or in combination with oxandrolone, is used in patients affected by Turner syndrome to improve growth velocity and adult height. Since GH interacts with gonadotropins in the stimulation of the human ovary, the aim of our study was to evaluate the possible effects of GH administration on uterine and ovarian characteristics. We performed pelvic ultrasound assessment in 29 patients with Turner syndrome aged 7.5-16.6 years (19 with 45,X karyotype; 10 with variant karyotypes) before and during treatment with GH alone. Uterine volume and ovarian size and morphology were compared to those of 23 age-matched girls with Turner syndrome not treated with GH. Both patients and controls were divided into prepubertal and pubertal groups. Cross-sectional and longitudinal studies (before and every 6 months during GH treatment for 2 years) were performed. We observed a significantly higher uterine anteroposterior diameter and volume in younger (< or = 11 years) GH-treated Turner syndrome girls than in those who were untreated. Also visualization and heterogeneous echopattern of the ovaries were significantly more frequent in treated than in untreated Turner syndrome patients, particularly before the age of 11 years. The longitudinal study showed a significant increase in uterine volume, more related to treatment than to age. Spontaneous breast development and menarche were found more frequently in GH-treated Turner syndrome girls. Growth hormone therapy can have a co-gonadotropin role in patients with Turner syndrome.


Real-time PCR assay for the detection and quantification of Legionella pneumophila in environmental water samples: utility for daily practice.
We developed a quantitative real-time PCR assay targeting the mip gene of Legionella pneumophila for a prospective study from September 2004 to April 2005. It was compared with a standard culture method (French guideline AFNOR T90-431), analysing 120 water samples collected to monitor the risk related to Legionellae at Nantes hospital and to investigate a case of legionellosis acquired from hospital environment. Samples from six distinct water distribution systems were analysed by DNA extraction, amplification and detection with specific primers and FRET probes. The detection limit was 100 genomic units of L. pneumophila per liter (GU/l), the positivity threshold about 600 GU/l and the quantification limit 800 GU/l. PCR results were divided into three groups: negative (n=63), positive but non-quantifiable (n=22) or positive (n=35). PCR showed higher sensitivity than culture, whereas four culture-positive samples appeared negative by PCR (PCR inhibitor detected for two of them). Although no correlation was observed between both methods and real-time PCR cannot substitute for the reference method, it represents an interesting complement. Its sensitivity, reproducibility and rapidity appear particularly interesting in epidemic contexts in order to identify the source of contamination or to evaluate critical points of contamination in water distribution systems.


A sensitive visual method for onsite detection of quarantine pathogenic bacteria from horticultural crops using an LbCas12a variant system.
Pre-planting testing of seeds and plantlets for the existence of quarantine pathogens is an important phytosanitary measure. The CRISPR-mediated molecular diagnostic methodologies are being developed for pathogens detection, but many challenges remain. Here, we profiled an engineered Crispr/LbCas12a variant (LbCas12a-5M) that has more robust trans-cleavage activity and a wider PAM sequences (TNTN) preference than wild type. We developed a procedure for screening specific sequences of bacterial plant pathogens, and the designed species-specific crRNA displayed no cross-reactions with other bacterial species. Combined with a simple extraction of bacterial DNA, an LbCas12a-5M-based visual detection technique was established and optimized for detecting quarantine pathogens Erwinia amylovora and Acidovorax citrulli with detection limits up to 40 CFU/reaction and a sensitivity consistent with qPCR assay. This protocol was faster and simpler than qPCR, requiring 40 min or less from sample preparation. We further validated the potential application of the method by showing that it can be used for rapid and accurate diagnosis of A. citrulli on seeds of watermelon, with 100% agreement with the results of qPCR assay. The developed method simplifies the detection of pathogens and provides cost-effective countermeasures to quarantine interventions.


[Digital electroencephalography in brain death diagnostics : Technical requirements and results of a survey on the compatibility with medical guidelines of digital EEG systems from providers in Germany].
The guidelines of the German Medical Association and the German Society for Clinical Neurophysiology and Functional Imaging (DGKN) require a high procedural and technical standard for electroencephalography (EEG) as an ancillary method for diagnosing the irreversible cessation of brain function (brain death). Nowadays, digital EEG systems are increasingly being applied in hospitals. So far it is unclear to what extent the digital EEG systems currently marketed in Germany meet the guidelines for diagnosing brain death. In the present article, the technical und safety-related requirements for digital EEG systems and the EEG documentation for diagnosing brain death are described in detail. On behalf of the DGKN, the authors sent out a questionnaire to all identified distributors of digital EEG systems in Germany with respect to the following technical demands: repeated recording of the calibration signals during an ongoing EEG recording, repeated recording of all electrode impedances during an ongoing EEG recording, assessability of intrasystem noise and galvanic isolation of measurement earthing from earthing conductor (floating input). For 15 of the identified 20 different digital EEG systems the specifications were provided by the distributors (among them all distributors based in Germany). All of these EEG systems are provided with a galvanic isolation (floating input). The internal noise can be tested with all systems; however, some systems do not allow repeated recording of the calibration signals and/or the electrode impedances during an ongoing EEG recording. The majority but not all of the currently available digital EEG systems offered for clinical use are eligible for use in brain death diagnostics as per German guidelines.


A phase Ib trial of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer.
Chemoimmunotherapy with anti-programmed cell death 1/ligand 1 and cytotoxic chemotherapy is a promising therapeutic modality for women with triple-negative breast cancer, but questions remain regarding optimal chemotherapy backbone and biomarkers for patient selection. We report final outcomes from a phase Ib trial evaluating pembrolizumab (200 mg IV every 3 weeks) with either weekly paclitaxel (80 mg/m2 weekly) or flat-dose capecitabine (2000 mg orally twice daily for 7 days of every 14-day cycle) in the 1st/2nd line setting. The primary endpoint is safety (receipt of 2 cycles without grade III/IV toxicities requiring discontinuation or ≥21-day delays). The secondary endpoint is efficacy (week 12 objective response). Exploratory aims are to characterize immunologic effects of treatment over time, and to evaluate novel biomarkers. The trial demonstrates that both regimens meet the pre-specified safety endpoint (paclitaxel: 87%; capecitabine: 100%). Objective response rate is 29% for pembrolizumab/paclitaxel (n = 4/13, 95% CI: 10-61%) and 43% for pembrolizumab/capecitabine (n = 6/14, 95% CI: 18-71%). Partial responses are observed in two subjects with chemo-refractory metaplastic carcinoma (both in capecitabine arm). Both regimens are associated with significant peripheral leukocyte contraction over time. Response is associated with clinical PD-L1 score, non-receipt of prior chemotherapy, and the H&E stromal tumor-infiltrating lymphocyte score, but also by a novel 27 gene IO score and spatial biomarkers (lymphocyte spatial skewness). In conclusion, pembrolizumab with paclitaxel or capecitabine is safe and clinically active. Both regimens are lymphodepleting, highlighting the competing immunostimulatory versus lymphotoxic effects of cytotoxic chemotherapy. Further exploration of the IO score and spatial TIL biomarkers is warranted. The clinical trial registration is NCT02734290.


Increased autonomy with capacity-based mental health legislation in Norway: a qualitative study of patient experiences of having come off a community treatment order.
Capacity-based mental health legislation was introduced in Norway on 1 September 2017. The aim was to increase the autonomy of patients with severe mental illness and to bring mental health care in line with human rights. The aim of this study is to explore patient experiences of how far the new legislation has enabled them to be involved in decisions on their treatment after they were assessed as capable of giving consent and had their community treatment order (CTO) revoked due to the change in the legislation. Individual in-depth interviews were conducted from September 2019 to March 2020 with twelve people with experience as CTO patients. Interviews were transcribed and analysed using thematic analysis inspired by hermeneutics. Almost all interviewees were receiving the same health care over two years after their CTO was terminated. Following the new legislation, they found it easier to be involved in treatment decisions when off a CTO than they had done in periods without a CTO before the amendment. Being assessed as having capacity to consent had enhanced their autonomy, their dialogues and their feeling of being respected in encounters with health care personnel. However, several participants felt insecure in such encounters and some still felt passive and lacking in initiative due to their previous experiences of coercion. They were worried about becoming acutely ill and again being subjected to involuntary treatment. The introduction of capacity-based mental health legislation seems to have fulfilled the intention that treatment and care should, as far as possible, be provided in accordance with patients' wishes. Systematic assessment of capacity to consent seems to increase the focus on patients' condition, level of functioning and opinions in care and treatment. Stricter requirements for health care providers to find solutions in cooperation with patients seem to lead to new forms of collaboration between patients and health care personnel, where patients have become more active participants in their own treatment and receive help to make more informed choices.


Comparative analysis of [3H]-thymidine labelling index and monoclonal antibody Ki-67 in non-Hodgkin's lymphomas.
The relation between the [3H]-thymidine labelling index (3H-Thy LI), which evaluates the S-phase cells, and the monoclonal antibody Ki-67 (MoAb Ki-67), which recognizes a nuclear antigen expressed during the cell cycle, was defined in 35 non-Hodgkin's lymphomas (NHL). Significantly higher median values of [3H]-Thy LI and Ki-67-positive cells were observed for high-grade than for low-grade malignancy tumours according to the Kiel classification, but with wide and overlapping values for the two morphologic subgroups. A significant correlation was observed between [3H]-Thy LI and Ki-67-positive cells (P less than 0.0001; r = 0.62). However, the ratio between the two cell kinetic variables on individual tumours was not constant. It sharply increased with decreasing [3H]-Thy LI values and was much higher in low-grade NHL than in high-grade NHL. Follow-up studies are needed to establish the role of the tumour growth fraction as evaluated by MoAb Ki-67 as a prognostic indicator in NHL.


Teaching endoscopic management of gastrointestinal hemorrhage using a modular simulation curriculum.
As flexible endoscopy is increasingly adopted as a minimally invasive approach to surgical challenges, an efficient curriculum is needed to train surgeons in therapeutic endoscopy. We developed a simulation-based approach to teaching endoscopic management of gastrointestinal hemorrhage as part of a modular curriculum, complete with task performance pre- and post-testing. Two sessions of our advanced flexible endoscopy course were taught using ex vivo porcine models to simulate active gastrointestinal hemorrhage and allow for training in hands-on endoscopic management. The module is composed of hands-on pretesting, didactics, mentored practice sessions, and postcourse assessments. Pre- and postcourse tests and surveys evaluated knowledge, confidence, and performance of participants and results were analyzed using the paired t test. Sixteen practicing surgeons participated in the course. After course completion, overall knowledge-based assessments improved from 3.4 (±1.9) to 5.8 (±2.0) (P < .001). Although participants with glove sizes >7.0 and ≥2 years in practice had higher pretest evaluator scores (P = .045 and P = .020), all participants demonstrated overall improvement in endoscopic management of hemorrhage, with postcourse evaluator score increases from 20.9 (±1.6) to 23.6 (±2.0) (P = .001) and specific improvements in identification of target bleeding (P = .015), endoscopic clip setup (P < .001), and clip deployment (P = .002). Surveys also found increased confidence in competency after curriculum completion, 11.6 (±3.4)-23.0 (±5.5) (P < .001). Our simulation-based approach to teaching the endoscopic management of gastrointestinal bleeding emphasizes hands-on pretesting and provides an effective training model to improve the knowledge, confidence, and technical performance of practicing surgeons.


Binding of hydrophobic ligands to plant lectins: titration with arylaminonaphthalenesulfonates.
Binding of the hydrophobic ligands 1,8-anilinonaphthalenesulfonic acid (ANS) and 2,6-toluidinylnaphthalenesulfonic acid (TNS) to a variety of plant lectins was studied by lectin-induced alteration of the fluorescence spectra of the two ligands. With one exception, all legume lectins examined bound ANS, with affinity constants ranging from 10(3) to 10(4) M-1. Similar ANS binding was noted for some nonlegume lectins. Titration of the five isolectins from Phaseolus vulgaris with ANS indicated positive cooperative binding of ANS to the two isolectins E4 and E3L1. Titrations with TNS revealed high-affinity sites for this ligand in a number of lectins. Addition of haptenic sugars did not inhibit binding of ANS, suggesting that the hydrophobic binding sites of lectins are independent of the carbohydrate binding sites.


Internet-based survey of the perceptions of surgical scars of Japanese patients.
The adverse aesthetic effects of post-surgical scars frequently impose a psychological burden on patients. We conducted an Internet-based questionnaire survey of Japanese individuals to explore patient satisfaction with respect to surgical scars and to identify the factors that affect their interest and experience of scar care. A cross-sectional study was conducted for the previous year on patients who had undergone the following surgeries: gastrointestinal; orthopaedic; obstetric; gynaecological; and plastic. The questionnaire included: (1) measures of participant characteristics; (2) measures of interest, experience and satisfaction with scar care; (3) measures of current and desired scar condition; and (4) measures of communication with physicians or nurses. A total of 214 participants were enrolled. Of these, only 90 individuals had experienced any treatment or self-care, and only 30 were satisfied with their experience. We found a significant gap between the current and desired thickness and colour of the scar (P < 0.01). On logistic regression analysis, scars located at a visible site and size of the scar were significant factors that affected the interest and experience of scar care. Only 40% of participants answered that their physician or nurse adequately understands their concerns pertaining to the scar condition. Only a small proportion of individuals were satisfied with their experience of scar care. Additional research in following areas is required: (1) mutual communication between patients and medical providers; and (2) development of a new care programme for the management of scars.


Analyzing the carbon emission effect and systematic emission reduction mechanism of the Sino-USA manufacturing trade.
This study analyzed the theoretical mechanism of the carbon emission effect embodied in the Sino-USA manufacturing trade. We constructed a trade and carbon emission input-output model for 16 manufacturing sub-sectors in China and the USA from 2000 to 2018. A comprehensive empirical test of the systematic emission reduction mechanism was conducted. There were four main findings: (1) indirect and direct carbon emissions indicators can comprehensively analyze the link between production and demand across sectors; (2) indirect carbon emissions are higher than direct carbon emissions in half of the sectors in both China and the USA, and other sectors bear part of the carbon emissions for these sectors; (3) compared to 2000, the change in net exports of both countries is the main reason for the change in indirect carbon emissions, while the change in net exports of intermediate goods is the main reason for the change in direct carbon emissions; and (4) the Sino-USA trade surplus comes at the expense of China's environmental losses, while the USA obtains environmental benefits. Overall, the theoretical analytical framework not only comprehensively considers the interlinkages between production and demand across sectors but also provides a more reasonable evaluation of the environmental effects of Sino-USA trade. Additionally, this study provides a solid theoretical and empirical basis for China to achieve its dual-cycle and dual-carbon goals, thus promoting the rapid transformation of China's economy toward green and high-quality development.


The metabolic activation of 7-methylbenz(a)anthracene: the induction of malignant transformation and mutation in mammalian cells by non-K-region dihydrodiols.
Four different dihydrodiols derived from 7-methylbenz(a)anthracene have been tested, together with the parent hydrocarbon, for their ability to induce the in vitro malignant transformation of mouse M2 fibroblasts and mutations in V79 Chinese hamster cells. In the transformation tests withe the non-K-region dihydrodiols, the 3,4-diol was the most active dihydrodiol tested and the 8,9-diol was also more active than 7-methylbenz(a)anthracene itself; the 1,2-diol showed only slight activity. The K-region dihydrodiol, the 5,6-diol, which cannot be directly metabolized to a vicinal diol-epoxide, was inactive. These differences in biological activity were similar to those apparent in the results from the mutagenicity tests. The data support the general hypothesis that non-I-region dihydrodiols, which can be metabolized to vicinal diol-epoxides, are important in the metabolic activation of the carcinogenic polycyclic hydrocarbons and, when taken together with other results, indicate that 3,4-dihydro-3,4-dihydroxy-7-methylbenz(a)anthracene is most probably involved in the metabolic activation of 7-methylbenz(a)anthracene presumably following conversion into the related diol-epoxide, 3,4-dihydro-3,4-dihydroxy-7-methylbenz(a)anthracene 1,2,-oxide.


SARS-CoV-2 genomic characterization and evolution in China.
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected global health worldwide due to its high contagiousness. During the viral spread, many mutations occurred within the virus genome. China has adopted nonpharmaceutical intervention (NPI) to contain COVID-19 outbreaks. In order to understand the evolution and genomic variation of SARS-CoV-2 in China under this policy, a total of 524 sequences downloaded from Global Initiative on Sharing All Influenza Data (GISAID) between 2019 and 2022 were included in this study. The time-scaled evolutionary analysis showed that these sequences clustered in three groups (Group A-C). Group B and C accounted for the majority of the sequences whose divergence times were around 2020 and distributed in multiple regions. Group A was mainly composed of G variants, which were mainly isolated from several regions. Moreover, we found that 191 sites had mutations with no less than 3 times, including 30 amino acids that were deleted. Finally, we found that spike and nucleocapsid genes underwent positive selection evolution, indicating that the mutations within spike and nucleocapsid genes increased the SARS-CoV-2 contagiousness. Hence, this study preliminarily elucidates the evolutionary characteristics and genomic mutations of SARS-CoV-2 under the implementation of the NPI policy in China, providing scientific basis for further understanding the control effect of the NPI policy on the epidemic.


Frailty in older breast cancer survivors: age, prevalence, and associated factors.
To describe frailty and associated factors in breast cancer survivors (BCSs) and evaluate whether BCSs are frail at an earlier age than female participants from in two large epidemiological studies. Descriptive, cross-sectional. School of Nursing at Oregon Health and Science University. 216 BCSs aged 53-87 years who were a mean 5-7 years post-treatment and not currently participating in exercise. Performance tests, clinical measures, and self-reported questionnaires provided baseline data on five criteria for frailty. Frailty was defined as meeting three of the five criteria of the frailty phenotype: shrinking, exhaustion, low activity, slowness, and weakness. Data were compared to published data from women in the Cardiovascular Health Study (CHS) and Women's Health and Aging Study (WHAS). Eighteen percent of BCSs aged 70-79 years were frail compared to 11% of women of the same age in the CHS and WHAS. Frailty was more common at a younger age in BCSs, and more BCSs were frail in all age groups compared to women in the CHS study until about age 80 years, when prevalence of frailty was similar in the two groups. Fifty percent of BCSs were classified as prefrail because they met one or two of the five frailty criteria. Higher body mass index increased the odds of frailty, and higher physical activity decreased the odds of frailty (odds ratio [OR] = 1.12, p = 0.003, and OR = 0.99, p = 0.000, respectively). Frailty and prefrailty may be common in BCSs and may occur at an earlier age than in adults without a history of breast cancer. Nurses should be alert to prefrailty or frailty at a younger age in BCSs. Awareness and early intervention may delay or prevent frailty. BCSs may be frail even when they are not yet considered older adults. Prefrailty in BCSs is important to recognize because it suggests impending frailty that could lead to reduced physical functioning or poor health. Prefrailty and frailty could be assessed in BCSs aged 50 years and older in a clinical setting using a few questions about weight, fatigue, and activity levels, in addition to simple tests of walking speed and grip strength, if warranted.


On the Verge of Neuro-Motion: Chad Bouton and His Team are Developing Breakthrough Neural Decoding Methods That Help People with Paralysis Move Again.
Chad Bouton, director of the Center for Bioelectronic Medicine and vice president of advanced engineering at the Feinstein Institute for Medical Research, which serves as the research arm of one of the largest health systems in the United States, has spent nearly two decades developing innovative medical technology and products that help diagnose and treat conditions including cancer, stroke, diabetes, and paralysis. Last year, in a groundbreaking effort, Bouton and his colleagues published their findings in Nature on neural-decoding methods that helped Ian Burkhart become the first paralyzed person with a brain implant to move again with his own thoughts.


Uric acid excretion in normal children.
Standard values were established for urinary excretion and clearance of uric acid in 95 normal, nonhospitalized children. We found that urinary uric acid excretion and serum uric values increase throughout childhood; that in early childhood, fractional excretion and clearance of uric acid are higher than adult norms; and that despite an increasing filtered load of uric acid, there is a progressive decrease in fractional excretion and clearance of uric acid with advancing age. Some tubular maturational change, either decreasing secretion or increasing reabsorption, must account for the progressive decline in fractional excretion and clearance of uric acid.


Mind the gap: Methods to study membrane contact sites.
Organelles are dynamic entities whose functions are essential for the optimum functioning of cells. It is now known that the juxtaposition of organellar membranes is essential for the exchange of metabolites and their communication. These functional apposition sites are termed membrane contact sites. Dynamic membrane contact sites between various sub-cellular structures such as mitochondria, endoplasmic reticulum, peroxisomes, Golgi apparatus, lysosomes, lipid droplets, plasma membrane, endosomes, etc. have been reported in various model systems. The burgeoning area of research on membrane contact sites has witnessed several manuscripts in recent years that identified the contact sites and components involved. Several methods have been developed to identify, measure and analyze the membrane contact sites. In this manuscript, we aim to discuss important methods developed to date that are used to study membrane contact sites.


Enlargement of the aortic annulus using a double-patch technique: a safe and effective method.
We have tested a new method to enlarge the aortic annulus using a double-patch technique after the Manouguian principle. Our study included 14 patients who had no operative mortality and no complications; long-term follow-up was 13 years. The method prevented mitral insufficiency and operative bleeding at the aortic root.


Activation of protein kinase CbetaI constitutes a new neurotrophic pathway for deafferented spiral ganglion neurons.
In mammals, degeneration of peripheral auditory neurons constitutes one of the main causes of sensorineural hearing loss. Unfortunately, to date, pharmacological interventions aimed at counteracting this condition have not presented complete effectiveness in protecting the integrity of cochlear neural elements. In this context, the protein kinase C (PKC) family of enzymes are important signalling molecules that play a role in preventing neurodegeneration after nervous system injury. The present study demonstrates, for the first time, that the PKC signalling pathway is directly neurotrophic to axotomised spiral ganglion neurons (SGNs). We found that PKCbetaI was strictly expressed by postnatal and adult SGNs both in situ and in vitro. In cultures of SGNs, we observed that activators of PKC, such as phorbol esters and bryostatin 1, induced neuronal survival and neurite regrowth in a manner dependent on the activation of PKCbetaI. The neuroprotective effects of PKC activators were suppressed by pre-treatment with LY294002 (a PI3K inhibitor) and with U0126 (a MEK inhibitor), indicating that PKC activators promote the survival and neurite outgrowth of SGNs by both PI3K/Akt and MEK/ERK-dependent mechanisms. In addition, whereas combining the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) was shown to provide only an additive effect on SGN survival, the interaction between PKC and neurotrophin signalling gave rise to a synergistic increase in SGN survival. Taken together, the data indicate that PKCbetaI activation represents a key factor for the protection of the integrity of neural elements in the cochlea.


The efficacy of two dosages of a continuous combined hormone replacement regimen.
To evaluate the efficacy of a low-dose combination of estradiol (E2) and norethisterone acetate (NETA) on bone markers, lipid and bleeding profiles and menopausal symptoms. Ninety-six healthy Chinese postmenopausal women were allocated randomly to receive 1 mg E2/0.5 mg NETA (low-dose hormone replacement therapy (HRT)) or 2 mg E2/1 mg NETA (high-dose HRT) for 6 months. Bone resorption markers (collagen I N-terminal telopeptides (NTX) and deoxypyridinoline (dPyr)) were significantly reduced; -66 and -32%, respectively, in high-dose HRT versus -55 and -24%, respectively, in low-dose HRT. Bone-specific alkaline phosphatase remained unchanged with either combination of hormones. Total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels were decreased significantly (-12 and -13%, respectively, in high-dose HRT vs. -7 and -8% in low-dose HRT). High density lipoprotein cholesterol (HDL-C) was decreased to a lesser extent in low-dose HRT and triglycerides (TG) levels remained unchanged. Both the low and high-dose HRT were effective in alleviating menopausal symptoms. After 6 months of treatment, 2% of women in the low-dose HRT were bleeding compared with 23% in the high-dose HRT. Breast pain occurred in 2% of women in low-dose HRT compared with 15% in high-dose HRT. The endometrium in the majority of the women remained normal. Menopausal symptoms were reduced effectively in postmenopausal women on either low-dose or high-dose HRT. TC, LDL-C levels and bone resorption markers were reduced in a dose-dependent manner. Low-dose HRT provided a better bleeding profile and the incidence of breast pain was low.


[Retracted] Resistance to the mTOR inhibitor everolimus is reversed by the downregulation of survivin in breast cancer cells.
[This retracts the article DOI: 10.3892/ol.2017.6597.].


[Postoperative management following decompressive hemicraniectomy for malignant middle cerebral artery infarction-A German nationwide survey study].
Malignant middle cerebral artery infarction is a potentially life-threatening disease. Decompressive hemicraniectomy constitutes an evidence-based treatment practice, especially in patients under 60 years of age; however, recommendations with respect to postoperative management and particularly duration of postoperative sedation lack standardization. This survey study aimed to analyze the current situation of patients with malignant middle cerebral artery infarction following hemicraniectomy in the neurointensive care setting. From 20 September 2021 to 31 October 2021, 43 members of the initiative of German neurointensive trial engagement (IGNITE) network were invited to participate in a standardized anonymous online survey. Descriptive data analysis was performed. Out of 43 centers 29 (67.4%) participated in the survey, including 24 university hospitals. Of the hospitals 21 have their own neurological intensive care unit. While 23.1% favored a standardized approach regarding postoperative sedation, the majority utilized individual criteria (e.g., intracranial pressure increase, weaning parameters, complications) to assess the need and duration. The timing of targeted extubation varied widely between hospitals (≤ 24 h 19.2%, ≤ 3 days in 30.8%, ≤ 5 days in 19.2%, > 5 days in 15.4%). Early tracheotomy (≤ 7 days) is performed in 19.2% and 80.8% of the centers aim for tracheotomy within 14 days. Hyperosmolar treatment is used on a regular basis in 53.9% and 22 centers (84.6%) agreed to participate in a clinical trial addressing the duration of postoperative sedation and ventilation. The results of this nationwide survey among neurointensive care units in Germany reflect a remarkable heterogeneity in the treatment practices of patients with malignant middle cerebral artery infarction undergoing hemicraniectomy, especially with respect to the duration of postoperative sedation and ventilation. A randomized trial in this matter seems warranted.


Toward Tailoring Chemistry of Silica-Based Phase Change Materials for Thermal Energy Storage.
Efficient thermal energy harvesting using phase change materials (PCMs) has great potential for thermal energy storage and thermal management applications. Benefiting from these merits of pore structure diversity, convenient controllability, and excellent thermophysical stability, SiO2-based composite PCMs have comparatively shown more promising prospect. In this regard, the microstructure-thermal property correlation of SiO2-based composite PCMs is still unclear despite the significant achievements in structural design. To enrich the fundamental understanding on the correlations between the microstructure and the thermal properties, we systematically summarize the state-of-the-art advances in SiO2-based composite PCMs for tuning thermal energy storage from the perspective of tailoring chemistry strategies. In this review, the tailoring chemistry influences of surface functional groups, pore sizes, dopants, single shell, and hybrid shells on the thermal properties of SiO2-based composite PCMs are systematically summarized and discussed. This review aims to provide in-depth insights into the correlation between structural designs and thermal properties, thus showing better guides on the tailor-made construction of high-performance SiO2-based composite PCMs. Finally, the current challenges and future recommendations for the tailoring chemistry are also highlighted.


The compatibility of theoretical frameworks with machine learning analyses in psychological research.
Supervised machine learning has been increasingly used in psychology and psychiatry research. Machine learning offers an important advantage over traditional statistical analyses: statistical model training in example data to enhance predictions in external test data. Additional advantages include advanced, improved statistical algorithms, and empirical methods to select a smaller set of predictor variables. Yet machine learning researchers often use large numbers of predictor variables, without using theory to guide variable selection. Such approach leads to Type I error, spurious findings, and decreased generalizability. We discuss the importance of theory to the psychology field. We offer suggestions for using theory to drive variable selection and data analyses using machine learning in psychological research, including an example from the cyberpsychology field.


The assessment of the HO. scavenging action of therapeutic agents.
A new method is reported for the assessment of the HO. scavenging action of therapeutic agents. It is based on the photolysis of zinc oxide and has a detection limit of 3.3%. The scavenging order of the compounds tested was penicillamine > rentiapril > ascorbic acid > cysteine > glutathione > thiomalic acid > N-acetylcysteine > myocrysin > methionine. None were as effective as DMSO. It is argued that these compounds can have an in vivo protective effect where HO. is produced from oxidant producing cells, thus limiting radical induced damage.


Morphological synthesis of Prussian blue analogue Zn3[Fe(CN)6]2⋅xH2O micro-/nanocrystals and their excellent adsorption performance toward methylene blue.
Prussian blue analogue Zn3[Fe(CN)6]2⋅xH2O (Zn-PBA) micro-/nanocrystals with well-defined spherical, cubic and polyhedral morphologies have been successfully synthesized by a simple room-temperature solution method. The morphologies and sizes of the micro-/nanocrystals can be easily tuned by HCl dosage and polymer additive. The as-prepared products are characterized by X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis and Brunauer Emmet Teller adsorption-desorption analysis. The possible formation mechanism for these Zn-PBA micro-/nanocrystals is then proposed. In addtion, adsorption performances of these micro-/nanocrystals toward organic dyes are systematically investigated. It is demonstrated that they exhibit strong adsorption selectivity to methylene blue (MB) with an extraordinary adsorption capacity as high as 1.016gg(-1) due to the proper pore size and large specific surface area (643.2m(2)g(-1)) of the product as well as the strong electrostatic interaction between MB molecules and Zn-PBA particles. It is found that the morphology and size of the micro-/nanocrystals have an important effect on their adsorption performance. Moreover, the adsorbed MB dye can be well released in some organic solvents such as ethanol and trichloromethane. The facile morphology-controlled synthesis and excellent adsorption property afford the materials promising application in adsorption related fields.


Erythropoietin-dependent association of phosphatidylinositol 3-kinase with tyrosine-phosphorylated erythropoietin receptor.
Erythropoietin (Epo) regulates the proliferation and differentiation of erythroid precursors. The Epo receptor (EpoR) belongs to the cytokine receptor family and lacks a tyrosine kinase domain. However, Epo induces tyrosine phosphorylation of cellular substrates including the EpoR. To explore the functional significance of receptor tyrosine phosphorylation, we examined the possible interaction of the receptor with the 85-kDa regulatory subunit (p85) of phosphatidylinositol (PI) 3-kinase. After Epo stimulation, p85 was found to associate with the tyrosine-phosphorylated 72-kDa form of EpoR as well as a 92-kDa phosphotyrosyl protein, and PI 3-kinase activity was detectable in anti-EpoR immunoprecipitates. Anti-EpoR blotting of anti-p85 immunoprecipitates revealed that p85 binds specifically to the 72-kDa form of the EpoR and not to unphosphorylated 66- and 64-kDa forms. Association of p85 with the EpoR was Epo dose- and time-dependent and correlated with tyrosine phosphorylation of the receptor. Consistent with a role for tyrosine phosphorylation of the EpoR, PI 3-kinase did not associate with a mitogenically active receptor mutant that lacked tyrosine-phosphorylation sites in the carboxyl-terminal region. A recombinant fusion protein containing the carboxyl-terminal SH-2 domain of p85 was shown to bind to tyrosine-phosphorylated EpoR in vitro. Taken together, these results indicate that, following Epo stimulation, the EpoR recruits PI 3-kinase to the cell membrane by binding between the carboxyl-terminal SH-2 domain of p85 and the tyrosine-phosphorylated carboxyl-terminal region of the receptor. The association with PI 3-kinase is, however, not required for the growth signal transduction from the EpoR.


Demand response in the workplace: A field experiment.
To increase the share of intermittent renewable energy in our production mix, occupants of buildings can be called upon to lower, anticipate or postpone their consumption according to the network balance. This article presents a small-scale field experiment aimed at introducing demand response in the workplace. We test the impact of load-shedding signals assorted with incentives on the energy consumption of workers in the tertiary sector. Two incentive schemes are tested, namely, an honorary contest and a monetary tournament. The results show a reduction in workers power demand during the load-shedding periods when the incentives are based on the honorary contest. In contrast, the monetary tournament where workers can win money according to their behavior seems to have no impact. The results also suggest that few workers can be responsible for a large part of energy consumption while the building is partially automatically controlled.


Brugia malayi: arachidonic acid uptake into lipid bodies of adult parasites.
Lipid bodies are non-membrane bound intracellular organelles, which have been recognized morphologically in a diversity of mammalian and nonmammalian cells, but are of uncertain function. In mammalian cells, in addition to serving as a storage site of cholesterol and triglyceride, lipid bodies can be a repository of esterified arachidonic acid. Adult worms of the human filarial parasite Brugia malayi have been found to esterify exogenous [3H]arachidonic acid into parasite phospholipids and neutral lipids. Electron microscopic autoradiography demonstrated that [3H]arachidonate was preferentially incorporated into filarial lipid bodies. The dominant incorporation of arachidonate into lipid bodies of a nematode establishes that lipid bodies are a site of arachidonic acid accumulation in nonmammalian, as well as mammalian, cells.


Gastroesophageal reflux disease (GERD) and chest pain. Results of laparoscopic antireflux surgery.
Laparoscopic fundoplication cures heartburn and regurgitation in patients with gastroesophageal reflux disease (GERD) but its effect on the chest pain that is also experienced by some patients is less clear. Confusion stems from the fact that it is difficult to determine preoperatively whether the chest pain is actually caused by the reflux. Therefore, we designed a study in patients with GERD and chest pain that would assess the value of pH monitoring in establishing a correlation between the symptom and the disease, the predictive value of pH monitoring on the results of surgical treatment, and the outcome of laparoscopic fundoplication on chest pain in patients with GERD. Of 487 patients who underwent laparoscopic fundoplication for GERD at our institution between October 1992 and July 2000, 165 (34%) complained of chest pain in addition to heartburn and regurgitation. Their symptoms had been present for an average of 118 months. The pH monitoring tracings were analyzed for a correlation between episodes of reflux and chest pain. The mean length of follow-up was 13 months. Among the 165 patients with chest pain, the relationship between pain and reflux during pH monitoring was as follows: 39 patients (group A) experienced no chest pain during the study; in 28 patients (group B), chest pain correlated with reflux in <40% of instances; in 98 patients (group C), chest pain correlated with reflux in ?40% of instances. Chest pain improved postoperatively in 65% of group A patients, 79% of group B patients, and 96% of group C patients (group C vs A and B: p <0.05). Heartburn and regurgitation resolved or improved in 97% and 95% of patients, respectively. These data show that pH monitoring helped to identify a relationship between chest pain and reflux; and when the two coincided, the chest pain was relieved by antireflux surgery.


[Eco-physiological investigations on wild and cultivated plants in the Negev Desert : III. Daily courses of net photosynthesis and transpiration at the end of the dry period].
The daily course of net photosynthesis and transpiration was measured with temperature and humidity controlled cuvettes at the end of the dry summer season in the Negev Desert. Species studied included: dominant species of the natural vegetation, cultivated plants in the run-off farm Avdat and permanently irrigated plants. An analysis of the influence of single climatic factors on gas exchange was given in part II of this publication. The reactions of the plants to complex changes in all the environmental parameters is the subject of this present study. 1. One-peaked daily courses of net photosynthesis occur in the irrigated species Citrullus colocynthis and Datura metel. After a high rate of net photosynthesis and transpiration before noon CO2 uptake is gradually reduced through stomatal closure even under good soil water conditions. Stomatal closure on C. colocynthis is controlled by the leaf temperatures whereas D. metel closes its stomata due to increasing water stress. 2. Without additional irrigation one-peaked daily courses are only possible with special constitutional adaptations to the extreme climate together with a balanced regulation of water loss. The annual Salsola inermis shows over the whole day no reduction in transpiration. Related to chlorophyll content, CO2 uptake almost attains the rates observed in the irrigated C. colocynthis. It is still unknown what type of water sources are at the disposal of this plant. The perennial chamaephytes Hammada scoparia and Reaumuria negevensis attain a stabilization of net photosynthesis at a lower level through reduction of stomatal water loss and through increased mesophyll resistance to water vapour. This reduces transpiration to a greater degree than CO2 uptake. The stomatal reactions of H. scoparia seem to be mainly controlled by the evaporation conditions in the atmosphere. Related to chlorophyll content in the assimilatory organs, net photosynthesis of both species is higher at noon than in all other chamaephytes. 3. Two-peaked daily courses of net photosynthesis are shown by plants of the run-off farm (Prunus armeniaca and Vitis vinifera). Both have a very high metabolic activity during the morning which is comparable even with that of D. metel and of H. scoparia. At noon, CO2 and H2O exchange is reduced through stomatal closure and falls below the level of all the other plants in the natural vegetation. In apricot, net photosynthesis of vertically oriented leaves does not drop to the compensation point at noon as was found with horizontally oriented leaves which had leaf temperatures some 6-8°C higher. 4. In the natural vegetation, only Noaea mucronata shows gas exchange reactions similar to those of apricot and grapvines. Also N. mucronata has high rates of net photosynthesis in the morning followed by a great reduction of gas exchange through stomatal closure at noon. At a higher water stress this type of an asymmetric two-peaked daily course is changed into a more flat symmetric two peaked curve with low metabolic activity during the morning. In Zygophyllum dumosum and in Artemisia herba-alba the reduction in CO2 uptake at noon is not caused by stomatal closure, but through temperatures above the optimum. The diffusion resistance for water vapour increases steadily during the day. 5. The daily balance of the CO2 exchange is calculated and is compared with the metabolic activity under optimal conditions. The potential photosynthetic capacity of wild plants under optimal conditions is more nearly met under the prevailing desert conditions than in the case with cultivated plants. The effects of the different types of daily courses of gas exchange on the distribution of plants of the Saharo-Arabian region (Reaumuria negevensis, Zygophyllum dumosum) and of plants of the Irano-Turanian vegetation (Hammada scoparia, Artemisia herbaalba) are discussed.


Cyclic Fatigue Resistance of Nickel-Titanium Reciprocating Instruments after Simulated Clinical Use.
The aim of this study was to evaluate the cyclic fatigue resistance of different heat-treated nickel-titanium reciprocating instruments in 2 different situations: new and used instruments after preparing 3 curved canals. A total sample of 60 nickel-titanium instruments of 3 systems (n = 20 per system) were used in this study: ProDesign R (tip 25, 0.06 taper; Easy Dental Equipment, Belo Horizonte, Brazil), Reciproc Blue (tip 25, 0.08v taper; VDW, Munich, Germany), and WaveOne Gold (tip 25, 0.07v taper; Dentsply Sirona, Ballaigues, Switzerland). Thirty new instruments (n = 10 per system) were used to prepare 90 curved single-rooted mandibular premolars (n = 30). Each instrument was used to prepare 3 root canals, and after each canal preparation the instrument was ultrasonic cleaned and submitted to autoclave sterilization procedures. The other 30 instruments (n = 10 per system) were kept without use. Then, the new and used instruments were subjected to the cyclic fatigue test in an artificial canal with a 30° angle and a 5-mm radius of curvature. The time and number of cycles to fatigue were recorded. Data were analyzed using the unpaired t test for intragroup comparison. For intergroup comparison, analysis of variance and the Tukey test for multiple comparisons were used. The intergroup comparison of new instruments showed that ProDesign R had the highest cyclic fatigue resistance followed by Reciproc Blue and WaveOne Gold (P < .05). Regarding the used instruments, WaveOne Gold had the lowest cyclic fatigue resistance (P < .05). The intragroup comparison between new and used instruments showed that WaveOne Gold and ProDesign R presented a significant reduction in the cyclic fatigue resistance after simulated clinical use (P < .05); no difference was found with the Reciproc Blue instruments (P > .05). ProDesign R had the highest cyclic fatigue resistance, whereas WaveOne Gold had the lowest for new and used instruments. Simulated clinical use affected the cyclic fatigue resistance of ProDesign R and WaveOne Gold but not of Reciproc Blue instruments.


Effects of seprafilm on peritoneal fibrinolytic system.
There is a high incidence of adhesions after ventral hernia repair with polypropylene mesh. The purpose of the present study was to evaluate the efficacy of Seprafilm in the prevention of adhesion formation and effect on peritoneal fibrinolytic activity. An incisional hernia model was created in rats. In the experimental group Seprafilm was placed between polypropylene mesh and abdominal organs. On the 14th day adhesions were evaluated and tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), plasminogen activator inhibitor (PAI) type 1 and 2 were measured in peritoneal biopsy specimens. Adhesions were significantly reduced in the Seprafilm group (P = 0.002). Nevertheless, there were no difference between the two groups in levels of tPA, PAI-1 and PAI-2. However, the levels of uPA were significantly decreased in the Seprafilm group. The adhesion preventive effect of Seprafilm is not directly related in peritoneal fibrinolytic activity. Instead, the physical properties (barrier, hydroflotation and sliconizing effect) of the membrane are primarily responsible for adhesion prevention.


Adenosarcoma arising in hepatic endometriosis.
We report a case of adenosarcoma arising in hepatic endometriosis. Both CT and MR scans demonstrated a huge heterogeneous mass containing septated, thick-walled cystic lesions. After enlarged right hepatectomy, the patient was asymptomatic with no abnormalities at liver and abdominal CT scan at 2-year follow-up.


Feasibility of artificial-intelligence-based synthetic computed tomography in a magnetic resonance-only radiotherapy workflow for brain radiotherapy: Two-way dose validation and 2D/2D kV-image-based positioning.
Magnetic Resonance Imaging (MRI)-only workflow eliminates the MRI-computed tomography (CT) registration inaccuracy, which degrades radiotherapy (RT) treatment accuracy. For an MRI-only workflow MRI sequences need to be converted to synthetic-CT (sCT). The purpose of this study was to evaluate a commercially available artificial intelligence (AI)-based sCT generation for dose calculation and 2D/2D kV-image daily positioning for brain RT workflow. T1-VIBE DIXON was acquired at the 1.5 T MRI for 26 patients in RT setup for sCTs generation. For each patient, a volumetric modulated arc therapy (VMAT) plan was optimized on the CT, then recalculated on the sCT; and vice versa. sCT-based digitally reconstructed radiographs (DRRs) were fused with stereoscopic X-ray images recorded as image guidance for clinical treatments. Dosimetric differences between planned/recalculated doses and the differences between the calculated and recorded clinical couch shift/rotation were evaluated. Mean ΔD50 between planned/recalculated doses for target volumes ranged between -0.2 % and 0.2 %; mean ΔD50 and ΔD0.01ccm were -0.6 % and 1.6 % and -1.4 % and 1.0 % for organ-at-risks, respectively. Differences were tested for clinical equivalence using intervals ±2 % (dose), ±1mm (translation), and ±1° (rotation). Dose equivalence was found using ±2 % interval (p < 0.001). The median differences between lat./long./vert. couch shift between CT-based/sCT-based DRRs were 0.3 mm/0.2 mm/0.3 mm (p < 0.05); median differences between lat./long./vert. couch rotation were -1.5°/0.1°/0.1° (after improvement of RT setup: -0.4°/-0.1°/-0.4°, p < 0.05). This in-silico study showed that the AI-based sCT provided equivalent results to the CT for dose calculation and daily stereoscopic X-ray positioning when using an optimal RT setup during MRI acquisition.


Dihydroergotamine ameliorates liver fibrosis by targeting transforming growth factor β type II receptor.
The transforming growth factor β (TGFβ) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFβ type II receptor (TGFβR2), followed by the recruitment of TGFβR1 finally triggering downstream signaling pathway. To find drugs targeting TGFβR2 that inhibit TGFβR1/TGFβR2 complex formation, theoretically inhibit TGFβ signaling pathway, and thereby ameliorate liver fibrosis. Food and Drug Administration-approved drugs were screened for binding affinity with TGFβR2 by virtual molecular docking. We identified 6 candidates and further explored their potential by Cell Counting Kit-8 (CCK-8) cell cytotoxic experiment to validate toxicity and titrated the best cellular working concentrations. Next, we further demonstrated the detailed molecular working mechanisms using mutagenesis analysis. Finally, we used a mouse model to investigate its potential anti-liver fibrosis effect. We identified 6 drug candidates. Among these 6 drugs, dihydroergotamine (DHE) shows great ability in reducing fibrotic gene expressions such as collagen, p-SMAD3, and α-SMA in TGFβ induced cellular model of liver fibrosis in LX-2 cells. Furthermore, we demonstrated that DHE binds to TGFβR2. Moreover, mutation of Leu27, Phe30, Thr51, Ser52, Ile53, and Glu55 of TGFβR2 disrupted the binding of TGFβR2 with DHE. In addition, DHE significantly improved liver fibrosis, as evidenced by Masson's trichrome staining of liver sections. This is further supported by the width and the velocity of the portal vein, and serum markers of liver function. In line with those observations, DHE also decreased macrophages infiltration and extracellular matrix deposition in the liver. DHE alleviates liver fibrosis by binding to TGFβR2 thereby suppressing TGFβ signaling pathway. We show here that as far as drug repurposing, DHE has great potential to treat liver fibrosis.


A Study of the Changes of T Helper 17 Cells and Regulatory T Cells in Herpes Zoster.
Immunosuppression and age-related deficiencies in cell-mediated immunity are important factors for the reactivation of latent varicella-zoster virus (VZV). CD4+CD25+Foxp3+ regulatory T (Treg) cells and T helper 17 (Th17) cells are closely associated with various viral infections. We analyzed Treg cells and Th17 cells in patients with herpes zoster and investigated their relationship with the reactivation of latent VZV. Treg and Th17 cells in peripheral blood and the ratio of Th17 to Treg cells were examined in patients with herpes zoster and healthy controls. Changes between pre-treatment and post-treatment estimates of Treg and Th17 cells and clinical parameters in patients with herpes zoster were also analyzed. The proportion of circulating Th17 cells and the Th17/Treg cell ratio were significantly higher in patients with herpes zoster than controls (p=0.012, 0.013), but there was no significant difference in the proportion of Treg cells between groups. There was no significant difference in the proportions of Treg and Th17 cells and the Th17/Treg cell ratio before and after treatment and between the non-postherpetic neuralgia and postherpetic neuralgia groups. Changes in Treg and Th17 cells and the Th17/Treg cell ratio were not significantly correlated with changes in the visual analog scale. Body surface area was significantly correlated with Treg cells, Th17 cells, and the Th17/Treg cell ratio (p=0.022, 0.002, 0.004). An imbalance between Th17 and Treg cells is associated with the reactivation of VZV, which may contribute to pathogenesis of herpes zoster.


Assessing treatment switch among patients with multiple sclerosis: A machine learning approach.
Patients with multiple sclerosis (MS) frequently switch their Disease-Modifying Agents (DMA) for effectiveness and safety concerns. This study aimed to develop and compare the random forest (RF) machine learning (ML) model with the logistic regression (LR) model for predicting DMA switching among MS patients. This retrospective longitudinal study used the TriNetX data from a federated electronic medical records (EMR) network. Between September 2010 and May 2017, adults (aged ≥18) MS patients with ≥1 DMA prescription were identified, and the earliest DMA date was assigned as the index date. Patients prescribed any DMAs different from their index DMAs were considered as treatment switch. . The RF and LR models were built with 72 baseline characteristics and trained with 70% of the randomly split data after up-sampling. Area Under the Curves (AUC), accuracy, recall, G-measure, and F-1 score were used to evaluate the model performance. In this study, 7258 MS patients with ≥1 DMA were identified. Within two years, 16% of MS patients switched to a different DMA. The RF model obtained significantly better discrimination than the LR model (AUC = 0.65 vs. 0.63, p < 0.0001); however, the RF model had a similar predictive performance to the LR model with respect to F- and G-measures (RF: 72% and 73% vs. LR: 72% and 73%, respectively). The most influential features identified from the RF model were age, type of index medication, and year of index. Compared to the LR model, RF performed better in predicting DMA switch in MS patients based on AUC measures; however, judged by F- and G-measures, the RF model performed similarly to LR. Further research is needed to understand the role of ML techniques in predicting treatment outcomes for the decision-making process to achieve optimal treatment goals.


Application of novel metal nanoparticles as optical/thermal agents in optical mammography and hyperthermic treatment for breast cancer.
Low heat (42-45 degrees C) hyperthermia is an effective cancer therapy with few side effects. Well engineered nanoparticles can effectively guide heat to the tumor without damaging the normal tissue. When nano-sized particles are injected to an organ with a tumor, they tend to accumulate in the tumor due to the unorganized nature of its vasculature. Magnetic nanoparticles, such as Fe3O4, are heated by a well selected alternating electromagnetic frequency. At a frequency of 450 KHz or lower, Fe3O4 nanoparticles at a size of 10-30 nm were heated effectively, without heating tissue main components. Gold nanoparticles are known as strong near infrared (NIR) absorbers. Nanogold particles at a diameter of 150 nm were added at 0.01 wt% to the tumor model, placed at depths of 1-2.5 cm, in an optically equivalent experimental breast model. Then the surface of the breast model was scanned with NIR light at 788 nm. The particles in the tumor model increased the optical contrast of the tumor by 1-3.5 dB. Considering that some of the FDA approved MRI contrast agents are made of Fe3O4, gold-coated Fe3O4 particles have a potential to be used as safe optical and thermal markers, allowing seamless breast cancer detection and cancer-specific hyperthermic treatment.


[Studies on the chemical constituents of marine sponge Iotrochota sp].
To study the chemical constituents from the marine sponge Iotrochota sp. The compounds were isolated and purified by various column chromatography methods, and their structure wer identified cholesterol (1), nonadecyl ethers of glycerol (2), p-hydroxybenzaldehyde (3), (E)-4-(3,4-dihydroxyphenyl) but-3-en-2-one (4), 3,4-dihydroxybenzaldehyde (5), ethyl vanillin (6), hendecanoic acid (7), tricosane (8). All compounds are isolated from marine sponge Iotrochota sp. for the first time.


Monitoring specific antibody responses against the hydrophilic domain of the 23 kDa membrane protein of Schistosoma japonicum for early detection of infection in sentinel mice.
Schistosomiasis remains an important public health problem throughout tropical and subtropical countries. Humans are infected through contact with water contaminated with schistosome cercariae. Therefore, issuing early warnings on the risk of infection is an important preventive measure against schistosomiasis. Sentinel mice are used to monitor water body infestations, and identifying appropriate antibody responses to schistosome antigens for early detection of infection would help to improve the efficiency of this system. In this study we explored the potential of detecting antibodies to the hydrophilic domain (HD) of the 23-kDa membrane protein (Sj23HD) and soluble egg antigen (SEA) of Schistosome japonicum for early detection of schistosome infection in sentinel mice. Development of IgM and IgG antibody levels against Sj23HD and SEA in S. japonicum infected mice was evaluated over the course of 42 days post-infection by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The Sj23HD and SEA specific IgM and IgG levels in mice all increased gradually over the course of infection, but IgM and IgG antibodies against Sj23HD presented earlier than those against SEA. Furthermore, the rates of positive antibody responses against Sj23HD were higher than those against SEA in the early stage of schistosome infection, suggesting that the likelihood of detecting early infection using anti-Sj23HD responses would be higher than that with anti-SEA responses. The use of immunoblotting could further improve the early detection of schistosome infection due to its greater sensitivity and specificity compared to ELISA. Additionally, the levels of Sj23HD and SEA specific antibodies positively correlated with the load of cercariae challenge and the duration of schistosome infection. This study demonstrated that antibody responses to the Sj23HD antigen could be monitored for early detection of schistosome infection in mice, especially by immunoblotting which demonstrated greater sensitivity and specificity than ELISA for detection Sj23HD antibodies.


Advance in the timing of the annual migration of the brown-veined white butterfly through Johannesburg, South Africa, over the period 1914-2020.
During the mid-summer month of January each year, the migrating brown-veined white butterflies (Belenois aurota, Fabricius, 1973) move through Johannesburg, South Africa, on their path from the Karoo to Mozambique. The result is a short period of approximately 3 days during which the skies of Johannesburg are filled with white butterflies, a spectacle that has been recorded in print media over the past century, and social media over the past decade. In this study, we mine these traditional and social media archives to produce the first multi-decadal phenological record of butterfly migration timing for South Africa, and explore the changes in timing and the role of climate thereof. We find a statistically significant advance in timing at a rate of 2.9 days per decade (r = 0.34, p = 0.0490). The climatic drivers of shifts in migratory species arrival are difficult to detect, as they involve the role of weather at the point of departure in determining the start of flight, and the weather en route to determine the path followed. However, statistically significant relationships are found between the arrival dates and both Tmin and precipitation in the month of December, and the combination thereof (r = 0.44, p = 0.0437 and r = 0.45, p = 0.0420 respectively). The findings of this study contribute to a growing literature documenting phenological shifts in South Africa, a previously under-represented region.


Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in rat lung DNA following subchronic inhalation of carbon black.
Chronic high-dose inhalation of carbon black (CB) can produce carcinomas in rat lungs. The mechanisms underlying this response are uncertain. It has been hypothesized that chronic inflammation and cell proliferation may play a role in the development of tumors after high dose, long-term contact of the particles with lung epithelial cells. In this investigation, we analyzed the formation of a known mutagenic lesion [8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG)] in the lung DNA of rats following subchronic inhalation of CB (Printex-90 and Sterling V). Briefly, female Fischer 344 rats were exposed for 6 h/day, 5 days/week for 13 weeks to 1, 7, and 50 mg/m(3) of Printex-90 (16 nm; specific surface area 300 m(2)/g) and to 50 mg/m(3) of Sterling V CB (70 nm; surface area of 37 m(2)/g). The exposure concentration of Sterling V was selected to be equivalent in terms of retained mass in the lung to the high dose of Printex-90 at the end of exposure. However, in terms of retained particle surface area, the retained lung dose of Sterling V was equivalent to the mid-dose of Printex 90. This design allows comparison of results on the basis of retained particle mass as well as retained particle surface area between the two CB particles. The formation of 8-oxo-dG in the lung DNA was assessed using a reverse phase HPLC system coupled with UV and electrochemical (EC) detection. After 13 weeks of exposure, measurements were made on lung samples obtained at the end of the exposure and a 44-week recovery period in clean air. Lung burdens of CB were determined at both time points as well as differential cell populations from bronchoalveolar lavage fluid (BAL). The results indicate that lung particle overload was achieved after exposure to 7 and 50 mg/m(3) (Printex-90) and 50 mg/m3 (Sterling V) but not at 1 mg/m(3) (Printex-90). Consistent with these results, a significant increase (P < 0.05) in 8-oxo-dG induction was observed following 13 weeks of exposure to 50 mg/m(3) Printex-90 and at 7 and 50 mg/m(3) after the 44-week recovery period. Interestingly, no increase in 8-oxo-dG was observed for Sterling V CB at either time point despite lung particle overload. Although the retained mass dose of Sterling V at the end of exposure was even higher than for Printex 90 (50 mg/m(3) exposure group) (approximately 7.6 vs 4.8 mg), the surface area of the retained Sterling V was similar to that of the retained Printex 90 of the mid-dose exposure (7 mg/m(3)) (approximately 0.2 m(2) in both groups). Since both Sterling V (50 mg/m(3)) and Printex 90 (7 mg/m(3)) did not induce significant increases in 8-oxo-dG in the lung at the end of the 13-week exposure, this finding indicates that a retained large particle mass is not always correlated with similar adverse effects but that particle surface area is a better dose parameter. The lower effect per unit mass dose seen with Sterling V is consistent with earlier studies showing that particle surface area of low toxicity particles is a more appropriate dosemetric for induction of inflammation in the lungs than particle mass (Oberdörster et al., 1994, 2001; Brown et al. 2001; Donaldson et al., 2002). An increase (p < 0.05) in lung lavage neutrophils was observed at 7 mg/m(3) (Printex-90) and 50 mg/m(3) (Printex-90 and Sterling V) at the 13-week exposure period and again at 50 mg/m(3) (Printex-90 and Sterling V, 44-week recovery period). Our current findings suggest that prolonged, high-dose exposure to CB can promote oxidative DNA damage that is consistent with the hypothesis that inflammatory cell-derived oxidants may play a role in the pathogenesis of rat lung tumors following long-term high-dose exposure to CB in rats.


Development of a bispecific monoclonal antibody for use in molecular hybridisation.
A mouse hybrid hybridoma (tetradoma) was prepared by fusing hybridomas producing monoclonal antibody to acetyl-aminofluorene with hybridomas producing antibody against calf intestine alkaline phosphatase. The tetradoma line established secreted immunoglobulin manifesting parental and bispecific binding characteristics. Bispecific monoclonal antibody was purified and used for a one-step immunodetection assay of non-radioactive DNA and RNA probes. The immunoassay developed was able to detect 5 pg DNA within 2 h and gave low background noise.


Natural occurrence of mycotoxins and mycotoxigenic fungi in cereals in the United Kingdom.
Approximately 50 samples of poorly stored cereals were examined for mycotoxins, fungi and biological activity. While some mycotoxins such as ochratoxin A and citrinin occurred frequently, many other fungal metabolites present could not be identified. Cereal extracts and isolates of some fungi, when grown in culture, were often toxic to brine shrimp larvae but, in some toxic extracts, no known mycotoxins were identified. A preliminary report of this study forms the subject of this paper.


Development of a novel protein biochip enabling validation of immunological assays and detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis.
In this study, we developed a novel protein biochip methodology that was characterized by dithiobis (succinimidyl undecanoate) (DSU) and specialized for detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis, respectively. The biochips were validated by a dimension of atomic force microscope (AFM). The visualized detection limit of IgG antibody on the biochip was 0.39μg/ml. Finally, 286 serum samples from the patients with syphilis were simultaneously tested on the rTpN15-17-47 coated biochips. The results were evaluated in comparison with the assays of T. pallidum particle agglutination (TPPA) and the toluidine red unheated serum test (TRUST). The result demonstrated that the relative positive rate in the 286 patients by biochip was 99.0%, similar to that by TPPA (97.9%, P>0.05) and higher than that by TRUST, (76.2%, P<0.01). The detection specificities were 100% for the biochip and the TPPA and 97.0% for the TRUST. Thus, the protein biochip would provide a useful platform not only for enabling concurrent detection of the infectious antibodies directed against T. pallidum on a larger scale, but also for monitoring therapy modality of the disease.


Association between chloroquine resistance phenotypes and point mutations in pfcrt and pfmdr1 in Plasmodium falciparum isolates from Thailand.
The relationship between the in vitro susceptibility of Plasmodium falciparum isolates to the quinoline antimalarials chloroquine (CQ), mefloquine (MQ), and quinine (QN), and pfcrt and pfmdr1 gene polymorphisms were investigated. Field isolates (110 samples) were collected from various endemic areas of Thailand throughout 2002-2004. The pfcrt 76T allele was identified in 109 isolates (99.1%) while pfcrt 76K was found in a single (0.9%) isolate. The pfmdr 86N, 86Y, and the combination (86N+86Y) alleles were identified in 83 (75.5%), 22 (20%), and 5 (4.5%) isolates, respectively. The pfmdr1 1042N, 1042D alleles and a mixture (1042N+1042D) of the alleles were found in 94 (85.5%), 12 (10.9%) and 4 (3.6%) isolates, respectively. The pfmdr1 1246Y allele was detected in a single (0.9%) isolate. The pfmdr1 gene polymorphisms (86-1042-1246) was grouped into seven haplotypes as follows: N-N-D (68 isolates; 61.2%), Y-N-D (22 isolates; 19.8%), N-D-D (11 isolates; 9.9%), N-D-Y (1 isolate; 0.9%), N/Y-N-D (4 isolates; 3.6%), N-N/D-D (3 isolates; 2.7%), and N/Y-N/D-D (1 isolate; 0.9%). Eight different combinations of pfcrt-pfmdr1 genotypes were observed. Only one CQ-, MQ- and QN-sensitive isolate was found at the Thai-Laos border and no cases of QN resistance were found in this study.


Tumor-to-tumor metastasis: lung cancer within a thymoma.
Tumor-to-tumor metastasis is a rare phenomenon. We present a rare case of an 83-year-old man with pulmonary squamous cell carcinoma and thymoma. Thymectomy and superior segmentectomy of the left lower lobe were successfully performed on the patient. This thymoma had a region of lung cancer. Metastasis from other tumors to thymoma is rare, and we found a report that described a pancreatic carcinoma metastasizing to thymoma. We report an extremely rare case of metastasis from lung cancer to a thymoma.


Green and Efficient Inkjet Printing of Cotton Fabrics Using Reactive Dye@Copolymer Nanospheres.
Digital inkjet printing of textiles possesses great advantages like high efficiency and flexible production, but the challenges like the risk of causing serious environmental problems due to the large usage of dyes and chemicals still remain a matter of concern. In response to this problem, herein, a novel kind of reactive dye@copolymer nanosphere was prepared through the adsorption of C. I. Reactive Red 218 dyes (RR218) onto cationic poly(styrene-butyl acrylate-vinylbenzyl trimethylammonium chloride) (PSBV) nanospheres and applied in inkjet printing on woven cotton fabric. Results show that the prepared RR218@PSBV nanospheres possessed homogeneous size and good stability for ink preparation. In comparison with the original RR218 solution, the color depth of RR218@PSBV-printed fabric increased by 1.4 times and the dye residues in the printing effluent were reduced by about 45%. Meanwhile, the consumptions of sodium carbonate and urea in conventional inkjet printing were reduced by about 3.3 and 22.8 mg/cm2, respectively, and the printing process was simplified with 30% energy saving. Furthermore, the mechanism of the color enhancement by nanospheres was revealed by the calculation of absorption and scattering coefficients based on the Kubelka-Munk function. This work provides a potential application of dye@polymer nanospheres to promote the optimization of the textile inkjet printing technique and alleviates the environmental impact of conventional textile coloration.


Nucleotide sequences of the Erwinia chrysanthemi ogl and pelE genes negatively regulated by the kdgR gene product.
The nucleotide sequences of the coding and regulatory regions of the genes encoding oligoglacturonate lyase (OGL) and pectate lyase e isoenzyme (PLe) from Erwinia chrysanthemi 3937 were determined. The ogl sequence contains an open reading frame (ORF) of 1164 bp coding for a 388-amino acid (aa) polypeptide with a predicted Mr of 44,124. A possible transcriptional start signal showing homology with the Escherichia coli promoter consensus sequence was detected. In addition, a sequence 3' to the coding region was found to be able to form a secondary structure which may function as an Rho-independent transcriptional termination signal. For the pelE sequence, a long ORF of 1212 bp coding for a 404-aa polypeptide was detected. PLe is secreted into the external medium by E. chrysanthemi, and a potential signal peptide sequence was identified in the pelE gene. In the 5' upstream pelE coding region, a putative promoter resembling E. coli promoter consensus sequences was detected. Furthermore, the region immediately 3' to the pelE translational stop codon may function as an Rho-independent translational termination signal. In strain 3937, the synthesis of OGL and PLe, as well as the other enzymes involved in the pectin-degradative pathway (particularly the kdgT product), are known to be regulated by the KdgR repressor, which mediates galacturonate and polygalacturonate induction. Synthesis of these enzymes is also regulated by the CRP-cAMP complex which mediates catabolite repression. Analysis of the regulatory regions of ogl and pelE allowed us to identify possible CRP-binding sites for these two genes.(ABSTRACT TRUNCATED AT 250 WORDS)